Title of Invention: A Catalyst For the Carbonylation of Alkenes

Technical Field

The present invention relates to a metal complex and a catalyst composition comprising the metal complex. The present invention also relates to a process for the preparation of a dicarboxylic acid or ester thereof from an alkenoic acid or ester thereof, or a process for the preparation of a carboxylic acid or ester thereof from an alkene or alkenoic acid with high selectivity and activity using said metal complex or catalyst composition.

Background Art Concerns for the availability of fossil feedstock and climate change have led to significant interest in chemicals and polymers derived from biomass. Among commercial polymers, Nylon monomers are exceedingly inefficient in terms of energy and chemical utilization. A process for making adipic acid from γ-valerolactone (GVL) has been disclosed in the past. GVL can be derived from the hydrogenation of levulinic acid, one of the so-called bio-based platform molecules which can be readily obtained from acid-catalyzed decomposition of cellulose or C6 sugars. The known process comprises two steps: (a) reactive distillation of GVL to a mixture of pentenoic acid isomers in the presence of an acid catalyst, (b) hydroxycarbonylation of the mixture of pentenoic acid isomers to adipic acid in the presence of a palladium catalyst, precipitation of adipic acid and recycling of the filtrate containing catalyst and unreacted pentenoic acid isomers, as shown in Fig. 1.

The carbonylation of pentenoic acid isomer(s) to adipic acid has been reported to proceed with high selectivity in the presence of a palladium catalyst such as those derived from a palladium compound, a sterically bulky diphosphine, and an acid. A particularly effective catalyst system is derived from palladium(II) acetate, l,2-bis[di(i-butyl)phosphinomethyl]benzene (DTBPX), and methanesulfonic acid (MSA). Although this catalyst system gives a remarkable selectivity to adipic acid in comparison with other diphosphines, improvements in selectivity and activity are still desired in order to improve catalyst recyclability and lower the catalyst cost.

There is therefore a need to provide a catalyst or composition thereof that overcomes or at least ameliorates, one or more of the disadvantages described above. Summary of Invention

In an aspect, there is provided a metal complex of Formula (I):

Formula (I); wherein M is a group 10 element;

R is C _{1 10} alkyl or R is an optionally substituted phenyl of formula II:

Formula (II); wherein * indicates the bond to Formula (I);

R ⁶ and R ⁷ may each independently represent hydrogen, a C _MO alkyl, nitro, halogen, -O- C _MO alkyl, a halogenated C _MO alkyl, carboxylic acid or ester, amide, amino, ammonium, -S0 ₃ H or an optionally substituted -S0 ₂ -; n is 1 or 2;

L is a ligand;

R ² and R ³ are either the same or different and independently represent a C _{4 12} tertiary alkyl or, together with the P atom to which they are attached, form a phosphorous-containing ring having formula (III);

R ⁴ and R ⁵ are either the same or different and independently represent a C _{4 12} tertiary alkyl or, together with the P atom to which they are attached, form a phosphorous-containing ring having formula (III):

Formula (III); wherein * indicates the connection to Formula (I);

Y represents an optionally substituted C _MO alkyl, optionally substituted C _MO alkylene or optionally substituted silicon, C=0, C=NR ¹⁶ , -CH-NR ¹⁷ R ¹⁸ , S=0, S0 ₂ , P(0)OH or P ⁺ R ²² R ²³ ; wherein the C _MO alkyl, C _MO alkylene or silicon may be substituted with - O- CMO alkyl or OH; and

R ⁸ , R ⁹ , R ¹⁰ , R ⁿ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² and R ²³ each independently represent hydrogen or an optionally substituted Q to C _u alkyl, provided that the metal complex does not have the following structure:

Advantageously, the metal complex may be capable of producing a dicarboxylic acid or ester thereof from an alkenoic acid or ester thereof, or producing a carboxylic acid or ester thereof from an alkene or alkenoic acid with high selectivity and activity.

In another aspect, there is provided a catalyst composition comprising the metal complex as defined above.

In an embodiment, the catalyst composition may further comprise an activating acid XH.

Advantageously, the activating acid may be capable of increasing the selectivity and activity of the metal complex as defined above. Further advantageously, high acid strength (i.e. low pKa) may result in a more active catalyst without compromising selectivity (>98%). Further advantageously, the catalyst composition may be more active in carboxylic acid and ester solvents rather than in ethers, without compromising the selectivity.

In an embodiment, the R ¹ may be an optionally substituted phenyl of formula II. Advantageously, introduction of substituents on the phenyl ring may result in the catalyst composition having improved selectivity without compromising the activity. Further advantageously, electron withdrawing substituents may provide the best improvement in selectivity.

Advantageously, the combination of the catalyst composition comprising metal complex as defined above and a strongly acidic co-catalyst gives comparative activity and improved selectivity for the hydroxycarbonylation of alkenoic acids isomers such as pentenoic acid isomers in a polar medium comprising pentenoic acid isomers and water. The catalyst composition may also advantageously give improved selectivity and activity in the hydroxy/alkoxycarbonylation of a wider range of substrates such as ethylene, butadiene, and unsaturated fatty acid esters. Further advantageously, the catalyst composition may provide a cost and time efficient method of producing dicarboxylic acids such as adipic acid from renewable feedstock.

In another aspect, there is provided a method for preparing a catalyst composition as defined above, comprising the step of combining a group 10 metal compound, and a bidentate diphosphine.

In an embodiment, method may further comprise the step of adding an activating acid XH.

Advantageously, the method may enable the facile formation of the catalyst composition. Further advantageously, the formation of the catalyst may be done in situ.

In another aspect, there is provided a process for preparing a dicarboxylic acid or an ester thereof, comprising the step of (2) contacting an alkenoic acid or an ester thereof with a catalyst composition as defined above in the presence of carbon monoxide.

Advantageously, the process may facilitate the conversion of alkenoic acid or an ester thereof to a dicarboxylic acid or an ester thereof with high yield and selectivity. Advantageously, the method may enable a conversion yield of greater than 40% and a selectivity greater than 96%. In another aspect, there is provided a process for the production of a carboxylic acid or ester thereof, comprising the step of contacting an alkene or alkenoic acid with a catalyst composition as defined above in the presence of carbon monoxide.

Advantageously, the process may facilitate the conversion of alkene or alkenoic acid to a carboxylic acid or an ester thereof with high yield and selectivity. Advantageously, the method may enable a conversion yield of greater than 80% and a selectivity greater than 95%.

In another aspect, there is provided a method of preparing Nylon 6-6 comprising the step of copolymerising adipic acid prepared in accordance with the process as defined above with hexamethylenediamine, to form Nylon 6-6.

Advantageously, the disclosed method may facilitate increased rate in production of Nylon 6-6 using bio-based starting materials.

Definitions

The following words and terms used herein shall have the meaning indicated:

In this specification a number of terms are used which are well known to a skilled addressee. Nevertheless for the purposes of clarity, a number of terms will be defined. The following words and terms used herein shall have the meaning indicated:

The term 'solvent' is to be defined herein as any substance, which upon addition to a composition increases the solubility of parts of the composition, without participating in the reaction process as a reactive partner or part of the catalyst system, i.e. there are no reaction products containing parts of the solvent. In the definitions of a number of substituents below it is stated that "the group may be a terminal group or a bridging group". This is intended to signify that the use of the term is intended to encompass the situation where the group is a linker between two other portions of the molecule as well as where it is a terminal moiety. Using the term alkyl as an example, some publications would use the term "alkylene" for a bridging group and hence in these other publications there is a distinction between the terms "alkyl" (terminal group) and "alkylene" (bridging group). In the present application no such distinction is made and most groups may be either a bridging group or a terminal group.

"Acyl" means an R-C(=0)- group in which the R group may be an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group as defined herein. Examples of acyl include acetyl and benzoyl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the carbonyl carbon.

"Acylamino" means an R-C(=0)-NH- group in which the R group may be an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the nitrogen atom.

"Alkenoic acid" as a group or part of a group donates an aliphatic carbon group containing at least one carbon-carbon double bond and a carboxylic acid, wherein the aliphatic carbon group may be straight or branched preferably having 2-20 carbon atoms, more preferably 2-12 carbon atoms, more preferably 2-10 carbon atoms, most preferably 2-6 carbon atoms, in the normal chain. The group may contain a plurality of double bonds in the normal chain and the orientation about each is independently E or Z. Exemplary alkenoic acid groups include, but are not limited to, acrylic acid, trans-2-butenoic acid, cis-2-butenoic acid, 3-butenoic acid, 4- pentenoic acid, trans-3-pentenoic acid, cis-3-pentenoic acid, trans-2-pentenoic acid and cis-2- pentenoic acid. The group may be a terminal group or a bridging group.

"Alkenyl" as a group or part of a group denotes an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and which may be straight or branched preferably having 2-12 carbon atoms, more preferably 2-10 carbon atoms, most preferably 2-6 carbon atoms, in the normal chain. The group may contain a plurality of double bonds in the normal chain and the orientation about each is independently E or Z. Exemplary alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl and nonenyl. The group may be a terminal group or a bridging group.

"Alkenyloxy" refers to an alkenyl-O- group in which alkenyl is as defined herein. Preferred alkenyloxy groups are Q-Ce alkenyloxy groups. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the oxygen atom.

"Alkyl" as a group or part of a group refers to a straight or branched aliphatic hydrocarbon group, preferably a Q-Q2 alkyl, more preferably a C C _w alkyl, most preferably C C ₆ unless otherwise noted. Examples of suitable straight and branched C C ₆ alkyl substituents include methyl, ethyl, n-propyl, 2-propyl, n-butyl, sec-butyl, t-butyl, hexyl, and the like. The group may be a terminal group or a bridging group.

"Alkylamino" includes both mono-alkylamino and dialkylamino, unless specified. "Mono- alkylamino" means a Alkyl-NH- group, in which alkyl is as defined herein. "Dialkylamino" means a (alkyl) ₂ N- group, in which each alkyl may be the same or different and are each as defined herein for alkyl. The alkyl group is preferably a C C ₆ alkyl group. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the nitrogen atom.

"Alkylaminocarbonyl" refers to a group of the formula (Alkyl) _x (H) _y NC(=0)- in which alkyl is as defined herein, x is 1 or 2, and the sum of X+Y =2. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the carbonyl carbon.

"Alkyloxy" refers to an alkyl-O- group in which alkyl is as defined herein. Preferably the alkyloxy is a Q-Ceaikyloxy. Examples include, but are not limited to, methoxy and ethoxy. The group may be a terminal group or a bridging group.

"Alkyloxyalkyl" refers to an alkyloxy-alkyl- group in which the alkyloxy and alkyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkyl group.

"Alkyloxyary" refers to an alkyloxy-aryl- group in which the alkyloxy and aryl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the aryl group.

"Alkyloxycarbonyl" refers to an alkyl-0-C(=0)- group in which alkyl is as defined herein. The alkyl group is preferably a Ci-Ce alkyl group. Examples include, but are not limited to, methoxycarbonyl and ethoxycarbonyl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the carbonyl carbon.

" Alkyloxy cycloalkyl" refers to an alkyloxy-cycloalkyl- group in which the alkyloxy and cycloalkyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the cycloalkyl group.

"Alkyloxyheteroaryl" refers to an alkyloxy-heteroaryl- group in which the alkyloxy and heteroaryl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the heteroaryl group.

"Alkyloxyheterocycloalkyl" refers to an alkyloxy-heterocycloalkyl- group in which the alkyloxy and heterocycloalkyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the heterocycloalkyl group.

"Alkylsulfinyl" means an alkyl-S-(=0)- group in which alkyl is as defined herein. The alkyl group is preferably a C C ₆ alkyl group. Exemplary alkylsulfinyl groups include, but not limited to, methylsulfinyl and ethylsulfinyl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the sulfur atom.

"Alkylsulfonyl" refers to an alkyl-S(=0) ₂ - group in which alkyl is as defined above. The alkyl group is preferably a Q-Ce alkyl group. Examples include, but not limited to methylsulfonyl and ethylsulfonyl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the sulfur atom.

"Alkynyl" as a group or part of a group means an aliphatic hydrocarbon group containing a carbon-carbon triple bond and which may be straight or branched preferably having from 2-12 carbon atoms, more preferably 2-10 carbon atoms, more preferably 2-6 carbon atoms in the normal chain. Exemplary structures include, but are not limited to, ethynyl and propynyl. The group may be a terminal group or a bridging group.

"Alkynyloxy" refers to an alkynyl-O- group in which alkynyl is as defined herein. Preferred alkynyloxy groups are C C ₆ alkynyloxy groups. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the oxygen atom.

"Amino" refers to groups of the form -NR _a R _b wherein R _a and R _b are individually selected from the group including but not limited to hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, and optionally substituted aryl groups.

"Aminoalkyl" means an NH ₂ -alkyl- group in which the alkyl group is as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkyl group.

"Aminosulfonyl" means an NH ₂ -S(=0) ₂ - group. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the sulfur atom. "Aryl" as a group or part of a group denotes (i) an optionally substituted monocyclic, or fused polycyclic, aromatic carbocycle (ring structure having ring atoms that are all carbon) preferably having from 5 to 12 atoms per ring. Examples of aryl groups include phenyl, naphthyl, and the like; (ii) an optionally substituted partially saturated bicyclic aromatic carbocyclic moiety in which a phenyl and a C5 7 cycloalkyl or C5 7 cycloalkenyl group are fused together to form a cyclic structure, such as tetrahydronaphthyl, indenyl or indanyl. The group may be a terminal group or a bridging group. Typically an aryl group is a Ce-Qs aryl group. "Arylalkenyl" means an aryl-alkenyl- group in which the aryl and alkenyl are as defined herein. Exemplary arylalkenyl groups include phenylallyl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkenyl group. "Arylalkyl" means an aryl-alkyl- group in which the aryl and alkyl moieties are as defined herein. Preferred arylalkyl groups contain a C _{1 5} alkyl moiety. Exemplary arylalkyl groups include benzyl, phenethyl, 1 -naphthalenemethyl and 2-naphthalenemethyl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkyl group. "Arylalkyloxy" refers to an aryl-alkyl-O- group in which the alkyl and aryl are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the oxygen atom.

"Arylamino" includes both mono-arylamino and di-arylamino unless specified. Mono-arylamino means a group of formula arylNH-, in which aryl is as defined herein. di-arylamino means a group of formula (aryl) ₂ N- where each aryl may be the same or different and are each as defined herein for aryl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the nitrogen atom.

"Arylheteroalkyl" means an aryl-heteroalkyl- group in which the aryl and heteroalkyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the heteroalkyl group.

"Aryloxy" refers to an aryl-O- group in which the aryl is as defined herein. Preferably the aryloxy is a Ce-Qsaryloxy, more preferably a Ce-Qoaryloxy. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the oxygen atom.

"Arylsulfonyl" means an aryl-S(=0) ₂ - group in which the aryl group is as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the sulfur atom.

A "bond" is a linkage between atoms in a compound or molecule. The bond may be a single bond, a double bond, or a triple bond.

"Cycloalkenyl" means a non-aromatic monocyclic or multicyclic ring system containing at least one carbon-carbon double bond and preferably having from 5-10 carbon atoms per ring. Exemplary monocyclic cycloalkenyl rings include cyclopentenyl, cyclohexenyl or cycloheptenyl. The cycloalkenyl group may be substituted by one or more substituent groups. A cycloalkenyl group typically is a C3-Q2 alkenyl group. The group may be a terminal group or a bridging group. "Cycloalkyl" refers to a saturated monocyclic or fused or spiro polycyclic, carbocycle preferably containing from 3 to 9 carbons per ring, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like, unless otherwise specified. It includes monocyclic systems such as cyclopropyl and cyclohexyl, bicyclic systems such as decalin, and polycyclic systems such as adamantane. A cycloalkyl group typically is a C ₃ -C ₁₂ alkyl group. The group may be a terminal group or a bridging group.

"Cycloalkylalkyl" means a cycloalkyl-alkyl- group in which the cycloalkyl and alkyl moieties are as defined herein. Exemplary monocycloaikylaikyl groups include cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl and cycloheptylmethyl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkyl group.

"Cycloalkylalkenyl" means a cycloalkyl-alkenyl- group in which the cycloalkyl and alkenyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkenyl group.

"Cycloalkylheteroalkyl" means a cycloalkyl-heteroalkyl- group in which the cycloalkyl and heteroalkyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the heteroalkyl group. "Cycloalkyloxy" refers to a cycloalkyl-O- group in which cycloalkyl is as defined herein. Preferably the cycloalkyloxy is a Ci-Cecycloalkyloxy. Examples include, but are not limited to, cyclopropanoxy and cyclobutanoxy. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the oxygen atom. "Cycloalkenyloxy" refers to a cycloalkenyl-O- group in which the cycloalkenyl is as defined herein. Preferably the cycloalkenyloxy is a Q-Cecycloaikenyloxy. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the oxygen atom.

"Cycloamino" refers to a saturated monocyclic, bicyclic, or polycyclic ring containing at least one nitrogen in at least one ring. Each ring is preferably from 3 to 10 membered, more preferably 4 to 7 membered. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the nitrogen atom.

"Haloalkyl" refers to an alkyl group as defined herein in which one or more of the hydrogen atoms has been replaced with a halogen atom selected from the group consisting of fluorine, chlorine, bromine and iodine. A haloalkyl group typically has the formula C _n H _(2n+ i _m) X _m wherein each X is independently selected from the group consisting of F, CI, Br and I . In groups of this type n is typically from 1 to 10, more preferably from 1 to 6, most preferably 1 to 3. m is typically 1 to 6, more preferably 1 to 3. Examples of haloalkyl include fluoromethyl, difluoromethyl and trifluoromethyl.

"Haloalkenyl" refers to an alkenyl group as defined herein in which one or more of the hydrogen atoms has been replaced with a halogen atom independently selected from the group consisting of F, CI, Br and I.

"Haloalkynyl" refers to an alkynyl group as defined herein in which one or more of the hydrogen atoms has been replaced with a halogen atom independently selected from the group consisting of F, CI, Br and I.

"Halogen" represents chlorine, fluorine, bromine or iodine. "Heteroalkyl" refers to a straight- or branched-chain alkyl group preferably having from 2 to 12 carbons, more preferably 2 to 6 carbons in the chain, one or more of which has been replaced by a heteroatom selected from S, O, P and N. Exemplary heteroalkyls include alkyl ethers, secondary and tertiary alkyl amines, amides, alkyl sulfides, and the like. Examples of heteroalkyl also include hydroxyCi-Cealkyl, Ci-CealkyloxyCi-Cealkyl, aminoCi-Cealkyl, Q- CealkylaminoCi-Cealkyl, and di(Ci-C ₆ alkyl)aminoCi-C ₆ alkyl. The group may be a terminal group or a bridging group.

"Heteroalkyloxy" refers to an heteroalkyl-O- group in which heteroalkyl is as defined herein. Preferably the heteroalkyloxy is a Q-Ceheteroaikyloxy. The group may be a terminal group or a bridging group. "Heteroaryl" either alone or part of a group refers to groups containing an aromatic ring (preferably a 5 or 6 membered aromatic ring) having one or more heteroatoms as ring atoms in the aromatic ring with the remainder of the ring atoms being carbon atoms. Suitable heteroatoms include nitrogen, oxygen and sulphur. Examples of heteroaryl include thiophene, benzothiophene, benzofuran, benzimidazole, benzoxazole, benzothiazole, benzisothiazole, naphtho[2,3-b]thiophene, furan, isoindolizine, xantholene, phenoxatine, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, tetrazole, indole, isoindole, lH-indazole, purine, quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline, cinnoline, carbazole, phenanthridine, acridine, phenazine, thiazole, isothiazole, phenothiazine, oxazole, isooxazole, furazane, phenoxazine, 2-, 3- or 4- pyridyl, 2-, 3-, 4-, 5-, or 8- quinolyl, 1-, 3-, 4-, or 5- isoquinolinyl 1-, 2-, or 3- indolyl, and 2-, or 3-thienyl. A heteroaryl group is typically a Q-Qg heteroaryl group. The group may be a terminal group or a bridging group.

"Heteroarylalkyl" means a heteroaryl-alkyl group in which the heteroaryl and alkyl moieties are as defined herein. Preferred heteroarylalkyl groups contain a lower alkyl moiety. Exemplary heteroarylalkyl groups include pyridylmethyl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkyl group.

"Heteroarylalkenyl" means a heteroaryl-alkenyl- group in which the heteroaryl and alkenyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkenyl group.

"Heteroarylheteroalkyl" means a heteroaryl-heteroalkyl- group in which the heteroaryl and heteroalkyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the heteroalkyl group.

"Heteroarylamino" refers to groups containing an aromatic ring (preferably 5 or 6 membered aromatic ring) having at least one nitrogen and at least another heteroatom as ring atoms in the aromatic ring, preferably from 1 to 3 heteroatoms in at least one ring. Suitable heteroatoms include nitrogen, oxygen and sulphur. Arylamino and aryl is as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the nitrogen atom.

"Heteroaryloxy" refers to a heteroaryl-O- group in which the heteroaryl is as defined herein. Preferably the heteroaryloxy is a Q-Qgheteroaryloxy. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the oxygen atom.

"Heterocyclic" refers to saturated, partially unsaturated or fully unsaturated monocyclic, bicyclic or polycyclic ring system containing at least one heteroatom selected from the group consisting of nitrogen, sulfur and oxygen as a ring atom. Examples of heterocyclic moieties include heterocycloalkyl, heterocycloalkenyl and heteroaryl.

"Heterocycloalkenyl" refers to a heterocycloalkyl as defined herein but containing at least one double bond. A heterocycloalkenyl group typically is a C ₂ -Cn heterocycloalkenyl group. The group may be a terminal group or a bridging group.

"Heterocycloalkyl" refers to a saturated monocyclic, bicyclic, or polycyclic ring containing at least one heteroatom selected from nitrogen, sulfur, oxygen, preferably from 1 to 3 heteroatoms in at least one ring. Each ring is preferably from 3 to 10 membered, more preferably 4 to 7 membered. Examples of suitable heterocycloalkyl substituents include pyrrolidyl, tetrahydrofuryl, tetrahydrothiofuranyl, piperidyl, piperazyl, tetrahydropyranyl, morphilino, 1,3- diazapane, 1 ,4-diazapane, 1 ,4-oxazepane, and 1,4-oxathiapane. A heterocycloalkyl group typically is a C ₂ -C ₁₂ heterocycloalkyl group. The group may be a terminal group or a bridging group.

"Heterocycloalkylalkyl" refers to a heterocycloalkyl-alkyl- group in which the heterocycloalkyl and alkyl moieties are as defined herein. Exemplary heterocycloalkylalkyl groups include (2- tetrahydrofuryl)methyl, (2-tetrahydrothiofuranyl) methyl. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkyl group.

"Heterocycloalkylalkenyl" refers to a heterocycloalkyl-alkenyl- group in which the heterocycloalkyl and alkenyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the alkenyl group.

"Heterocycloalkylheteroalkyl" means a heterocycloalkyl-heteroalkyl- group in which the heterocycloalkyl and heteroalkyl moieties are as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the heteroalkyl group.

"Heterocycloalkyloxy" refers to a heterocycloalkyl -O- group in which the heterocycloalkyl is as defined herein. Preferably the heterocycloalkyloxy is a Ci-Ceheterocycloaikyloxy. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the oxygen atom.

"Heterocycloalkenyloxy" refers to a heterocycloalkenyl-O- group in which heterocycloalkenyl is as defined herein. Preferably the Heterocycloalkenyloxy is a C C ₆ Heterocycloalkenyloxy. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the oxygen atom. "Heterocycloamino" refers to a saturated monocyclic, bicyclic, or polycyclic ring containing at least one nitrogen and at least another heteroatom selected from nitrogen, sulfur, oxygen, preferably from 1 to 3 heteroatoms in at least one ring. Each ring is preferably from 3 to 10 membered, more preferably 4 to 7 membered. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the nitrogen atom.

"Hydroxyalkyl" refers to an alkyl group as defined herein in which one or more of the hydrogen atoms has been replaced with an OH group. A hydroxyalkyl group typically has the formula C _n H _(2n+ i-x ₎ (OH) _x In groups of this type n is typically from 1 to 10, more preferably from 1 to 6, most preferably from 1 to 3. x is typically from 1 to 6, more preferably from 1 to 4. "Lower alkyl" as a group means unless otherwise specified, an aliphatic hydrocarbon group which may be straight or branched having 1 to 6 carbon atoms in the chain, more preferably 1 to 4 carbons such as methyl, ethyl, propyl (n-propyl or isopropyl) or butyl (n-butyl, isobutyl or tertiary-butyl). The group may be a terminal group or a bridging group.

"Subject" refers to a human or an animal. "Sulfinyl" means an R-S(=0)- group in which the R group may be OH, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the sulfur atom.

"Sulfinylamino" means an R-S(=0)-NH- group in which the R group may be OH, alkyl, cycloalkyl, heterocycloalkyl; aryl or heteroaryl group as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the nitrogen atom. "Sulfonyl" means an R-S(=0) ₂ - group in which the R group may be OH, alkyloxy, aryloxy, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group as defined herein. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the sulfur atom. "Sulfonylamino" means an R-S(=0) ₂ -NH- group. The group may be a terminal group or a bridging group. If the group is a terminal group it is bonded to the remainder of the molecule through the nitrogen atom.

It is understood that included in the family of compounds of Formula (I) are isomeric forms including diastereoisomers, enantiomers, tautomers, and geometrical isomers in "E" or "Z" configurational isomer or a mixture of E and Z isomers. It is also understood that some isomeric forms such as diastereomers, enantiomers, and geometrical isomers can be separated by physical and/or chemical methods and by those skilled in the art.

Some of the compounds of the disclosed embodiments may exist as single stereoisomers, racemates, and/or mixtures of enantiomers and /or diastereomers. All such single stereoisomers, racemates and mixtures thereof, are intended to be within the scope of the subject matter described and claimed.

Additionally, Formula (I) is intended to cover, where applicable, solvated as well as unsolvated forms of the compounds. Thus, each formula includes compounds having the indicated structure, including the hydrated as well as the non-hydrated forms. Further, it is possible that compounds of the invention may contain more than one asymmetric carbon atom. In those compounds, the use of a solid line to depict bonds to asymmetric carbon atoms is meant to indicate that all possible stereoisomers are meant to be included. The use of a solid line to depict bonds to one or more asymmetric carbon atoms in a compound of the invention and the use of a solid or dotted wedge to depict bonds to other asymmetric carbon atoms in the same compound is meant to indicate that a mixture of diastereomers is present.

The term "optionally substituted" as used herein means the group to which this term refers may be unsubstituted, or may be substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, thioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkylalkenyl, heterocycloalkyl, cycloalkylheteroalkyl, cycloalkyloxy, cycloalkenyloxy, cycloamino, halo, carboxyl, haloalkyl, haloalkynyl, alkynyloxy, heteroalkyl, heteroalkyloxy, hydroxyl, hydroxyalkyl, alkoxy, thioalkoxy, alkenyloxy, haloalkoxy, haloalkenyl, haloalkynyl, haloalkenyloxy, nitro, amino, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroheterocyclyl, alkylamino, dialkylamino, alkenylamine, aminoalkyl, alkynylamino, acyl, alkyloxy, alkyloxyalkyl, alkyloxyaryl, alkyloxycarbonyl, alkyloxycycloalkyl, alkyloxyheteroaryl, alkyloxyheterocycloalkyl, alkenoyl, alkynoyl, acylamino, diacylamino, acyloxy, alkylsulfonyloxy, heterocyclic, heterocycloalkenyl, heterocycloalkyl, heterocycloalkylalkyl, heterocycloalkylalkenyl, heterocycloalkylheteroalkyl, heterocycloalkyloxy, heterocycloalkenyloxy, heterocycloxy, heterocycloamino, haloheterocycloalkyl, alkylsulfinyl, alkylsulfonyl, alkylsulfenyl, alkylcarbonyloxy, alkylthio, acylthio, aminosulfonyl, phosphorus- containing groups such as phosphono and phosphinyl, sulfinyl, sulfinylamino, sulfonyl, sulfonylamino, aryl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylheteroalkyl, heteroarylamino, heteroaryloxy, arylalkenyl, arylalkyl, alkylaryl, alkylheteroaryl, aryloxy, arylsulfonyl, cyano, cyanate, isocyanate, -C(0)NH(alkyl), and -C(0)N(alkyl) ₂ . The word "substantially" does not exclude "completely" e.g. a composition which is "substantially free" from Y may be completely free from Y. Where necessary, the word "substantially" may be omitted from the definition of the invention.

Unless specified otherwise, the terms "comprising" and "comprise", and grammatical variants thereof, are intended to represent "open" or "inclusive" language such that they include recited elements but also permit inclusion of additional, unrecited elements.

As used herein, the term "about", in the context of concentrations of components of the formulations, typically means +/- 5% of the stated value, more typically +/- 4% of the stated value, more typically +/- 3% of the stated value, more typically, +/- 2% of the stated value, even more typically +/- 1% of the stated value, and even more typically +/- 0.5% of the stated value.

Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range. Certain embodiments may also be described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the disclosure. This includes the generic description of the embodiments with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

Detailed Disclosure of Optional Embodiments

Exemplary, non-limiting embodiments of a metal complex will now be disclosed. There is provided a metal complex of Formula (I):

Formula (I); wherein M is a group 10 element;

R ¹ is Ci ioalkyl or R ¹ is an optionally substituted phenyl of formula II:

Formula (II); wherein * indicates the bond to Formula (I);

R ⁶ and R ⁷ may each independently represent hydrogen, a C _MO alkyl, nitro, halogen, -O- C _MO alkyl, a halogenated C _{1 10} alkyl, carboxylic acid or ester, amide, amino, ammonium, -S0 ₃ H or an optionally substituted -S0 ₂ -; n is 1 or 2;

L is a ligand;

R ² and R ³ are either the same or different and independently represent a C ₄ _i ₂ tertiary alkyl or, together with the P atom to which they are attached, form a phosphorous-containing ring having formula (III);

R and R" are either the same or different and independently represent a C ₄ _i ₂ tertiary alkyl or, together with the P atom to which they are attached, form a phosphorous-containing ring having formula (III):

Formula (III); wherein * indicates the connection to Formula (I);

Y represents an optionally substituted C _M0 alkyl, optionally substituted C _M0 alkylene or optionally substituted silicon, C=0, C=NR ¹⁶ , -CH-NR ¹⁷ R ¹⁸ , S=0, S0 ₂ , P(0)OH or P ⁺ R ²² R ²³ ; wherein the C _{1 10} alkyl, C _{1 10} alkylene or silicon may be substituted with - O- C _MO alkyl or OH; and

R ⁸ , R ⁹ , R ¹⁰ , R ⁿ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² and R ²³ each independently represent hydrogen or an optionally substituted Q to C ₁₂ alkyl, provided that the metal complex does not have the following structure:

The alkyl may be a Q to C ₁₂ alkyl, C ₄ to C ₁₂ alkyl, Q to C ₁₀ alkyl, or selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, teri-butyl, pentyl, isopentyl, teri-pentyl, hexyl and isohexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl.

R ⁸ , R ⁹ , R ¹⁴ and R ¹⁵ may each independently be Q to C ₁₀ alkyl. R ⁸ , R ⁹ , R ¹⁴ and R ¹⁵ may each independently be methyl or R ⁸ , R ⁹ , R ¹⁴ and R ¹⁵ may all be methyl.

M may be nickel, palladium or platinum. M may be palladium. M may be palladium (II) or palladium (0).

The metal complex does not have the following structure, where L is a ligand:

The metal complex may not comprise l,2-bis[di(i-butyl)phosphinomethyl]benzene (DTBPX). The metal complex may be selected from the following:

Ph may be a phenyl group.

L may independently be a neutral ligand, monoanionic ligand or dianionic ligand.

When n is 2 and L is independently a neutral ligand, the two ligands may be connected to form a single bidentate ligand.

L may independently be selected from the group consisting of hydride, methyl, allyl, 1- methylallyl, acetate, trifluoroacetate, triflate, methanesulfonate, ,para-toluenesulfonate, propylsulfonate, camphorsulfonate, benzenesulfonate, phosphate, chloride, bromide, iodide, sulfate, carbonate, acetonitrile, 1,4-benzoquinone, pyridine, carbon monoxide, triphenylphosphine and dibenzilideneacetone, alkyl, carboxylate, sulfonate, carboxylic acid, ester, ketone, alkene, diene, nitrile, amine, phosphine, ether, alcohol, imine. L may independently be a deprotonated acid XH. The acid XH may have a pKa of less than about 5, less than about 4.5, less than about 4, less than about 3.5, less than about 3, less than about 2.5, less than about 2, less than about 1.5 or less than about 1, when measured in water at 18°C. The acid XH may be selected from the group consisting of sulfonic acids, sulfuric acids, phosphorous acids and carboxylic acids. The acid XH may be selected from the group consisting of methanesulfonic acid, para-toluenesulfonic acid, triflic acid, propylsulfonic acid, camphorsulfonic acid, benzenesulfonic acid, phosphoric acid, sulfuric acid, trifluoroacetic acid, and acetic acid. In an embodiment, M may be palladium (II), n may be 2 and each L may independently be a monoanionic ligand. In another embodiment, M may be palladium (II), n may be 1 and L may be a dianionic ligand. In another embodiment, M may be palladium (II), n may be 2, L may independently be a neutral ligand and the metal complex may have non-coordinating counter anions. In another embodiment, M may be palladium (0), n may be 1 or 2, and L may independently be a neutral ligand.

There is also provided a catalyst composition, wherein the catalyst composition may comprise the metal complex as defined above. The catalyst composition may further comprise an activating acid XH.

The composition may be substantially free of oxygen.

The composition may further comprise a solvent. The choice of solvent may depend on the selected catalyst and/or the selected substrate to be catalysed.

The solvent may be such that the product of the catalytic reaction can be separated from the unreacted reactants by reducing the temperature of the reaction. The solvent may be any substance which is not a reactant, catalyst component, a product or a precursor of the reactant.

The composition may be substantially free of an organic solvent or may be substantially free of a water-immiscible solvent.

The composition may comprise a biphasic system or may be substantially an emulsion. The activating acid XH may have a pKa of less than about 5, less than about 4.5, less than about 4, less than about 3.5, less than about 3, less than about 2.5, less than about 2, less than about 1.5 or less than about 1, when measured in water at 18°C.

The activating acid XH may be selected from the group consisting of sulfonic acids, sulphuric acids, phosphorous acids and carboxylic acids. The activating acid XH may be selected from the group consisting of methanesulfonic acid, para-toluenesulfonic acid, triflic acid, propylsulfonic acid, camphorsulfonic acid, phosphoric acid, sulfuric acid, trifluoroacetic acid, trifluoromethylsulfonic acid and acetic acid. The activating acid XH in the catalyst composition may be methane sulfonic acid.

The activating acid XH may be present in at least two molar equivalents relative to the metal. The activating acid XH may be present in at least about 2 molar excess, at least about 4 molar excess, at least about 6 molar excess, at least about 8 molar excess, at least about 10 molar excess, at least about 12 molar excess, at least about 14 molar excess, at least about 16 molar excess, at least about 17 molar excess or at least about 20 molar excess relative to the metal.

The composition may be used to convert an alkene to a carboxylic acid or an ester thereof.

The metal complex, the temperature and pressure of the composition may be such that the conversion of alkene to carboxylic acid or ester thereof is greater than about 95% in yield. There is also provided a method for preparing a catalyst composition as defined above, the method may comprise the step of combining a group 10 metal compound and a bidentate diphosphine.

The method may further comprise the step of adding an activating acid XH. The metal may be nickel, palladium or platinum. The metal may be palladium. The palladium compound may be selected from the group consisting of palladium carboxylate, palladium(O) compound, palladium acetate, tris(dibenzylideneacetone)dipalladium(0) and palladium acetylacetonate.

The bidentate diphosphine may have the formula (IV):

Formula (IV) wherein R ¹ is C _{1 10} alkyl or R ¹ is an optionally substituted phenyl of formula II:

Formula (II); wherein * indicates the bond to Formula (I);

R ⁶ and R ⁷ may each independently represent hydrogen, a C _M0 alkyl, nitro, halogen, -O-alkyl, a halogenated C _M0 alkyl, carboxylic acid or ester, amide, amino, ammonium, -S0 ₃ H or an optionally substituted -S0 ₂ -;

R ² and R ³ are either the same or different and independently represent a C _{4 12} tertiary alkyl or, together with the P atom to which they are attached, form a phosphorous-containing ring having formula (III);

R ⁴ and R ⁵ are either the same or different and independently represent a C ₄ _i ₂ tertiary alkyl or, together with the P atom to which they are attached, form a phosphorous-containing ring having formula (III):

Formula (III); wherein * indicates the connection to Formula (I);

Y represents an optionally substituted C _{1 10} alkyl, optionally substituted C _{1 10} alkylene or optionally substituted silicon, C=0, C=NR ¹⁶ , -CH-NR ¹⁷ R ¹⁸ , S=0, S0 ₂ , P(0)OH or P ⁺ R ²² R ²³ ; wherein the C _{1 10} alkyl, C _{1 10} alkylene or silicon may be substituted with - O- C _MO alkyl or OH; and

R ⁸ , R ⁹ , R ¹⁰ , R ⁿ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² and R ²³ each independently represent hydrogen or an optionally substituted Q to C ₂ alkyl, provided that the bidentate diphosphine does not have the following structure:

The alkyl may be a Q to C ₂ alkyl, C ₄ to C ₂ alkyl, Q to Ci ₀ alkyl, or selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, teri-butyl, pentyl, isopentyl, teri-pentyl, hexyl and isohexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl.

R ⁸ , R ⁹ , R ¹⁴ and R ¹⁵ may each independently be Q to C ₁₀ alkyl. R ⁸ , R ⁹ , R ¹⁴ and R ¹⁵ may each independently be methyl or R ⁸ , R ⁹ , R ¹⁴ and R ¹⁵ may all be methyl.

The bidentate diphosphine does not comprise l,2-bis[di(i-butyl)phosphinomethyl] benzene (DTBPX) having the following structure:

The bidentate diphosphine may be selected from the group consisting of the following:

l,2-Bis[(2,2,6,6-tetramethylphosphinan-4- l,2-Bis[(2,2,6,6-tetramethylphosphinan-4- on)methyl]benzene (BPX) ol)methyl]benzene (BPX-OH)

1 , 1 '-( 1 ,2-Phenylenebis(methylene))bis(2,2,6,6- l,2-Bis[(2,2,6,6-tetramethylphosphinan-l- tetramethyl-N-phenylphosphinan-4-imine) yl)methyl]benzene (BTMPX)

(BPPIX)

((4-(Trifluoromethyl)- 1 ,2- ((4-Nitro- 1 ,2- ((4-(teri-butyl)- 1 ,2- phenylene)¾i5'(methylene))Z7i5' phenylene)¾i5'(methylene))Z7i5' phenylene^ s^methylene))/? ,? (di-teri-butylphosphine) (di-teri-butylphosphine) (di-teri-butylphosphine) (4-CF ₃ -DTBPX) (4-N0 ₂ -DTBPX) (4-'Bu-DTBPX)

((4,5-Dichloro-l,2- ((4,5-(Dimethoxy)-l,2- ((4-(Phenylsulfonyl)-l,2- phenylene)bis(methylene))bis phenylene)¾i5'(methylene))Z7i5' phenylene)bis(methylene))bis (di-tert-butylphosphine) (di-teri-butylphosphine) (di-tert-butylphosphine) (4,5-Cl-DTBPX) (4,5-OMe-DTBPX) (4-PhS0 ₂ -DTBPX)

3,4-Bis((di-tert- Methyl 3,4-bis((di-tert- 3,4-Bis((di-tert- butylphosphanyl)methyl)benz butylphosphanyl)methyl)benz butylphosphanyl)methyl)benz enesulfonic acid enesulfonate oic acid.

(4-HO ₃ S-DTBPX) (4-Me0 ₃ S-DTBPX) (4-H0 ₂ C-DTBPX)

Methyl 3,4-bis((di-tert- butylphosphanyl)methyl)benz

oate

(4-Me0 ₂ C-DTBPX).

Ph may be a phenyl group.

The basicity of the phosphorous atom of the bidentate ligand may be reduced, either by the insertion of an electron-withdrawing group, for example a C=0, as substituent Y. The compression in the C-P-C angle in the phosphorinone ring relative to the corresponding angle in DTBPX also causes a decrease in the σ-donating character of the P lone pair and a concomitant increase in the π-accepting character of the phosphorus, overall reducing the basicity of the phosphorous atom. Additionally or alternatively, it may be caused by the substitution of R ⁶ and R ⁷ with electron-withdrawing groups, for example a nitro, halogen such as chloride, or a halogenated alkyl, such as trifluoromethyl. The activating acid XH may have a pKa of less than about 5, less than about 4.5, less than about 4, less than about 3.5, less than about 3, less than about 2.5, less than about 2, less than about 1.5 or less than about 1, when measured in water at 18°C.

The activating acid XH may be selected from the group consisting of sulfonic acids, sulphuric acids, phosphorous acids and carboxylic acids. The activating acid XH may be selected from the group consisting of methanesulfonic acid, para-toluene sulfonic acid, triflic acid, propylsulfonic acid, camphorsulfonic acid, phosphoric acid, sulfuric acid, trifluoroacetic acid, trifluoromethylsulfonic acid and acetic acid. The activating acid XH in the catalyst composition may be methane sulfonic acid.

The activating acid XH may be present in at least two molar equivalents relative to the metal. The activating acid XH may be present in at least about 2 molar equivalents, at least about 4 molar equivalents, at least about 6 molar equivalents, at least about 8 molar equivalents, at least about 10 molar equivalents, at least about 12 molar equivalents, at least about 14 molar equivalents, at least about 16 molar equivalents, at least about 18 molar equivalents or at least about 20 molar equivalents relative to the metal. The catalyst composition may be prepared in situ. If the catalyst composition is prepared in situ, the composition may comprise a group 10 metal and a bidentate disphosphine.

If the catalyst composition is prepared in situ, the composition may comprise a group 10 metal, a bidentate diphosphine and an activating acid XH. If the catalyst composition is prepared in situ, the composition may comprise a metal complex as defined above and a co-catalyst.

The group 10 metal may be nickel, palladium or platinum. The group 10 metal may be palladium. The group 10 metal may be palladium (II) or palladium (0).

As shown in Fig. 3, the catalyst composition may be formed in situ by mixing any palladium (0) compound, for example palladium tetrakis(triphenylphosphine), with a bidentate diphosphine ligand, as defined above, together with an activating acid HX. A cationic palladium (II) complex may then be formed by protonation of palladium (0), to first form L ₂ Pd(II) H(X), optionally followed by an additional equivalent of acid HX to generate L ₂ Pd(II)X ₂ .

The co-catalyst may be acid XH. Since the anion X- of acid XH is typically a weakly/non-coordinating ligand, the structure of the metal complexes in the catalyst composition prepared in situ may not have the anion X- of acid XH each occupying a coordination site on the metal. If the acid is multi-dentate, one anion X- of acid XH may occupy two coordination sites on the metal (e.g. two oxygens on a sulfonate), while the other anion may be present as a non-coordinating counter-anion. Furthermore, other ligands such as carbon monoxide, methanol solvent molecules and substrate molecules which may also be present in the reaction may occupy a coordinating site on the metal.

The catalyst composition may be pre -formed.

If the catalyst composition is pre-formed, then the catalyst composition may comprise a metal complex as defined above. If the catalyst composition is pre-formed, the catalyst composition may comprise a metal complex having the following structure:

Me may be a -CH ₃ group. OAc may be an acetate group, dba may be dibenzylideneacetone. The two anionic ligands in the divalent palladium complexes may each occupy one coordination site on palladium, or one anionic ligand may occupy two coordination sites on palladium (e.g. two oxygens on a sulfonate), while the other anion is present as a non-coordinating counter- anion.

If the pre -formed catalyst composition comprises acetate or trifluoroacetate ligands, the composition may inherently have very low activity, but the activity may increase by orders of magnitude by the addition of a co-catalyst such as sulfonic acid. How active the pre-formed complexes are, may depend on the coordinating strength of the respective ligand (such as carboxylate or sulfonate) in combination with the nature of the substrate and solvent present in the reaction mixture. In addition, the alkenoic acid that may be present as a reaction substrate may also function as the acidic co-catalyst, for example with the Pd(0)dba complex. If the group 10 metal in the catalyst composition or M in the metal complex is palladium(II) (i.e. divalent), an excess of acid HX may be optionally present. If the group 10 metal in the catalyst composition or M in the metal complex is palladium(O) (i.e. metallic Pd), then the activating acid HX may be essential to form an active catalyst composition.

The catalytically active form of the group 10 metal in the catalyst composition or M in the metal complex may be a palladium (II) hydride capable of inserting an alkene, but palladium (0) may also be present as an intermediate or dormant species in the catalytic carbonylation cycle.

There is also provided a process for preparing a dicarboxylic acid or an ester thereof, the process may comprise the step of (2) contacting an alkenoic acid or an ester thereof with a catalyst composition as defined above in the presence of carbon monoxide. The contacting step (2) may be carried out substantially in the absence of oxygen.

The contacting step (2) may be carried out under a carbon monoxide atmosphere.

The carbon monoxide may be in the form of carbon monoxide gas, or may be generated in situ using carbon monoxide surrogates that decompose to form carbon monoxide. The carbon monoxide surrogate may be formates such as N-formylsaccharin, formic acid or alkyl formates. The contacting step (2) may be performed in the presence or absence of a solvent.

The contacting step (2) may be carried out at a temperature of between about 50°C and about 150°C, or about 80°C and about 120°C.

The contacting step (2) may be carried out at a pressure of between about 100 kPa (1 bar) and about 15000 kPa (150 bar), about 300 kPa (3 bar) and about 8000 kPa (80 bar) or about 500 kPa (5 bar) and about 6000 kPa (60 bar).

The process may further comprise, before the contacting step (2), a process for preparing the alkenoic acid or ester thereof, comprising the step of either (la) heating a lactone in the presence of an acidic catalyst system and water or an alcohol to produce an alkenoic acid or ester thereof; or (lb) reacting a diene with carbon monoxide and the metal complex in the presence of water or an alcohol to produce an alkenoic acid or ester thereof. Step (la) may comprise reactive distillation, thereby providing a distillate comprising the alkenoic acid or ester thereof.

Step (la) may be carried out at a temperature at or above the normal boiling point of the lactone. Step (la) may be carried out at a temperature of between about 150°C to about 370°C, about 200°C to about 350°C, or about 250°C to about 300°C.

Step (la) may be carried out at a pressure of between about 50 kPa (0.5 bar) to about 3000 kPa (30 bar). Step (la) may be carried out at a pressure of about 100 kPa (1 bar).

The acidic catalyst system may comprise an acidic catalyst or a heterogeneous solid catalyst.

The acidic catalyst system may comprise alumina, silica, zeolite, clay or any mixture thereof. The acidic catalyst system may, for example, comprise a mixture of alumina and silica. The acidic catalyst system may, for example, comprise a mixture of zeolite and clay.

The clay may be montmorillonite or kaolinite.

The zeolite may be selected from the group consisting of analcime, chabazite, clinoptilite, heulandite, natrolite, phillipsite and stilbite. The alkenoic acid or ester thereof produced in step (la) may comprise a plurality of isomers.

Step (lb) may be carried out as an alternative method for the production of alkenoic acid or ester thereof. The reaction may be a hydroxycarbonylation reaction or an alkoxycarbonylation reaction.

The diene may be a C ₃ _i ₀ alkene. The alkene may comprise two double bonds. The alkene may be selected from the group consisting of allene, butadiene, pentadiene, hexadiene, heptadiene, octadiene, nonadiene, and decadiene.

The diene may be bio-based.

When a portion of the lactone is unreacted after step (la), the process may further comprise a step (3) of separating part or substantially all the unreacted lactone from the alkenoic acid or ester thereof and recycling part or substantially all of the separated unreacted lactone by carrying out heating step (la) as defined above on the part or substantially all of the separated unreacted lactone.

When the contacting step (2) results in unreacted alkenoic acid or ester thereof, the process may further comprise the steps of: (4) separating part or substantially all of the unreacted alkenoic acid or ester from the dicarboxylic acid or ester thereof and recycling part or substantially all of the separated unreacted alkenoic acid or ester thereof by carrying out contacting step (2) as defined above on the part or substantially all of the separated unreacted alkenoic acid or ester thereof. In one embodiment, the lactone used in step (la) may be γ-valerolactone and the alkenoic acid may be pentenoic acid. The pentenoic acid may comprise one or more, or optionally all, of 2- pentenoic acid, 3-pentenoic acid and 4-pentenoic acid. The double bond in 2-pentenoic acid and 3-pentenoic acid may be in the trans or in the cis configuration. The dicarboxylic acid may be adipic acid, methylglutaric acid, ethylsuccinic acid or propylmalonic acid.

In another embodiment, the lactone used in step (la) may be γ-valerolactone, and the alkenoic acid ester may be alkyl pentenoate. The alkyl pentenoate may comprise one or more, or optionally all, of alkyl 2-pentenoate, alkyl 3 -pentenoate and alkyl 4-pentenoate. The double bond in alkyl 2-pentenoate and alkyl 3 -pentenoate may be in the trans or in the cis configuration. The dicarboxylic acid ester may be dialkyl adipate.

The process may comprise the steps of:

(la) heating γ-valerolactone in the presence of an acidic catalyst system to produce pentenoic acid, the acidic catalyst system comprising an acidic catalyst; and

(2) contacting the pentenoic acid in the absence of an organic solvent with carbon monoxide, water and a catalyst composition, the catalyst composition comprising a palladium catalyst, to produce adipic acid, wherein step (la) is carried out with or without water and the heating of the γ-valerolactone in step (la) comprises reactive distillation, thereby providing a distillate comprising the pentenoic acid, and step (2), reacting pentenoic acid to adipic acid using a catalyst composition as defined above, wherein the palladium catalyst is prepared by combining palladium acetate, l,2-bis[(2,2,6,6-tetramethylphosphinan-4-on)methyl]benzene, and methanesulfonic acid.

The process may comprise the steps of:

(la) heating γ-valerolactone in the presence of an acidic catalyst system and methanol to produce methyl pentenoate, the acidic catalyst system comprising an acidic catalyst; and

(2) contacting the methyl pentenoate with carbon monoxide, methanol and a catalyst composition, the catalyst composition comprising a palladium catalyst, to produce dimethyl adipate, wherein step (la) is carried out with or without water and the heating of the y-valerolactone in step (la) comprises reactive distillation, thereby providing a distillate comprising the methyl pentenoate, and step (2), reacting methyl pentenoate to dimethyl adipate using a catalyst composition as defined above, wherein the palladium catalyst is prepared by combining palladium acetate, l,2-bis[(2,2,6,6-tetramethylphosphinan-4-on)methyl]benzene, and methanesulfonic acid. An alternative route to producing bio-based adipic acid may involve hydroxycarbonylation of bio-based butadiene to firstly 3-pentenoic acid and subsequent hydroxycarbonylation of the 3- pentenoic acid to adipic acid in the presence of a palladium catalyst. The reaction may therefore be applied not only to GVL-derived pentenoic acid isomers but also to compounds such as butadiene, ethylene and unsaturated fatty acids/esters.

The process may facilitate the conversion of alkenoic acid or an ester thereof to a dicarboxylic acid or an ester thereof with high yield and selectivity. The method may enable a conversion yield of greater than 40% and a selectivity greater than 96%.

In an embodiment, when the substrates pentenoic acids and water are used as the medium, the adipic acid product is a solid at reaction temperature and therefore has limited solubility. In theory, a much higher yield than 40% may be achieved if GVL or a carboxylic acid is used as a solvent (for example at >50% by volume). In such cases, the pentenoic acid conversion may be much higher, in principle, quantitative (>99%). Alternatively, the solid adipic acid may be easily separated from the reaction mixture by filtration, while the liquid phase, comprising among others unconverted pentenoic acids and catalyst, can be recycled to result in both an increased catalyst turnover number and a much higher overall pentenoic acids conversion. There is also provided a process for the production of a carboxylic acid or ester thereof, the process may comprise the step of contacting an alkene or alkenoic acid with a catalyst composition as defined above in the presence of carbon monoxide.

The contacting step may be carried out substantially in the absence of oxygen.

The contacting step may be carried out under a carbon monoxide atmosphere. The carbon monoxide may be in the form of carbon monoxide gas, or may be generated in situ using carbon monoxide surrogates that decompose to form carbon monoxide. The carbon monoxide surrogate may be formats such as N-formylsaccharin.

The contacting step may be carried out at a temperature of between about 50°C to about 150°C, or about 80°C to about 120°C. The contacting step may be carried out at a pressure of between about 100 kPa (1 bar) to about 15000 kPa (150 bar), about 300 kPa (3 bar) to about 8000 kPa (80 bar) or about 500 kPa (5 bar) to about 6000 kPa (60 bar).

The reaction may be a hydroxycarbonylation reaction or an alkoxycarbonylation reaction.

The alkene may be a C ₂ - ₂ o alkene comprising one or more double bonds, with the alkene positioned in a terminal or internal position.

The alkene may be selected from the group consisting of ethylene, propylene, butene, butadiene, pentene, pentadiene, hexene, hexadiene, heptene, heptadiene, octene, octadiene, nonene, nonadiene, decene and decadiene, methylpentenoate, 1 -hexene, 3-hexene, 3-pentenenitrile, methyl butenoate, unsaturated fatty acids or esters thereof, and monounsaturated fatty acids or esters thereof and polyunsaturated fatty acids or esters thereof. The fatty acid or ester thereof may be an odd-chain fatty acid or an ester thereof. An odd chain fatty acid may contain an odd number of carbon atoms in the structure..

The alkene or diene may be bio-based. The alkene or diene may be produced by alkene metathesis of monounsaturated fatty acids or esters thereof, or polyunsaturated fatty acids or esters thereof.

The alkene may be 1-decene produced by alkene cross-metathesis of oleic acid or an ester thereof with ethylene.

The alkene may be 9-octadecene produced by self-metathesis of the 1-decene described above or produced by self-metathesis of oleic acid or an ester thereof. The alkene may be an internal alkene, an isomeric mixture of alkenes of the same chain length, or a mixture of internal alkenes of different chain length. An internal alkene is where the double bond is positioned in an internal position of the aliphatic chain, in contrast to being a terminal alkene.

The product of the process may be saturated or unsaturated carboxylic acids or carboxylic esters.

The product of the process may be odd-chain saturated or unsaturated carboxylic acids or carboxylic esters.

The carboxylic acid may be a fatty acid. The carboxylic acid may be an odd-chain fatty acid.

The process may further comprise water as a co-reagent. If water is used as the co-reagent, then the process would be referred to as a hydroxycarbonylation reaction and the reaction product may comprise a carboxylic acid.

The process may further comprise alcohol as a co-reagent. If alcohol is used as a co-reagent, the process would be referred to as an alkoxycarbonylation reaction and the reaction product may comprise an alkyl ester, the alkyl being the alkyl moiety of the alcohol co-reagent. The alcohol co-reagent may be selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, pentanol and hexanol.

The alkene may be an alkyl alkenoate.

The alkyl alkenoate may be produced by a ring-opening reaction of a lactone.

The process may facilitate the conversion of alkene or diene to a carboxylic acid or an ester thereof with high yield and selectivity. The method may enable a conversion yield of greater than 80% and a selectivity greater than 95%. In the process of converting an alkene or diene to a carboxylic acid or an ester thereof, typically methanol was present in large excess as the solvent and the methyl ester product was generally a liquid as well. Quantitative conversion may also be possible for this reaction, depending on the substrate:catalyst ratio and reaction time. There is also provided a method of preparing Nylon 6-6, the method may comprise the step of copolymerising adipic acid prepared in accordance with the process as defined above with hexamethylenediamine, to form Nylon 6-6.

Brief Description of Drawings

The accompanying drawings illustrate a disclosed embodiment and serves to explain the principles of the disclosed embodiment. It is to be understood, however, that the drawings are designed for purposes of illustration only, and not as a definition of the limits of the invention.

Fig.l

[Fig. 1] is a schematic diagram showing a prior art process of converting GVL to adipic acid. Fig.2

[Fig. 2] is a schematic diagram showing some conversions of alkenoic acids to dicarboxylic acids using a catalyst.

Fig.3

[Fig. 3] is a schematic diagram showing the possible pathways for making a metal complex with the diphosphines and possible activation pathways leading to an active catalyst composition.

Detailed Description of Drawings

[Fig. 2] is a schematic diagram showing some conversions of alkenoic acids to dicarboxylic acids using a catalyst. A mixture of 4-pentenoic acid, trans-3- pentenoic acid, cis-3- pentenoic acid, trans-2- pentenoic acid and cis-2- pentenoic acid can be converted to dicarboxylic acids such as adipic acid, methylglutaric acid, ethylsuccinic acid and propylmalonic acid.

[Fig. 3] is a schematic diagram showing possible pathways for making a metal complex with the diphosphines and possible activation pathways leading to an active catalyst composition. The palladium complex may have an oxidation state of 0 or 2, and the type of ligand may depend accordingly. The ligand may be monoanionic, dianionic, neutral, monodentate or bidentate, and the resulting catalyst composition may have a weakly coordinating anion coordinated to the metal or present as a non-coordinating counterion. The oxidation of palladium(O) to palladium(II) as well as the reduction of palladium(II) to palladium(O) are both indicated. The position of the reaction may depend on the reaction conditions such as whether the environment is oxidising or reducing, and the strength of the acid present.

Examples Non-limiting examples of the invention and comparative examples will be further described in greater detail by reference to specific Examples, which should not be construed as in any way limiting the scope of the invention.

Example 1: Materials and Methods

Air- or moisture-sensitive reactions were carried out under an atmosphere of purified argon, and compounds were stored in a nitrogen or argon filled glove box. Solvents were dried using a Glass Contour solvent purification system where the solvents were passed through oxy- and moisture traps under an atmosphere of purified argon. CO gas was purified by passing through oxy- and moisture traps. NMR spectra were recorded on a Bruker 400 MHz Spectrometer. The chemical shifts were referenced to residual protio impurities in the NMR solvent used; ¹³ C chemical shifts were referenced to the ¹³ C chemical shift of the NMR solvent used; whereas ³¹ P chemical shifts were referenced against a H ₃ P0 ₄ external standard. Mass spectra were recorded on an Agilent G1969 A/6210 TOF-MS. Elemental analyses were determined using an Organic Elemental Analysis Flash 2000 CHNS/O Elemental Analyzer. DTBPX ligand was purchased from commercial sources. Example 2: Synthesis of Ligands

Synthesis of tetrabutyl(l,2-phenylenebis(methylene))Z ^' s(phosphonate)

α,α-Dibromo-o-xylene (19.5 g, 73.9 mrnol) and tri(«-butyl)phosphite (74.0 g, 80 mL, 296.0 mmol) were heated at 120°C for 16 hours. After which time the excess tri(«- butyl)phosphite and bromobutane were distilled off to leave a colourless oil. Yield = (35.0 g, 97%). *H NMR (400 MHz, CDC1 ₃ ): δ 7.25 - 7.21 (2H, m, ArH), 7.19 - 7.16 (2Η, m, ArH), 3.97 - 3.85 (8Η, m, OCH ₂ ), 3.39 (4Η, d, ² J _HP = 20.3 Hz CH ₂ ), 1.59 - 1.52 (8Η, m, OCH ₂ CH ₂ ), 1.34 - 1.28 (8Η, m, CH ₂ ) and 0.88 (12Η, t, ³ J _HH = 7.4 Hz, CH ₃ ). ¹³ C NMR (101 MHz, CDC1 ₃ ): δ 131.6 (s, ArQ, 131.2 (s, ArC _q ), 127.3 (s, ArQ, 65.9 (t, ² Jpc = 3.5 Hz, O H ₂ ), 32.7 (t, ³ J _PC = 3.0 Hz, OCH ₂ H ₂ -), 31.3 (dd, ¾ _α = 137.6 Hz and ⁴ J _PC = 2.0 Hz, H ₂ ), 18.8 (s, H ₂ ) and 13.7 (s, H ₃ ). ³¹ P NMR (162 MHz, CDC1 ₃ ): δ 26.8. HR-MS (+ve ESI): 491.2706 [M+H] ⁺ calc. 491.2686. Elem. Anal. Calcd for C ₂₄ H ₄₄ 0 ₆ P ₂ : C, 58.76; H, 9.04. Found: C, 58.39; H, 8.66. Synthesis of l,2-Z»i ^' s(Phosphinomethyl)benzene

Chlorotrimethylsilane (10.3 mL, 81.5 mmol) was added dropwise to LiAlH ₄ (3.09 g, 81.5 mmol) suspended in THF (150 mL) at -78°C. After complete addition, the reaction was allowed to warm to room temperature and stirred. After 2 hours the reaction was cooled to -50°C and a solution of tetrabutyl(l ,2-phenylenebis(methylene))bis(phosphonate) (10.0 g, 20.4 mmol) in THF (100 mL) was added dropwise, after which the reaction was allowed to warm to room temperature and stirred an additional 2 hours. The reaction was quenched by the slow addition of degassed deionised water (10 mL) followed by addition of degassed 20% aqueous NaOH (10 mL). After the addition of MgS0 ₄ , the suspension was filtered and the residue washed with THF (3 x 25 mL). Concentration of the filtrate in vacuo afforded an oily emulsion which was then passed through an alumina plug (neutral, activated), eluting with CH ₂ C1 ₂ . Subsequent removal of solvent in vacuo yielded the product as a colourless pyrophoric oil (3.45 g, quantitative). *H NMR (400 MHz, CDC1 ₃ ): δ 7.19 - 7.10 (4H, m, ArH), 3.03 (4H, dt, ¾ _Ρ = 195.4 Hz and ³ J _HH = 7.2 Hz, PH ₂ ), 2.96 - 2.91 (4H, m, CH ₂ ). ¹³ C NMR (101 MHz, CDC1 ₃ ) δ 139.3 (ArQ, 129.6 - 129.2 (m, ArQ, 126.7 (ArQ, 18.0 (dt, % _Ρ = 9.9 Hz and ⁴ J _CP = 2.9 Hz, H ₂ ). ³¹ P NMR (162 MHz, CDC1 ₃ ): δ -125.5.

Synthesis of l,2-Bis[(2,2,6,6-tetramethylphosphinan-4-onyl)methyl]benzene (BPX)

l ,2-Bis(phosphinomethyl)benzene (3.40 g, 20.0 mmol) and 2,6-dimethylhepta-2,5-dien-4- one (6.25 mL, 40.0 mmol) were heated to 120°C for 22 hours. Upon cooling, a very viscous yellow oil was formed which crystallised on standing. The yellow crystals were triturated in MeOH overnight, filtered and recrystallised in boiling MeOH to yield BPX as a white solid (4.2 g, 47%). *H NMR (400 MHz, CDC1 ₃ ): δ 7.50 - 7.40 (2H, m, ArH), 7.15 - 7.12 (2Η, m, ArH), 3.25 (4Η, s, PCH ₂ ), 2.56 - 2.52 (4Η, m, CH ₂ ), 2.39 - 2.31 (4Η, m, CH ₂ ), 1.20 ( 12Η, d, ³ J _PH = 5.4 Hz, CH ₃ ) and 1.07 ppm ( 12H, d, ³ J _PH = 17.0 Hz, CH ₃ ). ¹³ C NMR (101 MHz, CDC1 ₃ ): δ 209.9 (d, ³ J _CP = 1.1 Hz, C=0), 136.9 (dd, ² J _CP = 7.7 Hz, ³ J _CP = 2.9 Hz, ArC _q ), 131.3 (d, ³ J _CP = 11.2 Hz, ArC), 126.4 (d, ⁴ J _CP = 1.8 Hz, ArC), 55.5 (d, ^ι 1 = 6.4 Hz, CH ₂ ), 35.4 (d, ^cp 19.1 Hz C _q ), 31.7 (d, ² J _CP = 25.2 Hz, CH ₃ ), 26.4 (dd, ^l J _c? 26.7 Hz and ⁴ J _CP = 8.7 Hz, PCH ₂ ) and 25.8 (s, CH ₃ ). ³¹ P NMR ( 162 MHz, CDC1 ₃ ): δ 5.6 ppm. IR (KBr): v 1700 (s) C=0 str. HR-MS (+ve ESI): 447.2576 [M+H] ⁺ calc. 447.2582. Elem. Anal. Calcd for C ₂₆ H ₄₀ O ₂ P ₂ : C, 69.93; H, 9.03. Found: C, 70.14; H, 8.82.

Synthesis of l,l'-(l _» 2-phenylenebis(methylene))bis(2,2,6,6-tetramethyl-N- phenylphosphinan-4-imine) (BPPIX).

BPX (0.16 g, 0.36 mmol) was dissolved in toluene (10 mL), aniline (0.067 g, 0.71 mmol) was added as well as a catalytic amount of -toluene sulfonic acid monohydrate (5 mg). After heating for 16 hours further aniline was added (0.10 g, 1.1 mmol) (due to incomplete conversion) and the mixture heated for additional 16 hours. Again the conversion was incomplete, therefore excess aniline (1 mL) was added and the mixture heated for an additional 16 hours. After this time the solvent was removed in vacuo to give the crude product. ³¹ Ρ{Ή} NMR (162 MHz, CDC1 ₃ ): δ 7.73 ppm. HR-MS (+ve ESI): m/z (calc.) [M+H]+ 597.3522; found 597.3537.

Synthesis of l,2-Bis[(2,2,6,6-tetramethylphosphinan-4-ol)methyl]benzene (BPX-OH)

L1AIH ₄ (2.0M in THF, 6.75 mL, 13.52 mmol) was diluted with THF (25 mL) and cooled to -10 °C. BPX (1.03 g, 2.3 mmol) in THF (8 mL) was added dropwise. The mixture was allowed to warm to room temperature and stirred for 16 hours. After this time (20% NaOH, 2 mL) was added cautiously to the mixture. The mixture was filtered and the solvent removed in vacuo. The product was a mixture of diastereomers.

³¹ P NMR (162 MHz, CDC1 ₃ ): δ 8.0, 6.6, 0.7 and -1.4 ppm. Synthesis of tetrabutyl propane-l,3-diylbis(phosphonate).

1 ,3-Dibromopropane (9.9 g, 5.0 mL, 49.2 mmol) and tri(«-butyl)phosphite (49.3 g, 53.0 mL, 197.0 mmol) were heated at 120 °C for 16 h. The volatiles were distilled off leaving behind a colourless liquid (16.7 g, 80% yield). *H NMR (400 MHz, CDC1 ₃ ): δ 4.06 - 3.94 (8H, m, OCH ₂ ), 1.94 - 1.79 (6Η, m, P(CH ₂ )jP), 1.66 - 1.59 (8Η, m, OCH ₂ CH ₂ ), 1.43 - 1.33 (8Η, m, CH ₂ CH ₃ ) and 0.92 ppm (12H, t, ³ J _HH = 7.4 Hz, CH ₃ ). ^3l P{ ^l H} NMR (162 MHz, CDC1 ₃ ): δ 30.7 ppm. HR-MS (+ve ESI): 429.2539 [M + H] ⁺ calc. 429.2529.

Synthesis of l,3-bis(phosphino)propane.

CAUTION: l ,3-bis(phosphino)propane is highly pyrophoric! Chlorotrimethylsilane (5.1 g, 5.9 mL, 46.7 mmol) was added dropwise to LiAlH ₄ (2.0 M in THF, 23.3 mL, 46.6 mmol) suspended in THF (150 mL) at -78 °C. After complete addition, the reaction was warmed to room temperature and stirred. After 1 hour the mixture was cooled to -78 °C and tetrabutyl propane- 1 , 3 -diylbis(phosphonate) (5.0 g, 11.7 mmol) in THF was added dropwise. CAUTION: Even at -78 °C a vigorous reaction ensued. The reaction mixture was then allowed to warm to room temperature and stirred under argon for 16 hours. The reaction was then cooled in an ice bath and quenched by dropwise addition of NaOH (20% aq, 2.5 mL). Additional THF (100 mL) was added to enable efficient stirring. The mixture was filtered, dried over MgS0 ₄ and then filtered again. The majority of the THF was distilled off under argon leaving behind a solution of the product l ,3-bis(phosphino)propane in THF and «-butanol which was used without further purification. Yield: 3.6 g (18.5 wt% by Ή NMR corresponding to 52% yield). H NMR (400 MHz, CDC1 ₃ ): δ 2.7 (4H, dt, 'J _HF = 194.8 Hz and ³ J _HH = 7.4 Hz, PH ₂ ), 1.78 - 1.67 (2Η, m, CH ₂ ) and 1.59 - 1.33 ppm (4Η, m, PCH ₂ ). ^P^H} NMR (162 MHz, CDC1 ₃ ): δ -138.6 ppm.

Synthesis of l,3-bis(4-phosphorinone)propane, BPPr.

l ,3-Bis(phosphino)propane (3.6 g, 18.5wt%, 6.2 mmol) and phorone (1.8 g, 13.0 mmol) were heated at 120 °C for 36 hours. The resulting sticky solid was washed with pentane (10 mL) and dried in vacuo to furnish a white solid (0.94 g, 40% yield). *H NMR (400 MHz, CDC1 ₃ ): δ 2.41 - 2.35 (8H, m, CH ₂ CO), 1.90 - 1.78 (2Η, m, CH ₂ ), 1.71 - 1.67 (4Η, m, PCH ₂ ), 1.20 (12Η, d, ³ JpH = 16.2 Hz, CH ₃ ) and 1.13 ppm (12H, d, ³ J _PH = 8.0 Hz, CH ₃ ). ^l3 C{ ^l U} NMR (101 MHz, CDCI ₃ ): δ 210.7 (C=0), 53.9 ( H ₂ CO), 34.7 (d, ¾ _Ρ = 17.5 Hz, C _q ), 31.2 (d, ² J _CP = 25.7 Hz, H ₃ ), 28.6 (t, ² J _C p = 9.3 Hz, H ₂ ), 27.4 (d, ² J _CP = 4.8 Hz, H ₃ ) and 22.8 ppm (dd, % _Ρ = 22.7 Hz and ³ J _CP = 13.4 Hz, P H ₂ ). ³¹ P{ ¹ H} NMR (162 MHz, CDC1 ₃ ): δ 6.4 ppm. HR-MS (+ve ESI): 385.2432 [M + H] ⁺ calc. 385.2420. Elem. Anal. Calcd for C ₂₁ H ₃₈ 0 ₂ P ₂ : C, 65.60; H, 9.96. Found: C, 65.50; H, 9.85. Synthesis of (4-(Trifluoromethyl)-l,2-phenylene)dimethanol

(4-(Trifluoromethyl)-l,2-phenylene)dimethanol (5.13 g) was dissolved in THF (50 mL) and cooled to -78°C. BH ₃ .THF (1.0 M in THF, 75 mL, 75.0 mmol) was added and the mixture allowed to warm to room temperature and stirred for 16 hours. Methanol (30 mL) was added slowly (effervescence) and then the volatiles were removed in vacuo. The residue was partitioned in diethyl ether (50 mL) and HC1 (aq) (1.0 M, 50 mL). The aqueous portion was extracted twice more with diethyl ether (2 x 50 mL) and the combined organic extracts washed with brine (50 mL), then saturated NaHC0 ₃ (50 mL) and dried over MgS0 ₄ . Filtration and concentration in vacuo gave a colourless oil which was taken up in methanol and concentrated in vacuo again to remove B(OMe) ₃ as an azeotrope (5.13 g, quantitative). NMR (400 MHz, CDC1 ₃ ): δ 7.63 (1H, s, ArH), 7.58 (1Η, d, ³ J _HH = 8.0 Hz, ArH), 7.49 (1Η, d, ³ J _HH = 7.6 Hz, ArH), 4.78 (4Η, s, CH ₂ ) and 2.56 (2Η, s br, OH).

Synthesis of (4-(Trifluoromethyl)-l,2-phenylene)Z»i ^' s(methylene) Ais(tosylate)

(4-(Trifluoromethyl)-l,2-phenylene)dimethanol (0.515 g, 2.5 mmol) was ground with tosyl chloride (1.43 g, 7.5 mmol) and potassium carbonate (2.5 g) for 10 mins, followed by grinding with potassium hydroxide (1.4 g, 25 mmol) to remove excess tosyl chloride. Subsequent extraction of the solid residue with Et ₂ 0 (3 x 10 mL), and concentration in vacuo afforded a yellow oil. Purification over silica gel (10-60% Et ₂ 0 in hexanes) yielded a colourless oil (0.65 g, 51%). *H NMR (400 MHz, CDC1 ₃ ): δ 7.76 - 7.71 (4H, m, ArH), 7.52 (1Η, dd, ³ J _HH = 7.8 and ⁴ J _HH = 1-0 Hz, ArH), 7.41 (1Η, d, ³ J _HH = 8.0 Hz, ArH), 7.38 (1Η, s, ArH), 7.34 - 7.30 (4H, m, ArH) 5.10 (2Η, s, CH ₂ ), 5.07 (2Η, s, CH ₂ ), 2.45 (3Η, s, CH ₃ ) and 2.44 (3Η, s, CH ₃ ).

Synthesis of ((4- (Trifluoromethyl)- 1 ,2-phenylene)Z»is (methylene))Z»i ^' s (di-tert- butylphosphine). (4-CF ₃ -DTBPX)

«-Butyl lithium (1.32 mL, 2.0 M in cyclohexane, 2.64 mmol) was added dropwise to a solution of di-teri-butylphosphine borane adduct (0.43 g, 2.64 mmol) in THF (5 mL) at -78°C. After complete addition, the reaction was warmed to room temperature and stirred. After 1 hour, the reaction was cooled to -78°C and a solution of ditosylate (0.65 g, 1.26 mmol) in THF (5 mL) was added dropwise. The reaction was warmed to room temperature and stirred overnight. Removal of volatiles in vacuo, followed by extraction with CH ₂ C1 ₂ and purification over silica gel (10% EtOAc in hexanes) provided the borane -protected diphosphine as a white solid (0.40 g, 65%). *H NMR (400 MHz, CDC1 ₃ ): δ 7.82 (1H, s, ArH), 7.79 (1Η, d, ³ J _HH = 8.3 Hz, ArH), 7.41 (1Η, d, ³ J _HH = 8.2 Hz, ArH), 3.44 (2Η, d, ² J _HP = 2.9 Hz, CH ₂ ), 3.41 (2Η, d, ² J _HP = 3.2 Hz, CH ₂ ), 1.28 (18Η, d, ³ J _HP = 2.3 Hz, ¾u), 1.25 (18H, d, ³ J _HP = 2.3 Hz, ¾u) and 0.85-0.24 (6H, m br, BHj). ³¹ P NMR (162 MHz, CDC1 ₃ ): 5 51.5, 51.1.

Quantitative deprotection was achieved by warming the protected phosphine (0.38 g, 0.78 mmol) in pyrrolidine at 50°C overnight followed by removal of the volatiles in vacuo and eluting the residue with CH ₂ C1 ₂ through a silica plug under argon. 'H NMR (400 MHz, CDC1 ₃ ): δ 7.79 (s, 1H, ArH), 7.68 (1H, d, ³ J _HH = 8.0 Hz, ArH), 7.31 (1Η, d, ³ J _HH = 8.1 Hz, ArH), 3.06 (4Η, s, CH ₂ ), 1.15 (18Η, d, ³ J _HP = 10.8 Hz, ¾u), 1.14 (18H, d, ³ J _HP = 11.0 Hz, ¾u). ¹³ C NMR (101 MHz, CDC1 ₃ ): δ 143.6 (ArQ, 140.0 (ArQ, 131.3 (d, / = 16.1 Hz, ArQ, 127.7 (dd, / = 15.3, 3.8 Hz, ArQ, 126.0 (ArQ, 122.1 (ArQ, 32.3, 32.2 (d, ¾ _Ρ = 22.6 Hz, C(CH ₃ ) ₃ ), 30.0 (d, ² J _CP = 13.1 Hz, H ₃ ), 30.0 (d, ² J _CP = 13.2 Hz, H ₃ ) 26.7 (ddd, / = 25.1, 8.6, 5.0 Hz, CH ₂ P). ³¹ P NMR (162 MHz, CDC1 ₃ ): δ 28.3, 26.7. HR-MS (+ve ESI): 463.281 [M+H] ⁺ calc. 463.287. Elem. Anal. Calcd for C ₂₅ H ₄₃ F ₃ P ₂ : C, 64.92; H, 9.37. Found: C, 63.90; H, 9.21.

Synthesis of ((4-(teri-butyl)-l,2-phenylene)bis(methylene))bis(di-tert-bu tylphosphane), (4- 'Bu-DTBPX)

«-Butyl lithium (6.6 mL, 2.0 M in cyclohexane, 13 mmol) was added dropwise to a solution of di-teri-butylphosphine borane adduct (2.1 g, 13 mmol) in THF (40 mL) at -78 °C. After complete addition, the reaction was warmed to rt and stirred. After 1 h, reaction was cooled to - 78 °C and a solution of dibromide (2.0 g, 6.3 mmol) in THF (10 mL) was added dropwise. The reaction was warmed to rt and stirred overnight. Removal of volatiles in vacuo, followed by extraction with CH ₂ C1 ₂ and purification over silica gel (5% EtOAc in hexanes) provided the borane-protected diphosphine as a white solid (1.45 g, 49%). Quantitative deprotection was achieved by warming protected phosphine (1.37 g, 3.0 mmol) in pyrrolidine at 50 °C overnight followed by removal of volatiles in vacuo and eluting residue with CH ₂ C1 ₂ through a silica plug under Ar. *H NMR (400 MHz, CDC1 ₃ ): δ 7.53 - 7.47 (m, 2H, ArH), 7.06 (dd, / = 8.1, 2.2 Hz, 1H, ArH), 3.05 (d, / = 2.2 Hz, 2H, CH ₂ ), 3.01 (d, / = 3.0 Hz, 2H, CH ₂ ), 1.28 (s, 9H, Ar'Bu), 1.14 (d, / = 10.8 Hz, 18H, P¾u), 1.13 (d, / = 10.8 Hz, 18H, P¾u). ¹³ C U} NMR (101 MHz, CDC1 ₃ ): δ 147.8 (d, ⁴ J _CP = 1.6 Hz, C _q ), 137.9 (dd, ² J _CP = 8.2 Hz, ³ J _CP = 3.0 Hz, C _q ), 135.9 (dd, ² J _CP = 10.3 Hz, ³ J _CP = 2.3 Hz, C _q ), 130.6 (d, ³ J _CP = 16.8 Hz), 128.4 (d, ³ J _CP = 12.9 Hz, ArQ, 122.1 (d, ⁴ J _CP = 1.7 Hz, ArQ, 34.4 (s, -C(CH ₃ ) ₃ ), 32.2 (d, ¾ _Ρ = 8.0 Hz, -C(CH ₃ ) ₃ ), 31.9 (d, ¾ _Ρ = 6.6 Hz, -C(CH ₃ ) ₃ ), 31.5 (s, C( H ₃ ) ₃ ), 30.2 (d, ² J _CP = 6.3 Hz, C( H ₃ ) ₃ ), 30.0 (d, ² J _CP = 6.5 Hz, C( H ₃ ) ₃ ), 27.4 (dd, % _Ρ = 25.0 Hz, ⁴ J _CP = 3.7 Hz, H ₂ ) and 25.8 ppm (dd, ¾ _Ρ = 22.9 Hz, ⁴ J _CP = 6.5 Hz, H ₂ ). ³¹ P{ ¹ H} NMR (162 MHz, CDC1 ₃ ): δ 26.1, 25.2. HR-MS (+ve ESI): 451.3625 [M+H]+ calc. 451.3617. Elem. Anal. Calcd for C ₂₈ H ₅₂ P ₂ : C, 74.62; H, 11.63. Found: C, 74.12; H, 11.43. Synthesis of l,2-bis(bromomethyl)-4-nitrobenzene. α,α-Dibromo-o-xylene (3.0 g, 11.4 mmol) was suspended in c.H ₂ S0 ₄ (25 mL) and stirred for 15 mins. After which time it was cooled in an ice bath. KN0 ₃ (5.2 g, 51.4 mmol) was added in small portions over a period of 1 hour taking care to ensure the temperature of the reaction mixture did not exceed 5°C. After the addition the reaction was stirred for a further 4 hours before it was poured onto crushed ice (300 mL) and stirred. The precipitated crude solid was filtered and dried in vacuo. The crude material was purified over silica gel chromatography (ethyl acetate: hexane 1:9, Rf product 0.3) giving a white crystalline solid. Yield = 1.1 g (31%).

*H NMR (400 MHz, CDC1 ₃ ): δ 8.25 (1H, d, ⁴ J _HH = 2.3 Hz, ArH), 8.16 (1Η, dd, ³ J _HH = 8.4 Hz and ⁴ J _HH = 2.4 Hz, ArH), 7.56 (1Η, d, ³ J _HH = 8.4 Hz, ArH), 4.67 (2Η, s, CH ₂ ) and 4.66 ppm (2Η, s, CH ₂ ).

Synthesis of ((4-nitro-l,2-phenylene)bis(methylene))bis(di-tert-butylphos phane), (4-N0 ₂ - DTBPX)

«-Butyl lithium (1.7 mL, 2.0 M in cyclohexane, 3.4 mmol) was added dropwise to a solution of di-teri-butylphosphine borane adduct (0.54 g, 3.4 mmol) in THF (10 mL) at -78 °C. After complete addition, the reaction was warmed to rt and stirred. After 1 h, the reaction was cooled to -78 °C and a solution of l,2-bis(bromomethyl)-4-nitrobenzene (0.5 g, 1.6 mmol) in THF (5 mL) was added dropwise. The reaction was warmed to rt and stirred for 16 hours. After which time the volatiles were removed in vacuo. Deprotection was achieved by heating in pyrrolidine for 16 hours at 50 °C followed by removal of volatiles in vacuo. The mixture was taken up in CH ₂ C1 ₂ (30 mL) and passed through a plug of silica. The compound was then washed with MeOH (5 mL) filtered and dried to give a pale orange solid. Yield = 0.09 g (12%). *H NMR (400 MHz, CDC1 ₃ ): δ 8.43 (1H, t, J = Hz, ArH), 7.91 (1Η, dd, J = 8.6 Hz, J = 2.5 Hz, ArH), 7.73 (1Η, dd, J = 8.6 Hz, J = 3.0 Hz, ArH), 3.09 (2Η, d, % _Ρ = 2.7 Hz, CH ₂ ), 3.08 (2Η, d, ¾ _Ρ = 2.1 Hz, CH ₂ ), 1.16 (18Η, d, ² J _CP = 2.3 Hz, ¾u) and 1.13 ppm (18H, d, ² J _CP = 2.4 Hz, ¾u). ^l3 C{ ^l U} NMR (101 MHz, CDC1 ₃ ): δ 147.9 (dd, ² J _CP = 10.3 Hz, ³ J _CP = 2.6 Hz, ArC _q ), 145.4 (d, ⁴ J _CP = 1.8 Hz, ArC _q ), 141.3 (dd, ² J _CP = 11.2 Hz, ³ J _CP = 2.5 Hz, ArC _q ), 131.8 (d, ³ J _CP = 16.4 Hz, ArQ, 125.8 (d, ³ J _CP = 15.6 Hz, ArQ, 120.4 (d, ⁴ J _CP = 1.1 Hz, ArQ, 32.4 (d, %ρ = 3.7 Hz, C(CH ₃ ) ₃ ), 32.2 (d, ¾ _Ρ = 4.1 Hz, C(CH ₃ ) ₃ ), 30.1 (d, ² J _CP = 4.2 Hz, C( H ₃ )j), 29.9 (d, ² J _CP = 4.2 Hz, C( H ₃ )j), 27.2 (dd, ^CF = 26.6 Hz, ⁴ J _CP = 5.4 Hz, H ₂ ) and 29.9 ppm (dd, ^l ] _C p = 26.6 Hz, ⁴ J _CP = 4.8 Hz, H ₂ ) ³¹ P{ ¹ H} NMR (162 MHz, CDC1 ₃ ): δ 30.4 and 27.8 ppm. HR-MS (+ve ESI): 440.2846 [M+H] ⁺ calc. 440.2842. Elem. Anal. Calcd for C ₂₄ H ₄₃ N0 ₂ P ₂ : C, 65.58; H, 9.86; N, 3.19. Found: C, 65.33; H, 9.33; N, 3.51. Synthesis of l,2-bis(bromomethyl)-4-(phenylsulfonyl)b

2-Dimethyl-4-(phenylsulfonyl)benzene (1.15 g, 4.7 mmol) was dissolved in ethyl acetate (10 mL), water (7 mL) was added. Sodium bromate (2.82 g, 18.7 mmol) was added and the mixture cooled in a water bath. NaHS0 ₃ (4.85 g, 18.7 mmol) was added dropwise to the vigorously stirred biphasic mixture over 10 mins. After 24 hours the mixture was poured onto diethyl ether (50 mL) and the organic phase separated. The aqueous phase was further extracted with diethyl ether (2 x 25 mL). The combined organic extracts were backwashed with Na ₂ S ₂ 0 ₃ (10% aq, 50 mL) and the combined organic extracts dried over Na ₂ S0 ₄ which was recrystallised twice from ethanol to give a white solid. *H NMR (400 MHz, CDC1 ₃ ): δ 7.97 - 7.94 (3H, m, ArH) 7.84 (1Η, dd, J _HH = 8.1 Hz, J _HH = 1.9 Hz, ArH) 7.62 - 7.49 (4Η, m, ArH) 4.62 (2Η, s, CH ₂ ) and 4.61 ppm (2Η, s, CH ₂ ).

Synthesis of (4-(phenylsulfonyl)-l,2-phenylene)bis(methylene) bis(tosylate). l,2-Bis(bromomethyl)-4-(phenylsulfonyl)benzene (0.29 g, 0.71 mmol) and silver p-toluene sulfonate (0.40 g, 1.41 mmol) were dissolved in acetonitrile (15 mL) and heated at reflux temperature (90 °C) for 16 hours. After this time the mixture was heated and the volatiles were removed in vacuo to give the crude material which was taken up in CH ₂ C1 ₂ and passed through a glass filter, evaporation of the CH ₂ C1 ₂ gave an off-white solid. ¾ NMR (400 MHz, CDC1 ₃ ): δ 7.91 - 7.87 (2H, m, ArH), 7.82 (1Η, dd, J _HH = 8.1 Hz, J _HH = 2.1 Hz, ArH) 7.77 - 7.69 (5Η, m, ArH), 7.61 - 7.57 (1Η, m, ArH), 7.54 - 7.49 (2Η, m, ArH) 7.42 (1Η, d, J _HH = 8.1 Hz, ArH) 7.32 - 7.28 (4Η, m, ArH), 5.06 (2Η, s, CH ₂ ), 5.03 (2Η, s, CH ₂ ), 2.44 (3Η, s, CH ₃ ) and 2.43 ppm (3Η, s, CHj). HR-MS (+ve ESI): 609.0694 [M+Na] ⁺ calc. 609.0682.

Synthesis of ((4-(phenylsulfonyl)-l,2-phenylene)bis(methylene))bis(di-ter t- butylphosphane) (4-PhS0 ₂ -DTBPX)

«-Butyl lithium (0.29 mL, 2.0 M in cyclohexane, 0.58 mmol) was added dropwise to a solution of di-teri-butylphosphine borane adduct (0.093 g, 0.58 mmol) in THF (5 mL) at -78 °C. After complete addition, the reaction was warmed to rt and stirred. After 1 h, the reaction was cooled to -78 °C and a solution of ditosylate (0.17 g, 0.28 mmol) in THF (5 mL) was added dropwise. The reaction was warmed to rt and stirred for 16 hours. After which time the volatiles were removed in vacuo to yield the borane protected phosphine. Deprotection was achieved by heating in pyrrolidine for 16 hours at 50 °C followed by removal of volatiles in vacuo. 'H NMR (400 MHz, CDC1 ₃ ): 8.03 - 7.99 (1H, m, ArH), 7.93 - 7.89 (2Η, m, ArH), 7.81 - 7.76 (1Η, m, ArH), 7.66 - 7.61 (1Η, m, ArH), 7.55 - 7.43 (3Η. m. ArH), 3.05 (4Η, br. s, CH ₂ ), 1.11 (18Η, d, ³ J _PH = 11.0 Hz, CH ₃ ) and 1.05 ppm (18H, and ³ J _PH = 10.8 Hz, CH ₃ ). ^P^H} NMR (162 MHz, CDC1 ₃ ): δ 29.3 and 26.3 ppm.

Synthesis of (4,5-Dichloro-l,2-phenylene)dimethanol 4,5-Dichlorophthalic anhydride (4.6 g, 21.2 mmol) was added in small portions to L1AIH ₄ (1M in THF, 31.2 mL, 31.2 mmol) in THF (20 mL) with cooling in an ice bath. When the addition had been complete the mixture was heated at reflux temperature for 5 hours and then cooled and quenched with water (1.7 mL), 15 wt% NaOH (aq) (1.7 mL) and water (4 mL). Filtration and drying over MgS0 ₄ , followed by evaporation gave a white solid. Yield = 2.50 g (57%). *H NMR (400 MHz, <¾-DMSO): δ 7.57 (2H, s, ArH), 5.33 (2Η, t, ³ J _HH = 5.5 Hz, OH) and 4.49 (4Η, d, ³ J _HH = 5.4 Hz, CH ₂ ).

Synthesis of (4,5-Dichloro-l,2-phenylene)Z»i ^' s(methylene) bis(tosylate)

Synthesised according to the procedure for (4-(trifluoromethyl)-l ,2-phenylene)bis(methylene) bis(tosylate) starting with (4,5-dichloro-l ,2-phenylene)dimethanol (0.275 g, 0.53 mmol). The title compound was purified over silica gel (50% Et ₂ 0 in hexanes) to yield an off white powder (0.36 g, 53%). *H NMR (400 MHz, CDC1 ₃ ): δ 7.76 - 7.71 (m, 4H, ArH), 7.36 - 7.31 (m, 4H, ArH), 7.26 (s, 2H, ArH), 4.97 (s, 4H, CH ₂ ) and 2.45 (d, / = 2.1 Hz, 6H, CH ₃ ).

Synthesis of ((4,5-Dichloro-l,2-phenylene)bis(methylene))bis(di-tert-buty lphosphine). (4,5- Cl-DTBPX)

Synthesised according to the procedure for 4-CF ₃ -DTBPX starting with (4,5-dichloro-l ,2- phenylene)bis(methylene) bis(tosylate) (0.36 g). Diphosphine borane adduct was purified over silica gel (10% EtOAc in hexane) to yield a white powder (0.21 g, 62%). H NMR (400 MHz, CDCI ₃ ): δ 7.73 (s, 2H, ArH), 3.29 (d, / = 11.5 Hz, 2H, CH ₂ ), 1.27 (d, / = 12.6 Hz, 36H, ¾u) and 0.47 (m br, 6H, BH ₃ ). ³¹ P NMR (162 MHz, CDC1 ₃ ): δ 51.2 (d, / = 53.4 Hz)

The diphosphine was obtained quantitatively via a similar deprotection to 4-CF ₃ -DTBPX.

*H NMR (400 MHz, CDC1 ₃ ): δ 7.65 (d, / = 3.2 Hz, 2H, ArH), 2.93 (d, / = 2.6 Hz, 4H, CH ₂ ), 1.14 (d, / = 10.9 Hz, 36H, ¾u). ³¹ P NMR (162 MHz, CDC1 ₃ ): δ 27.6. ¹³ C NMR (101 MHz, CDCI ₃ ): δ 139.77 (Ar), 132.41 (d, / = 16.8 Hz, Ar), 128.97 (Ar), 32.21 (d, / = 22.5 Hz, C(CH ₃ ) ₃ ), 30.02 (d, / = 13.1 Hz, CH ₃ ) and 25.93 (dd, / = 25.5, 4.7 Hz, CH ₂ P). HR-MS (+ve ESI): 463.214 [M+H] ⁺ calc. 463.222. Elem. Anal. Calcd for C24H42CI2P2: C, 62.20; H, 9.13. Found: C, 62.61; H, 8.98.

Synthesis of l,2-Bis(bromomethyl)-4,5-dimethoxybenzene

1 ,2-Dimethoxybenzene (2.6 mL, 20.2 mmol) was added to glacial acetic acid (12 mL), and paraformaldehyde (1.2 g, 40.0 mmol). HBr (45% w/v in AcOH, 8.6 mL, 48.0 mmol) was then added to the white suspension which dissolved giving a pale orange solution. After 24 hours a white precipitate had formed which was filtered and dried. The crude mixture was taken up in CH ₂ C1 ₂ and passed through a small plug of silica, evaporation of the solvent gave a white crystalline solid. Yield = 2.0 g (30%). *H NMR (400 MHz, CDC1 ₃ ): δ 6.83 (2H, s, ArH), 4.62 (4Η, s, CH ₂ ) and 3.88 (6Η, s, OMe). ¹³ C NMR (101 MHz, CDC1 ₃ ): δ 149.6 (ArC _? ), 129.2 (ArC _q ), 113.7 (ArCH), 56.2 (CH ₃ 0) and 30.8 (CH ₂ ).

Synthesis of ((4,5-(Dimethoxy)-l,2-phenylene)Z»i ^' s(methylene))Z»is(di-tert-butylphosphine) (4,5-OMe-DTBPX)

«-BuLi (2.0 M in cyclohexane, 6.2 mL, 12.4 mmol) was added dropwise to iBu ₂ PH.BH ₃ (1.98 g, 12.4 mmol) in THF (20 mL) at -78°C. The mixture was allowed to warm to room temperature and stirred for one hour before being recooled to -78°C and l,2-Bis(bromomethyl)-4,5- dimethoxybenzene (2.0 g, 6.2 mmol) in THF (10 mL) was added dropwise. The mixture was warmed to room temperature and stirred for 16 hours. After which time the solvent was removed in vacuo giving a white solid which was extracted with CH ₂ C1 ₂ and then evaporated to give a foamy white solid. Pyrrolidine (10 mL) was added and the mixture heated to 50°C for 16 hours. After this time the pyrrolidine was removed in vacuo and the residue taken up in CH ₂ C1 ₂ (20 mL) and passed through a plug of silica and washed with CH ₂ C1 ₂ (60 mL). The combined organics were evaporated and the white solid was dissolved in pentane (40 mL) and cooled to -10°C in an ice/salt bath whereupon colourless crystals formed which were filtered and washed with methanol. Yield 0.70 g (25%). *H NMR (400 MHz, CDC1 ₃ ): δ 7.1 (2H, d, ⁴ JHP = 3.2 Hz, ArH), 3.9 (6Η, s, OMe), 2.95 (4Η, d, ² J _HP = 2.4 Hz, CH ₂ ) and 1.14 (36Η, d, ³ J _HP = 10.7 Hz,

C(Ci¾)j). ¹³ C NMR (101 MHz, CDC1 ₃ ): δ 146.4 (d, ⁴ J _CP = 1.7 Hz, ArC _q ), 130.6 (dd, , ² J _CP = 2.9 Hz and ³ J _CP = 9.7 Hz, ArC _q ) , 114.4 (d, ³ J _CP = 16.0 Hz, ArCH), 56.1 (s, OMe), 32.0 (dd, ¾ _! > = 22.7 Hz, C(CH ₃ ) ₃ ), 30.1 (d, ² J _CP = 13.0 Hz, C(CH ₃ )J) and 25.9 (d, ¹ J _CP = 23.9 Hz and ⁴ J _CP = 3.9 Hz, CH ₂ ). ³¹ P NMR (162 MHz, CDC1 ₃ ): δ 26.8 ppm. HR-MS (+ve ESI): 455.322 [M+H] ⁺ calc. 455.3202. Elem. Anal. Calcd for CzeH^C^: C, 68.69; H, 10.64. Found: C, 68.27; H, 10.29. Example 3: Synthesis of Metal Complex

General In Situ Synthetic Scheme of Metal complex

Synthesis of (BPX)PdCl ₂

BPX (0.93 g, 2.09 mmol) and Pd(dba) ₂ (1.21 g, 2.09 mmol) were suspended in CH ₂ C1 ₂ (15 mL) and stirred at room temperature for 8 hours. HC1 (2.0M in diethyl ether, 2.1 mL, 4.19 mmol) was then added and the mixture stirred for a further 16 hours. The volatile s were then removed in vacuo and the residue washed with CH ₂ C1 ₂ (2 x 20 mL), the combined washings were reduced in volume and Et ₂ 0 added to induce precipitation. The precipitate was collected via filtration and washed with Et ₂ 0 (3 x 10 mL) to yield a yellow powder (1.04 g, 80%). ³¹ P NMR (162 MHz, CDC1 ₃ ): δ 26.8. Elem. Anal. Calcd for C ₂₆ H ₄₀ O ₂ P ₂ PdCl ₂ : C, 50.06; H, 6.46. Found: C, 49.25; H, 5.81.

Synthesis of (BPX)Pd(0 ₂ CF ₃ C) ₂

(BPX)PdCl ₂ (0.30 g, 0.48 mmol) and Ag(0 ₂ CCF ₃ ) (0.21 g, 0.96 mmol) were dissolved in CH ₂ C1 ₂ (20 mL), the yellow solution turned deep red after a few minutes. The mixture was stirred for 16 hours then the dark brown suspension was filtered and the residue was washed with pentane (10 mL), filtered and the combined organic phase was evaporated to yield a brown solid (0.36 g, 98%). *H NMR (400 MHz, CDC1 ₃ ): δ 7.49 - 7.45 (2H, m, ArH), 7.41 - 7.35 (2Η, m, ArH), 3.54 (4Η, d, ½> = 13.1 Hz, CH ₂ ), 3.38 (4Η, dd, J = 12.9 and 3.0 Hz, CH ₂ ), 2.20 (2Η, d, ³ JHP = 13.2 Hz, CH ₂ ), 2.13 (2Η, d, ³ J _HP = 13.0 Hz, CH ₂ ) and 1.9 - 1.3 (24Η, m, CH ₃ ). ³¹ P NMR (162 MHz, CDC1 ₃ ): δ 32.1 ppm. Elem. Anal. Calcd for C, 46.26; H, 5.18. Found: C, 45.86; H, 4.82. Synthesis of [(BPPr)Pd(0 ₂ CCF ₃ ) ₂ ] .

BPPr (0.24 g, 0.61 mmol) and Pd(0 ₂ CCF ₃ ) ₂ (0.20 g, 0.61 mmol) were stirred together in CH ₂ C1 ₂ ( 20 mL) for 4 h. The mixture was passed through a glass filter producing an orange filtrate. The reaction volume was reduced to 5 mL and then pentane (15 mL) was added to induce precipitation. The tan coloured solid was filtered off and dried. Yield = 0.26 g (60% yield). *H NMR (400 MHz, CDC1 ₃ ): δ 3.41 (4H, dd, ¾ _Ρ = 13.5 Hz, ³ J _CP = 2.1 Hz, P H ₂ ), 2.21 (4H, d, ² J _C p = 12.8 Hz, H ₂ CO), 2.15 (4H, d, ² J _CP = 12.8 Hz, H ₂ CO), 1.88 (12H, d, ² J _CP = 19.0 Hz, H _3)j 1.86 - 1.75 (2H, m, H ₂ ) and 1.28 ppm (12H, ² J _CP = 10.8 Hz). "Cj 'H} NMR (101 MHz, CDCI3): δ 206.6 (C=0), 163.0 (q, ² J _CF = 37.8 Hz, C0 ₂ ), 115.8 (q, _Ρ = 285.5 Hz, F ₃ ), 53.6 ( H ₂ ), 40.0 (dd, % _Ρ = 8.8 Hz, ³ J _CP = 6.8 Hz, C _q ) 39.8 (dd, ¾ _Ρ = 8.9 Hz, ³ J _CP = 8.8 Hz, C _q ), 32.5 ( H ₃ ), 27.9 ( H ₃ ), 20.4 ( H ₂ ) and 18.4 ppm (dd, ¾ _Ρ = 16.8 Hz, ³ J _CP = 13.7 Hz, P H ₂ ). ³¹ P{ ¹ H} NMR (162 MHz, CDC1 ₃ ): δ 35.4 ppm. Elem. Anal. Calcd for C ₂₅ H ₃₈ F ₆ 0 ₆ P ₂ Pd: C, 41.88; H, 5.34. Found: C, 41.00; H, 5.03.

Example 4: Preparation of Pentenoic Acid Isomers A mixture of pentenoic acid isomers was prepared via catalytic distillation of gamma- valerolactone. A continuous reactive distillation was set up consisting of a 1 litre round bottom flask with heating mantle and agitation, a 1.5 metre tall insulated distillation column (internal diameter 24 mm), a top condenser with reflux controller and a dual piston pump. The column was packed with stainless steel Raschig rings. The flask was initially loaded with 500 mL gamma-valerolactone and 5wt% (25 g) silica-alumina catalyst (grade 135). The mixture was then heated to a bottom temperature of around 220°C. Gamma-valerolactone was continuously fed at 0.1 ml/min to the bottom flask with the pump and pentenoic acids distillate was collected from the top at a rate of 0.1 ml/min. A typical composition of the distillate, determined by GC analysis, is: 16.7% trans-2 -pentenoic acid, 7.5% cis-2-pentenoic acid, 35.3% 3-pentenoic acids, 35.1 % 4-pentenoic acid, 4.3% gamma-valerolactone, 1.2% valeric acid.

Example 5: Hydroxycarbonylation of Pentenoic Acids to Adipic Acid With BPX Derivatives (Sample No. 1 to 7)

A stainless steel 300 ml Parr reactor was charged with degassed distillate from Example 4 (65 mL) and the amount of degassed water specified in Table 1 under a stream of argon gas. A preformed catalyst solution consisting of palladium(II) acetate (55 μιηοΐ), l ,2-bis[(2,2,6,6- tetramethylphosphinan-4-onyl)methyl]benzene (BPX, Ι ΙΟ μηιοΙ) or l,2-bis[(2,2,6,6- tetramethylphosphinan-4-ol)methyl]benzene (BPX-OH, 110 umol) and methanesulfonic acid (1.5 mmol) in degassed pentenoic acids distillate (15 mL) was then injected into the reactor. The Parr reactor was then purged with CO gas and pressurised to 40 bar CO. The reaction mixture was stirred at 1000 rpm and heated to the reaction temperature specified in Table 1. After 17 hours the reaction was terminated by the cessation of the stirring, followed by cooling the reactor to room temperature and then venting the excess CO gas. Precipitated adipic acid was filtered and analysed by GC and the filtrate was also analysed by GC and an overall adipic acid yield and selectivity were calculated (Table 1). In Sample No. 4 and 6, pre-formed complex Pd(BPX)(0 ₂ CCF ₃ ) ₂ (55 umol) was used instead of the palladium(II) acetate.

In Sample No. 5, the catalyst solution was prepared with 144 umol palladium(II) acetate and 288 umol l,2-bis[(2,2,6,6-tetramethylphosphinan-4-onyl)methyl]benzene in the absence of methanesulfonic acid. Comparative Example 1: Hydrox carbonylation of Pentenoic Acids to Adipic Acid With DTBPX and BPPr (Sample No. 8 to 10)

A stainless steel 300 ml Parr reactor was charged with degassed distillate from Example 4 (65 mL) and degassed water (10 ml) under a stream of argon gas. A preformed catalyst solution consisting of palladium(II) acetate (55 μιηοΐ), l,2-bis[di(i-butyl)phosphinomethyl] benzene (DTBPX or BPPr, 110 μιηοΐ) and methanesulfonic acid (0 or 1.5 mmol) in degassed pentenoic acids distillate (15 mL) was then injected into the reactor. The Parr reactor was then purged with CO gas and pressurised to 40 bar CO. The reaction mixture was stirred at 1000 rpm and heated to 115°C. After 17 hours the reaction was terminated by the cessation of the stirring, followed by cooling the reactor to room temperature and then venting the excess CO gas. Precipitated adipic acid was filtered and analysed by GC and the filtrate was also analysed by GC and an overall adipic acid yield and selectivity were calculated (Table ITable 1). 1,3- Bis(phosphorinone)propane. BPPr was used as a comparative example.

Example 6: Analysis of Hydroxycarbonylation of Pentenoic Acids to Adipic Acid With BPX Derivatives Previous investigations using a DTBPX/Pd/MSA catalyst used diglyme as a reaction diluent and as a solvent for catalyst preparation, typically composing -75% of the medium. Under these conditions, the DTBPX/Pd/MSA produced adipic acid with a good activity (TOF 100 - 200 IT ¹ ) and selectivity (96 - 98%). Subsequently the use of a medium consisting of only the 2 substrates (i.e. pentenoic acid isomers and water) was investigated because this would eliminate issues with diglyme recycle and would make better use of the reactor space. It was found that the DTBPX/Pd/MSA catalyst gave only 78% selectivity to adipic acid under these conditions (Sample No. 9, Table ITable 1). The reason why is not fully clear, but in evaluating various solvents a decrease in selectivity with increasing medium polarity was observed (Example 7, Table 2). By eliminating the strongly acidic co-catalyst MSA, the selectivity could be restored (Sample No. 8, Table ITable 1), but under these conditions the catalyst activity is lower than when diglyme is used as a diluent. This is believed to be due to the more coordinating character of the pentenoate counter-anion compared with methanesulfonate, hence rendering the palladium catalyst less reactive (albeit more selective).

The new catalyst system of the present disclosure based on ligand BPX does not follow the same trend as the benchmark catalyst. In the absence of an MSA co-catalyst, a catalyst with low activity is formed (Sample No. 5 and 6). However, by including MSA, the catalyst is both highly active and selective for the hydroxycarbonylation of pentenoic acid isomers (Sample No. 1-4).

Table 1. Hydroxycarbonylation of pentenoic acids to adipic acid.

2 Pd(OAc) ₂ BPX/2 1.5 115 18 47 6000 350 96

3 Pd(OAc) ₂ BPX/2 1.5 115 10 52 6500 380 98

4 Pd(BPX)(0 ₂ BPX/1 1.5 115 10 43 5250 310 97

CCF ₃ ) ₂

5* Pd(OAc) ₂ BPX/2 0 115 10 1 70 5 97

6 Pd(BPX)(0, BPX/1 0 115 10 1 90 6 98

CCF ₃ ) ₂

7 Pd(OAc) ₂ BPX-OH/2 1.5 115 18 15 2000 120 98

8 Pd(OAc) ₂ DTBPX/2 0 115 10 20 1000 60 98

9 Pd(OAc) ₂ DTBPX/2 1.5 115 10 10 1100 60 78

10 Pd(OAc) ₂ BPPr/2 1.5 115 18 13 1750 100 63

Conditions: [Pd(OAc) ₂ ] = 55 μηιοΐ (*144 umol), Ligand (2 equivalents w.r.t. Pd), 40 bar initial CO Pressure, 1000 rpm, 80 mL distillate (PEAs ~ 740 mmo! -17 hrs. Pentenoic acid isomer composition: see Example 4.

Example 7: Carbonylation of Pentenoic Acids to Adipic Acid with DTBPX in Different Solvents (Sample No. 11 to 17)

A catalyst solution was prepared by dissolving palladium(II) acetate (35 μηιοΐ), l,2-bis[di(i- butyl)phosphinomethyl] benzene (DTBPX, 70 μηιοΐ) in 3.0 ml of degassed solvent as specified in Table 2, followed by the addition of 0.35 mmol of MSA co-catalyst. This solution, degassed water (0.5 mL, 27.7 mmol), pentenoic acids distillate (1.5 ml) and an additional 4 ml of the solvent were then injected into a stainless steel 12 ml autoclave under a stream of argon gas. The reactor was purged with CO gas and pressurised to 50 bar CO. The reaction mixture was stirred magnetically at 2000 rpm at a temperature of 105°C for 3 hours. After this time the reactor was cooled and the product mixture was analysed by GC (Table 2Table ).

Table 2. Hydroxycarbonylation of pentenoic acids to adipic acid with DTBPX by varying solvent

Sample No. Solvent Average TOF (h ^_1 ) Selectivity to ADA (%)

11 diglyme 107 98%

12 dimethoxyethane 94 99%

13 1,4-dioxane 101 >99%

14 gamma-valerolactone 18 88%

15 3-pentenoic acid 33 87%

16 PEAs distillate 45 84%

17 hexanoic acid 17 92%

Conditions: Pd(OAc) ₂ (35 umol), DTBPX (70 umol), MSA (0.35 mmol), 7.0 mL solvent, 50 bar CO pressure, 1.5 mL distillate (PEAs ~ 13.9 mmol), 0.5 ml (27.7 mmol) water, 105°C, 3 hrs. Example 8: Hydroxycarbonylation of Pentenoic Acids to Adipic Acid with BPX and Different Co-Catalysts (Sample No. 18 to 27)

A catalyst solution was prepared by dissolving palladium(II) acetate (20 umol) and 1,2- bis[(2,2,6,6-tetramethylphosphinan-4-onyl)methyl]benzene (BPX, 40 μιηοΐ) in 8.5 ml of degassed pentenoic acids distillate from Example 4 followed by the addition of 0.2 mmol of co- catalyst as specified in Table 3. This solution and degassed water (0.5 mL, 27.7 mmol) were then injected into a stainless steel 12 ml autoclave under a stream of argon gas. The reactor was purged with CO gas and pressurised to 50 bar CO. The reaction mixture was stirred magnetically at 2000 rpm at a temperature of 115°C for 12 hours. After this time the reactor was cooled and the product mixture was analysed by GC (Table 3). Table 3. Hydroxycarbonylation of pentenoic acids to adipic acid by varying the co-catalyst

Sample No Co-catalyst Yield of TON Average TOF Selectivity to

ADA (%) (h ^"1 ) ADA (%)

18 - 0 0 0 -

19 MSA 14 550 45 98

20 /7-TSA 17 650 55 98

21 CF ₃ C0 ₂ H 5 200 15 98

22 CH ₃ CH ₂ CH ₂ S0 ₃ H 16 600 50 98

23 Camphorsulfonic 23 900 75 99

Acid

24 9-Anthracene <1 10 <1 94†

Carboxylic Acid

25 C.H ₃ PO ₄ (aq) 2 70 5 99

26 H ₂ S0 ₄ 8 300 25 97

27 CF ₃ SO ₃ H 21 800 65 99

Conditions: Pd(OAc) ₂ (20 umol), BPX (40 umol), co-catalyst (0.2 mmol), 50 bar CO Pressure, 8.5 mL distillate (PEAs ~ 78.8 mmol), 0.5 ml water, 115°C, 12 hrs.†In this case the low activity results in a larger error in the value of the selectivity. Further evaluation of the co-catalyst showed that a high acid strength (i.e low pKa), led to a more active catalyst without reducing the selectivity (-98% throughout this series, Table 3).

Example 9: Carbonylation of Pentenoic Acids to Adipic Acid with BPX in Different Solvents (Sample No. 28 to 32)

A catalyst solution was prepared by dissolving palladium(II) acetate (20 umol), l,2-bis[(2,2,6,6- tetramethylphosphinan-4-onyl)methyl]benzene (BPX, 40 μιηοΐ) in 3.0 ml of degassed pentenoic acids distillate from Example 4 followed by the addition of 0.2 mmol of MSA co-catalyst. This solution, degassed water (0.5 mL, 27.7 mmol) and 5.5 ml of a co-solvent as specified in Table 4 were then injected into a stainless steel 12 ml autoclave under a stream of argon gas. The reactor was purged with CO gas and pressurised to 50 bar CO. The reaction mixture was stirred magnetically at 2000 rpm at a temperature of 115°C for 12 hours. After this time the reactor was cooled and the product mixture was analysed by GC (Table 4).

Table 4. Hydroxycarbonylation of pentenoic acids to adipic acid by varying solvent

Sample No. Solvent Yield of TON Average TOF Selectivity to

ADA (%) (h- ¹ ) ADA (%)

28 diglyme 9 120 10 97

29 gamma- 63 850 70 98

valerolactone

30 dimethoxyethane 6 80 7 98

31 1,4-dioxane 2 30 3 99

32 propanoic acid 43 580 50 98

Conditions: Pd(OAc) ₂ (20 umol), BPX (40 umol), MSA (0.2 mmol), solvent (5.5 mL), 50 bar CO Pressure, 3.0 mL distillate (PEAs ~ 27.8 mmol), 0.5 ml water, 115°C, 12 hrs.

Comparison of solvents shows that the BPX/Pd/MSA catalyst is more active in carboxylic acids and esters than in ethers, without affecting the selectivity (Table 4Table . Note: the reactor configuration in Tables 2 to 4 is different and hence the data cannot be compared directly with Table 1). A medium consisting of pentenoic acid isomers, water and possibly some GVL would be preferred for the process.

Example 10: Analysis of BPX/PdVMSA Catalyst The reason for the markedly different behaviour of the BPX/Pd catalyst compared to its DTBPX counterpart is not clear, but without being bound to theory, some possibilities ,may include (1) the rigidity of the phosphorinanone ring in BPX in contrast to the P¾u ₂ fragment in DTBPX, as selectivity appears to be highly dependent on the alkyl substituents on P or (2) the involvement of the carbonyl group in the hydrolysis of the palladium-acyl, as modelling studies appear to show the involvement of a water cluster and the counter-anion in this rate -determining step, (3) the basicity of the phosphorous atom of the bidentate ligand may be reduced by the insertion of an electron-withdrawing C=0 group and/or by the compression in the C-P-C angle in the phosphorinone ring relative to the corresponding angle in DTBPX.

The combination of the BPX ligand with a palladium source and strongly acidic co-catalyst outperforms the benchmark DTBPX catalyst in activity and selectivity for the hydroxycarbonylation of pentenoic acid isomers in a polar medium comprising pentenoic acid isomers and water. The catalyst system can also be applied to the hydroxy/alkoxycarbonylation of a wider range of substrates, including but not limited to methylpentenoates, 1 -hexene, 3- hexene, 3-pentenitrile, butadiene, unsaturated fatty acids/esters, 3-butenoic acid, and methyl but-3-enoate.

Example 11: Methoxycarbonylation of Methyl Pent-2-enoate (Sample No. 33 to 35)

A catalyst solution was prepared by dissolving palladium(II) acetate (20 μιηοΐ), diphosphine specified in Table 5 (BPX, 40 umol) in 6.0 ml of degassed methanol followed by the addition of 0.2 mmol of MSA co-catalyst. This solution and 3.0 ml of 2-methyl pentenoate were then injected into a stainless steel 12 ml autoclave under a stream of argon gas. The reactor was purged with CO gas and pressurised to 50 bar CO. The reaction mixture was stirred magnetically at 2000 rpm at a temperature of 105°C for 12 hours. After this time the reactor was cooled and the product mixture was analysed by GC (Table 5). DTBPX (Sample 33) is included as a control.

Table 5. Methoxycarbonylation of 2-methyl pentenoate by varying the diphosphine

Sample No. Diphosphine Yield of TON Average TOF Selectivity to

DMA ( %) (h- ¹ ) DMA (%)

^" 33 DTBPX 30 450 40 ^" 97

34 BPX 50 700 60 97

35 BPPr 60 950 80 90

Conditions: Pd(OAc) ₂ (20 umol), Diphosphine (40 umol), MSA (0.2 mmol), MeOH (6.0 mL), 50 bar CO Pressure, 2-methyl pentenoate (3.0 mL), 105°C, 12 hrs. DMA = dimethyl adipate

Example 12: Carbonylation of Other Substrates The catalyst system can also be applied to the hydroxy/alkoxycarbonylation of a wider range of substrates as shown below.

Methoxycarbonylation of ethylene (Sample No. 36)

A catalyst solution was prepared by dissolving palladium(II) acetate (10 μιηοΐ), and BPX (180 μιηοΐ) in 10.0 ml of degassed methanol followed by the addition of 2.0 mmol of MSA co- catalyst. A portion of this solution (5.0 mL: 5 umol Pd) was injected into a stainless steel 300 ml autoclave followed by methanol (100 mL) under a stream of argon gas. The reactor was then flushed and pressurised with 8 bar of ethylene and then an additional 8 bar of CO. The reaction mixture was stirred at 1000 rpm at a temperature of 80°C for 0.5 hours. After this time the reactor was cooled, anisole (0.4309 g) (GC internal standard) was added and the product mixture was analysed by GC. The TOF was 2500 h ¹ and the selectivity to methyl propanoate was 99%.

Methoxycarbonylation of 1-hexene (Sample No. 37)

A catalyst solution was prepared by dissolving palladium(II) acetate (80 umol), l,2-bis[(2,2,6,6- tetramethylphosphinan-4-onyl)methyl]benzene (BPX, 160 μιηοΐ) in 24.0 ml of degassed methanol followed by the addition of 0.1 ml of MSA co-catalyst. A portion of this solution (6.0 ml: 20 μιηοΐ Pd) and 1-hexene (3.0 mL) were then injected into a stainless steel 12 ml autoclave under a stream of argon gas. The reactor was purged with CO gas and pressurised to 50 bar CO. The reaction mixture was stirred magnetically at 2000 rpm at a temperature of 105°C for 12 hours. After this time the reactor was cooled and the product mixture was analysed by GC. The average TOF was 80 h ¹ and the selectivity to methyl heptanoate was 95%, the conversion of substrate was 83%. Methoxycarbonylation of trans-3-hexene (Sample No. 38)

The same procedure as for Sample No. 37 except using trans -3 -hexene (3.0 mL) instead of 1- hexene. The average TOF was 80 h ¹ and the selectivity to methyl heptanoate was 95%, the conversion of substrate was 83%. Hydroxycarbonylation of 3-pentenenitrile (Sample No. 39)

A catalyst solution was prepared by dissolving palladium(II) acetate (80 umol), l,2-bis[(2,2,6,6- tetramethylphosphinan-4-onyl)methyl]benzene (BPX, 160 μιηοΐ) in 22.0 ml of degassed diglyme followed by the addition of 0.1 ml of MSA co-catalyst. A portion of this solution (5.5 ml: 20 μιηοΐ Pd), degassed water (0.5 mL, 27.7 mmol) and 3-pentenenitrile (3.0 mL) were then injected into a stainless steel 12 ml autoclave under a stream of argon gas. The reactor was purged with CO gas and pressurised to 50 bar CO. The reaction mixture was stirred magnetically at 2000 rpm at a temperature of 105°C for 12 hours. After this time the reactor was cooled and the product mixture was analysed by GC. The average TOF was 12 h \ the selectivity to 5-cyanopentanoic acid was 97% and the conversion of substrate was 9%. Example 13: Hydroxycarbonylation of Pentenoic Acids to Adipic Acid with Functionalized DTBPX (Sample No. 40 to 45)

A stainless steel 300 ml Parr reactor was charged with degassed distillate from Example 4 (65 mL) and the amount of degassed water specified in Table 6 under a stream of argon gas. A preformed catalyst solution consisting of palladium(II) acetate (55 umol), bidentate phosphine specified in Table 6 and methanesulfonic acid (1.5 mmol) in degassed pentenoic acids distillate (15 mL) was then injected into the reactor. The Parr reactor was then purged with CO gas and pressurised to 40 bar CO. The reaction mixture was stirred at 1000 rpm and heated to 105°C. After 17 hours the reaction was terminated by the cessation of the stirring, followed by cooling the reactor to room temperature and then venting the excess CO gas. Precipitated adipic acid was filtered and analysed by GC and the filtrate was also analysed by GC and an overall adipic acid yield and selectivity were calculated (Table 6). DTBPX (Sample 40) is included as a control.

The introduction of substituents on the phenyl ring of the DTBPX ligand gives a catalyst with comparable activity but with improved selectivity, with electron withdrawing substituents (such as CF ₃ , CI and N0 ₂ - Sample No. 41 to 43) giving the best improvements in selectivity.

Example 14: Hydroxycarbonylation of Pentenoic Acids to Adipic Acid with Functionalized DTBPX Without Methane Sulfonic Acid Co-Catalyst (Sample No. 46 to 48)

A stainless steel 300 ml Parr reactor was charged with degassed distillate from Example 4 (65 mL) and degassed water (10 ml) under a stream of argon gas. A preformed catalyst solution consisting of palladium(II) acetate (55 umol) and bidentate phosphine specified in Table 6 in degassed pentenoic acids distillate (15 mL) was then injected into the reactor. The Parr reactor was then purged with CO gas and pressurised to 40 bar CO. The reaction mixture was stirred at 1000 rpm and heated to 115°C. After 17 hours the reaction was terminated by the cessation of the stirring, followed by cooling the reactor to room temperature and then venting the excess CO gas. Precipitated adipic acid was filtered and analysed by GC and the filtrate was also analysed by GC and an overall adipic acid yield and selectivity were calculated (Table 6). DTBPX (Sample 46) is included as a control.

It can be seen that the functionalized DTBPX having electron withdrawing groups perform better with higher selectivity relative to unfunctionalized DTBPX both in the presence of methane sulfonic acid (samples 41 to 43) and absence of methane sulfonic acid (samples 47 to 48).

Table 6. Hydroxycarbonylation of pentenoic acids to adipic acid with functionalized DTBPX.

Sample No. Ligand MSA Temp. TON Average TOF 2 ^nd hour TOF Selec

(mmol) (°C) (%) (h ¹ ) (h ¹ )

40 DTBPX 1.5 105 30 3500 200 425 91.8

41 4-CF ₃ -DTBPX 1.5 105 20 2500 140 305 94.7

42 4,5-Cl-DTBPX 1.5 105 25 3100 175 385 95.6

43 4-NC- ₂ - 1.5 105 25 3300 195 465 95.4

DTBPX

44 4-tBu-DTBPX 1.5 105 25 3000 175 400 91.4

45 4,5-OMe- 1.5 105 25 2800 165 400 91.0

DTBPX

46 DTBPX - 115 20 1000 60 100 96.6

47 4-CF ₃ -DTBPX - 115 10 1100 65 150 97.8

48 4,5-Cl-DTBPX - 115 10 1200 70 160 97.4

Conditions: [Pd(OAc) ₂ ] = 55 μηιοΐ, Ligand (2 equivalents w.r.t. Pd), water ( 17.8 mL), 40 bar initial CO Pressure, 1000 rpm, 80 mL distillate (PEAs ~ 74 mmol), -17 hrs. Pentenoic acid isomer composition: see Example 4.

Industrial Applicability

The metal complex and composition thereof disclosed in the present application have useful applications in preparing a dicarboxylic acid or ester thereof from an alkenoic acid or ester thereof, or in preparing a carboxylic acid or ester thereof from an alkene or diene with high selectivity and activity.

The catalyst and composition thereof may also be useful in preparing Nylon 6-6 from adipic acid prepared using the metal complex and composition thereof disclosed in the present application.

The catalyst and composition thereof may also be useful in preparing long chain aliphatic polyesters or poly amides from long chain aliphatic alpha -omega-dicarboxylic acids or esters prepared using the metal complex and composition thereof disclosed in the present application.

The catalyst and composition thereof may also be useful in preparing odd chain fatty acids or esters from even internal or terminal alkenes.

It will be apparent that various other modifications and adaptations of the invention will be apparent to the person skilled in the art after reading the foregoing disclosure without departing from the spirit and scope of the invention and it is intended that all such modifications and adaptations come within the scope of the appended claims.