WO2012017211A1

WO2012017211A1 - Carbene transfer agents

Info

Publication number: WO2012017211A1
Application number: PCT/GB2011/001176
Authority: WO
Inventors: Catherine Cazin
Original assignee: University Court Of The University Of St Andrews
Priority date: 2010-08-06
Filing date: 2011-08-05
Publication date: 2012-02-09
Also published as: GB201013257D0

Abstract

The use of copper (I) and copper (II) carbene complexes as carbene transfer agents is described. The methods can be used to transfer a carbene ligand from copper complexes to a target such as a metal centre.

Description

Carbene Transfer Agents

Field of the invention

The present invention relates to carbene transfer agents and provides methods for transferring a carbene ligand from copper complexes to a target such as a metal centre.

Background to the Invention Transition metal catalysed reactions represent powerful synthetic tools. Reactions permitting the creation of carbon-carbon bonds using palladium as a cross coupling catalyst are amongst the most important and have found numerous applications in the pharmaceutical industry and in the synthesis of natural products and liquid crystals. A more recent burgeoning area of transition metal mediated transformations has centered on the use of gold in catalysis (reference 1 ). In this context the use of numerous gold-phosphine and gold carbene, especially gold complexes with nitrogen containing heterocyclic carbene (NHC) ligands has proven very useful in the assembly of both simple and complex architectures (references 2 and 3).

Catalyst development and ultimate usefulness is often associated with the cost of their synthesis. The assembly of carbene containing complexes especially NHC-transition metal complexes can be problematic. The typical route for NHC-transition metal complexes is by generating the free NHC followed by its binding to a metal centre either in a ligand substitution reaction or in a dimer scission reaction (reference 4).

The direct NHC transfer from one metal centre to another, in one reaction, is another approach. As an example of this transmetallation technique, the silver-mediated reaction is the most practiced solution to NHC transfer (reference 5). In this manner, transmetallation can be achieved successfully to numerous metal targets (e.g. Cu(l), Cu(ll), Ni(ll), Pd(ll), Pt(ll), Au(l), lr(l), Ir(lll), Rh(l), Rh(lll), Ru(ll), Ru(lll), Ru(IV)) (reference 6). However, the NHC transfer from silver to palladium does not always proceed cleanly (reference 7). An alternative route, recently reported, makes use of a gold (l)-NHC complex as transfer agent to palladium (II) (reference 8) This reaction appears to be more effective with the addition of PPh₃.

Both the NHC transfer reactions from gold or silver come with some drawbacks: the transfer from silver (I) must be conducted in the dark and for the use of gold, the required use of PPh₃ requires an oxygen-free atmosphere. Moreover, the gold approach has obvious economic disadvantages. A more effective, practical and cost effective method would be highly desirable. A further alternative transmetallation technique has been described by Albrecht (reference 9). A small number of copper complexes of the general form [Cu(carbene)₂]X i.e. biscarbene copper complexes, having two carbene ligands bonded to the copper atom, were shown to be capable, in some cases, to transfer their carbene ligands to sulphur and in one example to a ruthenium (II) species is only described in respect of transfer to sulphur and of one particular relatively small carbene to ruthenium.

Description of the invention

The present invention provides the use of a copper (I) complex of general formula I or general formula II:

wherein A is a carbene ligand, A¹ is a polycarbene ligand, X is a ligand that may be the same or different for each occurrence and n is, independently for each occurrence, 0 or 1 ; or

a copper (II) complex of general formula III or general formula IV:

wherein A, A¹, X and n have the same meaning as before, Z is a non-coordinating ligand that may be the same or different for each occurrence and in formula IV m is an integer selected so that their are sufficient non-coordinating ligands Z to balance the charge provided by the copper ions;

as a carbene transfer agent.

The carbene copper complexes of formulas I to IV can transfer the carbene ligands A or A¹ efficiently to a number of substrates as described hereafter and with reference to specific embodiments. The copper complexes employed may be made by a simple synthetic route (with almost atom economy). The method is versatile and can be used with hindered (bulky) ligands, and can be used to make commercially valuable products. Each carbene function (electron pair) is co-ordinated to a different copper, allowing easier access to the copper to carbene bond than in the case where two carbene ligands are coordinated to the same copper.

Examples of suitable ligands X include halide or pseudohalide. Suitable ligands X include, hydroxy, halide, carboxylate, alkoxy (for example C1-C18 or even C1-C14 that may be substituted or unsubstituted), aryloxy, alkylsulfonate (for example C1-C18 or even C1-C14 that may be substituted or unsubstituted), acetate, trifluoroacetate, cyanide, thiocyanates, isothiocyanates, cyanates, isocyanates, azides and selenocyanates. For example X may be chloride, bromide or iodide.

The ligands X may be bridging ligands in some examples i.e. a group X may be shared between copper ions. For example the complex may take the form of formula V:

wherein Α,Χ,Ζ have the same meaning as before and m is selected so that there are sufficient non-coordinating ligands Z to balance the charge provided by the copper ions in the complex of formula V.

The non-coordinating ligands Z may be for example selected from the group consisting of tetrafluoroborate, hexafluorophosphate and hexafluoroantimonate.

The carbene ligand A may be cyclic, for example containing a ring of from 4 to 7 members, or acyclic. Cyclic or acyclic carbenes may have one or more heteroatoms. The heteroatom (or heteroatoms) may be the same or different and may be N ,Ο, B, P or S for example. The presence of such heteroatoms stabilises the carbene ligand.

The carbene ligand A may be, for example selected from the group consisting of imidazolidinylidene, imidazolylidene, triazolylidene, tetrazolylidene, thiazolylidene, oxazolylidene, pyrrolidinylidene, diarylcarbenes, acyclic diaminocarbenes, acyclic aminooxycarbenes, acyclic aminothiocarbenes, cyclic diborycarbenes, acyclic diborylcarbenes, phosphinosilylcarbenes, phosphinophosphoniocarbenes, sulfenyltrifluoromethylcarbenes, and sulfenylpentafluorothiocarbenes.

The polycarbene ligands A¹ of formula II may have two three or four carbene functions. For example two carbene functions i.e. n is 0.

For example the carbene ligand A or A¹ may be selected from the following group of mono carbenes (A in formulas I, III, V) or polycarbenes (A¹ in formula II or formula IV):

wherein each R and R¹ may be, independently for each occurrence, selected from: H, a primary, secondary or tertiary alkyl group (for example C1-C18 or even C1 - C14) that may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl (for example substituted or unsubstituted phenyl, naphthyl, or anthracenyl), substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, alkoxyl, aryloxyl sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and siloxy;

each E is a substituent that may coordinate to copper and may be, independently for each occurrence, a primary, secondary or tertiary alkyl group (for example C1-C18 or even C1 -C14) that may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl (for example substituted or unsubstituted phenyl, naphthyl, or anthracenyl), substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, aikoxyl, aryloxyl, sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and silyloxy

each L is a linker group that may be a covalent bond or an alkanediyl group (for example C1-C18 or even C1-C14) that may be substituted or unsubstituted, substituted or unsubstituted aryl (for example benzene), substituted or unsubstituted heterocycle (for example pyridyl);

represents an optional fused ring or rings, for example having from 4 to 7 carbons that may be saturated or unsaturated and may include heteroatoms such as

0, P, S or N; and

- - represents optional unsaturation.

The groups E, R and R¹ may be, independently for each occurrence unsaturated alkyl

1. e. alkenyl (for example C2-C18 or even C2-C14), that may be substituted or unsubstituted and may be cyclic.

The carbene A or A¹ may be a heterocyclic carbene ligand in particular a nitrogen containing heterocyclic carbene ligand (NHC). The NHC may have a five or six membered ring, typically a five membered ring. N-heterocyclic carbene ligands (NHC ligands) have been shown to provide good stabilising effects for reactive intermediates and their use in organometallic chemistry, catalysis and medicine is increasing.

The NHC employed in the complexes may be saturated or unsaturated and may contain one or more nitrogen atoms an optionally may contain other heteroatoms (such as B, O, P and S) in the ring.

For example the ligand may have the form

wherein the groups

R may be the same or different, the groups R¹ where present may be the same or different and the dashed line in the ring represents optional unsaturation. One or more of the carbon atoms in the ring (apart from the carbene carbon) may be substituted with O, B, P or S. Each R and R¹ may be, independently for each occurrence, selected from: H, a primary, secondary or tertiary alkyl group (for example C1-C18 or even C1 - C14) that may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl (for example substituted or unsubstituted phenyl, naphthyl, or anthracenyl), substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, alkoxyl, aryloxyl, sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and silyloxy.

The groups R and R¹ may be, independently for each occurrence unsaturated alkyl i.e. alkenyl (for example C2-C18 or even C2-C1 ), that may be substituted or unsubstituted and may be cyclic. Advantageously NHC ligands bearing two nitrogen atoms in the ring, each adjacent the carbene carbon may be employed. The NHC carbene ligands of this type may have the form:

wherein each of the groups R, R¹ R², R³and R⁴ may be the same or different and the dashed line in the ring represents optional unsaturation, wherein R¹ and R² are absent. Each R and R\ R², R³ and R⁴ may be, independently for each occurrence, selected from: H, a primary, secondary or tertiary alkyi group (for example C1 -C18 or even C1- C14) that may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl (for example substituted or unsubstituted phenyl, naphthyl, or anthracenyl), substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, alkoxyl, aryloxyl. sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and siloxy.

Advantageously the groups R³ and R⁴ may be substituted or unsubstituted aromatic rings that may be heterocyclic aromatic rings. Substituents R, R¹ R², R³ and R⁴ in the structures above may include alkyi and unsaturated alkyi groups, aryl groups that may be substituted and may contain heteroatoms.

Examples of some suitable compounds which bear one or two nitrogen atoms in the ring are disclosed in Wurtz and Glorius (Accounts of Chemical Research, vol41 , No.11 , 2008, p1523-1533), the contents of which are hereby incorporated by way of reference.

Suitable examples of NHC carbene ligands include those according to formulas A-F below:

primary, secondary or tertiary alkyl group (for example C1-C18 or even C1-C14) that may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl (for example substituted or unsubstituted phenyl, naphthyl, or anthracenyl), substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, alkoxyl, aryloxyl, sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and siloxy; R⁸, R⁹, R¹⁰ and R¹¹ are each independently for each occurence H, a substituted or unsubstituted alkyl group (for example C1 -C10 or even C1-C4), an halide, alkoxide, hydroxide, substituted or unsubstituted aryl, or in formulas (II) and (IV) together with the carbons carrying them form a substituted or unsubstituted, fused 4-8 membered carbocylic ring or a substituted or unsubstituted, fused aromatic ring, preferably a fused phenyl ring; and R¹² is alkyl (for example C1-C18 or even C1-C14) or a cycloalkyl (for example C3 - C12). For the avoidance of doubt where two R⁵ groups, for example, may be present, such groups may be different.

For example these NHC carbenes:

are suitable examples of the NHC carbene family for the formation of the complexes, the alkyl substituted aromatic rings providing additional stabilisation to the carbene lone pair of electrons.

The copper complexes may be formed by any suitable route such as are known in the art. Methods for manufacture include:

1 ) Reaction of the free carbene with the metal salt. 2) When A is an NHC carbene or A¹ includes NHC carbenes, reaction of the corresponding salt in the presence of a base and a copper salt. For example reaction of an imidazolium salt of the form;

where the groups R, R¹ R², R³and R⁴ may be the same as described above, with a base and a copper salt.

In both cases, an inert atmosphere is usually required. The bases used are usually costly (NaOtBu, KOtBu, NaH) and purification is required to remove excess base, base residues, inorganic salts, etc.

3) Where A is an NHC carbene, a carbene transfer reaction from a silver-NHC complex may be used (ie a silver complex based transmetallation route). This relatively expensive and reactions must be run in the absence of light.

4) However a convenient route is available for the copper complexes used in the methods of the present invention.

Complexes of the form A-Cu-X may be made from reaction of copper oxide (Cu₂0) with a salt A⁺ X^", which acts as a carbene precursor. Such methods are described in respect of NHC copper complexes in, for example a) J. Chun, H. S. Lee, I. G. Jung, S. W. Lee, H. J. Kim and S. U. Son, Organometallics 2010, 29, 1518; and b) C. A. Citadelle, E. Le Nouy, F. Bisaro, A. M. Z. Slawin, C. S. J. Cazin, Dalton Trans. 2010, 39, 4489-4491. (reference 10)

An example of the convenient method is illustrated in Scheme 1 below where the dashed line indicates optional unsaturation in the ring and the groups R, R¹, R², R³ and R⁴ may be, for each occurrence, the same or different and any of a wide range of substituents for example those discussed above in respect of the structure:

Examples of NHC copper complexes that may be made for use in the method thus include those shown in Scheme 2 below.

The chloride may be replaced by other groups X. For example Br or I. For example alkoxy or aryloxy, or those others discussed above. The transfer of the carbene from the copper complexes has been shown to operate successfully with a wide range of targets. Transfer to metal (transmetallation) can occur readily and with high yields. For example transfer of a carbene to a metal centre selected from the group consisting of Cu, Ni, Pd, Pt, Al, Ag, Au, Ir, Rh, Ru, and Sn may be accomplished. Metals in different oxidation states may have carbenes attached by the method, for example Cu(l), Cu(ll), Ni(ll), Pd(0), Pd(ll), Pt(0), Pt(ll), Pt(IV), Al(l) Al (III), Ag(l), Au(l), Au(lll), lr(l), Ir(lll), Rh(l), Rh(lll), Ru(0), Ru(ll), Ru(lll), Ru(IV),Sn(ll) and Sn(IV). Other suitable targets include sulphur and other metals including the lanthanides and actinides.

The transfer of the carbene may be carried out in any suitable solvent. Conveniently where X is a halide such as chloride, the reaction may be carried out in a solvent in which the by-product copper chloride is insoluble and the product is soluble. Chlorinated solvents such as dichloromethane, toluene and water may be employed in this fashion as described hereafter with reference to specific embodiments. Examples of carbene transfer to metal are given in Scheme 3 below, where NHC is an nitrogen containing heterocyclic carbene ligand.

In some circumstances the carbene transfer is accompanied by further reaction. For example transmetaliation to a Pd(ll) centre can be accompanied by dimerisation as illustrated below in Scheme 4. Dimeric palladium complexes of the type 2 where the dashed lines indicate optional unsaturation are commercially useful catalysts

Gold or ruthenium complexes may be made in similar fashion as illustrated in schemes 5 and 6 below. The Ru complex 4 is a highly active catalyst for metathesis reactions, and is currently produced on an industrial scale.

Scheme 6

Thus it can be seen from the foregoing examples that the method of carbene transfer making use of complexes of the form A-Cu-X can be used to successfully transfer carbenes such as NHC carbenes to a target, even where the carbene includes (relatively) bulky aromatic substituents. Even carbenes carrying substituted aromatic substituents, such as the alkyl substituted benzene rings of the examples in schemes 4 to 6 above, can be transferred, often in good yields.

Where a complex of formula II is employed the reaction may produce a complex with more than one carbene function of the ligand A¹ bonded to the same target, for example a metal. This is illustrated in scheme 7 below where Lig_n represents a target complex of a metal M with ligands Lig where, in this example, n is 2 or more and n' is a lower number following replacement of one or more ligands Lig by the carbene ligand. Th ligand of type A¹ is a bis nitrogen-containing heterocyclic carbene:

with two NHC rings linked by an alkylidene bridge, methylene (-CH₂-) in this example.

Scheme 7

Alternatively each carbene function may be transferred to a separate metal as illustrated below for product complexes 5, 6 and 7, where in product 6 M' represents a different metal to that labelled M. Thus poly-hetero-metallic as well as poly-homo- metallic complexes may be prepared from a corresponding copper complex by using more than one metal target. These might be obtained in one-pot or in two steps, going through the intermediate complex 7.

Thus it can be seen that each carbene function of a polycarbene (A¹) may be transferred sequentially from copper to a substrate or substrates.

Description of Some Preferred Embodiments and Experimental Results

Reaction of the copper chloride NHC complexes of Scheme 2 with gold(l) and palladium (II)

Transmetallation reactions from copper(l) to gold(l) and palladium(ll) were performed in dichloromethane (DCM). Solubility properties of the starting materials and products dictated this choice of solvent. The insolubility of CuCI in DCM makes this the solvent of choice for these reactions but other solvents may be employed. The CuCI produced can be removed by simple filtration and its precipitation may drive the reaction forwards

Indeed when reactions are conducted in this manner, a precipitate is rapidly formed (CuCI) after only a few minutes. Reaction of 1a and 1 b with either [AuCI(DMS)] (DMS: SMe₂) or [PdCI₂(C₆H₅CN)] for only 1 hour lead to NHC transfer to gold and palladium, respectively in high yields (Tables 1 and 2). For 1c two hours were required.

During the progress of the gold reaction a grey colouration appeared (from the initially colourless solution). For the palladium reactions, the colour progressed from orange to brown. A similar colour evolution was expected for 1c, however, in both cases reaction mixtures adopted a dark colour after a few minutes. A black precipitate was observed and removed upon workup.

The method affords the expected complexes in good to excellent isolated yields. Experimental conditions and isolated yields for gold (Table 1 ) and palladium (Table 2) are presented below.

Synthesis of nitrogen-containing heterocyclic carbene ligand (NHC) gold (I) complexes The general reaction scheme for these examples is shown below where substituents Ar are as required for the complexes 1a, 1 b and 1c as shown in Scheme 2 above and the dashed line indicates unsaturation, where present (1a and 1c).

Table 1. Reactions leading to [AuCI(NHC)] complexes

Synthesis of nitrogen-containing heterocyclic carbene ligand (NHC) palladium(ll) complexes

The general reaction scheme for these examples is shown below where substituents Ar are as required for the complexes 1a, 1 b and 1c as shown in Scheme 2 above and the dashed line indicates unsaturation, where present (1a and 1c). The product formed is the dimeric Pd species as shown.

Table 2. Reactions leading to [Pd( -CI)CI(NHC)]₂ complexes

Reaction occurs in one or two hours, depending of the NHC copper(l) complex, which is equivalent to the typical reaction time necessary when silver(l) congeners are used as carbene transfer agents. One significant difference is the need for slight heating of the reactions with copper. The method was less successful with 1d (Scheme 2) for both gold and palladium where the desired reaction occurred but a clean transfer of the carbene was not achieved. This may be due to the increased steric hindrance found in the saturated analogues of such carbene complexes in comparison with the unsaturated analogues. In the case of 1d rapid formation of metallic precipitates at both room temperature and at 0°C were observed. The very bulky nature of the SIPr ligand may be a cause of the problem for these particular reactions.

Other transfers to metal centres

Transfers of N-Heterocyclic type carbenes to other metal centres as indicated in scheme 3 above were examined by the following general protocol.

A vial was charged with the metal salt (0.025 to 0.05 mmol), NHC-Cu-CI (0.0125 to 0.05 mmol) and solvent. The reaction mixture was heated at reflux for 24h. The solution was filtrated through a pad of celite. The solution was concentrated, pentane was added to precipitate the product which was collected by filtration and examined by spectroscopy (NMR) to confirm successful transfer of the NHC. The examples shown in scheme 3 illustrate the versatility of the method.

References

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3. a) E. Jimenez-NCinez and A. M. Echavarren, Chem. Rev., 2008, 108, 3326; b) A. S. K. Hashmi Chem. Rev. 2007, 107, 3180. 4. a) D. S. McGuiness and K. J. Cavell, Organometallics 2000, 19, 741 ;

b) M. Froseth, A. Dhindsa, H. Roise and M. Tilset, Dalton Trans., 2003, 4516.

5. a) S. T. Liddle, I. S. Edworthy and P. L. Arnold, Chem. Soc. Rev., 2007, 36,

1732;

b) H. M. J. Wang and I. J. B. Lin, Organometallics 1998, 17, 972.

6. a) I. J. B. Lin and C. S. Vasam, Coord. Chem. Rev. 2007, 251 , 64;

b) J. C. Garrison and W. J. Youngs, Chem. Rev. 2005, 105, 3978. 7. a) W. A. Hermann, S. K. Schneider, K. Ofele, M. Sakamoto and E. Herdtweck, J. Organomet. Chem. 2004, 689, 2441 ;

b) S. Roland, M. Audoin and P. Mangeney, Organometallics 2004, 23, 3075.

8. S. T. Liu, C. I. Lee, C. F. Fu, C. H. Chen, Y. H. Liu, C. J. Elsevier, S. M. Peng and J. T. Chen, Organometallics 2009, 28, 6957.

9. G. Venkatachalam, M. Heckenroth, A. Neels and M. Albrecht, Helvetica Chimica Acta, 2009, 92, 1034-1045. 10. a) J. Chun, H. S. Lee, I. G. Jung, S. W. Lee, H. J. Kim and S. U. Son, Organometallics 2010, 29, 1518;

b) C. A. Citadelle, E. Le Nouy, F. Bisaro, A. M. Z. Slawin, C. S. J. Cazin, Dalton Trans. 2010, 39, 4489-4491.

Claims

CLAIMS:

1. The use of a copper (I) complex of general formula I or general formula II

copper (II) com ex of general formula III or general formula IV:

wherein A, A¹, X and n have the same meaning as before, Z is a non-coordinating ligand that may be the same or different for each occurrence and in formula IV m is an integer selected so that their are sufficient non-coordinating ligands Z to balance the charge provided by the copper ions; or

a copper complex according to general formula V:

wherein Α,Χ,Ζ have the same meaning as before and m is selected so that there are sufficient non-coordinating ligands Z to balance the charge provided by the copper ions in the complex of formula V:

as a carbene transfer agent; wherein a carbene ligand A or at least one carbene function of a polycarbene ligand A¹ is transferred to a substrate.

2. The use of a copper complex as a carbene transfer agent according to claim 1 ligands X are halide or pseudohalide.

3. The use of a copper complex as a carbene transfer agent according to claim 1 ligands X are selected from the group consisting of hydroxy, halide, carboxylate, alkoxy, aryloxy, alkylsulfonate, acetate, trifluoroacetate, cyanide, thiocyanates, isothiocyanates, cyanates, isocyanates, azides and selenocyanates.

4. The use of a copper complex as a carbene transfer agent according any one of claims 1 to 3 wherein the non-coordinating ligands 2, where present, are selected from the group consisting of tetrafluoroborate, hexafluorophosphate and hexafluoroantimonate.

5. The use of a copper complex as a carbene transfer agent according any one of claims 1 to 4 wherein the complex contains a carbene ligand A selected from the group consisting of imidazolidinylidene, imidazolylidene, triazolylidene, tetrazolylidene, thiazolylidene, oxazolylidene, pyrrolidinylidene, diarylcarbenes, acyclic diaminocarbenes, acyclic aminooxycarbenes, acyclic aminothiocarbenes, cyclic diborycarbenes, acyclic diborylcarbenes, phosphinosilylcarbenes, phosphinophosphoniocarbenes, sulfenyltrifluoromethylcarbenes, and sulfenylpentafluorothiocarbenes.

6. The use of a copper complex as a carbene transfer agent according any one of claims 1 to 5 wherein the carbene ligands A or A¹, where present, are independently selected from:

 wherein each R and R¹ may be, independently for each occurrence, selected from: H, a primary, secondary or tertiary alkyl group (for example C1-C18 or even C1- C14) that may be unsaturated and may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl (for example substituted or unsubstituted phenyl, naphthyl, or anthracenyl), substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, alkoxyl, aryloxyl, sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and siloxy;

each E is a substituent that may coordinate to copper and may be, independently for each occurrence, a primary, secondary or tertiary alkyl group (for example C1-C18 or even C1-C14), that may be unsaturated and may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl, substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, aryloxyl, alkoxyl, sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and silyloxy

each L is a linker group that may be a covalent bond or an alkanediyl group (for example C1 -C18 or even C1 -C14) that may be substituted or unsubstituted, substituted or unsubstituted aryl (for example benzene), substituted or unsubstituted heterocycle (for example pyridyl)

represents an optional fused ring, for example having from 4 to 7 carbons that may be saturated or unsaturated and may include heteroatoms such as O, P, S or N; and

- - represents optional unsaturation.

7. The use of a copper complex as a carbene transfer agent according any one of claims 1 to 6 wherein the carbene ligands A or A¹, where present, are nitrogen containing heterocyclic carbene ligands, in particular having a five or six membered ring.

8. The use of a copper complex as a carbene transfer agent according claim 7 wherein the nitrogen containing heterocyclic carbene ligands have the form

wherein the groups R may be the same or different, the groups

R where present may be the same or different and the dashed line in the ring represents optional unsaturation;

wherein each R and R¹ is independently for each occurrence, selected from: H, a primary, secondary or tertiary alky! group (for example C1-C18 or even C1-C14) that may be unsaturated and may be may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl (for example substituted or unsubstituted phenyl, naphthyl, or anthracenyl), substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, alkoxyl, aryloxyl, sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and silyloxy; and

wherein one or more of the carbon atoms in the ring apart from the carbene carbon may be substituted with B, 0, P or S.

9. The use of a copper complex as a carbene transfer agent according claim 8 wherein the nitro en containing heterocyclic carbene ligands have the form:

wherein each of the groups R, R¹ R², R³ and R⁴ may be the same or different and the dashed line in the ring represents optional unsaturation, when R and R² are absent;

wherein R and R , R², R³ and R⁴ are, independently for each occurrence, selected from: H, a primary, secondary or tertiary alkyl group (for example C1-C18 or even C1-C14) that may be unsaturated and may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl (for example substituted or unsubstituted phenyl, naphthyl, or anthracenyl), substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, alkoxyl, aryloxyl, sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and siloxy.

10. The use of a copper complex as a carbene transfer agent according claim 9 wherein the nitrogen containing heterocyclic carbene ligands are selected from the group consisting of:

wherein each group R⁵, R⁶ and R⁷, is independently for each occurrence selected from: H, a primary, secondary or tertiary alkyl group (for example C1-C18 or even C1-C14) that may be substituted or unsubstituted and may be cyclic, substituted or unsubstituted aryl (for example substituted or unsubstituted phenyl, naphthyl, or anthracenyl), substituted or unsubstituted heterocycle, for example pyridine, or a functional group selected from the group consisting of halo, hydroxyl, aikoxyl, aryloxyl, sulfhydryl, cyano, cyanato, thiocyanato, amino, nitro, nitroso, sulfo, sulfonato, boryl, borono, phosphono, phosphonato, phosphinato, phospho, phosphino, and siloxy; and wherein R⁸, R⁹, R ⁰ and R¹¹ are each independently for each occurence H, a substituted or unsubstituted alkyl group (for example C1-C18 or even C1 -C14), substituted or unsubstituted aryl, an halide, alkoxide, hydroxide; or in formulas (B) and (D), together with the carbons carrying them, form a substituted or unsubstituted, fused 4-8 membered carbocylic ring or a substituted or unsubstituted, fused aromatic ring, preferably a fused phenyl ring; and

R¹² is alkyl (for example C1-C18 or even C1 -C1 ) or a cycloalkyl (for example C3 - C12).

11. The use of a copper complex as a carbene transfer agent according claim 10 wherein the nitrogen containing heterocyclic carbene ligands are selected from the group consisting of:

12. The use of a copper complex as a carbene transfer agent according to claim 10 wherein the copper complex is selected from the group consisting of:

wherein X is selected from the group consisting of CI, I, Br, hydroxy, alkoxy and aryloxy.

13. The use of a copper complex as a carbene transfer agent according to any preceding claim wherein: where present, a carbene A is transferred to a metal centre; or

where present, at least one carbene function of a polycarbene A¹ is transferred to a metal centre.

14. The use of a copper complex as a carbene transfer agent according to claim 13 wherein the metal centre is selected from the group consisting of Cu, Ni, Pd, Pt, Al, Ag, Au, Ir, Rh, Ru, Sn, lanthanides and actinides.

15. The use of a copper complex as a carbene transfer agent according to claim 14 wherein the metal centre is selected from the group consisting of Pt(ll), Ir(lll), Ni(ll), Al(lll), Ag(l), Sn(ll), Pd(ll), Au(l), Ru(ll).

16. The use of a copper complex as a carbene transfer agent according to any one of claims 1 to 12 wherein: where present, a carbene A is transferred to sulphur; or where present, at least one carbene function of a polycarbene A¹ is transferred to sulphur.