Patent Description:
Palladium (II) complexes comprising phosphine ligands are known as active catalysts for cross-coupling reactions. For example, the catalysts PdCl<NUM>(AmPhos)<NUM>, AmPhosPd(crotyl)CI, XPhosPd(crotyl)CI, RuPhosPd(crotyl)CI and [BrettPhosPd(crotyl)]OTf are available commercially by Johnson Matthey PLC.

Palladium (II) dimers are also known to be useful in certain cross-coupling reactions. For example, <NPL>) show that [Pd<NUM>Br<NUM>][Ph<NUM>PCH<NUM>C<NUM>H<NUM>CH<NUM>OC(O)CH<NUM>]<NUM> can be used for the Stille cross-coupling reaction. <NPL>) disclose [Pd<NUM>I<NUM>][NEt<NUM>H]<NUM> formed in-situ and is used as a precatalyst.

<NPL>) describes pre-catalysts having formula [RPPh<NUM>]<NUM>[Pd<NUM>X<NUM>] and their use in Heck cross-coupling reactions.

The inventors have developed alternative palladium (II) complexes which have simple routes of preparation using greener solvents.

The invention provides a compound of formula (I)
<CHM>
wherein:.

The invention further provides a process for the preparation of a compound of formula (IA).

[M<NUM>Cl<NUM>][HPR<NUM>R<NUM>R<NUM>]<NUM>     (IA).

wherein M, R<NUM>, R<NUM> and R<NUM> are as hereinbefore defined, said process comprising the step of reacting a compound of formula H<NUM>PdCl<NUM> with ligand PR<NUM>R<NUM>R<NUM> or a salt thereof.

The invention further provides a process for the preparation of a compound of formula (IB).

[M<NUM>X'<NUM>][HPR<NUM>R<NUM>R<NUM>]<NUM>     (IB).

wherein M, R<NUM>, R<NUM> and R<NUM> are as hereinbefore defined and X' is bromide, iodide or fluoride, said process comprising the step of reacting a compound of formula H<NUM>PdCl<NUM> with ligand PR<NUM>R<NUM>R<NUM> or a salt thereof and a compound ZX' wherein Z is hydrogen or a metal.

The invention further provides a process for carrying out a carbon-carbon coupling reaction in the presence of a catalyst, the process comprising the use of a compound of formula (I) as hereinbefore defined. Alternatively, the invention provides the use of a compound of formula (I) as hereinbefore defined to catalyse a carbon-carbon coupling reaction.

The invention further provides a process for carrying out a carbon-heteroatom coupling reaction, the process comprising the use of a compound of formula (I) as hereinbefore defined. Alternatively, the present invention provides the use of a compound of formula (I) as hereinbefore defined to catalyse a carbon-heteroatom coupling reaction.

The point of attachment of a moiety or substituent is represented by "-". For example,-OH is attached through the oxygen atom.

"Alkyl" refers to a straight-chain or branched saturated hydrocarbon group. In certain embodiments, the alkyl group has from <NUM>-<NUM> carbon atoms. In other embodiments, the alkyl group has from <NUM>-<NUM> carbon atoms. In other embodiments, the alkyl group has from <NUM>-<NUM> carbon atoms. Unless otherwise specified, the alkyl group is attached at any suitable carbon atom. The alkyl group may be unsubstituted. Alternatively, the alkyl group may be substituted at any suitable carbon atom. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl and the like.

"Alkoxy" refers to an optionally substituted group of the formula alkyl-O- or cycloalkyl-O-, wherein alkyl and cycloalkyl are as herein defined.

"Alkoxyalkyl" refers to an optionally substituted group of the formula alkoxy-alkyl-, wherein alkoxy and alkyl are as herein defined.

"Cycloalkyl" refers to a saturated carbocyclic hydrocarbon radical. The cycloalkyl group may have a single ring or multiple condensed rings. In certain embodiments, the cycloalkyl group has from <NUM>-<NUM> carbon atoms. In other embodiments the cycloalkyl group has from <NUM>-<NUM> carbon atoms. In other embodiments, the cycloalkyl group has from <NUM>-<NUM> carbon atoms. Unless otherwise specified, the cycloalkyl group is attached at any suitable carbon atom. The cycloalkyl group may be unsubstituted. Alternatively, the cycloalkyl group may be substituted at any suitable carbon atom. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, adamantyl and the like.

"Aryl" refers to an aromatic carbocyclic group. The aryl group may have a single ring or multiple condensed rings. In certain embodiments, the aryl group has from <NUM>-<NUM> carbon atoms. In other embodiments, the aryl group has from <NUM>-<NUM> carbon atoms. In other embodiments, the aryl group has from <NUM>-<NUM> carbon atoms. Unless otherwise specified, the aryl group is attached at any suitable carbon atom. The aryl group may be unsubstituted. Alternatively, the aryl group may be substituted at any suitable carbon atom. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl and the like.

"Arylalkyl" refers to an optionally substituted group of the formula aryl-alkyl-, where aryl and alkyl are as herein defined.

"Coupling" refers to a chemical reaction in which two molecules or parts of a molecule join together (<NPL>).

"Halo", "halide" or "hal" refers to -F, -Cl, -Br and -I.

"Heteroalkyl" refers to an alkyl group (wherein alkyl is herein defined) wherein one or more carbon atoms are independently replaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorus and/or sulphur atoms). Unless otherwise specified, the heteroalkyl group is attached at any suitable atom. The heteroalkyl group may be unsubstituted. Alternatively, the heteroalkyl group may be substituted at any suitable atom. Examples of heteroalkyl groups include, but are not limited to, ethers, thioethers, primary amines, secondary amines, tertiary amines and the like.

"Heterocycloalkyl" refers to a cycloalkyl group (wherein cycloalkyl is herein defined) wherein one or more carbon atoms are independently replaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorus and/or sulphur atoms). Unless otherwise specified, the heterocycloalkyl group is attached at any suitable atom. The heterocycloalkyl group may be unsubstituted. Alternatively, the heterocycloalkyl group may be substituted at any suitable atom. Examples of heterocycloalkyl groups include, but are not limited to, epoxide, morpholinyl, piperadinyl, piperazinyl, thirranyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, thiomorpholinyl and the like.

"Heteroaryl" refers to an aryl group (wherein aryl is herein defined) wherein one or more carbon atoms are independently replaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorus and/or sulphur atoms). Unless otherwise specified, the heteroaryl group is attached at any suitable atom. The heteroaryl group may be unsubstituted. Alternatively, the heteroaryl group may be substituted at any suitable atom. Examples of heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, thiophenyl, oxadiazolyl, pyridinyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, quinolinyl and the like.

"Metallocenyl" refers to a transition metal complex group wherein a transition metal atom or ion is "sandwiched" between two rings of atoms. The metallocenyl group may be substituted or unsubstituted. Unless otherwise specified, the metallocenyl group may be attached at any suitable atom and, if substituted, may be substituted at any suitable atom. Examples of transition metal atoms or ions include but are not limited to chromium, manganese, cobalt, ruthenium, osmium, nickel and iron. Any example of a suitable ring of atoms is a cyclopentadienyl ring. An example of a metallocenyl group includes, but is not limited to, ferrocenyl, which comprises a Fe(ll) ion sandwiched between two cyclopentadienyl rings, wherein each cyclopentadienyl ring may be independently unsubstituted or substituted.

"Substituted" refers to a group in which one or more hydrogen atoms are each independently replaced with substituents (e.g. <NUM>, <NUM>, <NUM>, <NUM>, <NUM> or more) which may be the same or different. Unless the context demands otherwise, all groups defined above and referred to below may be unsubstituted or substituted where substitution is possible.

Preferred and/or optional features of the invention will now be set out. Any aspect of the invention may be combined with any other aspect of the invention, unless the context demands otherwise. Any of the preferred or optional features of any aspect may be combined, singly or in combination, with any aspect of the invention, unless the context demands otherwise.

X is suitably C!, Br or I; more suitably CI or Br.

In one embodiment, R<NUM> and R<NUM> are the same.

In an alternative embodiment, R<NUM> and R<NUM> are different.

In one embodiment of the invention, R<NUM> and R<NUM> are linked to form a ring structure with the P atom to which they are attached. Suitably, the ring structure is a <NUM> - <NUM> membered ring.

Suitably, R<NUM> and R<NUM> are independently selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl wherein the heteroatoms are independently selected from sulphur, nitrogen and oxygen.

More suitably, R<NUM> and R<NUM> are independently selected from the group consisting of alkyl, cycloalkyl and aryl.

Examples of suitable alkyl groups for R<NUM> or R<NUM> include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl (e.g. n-pentyl or neopentyl), hexyl, heptyl, octyl, nonyl, decyl, dodecyl or stearyl (all either unsubstituted or substituted).

Examples of suitable cycloalkyl groups for R<NUM> or R<NUM> include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or adamantyl (all either unsubstituted or substituted). Examples of suitable aryl groups for R<NUM> or R<NUM> include phenyl, naphthyl or anthracyl (all either unsubstituted or substituted).

Examples of suitable heteroaryl groups for R<NUM> or R<NUM> includes pyridyl (either unsubstituted or substituted).

Any alkyl or cycloalkyl groups may be independently optionally substituted with one or more (e.g. <NUM>, <NUM>, <NUM>, <NUM>, or <NUM>) substituents each of which may be the same or different. Suitable substituents include, but are not limited to, halide (F, Cl, Br or I) or alkoxy groups, (e.g. methoxy, ethoxy or propoxy).

Any aryl or heteroaryl groups may be independently optionally substituted with one or more (e.g. <NUM>, <NUM>, <NUM>, <NUM>, or <NUM>) substituents each of which may be the same or different. Suitable substituents include, but are not limited to, halide (F, Cl, Br or I), straight- or branched-chain alkyl (e.g. C<NUM>-C<NUM>), alkoxy (e.g. C<NUM>-C<NUM> alkoxy), straight- or branched-chain (dialkyl)amino (e.g. (C<NUM>-C<NUM> dialkyl)amino), heterocycloalkyl (e.g. C<NUM>-<NUM> heterocycloalkyl groups, such as morpholinyl and piperadinyl) or tri(halo)methyl (e.g. F<NUM>C-). Suitable substituted aryl groups include but are not limited to <NUM>,<NUM>,<NUM>-trimethylphenyl and <NUM>,<NUM>-dimethoxyphenyl.

Preferably, R<NUM> and R<NUM> are independently selected from the group consisting of n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl (e.g. n-pentyl or neopentyl), hexyl, cyclopentyl, cyclohexyl or adamantyl and phenyl, wherein each group may be unsubstituted or substituted, for example with one or more substituents as hereinbefore mentioned.

More preferably, R<NUM> and R<NUM> are independently selected from the group consisting of tert-butyl, n-butyl, cyclohexyl, adamantyl <NUM>,<NUM>,<NUM>-trimethylphenyl and <NUM>,<NUM>-dimethoxyphenyl.

Suitably, R<NUM> is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl and metallocenyl.

Suitably, R<NUM> is selected from the group consisting of alkyl, cycloalkyl, aryl and metallocenyl.

In a first aspect of the invention, R<NUM> is alkyl.

The alkyl group is optionally substituted with one or more (e.g. <NUM>, <NUM>, <NUM>, <NUM>, or <NUM>) substituents each of which may be the same or different. Suitable substituents include, but are not limited to, halide (F, Cl, Br or I), alkoxy groups, (e.g. methoxy, ethoxy or propoxy) and aryl (itself optionally substituted) (e.g. phenyl).

Examples of suitable alkyl groups for R<NUM> include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl (e.g. n-pentyl or neopentyl), hexyl, heptyl, octyl, nonyl, decyl, dodecyl stearyl, wherein each group may be unsubstituted or substituted, for example with one or more substituents as hereinbefore mentioned.

Suitable R<NUM> alkyl groups include, t-butyl, hexyl and benzyl.

In a second aspect of the invention, R<NUM> is cycloalkyl.

Suitably, the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or adamantyl.

More suitably, the cycloalkyl group is cyclohexyl or adamantyl.

In a third aspect of the invention, R<NUM> is aryl.

Suitably, the aryl group is a group of formula (II)
<CHM>
wherein:
R<NUM>, R<NUM>, R<NUM>, R<NUM> and R<NUM> are independently hydrogen, or organic groups having <NUM>-<NUM> carbon atoms and are selected up to limitation imposed by stability and the rules of valence.

Suitably, R<NUM>, R<NUM>, R<NUM>, R<NUM> and R<NUM> are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycloalkyl, alkoxy, aryl, heteroaryl, -N(alkyl)<NUM> (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups), -N(cycloalkyl)<NUM> (wherein the cycloalkyl groups may be the same or different), -N(aryl)<NUM> (wherein the aryl groups may be the same or different), -N(heteroaryl)<NUM> (wherein the heteroaryl groups may be the same or different) and heterocycloalkyl groups. The heteroatoms in the heteroaryl or heterocycloalkyl groups may be independently selected from sulphur, nitrogen and/or oxygen.

More suitably, R<NUM>, R<NUM>, R<NUM>, R<NUM> and R<NUM> are independently selected from the group consisting of hydrogen, alkyl, heterocycloalkyl, alkoxy, aryl and -N(alkyl)<NUM> (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups).

Alkyl groups may include groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl (e.g. n-pentyl or neopentyl), hexyl, heptyl, octyl, nonyl, decyl, dodecyl or stearyl; suitably methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl; more suitably, methyl, ethyl, n-propyl, iso-propyl; preferably methyl or ethyl. The alkyl groups may be optionally substituted with one or more (e.g. <NUM>, <NUM>, <NUM>, <NUM>, or <NUM>) substituents each of which may be the same or different such as halide (F, Cl, Br or I), alkoxy groups, e.g. methoxy, ethoxy or propoxy.

Heterocycloalkyl groups may include groups such as epoxide, morpholinyl, piperadinyl, piperaxinyl, thirranyl, pyrrolidinyl, pyrazolidinyl, imazolidinyl, thiazonidinyl, thiomorpholinyl. Preferably, the heterocycloalkyl group is morpholinyl.

Alkoxy groups may include groups such as methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, -O-pentyl, -O-hexyl, -O-heptyl, -O-octyl, -O-nonyl, -O-decyl, -O-dodecyl. Suitably, the alkoxy group is methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy; more suitably, methoxy, ethoxy, n-propoxy, iso-propoxy; preferably, methoxy.

Aryl groups may include groups such as phenyl, napthyl and anthracenyl; suitably phenyl. The aryl group may be optionally substituted with one or more (e.g. <NUM>, <NUM>, <NUM>, <NUM>, or <NUM>) substituents each of which may be the same of different. Suitable substituent include, but are not limited to, alkyl, cycloalkyl, alkoxy, aryl, heteroaryl,-N(alkyl)<NUM> (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups),-N(cycloalkyl)<NUM> (wherein the cycloalkyl groups may be the same or different),-N(aryl)<NUM> (wherein the aryl groups may be the same or different),-N(heteroaryl)<NUM> (wherein the heteroaryl groups may be the same or different) and heterocycloalkyl groups. Suitably, the substituents are selected from alkyl or alkoxy. Suitable substituted aryl groups include, but are not limited to, <NUM>,<NUM>-dimethoxyphenyl, <NUM>,<NUM>-diisopropoxyphenyl and <NUM>,<NUM>,<NUM>-triisopropylphenyl.

-N(alkyl)<NUM> groups may include groups such as -NMe<NUM>, -NEt<NUM>, -N(n-Pr)<NUM> or -N(i-Pr)<NUM>.

In one embodiment of the third aspect of the invention, R<NUM>, R<NUM>, R<NUM> and R<NUM> are independently selected from the group consisting of hydrogen, alkyl, heterocycloalkyl, alkoxy, aryl and -N(alkyl)<NUM> (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups), suitably, hydrogen or alkoxy and R<NUM> is an aryl of formula (III)
<CHM>
wherein R<NUM>, R<NUM>, R<NUM>, R<NUM> and R<NUM> are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxy, aryl, heteroaryl,-N(alkyl)<NUM> (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups),-N(cycloalkyl)<NUM> (wherein the cycloalkyl groups may be the same or different),-N(aryl)<NUM> (wherein the aryl groups may be the same or different),-N(heteroaryl)<NUM> (wherein the heteroaryl groups may be the same or different) and heterocycloalkyl groups. The heteroatoms in the heteroaryl or heterocycloalkyl groups may be independently selected from sulphur, nitrogen or/and oxygen. Suitably, R<NUM>, R<NUM>, R<NUM>, R<NUM> and R<NUM> are independently selected from the group consisting of hydrogen, alkyl and alkoxy.

In an alternative embodiment of the third aspect of the invention, R<NUM>, R<NUM>, R<NUM> and R<NUM> may be independently selected from the group consisting of hydrogen, alkyl, heterocycloalkyl, alkoxy, aryl and -N(alkyl)<NUM> (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups), suitably, hydrogen or alkoxy and R<NUM> is an unsubstituted heterocycloalkyl group, such as a C<NUM>-<NUM> heterocycloalkyl groups, such as piperidinyl and morpholinyl, preferably morpholinyl.

In a yet further embodiment of the third aspect of the invention, R<NUM>, R<NUM>, R<NUM> and R<NUM> may be independently selected from the group consisting of hydrogen, alkyl, heterocycloalkyl, alkoxy, aryl and -N(alkyl)<NUM> (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups), suitably, hydrogen or alkoxy and R<NUM> is hydrogen.

In a fourth aspect of the invention, R<NUM> is heteroaryl. The heteroaryl group may be optionally substituted with one or more (e.g. <NUM>, <NUM>, <NUM>, <NUM> or <NUM>) substituents such as halide, straight- or branched-chain alkyl, alkoxy, substituted or unsubstituted aryl, straight-or branched-chain (dialkyl)amino, heterocycloalkyl or tri(halo)alkyl.

In a fifth aspect of the invention, R<NUM> is metallocenyl. Suitably, the metallocenyl group is ferrocenyl, preferably where the cyclopentadienyl rings are substituted.

Suitably, PR<NUM>R<NUM>R<NUM> is selected from the group consisting of:
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>
<CHM>.

Thus, a further aspect of the invention provides a process for the preparation of a compound of formula (IA).

wherein M, R<NUM>, R<NUM> and R<NUM> are as hereinbefore defined, said process comprising the step of reacting a compound of formula H<NUM>PdCl<NUM> with ligand PR<NUM>R<NUM>R<NUM> or a salt thereof. Suitable salts include but are not limited to, the chloride and tetrafluoroborate.

Another aspect of the invention provides a process for the preparation of a compound of formula (IB).

wherein M, R<NUM>, R<NUM> and R<NUM> are as hereinbefore defined and X' is bromide, iodide or fluoride (suitably bromide), said process comprising the step of reacting a compound of formula H<NUM>PdCl<NUM> with ligand PR<NUM>R<NUM>R<NUM> or a salt thereof and a compound ZX' wherein Z is hydrogen or a monovalent metal ion, such as Li or K. Suitable salts include but are not limited to, the chloride and tetrafluoroborate.

Compound H<NUM>PdCl<NUM> and ligands PR<NUM>R<NUM>R<NUM> are commercially available from Johnson Matthey PLC, or any other commercial supplier, such as Aldrich, Dalchem, TCI Chemicals.

Compound ZX' is commercially available, for example from Aldrich, Alfa Aesar etc..

The compound of formula H<NUM>PdCl<NUM>, ligand PR<NUM>R<NUM>R<NUM> and, where used, compound ZX' are combined in a solvent. In this case, the solvent is any suitable aprotic solvent or combination of aprotic solvents. Examples of aprotic solvents are toluene, benzene, tetrahydrofuran (THF), <NUM>-methyltetrahydrofuran, dichloromethane (DCM), dioxane, acetone, acetonitrile, dimethylformamide (DMF), N-methylpyrrolidine (NMP), dimethalacetamide (DMAc), methyltertbutylether (MTBE), diethylether, eucalyptol, hexane, heptane, pentane or ethylacetate. Alternatively, a protic solvent, such as ethanol, methanol or water, can be used or a combination of protic/aprotic solvent. The choice of solvent system is within the capability and knowledge of the skilled person knowing the starting materials which will be used.

In one embodiment, the solvent is acetone.

The concentration of the compound of formula H<NUM>PdCl<NUM> in the solvent is suitably about <NUM> mol/L to about <NUM> mol/L, more suitably about <NUM> mol/L to about <NUM> mol/L, preferably about <NUM> mol/L to about <NUM> mol/L.

Any suitable quantity of ligand PR<NUM>R<NUM>R<NUM> may be used, although it is preferred that the molar ratio of the compound of formula H<NUM>PdCl<NUM> to ligand PR<NUM>R<NUM>R<NUM> is from about <NUM>:<NUM> to about <NUM>:<NUM>, suitably from about <NUM>:<NUM> to about <NUM>:<NUM>, preferably from about <NUM>:<NUM> to about <NUM>:<NUM>. In one embodiment the molar ratio of the compound of formula H<NUM>PdCl<NUM> to ligand PR<NUM>R<NUM>R<NUM> is from about <NUM>:<NUM> to about <NUM>:<NUM>. If the ligand is insoluble in the solvent, an excess of the Pd salt is preferred.

When ZX' is added to the reaction mixture, suitably it is added in an excess compared to the compound of formula H<NUM>PdCl<NUM> and ligand PR<NUM>R<NUM>R<NUM>, such as at least <NUM> mole equivalents, suitably at least <NUM> mole equivalents.

The reaction is suitably carried out under an inert atmosphere, such as under nitrogen or argon; preferably, the reaction is carried out under nitrogen. Alternatively, if the ligand is stable, the reaction may be carried out in air.

The process of the invention may be carried out at a temperature in the range of -<NUM> to about <NUM>, suitably about <NUM> to about <NUM>, preferably about <NUM> to about <NUM> and more preferably at ambient temperature (i.e. about <NUM> to about <NUM>, such as about <NUM> to about <NUM>). It is preferred that the temperature is maintained below the decomposition temperature and so when the compound for formula (I) is known to decompose with the temperature ranges given above, the temperature should be maintained below the decomposition temperature.

The reaction may be carried out for a period of from about <NUM> minutes to about <NUM> hours. Usually, the reaction is complete within about <NUM> hours, such as within <NUM> hours, such as within <NUM> hour. Often the reaction is essentially instantaneous. After the reaction is complete, the resulting suspension is filtered, washed and dried. Drying may be performed using known methods, for example at temperatures in the range of about <NUM> to about <NUM>, preferably about <NUM> to about <NUM> under <NUM>-30mbar vacuum for <NUM> hour to <NUM> days. If desired, the compound may be recrystallised. An antisolvent may be used when the compound is soluble.

The compounds of the invention may be used for carbon-carbon coupling reactions. Examples of carbon-carbon coupling reactions include Heck, Suzuki or Negishi reactions, ketone α-arylation reactions, aldehyde α-arylations reactions, allylic substitution reactions and trifluoromethylation reactions. The catalysts of the present invention may also be used for carbon-heteroatom coupling reactions, such as carbon-nitrogen coupling reactions (ie Buchwald-Hartwig) or carbon-oxygen or carbon-sulphur coupling reactions.

Thus, in a further aspect the present invention provides a process for carrying out a carbon-carbon coupling reaction in the presence of a catalyst, the process comprising the use of a compound of formula (I) as hereinbefore defined. Alternatively, the present invention provides the use of a compound of formula (I) as hereinbefore define to catalyse a carbon-carbon coupling reaction.

In a still further aspect, the present invention provides a process for carrying out a carbon-heteroatom coupling reaction, the process comprising the use of a compound of formula (I) as hereinbefore defined. Alternatively, the present invention provides the use of a compound of formula (I) as hereinbefore defined to catalyse a carbon-heteroatom coupling reaction.

The invention will now be further described by way of the following non-limiting examples.

All solvents and reagents were purchased from commercial sources and used as received. All catalysts, ligands or precious metal precursors were obtained from Johnson Matthey PLC or commercial sources. All solution phase <NUM>H NMR, <NUM>C NMR, <NUM>P NMR and <NUM>F NMR spectra were recorded on a Bruker Avance DRX-<NUM> spectrometer at ambient temperature; chemical shifts (δ) are given in ppm. <NUM>H and <NUM>C NMR spectra were referenced to the NMR solvent peaks or internal TMS. <NUM>P NMR spectra were calibrated to an external phosphoric acid standard (<NUM>% in D<NUM>O as provided by Sigma Aldrich). Coupling constants (J) are reported in Hz and apparent splitting patterns are designated using the following abbreviations: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad), app. (apparent) and the appropriate combinations. Solid state <NUM>P NMR were acquired at a static magnetic field strength of <NUM> T (v<NUM> (<NUM>H) = <NUM>) on a Bruker Avance Neo console. The probe was tuned to <NUM>:<NUM> and referenced to ADP at <NUM>:<NUM> ppm. Powdered samples of known mass were packed into zirconia MAS rotors with Kel-F caps. The rotors were spun using ambient temperature purified compressed air. All spectra were recorded using cross polarisation (CP), in which magnetisation is transferred from <NUM>H to <NUM>P nuclei via dipolar coupling. A contact time of <NUM> was used for the <NUM>P experiments and high power (<NUM>) SPINAL-<NUM> decoupling was applied to the <NUM>H channel during acquisition.

Crystals of sufficient size and quality for analysis by single crystal Xray diffraction were isolated, and data were collected using a Rigaku Oxford Diffraction Supernova Dual Source (four-circle-diffractometer equipped with Oxford Cryosystems Cobra cooling device). The data were collected using Cu Kα radiation as stated in the experimental tables. Structures were solved and refined against F<NUM> values using the Bruker AXS SHELXTL suite or the OLEX<NUM> crystallographic software. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms attached to carbon were placed geometrically and allowed to refine with a riding isotropic displacement parameter. Hydrogen atoms attached to a phosphorus were located in a difference Fourier synthesis and were allowed to refine freely with an isotropic displacement parameter.

All GC were recorded on a Varian CP-<NUM> Gas Chromatograph with an Agilent DB-<NUM>, <NUM> x <NUM> column and CP-<NUM> Autosampler. All samples were run with a standard split injection mode using either He or N<NUM> carrier gas. Samples were run using ethyl acetate or acetonitrile eluent. Conversion was determined by comparative integration of appropriate reagents, products and impurities. Preferably conversion is determined from the ratio of product to aryl halide.

A <NUM> round bottomed flask equipped with a stir bar and condenser was charged with the ligand or a salt thereof and acetone. The flask was purged with nitrogen then a solution of H<NUM>PdCl<NUM> in acetone was added rapidly. The mixture was stirred for a minimum of <NUM> at ambient temperature (<NUM> - <NUM>). The resulting suspension was filtered then washed with acetone then heptane under air. The catalyst was dried in vacuo at ambient temperature. For reactions producing ><NUM> catalyst, the round bottomed flask and stir bar was replaced with either a <NUM> beaker or jacketed reactor with overhead stirrer.

A <NUM> round bottomed flask equipped with a stir bar and condenser was charged with the ligand or a salt thereof and acetone. The flask was purged with nitrogen then a solution of H<NUM>PdCl<NUM> in acetone was added rapidly. The mixture was stirred for a minimum of <NUM> at ambient temperature (<NUM> - <NUM>) then a solution of MBr (M = H, Li, K) in deionized water was added dropwise. The resulting suspension was stirred for a minimum of <NUM> mins then filtered. The solids were washed with acetone then heptane under air. The catalyst was dried in vacuo at ambient temperature. For reactions producing ><NUM> catalyst, the round bottomed flask and stir bar was replaced with either a <NUM> beaker or jacketed reactor with overhead stirrer.

[HAmPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mol) and AmPhos (<NUM>, <NUM> mol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HAmPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as beige solids. <NUM>P solid-state CPMAS NMR spectra: δ (ppm) <NUM>. Calc for C<NUM>H<NUM>N<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>. Pd Assay w/w% Calc: <NUM>. Found <NUM>.

[HCyAmPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and CyAmPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HCyAmPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as beige solids. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>). <NUM>P{<NUM>H} = <NUM> ppm in CDCl<NUM>.

[HRuPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and RuPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HRuPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as red solids. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (td, J = <NUM>, <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (s, J = <NUM>, <NUM>), <NUM> (dt, <NUM>JHP = <NUM>, <NUM>JHH = <NUM>, <NUM>), <NUM> (hept, J = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (d, J = Hz, <NUM>, <NUM>) <NUM> (d, J = <NUM>, <NUM>). <NUM>C{<NUM>H} NMR (CDCl<NUM>): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>O<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>. Pd Assay w/w% Calc: <NUM>. Found <NUM>.

[HRuPhos]<NUM>[Pd<NUM>Br<NUM>]: Following general procedure B, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and RuPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. To the suspension was added a solution of LiBr (<NUM>, <NUM> mmol) in deionized water (<NUM>) The resulting suspension is filtered, washed and dried to afford [HRuPhos]<NUM>[Pd<NUM>Br<NUM>] (<NUM>, <NUM>%) as red solids. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (dt, <NUM>JHP = <NUM>, <NUM>JHH = <NUM>, <NUM>), <NUM> (hept, J = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>). <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>).

[HSPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and SPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HSPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as orange solids. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM>-<NUM> (m, <NUM>). <NUM>C{<NUM>H} NMR (CDCl<NUM>): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>O<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>. Pd Assay w/w% Calc: <NUM>. Found <NUM>.

[HSPhos]<NUM>[Pd<NUM>Br<NUM>]: Following general procedure B, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and SPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. To the suspension was added a solution of LiBr (<NUM>, <NUM> mmol) in deionized water (<NUM>) The resulting suspension is filtered, washed and dried to afford [HSPhos]<NUM>[Pd<NUM>Br<NUM>] (<NUM>, <NUM>%) as red solids. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (dt, <NUM>JHP = <NUM>, <NUM>JHH = <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM><NUM> (m, <NUM>). <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>).

[HSPhos]<NUM>[Pd<NUM>Br<NUM>] was recrystallised from acetone to obtain red block crystals. The asymmetric unit contains one molecule of HSPhos, half of the Pd<NUM>Br<NUM> moiety and one molecule of acetone. Empirical formula: C<NUM>H<NUM>Br<NUM>O<NUM>P<NUM>Pd<NUM>; Formula weight: <NUM>; Temperature: <NUM>; Wavelength: <NUM>Å; Crystal size: <NUM> x <NUM> x <NUM>; Crystal habit: dark red cut block; Crystal system: Triclinic; Space group: P-<NUM>; Unit cell dimensions: a = <NUM>(<NUM>) Å, b = <NUM>(<NUM>) Å, c = <NUM>(<NUM>) Å, α= <NUM>(<NUM>)°, β= <NUM>(<NUM>)°, γ = <NUM>(<NUM>)°; Volume: <NUM>(<NUM>) Å<NUM>; Z=<NUM>; Density (calculated): <NUM>/m<NUM>; Absorption coefficient µ: <NUM>-<NUM>; F(<NUM>): <NUM>; Theta range for data collection: <NUM> to <NUM>°; Index ranges: -<NUM> ≤ h ≤ <NUM>,-<NUM> ≤ k ≤ <NUM>, -<NUM> ≤ l ≤ <NUM>; Reflections collected: <NUM>; Independent reflections: <NUM> [R(int) = <NUM>]; Coverage of independent reflections: <NUM> %; Data / restraints / parameters: <NUM> / <NUM> / <NUM>; Goodness-of-fit on F<NUM>: <NUM>; Δ/σmax: <NUM>; Final R indices: <NUM> data; I>2σ(I)R1 = <NUM>, wR2 = <NUM>; all data: R1 = <NUM>, wR2 = <NUM>; Δρ: <NUM> and -<NUM> eÅ-<NUM>.

A view of [HSPhos]<NUM>[Pd<NUM>Br<NUM>] from the crystal structure (grown fragment) is shown in <FIG>. Anisotropic atomic displacement ellipsoids for the non-hydrogen atoms are shown at the <NUM>% probability level. Hydrogen atoms are displayed with an arbitrarily small radius.

[HXPhos]<NUM>[Pd<NUM>Cl<NUM>]: A <NUM> round bottomed flask equipped with a stir bar and condenser was charged with XPhos (<NUM>, <NUM> mmol) and acetone (<NUM>). The flask was purged with nitrogen then <NUM>% w/w HCl (<NUM>, <NUM> mmol) was added dropwise until the XPhos fully dissolved. To the round bottomed flask, a solution of H<NUM>PdCl<NUM> (<NUM>, <NUM> mmol) in acetone (<NUM>) was added rapidly. The mixture was stirred for <NUM> at ambient temperature. The resulting suspension is filtered, washed and dried to afford [HXPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as peach solids. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (hept, J = <NUM>, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM><NUM> (m, <NUM>), <NUM><NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>). <NUM>C{<NUM>H} NMR (CDCl<NUM>): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>.

[HtBuXPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and tBuXPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HtBuXPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as orange solids. Reaction supernatant and acetone washings were combined and concentrated to furnish orange crystals. (<NUM>, <NUM>%). <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (hept, J = <NUM>, <NUM>), <NUM> (hept, J = <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>). <NUM>C{<NUM>H} NMR (CDCl<NUM>): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>. Pd Assay w/w% Calc: <NUM>. Found <NUM>.

Asymmetric unit contains two independent molecules of HtBuXPhos and one Pd<NUM>Cl<NUM> moiety. Empirical formula: C<NUM>H<NUM>Cl<NUM>PPd; Formula weight: <NUM>; Temperature: <NUM>(<NUM>) K; Wavelength: <NUM>Å; Crystal size: <NUM> x <NUM> x <NUM>; Crystal habit: dark orange fragment; Crystal system: Triclinic; Space group: P-<NUM>; Unit cell dimensions: a = <NUM>(<NUM>) Å b = <NUM>(<NUM>) Å c = <NUM>(<NUM>) Å α= <NUM>(<NUM>)° β= <NUM>(<NUM>)° γ = <NUM>(<NUM>)°; Volume: <NUM>(<NUM>) Å<NUM>; Z=<NUM>; Density (calculated): <NUM>/m<NUM>; Absorption coefficient µ: <NUM>-<NUM>; F(<NUM>): <NUM>; Theta range for data collection: <NUM> to <NUM>°; Index ranges: -<NUM> ≤ h ≤ <NUM>, -<NUM> ≤ k ≤ <NUM>, -<NUM> ≤ l ≤ <NUM>; Reflections collected: <NUM>; Independent reflections: <NUM> [R(int) = <NUM>]; Coverage of independent reflections: <NUM> %; Data / restraints / parameters: <NUM> / <NUM> / <NUM>; Goodness-of-fit on F<NUM>: <NUM>; Δ/σmax. <NUM>; Final R indices: <NUM> data; I>2σ(I)R1 = <NUM>, wR2 = <NUM>; all data: R1 = <NUM>, wR2 = <NUM>; Δρ: <NUM> and -<NUM> eÅ-<NUM>.

A view of [HtBuXPhos]<NUM>[Pd<NUM>Cl<NUM>] from the crystal structure is shown in <FIG>. Anisotropic atomic displacement ellipsoids for the non-hydrogen atoms are shown at the <NUM>% probability level. Hydrogen atoms are displayed with an arbitrarily small radius
<CHM>.

[HJohnPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and JohnPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HJohnPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as orange-brown solids. <NUM>H NMR (CD<NUM>CN): δ (ppm) <NUM> (m, <NUM>), <NUM> (tt, J = <NUM>, <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>). <NUM>C{<NUM>H} NMR (CD<NUM>CN): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CD<NUM>CN): δ (ppm) <NUM> (m, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>.

[HCyJohnPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and CyJohnPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HCyJohnPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as orange-brown solids. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (dt, <NUM>JHP = <NUM>, <NUM>JHH = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (m, <NUM>). <NUM>C{<NUM>H} NMR (CDCl<NUM>): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>.

[HBrettPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and BrettPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HBrettPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as orange solids. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (dt <NUM>JHP = <NUM>, <NUM>JHH = <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (hept, J = <NUM>, <NUM>), <NUM> (hept J = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>). <NUM>C{<NUM>H} NMR (CDCl<NUM>): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM>. <NUM> (d, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>O<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>. Pd Assay w/w% Calc: <NUM>. Found <NUM>.

[HtBuBrettPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and tBuBrettPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HtBuBrettPhos]<NUM>[Pd<NUM>Cl<NUM>] (<NUM>, <NUM>%) as red solids. Reaction supernatant and acetone washings were combined and layered with deionized water to furnish red crystals (<NUM>, <NUM>%). <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>). <NUM>C{<NUM>H} NMR (CDCl<NUM>): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>O<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>. Pd Assay w/w% Calc: <NUM>. Found <NUM>.

[HMorDalPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and MorDalPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HMorDalPhos]<NUM>[Pd<NUM>Cl<NUM> (<NUM>, <NUM>%) as brown solids. <NUM>H NMR (CD<NUM>CN): δ (ppm) <NUM> (t, J = <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> (td, J = <NUM>, <NUM>, <NUM>), <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>). <NUM>C{<NUM>H} NMR (CD<NUM>CN): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CD<NUM>CN): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>O<NUM>N<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>.

[HQPhos]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and QPhos (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HQPhos]<NUM>[Pd<NUM>Cl<NUM>] as red solids (<NUM>, <NUM>%). <NUM>H NMR (CD<NUM>CN): δ (ppm) <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>). <NUM>C{<NUM>H} NMR (CD<NUM>CN): δ (ppm) <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>. <NUM>P NMR (CD<NUM>CN): δ (ppm) <NUM> (m, <NUM>JHP = <NUM>). Calc for C<NUM>H<NUM>Fe<NUM>P<NUM>Cl<NUM>Pd<NUM>: C <NUM>; H <NUM>; N <NUM>. Found: C <NUM>; H <NUM>; N <NUM>.

[HPCys]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and PCy<NUM> (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HPCy<NUM>]<NUM>[Pd<NUM>Cl<NUM>] and (PCy<NUM>)PdCl<NUM> in approximately <NUM>:<NUM> ratio. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> - <NUM> (m, <NUM>). <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>JHP = <NUM>).

[HPCy<NUM>]<NUM>[Pd<NUM>Cl<NUM>] was recrystallised from chloroform to obtain orange plates. The asymmetric unit contains one molecule of HPCy<NUM>, half of the Pd<NUM>Cl<NUM> moiety and one molecule of chloroform. Empirical formula: C<NUM>H<NUM>Cl<NUM>PPd; Formula weight: <NUM>; Temperature: <NUM>(<NUM>) K; Wavelength: <NUM>Å; Crystal size: <NUM> x <NUM> x <NUM>; Crystal habit: pale orange plate; Crystal system: Monoclinic; Space group: P<NUM><NUM>/n; Unit cell dimensions: a = <NUM>(<NUM>) Å b = <NUM>(<NUM>) Å c = <NUM>(<NUM>) Å α= <NUM>° β= <NUM>(<NUM>)° γ = <NUM>°; Volume: <NUM>(<NUM>) Å<NUM>; Z=<NUM>; Density (calculated): <NUM>/m<NUM>; Absorption coefficient µ: <NUM>-<NUM>; F(<NUM>): <NUM>; Theta range for data collection: <NUM> to <NUM>°; Index ranges: -<NUM> ≤ h ≤ <NUM>, -<NUM> ≤ k ≤ <NUM>,-<NUM> ≤ l ≤ <NUM>; Reflections collected: <NUM>; Independent reflections: <NUM> [R(int) = <NUM>]; Coverage of independent reflections: <NUM> %; Data / restraints / parameters: <NUM> / <NUM> / <NUM>; Goodness-of-fit on F<NUM>: <NUM>; Δ/σmax: <NUM>; Final R indices: <NUM> data; I>2σ(I)R1 = <NUM>, wR2 = <NUM>; all data: R1 = <NUM>, wR2 = <NUM>; Δρ: <NUM> and -<NUM> eÅ-<NUM>.

A view of [HPCy<NUM>]<NUM>[Pd<NUM>Cl<NUM>] from the crystal structure (grown fragment) is shown in <FIG>. Anisotropic atomic displacement ellipsoids for the non-hydrogen atoms are shown at the <NUM>% probability level. Hydrogen atoms are displayed with an arbitrarily small radius.

[HPtBu<NUM>]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and PtBu<NUM> (<NUM> wt% in xylenes, <NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. Water (<NUM>) is added to the mixture and the resulting suspension is filtered, washed and dried to afford [HPtBu<NUM>]<NUM>[Pd<NUM>Cl<NUM>] as red solids. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>JHP = <NUM>).

[HPtBu<NUM>nhexyl]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and di-tert-butyl(n-hexyl)phosphonium tetrafluoroborate (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. Water (<NUM>) is added to the mixture and the product precipitates over <NUM>. The resulting suspension is filtered, washed and dried to afford [HPtBu<NUM>nhexyl]<NUM>[Pd<NUM>Cl<NUM>] as orange solids (<NUM>, <NUM>%). <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (t, J = <NUM>, <NUM>). <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>JHP = <NUM>).

[HPAd<NUM>]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and PAd<NUM> (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HPAd<NUM>]<NUM>[Pd<NUM>Cl<NUM>] as orange solids (<NUM>, <NUM>%). <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (s, <NUM>), <NUM>-<NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>). <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>JHP = <NUM>).

[HCataCXiumA]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and CataCXiumA (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. Water (<NUM>) is added to the mixture and the resulting suspension is filtered, washed and dried to afford [HCataCXiumA]<NUM>[Pd<NUM>Cl<NUM>] as orange solids (<NUM>, <NUM>%). <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (s, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>), <NUM> (m, <NUM>). <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>JHP = <NUM>).

[HCataCXiumABn]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and CataCXiumABn (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HCataCXiumABn]<NUM>[Pd<NUM>Cl<NUM>] as beige solids (<NUM>, <NUM>%). <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> - <NUM> (m, <NUM>), <NUM> (dt, <NUM>JHP = <NUM>, <NUM>JHH = <NUM>, <NUM>), <NUM> (dd, J = <NUM>, <NUM>, <NUM>), <NUM> - <NUM> (m, <NUM>), <NUM> (m, <NUM>). <NUM>P NMR (CDCl<NUM>): δ (ppm) <NUM> (m, <NUM>JHP = <NUM>).

[HP(<NUM>,<NUM>-dimethoxyphenyl)<NUM>]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and tris(<NUM>,<NUM>-dimethoxyphenyl)phosphine (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. The resulting suspension is filtered, washed and dried to afford [HP(<NUM>,<NUM>-dimethoxyphenyl)<NUM>]<NUM>[Pd<NUM>Cl<NUM>] as orange solids (<NUM>, <NUM>%). <NUM>H NMR (CD<NUM>CN): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (t, J = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (d, J = <NUM>, <NUM>), <NUM> (s, <NUM>). <NUM>P NMR (CD<NUM>CN): δ (ppm) -<NUM> (d, <NUM>JHP = <NUM>). (Ar = <NUM>,<NUM>-dimethoxyphenyl)
<CHM>.

[HP(<NUM>,<NUM>,<NUM>-trimethylphenyl)<NUM>]<NUM>[Pd<NUM>Cl<NUM>]: Following general procedure A, H<NUM>PdCl<NUM> solution (<NUM> Pd, <NUM> mmol) and tris(<NUM>,<NUM>,<NUM>-trimethylphenyl)phosphine (<NUM>, <NUM> mmol) are reacted in acetone (<NUM>) at rt for <NUM>. Water (<NUM>) is added to the mixture and the resulting suspension is filtered, washed and dried to afford [HP(<NUM>,<NUM>,<NUM>-trimethylphenyl)<NUM>]<NUM>[Pd<NUM>Cl<NUM>] as red solids (<NUM>, <NUM>%). Mother liquor and acetone washings were combined and concentrated to furnish orange crystals. <NUM>H NMR (CDCl<NUM>): δ (ppm) <NUM> (d, <NUM>JHP = <NUM>, <NUM>), <NUM> (m, br, <NUM>), <NUM> (s, br <NUM>), <NUM> (s, <NUM>), <NUM> (s, <NUM>). <NUM>P NMR (CDCl<NUM>): δ (ppm) -<NUM> (d, <NUM>JHP = <NUM>.

Asymmetric unit contains two independent molecules of HP(<NUM>,<NUM>,<NUM>-trimethylphenyl)<NUM> and one Pd<NUM>Cl<NUM> moiety. Empirical formula: C<NUM>H<NUM>Cl<NUM>PPd; Formula weight: <NUM>; Temperature: <NUM>(<NUM>) K; Wavelength: <NUM>Å; Crystal size: <NUM> x <NUM> x <NUM>; Crystal habit: dark orange fragment; Crystal system: Monoclinic; Space group: P<NUM><NUM>/c; Unit cell dimensions: a = <NUM>(<NUM>) Å b = <NUM>(<NUM>) Å c = <NUM>(<NUM>) Å α= <NUM>° β= <NUM>(<NUM>)° γ = <NUM>°; Volume: <NUM>(<NUM>) Å<NUM>; Z=<NUM>; Density (calculated): <NUM>/m<NUM>; Absorption coefficient: <NUM>-<NUM>; F(<NUM>): <NUM>; Theta range for data collection: <NUM> to <NUM>°; Index ranges: -<NUM> ≤ h ≤ <NUM>, -<NUM> ≤ k ≤ <NUM>, -<NUM> ≤ l ≤ <NUM>; Reflections collected: <NUM>; Independent reflections: <NUM> [R(int) = <NUM>]; Coverage of independent reflections: <NUM> %; = Data / restraints / parameters: <NUM>/<NUM>/<NUM>; Goodness-of-fit on F<NUM>: <NUM>; Δ/σmax. <NUM>; Final R indices <NUM> data; I>2σ(I)R1 = <NUM>, wR2 = <NUM>; all data: R1 = <NUM>, wR2 = <NUM>; = Δρ: <NUM> and -<NUM> eÅ-<NUM>.

A view of [HP(<NUM>,<NUM>,<NUM>-trimethylphenyl)<NUM>]<NUM>[Pd<NUM>Cl<NUM>] from the crystal structure (asymmetric part is) is shown in <FIG>. Anisotropic atomic displacement ellipsoids for the non-hydrogen atoms are shown at the <NUM>% probability level. Hydrogen atoms are displayed with an arbitrarily small radius.

A <NUM> vial quipped with a stir bar and polypropylene cap with PTFE-faced silicone septum was charged with catalyst and NaOtBu (<NUM> mmol) in the glovebox. On the bench <NUM>-chloro-<NUM>,<NUM>-dimethyl pyrazole (<NUM>. 0mmol), <NUM>-tetralone (<NUM> mmol) and dioxane (<NUM>) were added via needle. The vials were placed in a pre-heated aluminium block at <NUM> and stirred for <NUM> hours. After cooling to room temperature an aliquot was diluted in ethyl acetate and filtered for GC analysis.

A <NUM> vial equipped with a stir bar and polypropylene cap with PTFE-faced silicone septum was charged with catalyst and CsCOs (<NUM> mmol) in the glovebox. On the bench <NUM>-chloro-<NUM>,<NUM>-dimethylpyrazole (<NUM> mmol), <NUM>-decyne (<NUM> mmol) and acetontrile (<NUM>) were added via needle. The vials were placed in a pre-heated aluminium block at <NUM> and stirred for <NUM>. After cooling to room temperature an aliquot was diluted in ethyl acetate and filtered for GC analysis.

A <NUM> vial equipped with a stir bar and polypropylene cap with PTFE-faced silicone septum was charged with catalyst and K<NUM>PO<NUM> (<NUM> mmol) and <NUM>-thienylboronic acid (<NUM> mmol) in the glovebox. On the bench <NUM>-chloro-<NUM>,<NUM>-dimethylpyrazole (<NUM> mmol), THF (<NUM>) and water (<NUM>) were added via needle. The vials were placed in a pre-heated aluminium block at <NUM> and stirred for <NUM>. After cooling to room temperature an aliquot was diluted in ethyl acetate and filtered for GC analysis.

A <NUM> vial equipped with a stir bar and polypropylene cap with PTFE-faced silicone septum was charged with catalyst and NaOtBu (<NUM> mmol) in the glovebox. On the bench <NUM>-chloroanisole (<NUM> mmol), morpholine (<NUM> mmol) and THF (<NUM>) were added via needle. The vials were placed in a pre-heated aluminium block at <NUM> and stirred for <NUM>. After cooling to room temperature an aliquot was diluted in acetonitrile and filtered for GC analysis.

Claim 1:
A compound of formula (I)
<CHM>
wherein M is Pd(ll) or Ni(II);
X is a halide;
R<NUM> and R<NUM> are independently organic groups having <NUM>-<NUM> carbon atoms, or R<NUM> and R<NUM> are linked to form a ring structure with the phosphorus atom;
R<NUM> is an organic group having <NUM>-<NUM> carbon atoms;
provided that R<NUM>, R<NUM>, R<NUM> are not each phenyl.