Technical field

The present invention relates to the field of catalytic hydrogenation and, more particularly, to the use of Ru complexe with tetradentate ligand of formula (L), in hydrogenation processes for the reduction of ketone, aldehyde, ester or lactone into the corresponding alcohol or diol respectively. Background

Reduction of a carbonyl functional group such as an aldehyde, a ketone or an ester functional group to the corresponding alcohol is one of the fundamental reactions in organic chemistry, and is used in a large number of chemical processes. In general, two main types of processes are known to achieve such a transformation. Such types of processes are the following:

a) hydride processes, in which a silyl or metal hydride salt, such as LiAlH ₄ , is used;

b) hydrogenation processes, in which molecular hydrogen is used.

From a practical point of view, hydrogenation processes are more attractive as they can be run using small amounts of catalyst (typically 10 to 1000 ppm relative to the substrate) and in the presence of small quantities or even in the absence of solvent. Furthermore, hydrogenation processes do not require the use of highly reactive and expensive hydrides, and do not produce important amounts of aqueous waste.

One of the mandatory and characterizing elements of hydrogenation processes is the catalyst or the catalytic system which is used to activate the molecular hydrogen in view of the reduction. The development of useful catalysts or catalytic systems for the hydrogenation of an ester functional group represents still an important need in chemistry.

The first hydrogenation conditions reported were performed under harsh conditions, i.e. high temperature and pressure. An improvement of the efficiency of esters hydrogenation has been reported in W02006106484, WO2013023307 and more recently in Org. Lett., 2015, 17 (3), 454-457 or in CN103709196 wherein catalysts or catalytic systems comprising PNNP ligand or PNN ligand to perform such reductions have been disclosed. However there is still a need to improve the catalytic activity in such a reduction.

The present invention provides a solution to the above problem by performing said difficult hydrogenation of carbonyl group such an ester by using a novel PNNP ligand never reported in the literature so far.

Summary of the Invention

Surprisingly, it has now been discovered that a catalyst comprising a tetradentate ligand as described in the present invention has a higher catalytic activity and is particularly efficient for the hydrogenation in the presence of a base of a carbonyl group such as ester or ketone group. The hydrogenation using said catalyst allows obtaining the desired alcohol more rapidly than by using catalyst reported in the prior arts.

So, a first object of the present invention is a process for the reduction by hydrogenation, using molecular H ₂ , of a C3-C70 substrate containing one or two ketones, aldehydes, esters, or lactones functional groups into the corresponding alcohol, or diol, characterized in that said process is carried out in the presence of a base and at least one catalyst or pre-catalyst containing Ruthenium and a tetradentate ligand of formula

wherein one dotted line indicates a single bond and the other dotted line a single or a double bond, z is 1 when both dotted lines is a single bond or is 0 when one dotted line is a double bond and the other a single bond;

m is 0 or 1; n is a integer between 0 and 4;

q is 0 when the dotted line between N and C(R ⁹ )(R ¹⁰ ) indicates a double bond or is 1 when the dotted line between N and C(R ⁹ )(R ¹⁰ ) indicates a single bond;

q’ is 0 when the dotted line between N and C(R )(R ) indicates a double bond or is 1 when the dotted line between N and C(R 11 )(R 12 ) indicates a single bond; R 1 and R 2 , when taken separately, represent, simultaneously or independently, a linear to C ₈ alkyl group optionally substituted, a linear C ₂ to C ₈ alkenyl group optionally substituted, a branched or cyclic C ₃ to C ₈ alkyl or alkenyl group optionally substituted, a Ce to Cio aromatic group optionally substituted, or an OR or NR R group, R and R being a to C ₈ alkyl group or a C ₂ to C ₈ alkenyl group; or R and R , when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms and including the phosphorus atom to which said R and R groups are bonded;

R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ^{1 1} and R ¹² , taken separately, represent, simultaneously or independently, a hydrogen atom, a Ci-Cio linear alkyl group optionally substituted, a C ₂ - Cio linear alkenyl group optionally substituted, a C3-C10 branched or cyclic alkyl or alkenyl group optionally substituted or a C ₆ to Cio aromatic group optionally substituted; or R ³ and R ⁴ and/or R ⁴ and R ⁵ and/or R ⁵ and R ⁶ and/or R ⁶ and R ⁷ and/or R ⁷ and R ⁸ and/or R ⁸ and R ⁹ and/or R ⁹ and R ¹⁰ and/or R ⁹ and R ^{1 1} and/or R ^{1 1} and R ¹² , when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms;

R ¹³ and R ¹⁴ when taken separately, represent, simultaneously or independently, a C ₆ to Cio aromatic group optionally substituted or an OR or NR R group wherein R and R is a Ci to C ₈ alkyl group or a C ₂ to C ₈ alkenyl group; and

R ¹⁵ when taken separately, represent, simultaneously or independently, a hydrogen atom, a halogen atom, a linear to C ₈ alkyl group optionally substituted, a linear C ₂ to C ₈ alkenyl group optionally substituted, a branched or cyclic C ₃ to C ₈ alkyl or alkenyl group optionally substituted, or a halo- or perhalo-hydrocarbon, CN, S0 ₃ R ³ S0 ₂ R ³ , N0 ₂ , OR ³ or CONR ³ R ⁴ group, R ³ and R ⁴ , independently from each other, being a hydrogen atom or a Ci to C ₈ alkyl group or a C ₂ to C ₈ alkenyl group; two adjacent R ¹⁵ groups can be bonded together to form a C5 to Cio ring optionally substituted;

the optional substituents of R ¹ to R ¹⁵ groups are one or two halogen atoms, to Cio alkoxy, polyalkyleneglycols, halo- or perhalo-hydrocarbon, COOR, or R groups, wherein R is a Ci to Ce alkyl, or a C5 to ₂ cycloalkyl, aralkyl (such as benzyl, phenethyl etc..) or aromatic group, the latter being also optionally substituted by one, two or three halogen atoms or Ci-C ₈ alkyl, alkoxy, nitro, sulfonates, halo- or perhalo-hydrocarbon or ester groups.

A second object of the invention is a ligand of formula

wherein m, n, q, q’ z, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R 15 have the same meaning as above.

A last object of the invention is a complex of formula (1), as defined above.

Description of the invention

The invention relates to a novel and very efficient catalyst to be used in the very challenging hydrogenation, in particular for the hydrogenation of esters, hindered ketones or thermosensitive ketones.

So, a first object of the present invention is a process for the reduction by hydrogenation, using molecular H ₂ , of a C3-C70 substrate containing one or two ketones, aldehydes, esters, or lactones functional groups into the corresponding alcohol, or diol, characterized in that said process is carried out in the presence of a base and at least one catalyst or pre-catalyst containing a ruthenium and a tetradentate ligand of formula

wherein one dotted line indicates a single bond and the other dotted line a single or a double bond, z is 1 when both dotted lines is a single bond (i.e. the nitrogen atom belongs to an amino group) or is 0 when one dotted line is a double bond and the other a single bond (i.e. the nitrogen atom belongs to an imino group); m is 0 or 1; n is a integer between 0 and 4;

q is 0 when the dotted line between N and C(R ⁹ )(R ¹⁰ ) indicates a double bond or is 1 when the dotted line between N and C(R ⁹ )(R ¹⁰ ) indicates a single bond;

q’ is 0 when the dotted line between N and C(R )(R ) indicates a double bond or is 1 when the dotted line between N and C(R 11 )(R 12 ) indicates a single bond;

R and R , when taken separately, represent, simultaneously or independently, a linear Ci to Cg alkyl group optionally substituted, a linear C ₂ to Cg alkenyl group optionally substituted, a linear, branched or cyclic C ₃ to Cg alkyl or alkenyl group optionally substituted, a C ₆ to Cio aromatic group optionally substituted, or an OR or NR R group, R and R being a Ci to Cg alkyl group or a C ₂ to Cg alkenyl group; or R and R , when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms and including the phosphorus atom to which said R and R groups are bonded;

R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , taken separately, represent, simultaneously or independently, a hydrogen atom, a Ci-Cio linear alkyl group optionally substituted, a C ₂ -

Cio linear alkenyl group optionally substituted, a C3-C10 linear, branched or cyclic alkyl or alkenyl group optionally substituted or a C ₆ to Cio aromatic group optionally substituted; or R ³ and R ⁴ and/or R ⁴ and R ⁵ and/or R ⁵ and R ⁶ and/or R ⁶ and R ⁷ and/or R ⁷ and R ⁸ and/or R ⁸ and R ⁹ and/or R ⁹ and R ¹⁰ and/or R ⁹ and R ¹¹ and/or R ¹¹ and R ¹² , when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms;

R ¹³ and R ¹⁴ when taken separately, represent, simultaneously or independently, a linear to Cg alkyl group optionally substituted, a linear C ₂ to Cg alkenyl group optionally substituted, a linear, branched or cyclic C ₃ to Cg alkyl or alkenyl group optionally substituted, a C ₆ to Cio aromatic group optionally substituted, or an OR or NR R group, R and R being a to Cg alkyl group or a C ₂ to Cg alkenyl group; or R and R ¹⁴ , when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms and including the phosphorus atom to which said R ¹³ and R ¹⁴ groups are bonded ; and

R ¹⁵ , when taken separately, represent, simultaneously or independently, a hydrogen atom, a halogen atom, a linear Ci to Cg alkyl group optionally substituted, a linear C ₂ to Cg alkenyl group optionally substituted, a linear, branched or cyclic C ₃ to Cg alkyl or alkenyl group optionally substituted, or a halo- or perhalo-hydrocarbon, CN, S0 ₃ R , S0 ₂ R , N0 ₂ , OR ³ , or CONR ³ R ⁴ group, R ³ and R ⁴ , independently from each other, being a hydrogen atom or a Ci to C ₈ alkyl group or a C ₂ to C ₈ alkenyl group; two adjacent R ¹⁵ groups can be bonded together to form a C ₅ to C ₁₀ ring optionally substituted.

R ¹⁵ may be, relative to the phosphine substituent, an ortho, a meta, a para substituent of the aromatic ring.

According to a particular embodiment of the invention, the substrate can be a compound of formula (I)

Wherein p is 0 or 1 ; when p is 1, R ^a and R ^b represent, simultaneously or independently, a linear, branched or cyclic C ₁ -C ₃₀ aromatic, alkyl or alkenyl group, optionally substituted; or

when p is 0, R ^a represents a linear, branched or cyclic C ₁ -C ₃₀ aromatic, alkyl or alkenyl group, optionally substituted and R ^b represents a hydrogen atom, a linear, branched or cyclic C ₁ -C ₃₀ aromatic, alkyl or alkenyl group, optionally substituted; or

R ^a and R ^b are bonded together and form a C ₄ -C ₂ o saturated or unsaturated group, optionally substituted.

When p is 1, the corresponding alcohols (i.e (P-a) and (Il-b)), or the corresponding diol (IG), of said substrate (I), are of formula

wherein R ^a and R ^b are defined as in formula (I).

A compound of formula (P) (i.e. P-a or Il-b) will be obtained in the case where R ^a and R ^b are not bonded together, while a compound of formula (IG) will be obtained in the case where R ^a and R ^b are bonded together.

When p is 0, the corresponding alcohols of said substrate (I) are of formula

(II-c)

wherein R ^a and R ^b are defined as in formula (I).

It is understood that by“a linear, branched or cyclic . aromatic, alkyl, or alkenyl group” it is meant that said R ^a or R ^b can be in the form of, e.g., a linear alkyl group or can also be in the form of a mixture of said type of groups, e.g. a specific R ^a may comprises a linear alkyl, a branched alkenyl, a (poly)cyclic alkyl and an aryl moiety, unless a specific limitation to only one type is mentioned. Similarly, in all the below embodiments of the invention when a group is mentioned as being in the form of more than one type of topology (e.g. linear, cyclic or branched) and/or unsaturation (e.g. alkyl, aromatic or alkenyl) it is meant also a group which may comprise moieties having any one of said topologies or unsaturations, as above explained.

According to a further embodiment of the invention, the substrate is a ketone, an aldehyde, an ester, or a lactone that will provide an alcohol or a diol, which is useful in the pharmaceutical, agrochemical or perfumery industry as final product or as an intermediate. Particularly preferred substrate is a ketone, an aldehyde, an ester, or a lactone that will provide an alcohol or diol, which is useful in the perfumery industry as final product or as an intermediate. Even a more particularly preferred substrate is an ester, or a lactone that will provide an alcohol or diol, which is useful in the perfumery industry as final product or as an intermediate.

A particular embodiment of the invention’s process is shown in Scheme 1:

H

H ₂ > H

/

+

O

R 'CI I ₂ R ^b

Ru complex

w (Il-a) (Il-b)

According to any one of the above embodiments of the invention, p is 0 or 1. Preferably p is 1.

According to any one of the above embodiments of the invention, the substrate is a C5-C30 compound of formula (I), and in particular one may cite those wherein R ^a and R ^b represent simultaneously or independently a linear C1-C30 alkyl group optionally substituted, a branched or cyclic C ₃ -C ₃₀ alkyl or alkenyl group optionally substituted or a C ₅ -C ₃₀ aromatic group optionally substituted; or R ^a and R ^b are bonded together and form a C ₄ -C ₂₀ saturated or unsaturated linear, branched, mono-, di- or tri-cyclic group, optionally substituted.

According to a further embodiment of the invention the substrate is a C ₅ -C ₂₀ compound of formula (I), wherein R ^a and R ^b represent simultaneously or independently a linear, branched or cyclic C ₅ -C ₁₈ aromatic or alkyl group, optionally substituted, or a cyclic C ₅ -C ₁₈ alkenyl group, optionally substituted; or R ^a and R ^b are bonded together and form a C ₄ -C ₂₀ saturated or unsaturated linear, branched, mono-, di- or tri-cyclic group, optionally substituted.

Furthermore, according to a yet further embodiment, when R ^a and/or R ^b represent an alkenyl group then the carbon-carbon double bond is not terminal and is not conjugated.

Possible substituents of R ^a and R ^b are one, two or three halogen, OR ^c , NR ^C ₂ or R ^c groups, in which R ^c is a hydrogen atom, a halogenated C ₁ -C ₂ group or a to o cyclic, linear or branched alkyl, or alkenyl group, preferably a Ci to C ₄ linear or branched alkyl or alkenyl group. As other possible substituents one may also cite a group COOR ^c , which can also be reduced to the corresponding alcohol during the invention’s process, according to the molar amount of H ₂ used, as well known by a person skilled in the art.

Non-limiting examples of substrates are alkyl cinnamates, sorbates or salycilates, alkyl esters of natural (fatty or not) acids, Sclareolide, spirolactones, allylic ester, di alkyl diesters, (un) substituted benzoic esters, and unsaturated esters such as b-g unsaturated esters. In particular, the substrate can be selected from the group consisting of sclareolide, C ₉ -C ₁₅ spirolactones and C ₁ -C ₄ alkyl esters of 4-methyl-6-(2, 6, 6-trimethyl- l-cyclohexen- l-yl)-3-hexenoic acid. One can also cite the di alkyl esters of l,4-dicarboxylate- cyclohexane, the di C _1-5 alkyl esters of the C _2-10 alkanediyl-dicarboxylates, C _1-5 alkyl cyclopropanecarboxylates, mono-, di- or tri-methoxybenzoic esters.

The process of the invention is characterized by the use, as catalyst or pre-catalyst (hereinafter referred to as complexes unless specified otherwise), of a ruthenium complex as described above. The complex can be in the form of an ionic or neutral species.

According to an embodiment of the invention, the ruthenium complex can be of the general formula [RU(L)Y ₂ ] [RU(L)(X)(Y) ₂ ] [Ru(L)(X) _n (Y) _2-n ] (Z) _n

(1) (2) (3) wherein L represents a tetradentate ligand as defined above; and

each Y represents, simultaneously or independently, CO, a hydrogen or halogen atom, a hydroxyl group, or a Ci-C ₆ alkyl, alkenyl, alkoxy or carboxylic radical, or also a BH ₄ or AlH ₄ group;

X represents a C ₃ -C ₃₀ mono-phosphine or a solvent.

Z represents a non-coordinated anion; and

n is 0, 1 or 2.

In a particular embodiment of the invention, in formula (1), (2) or (3), each Y represents, simultaneously or independently, a hydrogen or chlorine atom, a hydroxy radical, a to C ₆ alkoxy radical, such as a methoxy, ethoxy or isopropoxy radical, or a Ci to C ₆ acyloxy radical such as a CH ₃ COO, CH ₃ CH ₂ COO or (CfR^CCOO radical. More preferably, each Y represents, simultaneously or independently, a hydrogen or chlorine atom, a methoxy, ethoxy or isopropoxy radical, or a CH ₃ COO, CH ₃ CH ₂ COO or (CH ₃ ) ₃ CCOO radical.

In a particular embodiment of the invention, in formula (2), the tetradendate ligand L is partly coordinated to a metal; i.e. only 3 atoms are coordinated to the Metal. When complex of formula (2) is used, the complex of formula (1) is formed in situ under the reaction conditions.

In a particular embodiment of the invention, in formula (2) or (3), X represents a mono-phosphine of formula PR ^d 3, wherein R ^d is a CrC _l2 group, such as linear, branched or cyclic alkyl, alkoxy or aryloxy group optionally substituted, substituted or unsubstituted phenyl, diphenyl or naphthyl or di-naphthyl group. More particularly R ^d may represent a substituted or unsubstituted phenyl, diphenyl or naphthyl or di-naphthyl group. Possible substituents are those cited below for the various groups R ¹ to R ¹⁵ . Preferably, X is a triphenylpho sphine .

In formula (3), X may also be a solvent, the term“solvent” has to be understood according to the usual meaning in the art and includes compounds used as diluent in the preparation of the complex or during the invention’s process, non-limiting examples are dimethylsulfoxide, acetonitrile, dimethylformamide, an alcohol (e.g. an Ci-C ₄ alcohol), or also THF, acetone, pyridine or a C ₃ -Cs ester or the substrate of the invention’s process.

In a particular embodiment of the invention, in formula (3), Z represents a halogen atom, a hydroxyl group, or a Ci-C ₆ alkoxy, phenoxy or carboxylic radical.

The complex of formula (1) represents, in general for practical reasons, a preferred embodiment of the invention.

Possible substituents of the various groups R ¹ to R ¹⁵ are one or two halogen atoms, Ci to Cio alkoxy, polyalkyleneglycols, halo- or perhalo-hydrocarbon, COOR, or R groups, wherein R is a Ci to C ₆ alkyl, or a C5 to C12 cycloalkyl, aralkyl (such as benzyl, phenethyl etc..) or aromatic group, the latter being also optionally substituted by one, two or three halogen atoms or C Cg alkyl, alkoxy, nitro, sulfonates, halo- or perhalo-hydrocarbon or ester groups. By“halo- or perhalo-hydrocarbon” it is meant groups such as CF ₃ or CClH ₂ for instance. Preferably, said substituents can be, and in particular when said groups are or contain phenyl groups, one or two halogen atoms, one or two Ci to C5 alkoxy or polyalkyleneglycols groups, COOR or R groups wherein R is a Ci to C ₄ alkyl, or a Cs_6 cycloalkyl, aralkyl or aromatic group, the latter being also optionally substituted as above defined. Alternatively, possible substituents of R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ^{1 1} and R ¹² are one or two halogen atoms or R ¹⁶ or OR ¹⁶ groups wherein R ¹⁶ being a Ci to C ₆ alkyl groups or a Ci to C ₄ alkyl groups.

According to a particular embodiment of the invention, m is 1. In other words, L can be a compound of formula

wherei

R ¹⁴ and R ¹⁵ have the same meaning as above.

According to a particular embodiment of the invention, m is 0. In other words, L can be a compound of formula

Wherein the dotted line, z, n, q, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ and R ¹⁵ have the same meaning as above.

According to a particular embodiment of the invention, L can be a compound of formula

wherein the dotted line, z, n, R ¹ , R ² , R ⁹ , R ¹³ , R ¹⁴ and R ¹⁵ have the same meaning as above.

According to a particular embodiment of the invention, L can be a compound of formula

wherein the dotted line, z, n, R ¹ , R ² , R ¹² , R ¹³ , R ¹⁴ and R 15 have the same meaning as above.

According to any one of the above embodiments of the invention, R 1 and R 2 may represent, when taken separately, simultaneously or independently, a linear to Cg alkyl group optionally substituted, a linear C ₂ to C ₈ alkenyl group optionally substituted, a branched or cyclic C ₃ to Cg alkyl or alkenyl group optionally substituted, a C ₆ to Cio aromatic group optionally substituted; or R and R , when taken together, may form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms and including the phosphorus atom to which said R and R groups are bonded. Preferably, R and R may represent, when taken separately, simultaneously or independently, a linear to C ₆ alkyl group optionally substituted, a branched or cyclic C ₃ to C ₆ alkyl group optionally substituted, a phenyl group optionally substituted; or R and R , when taken together, may form a saturated or unsaturated ring optionally substituted, having 4, 5, 6 or 7 carbon atoms and including the phosphorus atom to which said R and R groups are bonded. Preferably, R and R may represent a linear Ci to C ₆ alkyl group optionally substituted, a branched or cyclic C ₃ to C ₆ alkyl group optionally substituted or a phenyl group optionally substituted. Preferably, R and R may represent a linear Ci to C ₆ alkyl group, a branched or cyclic C ₃ to C ₆ alkyl group or a phenyl group. Even more preferably, R and R may represent a cyclohexyl, a phenyl, a tert- butyl, an /so-propyl or an ethyl group. Even more preferably, R and R may represent a phenyl or a tert- butyl group.

According to any one of the above embodiments of the invention, R ¹³ and R ¹⁴ , when taken separately, represent, simultaneously or independently, a C ₆ to Cio aromatic group optionally substituted or an OR or NR R group wherein R and R is a Ci to Cg alkyl group or a C ₂ to Cg alkenyl group. Preferably, R ¹³ and R ¹⁴ may represent phenyl group optionally substituted. Even more preferably, R ¹³ and R ¹⁴ may represent phenyl group substituted with at least one halogen atom, halo- or perhalo-hydrocarbon or R group wherein R is a Ci to C ₄ alkyl, or a C cycloalkyl, aralkyl or aromatic group, the latter being also optionally substituted as above defined.

According to any one of the above embodiments of the invention, R ³ , R ⁴ , R ⁵ , R ⁶ , R , R , R , R , R and R , taken separately, represent, simultaneously or independently, a hydrogen atom, a Ci-C ₆ linear alkyl group optionally substituted, a C ₂ -C ₆ linear alkenyl group optionally substituted, a C ₃ -C ₆ branched or cyclic alkyl or alkenyl group optionally substituted or a C ₆ to Cio aromatic group optionally substituted; or R ⁴ and R ⁵ and/or R ⁵ and R ⁶ and/or R ⁸ and R ⁹ , when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms; or R ⁹ and R ¹¹ , when taken together, form a saturated or unsaturated non aromatic ring optionally substituted, having 4 to 10 atoms. Preferably, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² , taken separately, may represent, simultaneously or independently, a hydrogen atom, a Ci-C ₄ linear alkyl group optionally substituted, a C ₅ -C ₆ branched or cyclic alkyl group optionally substituted or a phenyl group optionally substituted; R ⁴ and R ⁵ or R ⁵ and R ⁶ or R ⁸ and R ⁹ , when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 7 carbon atoms. Preferably, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹¹ and R ¹² may represent a hydrogen atom, a methyl or a phenyl group. Even more preferably, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹¹ and R ¹² may represent a hydrogen atom

According to any one of the above embodiments of the invention, n may be 0, 1 or 2. Preferably, n is 0 or 1. When n is 1, R ¹⁵ may be, relative to the phosphine substituent, a meta or a para substituent of the aromatic ring. Preferably, R ¹⁵ may be, relative to the phosphine substituent, a para substituent of the aromatic ring.

According to any one of the above embodiments of the invention, R ¹⁵ , when taken separately, may represent, simultaneously or independently, a halogen atom, a linear to C ₄ alkyl group optionally substituted, a linear C ₂ to C ₅ alkenyl group optionally substituted, a linear, branched or cyclic C ₃ to Cg alkyl or alkenyl group optionally substituted, or a halo- or perhalo-hydrocarbon group. Preferably, may represent, simultaneously or independently, a halogen atom, or a halo- or perhalo-hydrocarbon group such as CF ₃ .

Examples of suitable ligands includes, but are not limited to, l-(6- ( (diphenylpho sphaneyl)methyl)pyridin- 2-yl)-N- (2-

(diphenylphosphaneyl)phenyl)methanimine, 2-(diphenylphosphaneyl)-N-((6-

( (diphenylpho sphaneyl)methyl)pyridin- 2-yl)methyl)aniline, 2- (diphenylpho sphaneyl) -N- (l-(6-((diphenylphosphaneyl)methyl)pyridin-2-yl)ethyl)anilin e, l-(6-

((diphenylphosphaneyl)methyl)pyridin-2-yl)-N-(2-(diphenyl phosphaneyl)phenyl)ethan-l- imine, l-(6-((diphenylphosphaneyl)methyl)pyridin-2-yl)-N-(2-

(diphenylphosphaneyl)phenyl)-l-phenylmethanimine, 2-(diphenylphosphaneyl)-N-((6- ( (diphenylpho sphaneyl)methyl)pyridin- 2-yl) (phenyl) methyl) aniline, 2-

(diphenylphosphaneyl)-N-((6-((diphenylphosphaneyl)methyl) pyridin-2-yl)methyl)-5- (trifluoromethyl)aniline, N-(2-(diphenylphosphaneyl)-5-(trifluoromethyl)phenyl)-l-(6- ( (diphenylpho sphaneyl)methyl)pyridin- 2-yl)methanimine, N - (5 -chloro-2- (diphenylphosphaneyl)phenyl)-l-(6-((diphenylphosphaneyl)meth yl)pyridin-2- yl)methanimine, 5-chloro-2-(diphenylphosphaneyl)-N-((6-

((diphenylphosphaneyl)methyl)pyridin-2-yl)methyl)aniline, 4-chloro-2-

(diphenylphosphaneyl)-N-((6-((diphenylphosphaneyl)methyl) pyridin-2-yl)methyl)aniline, N - (4-chloro- 2- (diphenylpho sphaneyl)phenyl) - 1 - (6-

( (diphenylpho sphaneyl)methyl)pyridin- 2-yl)methanimine, N - (2- (diphenylpho sphaneyl) -4- (trifluoromethyl)phenyl)-l-(6-((diphenylphosphaneyl)methyl)p yridin-2-yl)methanimine, 2-(diphenylphosphaneyl)-N-((6-((diphenylphosphaneyl)methyl)p yridin-2-yl)methyl)-4- (trifluoromethyl)aniline, N-((6-((diisopropylphosphaneyl)methyl)pyridin-2-yl)methyl)-2 - (diphenylphosphaneyl)-4-(trifluoromethyl)aniline, l-(6-

((diisopropylphosphaneyl)methyl)pyridin-2-yl)-N-(2-(diphe nylphosphaneyl)-4- (trifluoromethyl)phenyl)methanimine, N-(4-chloro-2-(diphenylphosphaneyl)phenyl)-l-(6- ((diisopropylphosphaneyl)methyl)pyridin-2-yl)methanimine, 4-chloro-N-((6-

((diisopropylphosphaneyl)methyl)pyridin-2-yl)methyl)-2-(d iphenylphosphaneyl)aniline, 5-chloro-N-((6-((diisopropylphosphaneyl)methyl)pyridin-2-yl) methyl)-2- (diphenylphosphaneyl)aniline, N-(5-chloro-2-(diphenylphosphaneyl)phenyl)-l-(6-

((diisopropylphosphaneyl)methyl)pyridin-2-yl)methanimine, l-(6-

((diisopropylphosphaneyl)methyl)pyridin-2-yl)-N-(2-(diphe nylphosphaneyl)-5- (trifluoromethyl)phenyl)methanimine, ((6-((diisopropylphosphaneyl)methyl)pyridin-2- yl)methyl)-2-(diphenylphosphaneyl)-5-(trifluoromethyl)anilin e, ((6-((di-tert- butylpho sphaneyl)methyl)pyridin- 2-yl)methyl)- 2- (diphenylpho sphaneyl) -5 - (trifluoromethyl)aniline, l-(6-((di-tert-butylphosphaneyl)methyl)pyridin-2-yl)-N-(2-

(diphenylphosphaneyl)-5-(trifluoromethyl)phenyl)methanimi ne, N-(5-chloro-2-

(diphenylphosphaneyl)phenyl)-l-(6-((di-tert-butylphosphan eyl)methyl)pyridin-2- yl)methanimine, 5-chloro-N-((6-((di-tert-butylphosphaneyl)methyl)pyridin-2-y l)methyl)- 2-(diphenylphosphaneyl)aniline, N-(4-chloro-2-(diphenylphosphaneyl)phenyl)-l-(6-((di- tert-butylphosphaneyl)methyl)pyridin-2-yl)methanimine, 4-chloro-N-((6-((di-tert- butylpho sphaneyl)methyl)pyridin- 2-yl)methyl)- 2- (diphenylpho sphaneyl) aniline, N- ( (6- ((di-tert-butylphosphaneyl)methyl)pyridin-2-yl)methyl)-2-(di phenylphosphaneyl)-4- (trifluoromethyl)aniline, l-(6-((di-tert-butylphosphaneyl)methyl)pyridin-2-yl)-N-(2-

(diphenylphosphaneyl)-4-(trifluoromethyl)phenyl)methanimi ne, l-(6-((di-tert- butylphosphaneyl)methyl)pyridin-2-yl)-N-(2-(diphenylphosphan eyl)phenyl)ethan-l-imine, N-(l-(6-((di-tert-butylphosphaneyl)methyl)pyridin-2-yl)ethyl )-2-

(diphenylphosphaneyl)aniline, N-((6-((di-tert-butylphosphaneyl)methyl)pyridin-2- yl)(phenyl)methyl)-2-(diphenylphosphaneyl)aniline, l-(6-((di-tert- butylpho sphaneyl)methyl)pyridin- 2-yl)-N- (2- (diphenylpho sphaneyl)phenyl) - 1 - phenylmethanimine, l-(6-((di-tert-butylphosphaneyl)methyl)pyridin-2-yl)-N-(2-

(diphenylphosphaneyl)phenyl)methanimine, N-((6-((di-tert- butylpho sphaneyl)methyl)pyridin- 2-yl)methyl)- 2- (diphenylpho sphaneyl) aniline, N- ( (6- ((diisopropylphosphaneyl)methyl)pyridin-2-yl)methyl)-2-(diph enylphosphaneyl)aniline, l-(6-((diisopropylphosphaneyl)methyl)pyridin-2-yl)-N-(2-

(diphenylphosphaneyl)phenyl)methanimine, l-(6-((diethylphosphaneyl)methyl)pyridin-2- yl)-N-(2-(diphenylphosphaneyl)phenyl)methanimine, N-((6-

( (diethylpho sphaneyl)methyl)pyridin- 2-yl)methyl)- 2- (diphenylpho sphaneyl) aniline, 1 - (6- ( (dicyclohexylpho sphaneyl)methyl)pyridin- 2-yl)-N- (2-

(diphenylphosphaneyl)phenyl)methanimine, N-((6-

( (dicyclohexylpho sphaneyl)methyl)pyridin- 2-yl)methyl)- 2- (diphenylpho sphaneyl) aniline, N-(2-(6-((diphenylphosphaneyl)methyl)pyridin-2-yl)ethyl)-l-( 2-

(diphenylphosphaneyl)phenyl)methanimine, N-(2-(diphenylphosphaneyl)benzyl)-2-(6- ( (diphenylpho sphaneyl)methyl)pyridin-2-yl)ethan- 1 -amine, 2-(6-((di-tert- butylphosphaneyl)methyl)pyridin-2-yl)-N-(2-(diphenylphosphan eyl)benzyl)ethan-l-amine or N-(2-(6-((di-tert-butylphosphaneyl)methyl)pyridin-2-yl)ethyl )-l-(2-

(diphenylphosphaneyl)phenyl)methanimine.

When the ligand is an imine, said ligand may be in a Z or E configuration, preferably in E.

The ligands described above can be obtained by applying standard methods which are well known in the state of the art and by the person skilled in the art. Therefore, their preparation does not require a specific description. For example one may revert to Org. Lett., 2015, 17 (3), 454-457.

In general, the complexes of formula (1) can be prepared and isolated prior to their use in the process according to the general methods described in the literature. A method is described in the Example.

Moreover, the complexes can be prepared in situ, by several methods, in the hydrogenation medium, without isolation or purification, just before their use. One of the possible procedures to advantageously prepare in situ a complex of the invention consists in reacting an appropriate Ru complex of formula [Ru(“diene”)(“allyl”)2], wherein "diene" represents a cyclic or linear hydrocarbon containing two carbon-carbon double bonds, conjugated or not, such as for example l,5-cyclooctadiene (COD) or norbornadiene, and "allyl" represents a linear or branched C ₃ to C ₈ hydrocarbon radical containing one carbon-carbon double bond such as methylallyl or allyl, with a non-coordinating acid such as HBF ₄ Et ₂ 0, and then treating the resulting solution with the required amount of a ligands L, such as defined previously, to give a solution of a catalyst according to formula (3). Furthermore, the mixture thus obtained can also be treated with a base in the presence of a primary or secondary alcohol. Furthermore, the complexes of formula (1) or (2) can be prepared by reacting an appropriate Ru complex such as, [Ru(“diene”)(“allyl”)2], [RuCl ₂ (PPh ₃ ) ₃ ], [RuCl ₂ (COD)] or [RuCl2(arene)] ₂ with the required amount of a ligands F, such as defined previously (COD representing a cyclooctadiene and arene being e.g. a benzene or naphthalene).

It is also understood that the complex of the invention can also be obtained in situ from complexes which have a similar formula and which in presence of, for example an alcohol and a base, are converted into a invention’s ruthenium complex, for example, from a complex wherein Y has other meaning.

To carry out the processes of the invention it is required also to use a base. Said base can be the substrate itself, if the latter is basic, a corresponding alcoholate or any base having preferentially a pK _a above 11. According to a particular embodiment of the invention said base may have a pK _a above 14. It is also understood that preferably said base does not reduce itself a substrate of formula (I). As non-limiting examples one may cite the following type of base: alcoholate, hydroxides, alkaline or alkaline-earth carbonates, phosphazenes, alkylamidines, alkylguanidine amides, basic alox, siliconates (i.e. silicium derivatives having SiO or SiRO groups), hydrides such as NaBH ₄ , NaH or KH.

One can cite, as non-limiting examples, alkaline or alkaline-earth metal carbonates, such as cesium carbonate, an alkaline or alkaline-earth metal hydroxides, C _HO amidures, Cio-26 phosphazene or an alcoholate of formula (R 0) ₂ M or R OM’, wherein M is an alkaline-earth metal, M’ is an alkaline metal or an ammonium NR ¹⁸ ₄ ⁺ , R ¹⁷ stands for hydrogen or a Ci to C ₆ linear or branched alkyl radical and R stands for a Ci to Cio linear or branched alkyl radical, such as sodium, lithium, cesium or potassium alcoholates. Of course, other suitable bases can be used.

According to an embodiment of the invention, said base is an alkaline alcoholate of formula R ¹⁷ OM’.

As previously mentioned the processes of the invention consist in the hydrogenation of a substrate using a ruthenium complex and a base. A typical process implies the mixture of the substrate with the ruthenium complex, a base and optionally a solvent, and then treating such a mixture with molecular hydrogen at a chosen pressure and temperature.

The complex of the invention, an essential parameter of the process, can be added to the reaction medium in a large range of concentrations. As non-limiting examples, one can cite as complex concentration values those ranging from 1 ppm to 50000 ppm, relative to the amount of substrate. Preferably, the complex concentration will be comprised between 10 and 20000 ppm. Even more preferably, the complex concentration will be comprised between 10 and 5000 ppm. It goes without saying that the optimum concentration of complex will depend, as the person skilled in the art knows, on the nature of the latter, on the nature of the substrate and on the pressure of H ₂ used during the process, as well as the desired time of reaction.

Useful quantities of base, added to the reaction mixture, may be comprised in a relatively large range. One can cite, as non-limiting examples, ranges between 5 to 50000 molar equivalents, relative to the complex (e.g. base/com = 5 to 50000), preferably 20 to 10000.

The hydrogenation reaction can be carried out in the presence or absence of a solvent. When a solvent is required or used for practical reasons, then any solvent current in hydrogenation reactions can be used for the purposes of the invention. Non-limiting examples include aromatic solvents such as toluene, chlorobenzene or xylene, hydrocarbon solvents such as hexane or cyclohexane, ethers such as tetrahydrofuran, methyltetrahydrofuran or MTBE, polar solvents such as primary or secondary alcohols such as isopropanol or ethanol, or mixtures thereof. The choice of the solvent is a function of the nature of the complex and the person skilled in the art is well able to select the solvent most convenient in each case to optimize the hydrogenation reaction. In the hydrogenation process of the invention, the reaction can be carried out at a H ₂ pressure comprised between 10 ⁵ Pa and lOOxlO ⁵ Pa (1 to 100 bars) or even more if desired. Again, a person skilled in the art is well able to adjust the pressure as a function of the catalyst load and of the dilution of the substrate in the solvent. As examples, one can cite typical pressures of 1 to 50xl0 ⁵ Pa (1 to 50 bars).

The temperature at which the hydrogenation can be carried out is comprised between 0°C and l20°C, more preferably in the range of between 20 °C and l00°C. Of course, a person skilled in the art is also able to select the preferred temperature as a function of the melting and boiling point of the starting and final products as well as the desired time of reaction or conversion.

The ligand of formula (L) as defined above is also new. So another object of the present invention is the Ligand of formula (L).

In addition, the catalyst of the present invention is also novel. So a last object of the present invention is a ruthenium complex of the general formula (1) as defined above.

Examples

The invention will now be described in further detail by way of the following examples, wherein the temperatures are indicated in degrees centigrade and the abbreviations have the usual meaning in the art.

All the procedures described hereafter have been carried out under an inert atmosphere unless stated otherwise. Hydrogenations were carried out in open glass tubes placed inside a stainless steel autoclave. ¾ gas (99.99990%) was used as received. All substrates and solvents were distilled from appropriate drying agents under Ar. NMR spectra were recorded on a Bruker AM-400 (1H at 400.1 MHz, ¹³ C at 100.6 MHz, and ³¹ P at 161.9 MHz) spectrometer and normally measured at 300 K, in CDCl ₃ unless indicated otherwise. Chemical shifts are listed in ppm.

Example 1 Preparation of Ligand of the invention

a) N-(2-( diphenylphosphino jbenzyl)- 1-(6-(( diphenylphosphino jmelhyl )pyridin-2- yl)methanimine (L-l) • Preparation of 6-(( diphenylphosphino )methyl )picolinaldehyde:

6-((diphenylphosphino)methyl)picolinaldehyde was obtained according to some previously described procedure (Tan X., Wang Y., Liu Y., Wang F., Shi L., Lee K.-H., Lin Z., Lv H., Zhang X., Org. Lett., 2015, 17 (3), 454-457). Initially isolated by filtration as the hydrochloride salt upon hydrolysis reaction of the acetal derivative under acidic aqueous conditions, basic treatment of the recovered white solid with sodium carbonate afforded desired product as a pale yellow solid.

1H NMR (500 MHz, CD2C12): d (ppm) 3.71 (s, 2H, CH2), 7.17 (d, J =7.7 Hz, 1H, CH), 7.31 (m, 6H, 6CH), 7.44 (m, 4H, 4CH), 7.63 (t, J =7.7 Hz, 1H, CH), 7.68 (d, J =7.6 Hz, 1H, CH), 9.92 (s, 1H, CH).

¹³ C NMR (125 MHz, CD2C12): d (ppm) 38.7 (CH2), 119.2 (CH), 128.3 (CH), 128.8 (CH), 129.3 (CH), 133.3 (CH), 138.2 (C), 152.9 (C), 159.5 (C), 193.9 (CHO).

³¹ P NMR (202 MHz, CD2C12): d (ppm) -9.74 (s).

• (2-(diphenylphosphino)phenyl)methanamine:

(2-(diphenylphosphino)phenyl)methanamine may be synthesized in 2 steps from 2- bromobenzonitrile according to the following pathway

Step 1: Pd(PPh ₃ ) ₄ (0.8 mol.%), 2-bromobenzonitrile and degazed and dry toluene were loaded altogether in a round-bottomed flash equipped with a magnetic stirring bar and a dropping funnel. After purging with nitrogen, NEt ₃ (1.04 eq.) was slowly added a room temperature. Upon addition completion, diphenylphosphine (1.03 eq.) was also slowly added a room temperature and reaction mixture was then heated to reflux for l2h. After cooling down to room temperature, it was washed with degassed water, two times with 20 wt.% aqueous NH ₄ Cl to bring pH down to neutrality and then with water. After azetropic water removal, toluene was fully concentrated to afford crude product as a yellow-orange sticky solid. It was recrystallized from MeOH to afford desired 2- (diphenylphosphino)benzonitrile as a pale yellow solid in 80% yield.

2- (diphenylpho sphino)benzonitrile :

1H NMR (400 MHz, CDC13): d (ppm) 7.04 (ddd, J= 7.6, 4.5 and 1.1 Hz, 1H, CH), 7.27- 7.34 (m, 7H, 7CH), 7.34-7.40 (m, 6H, 6CH), 7.42 (dd, J= 7.6 and 1.1 Hz, 1H, CH), 7.47 (td, J = 7.8 and 1.4 Hz, 1H, CH), 7.71 (ddd, J = 7.8, 3.0 and 1.4 Hz, 1H, CH). ¹³ C NMR (100 MHz, CDC13): d (ppm) 117.8 (C), 128.8 (CH), 128.9 (CH), 129.4 (CH), 132.4 (CH), 133.4 (CH), 133.7 (C), 133.9 (CH), 134.2 (CH), 134.7 (C), 143.2 (C). ³¹ P NMR (162 MHz, CDC13): d (ppm) -7.79 (s, 1P).

Step 2: Degassed and dry THF was added under nitrogen to a round-bottomed flask equipped with a magnetic stirring bar and containing pre- weighted LiAlH4 (1.2 eq.). The suspention was cooled down to 0°C and 2-(diphenylphosphino)benzonitrile was added portionwise. After 2 additional hours at 0°C it was stirred at room temperature overnight. It was then cooled down back to 0°C and slowly quenched with aqueous sodium hydroxide. After THF removal, the remaining residue was dissolved in DCM, passed through a celite plug. The DCM solution was washed with water, dried other sodium sulfate and concentrated to dryness and further dried under high vacuum to afford desired product as a pale yellow solid.

(2-(diphenylphosphino)phenyl)methanamine:

1H NMR (400 MHz, CD2C12): d (ppm) 1.35 (broad s, 2H, NH2), 3.97 (d, J = 1.65 Hz, 2H, CH2), 6.87 (ddd, J= 7.6, 4.5 and 1.2 Hz, 1H, CH), 7.12 (td, J = 7.6 and 1.2 Hz, 1H, CH), 7.20-7.38 (m, 11H, 11CH), 7.42-7.48 (m, 1H, CH).

¹³ C NMR (100 MHz, CD2C12): d (ppm) 45.4 (CH2), 127.3 (CH), 128.2 (CH), 128.9 (CH), 129.1 (CH), 129.6 (CH), 133.8 (CH), 134.2 (CH), 135.4 (C), 137.1 (C), 148.2 (C).

³¹ P NMR (162 MHz, CD2C12): d (ppm) -15.55 (s, 1P).

• ( E)-N-( 2-( diphenylphosphino )benzyl)-l -( 6-

( ( diphenylphosphino )methyl )pyridin-2 -yl )methanimine (HI):

(E)-N-(2-(diphenylphosphino)benzyl)-l-(6-((diphenylphosph ino)methyl)pyridin-2- yl)methanimine was obtained by reaction at room temperature in THF of an equimolar mixture of 6-((diphenylphosphino)methyl)picolinaldehyde and ((2- (diphenylphosphino)phenyl)methanamine. Pure compound was obtained in quantitative yield as a pale yellow viscous oil upon solvent concentration and drying under high vacuum overnight.

1H NMR (500 MHz, CD2C12): d (ppm) 3.61 (s, 2H, CH2), 5.04 (broad s, 2H, CH2), 6.90-6.96 (m, 2H), 7.20-7.50 (m, 25H), 8.25 (s, 1H, CH imine).

¹³ C NMR (125 MHz, CD2C12): d (ppm) 38.7 (CH2), 63.4 (CH2), 118.5 (CH), 124.9 (CH), 127.7 (CH), 128.7 (CH), 128.9 (CH), 129.0 (CH), 129.2 (CH), 129.5 (CH), 133.3 (CH), 134.0 (CH), 134.2 (CH), 134.4 (CH), 136.1 (C), 136.7 (CH), 137.1 (C), 138.7 (C), 144.1 (C), 154.7 (C), 158.1 (C), 163.7 (CH). P NMR (202 MHz, CD2C12): d (ppm) -15.33 (s, 1P), -10.47 (s, 1P). b) Preparation of ( E)-N-(2-(diphenylphosphino)benzyl)-l-(6-((di-tert - butylphosphino)methyl)pyridin-2-yl)methanimine (L-2) · Preparation of 6-(( di-tert-butylphosphino )methyl)picolinaldehyde:

6-(( di-tert-butylphosphino)methyl)picolinaldehyde was obtained according to some similar multi-step synthesis as for 6-

((diphenylphosphino)methyl)picolinaldehyde. It was fully characterized by 1H, 13C and 31P NMR analysis.

1H-NMR (300 MHz, CDC13): d 9.96 (1H, s, CHO), 7.71-7.65 (2H, m, 2xHPy),

7.62-7.58 (1H, m, HPy), 3.07 (2H, d, J = 3.3 Hz, CH2P), 1.10 (18H, d, J = 11.2 Hz, 6xCH3);

13C-NMR (75 MHz, CDC13): d 193.8 (CHO), 163.2 (d, J = 14.7 Hz, CPy), 152.0 (CPy), 136.8 (CHPy), 128.3 (d, J = 9.3 Hz, CHPy), 118.8 (d, J = 1.3 Hz, CHPy), 32.0 (d, J = 21.5 Hz, 2xCP), 31.5 (d, J = 24.6 Hz, C H2P), 29.6 (d, J = 13.3 Hz,

6xCH3);

31P-NMR (121 MHz, CDC13): d +37.7 s;

• Preparation of ( E)-N-(2-(diphenylphosphino)benzyl)-l-(6-((di-tert - butylphosphino )methyl )pyridin-2 -yl )methanimine (L-2)

(E)-N-(2-(diphenylphosphino)benzyl)- l-(6-((di-tert- butylphosphino)methyl)pyridin-2-yl)methanimine was obtained by condensation at room temperature in THF of an equimolar mixture of 6-((di-tert- butylphosphino)methyl)picolinaldehyde and (2-

(diphenylphosphino)phenyl)methanamine. It was obtained in quantitative yield as a pale yellow viscous oil upon solvent concentration and drying under high vacuum overnight and used directly for complex synthesis

c) Preparation of (E)-N-(2-(diphenylphosphino)benzyl)-l-(6-((di-tert- butylphosphino)methyl)pyridin-2-yl) ethan-l-imine (L-3)

Preparation of l-(6-( (Di-tert. -butylphosphino )methyl )pyridin-2-yl )ethan-l - one): l-(6-((Di-tert.-butylphosphino)methyl)pyridin-2-yl)ethan-l-o ne was obtained according to some procedure previously described in Angew. Chem. Int. Ed. 2016, 55, 6671-6675. It was fully characterized by 1H, 13C and 31P NMR analysis, with data corresponding the the previously reported ones.

· Preparation of (E)-N-(2-(diphenylphosphino)benzyl)-l-(6-((di-tert- butylphosphino)methyl)pyridin-2-yl) ethan- 1 -imine (L-3)

E)-N-(2-(diphenylphosphino)benzyl)-l-(6-((di-tert-butylph osphino)methyl)pyridin-2-yl) ethan- 1 -imine was obtained by condensation at room temperature in THF of an equimolar mixture of l-(6-((Di-tert.-butylphosphino)methyl)pyridin-2-yl)ethan-l-o ne and (2- (diphenylphosphino)phenyl)methanamine. It was obtained in quantitative yield as a pale yellow solid upon solvent concentration and drying under high vacuum overnight and used directly for complex synthesis

Example 2

Preparation of invention Complex

a) Preparation of [RuCl ₂ ((E)-N-(2-(diphenylphosphino)benzyl)-l-(6-

( ( diphenylphosphino )methyl )pyridin-2-yl )methanimine )] ( Complex Cl )

Complex Cl was obtained by reaction of (PPh ₃ ) ₃ RuCl2 ruthenium complex with 1.05 equivalents of ligand Ll in toluene refluxing for 4h. Upon cooling down to room temperature, toluene was partly concentrated under vacuum and Et ₂ 0 was added for product precipitation. The suspension was filtered under nitrogen and the obtained purple solid was washed several times with a toluene/Et ₂ 0 mixture and then pure Et ₂ 0. After drying under high vacuum overnight, product was obtained in 85% yield as a 5/2 stereoisomers mixture.

³¹ P NMR (202 MHz, CD2C12): d (ppm) 46.27(d, J = 22.8 Hz, 1P major isomer), 47.34 (d, J = 28.6 Hz, 1P minor isomer), 48.49 (d, J = 22.8 Hz, 1P major isomer), 59.49 (d, J = 28.6 Hz, 1P mino isomer). b) Preparation of Complex [RuCl ₂ ((E)-N-(2-(diphenylphosphino)benzyl)-l-(6-((di- tert-butylphosphino)methyl)pyridin-2-yl)methanimine )] ( Complex C2) Complex C2 was obtained by reaction of (PPh ₃ ) ₃ RuCl2 ruthenium complex with 1.05 equivalents of (E)-N-(2-(diphenylphosphino)benzyl)- l-(6-((di-tert- butylphosphino)methyl)pyridin-2-yl)methanimine (L-2) in toluene refluxing for 4h. Upon cooling down to room temperature, toluene was partly concentrated under vacuum and Et ₂ 0 was added for product precipitation. The suspension was filtered under nitrogen and the obtained purple solid was washed several times with a toluene/Et ₂ 0 mixture and then pure Et ₂ 0. After drying under high vacuum overnight, product was obtained in 75% yield as a 4/1 stereoisomers mixture.

³¹ P NMR (202 MHz, CD2C12): d 38.38 (d, J = 18.5 Hz, 1P major isomer), 58.62 (broad s, 1P minor isomer), 61.82 (d, J = 18.5 Hz, 1P major isomer), 62.35 (broad s, 1P minor isomer). c) Preparation of Complex [RuCl ₂ ((E)-N-(2-(diphenylphosphino)benzyl)-l-(6-((di- tert-butylphosphino)methyl)pyridin-2-yl)ethan-l-imine)] ( Complex C3)

Complex C3 was obtained by reaction of (PPh ) RuCl ₂ ruthenium complex with 1.05 equivalents of (E)-N-(2-(diphenylphosphino)benzyl)- l-(6-((di-tert- butylphosphino)methyl)pyridin-2-yl)ethan-l-imine (L-3) in toluene refluxing for 4h. Upon cooling down to room temperature, toluene was partly concentrated under vacuum and Et ₂ 0 was added for product precipitation. The suspension was filtered under nitrogen and the obtained purple solid was washed several times with a toluene/Et ₂ 0 mixture and then pure Et ₂ 0. After drying under high vacuum overnight, product was obtained in 85% yield as a single isomer.

1H-NMR (500 MHz, CD2C12): d 7.80-7.70 (m, 5H), 7.58 (t, J = 1.80 Hz, 1H), 7.45-7.25 (m, 11H), 5.21 (t, J = 3.2 Hz, 2H, CH2), 3.79 (d, J = 8.8 Hz, 2H, CH2), 2.78 (s, 3H, CH3), 1.10 (s, 9H, 3 CH3), 1.07 (s, 9H, 3 CH3).

13C-NMR (125.76 MHz, CD2C12): d 169.26 (C), 166.09 (C), 159.58(C), 139.24 (C), 138.57 (C), 136.82 (C), 135.62 (CH), 135.10 (CH), 134.06 (CH), 132.09 (CH), 131.21 (CH), 129.78 (CH), 129.11 (CH), 128.88 (CH), 128.09 (CH), 128.00 (CH), 123.87 (CH), 122.47 (CH), 60.95 (CH2), 39.17 (CH2), 37.70 (C), 30.54 (CH3), 17.04 (CH3).

³¹ P NMR (202 MHz, CD2C12): d 35.84 (d, J = 19.5 Hz, 1P), 63.47 (d, J = 19.5 Hz, 1P). Example 3

Preparation of comparative Complexes

a) Preparation of [RuCl ₂ (2-(diphenylphosphino)-N-((6- (( diphenylphosphino )methyl )pyridin-2-yl )methyl )ethan-l -amine )] ( Comparative

Complex CC1 )

Complex [RuCl ₂ (2-(diphenylphosphino)-N-((6-((diphenylphosphino)methy l)pyridin-2- yl)methyl)ethan- 1 -amine)] was obtained according to some previously described procedure (Tan X., Wang Y., Liu Y., Wang F., Shi L., Lee K.-H., Lin Z., Lv H., Zhang X., Org. Lett., 2015, 17 (3), 454-457). b) Preparation of [RuCl ₂ ((E)-N-(2-(diphenylphosphino)ethyl)-l-(6-

( ( diphenylphosphino )methyl )pyridin-2-yl )methanimine )] ( comparative Complex CC2)

· (E)-N-(2-(diphenylphosphino)ethyl)-l-(6-

( ( diphenylphosphino )methyl )pyridin-2-yl )methanimine ligand (E) -N- (2- (diphenylpho sphaneyl)ethyl)- 1 - (6- ( (diphenylpho sphaneyl)methyl)pyridin- 2- yl)methanimine (E) -N- (2- (diphenylpho sphino)ethyl) - 1 - (6-

((diphenylphosphino)methyl)pyridin-2-yl)methanimine ligand was obtained by reaction at room temperature in THF of an equimolar mixture of 6-

((diphenylphosphino)methyl)picolinaldehyde and 2-(diphenylphosphino)ethan- 1 -amine. Pure compound was obtained in quantitative yield as a pale yellow viscous oil upon solvent concentration and drying under high vacuum overnight.

1H NMR (500 MHz, CD ₂ Cl ₂ ): d (ppm) 2.46 (tm, J = 7.8 Hz, 2H, CH ₂ ), 3.62 (s, 2H, CH ₂ ), 3.75 (qm, , J = 7.8 Hz, 2H, CH ₂ ) 6.94 (d, J = 7.8 Hz, 1H, CH), 7.31 (m, 12H,

12CH), 7.44 (m, 9H, 9CH), 7.63 (d, J =7.8 Hz, 1H, CH), 8.22 (s, 1H, CH).

¹³ C NMR (125 MHz, CD ₂ Cl ₂ ): d (ppm) 30.0 (CH ₂ ), 38.7 (CH ₂ ), 58.4 (CH ₂ ), 118.5 (CH) 124.9 (CH), 128.7 (CH), 128.8 (CH), 128.9 (CH), 129.1 (CH) 133.1 (CH), 133.2 (CH), 136.8 (CH), 138.8 (C), 138.9 (C), 154.6 (C), 158.2 (C), 162.8 (CH).

3 ¹ P NMR (202 MHz, CD ₂ Cl ₂ ): d (ppm) - 18.73 (s), - 10.41 (s).

• [RuCl2((E)-N-( 2-( diphenylphosphino)ethyl)-l -( 6-

( ( diphenylphosphino )methyl )pyridin-2-yl )methanimine )] ( Complex CC2 ) it was obtained by reaction of (PPh ₃ ) ₃ RuCl2 ruthenium complex with 1.05 equivalents of (E)-N-(2-(diphenylphosphino)ethyl)-l-(6-((diphenylphosphino) methyl)pyridin-2- yl)methanimine ligand in toluene refluxing for 4h. Upon cooling down to room temperature, toluene was partly concentrated under vacuum and Et ₂ 0 was added for product precipitation. The suspension was filtered under nitrogen and the obtained purple solid was washed several times with a toluene/Et ₂ 0 mixture and then pure Et ₂ 0. After drying under high vacuum overnight, pure product was obtained in 85% yield.

1H NMR (500 MHz, CD ₂ Cl ₂ ): 5 ( _PP m) 3.21 (qm, J = 7.8 Hz, 2H, CH ₂ ), 4.52 (d, J =10.4 Hz, 2H, CH ₂ ), 4.60-4.70 (m, 2H, CH ₂ ), 7.22-7.28 (m, 8H, 8CH), 7.30-7.38 (m, 4H, 4CH), 7.43-7.57 (m, 8H, 8CH), 7.74-7.86 (m, 3H, 3CH), 8.95 (dt, J =7.0 and 1.6 Hz, 1H, CH).

¹³ C NMR (125 MHz, CD ₂ Cl ₂ ): 5 ( _PP m) 35.8 (CH ₂ ), 47.7 (CH ₂ ), 58.6 (CH ₂ ), 122.5 (CH),

125.4 (CH), 127.8 (CH), 127.9 (CH), 129.6 (CH), 129.8 (CH), 133.8 (CH), 134.1 (CH), 135.0 (CH), 135.6 (C), 136.2 (C), 158.4 (C), 160.8 (CH) 162.5 (C).

³¹ P NMR (202 MHz, CD ₂ Cl ₂ ): d ( _PP m) 54.6 (d, J = 19.60 Hz), 60.5 (d, J = 19.60 Hz) c ) Preparation of [RuCl2((E)-l-(6-((diphenylphosphino)methyl)pyridin-2-yl)-N-( 3- ( diphenylphosphino)propyl)methanimine )] ( Comparative Complex CC3)

• (E)-l-(6-((diphenylphosphino)methyl)pyridin-2-yl)-N-(3- (diphenylphosphino)propyl) methanimine ligand

it was obtained by reaction at room temperature in THF of an equimolar mixture of 6- ((diphenylphosphino)methyl)picolinaldehyde and 3-(diphenylphosphino)propan- l-amine. Pure compound was obtained in quantitative yield as a pale yellow viscous oil upon solvent concentration and drying under high vacuum overnight.

1H NMR (500 MHz, CD ₂ Cl ₂ ): d (ppm) 1.75-1.87 (m, 2H, CH ₂ ), 2.09-2.16 (m, 2H, CH ₂ ), 3.62 (s, 2H, CH ₂ ), 3.70 (td, J = 6.8 and 1.2 Hz, 2H, CH ₂ ) 6.94 (dt, J =7.8 and 1.2 Hz, 1H, CH), 7.27-7.35 (m, 12H, 12CH), 7.38-7.46 (m, 8H, 8CH), 7.50 (t, J = 7.8 Hz, 1H, CH), 7.63 (d, J =7.8 Hz, 1H, CH), 8.26 (s, 1H, CH).

¹³ C NMR (125 MHz, CD ₂ Cl ₂ ): d (ppm) 25.8 (CH ₂ ), 27.7 (CH ₂ ), 38.7 (CH ₂ ), 62.4 (CH ₂ ),

118.4 (CH) 124.9 (CH), 128.7 (CH), 128.9 (CH), 129.1 (CH) 133.0 (CH), 133.2 (CH), 136.8 (CH), 138.7 (C), 139.3 (C), 154.8 (C), 158.2 (C), 162.8 (CH).

³¹ P NMR (202 MHz, CD ₂ Cl ₂ ): d (ppm) - 16.11 (s), - 10.42 (s). • [RuCl2((E)-l-(6-((diphenylphosphino)methyl)pyridin-2-yl)-N-( 3-

(diphenylphosphino)propyl)methanimine)] ( Comparative Complex CC3) it was obtained by reaction of (PPh ₃ ) ₃ RuCl2 ruthenium complex with 1.05 equivalents of (E)-l-(6-((diphenylphosphino)methyl)pyridin-2-yl)-N-(3 (diphenylphosphino)propyl) methanimine ligand in toluene refluxing for 4h. Upon cooling down to room temperature, toluene was partly concentrated under vacuum and Et ₂ 0 was added for product precipitation. The suspension was filtered under nitrogen and the obtained purple solid was washed several times with a toluene/Et ₂ 0 mixture and then pure Et ₂ 0. After drying under high vacuum overnight, pure product was obtained in 75% yield.

1H NMR (500 MHz, CD ₂ Cl ₂ ): d (ppm) 2.40-2.54 (m, 2H, CH ₂ ), 2.79-2.87 (m, 2H, CH ₂ ), 4.35-4.40 (m, 2H, CH ₂ ), 4,41 (d, J = 10.8 Hz, 2H, CH ₂ ), 7.08-7.14 (m, 8H, 8CH), 7.16-7.22 (m, 4H, 4CH), 7.23-7.30 (m, 4H, 4CH), 7.32-7.38 (m, 4H, 4CH), 7.61- 7.67 (m, 1H, CH, 7.75-7.81 (m, 2H, 2CH), 8.71 (dt, J = 5.8 and 1.8 Hz, 1H, CH).

¹³ C NMR (125 MHz, CD ₂ Cl ₂ ): d (ppm) 24.4 (CH ₂ ), 27.5 (CH ₂ ), 48.7 (CH ₂ ), 63.0 (CH ₂ ), 122.7 (CH) 125.4 (CH), 127.5 (CH), 127.6 (CH), 129.1 (CH), 129.6 (CH), 134.1 (CH), 134.2 (CH), 135.4 (CH), 135.8 (C), 138.0 (C), 155.6 (C), 162.4 (C), 165.0 (CH).

³¹ P NMR (202 MHz, CD ₂ Cl ₂ ): d (ppm) 36.12 (d, J = 30.4 Hz), 50.5 (d, J = 30.4 Hz). d) [RuCl2(triphenylphosphine)(bis(2-(ethylthio)ethyl)amine)] (Comparative Complex CC4)

Commercially available complex [ RuCl2(triphenylphosphine)(bis(2 -

(ethylthio)ethyl)amine)] was purchased from Sigma-Aldrich. e) [RuCl2(N,N' -(ethane-1, 2-diyl)bis(l -(2- (diphenylphosphaneyl)phenyl)methanimine))]( Comparative Complex CC5)

Complex [RuCl2(N,N’ -(ethane-1, 2-diyl)bis(l -(2-

(diphenylphosphaneyl)phenyl)methanimine))] was synthesized according to some

W0200610648) f) [ RuCl2(bis(2-(diphenylphosphino)ethylamine ))] (Comparative Complex CC6) Commercially available complex [ RuCl2(bis(2-(diphenylphosphino)ethylamine ))] was purchased from Sigma-Aldrich (CAS number: [506417-41-0] ).

Example 4

General hydrogenation reaction procedure:

Ester, ruthenium catalyst , metal alkoxide co-catalyst (used as a solid or some alcoholic solution) and optionally solvent (see Table 1) were loaded altogether in an 100 mL or 1L autoclave equipped with a mechanical stirring device, pressure and internal temperature sensors and a heating/cooling system for internal temperature regulation. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to required hydrogen pressure via an hydrogen tank equipped with a way out pressure regulator and also an internal pressure sensor to follow and determine hydrogen consumption. Reaction mixture was then heated to required temperature and hydrogen pressure into the autoclave was maintained to the desired value during the whole reaction. Upon reaction completion also determined by GC analysis with complete disappearance of both starting material and mixed ester coming from transesterification reaction with product and eventually with metal alkoxide co-catalyst and/or alcoholic solvent, autoclave was then cooled down to 25 °C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and lights compounds were removed under vacuum. Crude product was then flash distilled in order to determine the quantity of residues formed during the reaction and yield was calculated based on GC purity of distilled product.

Example 5

Catalytic hydrogenation of different esters using different catalyst of the invention and comparative catalyst:

The hydrogenation has been performed as reported in Example 4. Table 1: Hydrogenation of different esters using different complexes

1) Complete conversion was achieved with nearly no residues formation (< 1 wt.%).

2) Product was obtained with > 99% GC selectivity

The complete conversion was reached faster with the invention’s catalyst compared to prior art catalysts.

Table 2 : Structure and names of esters used

Example 6 Catalytic hydrogenation of ethyl benzoate using different catalysts of the invention and comparative catalysts in various solvents:

The hydrogenation has been performed as reported in Example 4.

Table 3: Hydrogenation of Ethyl benzoate using different complexes in various solvents

1) Reactions were run (when applicable) with 2 equivalents in volume of solvent.

2) Complete conversion was achieved with nearly no residues formation (< 1 wt.%).

The invention’s catalyst allows reaching complete conversion faster than the prior art catalyst regardless of the solvent used.

Example 7

Catalytic hydrogenation of different esters using complex Cl at various temperatures: The hydrogenation has been performed as reported in Example 4.

Table 4: Hydrogenation of ester using complex Cl at various temperature

1) Complete conversion was achieved with nearly no residues formation (< 1 wt.%).

Example 8 Catalytic hydrogenation under neat conditions of ethyl octanoate using complex Cl at various hydrogen pressures:

The hydrogenation has been performed as reported in Example 4.

Table 5: Hydrogenation of ethyl octanoate with Cl at various hydrogen pressures

1) Complete conversion was achieved with nearly no residues formation (< 1 wt.%).

Example 9

Catalytic hydrogenation under neat conditions of ethyl octanoate using complex Cl with various metal alkoxides as a base: The hydrogenation has been performed as reported in Example 4.

Table 6: Neat hydrogenation using various metal alkoxides as a base

1) Complete conversion was achieved with nearly no residues formation (< 1 wt.%).

Example 10

Catalytic hydrogenation under neat conditions of various esters using complex Cl:

The hydrogenation has been performed as reported in Example 4.

Table 7: Neat hydrogenation of various esters

1) Complete conversion was achieved with nearly no residues formation (< 1 wt.%).

2) Desired product was obtained with more than 99% GC selectivity at complete conversion.

3) Desired product was obtained with 95% GC selectivity at complete conversion.

Example 11

Catalytic _ hydrogenation _ of _ (+/-)-(3aR,5aS,9aS,9bR)-3a,6,6,9a- tetramethyldecahvdronaphthor2,l-b1furan-2 -one using different catalyst of the

invention and comparative catalyst in various solvents:

The hydrogenation has been performed as reported in Example 4.

Table 8: Neat Hydrogenation of (+/-)-(3aR,5aS,9aS,9bR)-3a,6,6,9a- tetramethyldecahydronaphtho[2,l-b]furan-2(lH)-one in solvent

1) Reactions run with 1 equivalent in volume of solvent.

2) Reactions run with 2 equivalents in volume of solvent.

3) Complete conversion was achieved with nearly no residues formation (< 1 wt.%).

Same results were obtained from enantiomerically enriched compound E16.