Synthetic and structural studies of copper, gold and palladium heterocyclic carbene complexes

and π ligands.48,49 Another key focus is on the application of copper and gold NHC complexes in catalysis and medicine.50 Recent developments in the chemistry of copper and gold NHC comp

Chapter 1 Introduction

1 General Properties of N-Heterocyclic Carbenes (NHCs)

N-heterocyclic carbenes (NHCs) have attracted significant interest over the

past decade as versatile and prolific ligands in catalysis, triggered mainly by the starting use of NHC complexes in catalysis by Herrmann and co-workers,1 and the preparation of Grubbs‘ second-generation and related catalysts.2-5

Back in 1993, transition metal heterocarbenes were believed to exhibit bonding properties similar to those of trialkylphosphines and alkylphosphinates.6 Six years later, Nolan et al reported that, based on

structural and thermochemical studies, NHCs, with the exception of the sterically demanding (adamantyl) carbene, generally behave as better donors than the best phosphines donor ligands.7 In numerous instances, simple substitution reaction routes involving replacement of phosphines by NHC ligands improved not only the catalytic activity but also thermal stability of the resulting organometallic complexes This is presumably due to the more powerful σ-donating ability of NHCs than the closely related phosphine ligands, forming stronger bonds to transition metals and thereby also leading

to electron-rich metal centers.8-11 As phosphine mimics, NHCs avoid the drawbacks of phosphine ligands such as air sensitivity, high toxicity and thermal instability In addition, it is relatively easy to modify the structural and electronic components of the NHC manifold to bring a range of desirable traits

to the NHC-stabilized compounds

As a result of the rapid and extensive development in NHCs work, many

review articles on NHCs have been published,12-18 and NHCs continue to be a hot research topic in organometallics, as evident from over 100 NHC-related

publications appearing in JACS alone in the two-year period of 2008-2009.19

However, most of these studies were focused on Pd-, Ni-, Ru- and Rh-NHC complexes NHC complexes of copper and gold have been relatively overlooked in spite of the wide use of copper and gold in catalysis, medicine etc.20-31

Preparations of copper and gold NHC complexes have been reported for decades.15 For example, Arduengo and co-worker isolated the first copper carbene complex in 1993.32 Study of gold NHC complexes started even earlier

In 1974, Lappert‘s group reported the generation of ionic complexes [Au(NHC)2]X (X = anion) from electron-rich olefins.33 In the same year, Fehlhammer‘s group also claimed the formation of Au(I)- and Au(III)-NHC complexes through the spontaneous cyclization of isocyanide ligands.34 In

1989, Au(I)-NHC complexes were isolated by Burini et al through the

reaction of AuCl(PPh3) with lithiated benzylimidazoles, followed by protonation.35 However, copper and gold NHC complexes did not attract significant research interest in the past

With fruitful advancement in the study of transition-metal NHC complexes, the value of copper and gold NHC complexes is being increasingly appreciated by current researchers.17,36-47 The research interest centers on the structural and bonding curiosities of σ-dominant carbene moiety on the electron-rich and soft late-metals that usually require an intricate balance of σ

and π ligands.48,49

Another key focus is on the application of copper and gold NHC complexes in catalysis and medicine.50 Recent developments in the chemistry of copper and gold NHC complexes are summarized herein.17,36-43

1.1 Copper(I) N-Heterocyclic Carbene Complexes

1.1.1 General Synthetic Methods for Cu(I)-NHC Complexes

Four methods are usually applied in the synthesis of Cu(I)-NHC complexes15

(Scheme 1.1): (1) Reaction of free carbenes with suitable copper sources.51 In this method, imidazolium salts are deprotonated by a strong base e.g NaOtBu,

KOtBu, or KH to produce free NHC ligands which are further used to react with copper sources e.g Cu(I) halide to obtain Cu(I)-NHC complexes in dry THF or acetonitrile (2) Transmetalation from relevant NHC complexes.52 In this method, Ag(I)-NHCs are often used as carbene transfer-agents to prepare Cu(I)-NHC complexes because the Cu-NHC bond is stronger than the Ag-NHC bond.53 (3) Alkylation of azolylcuprates.54 In this method, Cu(I)-NHC complexes are obtained from alkylation of thiazolyl or imidazolyl-cuprates complexes formed from the reaction of Cu(I) sources with lithiated azoles (4) Direct reaction of imidazolium salts with copper base.55,56

In this method, reactions of imidazolium halide with Cu2O or CuOAc or copper powder give Cu(I)-NHC complexes The acidity of the imidazolium moiety determines the ease of deprotonation of the C-proton by copper base

Scheme 1.1 Preparation methods for Cu(I)-NHC complexes

According to the survey of Lin et al., over 60% of Cu(I)-NHC complexes in

the literature were synthesized from free carbenes and only 22% of Cu(I)-NHC complexes were synthesized by the Ag-carbene transfer route.15

Although there are few reports comparing these two methods, Meyer et al

observed that the Ag-carbene transfer route could give a higher yield than the free carbene method.57 The third and fourth methods for the preparation of Cu(I)-NHC complexes are rarely used

1.1.2 Structure and Reactivity of Cu(I)-NHC Complexes

There are generally three types of copper NHC complexes: monocarbene [(NHC)CuX] and [(NHC)CuL]X, dicarbene [(NHC)2Cu]X (X = anion) and di-, tri- and multinuclear copper(I) NHC complexes

1.1.2.1 Monocarbene Cu(I)-NHC Complexes [(NHC)CuX] and [(NHC)CuL]X

For [(NHC)CuX]-type complexes, X can be a halide or other coordinating anion Among them, [(NHC)CuX] (X = halide) complexes are most important Nolan and co-workers prepared a series of [(NHC)CuX] (X = halide)

complexes through the free carbene method (examples are given in Fig 1.1)

with either unsaturated or saturated NHCs.58 Further studies indicated that [(NHC)CuX] (X = halide) complexes function not only as catalysts or catalyst precursors but also as starting materials for synthesis of [(NHC)CuX] (X ≠ halide) or cationic [(NHC)Cu(L)]+ species

Fig 1.1 Structures of [(NHC)CuCl] complexes

For example, [(NHC)Cu(OtBu)] complexes (I-8), which can be obtained from the reaction of [(NHC)CuCl] (I-7) with NaOtBu59, are known to be the active species in many transformations to yield [(NHC)CuX] (X ≠ halide) or cationic [(NHC)Cu(L)]+ species, as outlined in Scheme 1.2 Subsequent reaction of complexes I-8 with triethoxysilane in the presence of excess 3-hexyne yielded [(NHC)Cu(vinyl)] complexes (I-9) as the first hydrocupration product.59,60Complexes I-8 also react with triethoxysilane to form hydride copper NHCs (I-10) which are powerful catalysts for the hydrosilylation of ketones.61

[(NHC)CuOtBu]

[(NHC)Cu(CF3)]

Cu NHC

Cu NHC

Cu NHC

B

O O Cu

Ph

B(pin)

B(pin)

Cu Mes O

B(pin) Cu

[(NHC)CuMe]

([NHC)CuOAc]

AlMe 3

= B O

O

pin = pinacolate = 2,3-dimethyl-2,3-butanediolate

CO2

(EtO) 3 SiH

Ph

Ph O

O

CF3Si

Me3

(EtO) 3 SiH 3-hexyne

Mes HO B(pin) H

Mes H O

I-7

I-8 I-10

I-9

I-11

I-12 I-13

(NHC)Cu 2

NHC

Scheme 1.2 Reactions of [(NHC)CuOtBu] complexes

Complex I-11, obtained from the reaction of the Cu(I)-NHC complexes with

dibenzoylmethanoate (α,β-diketonate), is an efficient catalyst for the

three-component coupling of electrophilic alkenes, aldehydes and silane.62

Complex I-12, [(NHC)CuX] (X = cyclopentadienyl), could be prepared by

reacting a [CuCl(NHC)] or [(NHC)Cu(OtBu)]-type species with cyclopentadienyl lithium.63 X-ray structures show an η5-type bonding mode

for the cyclopentadienyl ligand in I-12 Although saturated NHC complex

[(SIPr)Cu(OtBu)] (SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-

2-ylidene) showed high catalytic activity in fluorination reaction, its

1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) recorded low activity

Through the study of complex I-13, Vicic et al found out the possible reason

was side reactions occurring on the unsaturated NHC ring backbone.64 The

carbene boryl copper complexes I-14 were formed from the reaction of I-8

with B(pin)2 (pin = pinacolate = 2,3-dimethyl-2,3-butandiolate) I-14 can

promote the reduction of CO2 to CO effectively through the formation of

I-1565 as well as activate the diboration of alkenes to form complexes I-16.66

Furthermore, it can serve as the intermediate for the catalysis of hydroboration

of aryl-substituted alkenes promoted by the corresponding copper NHC

complexes Compound I-17 was formed through the insertion of alkene to the Cu-boron bond and it can convert to complex I-18 through hydrogen

elimination and re-insertion.67,68 The mononuclear copper(I) alkyl complex

I-19, [(IPr)Cu(Me)], was obtained from the reaction of I-20 with AlMe3 and it

was reported to react with substrates possessing N-H, O-H, and acidic C-H bonds to form neutral type complexes [(IPr)Cu(X)] (X = anilido, phenoxide, ethoxide, phenylacetylide, or N-pyrrolyl).69 Such transformations could be integral to the development of catalytic cycles when metal-mediated bond-forming reactions are accessible with these and related copper systems The results also indicated that the acidity of the X-H bond could be a key factor, albeit not likely the sole factor, for kinetic accessibility to these

reactions Based on these results, Gunnoe et al predicted that inert bonds eg

arenes and alkanes might be activated by more electrophilic copper NHC

complexes In subsequent studies, Gunnoe et al claimed that Cu(I) NHC

anilido complexes were more active than Ru(II) anilido complexes in the traditional SN2 transformation of bromoethane.70 In addition, complex I-19 could react with α-borobenzyl alcohol to from complex I-16

To improve the stability and catalytic selectivity of copper NHC complexes, a series of mixed donor carbene complexes were studied Examples are given in

Fig 1.2 Compound I-21 was prepared by the treatment of a

pyridyl-functionalized imidazolium salt with Cu2O and crystallized as a monomer with the copper center taking up a T-shaped geometry.55 The Cu-C and Cu-N distances are 1.880(6) and 2.454(5) Å respectively Unlike carbonyl

or phosphine ligands, NHCs were initially known to be non-bridging ligands This misconception was shattered when the dinuclear copper complex [Cu2I2(PCP)] (PCP = (SP-4)-[-1,3-Bis[(R)-1- ((S)-2-diphenylphosphino-P-fer-

rocenyl)ethyl]imidazol-2-ylidene]) (I-22) emerged.56 Complex I-22, with a

tridentate PCP ligand based on a ferrocene scaffold, was prepared via the free carbene method with 92% yield while an alternative method involving the direct reaction of CuOAc with the imidazolium salt [PCPH]I achieved only 54% yield

Fig 1.2 Structures of copper NHC complexes with donor side-arm(s)

With μ-X (X = H, O, Cl, I), it is easy to form copper monocarbene dinuclear

compounds in solid state (Fig 1.3) For example, the first N,S-heterocyclic

carbene (NSHC) copper complex I-23 was prepared via the alkylation method

in 1994.71 (Scheme 1.3) The X-ray structure of I-23 indicates that the copper

atom bonds to the carbene carbon of the thiazolylidene ligand and the two bridging chloride atoms in trigonal planar state

Scheme 1.3 Preparation of copper(I)-NSHC complexes

Fig 1.3 Structures of copper NHC complexes with μ-X (X = H, O or I)

As shown in Scheme 1.2, the hydride bridged complex I-10 was obtained by

the reaction of [Cu(NHC)(OtBu)] with triethoxysilane.59 The hydride species

are powerful catalysts for the hydrosilylation of ketones and the conjugate

reduction of α,β-unsaturated cyclic enone and ester.61,72 In practical use, the hydride can be prepared by one-pot reaction of [CuX(NHC)]-type (X = halide)

complexes with NaO tBu or KOtBu in the presence of silane.60 NHC ligands were found to stabilize the Cu(I)-hydride species in lower nuclearity compared

with the phosphine ligands Complex I-24, with two bridging OtBu groups, was prepared by the same procedure as that for the mononuclear compound

I-9.64 (Scheme 1.2) The sterical bulk of N-substituents in [Cu(O tBu)(NHC)] complex determines the dinuclear or mononuclear formation Dinuclear

complexes I-25 and I-26 were all prepared via the free carbene route.73,74 In

complex I-25, the Cu2I2 core is bridged by a dicarbene ligand with short

Cu Cu (2.663(1) Å) distance and the average Cu-Ccarbene bond length is 1.923

Å The structure of I-26 consisting of a Cu3I3 core coordinated by three NHCs, could be viewed as an adduct of [Cu(NHC)I] and a dinuclear [Cu(NHC)I]2molecule, resulting in weak copper-copper interactions (Cu…Cu 2.635 and 2.658 Å respectively)

1.1.2.2 Dicarbene Cu(I)-NHC Complexes [Cu(NHC)2]X

Fig 1.4 describes some examples for dicarbene copper complexes For

azolium salts or copper sources with weak coordinating anions such as BF4- or

PF6-, the free carbene method usually yields cationic [Cu(NHC)2]+ species, instead of neutral [CuX(NHC)] complexes The first reported dicarbene

copper complex (I-27a) was prepared via the free carbene route.32 After that, a series of [Cu(NHC)2]+ species I-27b-d, containing both saturated and

unsaturated NHCs, were subsequently synthesized.75,76 In order to avoid the

steric congestion resulting from the linear arrangement of two NHC ligands on the copper center, large torsion angle between the two NHCs or long Cu-NHC bond distance were usually found in these complexes.15 For example,

compounds I-27b-c have large torsion angles (80°-85°) A long Cu-Ccarbene

bonddistance was found in complex I-27d (2.000 Å) More recently, the

analogue of I-27 with asymmetric N,N’-substituents was reported by Albrech

et al.77 Compound I-28 with a six-membered NHC ring was obtained by the

free carbene route.78 The distance between the Mes (Mes = 2,4,6-trimethylphenyl) group and the Cu(I) center in the six-membered ring is significantly shorter than that in five-membered rings, leading to a long Cu-Ccarbene bond of 1.934(2) Å and a large torsion angle (80.91°) between the

NHC rings Compound I-29 with a chelating ligand was synthesized by the

Ag-carbene transfer route.79 The Cu center was coordinated to two NHC rings

twisted at ca 53.4° Compound I-30 contains NHCs with a chelating pyridinyl

substituent on N The carbene ligands remain in a pseudo-trans arrangement

(C-Cu-C 168.5(2)o) with weak Cu-Npy coordination bond (2.310(4) and 2.439(4) Å) A strong deviation of the N-atoms from an ideal 90o angle with respect to the C-Cu-C axis (77.7(2)o and 110.4 (2)o respectively) leads to a disphenoidal geometry.77

Fig 1.4 Structures of dicarbene [(NHC)2Cu]+ species

1.1.2.3 Di-, Tri- and Multinuclear Cu(I)-NHC Complexes

Fig 1.5 shows both dinuclear and trinuclear copper NHC complexes The homoleptic crown complex I-31 was the first reported copper(I) halide

complexes with di(NHC) ligands and it was prepared via the Cu2O route.80X-ray structural study indicates the two Cu(NHC)2 moieties are associated with a Cu…Cu contact of 2.553(2) Ǻ Trinuclear compound I-32 can be

synthesized by both the free carbene route and the Ag-carbene transfer route, with the latter method giving a better yield (27% vs 56%).57 X-ray study indicates that there are three linear NHC-Cu-NHC units and a 3-fold axis passing through the central carbon atom anchoring three NHC ligands to

exhibit a D 3-symmetry in the solid state Compound I-33 was prepared via

Ag-carbene transfer route and each of the copper atom is linearly coordinated with two carbene centers.81 DFT calculation revealed the existence of both σ and π type interactions between the copper atom and the carbenoid carbon

I-31 I-32 I-33

Fig 1.5 Structures of multinuclear Cu(I)-NHC complexes

Complex I-34 was prepared via Ag-carbene transfer with commercially

available copper powder by Chen‘s group recently.82 (Scheme 1.4) Direct

reaction of bis(pyrimidylimidazoliumyl)methane dihexafluorophosphate (H2L2(PF6)2) with one equivalent of copper powder in acetonitrile yielded a

dinuclear copper complex (I-35) as dark green crystals In the presence of excess copper powder, the green solution of I-35 turns red to form I-34 On the other hand, I-34 also can be oxidized in air to I-35 reversibly X-ray structure establishes that the middle copper atom in compound I-34 is linearly

bound to two NHC carbon atoms with a C-Cu-C angle of 171.7(2)o and the two imidazolylidene rings are twisted by 88.62o relative to each other The two terminal copper atoms lie in triangular geometry connecting with a carbenoid carbon atom and a pyridine ring of the same ligand as well as an acetonitrile molecule The four Cu-Ccarbene bonds fall in the range of 1.902(5)–1.935(4) Ǻ and the distance of Cu Cu is 2.852(1) Ǻ in I-34 However, the Cu…Cu

distance shortens to 2.587 Ǻ in I-35 reflecting the formation of a covalent

Cu-Cu bond (the sum of covalent radii of two copper atoms is 2.64 Ǻ) Cu-Ccarbene bond lengths in complex I-35 are 1.920(8) and 1.932(9) Ǻ

respectively, which is consistent with those of other reported copper carbene complexes.83 The two imidazolylidene rings coordinated to the middle copper

atom are twisted by 79.64o relative to each other

Scheme 1.4 Preparation of compound I-34

Copper complexes of oligo- or polycarbene ligands are rare Several examples

are given in Fig 1.6 Gade and co-workers studied copper(I) complexes

containing NHC with oxazolinyl side arm (I-36a-b) and found that they are

monomeric in solution but aggregate in the solid state.84 The structure was

effected by substituents (R1 and R2) on the oxazolinyl moiety: a dimeric

structure for [{{2-(4,4-dimethyl)-oxazolinyl-(N-mesityl)imidazoylidene}}-

(bromo)copper(I)]2 (I-36a) and a coordination polymer with infinite chains for

the chiral derivative [{2-(4-S-isopropyl)-oxazolinyl-(N-mesityl)imidazolylide-

ne}(bromo)copper(I)] (I-36b) The structure of I-37 was found to be

remarkably affected by its solvent, forming a polymer in CDCl3, but a dimer

in a mixture of dichloromethane/ether This is possibly due to its low

solubility in the latter solvent system.55 The structure of I-38 is similar to that

of I-36b.85

Fig 1 6 Structures of polymeric Cu(I)-NHC complexes

Complex I-39 was prepared through free carbene route.86 Unlike the copper

atoms in complexes I-36-38 which connect to two different carbene ligands to

form (-L-Cu(Br)-L‘-)n polymer, each copper atom in complex I-39 connects

with the same carbene ligand resulting in a (-L-Cu-(μ-Br)2-Cu-L-)n polymer

As the first example of reversible substrate binding at Cu(I) centers in

Cu–NHCs chemistry, complex I-39 could react with nitrogen bases eg

N-tert-butylimidazole or piperidine to give the corresponding mononuclear

amine adducts I-40

1.1.3 Catalytic Activity of Cu(I)-NHC Complexes

Copper NHC complexes exhibit high activity in many reactions A brief account on Cu(I)-NHC complexes used in catalysis is presented as follows:

1.1.3.1 Carbene Transfer Reactions

Carbene dimerization often occurs in carbene transfer reaction and cannot be avoided with many different metal catalysts However, Nolan and co-workers

found that this drawback can be prevented with [(IPr)CuCl] (I-1) as the

catalyst in the reaction of :CHCO2Et group (from ethyl diazoacetate) with unsaturated and saturated substrates (olefins, amine and alcohols) to obtain

very high yields (Scheme 1.5)87

Scheme 1.5 Cu(I)-NHC complex catalyzed carbene transfer reaction

1.1.3.2 Cross-Coupling Reactions

Although it is challenging to activate ammonia due to the formation of stable

Werner complexes, the copper NHC complex [(SIPr)CuCl] (I-4) was found to

be an efficient catalyst for the preparation of anilines from ammonia.88

(Scheme 1.6) Despite a low catalytic activity obtained with electron-rich substrates, complex [(SIPr)CuCl] still shows good tolerance of different

functional groups such as nitro, cyano, trifluoromethyl, amide and ketone

Scheme 1.6 Cu(I)-NHC complex catalyzed cross-coupling reaction

1.1.3.3 Conjugate Reductions of α,β-unsaturated Carbonyl

Compounds

Conjugate addition of carbonyl compounds could be promoted by copper NHC complexes.52,89-91 The combination of catalytic amounts of [(IPr)CuCl] and NaOtBu with stoichiometric reductant, poly(methylhydrosiloxane) (PMHS), was found to be an active system for the 1,4-reduction of tri- and

tetrasubstituted α,β-unsaturated esters and cyclic enones.92 (Scheme 1.7)

Scheme 1.7 Cu(I)-NHC complex catalyzed conjugate reduction

1.1.3.4 Carboxylation Reactions

Carbon dioxide is an attractive, cheap and nontoxic carbon source However, the use of CO2 hasbeen limited due to its high thermodynamic stability and low reactivity AlthoughIwasawa and co-workers reported the carboxylation

of aryl- and alkenylboronic esters with CO2 in the presence of a rhodium(I) compound and additives, the rhodium catalytic systems show low activity towards functional groups.93 Recently, Hou et al found that the combination

of [(IPr)CuCl] with KOtBu can serve as an excellent catalytic system for the carboxylation of aryl- and alkenylboronic esters with CO2 to obtain various functionalized carboxylic acid derivatives in high yield.94 (Scheme 1.8)

Scheme 1.8 Cu(I)-NHC complex catalyzed carboxylation reaction

1.1.3.5 [3 + 2] Cycloaddition Reactions

Copper complexes have been widely used in reaction of organic azides and terminal alkynes to prepare 1,2,3-triazoles, known as click reaction.95 Among them, copper NHC complexes were found to promote the reaction very

effectively (Scheme 1.9) For example, Nolan et al reported that 0.8 mol%

copper NHC complexes could activate both active and inert internal alkynes to react.96 [(SIPr)CuCl] was found to promote the reactions to proceed smoothly

at 60 °C but not under ambient conditions, leading to its broad applications as efficient latent catalysts in this transformation, especially in biology and material science.97 More recently, ionic dicarbene copper complex, [(ICy)2Cu]PF6 (ICy = bis(cyclohexyl)imidazol-2-ylidene), was reported to catalyze the click reaction effectively with only 40-100 ppm copper loading.98Mechanistic studies on the [(NHC)2Cu]X system indicated that the high activity was attributed to one of the NHC ligands on the copper center acting

as a base to deprotonate the starting alkyne to generate a copper acetylide which triggered the catalytic cycle

Scheme 1.9 Cu(I)-NHC complex catalyzed [3 + 2] cycloaddition reactions

In addition, Chang et al recently reported the use of [(IPr)CuCl] in the

intermolecular formal [3+2] cycloaddition between terminal alkynes and α-aryldiazoesters to synthesize indene derivatives under mild condition.99

(Scheme 1.10)

Scheme 1.10 Cu(I)-NHC complex catalyzed [3 + 2] cycloaddition reactions to

synthesize indene derivatives

1.1.3.6 Hydrosilylation Reactions

Hydrosilylation is one of the important reactions catalyzed by copper NHC complexes.100,101 Nolan et al screened the activity of cationic di-NHC

complexes in the hydrosilylation of ketones and found that the catalytic

performance was affected by both the ligand and the counterion (Scheme 1.11) Moreover, the cationic species, [Cu(NHC)2]+ proved to be more efficient than its neutral monocarbene counterparts, [(NHC)CuCl], under similar reaction conditions for most cases.75,76 Mechanistic studies by 1H-NMR indicated that one of the NHC ligands in [Cu(IPr)2]+BF4- was replaced by

t

BuO from NaOtBu in the activation step to produce the neutral [Cu(OtBu)(IPr)] complex (I-24) which is known to be a direct precursor of an

Scheme 1.11 Cu(I)-NHC complex catalyzed hydrosilylation

1.3.7 Hydroboration Reactions

Hoveyda and co-worker reported the use of a readily available copper NHC

complex [(SIMes)CuCl] (SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydro-

imidazol-2-ylidene) (I-5) in catalytic boron-copper addition to acyclic and

cyclic aryl olefins to obtain >98:<2 site selectivity.102 (Scheme 1.12) This

catalytic activity is comparable to those obtained through transformations with borohydride reagents catalyzed by Rh- and Ir-based catalysts.103,104 For chiral copper NHC complexes, high enantioselectivities [enantiomeric ratio (er) values up to 99:1] were achieved Due to the superior activity of the more

strongly σ-donating Cu-NHC systems, NHC complexes are more effective

than phosphine-based system in this reaction

Scheme 1.12 Cu(I)-NHC complex catalyzed hydroboration reaction

1.3.8 Other Applications of Cu(I)-NHC Complexes

Besides the reactions described above, Cu(I)-NHC systems have also been

applied in a wide range of homogeneous catalytic reactions, such as cyclopropanation over C-H insertion87,105, trifluoromethylation,64Ullmann-Arylation reaction,106 conjugate additionof carbonyl aziridination of aliphatic alkenes,107 oxidative carbonylation of amino108 etc In addition, Cu(I)-NHC systems may find industrial applications, such as in the reduction

of CO2 to CO65,109, hydrogen storage110 and other medical applications111

1.2 Gold(I)/(III) N-Heterocyclic Carbene Complexes

1.2.1 General Synthetic Methods for Au(I)/(III)-NHC

Complexes

Five strategies have been developed for the preparation of Au(I)-NHC

complexes (Scheme 1.13)15,112 : (1) Reaction of Au(I) sources with free NHCs

In this method, free NHCs can be isolated or prepared in situ by reacting

azolium salts with a base such as NaOtBu, KOtBu, Na2CO3, etc (2) Transfer

of NHCs from group 6, 7 and 11 metal complexes In this method, Ag(I)-NHCs are the most popular transfer-reagent, and group 6 and 7 metal-NHCs are rarely utilized (3) Protonation or alkylation of gold carbeniate compounds In this method, Au(I)-NHC complexes are formed by the reaction of Au(I) sources with lithiated azoles followed by protonation or alkylation The known complexes are mainly those with thiazolyl NHC ligands (4) Insertion of a gold atom into electron rich double bonds In this method, [AuCl(PPh3)] is often used to react with electron-rich olefins at

100 °C to produce Au(I)-NHC complexes (5) Nucleophilic addition to Au(I)-coordinated isocyanide ligands

Scheme 1.13 Au(I)-NHC complexes formation

According to the survey of Lin et al., over 70% of the published Au(I)-NHC

complexes were synthesized through the Ag-carbene transfer route, and only 20% was obtained through the free carbene route, which is in contrast to copper NHC complexes preparation.15

Compared to Au(I)-NHC complexes, very few works on Au(III)-NHCs were reported There are four methods developed for Au(III)-NHC complexes preparation15,112: (1) Oxidative addition of halogens to Au(I)-NHC compounds (2) Transfer of NHCs from group 6 metal compounds to a Au(III) source (3) Cyclization of Au(III)-coordinated isocyanide ligands (4) Reaction of Au(III) source with free carbene

1.2.2 Structure and Reactivity of Au(I)/(III)-NHC Complexes

Unlike Cu(I)-NHC complexes with several coordination modes (two-, three- and four-coordination modes), Au(I)-NHC complexes only exhibit

four-coordination mode Au(I)-NHC complexes are discussed below, according to the three categories: monocarbene [AuX(NHC)] and [Au(NHC)L]X, dicarbene [(NHC)2Au]X, and di- and multinuclear gold NHC complexes

1.2.2.1 Monocarbene Au(I)-NHC Complexes [AuX(NHC)] and

[Au(NHC)L]X

Although Ag-NHC transfer is the powerful method for Au(I)-NHC complexes preparation, neutral [AuX(NHC)] (X = Br or I) complexes cannot be prepared via the direct reaction of [AuCl(SMe2)] with [AgX(NHC)] (X = Br or I) due to the formation of [AuCl(NHC)] instead of [AuBr(NHC)] or [AuI(NHC)] species Examples of [AuCl(NHC)] complexes containing imidazol-2-ylidene

with symmetrical or asymmetrical N,N’-substituents and saturated

imidazol-2-ylidene with symmetrical N-substituents are shown in Fig

1.7.41,113 These complexes not only serve as catalysts/precatalysts but also as starting materials in the formation of [(NHC)AuX] (X ≠ Cl) and cationic [(NHC)AuL]+ species, as outlined in Scheme 1.14

Fig 1.7 Structures of [(NHC)AuCl] complexes

The bromide and iodide complexes II-2 were obtained via the reaction of

[AuCl(NHC)] with suitable alkali metal bromide or iodide salts (LiBr, KI, etc.), similar to the procedure used for preparation of [AuX(NHC)] (X = SCN, SeCN, CN) complexes.114 [Au(pseudohalide)(NHC)] compounds (II-3) were

synthesized by the reaction of silver pseudohalide salts with [AuCl(NHC)].114-116 However, Au(I)-NHC fluoride complex (II-4) could not

be obtained with these two methods above It was prepared via reacting [Au(OtBu)(NHC)] with Et3N·HF.117 Complexes II-5a-5e, with a thioglucose

derivative as L, were prepared from the reaction of [AuCl(NHC)] with HL in the presence of a base.118,119 Complex II-6a, with a saccharin anion, was

obtained by reacting the corresponding [AuCl(NHC)] with a sodium saccharin salt in the presence of AgPF6.119 [(NHC)AuX] (X = N3, NCO, etc.) complexes

were similarly prepared.114 Compounds II-7 and II-8 were obtained from the

reaction of corresponding [(NHC)AuCl] compounds with [(HC≡C)MgCl] and [Mg(CH3)2] respectively.114 Two interesting [(NHC)Au(fluoroviyl)]

compounds, II-9a and II-9b, were obtained by reacting the [AuF(NHC)]

compound with unactivated alkynes of 3-hexyne and 1-phenyl-1-propyne respectively as the intermediate for hydrofluorination of alkynes.120

N N R

R

N N Bu

t Bu Au

O OAc AcO AcO

OAc

S N

N R

R

Au X

II-5a R = Me II-5b R = i Pr

II-5c R = Bu II-5d R = Cy II-5e R = Dipp

HX, base

N S O

O O

II-3

N N

Scheme 1.14 Reactions of [(NHC)AuCl] complexes

Fig 1.8 shows cationic [(NHC)AuL]+ species, in which the non-NHC ligand L

is neutral Compound II-10, with a strong coordinating ligand PPh3, was synthesized by directly reacting a [AuCl(NHC)]-type compound with PPh3 in the presence of KPF6 in CH2Cl2.118 By changing the silver salt and solvent to AgBF4 and EtOH, homoleptic [Au(NHC)2]+ and [Au(PPh3)2]+ species were obtained, instead of the expected [(NHC)Au(PPh3)]+ species This is possibly because AgBF4, as a good Cl- sponge, prefers the formation of

thermodynamically more stable complexes Compound II-11 with acetonitrile

ligand was prepared by the reaction of [AuCl(NHC)] with weakly

coordinating silver salt eg AgBF4 and AgPF6 in acetonitrile.121 A saturated

NHC complex II-12 with a Au-alkyne moiety was synthesized by treating the

corresponding [AuCl(NHC)] with AgBF4 and 3-hexyne.120

Fig 1.8 Structures of cationic monocarbene [(NHC)AuL]X complexes

Recently, Lin et al reported a series of Au(I)-NHC compounds containing

pyridine and imidazole (II-13 and II-14 in Fig 1.8) via the reaction of

[(NHC)AuCl] with AgNO3 and NH4PF6 together with pyridines or imidazoles.122,123 Compounds II-13 showed good catalytic activity towards oxidation of benzyl alcohol to aldehyde Complex II-14 was reported as the

first liquid crystalline Au(I)-NHC complex, achieved by modifying

N-substitute of benzimidazolium salts with long alkyl side chains With a short

Au Au distances of 3.6 Å for the bilayer lamellar structure, complexes (II-14)

were found to have low transition temperatures, broad mesophase temperature ranges and high thermal stabilities compared to other Au(I)-containing liquid crystals X-ray study indicated the distance of Au-Ccarbene bond in compound

II-14 (m = n =18) was shorter than that in II-13 (R = Et, R‘ = iPr) (1.980(6) vs

2.00(1) Ǻ), whereas the Au-N bond lengths are comparable

1.2.2.2 Dicarbene Au(I)-NHC Complexes [Au(NHC)2]X

Fig 1.9 shows cationic [Au(NHC)2]X compounds where the NHCs are

imidazol-2-ylidene Complexes II-15 were prepared by direct reaction of Au(I)

salt such as [AuX(SMe2)] (X = Br or Cl) and [AuCl(PEt3)] with two

equivalents of the appropriate imidazolium salt in the presence of a base eg

LiHMDS (lithium hexamethyldisilazide) or tBuLi These complexes exhibit antimitochondrial activity124,125 and were employed as catalysts in diboration

of terminal alkenes.126 Compound II-16 was prepared by reacting the

[(NHC)AuCl] complex with the corresponding imidazolium tetrafluoroborate and weak base K2CO3.127 Complexes II-17 were synthesized by reacting two

equivalents of the corresponding [AgCl(NHC)] compounds with [AuCl(SMe2)].128

Fig 1.9 Structures of cationic dicarbene [Au(NHC)2 ]X complexes

1.2.2.3 Di- and Multinuclear Au(I)-NHC Complexes

Fig 1.10 shows Au(I)-NHCs with two- or more gold centers Dinuclear compounds II-18 were obtained by directly reacting [AuCl(SMe2)] with the corresponding cyclo-diimidazolium salt in the presence of a mild base NaOAc.129 Recently, Hemmert et al reported the synthesis of Au(I)

complexes with alcohol functionalized di-NHC ligands in which the two azolium rings are bridged by a rigid pyridine unit or an aliphatic chain (C1 or

C3) (II-19-20).130 II-19 and 20a were obtained by direct metallation of the

imidazlium salts in the presence of sodium acetate and [AuCl(SMe2)], followed by an anionic metathesis in the presence of KPF6 The trimethylene

compound II-20b was prepared by silver transmetallation Au Au distance in

complex II-19 (3.2971 Ǻ) with the rigid pyridine spacer is significantly shorter than it in complex II-20 containing more flexible aliphatic C1 and C3

arms (3.514 and 6.34 Ǻ respectively) Electrochemical studies indicated that

the gold complexes II-19, II-20a and II-20b are all electroactive with

metal-centered processes involving Au(I)-Au(0) redox couples Similar dinuclear Au(I) complexes containing imidazolium-linked cyclophanes and related acyclic di(imidazolium) with short Au Au contact distance of 3.0485(3)

Ǻ has been reported by Baker et al.131

Fig 1.10 Structures of dinuclear Au(I)-NHC complexes

Fig 1.11 descripts the examples for di- and multinuclear Au(I)-NHC complexes The tridentate polycarbene complex II-21 was synthesized

through Ag-carbene transfer by Meyer and co-workers.57 In 2008, Hahn et

al reported the gold(I) complex (II-22) with cyclic tetracarbene ligands.132

Reaction of the dicarbene gold containing pyridyl side arm with silver salt

produced Au-Ag heteronuclear polymer such as compound II-23.133 Most

of these Au-Ag heteronuclear polymer show Au(I) Au(I)/Ag(I) interactions and exhibit luminescence properties

Fig 1.11 Structures of di- and multinuclear Au(I)-NHC complexes

1.2.2.4 Au(III)-NHC Complexes

Reports on Au(III)-NHC complexes are scarce Fig 1.12 depicts some

examples of Au(III)-NHC complexes The [(NHC)AuBr3]-type complexes,

II-24, were prepared by oxidative addition of elemental bromine to

[(NHC)AuBr].113,134Similarly, compound II-25 was the iodination product of

corresponding [Au(NHC)2][BF4] complex reported by Huynh‘s group.127

Recently, Yam et al reported the synthesis of compounds II-26 by free

carbene route using [AuCl(C∧N∧C)] (C∧N∧C = 2,6-diphenylpyridine) as the gold source and found that the presence of NHC ligands in the gold(III) metal center can enhance their luminescence properties.135

Fig 1.12 Structures of Au(III)-NHC complexes

1.2.3 Catalytic Activity of Au(I)/(III)-NHC Complexes

Although simple gold salts like AuCl or NaAuCl4 are known to catalyze many organic reactions, spontaneous reduction of Au(I) or Au(III) to inactive metal occurs in the absence of a stabilizing ligand This highlights the importance of the stabilizing phosphine and NHC ligands in this field.41 Therefore the application of gold NHC complexes in homogeneous catalysis has become a topic of intense research in the past few years A brief account is given herein

1.2.3.1 Hydration Reactions

Hydration of alkynes, allenes and alkenes represents an environmentally benign route to form C=O, C=N or C-F bonds from readily available hydrocarbon sources.12 (Scheme 1.15) Therefore, there is considerable interest

in the development of efficient protocols for this process and gold compounds have gradually taken a prominent place to replace toxic mercury(II) salts in this process.136-139 Although the use of a [(Ph3P)AuMe]/H+ catalytic system provided a high turnover frequency (TOF) in the hydration of 1-octyne, this catalyst needed the use of concentrated solutions of strong acids (H2SO4,

CF3SO3H) and high catalyst loadings for all other alkynes.140,141

Scheme 1.15 Au(I)-NHC complexes catalyzed hydration reactions

In 2003, Herrmann et al reported complexes II-1i and II-1j catalyzed the

addition of water to alkynes as the first application of gold NHC complexes in catalysis.142 (Scheme 1.16) In the following study, Nolan and co-workers found [(NHC)AuCl] (NHC = IPr) (II-1a) to be more effective than the IMes (II-1b) and ItBu (It Bu = 1,3-di(tert-butyl)imidazol-2-ylidene) (II-1f)

analogues, under acid-free conditions, in activating the hydration of both terminal and internal alkynes possessing any combination of alkyl and aryl substituents.143 Remarkably, only 10-100 ppm gold loading is necessary, significantly more effective than the typical gold-catalyzed reactions with 1-5 mol% gold loading

Scheme 1.16 Au(I)-NHC complex catalyzed the addition of water to alkynes

Scheme 1.17 Au(I)-NHC complex catalyzed the addition of O-H and N-H to alkynes

2,6-dimethylphenyl-imidazol-2-ylidene) as a highly regio- and stereoselective catalyst in intermolecular hydroalkoxylation and hydroamination at either of the allene C=C bonds.145,146 AgOTf was found

to be a better co-catalyst for [(Dipp)AuCl] than AgBF4 in both hydroalkoxylation and hydroamination Regioselectivity differs widely in the hydroalkoxylation and hydroamination of differently 1,3-disubstituted allenes The alcohol preferentially attacks at the less substituted terminus

while the amine prefers the more electron rich terminus Recently, Zeng et

al reported spirocyclic gold(I) (alkyl)(amino)carbene complexes to

promote hydroamination of internal alkynes with secondary dialkyl amines The catalytic system could even be extended to the one-pot three-component synthesis of 1,2-dihydroquinoline derivatives and related nitrogen-containing heterocycles.147

1.2.3.2 [4+2] Cycloisomerization Reactions

bis(trifluoromethylsulfonyl)amide) to be an effective catalyst in cycloisomerization to serve as the first approach for the construction of

furan-fused polycyclic compounds (Scheme 1.18)148 In addition, the combination of [(IPr)AuCl] with AgSbF6 in cycloisomerization of 1,4 and 1,5-enyne to produce tetracyclotridecan and tetracyclododecane respectively was reported recently.149

gold(I) NHC complexes (Scheme 1.19) This reaction allows a strict

comparison of both the counteranion and the neutral ligand bound to the gold center in addition to the NHC.150 The combination of [(IPr)AuCl]/AgBF4 exhibits high activity towards a variety of allylic esters

In contrast to the high catalytic activity of acetonitrile based Au(I) NHC complexes, their pyridine containing NHC analogues were not active at all.122

Scheme 1.19 Au(I)-NHC complex catalyzed [3,3] rearrangement

Rare study on Au(III)-NHCs leads to scare report on their catalytic activity

The first report on Au(III)-NHC complex in catalysis was the use of [(IPr)AuBr3] in the addition of water to alkynes by Nolan‘s group.113 The neutral [(IPr)AuBr3] showed modest activity The activity can be improved by adding silver salt AgBF4 as co-catalyst In addition, Au(III)-NHC complexes were also used to promote reaction of olefin polymerization.151

1.2.3.4 Other Application of Au(I)/(III)-HNC Complexes

Besides these reactions above, gold NHC complexes have been applied in hydrosilylation61, oxidation of benzyl alcohol to benzaldehyde104, methoxycyclization of 1,6-enynes44, etc In addition, gold NHC complexes also have wide application in medicine.24,27,37,112,129,152

1.3 Solvento Complexes of Palladium(I)/(II) Complexes with or without NHC

1.3.1 Pd(II) Complexes with Ferrocene-derivatized NHC

Palladium complexes have been well studied due to their wide use in synthetic organic chemistry and materials science Pd(II) monophosphine complexes are among the most useful synthetic palladium precursors because they are direct sources of 12-electron [Pd(PR3)] which are highly active in numerous coupling and reductive reactions.153-155 The increasing popularity of the use of NHCs as a phosphine alternative has led to vigorous pursuits of similarly unsaturated [Pd(NHC)] analogues.39 Many reviews covering palladium NHC complexes have been published.156-158 During the study, N-functionalization of

N,N-heterocyclic carbene was found to affect the steric and coordinating

abilities of the NHC In particular, N-ferrocene functionalization distinguishes

itself from functionalization with purely organic substituents because of: (i) unique steric bulk with special steric requirements of the ferrocenyl scaffold due to the cylindrical shape, (ii) electronic stabilization of adjacent electron-deficient centers due to participation of the iron atom in the dispersal

of the positive charge, and (iii) chemical stability and reversibility of the ferrocene/ferrocenium redox couple.159-163 These qualities make ferrocene-derivatized carbene ligand to be more redox active and efficient in charge distribution With the blooming development of NHCs in organometallic chemistry, ferrocene-derivatized carbenes have emerged for coordination mode and reactivity study164-168, and application in asymmetrical syntheses165,169-171

1.3.2 Mixed Ligands Pd(I)/(II) Complexes

―hetero-functionality‖ coordination mode not only increases the stability of the complexes but also enhances their catalytic activity by being electronically more sensitive to the needs of reaction substrates.172-174 Considering the well-established role of phosphines and NHCs in organometallics, mixed NHC-phosphane palladium system is especially attractive.175,176 Replacement

of labile ligand (e.g water, acetone or acetonitrile) with a stronger donor ligand such as phosphines, is a popular approach to prepare mixed NHC-phosphine complexes.177-180 Furthermore, labile ligand in compounds also could enhance the catalytic activity.181-184 For example, Sola et al

reported the synthesis and reactivity of the solvento complexes [IrClH(PiPr3)(NCCH3)3]BF4 and [IrH2(PiPr3)(NCCH3)3]BF4 containing three acetonitrile molecules and only one phosphine ligand These compounds can provide as many coordination and reaction sites as possible by minimizing the number of coordination positions occupied by strong unreactive ligands and are being applied to activate reactions involving alkenes.185

In contrast to the well-established role of Pd(II) and Pd(0) complexes, chemistry of Pd(I) complexes is still largely unexplored Although dinuclear Pd(I) is well known in small molecular activation, its value in catalysis is only beginning to emerge186-190 and its activity towards Suzuki coupling is almost

unknown Two rare examples are found in the work of Barder et al.188 and

Weissman et al.187, both of them reporting the use of phosphine arene-ligated Pd(I) dimer to promote Suzuki reaction The former attributed the activity to the disproportionation of Pd(I) to the catalytically active Pd(II) and Pd(0) However, it is still unclear if Pd(I) serves an intermediate role in any of the key steps (oxidative addition, transmetallation and reductive elimination) in the catalytic cycle Accordingly, we are interested in the catalytic chemistry of Pd(I) complexes As part of our current interest in catalysts with hemilabile ligands, we are especially interested in ligands that are weak donor, or better still, ‗‗ligandless‘‘ catalysts The use of such catalysts side-step problems such

as product contamination by the adventitious ligands, high toxicity, cost of multiple ligands, and possible undesirable reactions between the ligand and substrate Therefore, we have chosen the homoleptic complex [Pd2(CH3CN)6][BF4]2, earlier reported by Murahashi et al.191 as a model since

it meets our requirement To minimize anionic participation and possibility of metal coordination, we modified the method by using SbF6 － salt, viz

[Pd2(CH3CN)6][SbF6]2

1.4 General Property of N,S-heterocyclic Carbene

Subtle structural differences in the catalytically active species may induce significantly different levels of activity To further develop NHCs, targeted

efforts are being made in modifying the parent N,N-heterocycle by introducing

other heteroatoms such as the replacement of one of the N atoms in the imidazole by P (phosphazole), O(oxazole), or S(thiazole) to fine-tune the

electronic and donor properties of NHC ligands As a result, N, S-heterocyclic

carbenes (NSHC) started to receive more attention, with a series of wolfram, manganese, ruthenium, rhodium, iridium, nickel, palladium and platinum NSHC complexes emerging in the past decade.192 Although NSHC heterocyclic ring has only one exocyclic substituent adjacent to the carbenic centre which limited its flexibility in ligand derivatization, a range of substituents can still be introduced to the sole nitrogen centre For example, an additional donor function can be introduced to give hybrid carbene ligands This secondary moiety can also be a labile donor, thus achieving some form of hemilability in the catalyst design as evident in the use of 3-(2-propenyl)benzothiazolium bromide as carbene source to produce the corresponding iridium NSHC complexes.193a NSHC ligands were shown to exhibit some unusual bonding modes in different metal systems.192

Acceleration in the development of NSHC systems is also driven by their

application in catalysis Calo et al reported the first application of

palladium NSHC complexes in coupling reactions in 2000194, followed by a subsequent report in 2003195 More recently, both Huynh‘s group and our group also described the synthesis, structure and catalytic activity in C-C couplings (such as the Heck, Suzuki-coupling and Ullmann-type reactions)

of a series of d8 metal NSHC complexes.193,196-202 In addition, Grubbs et al

reported the use of a series of ruthenium NSHC complexes in metathesis.193b These ruthenium NSHC complexes have been found to be more stable than their phosphine-containing counterparts

Although there are reports on the catalytic activities of NSHC complexes, there is still a general lack of systematic and parallel studies of NSHC and other NNHC counterparts The immense potential of NSHC complexes in catalysis calls for more research to investigate the catalytic advantage (or disadvantage) that the sulfur atom in the heterocycle brings to the system

1.5 Objective and Significance of This Study

Although Cu- and Au-NSHC complexes have been known for long time,15very little study has been done on them Therefore, the catalytic activities

of these well-characterized Cu- and Au-NSHC complexes are still unknown Despite the wide application and well-established role of palladium complexes in the field of organometallics,203-208 study of palladium(II) complexes with ferrocene-derivatized carbene and palladium(I) complexes have been very limited In view of the significance of copper, gold and palladium carbene complexes in organic synthesis, materials and medicine,

the objectives of this work are given below: (1) synthesize and characterize novel copper, gold and palladium NHC complexes, (2) study the effect of

NHC modifications (N,S-heterocyclic carbene and N-substituent on

heterocyclic ring) on the metal coordination mode and reactivity, (3) examine the influence of oxidation state on the coordination mode and catalytic activity of Au(I)/Au(III) and Pd(I)/Pd(II) systems The ultimate aim is to develop new and effective synthetic methods for Cu- and Au-NSHC complexes, study their coordination mode and reactivity, as well

as to evaluate the influence of oxidation state of gold and palladium on their reactivity In addition to enriching the knowledge of copper, gold and palladium NHC complexes, the results of this research will be instructive for mechanistic study and future designs of copper, gold and palladium NHC catalysts

The main focus of this work are on copper(I), gold(I)/(III) NSHC complexes and solvento complexes of palladium(I)/(II) with or without NHC carbene Reported in the following chapters of this thesis are the synthetic methods and structures of a series of novel complexes as well as their catalytic applications

in cycloaddition of azides and alkynes, hydration and C-C coupling reactions respectively

Chapter 2 Novel Copper(I) N,S-Heterocyclic Carbene

Complexes: Synthesis, Structure and Catalysis

Section I Copper(I) Complex with Bridging NSHC

2.1 General Introduction on Bridging NHC

Carbonyl (CO) is among the best known ligands that are at ease with both terminal and bridging modes.209-211 Phosphine (PR3) is an overwhelmingly terminal ligand although its bridging mode is known.212-216 Ligand mobility and dynamics in di- and polynuclear complexes, as well as on metal surfaces,

is an important area of research as it is central to the understanding of many fluxional processes, catalytic mechanism, surface modifications, etc.217-219Carbenes have been coined as ״phosphine mimic״ because of their resemblance in bonding mode and electronic properties.6,7,39,220 Among the highlights of modern organometallic chemistry is the rapid emergence of

N-heterocyclic carbene (NHC) complexes, its proliferation to different forms

of heterocycles, and applications in molecular catalysis, organic syntheses, materials assemblies etc.12,14,17,18,157,221-231 Not surprisingly, like phosphines, the overwhelming majority of NHC carbenes (including the N,N232-, N,O47,233-, N,P234- and N,S197- variants) are terminal ligands Bridging forms are rare, and

so far, they are only observed in a few Ag(I)235-239 and Cu(I)56 complexes in the form of a tether, appendix or part of a chelating or difunctional unit, such

as complex A and B (Fig 2.1) Complexes with bridging NHC ligands in their

native unsubstituted or nonfunctional form are elusive Divalent carbenes such