The present invention relates to a process for producing an amine via a hydroaminoalkylation reaction of a non-aromatic C-C double bond or triple bond.

Amines are key structural elements in our life, as they constitute core elements of a variety of biologically active agents and crucial high-performance materials. Accordingly, the synthesis of amino compounds from abundant and readily available substrates is of crucial importance to chemistry, biology, medicine and materials science. In particular, the synthesis of amines starting from substituted or non-substituted alkenes and alkynes is of relevance. A direct functionalization of such alkenes and alkynes can be achieved by a hydroaminoalkylation reaction, addition of hydrogen and a alkylamine-unit across an olefin.

State-of-the-art protocols for hydroaminoalkylation of alkenes rely largely on transition-metal catalysis, which enables hydroaminoalkylation under highly designed and controlled conditions. Several metal-catalyzed hydroaminoalkylations of alkenes with amines have been reported in recent years. The intermolecular addition of the a-C-H bonds of a dialkylamine to an unactivated olefin in the presence of a chloro amido tantalum complex is described in“Hydroaminoalkylation of unactivated olefins with dialkylamines” of Herzon, S. B. & Hartwig, J. F., J. Am. Chem. Soc. 2008, 130, 14940-14941. A catalytic hydroaminoalkylation of an alkene with dimethylamine using a titanium catalyst is described in“Dimethylamine as a substrate in hydroaminoalkylation reactions” of Bielefeld, J. & Doye, S., Angew. Chem. Int. Ed. 2017, 56, 15155-15158. While proceeding under catalytic conditions and employing simple amines as starting materials, metal-catalyzed hydroaminoalkylation reactions, dominated by group 4 and group 5 metal catalysts, have shown some restrictions in terms of selectivity and functional group tolerance.

An alternative approach to the hydroaminoalkylation of alkenes lies in photocatalysis or dual catalysis using transition-metal and photocatalysis. a-Aminoalkyl radicals have been added to electron-deficient alkenes by visible-light-mediated electron transfer using transition metal polypyridyl complexes as photocatalysts (Miyake, Y., Nakajima, K. & Nishibayashi, Y., “Visible-light-mediated utilization of a-aminoalkyl radicals: addition to electron-deficient alkenes using photoredox catalysts”, J. Am. Chem. Soc. 2012, 134, 3338-3341 ). The coupling of photoredox-generated a-amino radical species with conjugated dienes using a unified cobalt and iridium catalytic system in order to access a variety of useful homoallylic amines from simple commercially available starting materials is described in “A mild hydroaminoalkylation of conjugated dienes using a unified cobalt and photoredox catalytic system” of Thullen, S. M. & Rovis, T., J. Am. Chem. Soc. 2017, 139, 15504-15508. Even though mild reaction conditions can be applied, photocatalytic hydroaminoalkylation reactions are limited to specific substrates.

In order to address these challenges, the present inventors became interested in the development of a redox-neutral hydroaminoalkylation reaction circumventing the need for early transition-metal catalysis and photocatalysis. In a hydroaminoalkylation reaction of 2- phenyl-2-norbornene with formaldehyde and dimethylamine in acetic acid, a mixture of compounds best explained by a 1 ,5-hydride shift in one intermediate step is produced (Manninen, K. & Haapala, J.,“The Reaction of 2-Phenyl-2-norbornene with Formaldehyde and Dimethylamine. Additional Evidence for the Occurrence of a 1 ,5-Hydride Shift during the Aminomethylation of a Strained Bicycloalkene Structure”, Acta Chem. Scand. B, 1974, 28, 433-440). A hydroaminoalkylation of 1 -alkenes with an iminium ion generated by the action of phosphoric or sulfuric acid on (tetramethyldiamino)methane in acetic acid results in secondary amines and unsaturated tertiary amines (Cohen, T. & Onopchenko, A., “Competing Hydride Transfer and Ene Reactions in the Aminoalkylation of 1 -Alkenes with N,N-Dimethyleniminium Ions. A Literature Correction”, J. Org. Chem., 1983, 48, 4531-4537). However, also known redox-neutral hydroaminoalkylation reactions suffer from certain limiations, such as formation of elimination products and other side products, low yields and limited functional group tolerance.

In the context of the present invention, it has been found that the use of an aminal or a hemiaminal ether as starting material and a trifluoroacetic acid in a hydroaminoalkylation reaction of non-aromatic C-C double bond or C-C triple bond can markedly influence this reaction in that competing elimination reactions are suppressed and high product yields, a broad functional group tolerance and linear selectivities are achieved. A broadly applicable, redox-neutral approach to hydroaminoalkylation of compounds comprising a non-aromatic C- C double bond or C-C triple bond, which can rely on cheap, readily available and bench- stable reactants, is thus made available. The reported hydroaminoalkylation affords the desired amines with excellent functional group tolerance and high regio- and stereoselectivity. Thus, the present invention provides a process for producing an amine via a hydroaminoalkylation reaction of a non-aromatic C-C double bond or a C-C triple bond, said process comprising a step of reacting a compound comprising a non-aromatic C-C double bond or C-C triple bond with a reactive component which is obtainable by combining an aminal or a hemiaminal ether with an acidic medium comprising trifluoroacetic acid (TFA), wherein the aminal contains two amino groups independently selected from a secondary and a tertiary amino group that are linked by a methylene group wherein one hydrogen atom may be replaced by a further substituent, and at least one of the amino groups carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and

the hemiaminal ether contains a secondary or a tertiary amino group which carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and the secondary or tertiary amino group is linked to an alkoxy group by a methylene group wherein one hydrogen atom may be replaced by a further substituent.

An exemplary hydroaminoalkylation reaction of a non-aromatic C-C double bond or C-C triple bond in accordance with the present invention is illustrated by the following reaction scheme 1.

TFA

R ^A - =-

(Reaction Scheme 1)

In this reaction, a non-aromatic C-C double bond or C-C triple bond is converted with an aminal in an acidic medium to an amine. The groups R and R ^A represent any desired atoms or groups, and it should be understood that the compound comprising a non-aromatic C-C double bond or C-C triple bond and the aminal used in the process of the present invention are not limited to the exemplified structures as shown in this scheme.

As noted above, the process of the present invention encompasses a hydroaminoalkylation reaction of a non-aromatic C-C double bond or C-C triple bond. Thus, it comprises a step of reacting a compound comprising a non-aromatic C-C double bond or triple bond with a reactive component which is obtainable by combining the aminal or the hemiaminal ether as defined herein with an acidic medium comprising trifluoroacetic acid. The process in accordance with the present invention thus encompasses, as embodiments:

(i) a process for producing an amine via a hydroaminoalkylation reaction of a nonaromatic C-C double bond, said process comprising

a step of reacting a compound comprising a non-aromatic C-C double bond with a reactive component which is obtainable by combining an aminal with an acidic medium comprising trifluoroacetic acid (TFA),

wherein the aminal contains two amino groups independently selected from a secondary and a tertiary amino group that are linked by a methylene group wherein one hydrogen atom may be replaced by a further substituent, and at least one of the amino groups carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom;

(ii) a process for producing an amine via a hydroaminoalkylation reaction of a C-C triple bond, said process comprising

a step of reacting a compound comprising a C-C triple bond with a reactive component which is obtainable by combining an aminal with an acidic medium comprising trifluoroacetic acid (TFA),

wherein the aminal contains two amino groups independently selected from a secondary and a tertiary amino group that are linked by a methylene group wherein one hydrogen atom may be replaced by a further substituent, and at least one of the amino groups carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom;

(iii) a process for producing an amine via a hydroaminoalkylation reaction of a non aromatic C-C double bond, said process comprising

a step of reacting a compound comprising a non-aromatic C-C double bond with a reactive component which is obtainable by combining a hemiaminal ether with an acidic medium comprising trifluoroacetic acid (TFA),

wherein the hemiaminal ether contains a secondary or a tertiary amino group which carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and the secondary or tertiary amino group is linked to an alkoxy group by a methylene group wherein one hydrogen atom may be replaced by a further substituent; and

(iv) a process for producing an amine via a hydroaminoalkylation reaction of a C-C triple bond, said process comprising

a step of reacting a compound comprising a C-C triple bond with a reactive component which is obtainable by combining a hemiaminal ether with an acidic medium comprising trifluoroacetic acid (TFA),

wherein the hemiaminal ether contains a secondary or a tertiary amino group which carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and the secondary or tertiary amino group is linked to an alkoxy group by a methylene group wherein one hydrogen atom may be replaced by a further substituent.

The process of the present invention, and the components which can be used to put its embodiments into practice, shall be discussed in further detail in the following.

Aminal

In the embodiments of the process in accordance with the present invention using an aminal, a compound comprising a non-aromatic C-C double bond or C-C triple bond is reacted with a reactive component which is obtainable by combining the aminal with an acidic medium comprising trifluoroacetic acid.

An aminal, also referred to as a geminal diamine in the art, contains two amino groups bound to the same carbon atom. In the process in accordance with the invention, the reactive component is obtainable using an aminal which contains two amino groups independently selected from a secondary and a tertiary amino group that are linked by a methylene group wherein one hydrogen atom may be replaced by a further substituent, and at least one of the amino groups carries a hydrogen atom at a carbon atom bound in a-position to the nitrogen atom. Preferably, the two amino groups linked by the optionally substituted methylene group are both tertiary amino groups.

As will be understood by the skilled reader, a secondary amino group represents an amino group, wherein two of the three substituents bound to the nitrogen atom are organic groups other than hydrogen. A tertiary amino group represents an amino group wherein the three substituents bound to the nitrogen atom are organic groups other than hydrogen. In the case of the amino groups contained in the aminal used in the process in accordance with the present invention, one of the three substituent positions is kept by the optionally substituted methylene group as an organic group which links the two amino groups. In other words, in the case of a secondary amino group, one further organic group which is not hydrogen is bound to the nitrogen atom besides the optionally substituted methylene group, and in the case of a tertiary amino group, two further organic groups which are not hydrogen are bound to the nitrogen atom besides the optionally substituted methylene group.

As noted above, the two amino groups of the aminal are linked by a methylene group wherein one hydrogen atom may be replaced by a further substituent. As will be understood by the skilled reader, the carbon atom of the methylene group carries the two amino groups as mandatory substituents, so that a further substituent of the methylene group is a substutituent other than the two amino groups, which substituent replaces one of the two hydrogen atoms of the methylene group. In other words, the two amino groups independently selected from a secondary and a tertiary amino group contained in the aminal are either linked by a methylene group -CH ₂ - or by a methylene group carrying one substituent other than a hydrogen atom -CHR-. The open bonds of these groups are attached to the nitrogen atoms of the amino groups in the aminal, and R is an organic group other than hydrogen. As will be appreciated by the skilled reader, a process in accordane with the presence invention using a reactive component obtainable from an aminal wherein the amino groups are linked by a methylene group -CH ₂ - without a further substituent will specifically involve a hydroaminomethylation reaction as the hydroaminoalkylation reaction.

Moreover, as noted above, at least one of the amino groups in the aminal carries a hydrogen atom at a carbon atom bound in a-position to the nitrogen atom. As will be understood by the skilled reader, a carbon atom bound in a-position to the nitrogen atom is a carbon atom (generally an sp ³ -hybridized carbon atom) which is directly bound to the nitrogen atom. The carbon atom bound in a-position to the nitrogen atom is one which is present in addition to the carbon atom of the optionally substituted methylene group linking the amino groups. Thus, the aminal contains a structural unit which may be represented as

or as

wherein the -CH ₂ - group represents the methylene group linking the two geminal amino groups of the aminal, and the -CHR- group represents a substituted methylene group linking the two geminal amino groups of the aminal, wherein one hydrogen atom of the methylene is replaced by a substituent R, which is an organic group other than hydrogen.

It is noted that the organic groups which are bound to the nitrogen atoms of the amino groups may include known protective groups for amino groups which may be removed after the hydroaminoalkylation reaction, such as a benzyl group, an allyl group or a Boc group (i.e. a fert-butyloxycarbonyl group). Preferably, the aminal which can be used to provide a reactive component in accordance with the present invention is represented by the following formula (I):

wherein

R ^1A and R ^3A are independently hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

R ^2A and R ^4A are independently selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

and R ^1A and R ^2A or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound, or one of R ^1A and R ^2A and one of R ^3A and R ^4A may be bound to each other to form a ring together with the methylene group and the nitrogen atoms to which they are bound,

and wherein R ^5A is selected from the group consisting of hydrogen, an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted, -CN, -C(0)0R ¹ °, and -P(0)(0R ¹¹ )(0R ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently an alkyl group.

More preferably, the aminal which can be used to provide a reactive component in accordance with the present invention is represented by the following formula (la):

R ^2A R ^1A N ^' NR ,3 ^J A ^A pR4‘A

wherein R ^1A , R ^2A , R ^3A and R ^4A are defined as for formula (I).

In formula (I) and (la), at least one of the amino groups -NR ^1A R ^2A and -NR ^3A R ^4A carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom. As will be understood by the skilled reader, this carbon atom in a-position to the nitrogen atom, generally an sp ³ - hybridized carbon atom, may be contained in any of R ^1A , R ^ZA , R ^3A and R ^4A . The amino groups -NR ^1A R ^2A and -NR ^3A R ^4A are preferably both tertiary amino groups, i.e. groups wherein R ^1A , R ^2A , R ^3A and R ^4A are groups other than hydrogen.

Preferably, R ^1A , R ^2A , R ^3A and R ^4A are selected such that -NR ^1A R ^2A and -NR ^3A R ^4A have the same structure. More preferably, R ^1A , R ^2A , R ^3A and R ^4A are selected such that -NR ^1A R ^2A and -NR ^3A R ^4A are both tertiary amino groups and that R ^1A , R ^2A , R ^3A and R ^4A have the same structure.

It is noted that, in the formulae described herein, any hydrogen atoms can generally be replaced by deuterium. This applies not only for formulae (I) and (la) above, but also to formulae (II), (III) and (IV) below.

In addition, for the definitions of R ^1A , R ^2A , R ^3A , R ^4A in formula (I) and (la), and for the definition of R ^5A in formula (I), the following preferred meanings apply.

The aliphatic hydrocarbon group has preferably 1 to 30 carbon atoms, more preferably 1 to 24 carbon atoms, and even more preferably 1 to 12 carbon atoms. The aromatic hydrocarbon group has preferably 6 to 30 carbon atoms, more preferably 6 to 22 carbon atoms, and even more preferably 6 to 14 carbon atoms. The aliphatic heterocyclic group has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. The aromatic heterocyclic group has preferably 2 to 30 carbon atoms, more preferably 3 to 22 carbon atoms, and even more preferably 3 to 12 carbon atoms. The aralkyl group has preferably 7 to 30 carbon atoms, more preferably 7 to 24 carbon atoms, and even more preferably 7 to 14 carbon atoms.

The aliphatic heterocyclic group and the aromatic heterocyclic group have independently preferably 1 to 5 heteroatoms, more preferably 1 to 3 heteroatoms. The heteroatom is preferably selected from the group consisting of a nitrogen atom, an oxygen atom and a sulphur atom.

The aliphatic hydrocarbon group, the aromatic hydrocarbon group, the aliphatic heterocyclic group, the aromatic heterocyclic group, alone or in combination, may be substituted with one or more, such as one, two or three, substituents. Exemplary substituents are an aliphatic hydrocarbon group having 1 to 12 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aliphatic heterocyclic group having 2 to 12 carbon atoms and 1 to 3 heteroatoms, an aromatic heterocyclic group having 3 to 12 carbon atoms and 1 to 3 heteroatoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may in turn carry one or more, such as one, two or three, substituents selected from an aliphatic hydrocarbon group having 1 to 12 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aliphatic heterocyclic group having 2 to 12 carbon atoms and 1 to 3 heteroatoms, an aromatic heterocyclic group having 3 to 12 carbon atoms and 1 to 3 heteroatoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

Suitable examples of an aliphatic hydrocarbon group are a linear or branched alkyl group, a cycloalkyl group, a linear or branched alkenyl group, a cycloalkenyl group and a linear or branched alkynyl group. Suitable examples of an aliphatic heterocyclic group are a heterocycloalkyl group and a heterocycloalkenyl group. The aromatic heterocyclic group may also be referred to as a heteroaromatic group.

A linear alkyl group as referred to herein has preferably 1 to 30 carbon atoms, more preferably 1 to 24 carbon atoms, and even more preferably 1 to 12 carbon atoms. A branched alkyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A cycloalkyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A linear alkenyl group as referred to herein has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. A branched alkenyl group as referred to herein has preferably 4 to 30 carbon atoms, more preferably 4 to 24 carbon atoms, and even more preferably 4 to 12 carbon atoms. A cycloalkenyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A linear alkynyl group as referred to herein has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. A branched alkynyl group as referred to herein has preferably 4 to 30 carbon atoms, more preferably 4 to 24 carbon atoms, and even more preferably 4 to 12 carbon atoms. An aromatic hydrocarbon group as referred to herein has preferably 6 to 30 carbon atoms, more preferably 6 to 22 carbon atoms, and even more preferably 6 to 14 carbon atoms. A heterocycloalkyl group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 2 to 24 carbon atoms and 1 to 5 heteroatoms, and even more preferably 2 to 12 carbon atoms and 1 to 3 heteroatoms. A heterocycloalkenyl group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 2 to 24 carbon atoms and 1 to 5 heteroatoms, and even more preferably 2 to 12 carbon atoms and 1 to 3 heteroatoms. A heteroaromatic hydrocarbon group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 3 to 22 carbon atoms and 1 to 5 heteroatoms, and even more preferably 3 to 12 carbon atoms and 1 to 3 heteroatoms. The heteroatom is preferably selected from the group consisting of a nitrogen atom, an oxygen atom and a sulphur atom.

In formula (I) and (la), R ^1A and R ^3A are preferably independently selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

R ^2A and R ^4A are preferably independently selected from the group consisting of a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

and R ^1A and R ^2A or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound.

Also with these preferred groups R ^1A , R ^2A , R ^3A and R ^4A , at least one of the amino groups - NR ^1A R ^2A and -NR ^3A R ^4A carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom. As will be understood by the skilled reader, this carbon atom in a-position to the nitrogen atom, generally an sp ³ -hybridized carbon atom, may be contained in any of R ^1A , R ^2A , R ^3A and R ^4A . The amino groups -NR ^1A R ^2A and -NR ^3A R ^4A are preferably both tertiary amino groups. Preferably, R ^1A , R ^2A , R ^3A and R ^4A are selected such that -NR ^1A R ^2A and - NR ^3A R ^4A have the same structure. More preferably, R ^1A , R ^2A , R ^3A and R ^4A are selected such that -NR ^1A R ^2A and -NR ^3A R ^4A are both tertiary amino groups and that R ^1A , R ^2A , R ^3A and R ^4A have the same structure.

The optionally substituted groups may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents for the optionally substituted groups are selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may carry in turn one or more, such as one, two or three, substituents selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

In formula (I) and (la), more preferably R ^1A , R ^2A , R ^3A and R ^4A are preferably independently selected from the group consisting of a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic hydrocarbon group which may be substituted, and wherein R ^1A and R ^2A or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound.

Also with these more preferred groups R ^1A , R ^2A , R ^3A and R ^4A , at least one of the amino groups -NR ^1A R ^2A and -NR ^3A R ^4A carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom. As will be understood by the skilled reader, this carbon atom in a-position to the nitrogen atom, generally an sp ³ -hybridized carbon atom, may be contained in any of R ^1A , R ^2A , R ^3A and R ^4A . Preferably, R ^1A , R ^2A , R ^3A and R ^4A are selected such that -NR ^1A R ^2A and - NR ^3A R ^4A have the same structure. More preferably, R ^1A , R ^2A , R ^3A and R ^4A have the same structure.

The optionally substituted groups may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents for the optionally substituted groups are selected from the group consisting of an alkyl group having 1 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

In formula (I) and (la), R ^1A , R ^2A , R ^3A and R ^4A are even more preferably independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl and allyl, and R ^1A and R ^2A or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound. As a preferred ring, a piperidin- 1-yl ring may be mentioned.

Also these even more preferred groups R ^1A , R ^2A , R ^3A and R ^4A are preferably selected such that -NR ^1A R ^2A and -NR ^3A R ^4A have the same structure. More preferably, R ^1A , R ^2A , R ^3A and R ^4A have the same structure.

Regarding the definition of R ^5A in formula (I), preferred embodiments of an aliphatic hydrocarbon group which may be substituted and of an aromatic hydrocarbon group which may be substituted are as defined above.

If R ^5A is an aralkyl group which may be substituted, the aralkyl group is preferably an aralkyl group having 7 to 30 carbon atoms, more preferably an aralkyl group having 7 to 12 carbon atoms. It may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents for the optionally substituted aralkyl group are selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

If R ^5A is -C(0)OR ¹⁰ or -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently an alkyl group, it is preferred that the alkyl group is an alkyl group having 1 to 12 carbon atoms, and more preferred that the alkyl group is an alkyl group having 1 to 6 carbon atoms.

In accordance with a more preferred definition, R ^5A is selected from hydrogen, C1-C6 alkyl optionally substituted by F, such as -CF ₃ , -CN, -C(0)OR ¹ °, and -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently a C1-C6 alkyl group. In accordance with a particularly preferred definition, R ^5A is selected from hydrogen, -CF ₃ , -CN, -C(0)OR ¹ °, and - P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently a C1-C3 alkyl group.

The aminal used in the context of the present invention can be prepared by conventional methods of synthesis, e.g. by reacting an amine, optionally a protected amine, with formaldehyde.

Hemiaminal ether

In the embodiments of the process in accordance with the present invention using a heminaminal ether, a compound comprising a non-aromatic C-C double bond or C-C triple bond is reacted with a reactive component which is obtainable by combining the heminaminal ether with an acidic medium comprising trifluoroacetic acid.

A hemiaminal ether contains an amino group and an alkoxy group bound to the same carbon atom. In the process in accordance with the invention, the reactive component is obtainable using a hemiaminal ether which contains a secondary or a tertiary amino group which carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and the secondary or tertiary amino group is linked to an alkoxy group by a methylene group wherein one hydrogen atom may be replaced by a further substituent. Preferably, the amino group is a tertiary amino group.

As will be understood by the skilled reader, a secondary amino group represents an amino group, wherein two of the three substituents bound to the nitrogen atom are organic groups other than hydrogen. A tertiary amino group represents an amino group wherein the three substituents bound to the nitrogen atom are organic groups other than hydrogen. In the case of the amino group contained in the hemiaminai ether used in the process in accordance with the present invention, one of the three substituent positions is kept by the optionally substituted methylene group as an organic group which links the amino group and the alkoxy group. In other words, in the case of a secondary amino group, one further organic group which is not hydrogen is bound to the nitrogen atom besides the optionally substituted methylene group, and in the case of a tertiary amino group, two further organic groups which are not hydrogen are bound to the nitrogen atom besides the optionally substituted methylene group.

As noted above, the amino group of the hemiaminai ether is linked to the alkoxy group by a methylene group wherein one hydrogen atom may be replaced by a further substituent. As will be understood by the skilled reader, the carbon atom of the methylene group carries the amino group and the alkoxy group as mandatory substituents, so that a further substituent of the methylene group is a substutituent other than the amino groups and the alkoxy group, which substituent replaces one of the two hydrogen atoms of the methylene group. In other words, the secondary or tertiary amino group and the alkoxy group contained in the hemiaminai ether are either linked by a methylene group -CH ₂ - or by a methylene group carrying one substituent other than a hydrogen atom -CHR-. One of the open bonds of these groups is attached to the nitrogen atom of the amino group in the hemiaminai ether, the other open bond is attached to the oxygen atom of the alkoxy group. R is an organic group other than hydrogen.

Moreover, as noted above, an amino group in the hemiaminai ether carries a hydrogen atom at a carbon atom bound in a-position to the nitrogen atom. As will be understood by the skilled reader, a carbon atom bound in a-position to the nitrogen atom is a carbon atom (generally an sp ³ -hybridized carbon atom) which is directly bound to the nitrogen atom. The carbon atom bound in a-position to the nitrogen atom is one which is present in addition to the carbon atom of the optionally substituted methylene group linking the amino groups and the alkoxy group. Thus, the heminaminal ether contains a structural unit which may be represented as or as wherein the -CH ₂ - group represents the methylene group linking the amino group and the alkyoxy group of the hemiaminal ether, and the -CHR- group represents a substituted methylene group linking the amino group and the alkoxy group of the hemiaminal ether, wherein one hydrogen atom of the methylene is replaced by a substituent R, which is an organic group other than hydrogen.

It is noted that the organic groups which are bound to the nitrogen atom of the amino group may include known protective groups for amino groups which may be removed after the hydroaminoalkylation reaction, such as a benzyl group, an allyl group or a Boc group (i.e. a fe/f-butyloxycarbonyl group).

Preferably, the hemiaminal ether which can be used to provide a reactive component in accordance with the present invention is represented by the following formula (II):

wherein

R ^1H is hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

R ^2H is selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted; R ^1H and R ^2H may be bound to each other to form a ring together with the nitrogen atom to which they are bound;

the amino group -NR ^{1 H} R ^2H carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom; R ^3H is an alkyl group;

and R ^4H is selected from the group consisting of hydrogen, an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted, -CN, -C(0)0R ¹ °, and -P(0)(0R ¹¹ )(0R ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently an alkyl group.

In addition, for the definitions of R ^{1 H} , R ^2H , and R ^4H in formula (II), the following preferred meanings apply.

The aliphatic hydrocarbon group has preferably 1 to 30 carbon atoms, more preferably 1 to 24 carbon atoms, and even more preferably 1 to 12 carbon atoms. The aromatic hydrocarbon group has preferably 6 to 30 carbon atoms, more preferably 6 to 22 carbon atoms, and even more preferably 6 to 14 carbon atoms. The aliphatic heterocyclic group has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. The aromatic heterocyclic group has preferably 2 to 30 carbon atoms, more preferably 3 to 22 carbon atoms, and even more preferably 3 to 12 carbon atoms. The aralkyl group has preferably 7 to 30 carbon atoms, more preferably 7 to 24 carbon atoms, and even more preferably 7 to 14 carbon atoms.

The aliphatic heterocyclic group and the aromatic heterocyclic group have independently preferably 1 to 5 heteroatoms, more preferably 1 to 3 heteroatoms. The heteroatom is preferably selected from the group consisting of a nitrogen atom, an oxygen atom and a sulphur atom.

The aliphatic hydrocarbon group, the aromatic hydrocarbon group, the aliphatic heterocyclic group, the aromatic heterocyclic group, alone or in combination, may be substituted with one or more, such as one, two or three, substituents. Exemplary substituents are an aliphatic hydrocarbon group having 1 to 12 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aliphatic heterocyclic group having 2 to 12 carbon atoms and 1 to 3 heteroatoms, an aromatic heterocyclic group having 3 to 12 carbon atoms and 1 to 3 heteroatoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may in turn carry one or more, such as one, two or three, substituents selected from an aliphatic hydrocarbon group having 1 to 12 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aliphatic heterocyclic group having 2 to 12 carbon atoms and 1 to 3 heteroatoms, an aromatic heterocyclic group having 3 to 12 carbon atoms and 1 to 3 heteroatoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

Suitable examples of an aliphatic hydrocarbon group are a linear or branched alkyl group, a cycloalkyl group, a linear or branched alkenyl group, a cycloalkenyl group and a linear or branched alkynyl group. Suitable examples of an aliphatic heterocyclic group are a heterocycloalkyl group and a heterocycloalkenyl group. The aromatic heterocyclic group may also be referred to as a heteroaromatic group.

A linear alkyl group as referred to herein has preferably 1 to 30 carbon atoms, more preferably 1 to 24 carbon atoms, and even more preferably 1 to 12 carbon atoms. A branched alkyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A cycloalkyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A linear alkenyl group as referred to herein has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. A branched alkenyl group as referred to herein has preferably 4 to 30 carbon atoms, more preferably 4 to 24 carbon atoms, and even more preferably 4 to 12 carbon atoms. A cycloalkenyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A linear alkynyl group as referred to herein has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. A branched alkynyl group as referred to herein has preferably 4 to 30 carbon atoms, more preferably 4 to 24 carbon atoms, and even more preferably 4 to 12 carbon atoms. An aromatic hydrocarbon group as referred to herein has preferably 6 to 30 carbon atoms, more preferably 6 to 22 carbon atoms, and even more preferably 6 to 14 carbon atoms. A heterocycloalkyl group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 2 to 24 carbon atoms and 1 to 5 heteroatoms, and even more preferably 2 to 12 carbon atoms and 1 to 3 heteroatoms. A heterocycloalkenyl group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 2 to 24 carbon atoms and 1 to 5 heteroatoms, and even more preferably 2 to 12 carbon atoms and 1 to 3 heteroatoms. A heteroaromatic hydrocarbon group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 3 to 22 carbon atoms and 1 to 5 heteroatoms, and even more preferably 3 to 12 carbon atoms and 1 to 3 heteroatoms. The heteroatom is preferably selected from the group consisting of a nitrogen atom, an oxygen atom and a sulphur atom.

In formula (II), R ^{1 H} is preferably selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

R ^2H is preferably selected from the group consisting of a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

and R ^1H and R ^2H may be bound to each other to form a ring together with the nitrogen atom to which they are bound.

Also with these preferred groups R ^1H and R ^2H , the amino group -NR ^1H R ^2H carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom. As will be understood by the skilled reader, this carbon atom in a-position to the nitrogen atom, generally an sp ³ -hybridized carbon atom, may be contained in any of R ^1H and R ^2H . The amino group -NR ^1H R ^2H is preferably a tertiary amino group. Preferably, R ^1H and R ^2H are selected such that -NR ^{1 H} R ^2H is a tertiary amino group and that R ^{1 H} and R ^2H have the same structure.

The optionally substituted groups may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents for the optionally substituted groups are selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may carry in turn one or more, such as one, two or three, substituents selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

In formula (II), more preferably R ^1H and R ^2H are preferably independently selected from the group consisting of a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic hydrocarbon group which may be substituted, and wherein R ^1H and R ^2H or may be bound to each other to form a ring together with the nitrogen atom to which they are bound.

Also with these more preferred groups R ^1H and R ^2H , the amino group -NR ^1H R ^2H carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom. As will be understood by the skilled reader, this carbon atom in a-position to the nitrogen atom, generally an sp ³ - hybridized carbon atom, may be contained in any of R ^1H and R ^2H . Preferably, R ^1H and R ^2H are selected such that R ^1H and R ^2H have the same structure.

The optionally substituted groups may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents for the optionally substituted groups are selected from the group consisting of an alkyl group having 1 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

In formula (II) R ^1H and R ^2H are even more preferably independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl and allyl, and R ^1H and R ^2H may be bound to each other to form a ring together with the nitrogen atom to which they are bound. As a preferred ring, a piperidin-1-yl ring may be mentioned.

Also these even more preferred groups R ^1H and R ^2H are preferably selected such that R ^{1 H} and R ^2H have the same structure.

R ^3H is an alkyl group, preferably an alkyl group having 1 to 12 carbon atoms, and more preferably an alkyl group having 1 to 6 carbon atoms. Most preferably, R ^3H is selected from from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, and isobutyl.

Regarding the definition of R ^4H in formula (II), preferred embodiments of an aliphatic hydrocarbon group which may be substituted and of an aromatic hydrocarbon group which may be substituted are as defined above.

If R ^4H is an aralkyl group which may be substituted, the aralkyl group is preferably an aralkyl group having 7 to 30 carbon atoms, more preferably an aralkyl group having 7 to 12 carbon atoms. It may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents for the optionally substituted aralkyl group are selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

If R ^4H is -C(0)OR ¹ ° or -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently an alkyl group, it is preferred that the alkyl group is an alkyl group having 1 to 12 carbon atoms, and more preferred that the alkyl group is an alkyl group having 1 to 6 carbon atoms.

In accordance with a more preferred definition, R ^4H is selected from hydrogen, C1-C6 alkyl optionally substituted by F, such as -CF ₃ , -CN, -C(0)OR ¹ °, and -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently a C1 -C6 alkyl group. In accordance with a particularly preferred definition, R ^4H is selected from hydrogen, -CF ₃ , -CN, -C(0)OR ¹ °, and - P(0)(0R ¹¹ )(0R ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently a C1 -C3 alkyl group.

The hemiaminal ether used in the context of the present invention can be prepared by conventional methods of synthesis, e.g. from DMF dimethylacetal, as reported by Risch et al. (Eur. J. Org. Chem. 2005, 387-394).

Compound comprising a non-aromatic C-C double bond

As noted above, embodiments of the invention involve a hydroaminoalkylation reaction of a non-aromatic C-C double bond, whereas other embodiments involvea hydroaminoalkylation reaction of a C-C triple bond.

The compound comprising a non-aromatic C-C double bond (i.e. a non-aromatic double bond which links two carbon atoms) which may be subjected to the reaction with the reactive component is an organic compound which may comprise one non-aromatic C-C double bond or multiple, i.e. two or more, non-aromatic C-C double bonds. If the compound comprises multiple C-C double bonds, the double bonds may be conjugated double bonds. In a case of multiple C-C double bonds, the process in accordance with the invention may be applicable for multiple hydroaminoalkylation reactions in a single compound.

Preferably, the compound comprising a non-aromatic C-C double bond comprises one or two non-aromatic C-C double bonds, more preferably one non-aromatic C-C double bond.

Since the non-aromatic C-C double bond represents the relevant functional feature of the compound subjected to the hydroaminoalkylation reaction, the compound comprising the non-aromatic C-C double bond may also be referred to as an “alkene” herein. Unless indicated otherwise, this reference to an alkene includes the optional presence of optional subsitituents bound to the hydrocarbon core structure of the alkene.

The structure of the compound comprising a non-aromatic C-C double bond is not particularly limited. For example, the non-aromatic C-C double bond may form part of a linear, a branched or a ring structure, or of a linear, a branched or a ring substructure in the compound comprising the non-aromatic C-C double bond. In addition to the non-aromatic C- C double bond, the compound may comprise one or more additional functional groups and/or aromatic double bonds. Moreover, the reference herein to a reaction of a non-aromatic C-C double bond or C-C triple bond does not use the“or” in an exclusive manner, so that the two types of bonds may occur in a single compound.

Preferably, the non-aromatic C-C double bond (or the non-aromatic C-C double bonds, if multiple double bonds are present) is/are selected from a non-substituted, a monosubstituted, a disubstituted and a trisubstituted non-aromatic C-C double bond. More preferably, the non-aromatic C-C double bond (or the non-aromatic C-C double bonds, if multiple double bonds are present) is/are selected from a monosubstited and a disubstituted non-aromatic C-C double bond. As will be understood by the skilled reader, a non-substituted C-C double bond is a C-C double bond wherein neither one of the two carbon atoms linked by the double bond carries a substituent other than a hydrogen (i.e. the compound comprising the non-substituted C-C double bond is ethene). In a monsubstituted C-C double bond, one of the carbon atoms linked by the double bond carries one substituent other than hydrogen. Reference to a disubstituted C-C double bond herein refers, unless specifically indicated otherwise, to a C-C double bond wherein each of the two carbon atoms linked by the double bond carries one substituent other than a hydrogen atom. Accordingly, in a trisubstituted C-C double bond, one of the carbon atoms linked by the double bond carries two substituents other than hydrogen, the other one carries one substituent other than hydrogen. Preferably, the substituents other than hydrogen are substituted or non-substituted hydrocarbon groups.

A preferred, exemplary compound comprising a non-aromatic C-C double bond for use in the process in accordance with the present invention is represented by the following formula (III):

wherein R ⁵ , R ⁶ and R ⁷ are independently hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted, and of combinations thereof, such as an aralkyl group which may be substituted, and wherein R ⁵ and R ⁶ may be bound to each other to form a ring together with the carbon atoms to which they are bound.

The aliphatic hydrocarbon group has preferably 1 to 30 carbon atoms, more preferably 1 to 24 carbon atoms, and even more preferably 1 to 12 carbon atoms. The aromatic hydrocarbon group has preferably 6 to 30 carbon atoms, more preferably 6 to 22 carbon atoms, and even more preferably 6 to 14 carbon atoms. The aliphatic heterocyclic group has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. The aromatic heterocyclic group has preferably 2 to 30 carbon atoms, more preferably 3 to 22 carbon atoms, and even more preferably 3 to 12 carbon atoms. The aralkyl group has preferably 7 to 30 carbon atoms, more preferably 7 to 24 carbon atoms, and even more preferably 7 to 14 carbon atoms.

The aliphatic heterocyclic group and the aromatic heterocyclic group contain independently preferably 1 to 5 heteroatoms, more preferably 1 to 3 heteroatoms. The heteroatom is preferably selected from a nitrogen atom, an oxygen atom and a sulphur atom.

The aliphatic hydrocarbon group, the aromatic hydrocarbon group, the aliphatic heterocyclic group, the aromatic heterocyclic group, alone or in combination, may be substituted by one or more, such as one two or three, substituents. Exemplary substituents are aliphatic hydrocarbon groups having 1 to 12 carbon atoms, aromatic hydrocarbon groups having 6 to 14 carbon atoms, aliphatic heterocyclic groups having 2 to 12 carbon atoms and 1 to 3 heteroatoms, aromatic heterocyclic groups having 3 to 12 carbon atoms and 1 to 3 heteroatoms, halogen atoms, oxo groups, hydroxyl groups, cyano groups, amino groups, carbamoyl groups, carboxyl groups, alkoxy groups having 1 to 10 carbon atoms, alkoxycarbonyl groups having 2 to 10 carbon atoms, alkanoyloxy groups having 2 to 10 carbon atoms, phosphonate groups and trialkylsilyl groups having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may in turn be substituted by one or more, such as one, two or three, substituents selected from aliphatic hydrocarbon groups having 1 to 12 carbon atoms, aromatic hydrocarbon groups having 5 to 14 carbon atoms, aliphatic heterocyclic groups having 2 to 12 carbon atoms and 1 to 3 heteroatoms, aromatic heterocyclic groups having 3 to 12 carbon atoms and 1 to 3 heteroatoms, halogen atoms, oxo groups, hydroxyl groups, cyano groups, amino groups, carbamoyl groups, carboxyl groups, alkoxy groups having 1 to 10 carbon atoms, alkoxycarbonyl groups having 2 to 10 carbon atoms, alkanoyloxy groups having 2 to 10 carbon atoms, phosphonate groups and trialkylsilyl groups having 3 to 30 carbon atoms.

Suitable examples of an aliphatic hydrocarbon group are a linear or branched alkyl group, a cycloalkyl group, a linear or branched alkenyl group, a cycloalkenyl group and a linear or branched alkynyl group. Suitable examples of an aliphatic heterocyclic group are a heterocycloalkyl group and a heterocycloalkenyl group. The aromatic heterocyclic group may also be referred to as a heteroaromatic group.

A linear alkyl group as referred to herein has preferably 1 to 30 carbon atoms, more preferably 1 to 24 carbon atoms, and even more preferably 1 to 12 carbon atoms. A branched alkyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A cycloalkyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A linear alkenyl group as referred to herein has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. A branched alkenyl group as referred to herein has preferably 4 to 30 carbon atoms, more preferably 4 to 24 carbon atoms, and even more preferably 4 to 12 carbon atoms. A cycloalkenyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A linear alkynyl group as referred to herein has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. A branched alkynyl group as referred to herein has preferably 4 to 30 carbon atoms, more preferably 4 to 24 carbon atoms, and even more preferably 4 to 12 carbon atoms. An aromatic hydrocarbon group as referred to herein has preferably 6 to 30 carbon atoms, more preferably 6 to 22 carbon atoms, and even more preferably 6 to 14 carbon atoms. A heterocycloalkyl group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 2 to 24 carbon atoms and 1 to 5 heteroatoms, and even more preferably 2 to 12 carbon atoms and 1 to 3 heteroatoms. A heterocycloalkenyl group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 2 to 24 carbon atoms and 1 to 5 heteroatoms, and even more preferably 2 to 12 carbon atoms and 1 to 3 heteroatoms. A heteroaromatic hydrocarbon group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 3 to 22 carbon atoms and 1 to 5 heteroatoms, and even more preferably 3 to 12 carbon atoms and 1 to 3 heteroatoms. The heteroatom is preferably selected from the group consisting of a nitrogen atom, an oxygen atom and a sulphur atom.

In formula (III), R ⁵ , R ⁶ and R ⁷ are preferably independently selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted, and R ⁵ and R ⁶ may be bound to each other to form a ring together with the carbon atoms to which they are bound.

The optionally substituted groups may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents for the optionally substituted groups are selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, a heteroaromatic group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may in turn carry one or more, such as one, two or three, substituents selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, a heteroaromatic group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

In formula (III), more preferably R ⁵ is selected from the group consisting of hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, an alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic hydrocarbon group which may be substituted; and either

(i) R ⁶ is selected from the group consisting of hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, an alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted; R ⁵ and R ⁶ may be bound to each other to form a ring together with the carbon atoms to which they are bound; and R ⁷ is selected from the group consisting of hydrogen and methyl, and is more preferably hydrogen; or

(ii) R ⁷ is selected from the group consisting of hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, an alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted; and R ⁶ is selected from the group consisting of hydrogen and methyl, and is more preferably hydrogen.

Also in this case, the optionally substituted groups may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents for the optionally substituted groups are selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may in turn carry one or more, such as one, two or three, substituents selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

In formula (III), even more preferably R ⁵ is selected from the group consisting of hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted; and either

(i) R ⁶ is selected from the group consisting of hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, an aromatic hydrocarbon group which may be substituted and an aralkyl group which may be substituted; and R ⁵ and R ⁶ may be bound to each other to form a ring together with the carbon atoms to which they are bound; and R ⁷ is selected from the group consisting of hydrogen and methyl, and is still more preferably hydrogen; or

(ii) R ⁷ is selected from the group consisting of hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, an aromatic hydrocarbon group which may be substituted and an aralkyl group which may be substituted; and R ⁶ is selected from the group consisting of hydrogen and methyl, and is still more preferably hydrogen.

The optionally substituted groups may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents for the optionally substituted groups are selected from an alkyl group having 1 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may in turn carry one or more, such as one, two or three, substituents selected from an alkyl group having 1 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

Compound comprising a C-C triple bond

The compound comprising a C-C triple bond (i.e. a triple bond which links two carbon atoms) which may be subjected to the reaction with the reactive component in accordance with the process of the present invention is an organic compound which may comprise one C-C triple bond or multiple, i.e. two or more, C-C triple bonds. As will be understood by the skilled reader, the triple bond is also a non-aromatic bond. In a case of multiple C-C triple bonds, the process in accordance with the invention may be applicable for multiple hydroaminoalkylation reactions in a single compound.

Preferably, the compound comprising a C-C triple bond comprises one or two C-C triple bonds, more preferably one C-C triple bond.

Since the C-C triple bond represents the relevant functional feature of the compound subjected to the hydroaminoalkylation reaction in accordance with the second aspect of the invention, the compound comprising the C-C triple bond may also be referred to as an “alkyne” herein. Unless indicated otherwise, this reference to an alkyne includes the presence of optional subsitituents bound to the hydrocarbon core structure of the alkyne.

The structure of the compound comprising a C-C triple bond is not particularly limited. For example, the C-C triple bond may form part of a linear, a branched or a ring structure, or of a linear, a branched or a ring substructure in the compound comprising the C-C triple bond. In addition to the C-C triple bond, the compound may comprise one or more further functional groups and/or aromatic double bonds. Moreover, the reference herein to a reaction of a non aromatic C-C double bond or C-C triple bond does not use the“or” in an exclusive manner, so that the two types of bonds may occur in a single compound.

A preferred, exemplary compound comprising a C-C triple bond for use in the process in accordance with the present invention is represented by the following formula (IV): wherein R ⁸ and R ⁹ are independently hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted, and wherein R ⁸ and R ⁹ may be bound to each other to form a ring together with the carbon atoms to which they are bound.

The aliphatic hydrocarbon group has preferably 1 to 30 carbon atoms, more preferably 1 to 24 carbon atoms, and even more preferably 1 to 12 carbon atoms. The aromatic hydrocarbon group has preferably 6 to 30 carbon atoms, more preferably 6 to 22 carbon atoms, and even more preferably 6 to 14 carbon atoms. The aliphatic heterocyclic group has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. The aromatic heterocyclic group has preferably 2 to 30 carbon atoms, more preferably 3 to 22 carbon atoms, and even more preferably 3 to 12 carbon atoms. The aralkyl group has preferably 7 to 30 carbon atoms, more preferably 7 to 24 carbon atoms, and even more preferably 7 to 14 carbon atoms.

The aliphatic heterocyclic group and the aromatic heterocyclic group contain independently preferably 1 to 5 heteroatoms, more preferably 1 to 3 heteroatoms. The heteroatom may be selected from the group consisting of a nitrogen atom, an oxygen atom and a sulphur atom.

The aliphatic hydrocarbon group, the aromatic hydrocarbon group, the aliphatic heterocyclic group, the aromatic heterocyclic group, alone or in combination, may be substituted by one or more, such as one, two or three, substituents. Exemplary substituents are an aliphatic hydrocarbon group having 1 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, an aliphatic heterocyclic group having 2 to 12 carbon atoms and 1 to 3 heteroatoms, an aromatic heterocyclic group having 3 to 12 carbon atoms and 1 to 3 heteroatoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may in turn be substituted by one or more, such as one, two or three, substituents selected from an aliphatic hydrocarbon group having 1 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, an aliphatic heterocyclic group having 2 to 12 carbon atoms and 1 to 3 heteroatoms, an aromatic heterocyclic group having 3 to 12 carbon atoms and 1 to 3 heteroatoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

Suitable examples of an aliphatic hydrocarbon group are a linear or branched alkyl group, a cycloalkyl group, a linear or branched alkenyl group, a cycloalkenyl group and a linear or branched alkynyl group. Suitable examples of an aliphatic heterocyclic group are a heterocycloalkyl group and a heterocycloalkenyl group. The aromatic heterocyclic group may also be referred to as a heteroaromatic group.

A linear alkyl group as referred to herein has preferably 1 to 30 carbon atoms, more preferably 1 to 24 carbon atoms, and even more preferably 1 to 12 carbon atoms. A branched alkyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A cycloalkyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A linear alkenyl group as referred to herein has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. A branched alkenyl group as referred to herein has preferably 4 to 30 carbon atoms, more preferably 4 to 24 carbon atoms, and even more preferably 4 to 12 carbon atoms. A cycloalkenyl group as referred to herein has preferably 3 to 30 carbon atoms, more preferably 3 to 24 carbon atoms, and even more preferably 3 to 12 carbon atoms. A linear alkynyl group as referred to herein has preferably 2 to 30 carbon atoms, more preferably 2 to 24 carbon atoms, and even more preferably 2 to 12 carbon atoms. A branched alkynyl group as referred to herein has preferably 4 to 30 carbon atoms, more preferably 4 to 24 carbon atoms, and even more preferably 4 to 12 carbon atoms. An aromatic hydrocarbon group as referred to herein has preferably 6 to 30 carbon atoms, more preferably 6 to 22 carbon atoms, and even more preferably 6 to 14 carbon atoms. A heterocycloalkyl group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 2 to 24 carbon atoms and 1 to 5 heteroatoms, and even more preferably 2 to 12 carbon atoms and 1 to 3 heteroatoms. A heterocycloalkenyl group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 2 to 24 carbon atoms and 1 to 5 heteroatoms, and even more preferably 2 to 12 carbon atoms and 1 to 3 heteroatoms. A heteroaromatic hydrocarbon group as referred to herein has preferably 2 to 30 carbon atoms and 1 to 5 heteroatoms, more preferably 3 to 22 carbon atoms and 1 to 5 heteroatoms, and even more preferably 3 to 12 carbon atoms and 1 to 3 heteroatoms. The heteroatom is preferably selected from the group consisting of a nitrogen atom, an oxygen atom and a sulphur atom.

In formula (IV), R ⁸ and R ⁹ are preferably independently selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic hydrocarbon group which may be substituted, and wherein R ⁸ and R ⁹ may be bound to each other to form a ring together with the carbon atoms to which they are bound.

The optionally substituted groups may be substituted with a substituent selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may in turn carry one or more, such as one, two or three, substituents selected from an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 12 carbon atoms, a heterocycloalkyl group having 2 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, a cycloalkenyl group having 3 to 12 carbon atoms, an alkynyl group having 2 to 12 carbon atoms, an aromatic hydrocarbon group having 5 to 14 carbon atoms, a heteroaromatic hydrocarbon group having 3 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms.

In formula (IV), more preferably R ⁸ and R ⁹ are independently selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic hydrocarbon group which may be substituted.

The optionally substituted groups may be substituted with a substituent selected from an alkyl group having 1 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Where suitable, these exemplary substituents may in turn carry one or more, such as one, two or three, substituents selected from an alkyl group having 1 to 12 carbon atoms, a halogen atom, an oxo group, a hydroxyl group, a cyano group, an amino group, a carbamoyl group, a carboxyl group, an alkoxy group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 2 to 10 carbon atoms, an alkanoyloxy group having 2 to 10 carbon atoms, a phosphonate group and a trialkylsilyl group having 3 to 30 carbon atoms. Reactive

In the process of the present invention, the compound comprising a non-aromatic C-C double bond or C-C triple bond as discussed above is reacted with a reactive component which is obtainable by combining the aminal or the hemiaminal ether with an acidic medium comprising trifluoroacetic acid (TFA). Thus, the process in accordance with the invention preferably comprises a further step of preparing a reactive component by combining the aminal or the hemiaminal ether with an acidic medium comprising trifluoroacetic acid.

Such a preferred process in accordance with the invention is therefore defined as a process for producing an amine via a hydroaminoalkylation reaction of a non-aromatic C-C double bond or C-C triple bond, said process comprising

a step of preparing a reactive component by combining an aminal or a hemiaminal ether with an acidic medium comprising trifluoroacetic acid, and

a step of reacting a compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component obtained by combining the aminal or the hemiaminal ether with the acidic medium comprising trifluoroacetic acid,

wherein the aminal contains two amino groups independently selected from a secondary and a tertiary amino group that are linked by a methylene group wherein one hydrogen atom may be replaced by a further substituent, and at least one of the amino groups carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and

the hemiaminal ether contains a secondary or a tertiary amino group which carries a hydrogen atom at a carbon atom bound in oposition to its nitrogen atom, and the secondary or tertiary amino group is linked to an alkoxy group by a methylene group wherein one hydrogen atom may be replaced by a further substituent.

The step of preparing the reactive component may be carried out prior to the step of reacting the compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component, or concurrently with the step of reacting the compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component. Preferably, it is carried out prior to the step of reacting the compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component.

Typically, the aminal is combined with the acidic medium simply by mixing the aminal and the acidic medium, with at least the acidic medium being in the form of a liquid. The aminal may be combined with the acidic medium to provide the reactive component e.g. by first providing the acidic medium in a reaction vessel, and adding the aminal, or by first providing the aminal as a first component in a reaction vessel, and adding the acidic medium to the aminal. If the acidic medium comprises more than one component (e.g. TFA and a further organic solvent), the combination of the aminal with the acidic medium may be accomplished in multiple steps, e.g. by first combining the aminal with the organic solvent, and subsequently combining the mixture with the TFA.

Likewise, the hemiaminal ether is typically combined with the acidic medium simply by mixing the hemiaminal ether and the acidic medium, with at least the acidic medium being in the form of a liquid. The hemiaminal ether may be combined with the acidic medium to provide the reactive component e.g. by first providing the acidic medium in a reaction vessel, and adding the hemiaminal ether, or by first providing the hemiaminal ether as a first component in a reaction vessel, and adding the acidic medium to the hemiaminal ether. If the acidic medium comprises more than one component (e.g. TFA and a further organic solvent), the combination of the hemiaminal ether with the acidic medium may be accomplished in multiple steps, e.g. by first combining the hemiaminal ether with the organic solvent, and subsequently combining the mixture with the TFA.

The acidic medium with which the aminal or the hemiaminal ether is combined to provide the reactive component comprises trifluoroacetic acid (TFA) or consists of TFA.

The acidic medium may be neat TFA. Neat TFA means TFA to which no further compounds have been added. Typically, neat TFA has a purity of at least 95 wt%, preferably at least 98 wt%, and more preferably of at least 99 wt%. Since TFA is a hygroscopic substance, the TFA may comprise water, and it is not necessary to dry it before it is used in the process in accordance with the invention.

In an acidic medium comprising TFA, further components may be contained. Preferably, no other proton donating acids (e.g. acids with a pK _A value at 25°C in water of 10 or less) apart from TFA are contained in the acidic medium.

In the acidic medium comprising TFA, the TFA may be present in combination with a further organic solvent. The acidic medium may also consist of TFA and a further organic solvent. Examples of the further organic solvent include benzene, substituted benzene such as chlorbenzene or toluene, dichloroethene (DCE), acetonitrile, ester solvents such as ethyl acetate, dimethylformamide (DMF), dimethylsulfoxide (DMSO), chloroform, dichloromethane (DCM), and alcohols such as methanol, ethanol and isopropanol. The further organic solvent is preferably a polar organic solvent, and more preferably a polar aprotic organic solvent, such as DCE, toluene or acetonitrile. When the acidic medium comprises a further organic solvent, or when it consists of TFA and a further organic solvent, the volume ratio (at 25 °C) of TFA and the further organic solvent in the acidic medium is preferably in the range of 1 :5 to 5:1 , more preferably in the range of 1 :2 to 2:1.

Generally, the TFA is present in the acidic medium in an amount of 1 molar equivalent or more for each mole of C-C double bond or C-C triple bond that is subjected to the hydroaminoalkylation reaction. Preferably, the TFA is present in the acidic medium in an amount of 10 molar equivalents or more, and still more preferably in an amount of 20 molar equivalents or more for each mole of C-C double bond or C-C triple bond that is subjected to the hydroaminoalkylation reaction. Maximum amounts are not particularly limited. However, too high amounts may not be economic. Typically, amounts of 150 molar equivalents or less are used. It is noted that, within these preferred ranges, the optimum amount of the TFA relative to the amount of double or triple bonds can be suitably adjusted depending on the specific structure of the reactants used. For example, it has been found that for reactive components obtained from aminals carrying no further substituent on their methylene group, or from aminals carrying an ester group as a further substituent, particularly preferred results could be obtained if the TFA is present in the acidic medium in amounts of 10 molar equivalents or more, even more preferably 20 molar equivalents or more, and 30 molar equivalents or less, for each mole of C-C double bond or C-C triple bond that is subjected to the hydroaminoalkylation reaction. For reactive components obtained from aminals carrying a fluoroalkyl group as a further substituent on their methylene group, or from hemiaminal ethers, particularly preferred results could be obtained if the TFA is present in the acidic medium in amounts of 100 molar equivalents or more, even more preferably 130 molar equivalents or more, and 150 molar equivalents or less, for each mole of C-C double bond or C-C triple bond that is subjected to the hydroaminoalkylation reaction. The amount of the acidic medium used in the process of the present invention can be adjusted accordingly, depending on the concentration of the TFA in the acidic medium. It will be understood in this regard that the amount of TFA that is present in the reactive component includes the deprotonated form (i.e. a carboxylate anion) of the TFA that may be formed when the acidic medium is combined with the aminal or the hemiaminal ether.

Preferably, to provide the reactive component, the aminal or the heminaminal ether is combined with the acidic medium in an amount of the aminal or the hemiaminal ether of 1 molar equivalent or more, more preferably 1.5 molar equivalents or more, and still more preferably 3 molar equivalents or more, for each mole of C-C double bond or C-C triple bond that is subjected to the hydroaminoalkylation reaction. Maximum amounts are not particularly limited. However, too high amounts may not be economic. Typically, amounts of the aminal or the heminaminal ether of 10 molar equivalents or less, preferably 5 molar equivalents or less are used for each mole of C-C double bond or C-C triple bond that is subjected to the hydroaminoalkylation reaction. It will be understood in this regard that the amount of aminal or hemiaminal ether that is present in the reactive component, together with the amount of iminium ions that may be formed when the acidic medium is combined with the aminal or the hemiaminal ether, corresponds to the amount that is initially combined with the acidic medium.

While the aminal or the hemiaminal ether is combined with the acidic medium, it is advantageous to control the temperature of the mixture wherein the aminal comes into contact with TFA. Preferably, the temperature is controlled to 10 °C or less, more preferably 0 °C or less. As will be understood by the skilled person, the minimum temperature should be higher than the freezing point of the mixture.

Without wishing to be bound by theory, it is assumed that the TFA of the acidic medium interacts as an acid with the aminal (e.g. (1 ), cf. the exemplary reaction scheme 2 in the following) or the hemiaminal ether to provide an iminium ion (e.g. (1a)) as a reactive species in the reactive component. Subsequently, a hydroaminoalkylation reaction takes place, wherein the iminium ion is added as an electrophile to the non-aromatic double bond (e.g. in compound (2)) or triple bond (e.g. in compound (3)), including a hydride shift from a substituent that was originally bound to the nitrogen atom of the aminal. This sequence is shown in the following reaction scheme 2, which is intended as an illustration of the possible mechanism of the reaction underlying the claimed process, and not as a limitation thereof. The dashed bond indicates the position where a single bond will be present if compound (2) is used as a reactant, and a double bond is present if compound (3) is used as a reactant. The groups R, R ^A and R ^B represent any desired atoms or groups, and the aminal, the compound comprising non-aromatic double bond or the compound comprising a triple bond used in the present invention are not limited to the exemplified structures (1 ), (2) and (3).

(Reaction Scheme 2)

The present inventors surprisingly found that the interaction of the aminal or hemiaminal ether with TFA to provide the reactive component allows the hydroaminoalkylation reaction to proceed with an advantageous efficiency, in particular in terms of the yield and the selectivity, compared to reactive species/iminium ions from other sources.

Hvdroaminoalkylation Reaction

In the process of the present invention, the compound comprising a non-aromatic C-C double bond or the compound comprising a C-C triple bond is reacted with the reactive component. All the reactants and their preferred embodiments are described in detail above.

The reaction can be initiated e.g. by simply adding the compound comprising a non-aromatic C-C double bond or triple bond to the reactive component, or by adding the reactive component to the compound comprising a non-aromatic C-C double bond or C-C triple bond, and mixing the two. Alternatively, the reactive component may be formed in the presence of the compound comprising a non-aromatic C-C double bond or triple bond, e.g. by mixing the compound comprising a non-aromatic C-C double bond or triple bond in separate steps with the aminal or heminaminal ether and with the acidic medium, or by mixing it with the aminal or the hemiaminal ether, with TFA, and with any optional constituents of the acidic medium, such as an organic solvent. If necessary, e.g. if a compound comprising a non-aromatic C-C double bond is used which is in a gaseous state under standard conditions (e.g. 25 °C, 100 kPa), the reaction can be carried out under increased pressure in a suitable apparatus.

Generally, no further components are required to carry out the reaction, and the reactive component which comprises TFA optionally in combination with a further organic solvent can be conveniently used as a reaction medium. However, if considered expedient, a further solvent can be used as an additional reaction medium.

The reaction of the compound comprising a non-aromatic C-C double bond or triple bond with the reactive component is typically carried out in the absence of a metal catalyst or a photocatalyst, preferably in the absence of both a metal catalyst and a photocatalyst. As will be understood by the skilled reader, such catalytically active components do not act as reactants themselves, but promote the reaction, e.g. by reducing the required activation energy, or, especially in the case of a photocatalyst, by absorbing light and making the energy of the absorbed light available for the reaction that is to be catalyzed.

The reaction temperature for the reaction between the compound comprising a non-aromatic C-C double bond or the compound comprising a C-C triple bond with the reactive component can be suitably adjusted so that the reaction proceeds at an appropriate rate. In fact, the inventors have found that the reaction can be efficiently carried out at temperatures which are lower than those reported for known hydroaminoalkylation reactions. For example, the reaction can be carried out at a reaction temperature in the range of -20°C to 150°C, preferably -15°C to 100°C, and more preferably -10°C to 90°C. It is noted that, within these preferred ranges, the optimum temperature can be suitably adjusted depending on the specific structure of the reactants used. For example, it has been found that for reactive components obtained from aminals carrying no further substituent on their methylene group, it is advantageous to choose a temperature in the range of 0°C to 150 °C, more preferably 20°C to 100°, and still more preferably 50°C to 90°C. For reactive components obtained from aminals carrying a further substituent on their methylene group, or from hemiaminal ethers, it is advantageous to choose a temperature in the range of -20°C to 50 °C, more preferably - 15°C to 50°, and still more preferably -10°C to 50°C.

A suitable reaction time for the reaction between the compound comprising a non-aromatic C-C double bond or the compound comprising a C-C triple bond with the reactive component is from 10 min to 72 h, preferably from 2 h to 20 h and more preferably from 8 h to 20 h.

Following the reaction of the compound comprising a non-aromatic C-C double bond or triple bond with the reactive component, the process in accordance with the invention allows the structure of the resulting amine to be varied via a further reaction of the product which is obtained from the reaction of the compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component. As illustrated in the above reaction scheme 2, and without wishing to be bound by theory, it is assumed that the combination of the aminal or the hemiaminal ether and the TFA in the reactive component provides an iminium ion as a reactive species, which is added as an electrophile to the non-aromatic double bond or triple bond when the compound comprising a non-aromatic C-C double bond or C-C triple bond is reacted with the reactive component. This addition reaction and a subsequent hydride shift would provide an intermediate product which contains an iminium group.

As a result of the hydroaminoalkylation reaction, the C-C double bond is thus converted into a single bond, and the C-C triple bond is converted into a C-C double bond.

The addition of water to the reaction mixture resulting from the reaction of the compound comprising a non-aromatic C-C double bond or triple bond with the reactive component thus results in the formation of a compound containing a secondary amino group, as illustrated in reaction scheme 2. If a compound comprising a C-C double bond is used as a starting material, this secondary amino group is bound via a methylene group to one of the carbon atoms of the former C-C double bond that has been converted into a single bond by the hydroaminoalkylation reaction. If a compound comprising a C-C triple bond is used as a starting material, the secondary amino group is typically an allylic amino group, i.e. the former C-C triple bond is converted into a double bond by the hydroaminoalkylation reaction, and the secondary amino group is bound via a methylene group to one of the carbon atoms of the former C-C triple bond that has been converted into a double bond.

Thus, in one preferred embodiment, the process in in accordance with the invention further comprises a step wherein water is added to the reaction mixture resulting from the step of reacting a compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component.

For example, the water may be conveniently added in the form of a solution of a base in water. Thus, the addition of the water also accomplishes a work-up of the reaction mixture comprising an acid by neutralizing the acid before the product is isolated. For example, the solution of the base can have a concentration of the base between 0.1 mol/I and 4 mol/l, preferably between 0.5 mol/l and 2 mol/l. Examples of the base comprise ammonia, a metal carbonate, a metal hydrogencarbonate and a metal hydroxide. The metal is preferably selected from sodium, potassium, calcium, lithium and magnesium. Preferred examples of the base are sodium hydroxide, potassium hydroxide, calcium carbonate and calcium hydrogencarbonate. In another preferred embodiment, the process in accordance with the invention further comprises a step wherein an organic nucleophilic reactant is added to the reaction mixture resulting from the step of reacting a compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component.

The addition of such a nucleophilic organic reactant allows a tertiary amine to be provided. In this regard, it is assumed that the nucleophilic organic reactant can undergo a direct reaction with an intermediate product which contains an iminium group as illustrated in reaction scheme 2 above. The resulting amine contains a tertiary amino group. If a compound comprising a C-C double bond is used as a starting material, also this tertiary amino group is bound via a methylene group to one of the carbon atoms of the former C-C double bond that has been converted into a single bond by the hydroaminoalkylation reaction. If a compound comprising a C-C triple bond is used as a starting material, this tertiary amino group is typically an allylic amino group, i.e. the former C-C triple bond is converted into a double bond by the hydroaminoalkylation reaction, and the tertiary amino group is bound via a methylene group to one of the carbon atoms of the former C-C triple bond that has been converted into a double bond.

Examples of suitable nucleophilic reactants include a-CH acidic compounds as they are used as reactants in a Mannich reaction, e.g. ketones with an a-CH group such as acetone or acetophenone. They further include electron-rich aromatic rings or heteroaromatic rings, such as 1 ,3,5-trimethoxybenzene, indole, pyrrole or benzothiophene. These aromatic or heteroaromatic rings can undergo a Friedel-Crafts-type alkylation reaction with a cationic intermediate product as shown in reaction scheme 2. Following the reaction with the nucleophilic organic reactant, a solution of a base in water can be added before the product is isolated.

In line with the above, in a preferred embodiment the process in accordance with the present invention can be defined as a process for producing an amine via a hydroaminoalkylation reaction of a non-aromatic C-C double bond or C-C triple bond, said process comprising a step of reacting a compound comprising a non-aromatic C-C double bond or C-C triple bond with a reactive component obtainable by combining an aminal or a hemiaminal ether with an acidic medium comprising trifluoroacetic acid, and

a step of adding water or a nucleophilic organic reactant to the reaction mixture resulting from the step of reacting a compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component,

wherein the aminal contains two amino groups independently selected from a secondary and a tertiary amino group that are linked by a methylene group wherein one hydrogen atom may be replaced by a further substituent, and at least one of the amino groups carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and

the hemiaminal ether contains a secondary or a tertiary amino group which carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and the secondary or tertiary amino group is linked to an alkoxy group by a methylene group wherein one hydrogen atom may be replaced by a further substituent.

In a still further preferred embodiment, as indicated above, the process for producing an amine via a hydroaminoalkylation reaction of a non-aromatic C-C double bond or C-C triple bond, is thus a process comprising

a step of preparing a reactive component by combining an aminal or a hemiaminal ether with an acidic medium comprising trifluoroacetic acid,

a step of reacting a compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component obtained by combining the aminal or the hemiaminal ether with the acidic medium comprising trifluoroacetic acid, and

a step of adding water to the reaction mixture resulting from the step of reacting a compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component, wherein the aminal contains two amino groups independently selected from a secondary and a tertiary amino group that are linked by a methylene group wherein one hydrogen atom may be replaced by a further substituent, and at least one of the amino groups carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and

the hemiaminal ether contains a secondary or a tertiary amino group which carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and the secondary or tertiary amino group is linked to an alkoxy group by a methylene group wherein one hydrogen atom may be replaced by a further substituent.

Moreover, conventional steps in amine synthesis reactions can be comprised in the process according to the present invention, such as the protection or the deprotection of an amino group. For example, if an aminal is used in the process in accordance with the invention wherein an amino group is a protected amino group, such as an amino group protected by a benzyl group, an allyl group or a Boc-group, the process of the present invention may further comprise a step of a deprotection of the amino group following the reaction of a compound comprising a non-aromatic C-C double bond or C-C triple bond with the reactive component. The deprotection reaction is not particularly limited and typical deprotection reactions are known in the art. Alternatively, where desired, it is also possible to protect an amine resulting from the hydroaminoalkylation reaction by introducing a protective group for the amine, e,g, a benzyl group, an allyl group or a Boc-group.

Finally, it will be understood that also typical steps for the isolation and/or the purification of a desired product can form part of the process in accordance with the invention, so that the desired product or products can be obtained in high yields and a good quality.

Important aspects of the present invention are summarised in the following items. It will be understood that those items referring back to a preceding item reflect preferred embodiments of the invention.

1. A process for producing an amine via a hydroaminoalkylation reaction of a non-aromatic C-C double bond or C-C triple bond, said process comprising

a step of reacting a compound comprising a non-aromatic C-C double bond or C-C triple bond with a reactive component which is obtainable by combining an aminal or a hemiaminal ether with an acidic medium comprising trifluoroacetic acid (TFA),

wherein the aminal contains two amino groups independently selected from a secondary and a tertiary amino group that are linked by a methylene group wherein one hydrogen atom may be replaced by a further substituent, and at least one of the amino groups carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and

the hemiaminal ether contains a secondary or a tertiary amino group which carries a hydrogen atom at a carbon atom bound in a-position to its nitrogen atom, and the secondary or tertiary amino group is linked to an alkoxy group by a methylene group wherein one hydrogen atom may be replaced by a further substituent.

2. The process according to item 1 , which is a process for producing an amine via a hydroaminoalkylation reaction of a non-aromatic C-C double bond, and which comprises a step of reacting a compound comprising a non-aromatic C-C double bond with a reactive component which is obtainable by combining the aminal with an acidic medium comprising trifluoroacetic acid.

3. The process according to item 2, which comprises a step of preparing the reactive component by combining the aminal with the acidic medium comprising trifluoroacetic acid.

4. The process according to item 2 or 3, wherein the acidic medium is neat TFA. 5. The process according to item 2 or 3, wherein the acidic medium comprises a further organic solvent, more preferably selected from the group consisting of benzene which may be substituted, dichloroethene, acetonitrile, ester solvents, dimethylformamide, dimethylsulfoxide, chloroform, dichloromethane, and alcohols.

6. The process according to any of items 2 to 5, wherein the acidic medium comprises TFA in an amount of 1 molar equivalent or more, more preferably 10 molar equivalents or more, and still more preferably 20 molar equivalents or more, for each mole of non-aromatic C-C double bond that is subjected to the hydroaminoalkylation reaction.

7. The process according to any of items 2 to 6, wherein the aminal is represented by the following formula (I):

wherein

R ^1A and R ^3A are independently hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

R ^2A and R ^4A are independently selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

and R ^1A and R ^2A or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound, or one of R ^1A and R ^2A and one of R ^3A and R ^4A may be bound to each other to form a ring together with the optionally substituted methylene group and the nitrogen atoms to which they are bound;

and at least one of the amino groups -NR ^1A R ^2A and -NR ^3A R ^4A carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom,

and wherein R ^5A is selected from the group consisting of hydrogen, an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted, -CN, -C(0)0R ¹ °, and -P(0)(0R ¹¹ )(0R ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently an alkyl group.

8. The process according to item 7, wherein, in formula (I), R ^5A is selected from hydrogen, C1-C6 alkyl optionally substituted by F, -CN, -C(0)OR ¹ °, and -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently a C1-C6 alkyl group.

9. The process according to any of items 2 to 6, wherein the aminal is represented by the following formula (la):

R ^2A R ^1A N ^{' '} NR ,3 ³ A ^A _D R4A

/ \ wherein

R ^1A and R ^3A are independently hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

R ² ' ⁴ and R ^4A are independently selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

and R ^1A and R ^2A or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound, or one of R ^1A and R ^2A and one of R ^3A and R ^4A may be bound to each other to form a ring together with the methylene group and the nitrogen atoms to which they are bound;

and at least one of the amino groups -NR ^1A R ^2A and -NR ^3A R ^4A carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom.

10. The process according to any of items 7 to 9, wherein, in formula (I) and (la),

R ^1A and R ^3A are independently selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

R ^2A and R ^4A are independently selected from the group consisting of a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

and R ^1A and R ^¾ or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound.

11. The process according to any of items 7 to 10, wherein R ^1A , R ^2A , R ^3A and R ^4A are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl and allyl.

12. The process according to any of items 7 to 10, wherein R ^1A and R ^2A or R ^3A and R ^4A , respectively, are bound to each other to form a ring together with the nitrogen atom to which they are bound, more preferably a piperidin-1-yl ring.

13. The process according to any of items 7 to 12, wherein R ^1A , R ^2A , R ^3A and R ^4A are selected such that the groups -NR ^1A R ^2A and -NR ^3A R ^4A are identical.

14. The process according to any of items 7 to 13, wherein R ^1A , R ^2A , R ^3A and R ^4A are identical.

15. The process according to any of items 2 to 14, wherein the aminal is combined in an amount of 1 molar equivalent or more, more preferably 1.5 molar equivalents or more, and still more preferably 3 molar equivalents or more, for each mole of non-aromatic C-C double bond that is subjected to the hydroaminoalkylation reaction, with the acidic medium.

16. The process according to item 1 , which is a process for producing an amine via a hydroaminoalkylation reaction of a non-aromatic C-C double bond, and which comprises a step of reacting a compound comprising a non-aromatic C-C double bond with a reactive component which is obtainable by combining the hemiaminal ether with an acidic medium comprising trifluoroacetic acid.

17. The process according to item 16, which comprises a step of preparing the reactive component by combining the hemiaminal ether with the acidic medium comprising trifluoroacetic acid.

18. The process according to item 16 or 17, wherein the acidic medium is neat TFA.

19. The process according to item 16 or 17, wherein the acidic medium comprises a further organic solvent, more preferably selected from the group consisting of benzene which may be substituted, dichloroethene, acetonitrile, ester solvents, dimethylformamide, dimethylsulfoxide, chloroform, dichloromethane, and alcohols.

20. The process according to any of items 16 to 19, wherein the acidic medium comprises TFA in an amount of 1 molar equivalent or more, more preferably 10 molar equivalents or more, still more preferably 20 molar equivalents or more, even more preferably 100 molar equivalents or more, and most preferably 130 molar equivalents or more, for each mole of non-aromatic C-C double bond that is subjected to the hydroaminoalkylation reaction.

21. The process according to any of items 16 to 20, wherein the hemiaminal ether is represented by the following formula (II):

wherein

R ^1H is hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

R ^2H is selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted; R ^1H and R ^2H may be bound to each other to form a ring together with the nitrogen atom to which they are bound;

the amino group -NR ^1H R ^2H carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom;

R ^3H is an alkyl group;

and R ^4H is selected from the group consisting of hydrogen, an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted, -CN, -C(0)0R ¹ °, and -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently an alkyl group.

22. The process according to item 21 , wherein, in formula (II), R ^4H is selected from hydrogen, C1-C6 alkyl optionally substituted by F, -CN, -C(0)0R ¹ °, and -P(0)(0R ¹¹ )(0R ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently a C1 -C6 alkyl group.

23. The process according to any of items 21 or 22, wherein, in formula (II),

R ^1H is selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

R ^2H is selected from the group consisting of a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

R ^1H and R ^2H may be bound to each other to form a ring together with the nitrogen atom to which they are bound;

and R ^3H is an alkyl group.

24. The process according to any of items 21 to 23, wherein R ^1H , and R ^2H are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl and allyl,

and R ^3H is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, and isobutyl.

25. The process according to any of items 21 to 24, wherein R ^1H and R ^2H are identical. 26. The process according to any of items 16 to 25, wherein the hemiaminal ether is combined in an amount of 1 molar equivalent or more, more preferably 1.5 molar equivalents or more, and still more preferably 3 molar equivalents or more, for each mole of non-aromatic C-C double bond that is subjected to the hydroaminoalkylation reaction, with the acidic medium.

27. The process according to any of items 2 to 26, wherein the compound comprising a non-aromatic C-C double bond is represented by the following formula (III):

wherein R ⁵ , R ⁶ and R ⁷ are independently hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, and wherein R ⁵ and R ⁶ may be bound to each other to form a ring together with the carbon atoms to which they are bound.

27. The process according to item 27, wherein R ⁵ , R ⁶ and R ⁷ are independently selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted, and R ⁵ and R ⁶ may be bound to each other to form a ring together with the carbon atoms to which they are bound.

28. The process according to item 27 or 28, wherein

R ⁵ is selected from the group consisting of hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, an alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic hydrocarbon group which may be substituted; and either

(i) R ⁶ is selected from the group consisting of hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, an alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted; R ⁵ and R ⁶ may be bound to each other to form a ring together with the carbon atoms to which they are bound; and R ⁷ is selected from the group consisting of hydrogen and methyl, and is more preferably hydrogen; or

(ii) R ⁷ is selected from the group consisting of hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, an alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted; and R ⁶ is selected from the group consisting of hydrogen and methyl, and is more preferably hydrogen.

29. The process according to any of items 2 to 28, wherein said step of reacting the compound comprising a non-aromatic C-C double bond with the reactive component is carried out in the absence of a metal catalyst.

30. The process according to any of items 2 to 29, wherein said step of reacting the compound comprising a non-aromatic C-C double bond with the reactive component is carried out in the absence of a photocatalyst.

31. The process according to any of items 2 to 30, wherein said step of reacting the compound comprising a non-aromatic C-C double bond with the reactive component is carried out at a reaction temperature in the range of -20°C to 150°C, more preferably -15 to 100 °C, still more preferably -10 to 90°C.

32. The process according to any of items 2 to 31 , wherein the reaction time for the reaction of the compound comprising a non-aromatic C-C double bond with the reactive component ranges from 10 min to 72 h, more preferably from 2 h to 20 h, still more preferably from 8 h to 20 h.

33. The process according to any of items 2 to 32, which further comprises a step wherein water is added to the reaction mixture resulting from the step of reacting a compound comprising a non-aromatic C-C double bond with the reactive component. 34. The process according to any of items 2 to 32, which further comprises a step wherein an organic nucleophilic reactant is added to the reaction mixture resulting from the step of reacting a compound comprising a non-aromatic C-C double bond with the reactive component.

35. The process according to any of items 2 to 34, wherein at least one of the amino groups of the aminal or the amino group of the hemiaminal ether is a protected amino group, and wherein said process further comprises a step of a deprotection of the amino group following the reaction of a compound comprising a non-aromatic C-C double bond.

36. The process according to item 1 , which is a process for producing an amine via a hydroaminoalkylation reaction of a compound comprising a C-C triple bond, and which comprises a step of reacting a compound comprising a C-C triple bond with a reactive component which is obtainable by combining the aminal with an acidic medium comprising trifluoroacetic acid.

37. The process according to item 36, wherein the process yields an allylic amine.

38. The process according to item 36 or 37, which comprises a step of preparing the reactive component by combining the aminal with the acidic medium comprising trifluoroacetic acid.

39. The process according to any of items 36 to 38, wherein the acidic medium is neat TFA.

40. The process according to any of items 36 to 38, wherein the acidic medium comprises a further organic solvent, more preferably selected from the group consisting of benzene which may be substituted, dichloroethene, acetonitrile, ester solvents, dimethylformamide, dimethylsulfoxide, chloroform, dichloromethane, and alcohols.

41. The process according to any of items 36 to 40, wherein the acidic medium comprises TFA in an amount of 1 molar equivalents or more, more preferably 10 molar equivalents or more, and still more preferably 20 molar equivalents or more, for each mole of C-C triple bond that is subjected to the hydroaminoalkylation reaction.

42. The process according to any of items 36 to 41 , wherein the aminal is represented by the following formula (I): wherein

R ^1A and R ^3A are independently hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

R ^2A and R ^4A are independently selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

and R ^1A and R ^2A or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound, or one of R ^1A and R ^2A and one of R ^3A and R ^4A may be bound to each other to form a ring together with the optionally substituted methylene group and the nitrogen atoms to which they are bound;

and at least one of the amino groups -NR ^1A R ^2A and -NR ^3A R ^4A carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom;

and wherein R ^5A is selected from the group consisting of hydrogen, an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted, -CN, -C(0)OR ¹ °, and -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently an alkyl group.

43. The process according to item 42, wherein, in formula (I), R ^5A is selected from hydrogen, C1 -C6 alkyl optionally substituted by F, -CN, -C(0)OR ¹ °, and -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently a C1 -C6 alkyl group.

44. The process according to any of items 36 to 41 , wherein the aminal is represented by the following formula (la):

R i2A ^A pR 1 ¹ A ^A iN ^' NR ,3 ^J A ^A pR4' A

(la), wherein

R ^1A and R ^3A are independently hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

R ^2A and R ^4A are independently selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

and R ^1A and R ^2A or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound, or one of R ^1A and R ^2A and one of R ^3A and R ^4A may be bound to each other to form a ring together with the methylene group and the nitrogen atoms to which they are bound;

and at least one of the amino groups -NR ^1A R ^2A and -NR ^3A R ^4A carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom.

45. The process according to any of items 42 to 44, wherein, in formula (I) and (la),

R ^1A and R ^3A are independently selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

R ^2A and R ^4A are independently selected from the group consisting of a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

and R ^1A and R ^2A or R ^3A and R ^4A , respectively, may be bound to each other to form a ring together with the nitrogen atom to which they are bound.

46. The process according to any of items 42 to 45, wherein R ^1A , R ^2A , R ^3A and R ^4A are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl and allyl.

47. The process according to any of items 42 to 45, wherein R ^1A and or R ^3A and R ^4A , respectively, are bound to each other to form a ring together with the nitrogen atom to which they are bound, more preferably a piperidin-1-yl ring.

48. The process according to any of items 42 to 47, wherein R ^1A , R ^2A , R ^3A and R ^4A are selected such that the groups -NR ^1A R ^2A and -NR ^3A R ^4A are identical.

49. The process according to any of items 42 to 48, wherein R ^1A , R ^2A , R ^3A and R ^4A are identical.

50. The process according to any of items 36 to 49, wherein the aminal is combined in an amount of 1 molar equivalent or more, more preferably 1.5 molar equivalents or more, and still more preferably 3 molar equivalents or more, for each mole of C-C triple bond that is subjected to the hydroaminoalkylation reaction, with the acidic medium.

51. The process according to item 1 , which is a process for producing an amine via a hydroaminoalkylation reaction of a C-C triple bond, and which comprises a step of reacting a compound comprising a C-C triple bond with a reactive component which is obtainable by combining the hemiaminal ether with an acidic medium comprising trifluoroacetic acid.

52. The process according to item 51 , wherein the process yields an allylic amine.

53. The process according to item 51 or 52, which comprises a step of preparing the reactive component by combining the hemiaminal ether with the acidic medium comprising trifluoroacetic acid.

54. The process according to any of items 51 to 53, wherein the acidic medium is neat TFA.

55. The process according to any of items 51 to 53, wherein the acidic medium comprises a further organic solvent, more preferably selected from the group consisting of benzene which may be substituted, dichloroethene, acetonitrile, ester solvents, dimethylformamide, dimethylsulfoxide, chloroform, dichloromethane, and alcohols. 56. The process according to any of items 51 to 55, wherein the acidic medium comprises TFA in an amount of 1 molar equivalent or more, more preferably 10 molar equivalents or more, still more preferably 20 molar equivalents or more, even more preferably 100 molar equivalents or more, and most preferably 130 molar equivalents or more, for each mole of C-C triple bond that is subjected to the hydroaminoalkylation reaction.

57. The process according to any of items 51 to 56, wherein the hemiaminal ether is represented by the following formula (II):

wherein

R ^1H is hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted;

R ^2H is selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, such as an aralkyl group which may be substituted; R ^1H and R ^2H may be bound to each other to form a ring together with the nitrogen atom to which they are bound;

the amino group -NR ^1H R ^2H carries a hydrogen atom at a carbon atom in a-position to the nitrogen atom;

R ^3H is an alkyl group;

and R ^4H is selected from the group consisting of hydrogen, an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted, -CN, -C(0)OR ¹ °, and -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently an alkyl group.

58. The process according to item 57, wherein, in formula (II), R ^4H is selected from hydrogen, C1-C6 alkyl optionally substituted by F, -CN, -C(0)OR ¹ °, and -P(0)(OR ¹¹ )(OR ¹² ), wherein R ¹⁰ , R ¹¹ and R ¹² are independently a C1-C6 alkyl group. 59. The process according to any of items 57 or 58, wherein, in formula (II),

R ^1H is selected from the group consisting of hydrogen, a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

R ^2H is selected from the group consisting of a linear or branched alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, a linear or branched alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, a linear or branched alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic group which may be substituted;

R ^1H and R ^2H may be bound to each other to form a ring together with the nitrogen atom to which they are bound;

and R ^3H is an alkyl group.

60. The process according to any of items 57 to 59, wherein R ^1H and R ^2H are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl and allyl, and , R ^3H is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl and allyl

61. The process according to any of items 57 to 60, wherein R ^1H and R ^2H are identical.

62. The process according to any of items 57 to 61 , wherein the hemiaminal ether is combined in an amount of 1 molar equivalent or more, more preferably 1.5 molar equivalents or more, and still more preferably 3 molar equivalents or more, for each mole of non-aromatic C-C triple bond that is subjected to the hydroaminoalkylation reaction, with the acidic medium.

63. The process according to any of items 36 to 62, wherein the compound comprising a C-C triple bond is represented by the following formula (IV): wherein R ⁸ and R ⁹ are independently hydrogen or selected from the group consisting of an aliphatic hydrocarbon group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aliphatic heterocyclic group which may be substituted, an aromatic heterocyclic group which may be substituted and of combinations thereof, and

wherein R ⁸ and R ⁹ may be bound to each other to form a ring together with the carbon atoms to which they are bound.

64. The process according to item 63, wherein R ⁸ and R ⁹ are independently selected from the group consisting of a hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, an alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic hydrocarbon group which may be substituted, and

wherein R ⁸ and R ⁹ may be bound to each other to form a ring together with the carbon atoms to which they are bound.

65. The process according to item 63 or 64, wherein R ⁸ and R ⁹ are independently selected from the group consisting of a hydrogen, an alkyl group which may be substituted, a cycloalkyl group which may be substituted, a heterocycloalkyl group which may be substituted, an alkenyl group which may be substituted, a cycloalkenyl group which may be substituted, an alkynyl group which may be substituted, an aromatic hydrocarbon group which may be substituted, an aralkyl group which may be substituted and a heteroaromatic hydrocarbon group which may be substituted.

66. The process according to any of items 36 to 65, wherein said step of reacting the compound comprising a C-C triple bond with the reactive component is carried out in the absence of a metal catalyst.

67. The process according to any of items 36 to 66, wherein said step of reacting the compound comprising a C-C triple bond with the reactive component is carried out in the absence of a photocatalyst.

68. The process according to any of items 36 to 67, wherein said step of reacting the compound comprising a C-C triple bond with the reactive component is carried out at a reaction temperature in the range of -20°C to 150°C, more preferably -15 to 100 °C, still more preferably -10 to 90°C. 69. The process according to any of items 36 to 68, wherein the reaction time for the reaction of the compound comprising a C-C triple bond with the reactive component ranges from 10 min to 72 h, more preferably from 2 h to 20 h, still more preferably from 8 h to 20 h. 70. The process according to any of items 36 to 69, which further comprises a step wherein water is added to the reaction mixture resulting from the step of reacting a compound comprising a C-C triple bond with the reactive component.

71. The process according to any of items 36 to 69, which further comprises a step wherein an organic nucleophilic reactant is added to the reaction mixture resulting from the step of reacting a compound comprising a C-C triple bond with the reactive component.

72. The process according to any of items 36 to 71 , wherein at least one of the amino groups of the aminal or the amino group of the hemiaminal ether is a protected amino group, and wherein said process further comprises a step of a deprotection of the amino group following the reaction of a compound comprising a C-C triple bond.

Examples

Hvdroaminoalkylation of Alkenes or Alkvnes using a Reactive Component obtained from non-substituted Aminals R _? N-CH?-NR?

General Information

All glassware was oven dried at 100 °C before use. All solvents were distilled from appropriate drying agents prior to use. All reagents were used as received from commercial suppliers unless otherwise stated. Neat infrared spectra were recorded using a Perkin-Elmer Spectrum 100 FT-IR spectrometer. Wavenumbers (v = 1/l) are reported in crrf ¹ . Mass spectra were obtained using a Finnigan MAT 8200 (70 eV) or an Agilent 5973 (70 eV) spectrometer, using electrospray ionization (ESI) All ¹ H NMR and ¹³ C NMR experiments were recorded using Bruker AV-400, AV-600 and AV-700 spectrometers at 300 K. Chemical shifts (d) are quoted in ppm and coupling constants (J) are quoted in Hz. The 7.26 ppm resonance of residual CHCI ₃ for proton spectra and 77.16 ppm resonance for carbon spectra were used as internal references. ¹ H NMR splitting patterns were designated as singlet (s), doublet (d), triplet (t), quartet (q) or combinations thereof, as well as broad (br). Splitting patterns that could not be interpreted were designated as multiplet (m). Reaction progress was monitored by thin layer chromatography (TLC) performed on aluminum plates coated with kieselgel F254 with 0.2 mm thickness. Visualization was achieved by a combination of ultraviolet light (254 nm) and acidic potassium permanganate. Flash column chromatography was performed using silica gel 60 (230-400 mesh, Merck and co.).

Procedures for the Synthesis of Starting Materials

General Procedure for the Synthesis of Aminals

O Rl ,R ² neat, 23 °C, 12 h

Jl + N - ►-

H H ^H

(37% aq.) (2 equiv.)

To a round-bottom flask charged with the corresponding free secondary amine (for amines available only as the corresponding salts, 2.00 equiv. of potassium carbonate are added to the reaction mixture) (2.00 equiv.) and a magnetic stir-bar at 0 °C, an aqueous solution of formaldehyde (37%, 1.00 equiv.) was added dropwise and the resulting biphasic mixture was stirred vigorously at ambient temperature (23 °C) for 12 h. The following work-up was dependent on the volatility of the resulting aminal.

Work-up A (for volatile products): Solid potassium hydroxide was added to the reaction mixture until saturation of the aqueous layer was observed. The phases were subsequently separated and the aqueous phase was extracted with diethyl ether (2 *). The organic phases were combined, dried over anhydrous potassium carbonate and filtered. The filtrate was then carefully concentrated under reduced pressure with mild heating, affording the title compound is sufficient purity for further use.

Work-up B (for non-volatile products): The biphasic mixture was separated and the aqueous phase was extracted with ethyl acetate (3 *). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure, in most cases affording the title compound in sufficient purity for further use. In the case of incomplete conversion, remaining unreacted amine could be removed by subjection to high vacuum. V,W,A/',/V'-Tetrabutyldiaminomethane (2b)

quant.; ¹ H NMR (400 MHz, CDCI ₃ ) d 2.99 (s, 2H), 2.43 (t, J = 7.5 Hz, 8H), 1.42-1.23 (m, 16H), 0.90 (t, J = 7.3 Hz, 12H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 75.7, 52.1 (4C), 29.5 (4C), 20.9 (4C), 14.3 (4C); IR (neat) v _max : 2955, 2928, 2860, 2799, 2737, 1462, 1375, 1304, 1266, 1240,

1182, 1079; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₇ H ₃₉ N ₂ ) requires mlz 271.3108, found m/z 130.1592 (corresponding to L/,/V-dibutylamine).

N,N,N',N'- Tetrapropyldiaminomethane (2c)

80% yield; used as a crude containing 20% dipropylamine ¹ H NMR (400 MHz, CDCI ₃ ) d 3.01 (s, 2H), 2.42-2.39 (m, 8H), 1.45-1.39 (m, 8H), 0.86 (t, J = 7.5 Hz, 12H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 75.7, 54.4 (4C), 20.5 (4C), 12.6 (4C); IR (neat) 2957, 2932, 2872, 2800, 1463, 1377, 1192, 1172; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₃ H ₃₁ N ₂ ) requires mlz 215.2482, found m/z 102.1278 (corresponding to A/,/\/-dipropylamine). /V,/V,/V',A/'-Tetraisobutyldiaminomethane (2d)

Ca. 30% yield, used as a crude mixture; ¹ H NMR (400 MHz, CDCI ₃ ) d 3.28 (s, 2H), 2.37 (d, J = 7.3 Hz, 8H), 1.78-1.70 (m, 4H), 0.90 (d, J = 6.6 Hz, 24H).

Lί,L/,L ,/V'-Tetrabenzyldiaminomethane (2e)

92% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.33-7.26 (m, 16H), 7.26-7.22 (m, 4H), 3.63 (s, 8H), 3.1 1 (s, 2H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 139.9 (4C), 129.1 (8C), 128.3 (8C), 126.9 (4C),

72.4, 56.3 (4C); IR (neat) v _max : 3060, 3026, 2927, 2795, 1493, 1451 , 1245, 1 125, 1072, 1028, 974, 914; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C29H ₃₁ N ₂ ) requires m/z 407.2482, found m/z 198.1281 (corresponding to A/,A/-dibenzylamine).

L/,L/,L/',LG-Tetraallyldiaminomethane (2f)

70% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 5.89-5.77 (m, 4H), 5.17-5.06 (m, 8H), 3.15 (dt, J = 6.4, 1.3 Hz, 8H), 3.1 1 (s, 2H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 136.4 (4C), 1 16.8 (4C), 72.5, 54.7 (4C); IR (neat) v _max : 3077, 2978, 2920, 2801 , 1642, 1446, 1417, 1399, 1350, 1259, 1 159, 994, 913; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₃ H ₂ 3N ₂ ) requires m/z 207.1865, found m/z 98.0694 (corresponding to /V,/V-diallylamine). /V,/V,/V’,Ar-Tetrakis(methyl-d ₃ )diaminomethane (2a-d ₁₂ )

yield not determined-isolated as a ~30 mol% solution in diethyl ether and used without further purification; ¹ H NMR (600 MHz, CDCI ₃ ) d 2.69 (s, 2H);

A/,A/'-Dibutyl-A/,A/’-bis(butyl-d ₉ )diami nomethane (2b-d ₁₈ )

87% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 2.99 (s, 2H), 2.43 (t, J = 7.5 Hz, 4H), 1.42-1.24 (m, 8H), 0.90 (t, J = 7.2 Hz, 6H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 75.6, 52.0 (2C), 51.1 (t, J = 20.3

Hz), 29.6 (2C), 20.9 (2C), 14.3 (2C), 13.0 (t, J = 19.1 Hz)-two signals could not be identified; IR (neat) v _max : 2956, 2929, 2861 , 2215, 1463, 1376, 1 190, 1057; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₇ H2iD ₁₈ N ₂ ) requires mlz 289.4238, found m/z 139.2156 (corresponding to A/-butylbutan-d _g -1 -amine).

Di(piperidin-1-yl)methane (2g)

92% yield; NMR (400 MHz, CDCI ₃ ) d 2.83 (s, 2H), 2.40 (t, J = 5.5 Hz, 8H), 1.54 (pent, J = 5.5 Hz, 8H), 1.46-1.39 (m, 4H).

Synthesis of Alkene Substrates

1 -(1-Pyrrolidinyl)-10-undecen-1 -one (1a) To a solution of pyrrolidine (0.452 ml_, 0.391 g, 5.5 mmol, 1.1 equiv.) and triethylamine (1 39 mL, 1.012 g, 10 mmol, 2.00 equiv.) in DCM (20 mL) at 0 °C, 10-undecenoyl chloride (1.08 mL, 1.014 g, 5 mmol, 1 equiv.) was added dropwise and the resulting reaction mixture was allowed to warm to room temperature while stirring overnight (14 h). After this time, a saturated aqueous solution of sodium bicarbonate was added and the biphasic system was separated. The aqueous phase was extracted with DCM (1 *) and the organic phases were combined and dried over anhydrous sodium sulfate. The dried solution was filtered and concentrated under reduced pressure. The resulting crude material was purified by flash column chromatography on silica gel (heptane/ethyl acetate) to afford the desired compound; Quant.; ¹ H NMR (400 MHz, CDCI ₃ ) d 5.80 (ddt, J = 16.9, 10.2, 6.7 Hz, 1 H), 4.97 (ddd, = 17.1 , 3.7, 1.6 Hz, 1 H), 4.91 (ddt, J = 10.2, 2.3, 1.2 Hz, 1 H), 3.45 (t, J = 6.9 Hz, 2H), 3.39 (t, J = 6.8 Hz, 2H), 2.25-2.03 (m, 2H), 2.01-1.99 (m, 2H), 1.97-1.95 (m, 2H), 1.87-1.80 (m, 2H), 1.65-1.59 (m, 2H), 1.39-1.22 (m, 10H).

Undec-10-en-1-yl acetate (1w)

To a solution of 10-undecen-1-ol (0.50 g, 3.20 mmol, 1.00 equiv.) in pyridine (10 mL) was added acetic anhydride (0.91 mL, 9.60 mmol, 3.00 equiv.). After stirring for 3 h at 60 °C, the reaction mixture was diluted with ethyl acetate (25 mL) and washed sequentially with 1 N HCI (25 mL x 5) and brine (25 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The crude material was purified by flash column chromatography on silica gel (pentane/ethyl acetate) to afford the title compound. 75% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 5.83-5.78 (m, 1 H), 5.00-4.91 (m, 2H), 2.04 (s, 3H), 1.62-1.59 (m, 2H), 1.38-1.27 (m, 14H).

Diethyl oct-7-en-1-ylphosphonate (1y)

To a round-bottomed flask under Ar atmosphere, sodium hydride (60% dispersion in mineral oil, 520 mg, 13.0 mmol, 1.30 equiv.), anhydrous THF (70 mL), and diethyl phosphite (1.80 g, 13.0 mmol, 1.30 equiv.) were added. After stirring at 0 °C for 0.5 h, and subsequently at reflux (66 °C) for 1.5 h, 8-bromo-1-octene (1.91 g, 10.0 mmol, 1.00 equiv.) was added at 0 °C. After stirring at ambient temperature (23 °C) for 24 h, water (50 mL) was added. The phases were separated and the aqueous phase was extracted with dichloromethane (3 ^c 50 mL). The organic phases were dried over anhydrous magnesium sulfate, filtered and concentrated. The crude residue was purified by flash column chromatography over silica gel (n-heptane/ethyl acetate). 90% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 5.80 (ddt, J = 16.9, 10.2, 6.7 Hz, 1 H), 5.01-4.91 (m, 2H), 4.15-4.04 (m, 4H), 2.06-2.01 (m, 2H), 1.76-1.68 (m, 2H), 1.68-1.54 (m, 2H), 1.40-1.24 (m, 11 H).

/V-(Pyridin-4-yI)undec-10-enamide (1z)

To a mixture of pyridin-4-amine (471 mg, 5.00 mmol, 1.00 equiv.) and triethylamine (1.50 ml_, 1 1.0 mmol, 2.20 equiv.) in DCM (20 mL) was added 10-undecenoylchloride (1.00 mL, 5.00 mmol, 1.00 equiv.) at 0 °C. The mixture was stirred for 12 h at ambient temperature (23 °C), after which aqueous HCI (1 M, 10 mL) was added. The phases were separated and the aqueous phase was extracted with DCM (3 >< 15 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and subsequently concentrated under reduced pressure. Flash column chromatography on silica gel (heptane/ethyl acetate) of the resulting crude material afforded the title compound. 85% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 8.51 (dd, J = 4.8, 1.5 Hz, 2H), 7.66 (s, 1 H), 7.51 (dd, J = 4.8, 1.5 Hz, 2H), 5.82 (ddt, J = 16.9, 10.2, 6.7 Hz, 1 H), 5.01 (ddd, J = 17.1 , 3.5, 1.5 Hz, 1 H), 4.96-4.94 (m, 1 H), 2.42-2.39 (m, 2H), 2.07- 2.04 (m, 2H), 1.74-1.73 (m, 2H), 1.39-1.28 (m, 10H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 172.3, 150.7, 150.6, 145.3, 139.3, 1 14.3, 1 13.6, 1 13.6, 38.0, 33.9, 29.4 (2C), 29.3, 29.2, 29.0, 25.4;

; IR (neat) v _max : 2925, 2854, 1707, 1683, 1592, 1517, 1415, 1329, 1294, 1210, 999; HRMS (ESI+): exact mass calculated for [M+Hf (C ₁₆ H ₂₅ N ₂ 0) requires m/z 261.1961 , found m/z 261.1958.

Dodec-11-enenitrile (1aa)

A mixture of 9-decen-1 -ol (0.892 mL, 0.781 g, 5 mmol, 1 equiv.), triethylamine (0.767 mL, 0.557 g, 5.5 mmol, 1.5 equiv.), and p-toluenesulfonyl chloride (0.953 g, 5 mmol, 1 equiv.) in DCM (20 mL) was stirred for 12 h at ambient temperature (23 °C). After this time, the reaction mixture was diluted with water (20 mL) and extracted with chloroform (3 ^c 20 mL). The combined organic phases were washed with a saturated aqueous solution of ammonium chloride, and subsequently dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, potassium cyanide (0.358 g, 5.5 mmol, 1.1 equiv.) and DMSO (30 mL) were added and the resulting suspension was stirred at ambient temperature (23 °C) for 14 h. After this time, water (100 mL) was added and the resulting solution was extracted with diethyl ether (4 * 30 mL). The combined organic phases were washed with a saturated aqueous solution of sodium bicarbonate (70 mL) and subsequently dried over anhydrous magnesium sulfate. The dried solution was filtered and the filtrate was concentrated under reduced pressure to afford the crude product. The crude material was purified by flash column chromatography on silica gel (heptane/ethyl acetate) to afford the title compound. 67% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 5.86-5.80 (m, 1 H), 5.03-4.95 (m, 2H), 2.37-2.35 (t, J = 7.8 Hz, 2H), 2.08-2.04 (q, J = 7.2 Hz, 2H), 1.70-1.65 (q, J = 6.6 Hz, 2H), 1.47-1.45 (m, 2H), 1.40-1.38 (m, 2H), 1.28 (m, 8H).

/V-Butylundec-10-en-1 -amine (1ad)

To a stirred solution of 10-undecenal (505 mg, 3.00 mmol, 1.00 equiv.) in MeOH (3 mL) was added n-butylamine (594 pL, 6.00 mmol, 2.00 equiv.), and the mixture was stirred at ambient temperature (23 °C) for 2 h. After this time, the reaction mixture was cooled to 0 °C and sodium borohydride (57.0 mg, 1.50 mmol, 0.75 equiv.) was added. The resulting mixture was stirred at 0 °C for 30 min, after which excess reductant was quenched by the addition of water (3 mL). The crude mixture was extracted with DCM (3 ^c 5 mL), the combined organic phases were dried over anhydrous magnesium sulfate and the dried solution was filtered. The filtrate was concentrated under reduced pressure and the resulting crude material was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH ₄ OH) to afford the title compound. 66% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 5.81 (ddt, J = 16.9, 10.2, 6.7 Hz, 1 H), 4.99 (dd, J = 17.1 , 1.4 Hz, 1 H), 4.93-4.90 (m, 1 H), 2.67 (ddd, J = 12.7, 8.0, 3.0 Hz, 3H), 2.03 (q, J = 7.0 Hz, 2H), 1.67-1.51 (m, 3H), 1.43-1.20 (m, 15H), 0.92 (t, J = 7.3 Hz,

3H).

A/,/V-Diethylundec-10-en-1 -amine (1ae) To a stirred solution of 10-undecenal (505 mg, 3.00 mmol, 1.00 equiv.) in MeOH (3 mL) was added A/,A/-diethylamine (621 pL, 6.00 mmol, 2.00 equiv.), and the mixture was stirred at ambient temperature (23 °C) for 2 h. After this time, the reaction mixture was cooled to 0 °C and sodium borohydride (57.0 mg, 1.50 mmol, 0.75 equiv.) was added. The resulting mixture was stirred at 0 °C for 30 min, after which excess reductant was quenched by the addition of water (3 mL). The crude mixture was extracted with DCM (3 * 5 mL), the combined organic phases were dried over anhydrous magnesium sulfate and the dried solution was filtered. The filtrate was concentrated under reduced pressure and the resulting crude material was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH ₄ OH) to afford the title compound. 30% yield. ¹ H NMR (600 MHz, CDCI ₃ ) d 5.81 (ddt, J = 16.9, 10.2, 6.7 Hz, 1 H), 4.99 (ddd, J = 17.1 , 3.6, 1.6 Hz, 1 H), 4.93-4.91 (m, 1 H), 2.51 (q, J = 7.2 Hz, 4H), 2.40-2.38 (m, 2H), 2.05-2.01 (m, 2H), 1.44-1.42 (m, 2H), 1.38-1.36 (m, 2H), 1.27-1.24 (m, 10H), 1.01 (t, J = 7.2 Hz, 6H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 139.4, 1 14.2, 53.2, 47.0 (2C), 34.0, 29.8, 29.7, 29.6, 29.3, 29.1 , 27.9, 27.2, 11.8 (2C); IR (neat) v _max : 2968, 2923, 2853, 2797, 1464, 1380, 1202, 1070, 991 , 908; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₅ H ₃₂ N) requires m/z 226.2529, found m/z 226.2527.

General Procedure A for Hydroaminoalkylation of Alkenes and Alkynes

A round-bottom flask charged with L/,A/,L/',L/’-tetraalkyldiaminomethane (4 equiv. with respect to the alkene or the alkyne) and a magnetic stir-bar under argon-atmosphere was cooled to 0 °C. After this, trifluoroacetic acid (neat TFA, 22.4 equiv. with respect to the alkene or alkyne) was added slowly, maintaining the low temperature of the contents of the flask. After completed addition of TFA, the alkene or alkyne was added in one portion in a concentration of 0.5 mmol (to yield a concentration of 0.6 M of alkene or alkyne in TFA), the flask was sealed and placed in an oil bath at 75 °C. The reaction was vigorously stirred at this temperature for 15 h, after which it was allowed to cool to room temperature. Subsequently, volatile components were removed under reduced pressure. The crude mixture was then treated with aqueous sodium hydroxide (1 -2 mL/1 mmol substrate) and chloroform (1 mL/1 mmol substrate) and stirred vigorously at room temperature for 1 h. After this time, aqueous sodium hydroxide (5 M) was added until the reaction mixture reaches pH 12. The resulting biphasic mixture was separated and the aqueous phase was extracted with chloroform (3 x 200 mL). The combined organic phases were then dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH ₄ OH 19:1 :0.15) to afford the analytically pure desired product.

General Procedure B for Hydroaminoalkylation of Alkyne s

A round-bottom flask charged with A/,A/,A/’A/-tetraalkyldiaminomethane (4 equiv.) and a magnetic stir-bar under argon-atmosphere was cooled to 0 °C and dissolved in DCE (1.2 M with respect to the alkyne). After this, trifluoroacetic acid (11.2 equiv. with respect to the alkyne) was added slowly, maintaining the low temperature of the contents of the flask. After completed addition of TFA, the alkyne (0.5 mmol, a concentration of 0.6 M of alkyne in the combined amounts of TFA and DCE) was added in one portion, the flask was sealed and placed in an oil bath at 75 °C. The reaction was vigorously stirred at this temperature for 15 h, after which it was allowed to cool to room temperature. Subsequently, volatile components were removed under reduced pressure. After this time, aqueous sodium hydroxide (1 M) was added until the reaction mixture reaches pH 12 and the mixture was extracted with chloroform (3 x 200 ml_). The combined organic phases were then dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH ₄ OH 19:1:0.15) to afford the analytically pure desired product.

General Procedure C for Hydroaminoalkylation of Alky nes

A round-bottom flask charged with L/,L/,L/',L/'-tetrabenzyldiaminomethane (1.5 equiv.) and a magnetic stir-bar under argon-atmosphere is cooled to 0 °C and dissolved in DCE (1.2 M with respect to the alkyne) slowly, maintaining the low temperature of the contents of the flask. After this, trifluoroacetic acid (11.2 equiv. with respect to the alkyne) was added slowly, maintaining the low temperature of the contents of the flask. After completed addition of TFA, the alkyne (0.5 mmol, to yield a concentration of 0.6 M of alkyne in the combined amounts of TFA and DCE) was added in one portion, the flask was sealed and placed in an oil bath at 75 °C. The reaction was vigorously stirred at this temperature for 15 h, after which it is allowed to cool to room temperature. Subsequently, volatile components were removed under reduced pressure. After this time, aqueous sodium hydroxide (1 M) was added until the reaction mixture reaches pH 12 and the mixture was extracted with chloroform (3 x 200 mL). The combined organic phases were then dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH ₄ OH 19:1 :0.15) to afford the analytically pure desired product.

Example 1: 12-(Methylamino)-1-(pyrrolidin-1-yl)dodecan-1-one (3a)

Prepared with 4 equiv. L/,L/,L/' L/’-tetramethyldiaminomethane according to general procedure A; 84% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 3.45 (t, J = 6.8 Hz, 2H), 3.40 (t, J = 6.9 Hz, 2H), 2.54 (t, J = 7.2 Hz, 2H), 2.42 (s, 3H), 2.24 (t, J = 7.8 Hz, 2H), 1.93 (app quin, J = 6.6 Hz, 2H), 1.83 (app quin, J = 6.6 Hz, 2H), 1.63 (app quin, J = 7.3 Hz, 2H), 1.46 (app quin, J = 6.9 Hz, 2H), 1.35-1.22 (m, 14H), 1.07 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 171 .9, 52.4, 46.7, 45.7, 36.7, 35.0, 30.1 , 29.7 (2C), 29.7 (2C), 29.6, 29.6, 27.5, 26.3, 25.1 , 24.6; IR (neat) v _max : 3439, 2924, 2852, 1636, 1558, 1439, 1382, 1345, 1310, 1254, 1227; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₇ H ₃₅ N ₂ 0) requires mlz 283.2744, found m/z 283.2743.

Example 2: 12-(Butylamino)-1-(pyrrolidin-1-yl)dodecan-1-one (3b)

Prepared with 4 equiv. A/,/\/,A/’,/V-tetrabutyldiaminomethane according to general procedure A; 85% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 3.45 (t, J = 6.8 Hz, 2H), 3.40 (t, J = 6.9 Hz, 2H), 2.61-2.54 (m, 4H), 2.24 (t, J = 7.8 Hz, 2H), 1.98-1 .90 (m, 2H), 1.87-1.80 (m, 2H), 1.63 (app quin, J = 7.3 Hz, 2H), 1.51-1.41 (m, 4H), 1.37-1.23 (m, 16H), 1.06 (br s, 1 H), 0.91 (t, J = 7.4 Hz, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 172.0, 50.3, 50.0, 46.7, 45.7, 35.0, 32.5, 30.4, 29.7 (2C), 29.7 (2C), 29.6, 29.6, 27.6, 26.3, 25.1 , 24.6, 20.7, 14.2; IR (neat) v _max : 2924, 2854, 1643, 1432, 1345; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₂ oH _4i N ₂ 0) requires mlz 325.3213, found m/z 325.3214.

Example 3: 12-(Propylamino)-1-(pyrrolidin-1-yl)dodecan-1-one (3c)

Prepared with 4 equiv. A/,A/,A/’,A/-tetrapropyldiaminomethane according to general procedure A; 92% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 3.45 (t, J = 6.8 Hz, 2H), 3.40 (t, J = 6.9 Hz, 2H), 2.54 (app dt, J = 1 1.7, 7.3 Hz, 4H), 2.23 (t, J = 7.8 Hz, 2H), 1.93 (app quin, J = 6.8 Hz, 2H), 1.83 (app quin, J = 6.8 Hz, 2H), 1.63 (app quin, J = 7.4 Hz, 2H), 1.53-1.42 (m, 4H), 1.35- 1.20 (m, 15H), 0.90 (t, J = 7.4 Hz, 3H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 171 .9, 52.4, 50.3, 46.7, 45.7, 35.0, 30.4, 29.7 (2C), 29.7, 29.7, 29.6, 29.6, 27.6, 26.3, 25.1 , 24.6, 23.4, 12.0; IR (neat) v _max : 2924, 2853, 1641 , 1432, 1343; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₉ H ₃₉ N ₂ 0) requires mlz 31 1.3057, found m/z 31 1.3058.

Example 4: 11-(lsobutylamino)-1-(pyrrolidin-1-yl)undecan-1-one (3d)

Prepared with 4 equiv. A/,A/,/V’,A/ -tetraisobutyldiaminomethane according to general procedure A, 84% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 3.45 (t, J = 6.9 Hz, 2H), 3.40 (t, J = 6.8 Hz, 2H), 2.58-2.56 (m, 2H), 2.41 (d, J = 6.8 Hz, 2H), 2.25-2.23 (m, 2H), 1 .93 (dd, J = 13.5, 6.8 Hz, 2H), 1.85 (dd, J = 13.7, 6.8 Hz, 2H), 1.75 (m, 1 H), 1.63 (dt, J = 15.1 , 7.5 Hz, 2H), 1.49-1.46 (m, 2H), 1.35-1.22 (m, 13H), 0.90 (d, J = 6.6 Hz, 6H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 172.0, 58.3, 50.3, 46.8, 45.7, 35.0, 30.2, 29.7 (2C), 29.7 (2C), 29.6, 29.6, 28.4, 27.5, 26.3, 25.1 , 24.7, 20.9 (2C) ppm; IR (neat) v _max : 2922, 2852, 2808, 1641 , 1429, 1365, 1 194, 1 127; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₂₀ H ₄₁ N ₂ O) requires mlz = 325.3213, found m/z 325.3209. Example 5: 12-(Benzylamino)-1-(pyrrolidin-1-yl)dodecan-1-one (3e)

Prepared with 1 .5 equiv. /V,/V,/V’,/V-tetrabenzyldiaminomethane according to general procedure A, 86% yield. ¹ H NMR (400 MHz, CDCI ₃ ) d 7.27-7.25 (m, 4H), 7.21-7.15 (m, 1 H), 3.73 (s, 2H), 3.39 (t, J = 6.9 Hz, 2H), 3.33 (t, J = 6.8 Hz, 2H), 2.58-2.54 (m, 2H), 2.20-2.16 (m, 2H), 1.98 (br s, 1 H), 1.88-1.75 (m, 2H), 1.79-1.75 (m, 2H), 1.59-1.56 (m, 2H), 1.47-1.43 (m, 2H), 1.22 (m, 15H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 171.8, 140.1 , 128.4 (2C), 128.2 (2C), 54.0, 53.2, 49.4, 46.6, 45.6, 34.8, 29.9, 29.5 (2C), 29.5 (2C), 29.5, 29.4, 27.3, 26.1 , 24.9, 26.4; IR (neat) v _max : 3061 , 3026, 2917, 2812, 1602, 1494, 1453, 1 1 15, 734, 697; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₂₃ H ₃₉ N ₂ O) requires mlz 359.3057, found m/z 359.3056.

Example 6: 12-(Allylamino)-1-(pyrrolidin-1-yl)dodecan-1-one (3f)

Prepared with 4 equiv. A/,/V,/V’,A/-tetraallyldiaminomethane according to general procedure A, 86% yield. ¹ H NMR (400 MHz, CDCI ₃ ) d 5.96-5.86 (m, 1 H), 5.12 (dddd, J = 32.1 , 10.2, 3.2, 1.4 Hz, 2H), 3.43 (dt, J = 21.7, 6.9 Hz, 4H), 3.24 (dt, J = 6.0, 1.4 Hz, 2H), 2.61-2.58 (m, 2H), 2.26-2.22 (m, 2H), 1 .96-1.91 (m, 2H), 1.88-1.83 (m, 2H), 1.66-1.60 (m, 2H), 1.50-1.44 (m, 2H), 1.30-1.27 (m, 14H), 0.84 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 172.0, 137.3, 1 15.7, 52.8, 49.7, 46.8, 45.7, 35.0, 30.3, 29.7 (2C), 29.7 (2C), 29.6, 29.6, 27.5, 26.3, 25.1 , 24.6.; IR (neat) v _max : 2922, 2852, 1641 , 1432, 1 168, 1033, 994, 914; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₉ H ₃₇ N ₂ 0) requires mlz 309.2900, found m/z 309.2928.

Example 7: 12-Amino-1-(pyrrolidin-1-yl)dodecan-1-one (4f)

The N- allyl compound (3f, 0.095 mmol, 29.3 mg) was dissolved in 2 ml ethanol and palladium on charcoal (10%, 0.5 equivalents, 5 mg) was added. The mixture was refluxed for 24h. The solid was filtered off over celite, the ethanol was removed at reduced pressure and the crude residue was purified by flash column chromatography over silica gel (dichloromethane/MeOH/NH ₄ OH 18/1/0.15) to afford the title compound.

86% yield. ¹ H NMR (600 MHz, CDCI ₃ ) d 3.45 (t, J = 6.9 Hz, 2H), 3.40 (t, J = 6.8 Hz, 2H), 2.66 (t, J = 7.1 Hz, 1 H), 2.30-2.18 (m, 2H), 1.93 (p, J = 6.8 Hz, 2H), 1.84 (p, J = 6.9 Hz, 2H), 1.64-1 .61 (m, 2H), 1.47-1.25 (m, 17H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 172.0, 46.7, 45.7, 42.4, 35.0, 34.0, 29.7, 29.7, 29.6, 29.6, 27.0, 26.3, 25.1 , 24.6; IR (neat) v _max : 3415, 2922, 2851 , 1630, 1430, 1342, 1008; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₆ H ₃₃ NO) requires m/z 269.2587, found m/z 269.2590.

Example 8: /V-Methyldodecan-1 -amine (3g)

Prepared with 4 equiv. A/,A/,A/’,A/’-tetramethyIdiaminomethane according to general procedure A; 61 % yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 2.54 (t, J = 7.3 Hz, 2H), 2.42 (s, 3H), 1.46 (app quin, J = 7.1 Hz, 2H), 1.32-1.21 (m, 18H), 1.10 (br s, 1 H), 0.87 (t, J = 7.0 Hz, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 52.4, 36.8, 32.1 , 30.1 , 29.8, 29.8, 29.7 (2C), 29.7, 29.5, 27.5, 22.8, 14.3; IR (neat) v _max : 2955, 2921 , 2852, 1465, 1380, 1308, 722; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₃ H ₃₀ N) requires m/z 200.2373, found m/z 200.2367.

Example 9: /V-Benzyl-3,4,4-trimethylpentan-1-amine (3h)

Prepared with 1.5 equiv. A/,/V,/\/’,A/ -tetrabenzyldiaminomethane according to general procedure A; 52% yield. ¹ H NMR (400 MHz, CDCI ₃ ) d 7.36-7.27 (m, 5H), 3.87-3.79 (m, 2H), 2.75 (ddd, J = 10.9, 9.8, 4.5 Hz, 1 H), 2.59 (ddd, J = 1 1.2, 8.8, 6.6 Hz, 1 H), 1.80-1.73 (m, 1 H), 1.65 (br s, 1 H, NH), 1 .28-1.14 (m, 2H), 0.87 (s, 9H), 0.85 (d, J = 6.5 Hz, 3H) ppm; ¹³ C NMR (100 MHz, CDCIs) d 140.5, 128.5 (2C), 128.3 (2C), 127.1 , 54.3, 49.0, 41.1 , 33.1 , 32.2, 27.4 (3C), 14.6 ppm; IR (neat) v _max : 2958, 2865, 2831 , 1453, 1364, 1 1 19, 1028, 732, 697; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₅ H ₂₆ N) requires m/z 220.2060, found m/z 220.2057. Example 10: ferf-Butyl (cycloheptylmethyl)(methyl)carbamate (3i)

Prepared with 4 equiv. A/,A/,A/’,A/-tetramethyldiaminomethane according to general procedure A followed by the protection of the amino group by a Boc protective group; 78% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 3.01-2.99 (m, 2H), 2.81 (s, 3H), 1.82-1.72 (m, 1 H), 1.70-1.46 (m, 8H), 1.45 (s, 9H), 1.41-1.34 (m, 2H), 1.17-1.07 (m, 2H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 156.3, 79.2, 55.1 , 38.0, 34.5, 31.7 (2C), 28.8 (2C), 28.6 (3C), 26.3 (2C); IR (neat) v _max : 2919, 2853, 1692, 1479, 1457, 1393, 1364, 1276, 1245, 1 161 , 1 132, 881 , 769; HRMS (ESI+): exact mass calculated for [M+Naf (C ₁₄ H ₂₇ N0 ₂ Na) requires m/z 264.1934, found m/z 264.1934.

Example 11 : ferf-Butyl (((1 S,2S,4/?)-bicyclo[2.2.1]heptan-2- yl)methyl)(methyl)carbamate (3j)

Prepared with 4 equiv. A/,/V,A/’,/V-tetramethyldiaminomethane according to general procedure A followed by the protection of the amino group by a Boc protective group; 79% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 3.23-3.09 (m, 1 H), 2.97-2.72 (m, 4H),2.21 (s, 1 H), 2.02 (s, 1 H), 1.75-1.68 (m, 1 H), 1.53-1.46 (m, 2H), 1.45 (s, 9H), 1.33-1.28 (m, 2H), 1.16-1.06 (m, 3H), 1.00 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 156.2, 79.2, 53.3, 40.8, 38.6, 36.6, 35.2, 34.9, 34.1 , 29.9, 29.2, 28.6 (3C); IR (neat) v _max : 2951 , 2870, 1696, 1454, 1396, 1365, 1 158, 1 128; HRMS (ESI+): exact mass calculated for [M+Na] ⁺ (Ci ₄ H ₂₅ N0 ₂ Na) requires m/z 262.1778, found m/z 262.1779.

Example 12: V-Benzyl-1-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)methanamine (3k)

Prepared according to general procedure A, except for the fact that 1.5 equiv. N,N,N',N’- tetrabenzyldiaminomethane were used; 39% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.35-7.29 (m, 4H), 7.27-7.21 (m, 1 H), 3.78 (s, 2H), 2.50 (dd, = 11.5, 8.1 Hz, 1 H), 2.34 (dd, J = 1 1.5, 6.9 Hz, 1 H), 2.19 (br s, 1 H), 2.07 (br s, 1 H), 1.67-1.58 (m, 1 H), 1.54-1.46 (m, 2H), 1.46-1.30 (m, 2H), 1.29-1.24 (m, 1 H), 1.21-0.99 (m, 4H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 140.9, 128.5 (2C), 128.2 (2C), 126.9, 55.3, 54.3, 42.6, 39.6, 36.4, 36.4, 35.5, 30.1 , 29.0; IR (neat) v _max : 2947, 2868, 2801 , 1453, 1122, 733, 698; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₅ H ₂₂ N) requires mlz 216.1747, found m/z 216.1745.

Example 13: W-MethyI-5-phenyIpentan-1 -amine (3I)

Prepared with 4 equiv. /V,A/,/V’,/V-tetramethyldiaminomethane according to general procedure A; 91 % yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.30-7.24 (m, 2H), 7.21-7.15 (m, 3H), 2.62 (t, J = 7.8 Hz, 2H), 2.56 (t, J = 7.2 Hz, 2H), 2.42 (s, 3H), 1.69-1.60 (m, 2H), 1.56-1.47 (m, 2H), 1.42-1.33 (m, 2H), 0.91 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 142.8, 128.5 (2C), 128.4 (2C), 125.7, 52.3, 36.7, 36.0, 31.5, 30.0, 27.1 ; IR (neat) v _max : 3025, 2927, 2854, 2788, 1454, 1381 , 1308, 81 1 , 744, 698; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₂ H ₂ oN) requires mlz 178.1590, found m/z 178.1590.

Example 14: /V-Methyl-3-phenylpropan-1 -amine (3m)

Prepared with 4 equiv. /V,/V,/V’,/V-tetramethyldiaminomethane according to general procedure A; 82% yield (50 mmol: 86% yield); ¹ H NMR (400 MHz, CDCI ₃ ) d 7.30-7.25 (m, 2H), 7.22- 7.15 (m, 3H), 2.66 (t, J = 7.8 Hz, 2H), 2.61 (t, J = 7.2 Hz, 2H), 2.43 (s, 3H), 1.86-1.77 (m, 2H), 1.02 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 142.4, 128.5 (2C), 128.4 (2C), 125.9, 51.8, 36.7, 33.8, 31.7; IR (neat) v _max : 3026, 2932, 2859, 1541 , 1493, 1454, 1383, 1306, 1252, 748, 700; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₀ H ₆ N) requires mlz 150.1277, found mlz 150.1274.

Example 15: W-Methyl-3-(p-tolyl)propan-1 -amine (3n) Prepared with 4 equiv. /V,A/,A/’,A/-tetramethyldiaminomethane according to general procedure A; 85% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.09 (app s, 4H), 2.65-2.57 (m, 4H), 2.43 (s, 3H), 2.32 (s, 3H), 1.84-1.76 (m, 2H), 1.06 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 139.3, 135.3, 129.1 (2C), 128.4 (2C), 51.8, 36.6, 33.3 31.8, 21.1 ; IR (neat) v _max : 2025, 2855, 2794, 1515, 1457, 1381 , 805; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C-nH ₁₈ N) requires mlz 164.1434, found m/z 164.1435.

Example 16: 3-(4-ChIorophenyI)-W-methylpropan-1 -amine (3o)

Prepared with 4 equiv. A/,A/,A/’,A/’-tetramethyldiaminomethane according to general procedure A; 86% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.26-7.21 (m, 2H), 7.13-7.09 (m, 2H), 2.65-2.56 (m, 4H), 2.42 (s, 3H), 1.82-1.73 (m, 2H), 0.99 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 140.8, 131.6, 129.8 (2C), 128.5 (2C), 51.6, 36.7, 33.1 , 31.6; IR (neat) v _max : 2936, 2860, 1542, 1491 , 1408, 1383, 1308, 1251 , 1093, 1015, 833, 801 ; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₀ H ₁₅ ³⁵ CIN) requires m/z 184.0888, found m/z 184.0880.

Example 17: Af-Methyl-3-(naphthalen-2-yl)propan-1-amine (3p)

Prepared with 4 equiv. A/,/V,A/',/V -tetramethyldiaminomethane according to general procedure A; 55% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.83-7.74 (m, 3H), 7.63 (s, 1 H), 7.48-7.38 (m, 2H), 7.36-7.32 (m, 1 H), 2.87-2.80 (m, 2H), 2.69-2.62 (m, 2H), 2.44 (s, 3H), 1.97-1.86 (m, 2H), 1.10 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 139.9, 133.8, 132.1 , 128.0, 127.7, 127.5, 127.4, 126.5, 126.0, 125.2, 51.8, 36.7, 33.9, 31.6; IR (neat) v _max : 2930, 2855, 1538, 1506, 1476, 1381 , 1307, 816, 747; HRMS (ESI+): exact mass calculated for [M+Hf (CI ₄ H ₁₈ N) requires mlz 200.1434, found m/z 200.1438.

Example 18: A/-Benzyl-3-phenylpropan-1 -amine (3q) Prepared with 4 equiv. /V,A/,A/',A/-tetrabenzyldiaminomethane according to general procedure A, 42% yield. ¹ H NMR (400 MHz, CDCI ₃ ) d 7.27-7.26 (m, 3H), 7.22-7.20 (m, 4H), 7.14-7.1 1

(m, 3H), 3.73 (s, 2H), 2.62 (m, 2H), 1.86-1.73 (m, 2H,), 1.49 (br s, 1 H); ¹³ C NMR (150 MHz, CDCIs) d 142.3, 140.5, 128.5 (2C), 128.5 (2C), 128.5 (2C), 128.5 (2C), 128.3, 127.1 , 125.9, 54.1 , 49.0, 33.8, 31.8; IR (neat) v _max : 3026, 2958, 2919, 2853, 1494, 1453, 1275, 1261 , 749,

698; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₆ H ₂ oN) requires m/z = 226.1590, found m/z 226.1590.

Example 19: /V-(3-Phenylpropyl)butan-1 -amine (3r)

Prepared with 4 equiv. A/,A/,A/’,A/-tetrabutyldiaminomethane according to general procedure A; 86% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.30-7.23 (m, 2H), 7.22-7.15 (m, 3H), 2.69-2.62 (m, 4H), 2.62-2.57 (m, 2H), 1.87-1.78 (m, 2H), 1.50-1.42 (m, 2H), 1.38-1.29 (m, 2H), 1.00- 0.85 (m, 4H),; ¹³ C NMR (100 MHz, CDCI ₃ ) d 142.4, 128.5 (2C), 128.4 (2C), 125.9, 49.9, 49.8, 33.9, 32.5, 32.0, 20.7, 14.2; IR (neat) v _max : 2956, 2927, 2858, 1495, 1455, 1 129, 699; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₃ H ₂₂ N) requires m/z 192.1747, found /z 192.1752.

Example 20: A/-(3-Phenylpropyl)prop-2-en-1 -amine (3s)

Prepared with 4 equiv. A/,A/,/V’,A/-tetraallyldiaminomethane according to general procedure A, 69% yield. ¹ H NMR (400 MHz, CDCI ₃ ) d 7.30-7.26 (m, 2H), 7.20-7.16 (m, 3H), 5.91 (ddt, J = 16.3, 10.3, 6.0 Hz, 1 H), 5.19-5.07 (m, 2H), 3.25 (m, 2H), 2.69-2.64 (m, 4H), 1.84 (m, 2H), 1.34 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 142.3, 137.0, 128.5 (2C), 128.5 (2C), 125.9, 1 16.0, 52.6, 49.1 , 33.8, 31 .9; IR (neat) v _max : 2926, 2853, 1675, 1643, 1452, 1 153, 1 1 18, 917, 749, 700; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₂ H ₁₈ N) requires m/z 176.1434, found m/z 176.1435. Example 21 : A/-lsobutyI-2-methyl-3-phenylpropan-1 -amine (3t)

Prepared with 4 equiv. N,N,N', A/’-tetraisobutyldiaminomethane according to general procedure A from c/s-p-methylstyrene-61 % yield, trans-b- methylstyrene-60% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.30-7.24 (m, 2H), 7.21-7.14 (m, 3H), 2.73 (dd, J = 13.4, 6.0 Hz, 1 H), 2.55 (dd, J = 1 1.7, 6.0 Hz, 1 H), 2.47-2.35 (m, 4H), 2.00-1.88 (m, 1 H), 1 .78-1.66 (m, 1 H), 1.08 (br s, 1 H), 0.91-0.86 (m, 9H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 141 .3, 129.3 (2C), 128.3 (2C), 125.9, 58.5, 56.4, 41.8, 35.4, 28.4, 20.8, 20.8, 18.1 ; IR (neat) v _max : 3027, 2954, 2927, 1495, 1457, 1094, 739, 700; HRMS (ESI+): exact mass calculated for [M+Hf (C ₁₄ H ₂₄ N) requires mlz 206.1903, found mlz 206.1904.

Example 22: Af,2-Dimethyl-3-phenylpropan-1 -amine (3u)

Prepared with 4 equiv. N,N,N’, A/’-tetramethyldiaminomethane according to general procedure A from c/s-p-methylstyrene; 39% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.30-7.24 (m, 2H), 7.21-7.14 (m, 3H), 2.73 (dd, J = 13.4, 6.0 Hz, 1 H), 2.53 (dd, J = 1 1.6, 6.0 Hz, 1 H), 2.45-2.35 (m, 5H), 2.00-1.87 (m, 1 H), 1.01 (br s, 1 H), 0.89 (d, J = 6.7 Hz, 3H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 141 .2, 129.3 (2C), 128.3 (2C), 125.9, 58.5, 41.7, 36.9, 35.4, 18.1 ; IR (neat) v _max : 3174, 2960, 2924, 1668, 1630, 1545, 1454, 1384, 740, 701 ; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (CnH ₁₈ N) requires mlz 164.1434, found m/z 164.1434.

Example 23: A/-Methyl-3,3-diphenylpropan-1 -amine (3v)

Prepared with 4 equiv. A/,A/,A/',A/-tetramethyldiaminomethane according to general procedure A; 23% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 7.30-7.24 (m, 8H), 7.17 (t, J = 6.9 Hz, 2H), 4.01 (t, J = 7.8 Hz, 1 H), 2.54 (t, J = 7.1 Hz, 2H), 2.39 (s, 3H), 2.24 (app q, J = 7.4 Hz, 2H), 1.31 (br s, 1 H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 144.9 (2C), 128.6 (4C), 127.9 (4C), 126.3 (2C), 50.6, 49.2, 36.6, 35.8; IR (neat) v _max : 2815, 2766, 1493, 1445, 1367, 1024, 760, 699; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₆ H ₂ oN) requires m/z 226.1590, found m/z 226.1592.

Example 24: 12-(Methylamino)dodecyl acetate (3w)

Prepared with 4 equiv. N,N,N’, A/’-tetramethyldiaminomethane according to general procedure A; 93% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 4.04 (t, J = 6.8 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.42 (s, 3H), 2.04 (s, 3H), 1.64-1.57 (m, 2H), 1.50-1.43 (m, 2H), 1.36-1.20 (m, 17H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 171.4, 64.8, 52.4, 36.7, 30.1 , 29.7 (2C), 29.7, 29.7, 29.6, 29.4, 28.7, 27.5, 26.0, 21.2; IR (neat) v _max : 2922, 2852, 1738, 1465, 1386, 1366, 1235, 1039; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₅ H ₃₂ NO ₂ ) requires m/z 258.2428, found m/z 258.2423.

Example 25: Methyl 7-(methylamino)heptanoate (3x)

Prepared with 4 equiv. /V,W,A/',/V -tetramethyldiaminomethane according to general procedure A; 64% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 3.65 (s, 3H), 2.54 (t, J = 7.1 Hz, 2H), 2.41 (s, 3H), 2.29 (t, J = 7.6 Hz, 2H), 1.66-1.57 (m, 2H), 1.51-1.42 (m, 2H), 1.37-1.29 (m, 4H), 1.06 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 174.3, 52.2, 51.5, 36.7, 34.1 , 29.9, 29.2, 27.1 , 25.0; IR (neat) v _max : 3359, 3199, 1664, 1557, 1396, 636; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₉ H ₂₀ NO ₂ ) requires m/z 174.1489, found m/z 174.1486.

Example 26: Diethyl (9-(methylamino)nonyl)phosphonate (3y)

Prepared with 4 equiv. A/,A/,A/’,A/-tetramethylldiaminomethane according to general procedure A, 80% yield. ¹ H NMR (600 MHz, CDCI ₃ ) d 4.11-4.03 (m, 4H), 2.54 (t, J = 7.2 Hz, 2H), 2.42 (s, 3H), 1.73-1.66 (m, 2H), 1.61-1.55 (m, 2H), 1.52 (br s, 1 H), 1.47-1.45 (m, 2H), 1.36-1.34 (m, 2H), 1.30 (m, 14H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 61.5 (d, J = 6.5 Hz, 2C), 52.3, 36.6, 30.7 (d, J = 17.0), 30.0, 29.6, 29.4, 29.2, 27.4, 25.8 (d, J = 140.3), 22.5 (d, J = 5.2 Hz), 16.6 (d, J = 6.0 Hz, 2C); IR (neat) v _max : 3427, 2925, 2853, 1465, 1386, 1235, 1054, 1024, 958; HRMS (ESI+): exact mass calculated for [M+Hf (C ₁₄ H ₃₃ N0 ₃ P) requires m/z 294.2193, found m/z 294.2192.

Example 27: 12-(Methylamino)-/V-(pyridin-4-yl)dodecanamide (3z)

Prepared with 4 equiv. A/,/V,/V’,/V-tetramethyldiaminomethane according to general procedure A, 72% yield. ¹ H NMR (400 MHz, CDCI ₃ ) d 8.48 (dd, J = 4.9, 1.4 Hz, 2H), 7.71 (br s, 1 H), 7.49-7.48 (m, 2H), 3.48 (s, 1 H), 2.57 (t, J = 7.2 Hz, 2H), 2.44 (s, 3H), 2.41-2.32 (m, 2H), 1.75-1.68 (m, 4H), 1.50-47 (m, 2H), 1.34-1.27 (m, 13H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 172.3, 150.8 (2C), 145.3, 1 13.6 (2C), 52.3, 37.9, 36.5, 29.9, 29.6, 29.5 (2C), 29.4, 29.3, 29.3, 27.4, 25.4; IR (neat) v _max : 2925, 2853, 1703, 1594, 1522, 1329, 1296, 1210, 832; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₈ H ₃₂ N ₃ 0) requires m/z 306.2540, found m/z 306.2539.

Example 28: 13-(Methylamino)tridecanenitrile (3aa)

Prepared with 4 equiv. A/,/V,A/’,A/-tetramethyldiaminomethane according to general procedure A; 84% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 2.55 (t, J = 7.1 Hz, 2H), 2.42 (s, 3H), 2.32 (t, J = 7.1 Hz, 2H), 1.64 (app quin, J = 7.5 Hz, 2H), 1.49-1.40 (m, 4H), 1.33-1.24 (m, 14H), 1.19 (br s, 1 H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 120.0, 52.4, 36.7, 30.1 , 29.7, 29.7, 29.6, 29.6, 29.4, 28.9, 28.8, 27.5, 25.5, 17.3; IR (neat) v _max : 2922, 2852, 2243, 1465, 1426, 1382, 1308, 722; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₄ H ₂ 9N ₂ ) requires m/z 225.2325, found /z 225.2324.

Example 29: A/-Benzyl-9-bromononan-1 -amine (3ab) Prepared according to general procedure A, except that 1.5 equiv. N,N,N',N’- tetrabenzyldiaminomethane were used, 40% yield ¹ H NMR (400 MHz, CDCI ₃ ) d 7.33 (d, J = 4.1 Hz, 4H), 7.25 (m, 1 H), 3.80 (s, 2H), 3.40 (t, J = 6.9 Hz, 2H), 2.63 (t, J = 7.3 Hz, 2H), 1.88-1.81 (m, 2H,), 1.54-1.51 (m, 2H), 1.43-1.40 (m, 2H), 1.29-1.26 (m, 8H); ¹³ C NMR (150 MHz, CDCIs) d 138.7, 128.7 (2C), 128.7 (2C), 127.5, 53.6, 49.9, 34.2, 32.9, 29.5, 28.8, 28.3, 27.3; IR (neat) v _max : 2920, 2851 , 2795, 1457, 1435, 734, 696; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₆ H ₂ 7NBr) requires m/z 312.1321 , found m/z 312.1319.

Example 30: 12-(Methylamino)dodecan-1-ol (3ac)

Prepared with 4 equiv. A/,/V,/\/’,A/ -tetramethyldiaminomethane according to general procedure A; 82% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 3.63 (t, J = 6.6 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.42 (s, 3H), 1.60-1.51 (m, 2H), 1.51-1.42 (m, 2H), 1.38-1.24 (m, 18H); ¹³ C NMR (100 MHz, CDCIs) d 63.2, 52.4, 36.7, 33.0, 30.1 , 29.7 (3C), 29.7 (2C), 29.5, 27.5, 25.9; IR (neat) v _max : 3304, 2918, 2850, 1680, 1468, 1387, 1202, 1 180, 1 134, 1059; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₃ H ₃₀ NO) requires m/z 216.2322, found m/z 216.2314.

Example 31 : A^-Butyl-A/^-methyldodecane-l , 12-diamine (3ad)

Prepared with 4 equiv. /V,A/,A/’,/V’-tetramethyldiaminomethane according to general procedure A; 60% yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 2.61-2.52 (m, 6H), 2.42 (s, 3H), 1.51-1.41 (m, 6H), 1.37-1.24 (m, 18H), 1.00-0.85 (m, 5H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 52.4, 50.4, 50.0, 36.8, 32.5, 30.4, 30.1 , 29.7 (7C), 27.6, 27.5, 20.7, 14.2; IR (neat) v _max : 2921 , 2850, 281 1 , 1466, 1377, 1 128, 733; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₇ H ₃₉ N ₂ ) requires m/z 271.3108, found m/z 271.3108.

Example 32: Af^/N^-Diethyl-A/^-methyldodecane-l , 12-diamine (3ae) Prepared with 4 equiv. N, N, N’, A/’-tetramethyldiaminomethane according to general procedure A; 75% yield. ¹ H NMR (400 MHz, CDCI ₃ ) d 2.55 (m, 6H), 2.43 (s, 3H), 2.44-2.40 (m, 2H), 1.68 (br s, 1 H), 1 .47-1 .44 (m, 4H), 1.26 (s, 16H), 1.03 (t, J = 7.2 Hz, 6H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 53.0, 52.3, 46.9 (2C), 36.6, 30.0, 29.8, 29.7 (2C), 29.7 (2C), 27.8 (2C), 27.5, 26.9, 1 1.7 (2C); IR (neat) v _max : 2967, 2922, 2851 , 1466, 1381 , 1201 , 1 130, 721 ; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₇ H ₃₉ N ₂ 0) requires m/z 271.3108, found m/z 271.31 10.

Example 33: (E)-/V-BenzyIundec-2-en-1-amine (6a)

Procedure A, but with 1.5 equiv. A/,A/,/\/’,A/ -tetrabenzyldiaminomethane, 53% yield. ¹ H NMR (600 MHz, CDCI ₃ ) d 7.32 (d, J = 4.5 Hz, 3H), 7.26-7.24 (m, 2H), 5.62-5.57 (m, 1 H), 5.53 (dt, J = 15.3, 6.0 Hz, 1 H), 3.78 (s, 2H), 3.21 (d, J = 6.0 Hz, 2H), 2.02 (app q, J = 6.9 Hz, 2H), 1.53 (br s, 1 H), 1.37-33 (m, 2H,), 1.30-1.26 (m, 10H), 0.87 (t, J = 7.0 Hz, 3H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 140.5 (C), 133.3, 128.5 (2C), 128.4 (2C), 128.1 , 127.0, 53.4, 51.3, 32.6, 32.0, 29.6, 29.5, 29.4, 29.3, 22.8, 14.3; IR (neat) v _max : 3027, 2955, 2852, 1454, 969, 731 , 698; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₈ H ₃₀ N) requires mlz 260.2373, found m/z 260.2369.

Example 34: (E)-3-Cyclohexyl-N-methylprop-2-en-1 -amine (6b)

Procedure A with 4 equiv. N,N,N’, A/'-tetramethyldiaminomethane; 65% yield. ¹ H NMR (400 MHz, CDCI ₃ ) d 5.54 (dd, J = 15.5, 6.3 Hz, 1 H), 5.49-5.42 (m, 1 H), 3.14 (d, J = 5.9 Hz, 2H), 2.41 (s, 3H), 1.94 (ddd, J = 14.1 , 1 1.2, 3.0 Hz, 1 H), 1.72 (dd, J = 9.2, 6.7 Hz, 4H), 1 .66-1.62 (m, 1 H), 1.33-1.01 (m, 6H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 138.9, 125.5, 54.0, 40.6, 35.9, 33.2 (2C), 26.4 (2C), 26.2; IR (neat) v _max : 2921 , 2849, 2789, 1447, 1379, 1315, 1286, 1254, 1031 , 970; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₀ H ₁₉ N) requires mlz 154.1590, found m/z 154.1590. Example 35: (£)-A/-Benzyl-3-(cyclohex-1-en-1-yI)prop-2-en-1 -amine (6c)

Procedure C with 1.5 equiv. A/,A/,A/’,AT-tetrabenzyldiaminomethane, 68% yield. ¹ H NMR (400 MHz, CDCIg) d 7.35-7.30 (m, 4H), 7.28-7.23 (m, 1 H), 6.17 (d, J = 15.7 Hz, 1 H), 5.71 (br s, 1 H), 5.69-5.59 (m, 1 H), 3.80 (s, 2H), 3.32 (d, J = 6.3 Hz, 2H), 2.13-2.12 (m, 4H), 2.03 (s, 1 H), 1.66 (ddd, J = 6.4, 4.6, 2.9 Hz, 2H), 1.63-1.54 (m, 2H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 140.2, 135.7, 135.5, 129.2, 128.6 (2C), 128.4 (2C), 127.1 , 123.8, 53.3, 51.4, 26.0, 24.7, 22.7, 22.6; IR (neat) v _max : 3025, 2922, 2855, 1493, 1450, 1072, 964, 731 , 696; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₆ H ₂₂ N) requires mlz 228.1747, found m/z 228.1744.

Example 36: (E)-/V-BenzyI-3-cyclopropylprop-2-en-1 -amine (6d)

Procedure C with 1.5 equiv. /V,/V,A/’,/V -tetrabenzyldiaminomethane. 85%, 10:1 mixture of isomers. ¹ H NMR (600 MHz, CDCi ₃ ) d 7.34-7.30 (m, 4H), 5.64 (dt, 1 H, J = 15.0, 6.4 Hz), 5.14 (dd, J = 15.3, 8.7 Hz, 1 H), 3.78 (s, 2H), 3.21 (d, J = 6.4 Hz, 2H), 1.40-1.38 (m, 1 H), 0.70- 0.67 (m, 2H), 0.36-0.34 (m, 2H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 140.5, 136.6, 128.5 (2C), 128.3 (2C), 127.0, 126.0, 53.4, 51 .2, 13.6, 6.7 (2C); IR (neat) v _max : 3083, 3064, 3025, 3005, 2958, 2924, 2853, 2807, 1495, 1453, 963, 735, 698; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₃ H ₁₈ N) requires m/z 188.1434, found m/z 188.1433.

Example 37: (£)-/V-MethyI-2-propylhex-2-en-1 -amine (6e)

Procedure A with 4 equiv. A/,/V,A/’,/V-tetramethyldiaminomethane;, 41 % yield. ¹ H NMR (600 MHz, CDCIs) d 5.32-5.29 (m, 1 H), 3.10 (s, 2H), 2.38 (s, 3H), 2.04-1.99 (m, 4H), 1 .67 (s, 1 H), 1.38 (dt, J = 23.9, 7.5 Hz, 4H), 0.90 (t, J = 7.3 Hz, 6H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 137.3, 127.1 , 57.6, 35.9, 31.1 , 29.8, 23.2, 21.9, 14.3, 14.1 ; IR (neat) v _max : 3446, 2965, 2918, 1455, 1396, 764, 703; ; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₀ H ₂ IN) requires m/z 156.1747, found m/z 156.1743. Example 38: (£)-/V-Methyl-3-(p-tolyl)prop-2-en-1-amine (6f)

Procedure A with 4 equiv. A/,/V,A/’,A/ -tetramethyldiaminomethane; 51 % yield, 10: 1 mixture of isomers. ¹ H NMR (400 MHz, CDCI ₃ ) d 7.27 (d, J = 7.9 Hz, 2H), 7.1 1 (d, J = 7.9 Hz, 2H), 6.50 (d, J = 15.9 Hz, 1 H), 6.24 (dt, J = 15.9, 6.3 Hz, 1 H), 3.37 (dd, J = 6.3, 1 .4 Hz, 2H), 2.48 (s, 3H), 2.33 (s, 3H), 1.40 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 137.3, 134.5, 131.4, 129.4 (2C), 127.4, 126.3 (2C), 54.0, 36.2, 21 .3; IR (neat) v _max : 3045, 2922, 2853, 1669, 1513, 1451 , 1382, 970, 766, 749; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (CnH ₁₆ N) requires m/z 162.1277, found m/z 162.1274.

Example 39: (£)-3-(4-Fluorophenyl)-Af-methylprop-2-en-1 -amine (6g)

Procedure A with 4 equiv. N,N,N’, AT-tetramethyldiaminomethane; 31 % yield. ¹ H NMR (700 MHz, CDCI ₃ ) d 7.34-7.32 (m, 2H), 6.99 (t, J = 8.7 Hz, 2H), 6.49 (d, J = 15.9 Hz, 1 H), 6.20 (dt, J = 15.9, 6.3 Hz, 1 H), 3.36 (dd, J = 6.3, 0.9 Hz, 2H), 2.48 (s, 3H), 1.25 (br s, 1 H); ¹³ C NMR (175 MHz, CDCI ₃ ) d 162.3 (d, J = 246 Hz), 133.5 (d, J = 3.3 Hz), 130.2, 128.3 (d, J = 2.1 Hz) , 127.8 (d, J = 7.9 Hz, 2C), 1 15.6 (J = 21 .5 Hz, 2C), 53.9, 36.2; IR (neat) v _max : 2360, 2177, 2045, 1509, 1227, 763, 749; HRMS (ESI+): exact mass calculated for [M+Hf (C ₁₀ H ₁₃ N) requires m/z 166.1027, found m/z 166.1021 .

Example 40: (E)-2-(4-(3-(Methylamino)prop-1-en-1-yl)phenyl)acetonitrile (6h)

Procedure B with 4 equiv. A/,/V,A/’,A/ -tetramethyldiaminomethane; 37% yield. ¹ H NMR (600 MHz, CDCIs) d 7.38 (d, J = 8.2 Hz, 2H), 7.27-7.26 (m, 2H), 6.52 (d, J = 15.9 Hz, 1 H), 6.31 (dt, J = 15.9, 6.2 Hz, 1 H), 3.73 (s, 2H), 3.39 (dd, J = 6.3, 1 .4 Hz, 2H), 2.48 (s, 3H), 1 .63 (s, 1 H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 137.0, 130.3, 129.2, 128.6, 128.1 (2C), 126.9 (2C), 1 17.8, 53.7, 36.0, 23.3; IR (neat) v _max : 2981 , 2898, 1670, 1512, 1361 , 1275, 1261 , 972, 764, 750; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₂ H ₁₅ N) requires m/z 187.1230, found m/z 187.1224. Example 41 : (E)-/V,2-Dimethyl-3-phenylprop-2-en-1-amine (6i)

Procedure A with 4 equiv. /V,/V,/V’,/V’-tetramethyldiaminomethane; 48% yield. ¹ H NMR (600 MHz, CDCI ₃ ) d 7.33 (t, J = 7.6 Hz, 2H), 7.27 (d, J = 7.3 Hz, 2H), 7.20 (t, J = 7.3 Hz, 1 H), 6.44 (s, 1 H), 3.30 (s, 2H), 2.47 (s, 3H), 1.90 (d, J = 0.9 Hz, 3H), 1.57 (br s, 1 H); ¹³ C NMR (150

MHz, CDCI ₃ ) 5 138.1 , 136.8, 129.0 (2C), 128.2 (2C), 126.3, 126.0, 60.4, 35.9, 16.7; IR (neat) v _max : 3024, 2925, 2853, 2794, 2770, 2714, 1680, 1491 , 1448, 1387, 1357, 1037, 748, 699; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (CnH ₁₆ N) requires m/z 162.1277, found m/z 162.1277.

Example 42: Methyl (£)-7-(benzylamino)hept-5-enoate (6j)

Procedure A, but with with 1.5 equiv. A/,A/,/V’,A/-tetrabenzyldiaminomethane; 41 % yield, 12:1 mixture of isomers. ¹ H NMR (400 MHz, CDCI3) d 7.26 (d, J = 4.5 Hz, 4H), 7.19-7.17 (m, 1 H), 5.53-5.51 (m, 2H), 3.73 (s, 2H), 3.61 (s, 3H), 3.17 (dd, J = 3.7, 1.0 Hz, 2H), 2.26 (t, J = 7.5

Hz, 2H), 2.03-2.01 (m, 2H), 1.82 (br s, 1 H), 1.67 (p, J = 7.5 Hz, 2H); ¹³ C NMR (100 MHz, CDCI3) d 174.2, 140.3, 131.7, 129.4, 128.5 (2C), 128.4 (2C), 127.1 , 53.4, 51.6, 51.1 , 33.5, 31.8, 24.6; IR (neat) v _max : 2926, 2797, 1734, 1602, 1451 , 1436, 1 154, 1121 , 970, 734, 698; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C15H22NO2) requires m/z 248.1645, found m/z 248.1644.

Example 43: (£)-8-(Methylamino)oct-6-enenitrile (6k)

Procedure B with 4 equiv. A/,A/,A/’,/\/-tetramethyldiaminomethane; 97% yield, 10:1 mixture of isomers. ¹ H NMR (400 MHz, CDCI ₃ ) d 5.54 (td, J = 5.1 , 3.0 Hz, 2H), 3.16-3.14 (m, 2H), 2.41 (s, 3H), 2.33 (t, J = 7.0 Hz, 2H), 2.07 (dd, J = 12.2, 7.2 Hz, 2H), 1.70-1.63 (m, 2H), 1.57- 1.50 (m, 2H), 1.32 (br s, 1 H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 131.4, 129.4, 1 19.8, 53.7, 36.0, 31.5, 28.3, 24.9, 17.2; IR (neat) v _max : 2932, 2857, 2790, 1541 , 1460, 1381 , 1262, 1032, 974, 764, 750; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (0 ₉ H ₁₇ N ₂ ) requires m/z 153.1386, found m/z 153.1386. Example 44: (E)-11-(Methylamino)undec-9-en-1-ol (6I)

Procedure B with 4 equiv. A/,A/,/V’,A/ -tetramethyldiaminomethane, stirred for 5 h at 75 °C instead of 16 h; 59% yield. ¹ H NMR (600 MHz, CDCI ₃ ) d 5.53 (dtd, 2H), 3.62 (t, J = 6.6 Hz, 2H), 3.14 (d, J = 6.1 Hz, 2H), 2.40 (s, 3H), 2.01 (q, J = 6.8 Hz, 2H), 1.63-1.53 (m, 4H), 1.35- 1.24 (m, 10H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 133.2, 128.0, 63.1 , 53.8, 35.9, 32.9, 32.4, 29.4, 29.3, 29.1 , 25.8; IR (neat) v _max : 3405, 3368, 2925, 2854, 1541 , 1460, 1382, 1260, 1059, 971 ; HRMS (ESI+): exact mass calculated for requires m/z 200.2009, found m/z 200.2009.

Example 45: (E)-Af-Methyl-4-(triisopropylsilyl)but-2-en-1 -amine (6m)

Procedure B with 4 equiv. A/,A/,A/’,A/-tetramethyldiaminomethane; stirred at room temperature instead of 75 °C, 34% yield. ¹ H NMR (400 MHz, CDCI ₃ ) d 5.68-5.60 (m, 1 H), 5.46-5.38 (m, 1 H), 3.12 (dd, J = 6.5, 0.8 Hz, 2H), 2.40 (s, 3H), 1.59 (dd, J = 8.0, 1 .1 Hz, 2H), 1.15 (br s, 1 H), 1.05 (s, 9H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 130.1 , 126.9, 54.4, 36.0, 18.8 (6C), 15.5, 1 1.2 (3C); IR (neat) v _max : 2940, 2889, 2864, 1461 , 1381 , 1253, 1 154, 966, 809, 749, 701 , 658; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₄ H ₃₂ N) requires m/z 242.2294, found m/z 242.2295.

C-C Bond Formation on the Reaction Intermediate

i) tetramethyldiaminomethane (4 eq.)

TFA (0.6 M), 75 °C, 15 h Example 46: 4-(Methyl(3-phenylpropyl)amino)butan-2-one (8a)

Following procedure A, styrene was subjected to hydroaminoalkylation-conditions using /V,/V,/V’,/V-tetramethyldiaminomethane. After the hydroaminoalkylation reaction and cooling to 23 °C, acetone (55 equiv.) was added directly to the reaction mixture and the resulting solution was stirred at 23 °C for 8 h. After this time, volatile components were removed under reduced pressure and the residue was dissolved in chloroform. The resulting solution was treated with a 1 M aqueous solution of sodium hydroxide until basic and the aqueous phase was subsequently extracted with chloroform (3 x). The combined organic phases were dried over anhydrous sodium sulfate, the dried solution was filtered and the filtrate was concentrated under reduced pressure. The crude residue was purified by flash column chromatography over silica gel (dichloromethane/MeOH/NH ₄ OH 18/1/0.15) to afford the title compound.

71 % yield; ¹ H NMR (400 MHz, CDCI ₃ ) d 7.30-7.24 (m, 2H), 7.20-7.14 (m, 3H), 2.68-2.54 (m, 6H), 2.39-2.33 (m, 2H), 2.20 (s, 3H), 2.15 (s, 3H), 1 .83-1.74 (m, 2H); ¹³ C NMR (100 MHz, CDCI ₃ ) d 208.2, 142.4, 128.5 (2C), 128.4 (2C), 125.9, 57.2, 52.2, 42.1 , 41.8, 33.7, 30.3, 29.1 ; IR (neat) v _max : 2942, 2847, 2793, 171 1 , 1495, 1454, 1356, 1 161 , 747, 700; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₄ H ₂ 2NO) requires mlz 220.1696, found m/z 220.1696.

Example 47: 3-(Methyl(3-phenylpropyl)amino)-1-phenyIpropan-1-one (8b)

Following procedure A, styrene was subjected to hydroaminoalkylation-conditions using 4 equivalents of A/,A/,A/’,/V -tetramethyldiaminomethane. After the hydroaminoalkylation reaction and cooling to 23 °C, acetophenone (10 equiv.) was added directly to the reaction mixture and the resulting solution was stirred at 23 °C for 8 h. After this time, volatile components were removed under reduced pressure and the residue was dissolved in chloroform. The resulting solution was treated with a 1 M aqueous solution of sodium hydroxide until basic and the aqueous phase was subsequently extracted with chloroform (3 x). The combined organic phases were dried over anhydrous sodium sulfate, the dried solution was filtered and the filtrate was concentrated under reduced pressure. The crude residue was purified by flash column chromatography over silica gel (dichloromethane/MeOH/NH ₄ OH 18/1/0.15) to afford the title compound.

59% yield; ¹ NMR (600 MHz, CDCI ₃ ) d 7.96-7.95 (m, 2H), 7.58-7.55 (m, 1 H), 7.48-7.45 (m, 2H), 7.28-7.26 (m, 2H), 7.19-7.16 (m, 3H), 3.15-3.12 (m, 2H), 2.85-2.83 (m, 2H), 2.63- 2.61 (m, 2H), 2.44-2.42 (m, 2H), 2.29 (s, 1 H), 1.81 (dt, J = 15.0, 7.6 Hz, 2H); ¹³ C NMR (150 MHz, CDCIs) d 199.6, 142.3, 137.1 , 133.2, 128.7 (2C), 128.6 (2C), 128.4 (2C), 128.2 (2C), 125.9, 57.2, 52.7, 42.4, 36.7, 33.7, 29.1 ; IR (neat) v _max : 2939, 2849, 2794, 1682, 1598, 1495, 1450, 1206, 1 180, 745, 696; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₁₉ H ₂₄ N0 ₃ ) requires mlz 282.1852, found m/z 282.1854.

Example 48: /V-Methyl-3-phenyl-/V-(2,4,6-trimethoxybenzyl)propan-1-amine (8c)

Following procedure A, styrene was subjected to hydroaminoalkylation-conditions using 4 equivalents of /V,/\/,A/’A/ -tetramethyldiaminomethane. After the hydroaminoalkylation reaction and cooling to 23 °C, 1 ,3,5-trimethoxybenzene (15 equiv.) was added directly to the reaction mixture and the resulting solution was warmed up to 50 °C and stirred for 8 h. After this time, volatile components were removed under reduced pressure and the residue was dissolved in chloroform. The resulting solution was treated with a 1 M aqueous solution of sodium hydroxide until basic and the aqueous phase was subsequently extracted with chloroform (3 x). The combined organic phases were dried over anhydrous sodium sulfate, the dried solution was filtered and the filtrate was concentrated under reduced pressure. The crude residue was purified by flash column chromatography over silica gel (dichloromethane/MeOH/NH ₄ OH 18/1/0.15) to afford the title compound.

54% yield; ¹ H NMR (600 MHz, CDCI ₃ ) d 7.29-7.26 (m, 2H), 7.20 (t, J = 7.4 Hz, 1 H), 7.16 (d, J = 7.0 Hz, 2H), 6.1 1 (s, 2H), 4.24 (m, 1 H), 4.12 (m, 1 H), 3.82 (s, 3H), 3.79 (s, 6H), 3.09 (br s, 1 H), 2.80 (br s, 1 H), 2.68 (t, J = 6.2 Hz, 2H), 2.61 (s, 3H), 2.28 (br s, 1 H), 2.17 (br s, 1 H); ¹³ C NMR (150 MHz, CDCI ₃ ) d 163.3 (2C), 161.1 , 160.6, 140.1 , 128.7 (2C), 128.5 (2C), 126.5, 90.6 (2C), 55.9 (2C), 55.6, 55.1 , 47.5, 39.6, 33.2, 25.6; IR (neat) v _max : 3397, 2941 , 2845, 2613, 1609, 1594, 1458, 1421 , 1232, 1204, 1 152, 1055, 1033, 951 , 819; HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C ₂ oH ₂₈ N0 ₃ ) requires mlz 330.2064, found m/z 330.2055.

General Procedure for Comparative Examples 1 to 4 A round bottom flask charged with N,N-tetramethyldiaminomethane (4 equiv. with respect to the alkene) and a magnetic stir-bar was cooled to 0 C. After this, sulfuric or phosphoric acid (1.8 equivalents with respect to the alkene) and acetic acid were added, followed by the alkene in one portion, in a 0.6M concentration with respect to the acetic acid. The flask was sealed, placed in an oil bath and heated to 75 °C for the time indicatded in tables 1 and 2. Subsequently, the volatile components were removed at reduced pressure. The crude mixture was then treated with aqueous sodium hydroxide (1-2 mol/L) and chloroform and stirred vigorously for one hour. After that, aqueous sodium hydroxide was added unil the mixture reached pH 12. The resulted biphasic mixture was then separated and the aqueous phase extracted with chloroform (3x200 ml_). The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure.

Table 1

4 equiv.

Ph

acid, 0 to 75 °C

16h

Table 2

As can be taken from Table 1 and Table 2, the hydroaminoalkylation reaction according to the present invention resulted in high yields and high selectivity (Examples 8 and 14). In contrast, the hydroaminoalkylation using sulfuric acid or phosphoric acid in acetic acid resulted in low yields and the formation of side products (Comparative Examples 1 to 4).

Table 3

^* The Examples were carried out according to General Procedure C, but with the

concentration of the TFA, the additional solvent and the alkyne as indicated.

^** The Example was carried out according to General Procedure C. As can be seen in Table 3, high yields of the amine were obtained, i.e. above 50%, in a hydroaminoalkylation reaction carried out in TFA alone and also for solvent mixtures of TFA and an organic solvent, such as dichloroethane (DCE), acetonitrile (MeCN) and toluene. Hydroaminoalkylation of Alkenes or Alkynes using a Reactive Component obtained from substituted Aminals R ₂ N-CHR-NR ₂ or Hemiaminal Ethers

General Information

All glassware was oven dried at 100 °C before use and all reactions were performed under an atmosphere of argon unless otherwise stated. All reagents were used as received from commercial suppliers unless otherwise stated. Reaction progress was monitored by thin layer chromatography (TLC) performed on aluminum plates coated with silica gel F254 with 0.2 mm thickness.

Visualization was achieved by a combination of ultraviolet light (254 nm) and potassium permanganate or ninhydrin solutions. Flash column chromatography was performed using silica gel 60 (230-400 mesh, Merck and co.).

¹ H and ¹³ C NMR spectra were recorded on Bruker AV 400 or AV 600 spectrometers. ¹⁹ F NMR spectra were recorded on an AV 700 spectrometer. Chemical shifts (d) values are presented in parts per million (ppm), referenced to the solvent peak. Data are reported as follows: chemical shift (d), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, bs = broad singlet, dd = doublet of doublet, dt = doublet of triplets, tt = triplet of triplet), coupling constants (J, Hz) and integration.

Mass spectra were obtained using a Finnigan MAT 8200 or (70 eV) or an Agilent 5973 (70 eV) spectrometer, using electrospray ionization (ESI). Infrared spectra were recorded with a Perkin-Elmer Spectrum 100 FT-IR spectrometer.

General procedure D for Hydroaminoalkylation of Alkenes and Alkynes with 2,2,2-Trifluoro- N, N, N', N'-tetramethylethane- 1, 1 -diamine

2,2,2-Trifluoro-A/,A/,A/',A/-tetramethylethane-1 ,1-diamine (0.8 mmol, 4 equiv., 0.14 ml.) was added to TFA (135 equiv., 2 mL, to yield a concentration of the alkene or alkyne with respect to TFA of 0.1 M) at 0 °C and stirred for 5 minutes, then cooled to -10 °C and stirred for 10 min. The alkene (or alkyne, 0.2 mmol, 1 equiv.) was then added and the mixture was stirred at -10 °C for 16 h, after which excess acid was quenched with ca. 5 mL aqueous NaOH (1 M). The aqueous layer was extracted with dichloromethane (4 ^c 15 mL), the combined organic layers were dried over anhydrous potassium carbonate and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel with DCM/DMA (10:1 ; DMA = solvent mixture of dichloromethane, methanol, aq. NH ₄ OH in the ratio 9:1 :0.15).

General procedure E for Hydroaminoalkylation of Alkenes and Alkynes with 2,2- bis( dimethylamino)acetate

A round-bottom flask was charged with ethyl 2,2-bis(dimethylamino)acetate (4 equiv.) and a magnetic stir-bar under argon-atmosphere was cooled to 0 °C, and then trifloroacetic acid (22.4 equiv., to yield a concentration of the alkene or alkyne with respect to TFA of 0.6 M) was added and stirred for 5min. After this, alkene or alkyne (1 equivalent, 0.216 mmol) was added. After completed addition of the solvent, the flask was sealed and placed at the temperature as indicated in the example. The reaction was vigorously stirred at this temperature for 20 h, after which it was cooled to 0 °C. Then saturated aqueous NaHC0 ₃ was added until the reaction mixture reached a basic pH. The resulting biphasic mixture was separated and the aqueous phase was extracted with dichloromethane (3 x 200 mL/mmol). The combined organic phases were then dried over anhydrous potassium carbonate and filtered. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH40H 24:1 :0.15) to afford the analytically pure desired product.

General procedure F for Hydroaminoalkylation of Alkenes and Alkynes with diethyl

A round-bottom flask was charged with diethyl

((dimethylamino)(methoxy)methyl)phosphonate (4 equiv.) and a magnetic stir-bar under argon-atmosphere was cooled to 0 °C, and then trifloroacetic acid (135 equiv., to yield a concentration of the alkene or alkyne with respect to TFA of 0.1 M) was added and stirred for 5 minutes. After completed addition of the solvent, the flask was sealed and placed at the temperature as indicated in the example. After this, alkene or alkyne (1 equiv., 0.216 mmol) was added. The reaction was vigorously stirred at this temperature for 20 h, after which it was allowed to to reach 0 °C. Then aqueous saturated NaHC0 ₃ was added until the reaction mixture reached a basic pH (higher than 7). The resulting biphasic mixture was separated and the aqueous phase was extracted with dichloromethane (3 x 200 mL/mmol). The combined organic phases were then dried over anhydrous potassium carbonate and filtered. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH ₄ OH 24:1 :0.15) to afford the analytically pure desired product.

Example 54: (E)-2-(8,8,8-Trifluoro7-(methylamino)oct-5-en-1-yl)isoindoii ne-1,3-dione (3af)

Prepared according to general procedure D (38% yield).

¹ H NMR (600 MHz, CDCI ₃ ): d 7.86 - 7.81 (m, 2H), 7.73 - 7.68 (m, 2H), 5.78 (dt, J = 15.4, 6.8 Hz, 1 H), 5.33 - 5.27 (m, 1 H), 3.69 (t, J = 7.2 Hz, 2H), 3.37 (p, J = 7.5 Hz, 1 H), 2.43 (s, 3H), 2.20 - 2.09 (m, 2H), 1.76 - 1.63 (m, 2H), 1.52 - 1.41 (m, 2H) ppm.

¹³ C NMR (150 MHz, CDCI ₃ ): d 168.6 (2C), 137.9, 134.0 (2C), 132.3 (2C), 125.7 (q, J = 282 Hz), 123.3 (2C), 123.1 (m), 64.3 (q, J = 29 Hz), 37.8, 34.2, 32.0, 28.1 , 26.2 ppm.

¹⁹ F NMR (565 MHz, CDCI ₃ ): d -75.2 (d, J = 7.2 Hz) ppm.

HRMS (ESI+): calculated for [M+H] ⁺ C ₁₇ H ₂ oF ₃ N ₂ 0 ₂ ⁺ : 341.1471 , found: 341.1473.

IR (cm ¹ ): 2939, 2861 , 1771 , 1706, 1396, 1369, 1264, 1154, 1130, 1102, 923, 718. Example 55: (E)-4-(cyclohex-1-en-1-yl)-1,1,1-trifluoro-N-methylbut-3-en- 2-amine (3ag)

Prepared according to general procedure D (37% yield).

¹ H NMR (600 MHz, CDCI ₃ ): d 6.31 (d, J = 15.7 Hz, 1 H), 5.83 (s, 1 H), 5.32 (dd, J = 15.8, 8.5 Hz, 1 H), 3.46 (p, J = 7.4 Hz, 1 H), 2.45 (s, 3H), 2.17 - 2.1 1 (m, 4H), 1.72 - 1.66 (m, 2H), 1.64 - 1.58 (m, 2H) ppm.

¹³ C NMR (150 MHz, CDCI ₃ ): d 140.3, 134.8, 132.0, 125.8 (q, J = 282 Hz), 1 17.3, 64.7 (q, J = 29 Hz), 34.3, 26.0, 24.5, 22.5, 22.4 ppm.

¹⁹ F NMR (565 MHz, CDCI ₃ ): d -75.1 (d, J = 7.2 Hz) ppm.

HRMS (ESI+): calculated for [M-NHMe] ⁺ C ₁₀ HI ₂ F ₃ ⁺ : 189.0886, found: 189.0889.

IR (cm ¹ ): 2928, 2860, 1650, 1450, 1365, 1261 , 1 155, 1127, 1 101 , 966, 792.

Example 56: (E)-1 ,1,1-Trifluoro-N-methyldodec-3-en-7-yn-2-amine (3ah)

Prepared according to general procedure D(43% yield).

¹ H NMR (600 MHz, CDCI ₃ ): d 5.86 (dt, J = 15.3, 6.2 Hz, 1 H), 5.36 (dd, J = 15.3, 8.3 Hz, 1 H),

3.41 (p, J = 7.4 Hz, 1 H), 2.45 (s, 3H), 2.29 - 2.25 (m, 4H), 2.15 - 2.1 1 (m, 2H), 1.47 - 1.42 (m, 2H), 1.41 - 1.36 (m, 2H), 0.90 (t, J = 7.2 Hz, 3H) ppm.

¹³ C NMR (150 MHz, CDCI ₃ ): d 136.9, 125.7 (q, J = 282 Hz), 123.6 (m), 81.3, 78.9, 64.3 (q, J = 29 Hz), 34.1 , 32.1 , 31.3, 22.2, 18.8, 18.5, 13.7 ppm.

¹⁹ F NMR (565 MHz, CDCI ₃ ): d -75.2 (d, J = 7.2 Hz) ppm.

HRMS (ESI+): calculated for [M+H] ⁺ C ₁₃ H ₂ IF ₃ N ⁺ : 248.1621 , found: 248.1625.

IR (cm ¹ ): 2932, 2864, 1455, 1365, 1259, 1 180, 1 156, 1 106, 969, 695.

Example 57: Methyl (E)-4-(4,4,4-trifluoro-3-(methylamino)but-1-en-1-yl)benzoate (3ai) Prepared according to general procedure D (71 % yield).

¹ H NMR (600 MHz, CDCI ₃ ): d 8.01 (d, J = 8.3 Hz, 1 H), 7.46 (d, J = 8.3 Hz, 2H), 6.75 (d, J = 15.9 Hz, 1 H), 6.14 (dd, J = 15.9, 8.0 Hz, 1 H), 3.91 (s, 3H), 3.65 (p, J = 7.3 Hz, 1 H), 2.51 (s, 3H) ppm.

¹³ C NMR (150 MHz, CDCI ₃ ): d 166.8, 140.2, 135.5, 130.1 (2C), 130.0, 126.7 (2C), 125.5 (q, J = 282 Hz), 124.3, 64.4 (q, J = 29 Hz), 52.3, 34.3 ppm.

¹⁹ F NMR (565 MHz, CDCI ₃ ): d -74.6 (d, J = 7.1 Hz) ppm.

HRMS (ESI+): calculated for [M+H] ⁺ C ₁₃ H ₁₅ F ₃ N0 ₂ ⁺ : 274.1049, found: 274.1043.

IR (crrf ¹ ): 2954, 1715, 1608, 1436, 1277, 1 156, 1 102, 971 , 762.

Example 58: (Z)-1,1,1-Trifluoro-N-methyl-3-propylhept-3-en-2-amine (3aj)

Prepared according to general procedure D (54% yield).

¹ H NMR (600 MHz, CDCI ₃ ): d 5.54 (t, J = 7.2 Hz, 1 H), 3.34 (q, J = 7.7 Hz, 1 H), 2.39 (s, 3H), 2.16 - 2.05 (m, 3H), 1.94 (ddd, J = 13.9, 10.6, 5.2 Hz, 1 H), 1.47 - 1.36 (m, 4H), 0.93 (t, J = 7.3 Hz, 3H), 0.91 (t, J = 7.4 Hz, 3H) ppm.

¹³ C NMR (150 MHz, CDCI ₃ ): d 132.9, 132.7, 125.9 (q, J = 282 Hz), 67.2 (q, J = 28 Hz), 34.5, 31.3, 30.0, 22.8, 22.1 , 14.5, 13.9 ppm.

¹⁹ F NMR (565 MHz, CDCI ₃ ): d -73.2 (d, J = 7.6 Hz) ppm.

HRMS (ESI+): calculated for [M+H] ⁺ C ₁₂ H ₁₅ F ₃ N ⁺ : 230.1 151 , found: 230.1 154.

IR (cm ¹ ):, 2961 , 2873, 1459, 1353, 1261 , 1 156, 1 126, 1094, 708.

Example 59: (E)-1,1,1-Trifluoro-N,3-dimethyl-4-phenylbut-3-en-2-amine (3ak)

Prepared according to general procedure D (65% yield).

¹ H NMR (600 MHz, CDCI ₃ ): d 7.40 - 7.34 (m, 1 H), 7.34 - 7.30 (m, 1 H), 7.29 - 7.25 (m, 1 H), 6.61 (s, 1 H), 3.60 (q, J = 7.7 Hz, 1 H), 2.47 (s, 2H), 1.92 (s, 2H) ppm. ¹³ C NMR (150 MHz, CDCI ₃ ): d 136.6, 132.9, 130.6, 129.1 (2C), 128.2 (2C), 127.1 , 125.5 (q, J = 283 Hz), 69.7 (q, J = 28 Hz), 34.0, 13.6, 13.6 ppm.

¹⁹ F NMR (565 MHz, CDCI ₃ ): d -72.6 (d, J = 7.6 Hz) ppm.

HRMS (ESI+): calculated for [M+H] ⁺ CI ₂ H ₁₅ F ₃ N ⁺ : 230.1 151 , found: 230.1 154.

IR (cm ¹ ): 1447, 1350, 1257, 1 154, 1134, 1091 , 1014, 836, 752, 697.

Example 60: 12,12,12-trifluoro-11-(methylamino)dodecan-1-ol (3al)

Prepared according to general procedure D (67% yield).

¹ H NMR (600 MHz, CDCI ₃ ) d 3.63 (t, J = 6.6 Hz, 2H), 2.91 - 2.87 (m, 1 H), 2.53 (s, 3H), 1.68 - 1.44 (m, 6H), 1.39 - 1.29 (m, 15H).

¹³ C NMR (175 MHz, CDCI ₃ ) d 127.2 (q, J = 284.5 Hz), 63.2 , 61.0 (q, J = 26.9 Hz), 34.9 , 32.9, 29.7, 29.6 (2C), 29.5, 29.5, 28.5, 25.9, 25.8.

¹⁹ F NMR (700 MHz, CDCI ₃ ) d -74.36 (d, J = 5.1 Hz).

HRMS (ESI) calculated for[M+H ⁺ ] C ₁₃ H ₂₇ NOF ₃ = 270.2039, found 270.2042.

IR (cm ¹ ): 3338, 2925, 2855, 1676, 1463, 1264, 1 148, 1 1 17, 1056.

Example 61 : 10-bromo-1 ,1 ,1-trifluoro-N-methyldecan-2-amine (3am)

Prepared according to general procedure D (82% yield).

¹ H NMR (600 MHz, CDCI ₃ ) d 3.41 (t, J = 6.8 Hz, 2H), 2.86 (ddd, J = 12.0, 7.8, 3.9 Hz, 1 H), 2.53 (s, 3H), 1.88 - 1.83 (m, 2H), 1.67 - 1.66 (m, 1 H), 1.45 - 1.32 (m, 6H), 1.02 (bs, 1 H).

¹³ C NMR (175 MHz, CDCI ₃ ) d 127.3 (q, J = 284.6 Hz), 61.1 (q, J = 26.8), 35.0, 34.1 , 32.9, 29.5, 29.3, 28.8, 28.6 (q, J = 1.7 Hz), 28.2, 25.8.

¹⁹ F NMR (700 MHz, CDCI ₃ ) d -74. 62 (d, J = 7.6 Hz).

HRMS (ESI) calculated for [M+H ⁺ ] CnH^NFsBr = 304.0882, found 304.0884.

IR (cm ¹ ) 2928, 2857, 1461 , 1263, 1 146, 1 11 1. Example 62: Ethyl 2-(methylamino)-4-phenylbutanoate (5a)

Accroding to general procedure E: A round-bottom flask was charged with ethyl 2,2- bis(dimethylamino)acetate (4 equiv.) and a magnetic stir-bar under argon-atmosphere was cooled to 0 °C, and then trifloroacetic acid (to provide a concentration of alkene of 0.6 M with respect to TFA) was added and stirred for 5 minutes. After this, alkene (1 equiv., 0.216 mmol) was added. The flask was sealed and placed at room temperature. The reaction was vigorously stirred at this temperature for 20 h, after which it was cooled to 0 °C. Then aqueous saturated NaHC0 ₃ was added until the reaction mixture reached a pH higher than 7. The resulting biphasic mixture was separated and the aqueous phase was extracted with dichloromethane (3 x 200 mL/mmol). The combined organic phases were then dried over anhydrous potassium carbonate and filtered. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH40H 24:1 :0.15) to afford the analytically pure desired product in 39% yield.

¹ H NMR (600 MHz, CDCI3) d 7.30 - 7.24 (m, 2H), 7.21 - 7.17 (m, 3H), 4.20 (q, J = 7.0 Hz, 2H), 3.15 (t, J = 6.8 Hz, 1 H), 2.75 - 2.65 (m, 2H), 2.38 (s, 3H), 2.01 - 1.84 (m, 2H), 1.29 (t, J = 7.0 Hz, 3H)

¹³ C NMR (125 MHz, CDCI3) d 175.2, 141.4, 128.4 (2C), 128.3 (2C), 125.9, 62.7, 60.6, 34.9, 34.7, 32.0, 14.4; HRMS (ESI+): exact mass calculated for [M+H]+ (C13H19N0 ₂ ) requires m/z 222.1489, found m/z 222.1487.

IR (cm ¹ ) 2930, 1731 , 1181 , 510, 446.

Example 63: Ethyl 2-(methylamino)-6-phenylhexanoate (5b)

According to general procedure E: A round-bottom flask was charged with ethyl 2,2- bis(dimethylamino)acetate (4 equiv.) and a magnetic stir-bar under argon-atmosphere was cooled to 0 °C, and then trifloroacetic acid (to provide a concentration of the alkene of 0.6 M with respect to TFA) was added and stirred for 5 minutes. After this, alkene (1 equiv., 0.216 mmol) was added. The flask was sealed and placed at 50 °C. The reaction was vigorously stirred at this temperature for 20 h, after which it was cooled to 0 °C. Then aqueous saturated NaHC0 ₃ was added until the reaction mixture reached a pH higher than 7. The resulting biphasic mixture was separated and the aqueous phase was extracted with dichloromethane (3 x 200 mL/mmol). The combined organic phases were then dried over anhydrous potassium carbonate and filtered. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH40H 24:1 :0.15) to afford the analytically pure desired product in 53% yield.

¹ H NMR (600 MHz, CDCI3) d 7.30 - 7.24 (m, 2H), 7.21 - 7.14 (m, 3H), 4.18 (q, J = 7.1 Hz, 2H), 3.12 (t, J = 6.7 Hz, 1 H), 2.60 (t, J = 7.9 Hz, 2H), 2.36 (s, 3H), 1.70 - 1.58 (m, 4H), 1.46 - 1.34 (m, 2H), 1.26 (t, J = 7.1 Hz, 3H)

¹³ C NMR (125 MHz, CDCI3) d 175.4, 142.4, 128.4 (2C), 128.3 (2C), 125.7, 63.2, 60.5, 35.7, 34.8, 33.3, 31.3, 25.4, 14.3.

HRMS (ESI+): exact mass calculated for [M+H]+ (C15H23N0 ₂ ) requires m/z 250.1802, found m/z 250.1800.

IR (cm ¹ ) 2933, 1729, 1453, 1177, 698.

Example 64: Diethyl (1-(methylamino)-3-phenylpropyl)phosphonate (7a)

According to general procedure F: A round-bottom flask was charged with diethyl ((dimethylamino)(methoxy)methyl)phosphonate (4 equiv.) and a magnetic stir-bar under argon-atmosphere was cooled to 0 °C, and then trifloroacetic acid (to provide a concentration of the alkene of 0.1 M with respect to TFA) was added and stirred for 5 minutes. After completed addition of the solvent, the flask was sealed and placed at - 10 °C. After this, alkene (1 equiv., 0.216 mmol) was added. The reaction was vigorously stirred at - 10 °C for 20 h, after which it was allowed to warm upto 0 °C. Then aqueous saturated NaHC0 ₃ was added until the reaction mixture reached a basic pH (higher than 7). The resulting biphasic mixture was separated and the aqueous phase was extracted with dichloromethane (3 x 200 mL/mmol). The combined organic phases were then dried over anhydrous potassium carbonate and filtered. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH40H 24:1 :0.15) to afford the analytically pure desired product in 34% yield.

¹ H NMR (600 MHz, CDCI3) d 7.32 - 7.25 (m, 2H), 7.23 - 7.16 (m, 3H), 4.16 - 4.09 (m, 4H), 2.90 - 2.83 (m, 1 H), 2.78 - 2.70 (m, 2H), 2.52 (d, ⁴ J _H,P = 1 .3 Hz, 3H), 2.13 - 2.03 (m, 1 H),

I .93 - 1.83 (m, 1 H), 1.34 - 1.30 (m, 6H).

¹³ C NMR (125 MHz, CDCI3) d 141.6, 128.5 (2C), 128.4 (2C), 125.9, 61.9 (d, ² J _C,P = 7.3 Hz), 61.8 (d, ² J _C,P = 7.3 Hz), 55.9 (d, ¹ J _C,P = 146.6 Hz), 35.1 (d, ³ J _C,P = 6.2 Hz), 32.2 (d, ³ J _C,P =

I I .2 Hz), 31.1 (d, ⁴ J _C,P = 2.7 Hz), 16.5 (d, ³ J _C,P = 5.4 Hz).

³¹ P NMR (600 MHz, CDCI ₃ ) d 28.6.

HRMS (ESI+): exact mass calculated for [M+HJ+ (C14H24N0 ₃ P) requires m/z 286.1567, found m/z 286.1565.

Example 65: Diethyl (1-(methylamino)-5-phenylpentyl)phosphonate (7b)

According to general procedure F: A round-bottom flask was charged with diethyl ((dimethylamino)(methoxy)methyl)phosphonate (4 equiv.) and a magnetic stir-bar under argon-atmosphere was cooled to 0 °C, and then trifloroacetic acid (to provide a concentration of the alkene of 0.1 M with respect to TFA) was added and stirred for 5 minutes. After this, alkene (1 equiv., 0.216 mmol) was added. After completed addition of the solvent, the flask was sealed and placed at room temperature. The reaction was vigorously stirred at this temperature for 20 h, after which it was allowed to cool to 0 °C. Then aqueous saturated NaHC0 ₃ was added until the reaction mixture reached higher than pH 7. The resulting biphasic mixture was separated and the aqueous phase was extracted with dichloromethane (3 x 200 mL/mmol). The combined organic phases were then dried over anhydrous potassium carbonate and filtered. The filtrate was concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography on silica gel (dichloromethane/MeOH/NH40H 24:1 :0.15) to afford the analytically pure desired product in 52% yield.

¹ H NMR (600 MHz, CDCI3) d 7.31 - 7.23 (m, 2H), 7.21 - 7.13 (m, 3H), 4.18 - 4.08 (m, 4H), 2.75 - 2.68 (m, 1 H), 2.67 - 2.58 (m, 2H), 2.51 (d, ⁴ J _KP = 1.3 Hz, 3H), 1.86 - 1.75 (m, 1 H), 1.69 - 1.54 (m, 4H), 1.50 - 1.38 (m, 2H), 1.32 (td, J = 7.2, ⁴ J _H P = 1.1 Hz, 6H).

¹³ C NMR (125 MHz, CDCI3) d 142.5, 128.4 (2C), 128.3 (2C), 125.7, 61.9 (d, ² J _C,P = 7.2 Hz), 61.8 (d, ² J _C,P = 7.1 Hz), 56.8 (d, ¹ J _C,P = 148.4 Hz), 35.8, 35.3 (d, ³ J _{C P} = 6.9 Hz), 31.4, 29.3 (d,

⁴ JC,P = 1.6 Hz), 25.9 (d, ³ J _C,P = 10.6 Hz), 16.5 (dd, ³ J _C,P = 5.6, 1.5 Hz)

³¹ P NMR (600 MHz, CDCI ₃ ) d 28.6.

HRMS (ESI+): exact mass calculated for [M+H] ⁺ (C16H28N0 ₃ P) requires m/z 314.1880, found m/z 314.1879.