Chemists have been fascinated with carbenes for more than 150 years.^1,2  The simplest member of this class of compounds, possessing a neutral divalent carbon atom and six electrons in its valence shell, is methylene, CH₂. Numerous attempts to isolate methylene or related compounds failed,³  although “carbenic reactivity” of methylene derivatives was described^4,5  in connection with cyclopropanation reactions^5–8  as early as 1953.

Even if free carbenes could not be isolated, carbene complexes have been known for a long time. The first complex with a heteroatom-stabilized carbene ligand, most likely unrecognized as such, was prepared as early as 1925 by Tschugajeff (English transcription Chugaev). Tschugajeff’s “red salt” 1 was obtained by the reaction of the tetrakis(methylisocyanide) platinum(ii) cation with hydrazine. The “yellow salt” 2 was formed upon treatment of 1 with HCl in a reversible reaction.⁹  The determination of the molecular structures of 1 and 2 in 1970 demonstrated that these compounds were correctly described as diaminocarbene complexes (Scheme 1.1).¹⁰ 

In 1964, Fischer prepared and characterized unambiguously the first metal carbene complex 3 obtained by nucleophilic attack of phenyl lithium at tungsten hexacarbonyl followed by O-alkylation.¹¹  This was followed by Schrock’s synthesis of a high oxidation state metal alkylidene complex 4 obtained by α-hydrogen abstraction from tris(neopentyl) tantalum(v) dichloride (Scheme 1.1).¹² 

Parallel to these efforts, Wanzlick tried to prepare a stable N-heterocyclic carbene by α-elimination of chloroform from 5.¹³  The free carbene, however, could not be isolated and instead its dimer, the entetraamine 6=6, was always obtained (Scheme 1.2). Wanzlick’s initially postulated cleavage of the entetraamine according to 6=6 → 2 × 6 could not be demonstrated conclusively. Cross metathesis experiments with differently N,N′-substituted entetraamines failed, excluding an equilibrium between the monomer 6 and the dimer 6=6 (Scheme 1.2).¹⁴ 

Around 1960, it was already known that unsaturated heterocyclic azolium cations reacted in a base-catalyzed H,D-exchange reaction.¹⁵  Hoping that the delocalization of the six π-electrons in such derivatives might stabilize the intermediately formed carbene species, Wanzlick attempted to prepare free carbene 7 by deprotonation of tetraphenylimidazolium perchlorate with KOt-Bu [eqn (1.1)]. Again, he could not isolate free 7 but its intermediate formation was demonstrated indirectly by identification of some of its reaction products with water or with [Hg(OAc)₂].¹⁶  Almost three decades later, Arduengo succeeded in the preparation of free¹⁷  by the deprotonation method originally suggested by Wanzlick.¹⁶ 

While, up to 1990, all attempts to isolate a stable N-heterocyclic carbene failed, metal complexes of unsaturated imidazol-2-ylidenes were known as early as 1968. The first complexes of this type were obtained by in situ deprotonation of imidazolium salts using mercury(ii) acetate¹⁸  or dimethylimidazolium hydridopentacarbonylchromate(−ii)¹⁹  followed by coordination of the carbene to the metal center (Scheme 1.3). Shortly thereafter, the stabilization of the saturated imidazolin-2-ylidene in a metal complex was described by Lappert who treated electron-rich entetraamines of type 6=6 with coordinatively unsaturated transition metal complexes to obtain complexes with imidazolin-2-ylidene ligands (Scheme 1.3).²⁰ 

While Bertrand and co-workers described in 1988 the stable λ³-phosphinocarbene 8, which did not act as a ligand,²¹  Arduengo et al. prepared in 1991 the first free and stable “bottleable” N-heterocyclic carbene 9 by deprotonation of the corresponding imidazolium salt (Scheme 1.4).²²  This deprotonation method was later supplemented by Kuhn, who introduced the reductive desulfurization of thiones for the preparation of stable imidazol-2-ylidenes.²³ 

The isolation of compound 9 demonstrated that free carbenes were not invariably unstable intermediates. Its isolation initiated an intensive search for additional stable N-heterocyclic carbenes (NHCs), leading to the isolation of derivatives with different heteroatoms in the carbene ring and different N-heterocyclic ring sizes. General aspects of the synthesis of NHCs^24–26  and their coordination chemistry with transition metals,^26–30  coinage metals,³¹  f-block metals,³²  Group 1 and 2 elements,³³  main group elements³⁴  and carbene-stabilized main group radicals³⁵  have already been reviewed. Additional reviews deal with selected classes of polydentate ligands containing NHC donor functions^36,37  and chiral NHC ligands^38,39  or NHCs as organocatalysts.^40,41  Important aspects of carbene dimerization⁴²  and the application of NHC complexes in different catalytic reactions,⁴³  even in aqueous media,⁴⁴  or of heterometallic NHC complexes as tandem catalyst have also been reviewed.⁴⁵ 

Carbenes are defined as neutral compounds of divalent carbon where the carbon atom possesses only six valence electrons. If methylene, CH₂, is considered the simplest carbene, a linear or bent geometry at the carbene carbon atom can be considered. The linear geometry is based on a sp-hybridized carbene carbon atom, leading to two energetically degenerated p orbitals (p_x, p_y). This geometry constitutes an extreme, and most carbenes contain a sp²-hybridized carbon atom with a non-linear geometry at this atom. The energy of the non-bonding p orbital (p_y), conventionally called p_π after sp²-hybridization, practically does not change upon the sp → sp² transition. The sp²-hybrid orbital, normally described as the σ orbital, possesses partial s-character and is thus energetically stabilized relative to the original p_x orbital (Figure 1.1).

The two non-bonding electrons at the sp²-hybridized carbene carbon atom can occupy the two empty orbitals (p_π and σ) with a parallel spin orientation, leading to a triplet ground state (σ¹p_π¹, ³B₁ state, Figure 1.1). Alternatively, the two electrons occupy the σ orbital with an antiparallel spin orientation (σ²p_π⁰, ¹A₁ state). An additional, generally less stable, singlet state (σ⁰p_π², ¹A₁ state) and an excited singlet state with an antiparallel occupation of the p_π and σ orbitals (σ¹p_π¹, ¹B₁ state) are conceivable but of no relevance for the present discussion.

The multiplicity of the ground state determines the properties and the reactivity of a carbene.⁴⁶  Singlet carbenes possessing a filled σ and an empty p_π orbital exhibit an ambiphilic behavior, while triplet carbenes can be considered as diradicals. The multiplicity of the ground state is determined by the relative energies of the σ and p_π orbitals, as depicted in Figure 1.1. Quantum chemical calculations showed that an energy difference of about 2 eV is required for the stabilization of the singlet ground state (¹A₁), while an energy difference of less than 1.5 eV between the relative energies of the σ and p_π orbitals favored the triplet ground state (³B₁).⁴⁷ 

Steric and electronic effects of the α substituents at the carbene carbon atom control the multiplicity of the ground state. It is generally accepted that the singlet ground state is stabilized by σ-electron withdrawing, generally more electronegative, substituents.⁴⁸  This negative inductive effect causes a lowering of the relative energy of the non-bonding σ orbital, while the relative energy of the p_π orbital remains essentially unchanged. Substituents with σ-electron donating properties decrease the energy gap between the σ and the p_π orbital and thus stabilize the triplet ground state.

In addition, mesomeric effects play a crucial role.^47,49  The substituents at the carbene carbon atom can be classified into different categories depending on their π-donor/π-acceptor properties.^24,27  Singlet carbenes of type X₂C:, substituted with two π donors X, are strongly bent at the carbene carbon atom. The interaction of the π-electron pairs at the α substituents with the p_π orbital at the carbene carbon atom raises the relative energy of this orbital. The relative energy of the σ orbital at the carbene carbon atom is not affected by the π-interaction. Consequently, the σ–p_π energy gap becomes larger, leading to a further stabilization of the bent singlet ground state. The interaction of the π electrons of the substituents with the p_π orbital at the carbene carbon atom leads to some extent to the formation of a four-electron three-center π-system where the X–C bonds acquire partial double bond character (Figure 1.2). Important members of this class of compounds are the dimethoxycarbenes⁵⁰  and the dihalocarbenes.⁵¹  The most important singlet carbenes stabilized by two π-donors are the NHCs. The bonding situation in NHCs derived from five-membered heterocycles has been discussed in detail.⁵² 

The isolation of the first stable NHCs and their successful use as ancillary ligands for the preparation of various metal complexes initiated an intensive search for new NHC ligands by variation of the size of the heterocycle, the heteroatoms within the cycle and the substituents at the nitrogen atoms of the heterocycle and the heterocycle itself. Access to NHCs is largely controlled by the availability of suitable NHC precursors. Most NHCs are prepared by deprotonation of azolium cations found in imidazolium, triazolium, benzimidazolium, imidazolinium or thiazolium salts or by reductive desulfurization of imidazol-, benzimidazol- and imidazolin-2-thiones. In addition, stable NHCs have also been obtained from various imidazolidines by thermally induced α-elimination reactions (Scheme 1.5). The preparation of suitable azolium salts, 2-thiones and imidazolines is presented in this section, followed by the description of methods for the liberation of the free NHCs from these compounds. Imidazol-2-ylidenes are the most widely used NHC ligands and therefore special emphasis is placed on synthetic procedures leading to these unsaturated NHC ligands featuring a five-membered diazaheterocycle.

Several methods for the preparation of imidazolium salts 10 (Scheme 1.6) have been described. The two most common routes are the alkylation of the nitrogen atoms of imidazole⁵³  and the multi-component reactions of primary amines, glyoxal and formaldehyde giving symmetrical N,N′-substituted azolium salts (Scheme 1.6a and b).⁵⁴  The second method is particularly useful for the synthesis of imidazolium salts bearing aromatic, very bulky or functionalized N,N′-substituents.^54,55  Unsymmetrically substituted imidazolium salts can be obtained by either stepwise alkylation of imidazole (Scheme 1.6a) or by combination of a multi-component cyclization⁵⁶  with a subsequent N-alkylation reaction (Scheme 1.6c).⁵⁷  N-Aryl imidazole derivatives can also be prepared from imidazole via a copper-catalyzed Ullman-coupling reaction.⁵⁸  Imidazolium salts bearing two different aryl substituents at the nitrogen atoms⁵⁹  or bisoxazoline derived imidazolium salts leading to NHC ligands with a flexible steric bulk have also been described.⁶⁰ 

The saturated imidazolinium salts of type 11 (Scheme 1.7) can be obtained by alkylation of dihydroimidazole or by the cyclization reactions between N,N′-dialkyl-α,β-ethyldiamines and orthoesters (Scheme 1.7a).⁶¹  A multi-component reaction leading to unsymmetrical derivatives of type 11, which is particularly interesting for the synthesis of imidazolinium salts with substituents at the C4 and C5 positions of the heterocycle, was reported by Orru and co-workers (Scheme 1.7b).⁶²  The reaction of stable N-(2-iodoethyl)arylammonium salts with an amine and triethyl orthoformate was reported to yield various imidazolinium salts of type 11 (Scheme 1.7c).⁶³  Precursor 12 for a N-heterocyclic diaminocarbene possessing a six-membered heterocycle was obtained from the reaction of a suitable 1,3-diaminopropane with triethyl orthoformate (Scheme 1.7d).⁶⁴  Related compounds with an aromatic backbone were obtained from diaminonaphthalene.⁶⁵  While these methods are based on the ring closure by introduction of a CH⁺ fragment,⁶⁶  Bertrand and co-workers presented a different approach based on the reaction of a 1,3-diazaallyl anion with compounds featuring two leaving groups.⁶⁷  Amidinium salts with six-, seven- or even eight-membered heterocycles (12–14) were obtained by this method (Scheme 1.7e), which was further developed by Cavell⁶⁸  and others⁶⁹  to yield a variety of derivatives with different ring sizes and substituents at the nitrogen atoms.

Alternative precursors for the synthesis of NHCs are thiourea derivatives of type 15. Kuhn and Kratz first reported a facile method for the synthesis of symmetrically substituted imidazol-2-thiones by the reaction of 3-hydroxy-2-butanone with suitable thiourea derivatives (Scheme 1.8a).²³  Related saturated imidazolin-2-thiones⁷⁰  16 or benzimidazol-2-thiones⁷¹  17 were obtained by reaction of aliphatic or aromatic 1,2-diamino compounds with thiophosgene (Scheme 1.8b). Unsymmetrically substituted imidazolin-2-thiones 18 were obtained by the reaction of lithium-N-lithiomethyldithiocarbamates with aldimines and ketimines, respectively (Scheme 1.8c).⁷² 

N-Heterocyclic carbenes can also be prepared by α-elimination from imidazolidines (see Scheme 1.5). Differently substituted imidazolidines or benzimidazolines were prepared by addition of alkali metal alkoxides to azolium salts⁷³  or by condensation of suitable diamines with benzaldehydes bearing fluorinated aromatic rings.⁷⁴  Some remarkable diaminocarbene precursors, such as 1,3-dimethyltetrahydropyrimidin-2-ium chloride, were described by Bertrand and co-workers.⁷⁵ 

Reports on N,N′-donor-functionalized, chiral and polydentate NHCs appeared almost immediately after the reports on the preparation of the first stable NHCs. Herrmann’s report on the first donor-functionalized imidazolium cations 19 and 20 (Figure 1.3) from 1996 ^54a  was followed by a large number of publications dealing with imidazolium precursors for donor-functionalized carbene ligands.^36,37,76  The preparation of NHCs from imidazolium precursors bearing acidic N-substituents such as alcohols or secondary amines was also attempted. Studies by Arnold and co-workers demonstrated that alcohol-functionalized imidazolium salts 21 (Figure 1.3) were readily accessible by nucleophilic opening of epoxides.⁷⁷  Imidazolium salts 22 bearing N-s-amine substituents were also prepared.^77a  Fryzuk and co-workers succeeded with the synthesis of an N,N′-di(s-amine) substituted imidazolium salt.⁷⁸  Indenyl-^79,80  (23) and fluorenyl-⁸⁰  (24) substituted imidazolium cations were also described (Figure 1.3).

A large number of differently alkylene-bridged diazolium salts of type 25 (Figure 1.4) has been described,⁸¹  next to the similar dibenzimidazolium salts.⁸²  The phenylene-bridged diazolium salt 26 ⁸³  functions, depending on the transition metal used, as a suitable precursor for the synthesis of either dinuclear double-stranded tetracarbene complexes^83a  or doubly orthometalated heterobimetallic complexes.^83b  Compound 27, the precursor for an interesting tridentate ligand containing carbene and alcoholato donor functions, was prepared by the reaction of two equivalents of an N-alkylimidazole with a functionalized epichlorhydrin (Figure 1.4).⁸⁴  Peris and co-workers prepared the Y-shaped tris(imidazolium) salt 28 and described the formation of homo-⁸⁵  and heterobinuclear complexes derived from this NHC precursor,^85b  together with a successful application of these complexes in tandem catalysis.^85b  Tris(imidazolium) salt 29 was first described by Dias and Jin,⁸⁶  shortly followed by the description of triazolium salts of type 30.⁸⁷  Additional tripodal tris(imidazolium) salts of types 31 and 32 and their NHC complexes were also prepared.⁸⁸  A number of phenylene-bridged polyazolium salts has been described.^89–93  Both homo- and heteronuclear NHC complexes have been obtained from the phenylene-linked tris(imidazolium) salts 33 ⁸⁹  and 34.⁹⁰  The 1,3,5-phenylene-linked tris(imidazolium) salt 34 as well as the phenylene-linked tetra- (35) and hexakis(imidazolium) salts 36 are also capable of forming molecular cylinders by connecting two polycarbene ligands via linear bound coinage metals. These cylinders have been prepared by treatment of the polyazolium salts with Ag₂O followed by transmetallation to gold or copper. This reaction proceeds with retention of the metalosupramolecular structure, and no formation of heteronuclear complexes was observed. Applying this procedure, access to nanometer-sized molecular cylinders is also possible by metalation of the 1,3,5-triphenylbenzene-bridged tris(imidazolium) salt 37.⁹³  A similar tris(imidazolium) salt has been used for the generation of supported and catalytically active palladium nanoparticles.⁹⁴ 

The development of pincer ligands containing phosphine or amine donor groups by Milstein⁹⁵  and van Koten⁹⁶  led to attempts to transfer this useful rigid ligand topology to tridentate ligands with NHC donor groups.³⁷  Today, pyridine- (38),⁹⁷  lutidine- (39),⁹⁸  and phenylene-bridged 40 ⁹⁹  and 41 ⁹⁸  bis(imidazolium) salts are known, in addition to the diethyl amine-bridged derivative 44.¹⁰⁰  The lutidine- and phenylene-bridged benzimidazolium salts 42 ¹⁰¹  and 43 ¹⁰²  have also been described (Figure 1.5).

Precursors for pincer ligands containing only one NHC and two additional donor groups are also known. Phosphines (45),¹⁰³  s-amines (46),⁷⁸  pyridyl (47),¹⁰⁴  or phenoxy groups (48)¹⁰⁵  can function as additional donors. A double phosphine substituted benzimidazolium salt 49 ^106a  (Figure 1.5) and a similar imidazolinium derivative^106b  have been reported in addition to an N,N′-diallyl substituted derivative.¹⁰⁷ 

Among the polydentate carbene ligands, particular interest has recently been paid to cyclic polycarbenes. The synthesis of such ligands required the preparation of suitable (macro)cyclic polyazolium salts. The first cyclic bis(benzimidazolium) salt 50 (Figure 1.6) was reported in 1994.¹⁰⁸  Related bis(imidazolium) salts 51 ¹⁰⁹  were subsequently prepared. Cyclic tetrakis(benzimidazolium)^108c,110  and tetrakis(imidazolium) salts¹¹⁰  such as 52 and 53 were synthesized during the search for new anion receptors. In addition, salts 52 and 53, in addition to the cyclic tetrakis(imidazolium) salts of types 54 ¹¹¹  and 55,¹¹²  yield with suitable metal precursors complexes bearing macrocyclic tetracarbene ligands.

Macrocyclic bis(imidazolium) salt 56 ¹¹³  possesses after C2 deprotonation both NHC and pyridine donor functions. The doubly lutidine-bridged tetrakis(imidazolium) salt 57 ¹¹⁴  gave, after fourfold C2 deprotonation, a ligand containing two endocyclic pincer subunits.¹¹⁵  This ligand is capable of binding two linearly coordinated metal ions within the macrocycle. Shortening of the aromatic linker to pyridine¹¹⁶  or ortho-xylene, as in salt 58, has been achieved with consequences for the coordination chemistry of the tetracarbene ligands obtained from these salts.¹¹⁷  Even a cyclic triply lutidine-bridged hexakis(imidazolium) salt has been described.¹¹⁵ 

A classification for chiral precursors of NHCs has been developed, leading to the division of these derivatives into five groups (Figure 1.7).¹¹⁸  The first group comprises imidazolium salts such as 59, featuring a center of chirality within the N-substituents.¹¹⁹  Additional imidazolium salts with chiral N,N′-substituents, such as 60,¹²⁰  61 ¹²¹  and 62,¹²²  were subsequently synthesized. Triazolium salts 63,¹²³  64 ¹²⁴  and related compounds¹²⁵  containing chiral N-substituents have also been described.

The second type of chiral azolium precursors possesses a chiral center attached to the N-heterocyclic ring, normally at the C4 and C5 positions, as in compounds 65 ¹²⁶  or 66.¹²⁷ 

Bridging of two carbene precursor groups with the 1,1′-binaphthyl moiety led to ligand precursors with axial chirality. Bis(imidazolium) salt 67 ¹²⁸  and the analogous benzimidazolium derivative¹²⁹  belong to this kind of ligand precursor, as well as the hydroxyl substituted mono(imidazolium) derivative 68.¹³⁰  Additional examples for carbenes and carbene precursors derived from chirally modified N-heterocycles are presented in Schemes 1.7 and 1.8.

The fourth group of chiral imidazolium precursors is made up from planar-chiral derivatives. The first representative of this type, 69, was prepared by Bolm et al.¹³¹  Togni and co-workers described the C₂-symmetrical ferrocenyl-substituted imidazolium salt 70,¹³²  and related derivatives are also known.^133,134  The planar-chiral imidazolium salt with N-paracyclophane substituents 71 ¹³⁵  and some derivatives¹³⁶  are also known. The enantiomerically pure trans-1,2-diaminocyclohexane proved to be a useful starting material for the generation of the chiral bis(imidazolium) salts 72 ¹³⁷  and 73 ¹³⁸  and of mono(imidazolium) salts.¹³⁹ 

The last group of chiral NHC ligand precursors is composed of oxazoline-substituted imidazolium salts. The first derivative of this type, 74, was reported in 1998.¹⁴⁰  A slight modification of the ligand backbone and use of the oxazoline C4 atom for linkage to the imidazolium moiety NHC gave the imidazolium salt 75.¹⁴¹  The direct connection of the two heterocycles led to 76.¹⁴²  Imidazolium salts built from oxazoline heterocycles like 77 were described by Glorius et al.¹⁴³ 

Azolium salts are easily accessible, and different types of imidazolium, imidazolinium and benzimidazolium salt can be deprotonated at the C2 position to yield the free NHCs. The first successful deprotonation of an imidazolium salt to the free NHC was achieved with NaH in THF/DMSO (see Scheme 1.4).²²  Subsequently, other bases such as KOt-Bu or KH in THF^52g,61b  or NaH in liquid ammonia¹⁴⁴  were used (Scheme 1.9). For azolium salts with acidic substituents or in the case of the formamidinium salts derived from six- or seven-membered heterocycles,^68,69  the use of a sterically demanding base such as MHMDS (M = Li, Na, K; HMDS = hexamethyldisilazide) was required for the selective deprotonation at C2.

The reductive desulfurization of N-heterocyclic thiones (Scheme 1.9) has become an alternative method for the preparation of saturated,^70,72,145  unsaturated²³  or benzannulated NHCs.^71,146  This method is, however, less frequently used than the deprotonation of azolium salts. The choice of reducing agent depends on the starting thione. Imidazol-2-thiones were reduced to the free carbenes with potassium in boiling THF within four hours,²³  while benzimidazol-2-thiones were reduced with a Na/K-alloy in toluene,⁷¹  requiring a reaction time of up to three weeks at ambient temperature.

Certain imidazolinium salts, particularly derivatives bearing bulky N,N′-substituents and some triazolium salts, could not be deprotonated with strong bases like NaH, but a thermally induced α-elimination reaction proved successful in these cases. The α-elimination was described as early as 1960 by Wanzlick and Schikora, who heated C2-trichloromethyl substituted imidazolidine with formation of the carbene dimer (see Scheme 1.2).¹³  Enders et al. successfully heated triazoline 78 under elimination of methanol from the C5 carbon atom and the formation of triazol-5-ylidene 79 (Scheme 1.10a).¹⁴⁷ 

The corresponding alcohol elimination from 2-alkoxyimidazolidines 80 to give imidazolin-2-ylidenes of type 81 was reported by Grubbs and co-workers⁷³  after early unsuccessful attempts by Wanzlick and Kleiner.¹⁴⁸  Imidazolin-2-ylidenes 81 were also accessible by α-elimination of fluorinated aryls from 2-(fluorophenyl)imidazolines 82 (Scheme 1.10b).⁷⁴  The α-elimination of acetonitrile from 83 to yield the benzimidazol-2-ylidene 84 has also been described (Scheme 1.10c).¹⁴⁹  Bertrand and co-workers reported the interesting dechlorination reaction between tetrahydropyrimidinium chloride 85 and bis(trimethylsilyl)mercury leading to NHC 86 (Scheme 1.10d).⁷⁵  This reaction is of general applicability for the dechlorination of various chloroiminium and chloroamidinium salts. The electrochemical reduction of N,N-dimesitylimidazolium chloride (IMes·HCl) has also been reported.¹⁵⁰ 

Air and moisture stable imidazolium-2-carboxylates can act as NHC precursors for the preparation of carbene complexes of metals such as Rh, Ru, Ir and Pd.^151a  However, access to the carboxylate derivatives is limited. Therefore, readily available N,N′-dimesitylimidazolium-2-isobutylester was used as an alternative carbene source.^151b  Exclusion of air and moisture is not necessary during the preparation of complexes from these NHC precursors, making free NHCs unlikely intermediates in the reaction. In general, the use of azolium-2-carboxylates constitutes an interesting high yield procedure for the preparation of NHC complexes under mild reaction conditions.

The simplest stable singlet carbene derived from a cyclic precursor is cyclopropylidene.¹⁵²  Like other carbocyclic carbenes,¹⁵³  it does not contain a heteroatom within the ring and is therefore not further discussed here. The first cyclic carbene based on a four-membered heterocycle was described in 2004. Deprotonation of iminium salt 87a with KHMDS gave carbene dimer 88a=88a while the same reaction with 87b, bearing even bulkier N,N′-substituents, led to the isolation of 88b (Scheme 1.11).¹⁵⁴  Attempts to deprotonate 87a with KOt-Bu resulted in the opening of an endocyclic P–N bond, demonstrating the electrophilic character of the phosphorus atom in this compound.

Carbene 88b exhibited a remarkable downfield shift for the resonance of the carbene carbon atom (δ = 285 ppm) in the ¹³C NMR spectrum. The molecular structure analysis revealed that 88b does not possess C₂ symmetry in the solid state and lacks perfectly planarized endocyclic nitrogen atoms, resulting in a suboptimal stabilization of the carbene center which was most likely responsible for the formation of the carbene dimer 88a=88a bearing sterically less demanding N,N′-substituents. The N–C–N bond angle in 88b was close to rectangular, measuring 96.72(13)°. Ruthenium and rhodium complexes¹⁵⁵  were prepared with carbene ligand 88b, which is also suitable for the stabilization of dihaloborenium cations.¹⁵⁶ 

Most of the known NHCs are derived from five-membered heterocycles with additional oxygen, sulfur or phosphorus heteroatoms. Stable NHCs with up to four heteroatoms and saturated or unsaturated five-membered heterocycles are discussed in this section.

Unsaturated imidazol-2-ylidenes 89 (Scheme 1.12) form the largest group of stable N-heterocyclic diaminocarbenes.²⁴  Following the isolation of the first derivative in 1991,²²  a large number of differently substituted compounds of type 89 was prepared by deprotonation of azolium salts or reductive desulfurization of imidazol-2-thiones (see Section 1.3.2). NHCs 89 are normally obtained as colorless, diamagnetic, crystalline solids which show remarkably high melting points, with the exception of N,N′-dimethylimidazol-2-ylidene which is a colorless liquid.^52g  Imidazol-2-ylidenes are stable under an inert gas atmosphere for months. ^ClIMes 91, which was obtained by chlorination of 90 with CCl₄, was even stable in air at ambient temperature for some days (Scheme 1.12).¹⁵⁷ 

Formation of imidazol-2-ylidenes 89 from imidazolium salts (10, see Scheme 1.6) or imidazol-2-thiones (15, see Scheme 1.8) can be detected by the characteristic downfield shift of the resonance of the C2 carbon atom from about δ = 140–150 ppm (10) or δ = 161–162 ppm (15) to δ = 211–220 ppm (89) in the ¹³C NMR spectra. The N–C–N bond angles in imidazol-2-ylidenes (101–102°) are significantly smaller than the equivalent angles in the parent imidazolium salts. In addition, a lengthening of the N–C_carbene bond distances of approximately 0.05 Å was observed upon NHC formation by deprotonation of imidazolium salts, indicative of a reduced π-delocalization in the imidazol-2-ylidenes 89 in comparison to the precursor salts 10.

Regardless of the substitution pattern, no dimerization to the electron-rich tetraazafulvalenes was observed for unsaturated 89. The ¹A₁ singlet ground state (see Figure 1.1) is sufficiently stabilized by inductive and mesomeric effects. Quantum chemical calculations^52g,158  demonstrated that the energy gap between the singlet and triplet states amounted to about 85 kcal mol⁻¹. Based on these calculations the strength of the C=C double bond which would result from the dimerization of two unsaturated imidazol-2-ylidenes was estimated to be approximately 2 kcal mol⁻¹.^158a  According to the Carter and Goddard estimate,¹⁵⁹  the strength of the central C=C double bond in a dimer of two imidazol-2-ylidenes should correspond to that of a canonical C=C bond (normally that of ethane, 172 kcal mol⁻¹) minus the sum of the singlet–triplet energy difference for the two carbenes involved. For the dimer of two imidazol-2-ylidenes one would thus expect a bond strength of [172 − (2 × 85)] ≈ 2 kcal mol⁻¹. Experimental evidence for the weakness of the C=C double bond in tetraazafulvalenes was presented by Taton and Chen (Scheme 1.13).^158a  Both the deprotonation of the doubly propylene-bridged bis(imidazolium) salt 92 and the two-electron reduction of derivative 93 gave the doubly bridged tetraazafulvalene 94 with a true C=C double bond [d(C=C) = 1.337(5) Å], while the deprotonation of the more flexible doubly butylene-bridged analogue 95 always led to the bis(imidazol-2-ylidene) 96 and no formation of a C=C double bond was observed.

Wanzlick et al. were the first to attempt the preparation of saturated imidazolin-2-ylidenes by α-elimination of chloroform from imidazoline derivatives. They could, however, only isolate the electron-rich entetraamines (see Scheme 1.2).¹³  It was Arduengo et al. who presented the first stable crystalline imidazolin-2-ylidene 97a (Figure 1.8) obtained by deprotonation of the corresponding imidazolinium salt.¹⁶⁰  Shortly thereafter, Denk et al. used the reductive desulfurization of imidazolin-2-thiones to obtain the N,N′-di(tert-butyl) substituted stable carbene 97b and the entetraamine 97c=97c with the sterically less demanding N,N′-dimethyl substituents (Figure 1.8).⁷⁰  Additional imidazolin-2-ylidenes were generated by α-elimination from imidazolidines^73,74  and were stabilized by coordination. Unsymmetrically substituted derivatives such as 98 were obtained as racemic mixtures of the stereoisomers,^72a  and spirocyclic derivatives 99 have also been reported.^72b 

The isolation of imidazolin-2-ylidenes of type 97 clearly showed that an aromatic 6π-electron system within the heterocycle is not required for the stabilization of an N-heterocyclic diaminocarbene. The singlet carbene center is sufficiently stabilized by inductive and mesomeric effects caused by the nitrogen substituents leading to N1–C2–N3 π-delocalization. The smaller energy gap between the singlet and triplet states in carbenes of type 97,^42,158  however, causes a rapid dimerization of derivatives with sterically less demanding N,N′-substituents to yield, for example, entetraamine 97c=97c. Kinetic stabilization of the imidazolin-2-ylidenes by sterically demanding N,N′-substituents is much more important for NHCs of type 97 than for imidazol-2-ylidenes of type 89 where even the N,N′-dimethyl substituted derivative was stable towards dimerization.²³  Alder et al.⁴²  and Graham et al.^158b  studied the dimerization reaction of imidazolin-2-ylidenes in detail. From these studies, it was concluded that dimerization of imidazolin-2-ylidenes was most likely a proton-catalyzed process, which in exceptional cases could also be catalyzed by other Lewis acids.¹⁶¹  In addition, the dimerization reaction depends on factors such as the N–C_carbene–N bond angle and the basicity of the carbene carbon atom.

Molecular structure data of saturated imidazolin-2-ylidenes 97 revealed N–C_carbene–N angles in the range of 104.7(3)–106.4(1)°,²⁴  significantly larger than the equivalent angles observed for the unsaturated analogues of type 89 (101–102°). As was observed for 89, the N–C_carbene–N angles were smaller and the N–C_carbene bond distances were slightly longer in 97 in comparison to the equivalent values found in the parent imidazolinium salts. The nitrogen atoms within the heterocycle in 97 are planarized, but the heterocycle itself was not always planar, which contrasted with the situation found in imidazol-2-ylidenes of type 89. Dimerization of NHCs 97 to entetraamines 97=97 caused an expansion of the N–C2 distances (1.418(1)–1.443(1) Å) and the N–C2–N bond angles (108.7(1)–111.3(1)°).²⁴  In addition, the nitrogen atoms in the entetraamines become significantly pyramidalized in the dimerization.

Imidazolin-2-ylidenes can be identified by the characteristic downfield resonance for the carbene carbon atom at δ ≈ 240 ppm in the ¹³C NMR spectra relative to imidazolinium salts 11 (δ = 157.2–160.9 ppm, Scheme 1.7) or imidazolin-2-thiones of type 18 (δ = 180.8–183.1 ppm, Scheme 1.8).²⁴  The downfield shift of the carbene carbon resonance is more pronounced for saturated imidazolin-2-ylidenes than for unsaturated imidazol-2-ylidenes (Δδ ≈ 25 ppm). Entetraamines 97=97 show a ¹³C NMR resonance in the range δ = 124.3–130.4 ppm.

Deprotonation of benzimidazolium salts or reduction of benzimidazol-2-thiones yielded benzimidazol-2-ylidenes 100 ^{71,146,149,162}  or dibenzotetraazafulvalenes 100=100 ^71,146,163  depending on the steric demand of the N,N′-substituents (Figure 1.9).

Bielawski and co-workers described “Janus-head” like benzobis(imidazol-2-ylidenes) 101,¹⁶⁴  which were obtained by deprotonation of the corresponding benzobis(imidazolium) salts.¹⁶⁵  Depending on the steric demand of the N,N′-substituents, these dicarbenes formed monomers 101,¹⁶⁴  dimers 103 ¹⁶⁴  or polymers 102 ¹⁶⁶  (Figure 1.9). These rigid carbenes were also used for the generation of dinuclear complexes¹⁶⁷  of organometallic polymers¹⁶⁸  and for the synthesis of polynuclear metalosupramolecular assemblies featuring NHC donors.¹⁶⁹ 

With the aim of modifying the electronic properties of the carbene carbon atom, a number of carbo- and heterocycle-annulated NHCs were prepared and studied. Single annulated NHCs (104–107)¹⁷⁰  as well as the doubly annulated carbene 108 ¹⁷¹  were obtained by deprotonation of the corresponding azolium salts. NHCs such as the quinone-annulated carbene 109,¹⁷²  the naphtho-annulated carbene 110 ^170c  and related polycyclic compounds have also been obtained from more extended ring systems.¹⁷³  Bielawski and co-workers described the synthesis and coordination chemistry of the quinobis(imidazolylidene) 111.¹⁷⁴  A planar triphenylene-based tris(carbene) 112 was described by Peris et al.¹⁷⁵  and Chiu and co-workers.¹⁷⁶  Depending on the metal center used for metalation, this ligand gives access to trinuclear complexes^175,176  or organometallic polymers.¹⁷⁶  Related tris(carbene) ligands, not featuring an aromatic backbone, are the Cerberus-type¹⁷⁷  and the tribenzotriquinacene-based tris(carbene) ligands,¹⁷⁸  which were described by Bielawski et al. and Peris et al., respectively. While the Cerberus-type ligand possesses D_3h-symmetry,¹⁷⁷  the latter leads to complexes with a C_3v-symmetry.¹⁷⁸ 

Density functional theory studies have shown that annulation of imidazol-2-ylidenes generally destabilizes the NHC.¹⁷⁹  This becomes apparent also when analogies between benzannulated NHCs and saturated imidazolin-2-ylidenes of type 97 (see Figure 1.8) are considered. Both types of NHC dimerize rapidly if the nitrogen atoms of the heterocycle are substituted with sterically less demanding substituents. No such dimerization is observed with unsaturated imidazol-2-ylidenes 89 (Scheme 1.12), which also possess an unsaturated heterocycle similar to benzimidazol-2-ylidenes.

A detailed inspection of structural and ¹³C NMR spectroscopic parameters has provided additional evidence for some special properties of benzimidazol-2-ylidenes 100 and their dibenzotetraazafulvalene dimers 100=100. The ¹³C NMR resonance for the C_carbene atom in compounds 100, for example, is observed at a chemical shift which lies between the typical values for the C_carbene resonance of saturated imidazolin-2-ylidenes 97 and unsaturated imidazol-2-ylidenes 89. In spite of the unsaturated nature of the five-membered carbene ring in 100, N1–C2–N3 angles which are typical for saturated imidazolin-2-ylidenes 97 were determined crystallographically.⁷¹  It appears that the five-membered ring in carbenes 100 possesses the topology of an unsaturated NHC but exhibits spectroscopic and structural parameters similar to those observed for the saturated imidazolin-2-ylidenes 97. This intermediate position of the benzimidazol-2-ylidenes between unsaturated and saturated NHCs indicates, even in the absence of experimental data, that the energy gap between the singlet and triplet states for compounds 100 must also assume an intermediate position between that of the stable imidazol-2-ylidenes 89 and the rapidly dimerizing imidazolin-2-ylidenes 97.

The dimerization behavior of benzimidazol-2-ylidenes is, as expected, determined by kinetic factors (steric demand of the N,N′-substituents). N,N′-Dimethylbenzimidazol-2-ylidene dimerized to give the dibenzotetraazafulvalene 100=100 (Figure 1.9).⁷¹  Sterically more demanding N,N′-substituents (neopentyl,⁷¹  adamantyl¹⁴⁹ ) enabled the isolation of the monomeric benzimidazol-2-ylidenes 100. Variation of the steric demand of the N,N′-substituents between those extremes led to the synthesis of N,N′-di(isobutyl)benzimidazol-2-ylidene which in solution co-existed together with its dibenzotetraazafulvalene dimer.¹⁴⁶  The thermally induced cleavage of a dibenzotetraazafulvalene 100=100 (R = Me) at 110–140 °C and of the N,N′,N″,N‴-tetraethyl substituted derivative into two benzimidazol-2-ylidenes was also reported.¹⁸⁰  No conclusive mechanistic information about the cleavage of dibenzotetraazafulvalenes into benzannulated N-heterocyclic carbenes is available at this time. Both a monomolecular cleavage as well as an electrophile-catalyzed reaction,⁴²  leading to a monomer–dimer mixture, are conceivable. The rapid dimerization of benzimidazol-2-ylidenes with sterically less demanding N,N′-substituents led to an interesting observation: when the nitrogen atoms bear allyl groups, and after C2-deprotonation of the N,N′-diallylbenzimidazolium salt a dibenzotetraazafulvalene was obtained which rearranged under cleavage of one or two N–C_allyl bonds.¹⁸¹ 

The ¹³C NMR resonances for the carbene carbon atom in monomeric benzimidazol-2-ylidenes 100 fall in the range of δ = 223.0–231.5 ppm while the C2 resonance for dibenzotetraazafulvalenes 100=100 is observed at higher field, at δ ≈ 119.0 ppm. The geometry of the nitrogen atoms in carbenes 100 is trigonal-planar, while pyramidalized nitrogen atoms and a non-planar N₂C=CN₂ moiety are found in the dibenzotetraazafulvalenes 100=100.

Enders et al. isolated the first triazol-5-ylidene 79 by thermal α-elimination of methanol from 5-methoxytriazoline in 1995 (see Scheme 1.10a).¹⁴⁷  79 was stable up to a temperature of 150 °C. ¹³C NMR spectroscopic [δ(C5) = 214.6 ppm] and structural parameters such as the short C_carbene–N bond lengths [1.351(3) Å and 1.373(4) Å] and the small N–C_carbene–N bond angle [100.6(2)°] confirmed similar properties of 79 and the unsaturated imidazol-2-ylidenes 89. NHC 79 showed no tendency to dimerize to the entetraamine and thus also behaved chemically like an unsaturated imidazol-2-ylidene.

Different chiral triazolium salts such as 113–114 (Figure 1.10) were used after C5 deprotonation as nucleophiles in organocatalysis.^40,182  Bertrand and co-workers succeeded with the isolation of crystalline 1,2,3-triazol-5-ylidenes of type 115, which are stable at −30 °C for several days.¹⁸³  The mesoionic carbenes 115 are obtained by simple deprotonation of the parent triazolium salts with a base such as KN(SiMe₃)₂ or KOt-Bu, which is in contrast to the similar stable 1,2,4-triazol-5-ylidenes of type 79, which cannot be obtained by deprotonation of the azolium salts. The resonances of the carbene carbon atom are detected in the ¹³C NMR spectrum [δ(C5) = 202.1–198.3 ppm], highfield shifted [Δδ(C5) ≈ 15 ppm] compared to the resonances of stable 1,2,4-triazolin-5-ylidenes 79. Structural parameters obtained for a carbene of type 115 exhibit an elongation of the C_carbene–N1 and C_carbene–C4 bonds as well as a more acute N1–C_carbene–C4 bond angle [99.70(8)°] upon deprotonation of the triazolium salt. In addition to the monodentate 1,2,3-triazol-5-ylidene ligand, bidentate C–C linked bis(1,2,3-triazol-5-ylidenes) of type 116 have been synthesized and were fully characterized.¹⁸⁴  The spectroscopic and structural data of mesoionic dicarbenes 116 resemble those of the monodentate analogues 115. A similar stable dicarbene ligand cannot be obtained from the 1,2,4-triazol-5-ylidenes, because these would possess an unstable N–N bond between the two carbene units, resulting in a rearrangement reaction.¹⁸⁵ 

The 1,2,4-triazolium salt 117 (Figure 1.10) was prepared by Bertrand and co-workers.¹⁸⁶  Although all attempts to isolate the free dicarbene by deprotonation of the dication had failed thus far, it was possible to obtain the mono- and disilver complexes by deprotonation and metalation of the carbon atoms of the heterocycle.¹⁸⁶  Several other homo- and heterodinuclear complexes have been prepared from triazolium salt 117.¹⁸⁷  Peris and co-workers obtained the diiridium complex by reaction of 117 (R = Me) with two equivalents of [IrCl(COD)]₂ in the presence of KOt-Bu. A heterobimetallic Ir ⁱ–Rhⁱ complex was obtained by successive reaction of 117 with [IrCl(COD)]₂ and [RhCl(COD)]₂.^187a 

Arduengo et al. obtained the first stable thiazol-2-ylidene 119 by deprotonation of the thiazolium salt 118 with potassium hydride in THF (Scheme 1.14).¹⁸⁸  In the presence of protons, NHC 119 dimerized to yield olefin 119=119, and an equilibrium between monomer and dimer was observed. Both 119 and 119=119 were the first and only carbene/olefin pair where both components could be characterized crystallographically. Thiazol-2-ylidenes with sterically less demanding N-substituents such as mesityl or methyl, however, dimerize rapidly at room temperature and only their dimers can be isolated.^188,189  None of the analogous benzothiazol-2-ylidenes could be isolated up to now, although benzothiazolium salts 120 and complexes of benzothiazol-2-ylidenes are readily accessible.¹⁹⁰ 

Thiazol-2-ylidenes exhibit spectroscopic and structural properties similar to those of saturated imidazolin-2-ylidenes of type 97. Upon deprotonation of the thiazolium salts to thiazol-2-ylidenes the N–C–S angle becomes smaller and the endocyclic N–C2 bond length increases slightly within an essentially planar heterocycle.¹⁸⁸  The ¹³C NMR spectra of thiazol-2-ylidenes exhibit a significant downfield shift of the resonance for the C2 atom (δ = 252–254 ppm) compared to the parent thiazolium salts (δ = 155–160 ppm) or the (N,S)C=C(N,S) carbene dimers (δ = 110–120 ppm).^188,189  Thiazolium cations such as thiamin (vitamin B1) play an important role in various enzymatic C–C coupling reactions.¹⁹¹  Breslow¹⁹²  and others¹⁹³  used model compounds to demonstrate that this enzymatic activity was caused by deprotonation of the C2 atom of the imidazolium salt under formation of a nucleophilic carbene.

The isolation of the non-cyclic amino(aryl)carbenes¹⁹⁴  and amino(alkyl)carbenes¹⁹⁵  demonstrated that singlet carbene centers can be sufficiently stabilized by only one α-nitrogen atom. In 2005, Bertrand and co-workers succeeded in preparing the first cyclic alkyl(amino)carbenes (CAACs, Scheme 1.15).¹⁹⁶  The precursor for CAAC 123 was obtained from an imine by deprotonation with LDA (LDA = lithium diisopropylamide) and subsequent reaction with 1,2-epoxy-2-methylpropane to give 121, which was converted into cyclic aldiminium salt 122 by reaction with trifluoromethanesulfonic acid anhydride. Deprotonation of 122 with LDA afforded CAAC 123 as a colorless solid (Scheme 1.15). The presence of a quaternary carbon atom in α-position to the carbene center offered the possibility of constructing ligands with a large variety of steric environments. CAAC 124, for example, contained a spiro-carbon atom next to the carbene center, leading to a flexible steric demand caused by conformational changes of the cyclohexyl ring. Similar behavior was observed for related bisoxazoline derived NHC ligands.⁶⁰  The influence of the “flexible cyclohexyl wing” reached a maximum in 125, where an intelligent substitution pattern of the cyclohexyl ring fixes the “wing” in one conformation, giving maximum steric protection to the carbene carbon atom. Coordination of CAAC 125 to transition metals led to complexes with low coordination number and strong steric protection of the coordinated metal center.^196b,197  CAACs with other bulky substituents at the carbon atom in the α-position to the carbene center were also prepared by Bertrand and co-workers.¹⁹⁸ 

The substitution of one electronegative amine substituent in classical NHCs for the strong σ-donor carbon makes CAACs particularly electron-rich. Consequently, CAACs are excellent donor ligands with a donor strength which is often superior to those of phosphines or classical NHCs. The N–C_carbene bond length [1.315(3) Å]^196a  is comparable to the value found in the saturated imidazolin-2-ylidenes 97, while the C_carbene–C bond length is typical for a C–C single bond. The similarity between CAACs and imidazolin-2-ylidenes is also apparent from the N–C_carbene–C bond angle in CAAC 125 [106.5(2)°],^196a  which is significantly larger than the equivalent N–C–N bond angle in imidazol-2-ylidenes 89, but similar to the N–C_carbene–N angles observed in imidazolin-2-ylidenes 97. The carbene carbon atom in CAACs is strongly deshielded, leading to downfield shifted ¹³C NMR resonances (123 δ = 304.2 ppm, 124 δ = 309.4 ppm, 125 δ = 319.0 ppm).^196a 

The preparation of CAAC precursors depicted in Scheme 1.15 is tedious and time consuming. To overcome this problem, Bertrand and co-workers developed the “hydroiminiumation” reaction for the preparation of the cyclic aldiminium salts of type 122.¹⁹⁹  The cyclization step in this reaction is based on the addition of an imine to a double bond and also allows the preparation of larger heterocycles. An asymmetric version of the reaction was described, generating a stereocenter at an atom of the heterocyclic backbone.²⁰⁰ 

Bertrand et al. also demonstrated that CAAC 125 could activate dihydrogen to give compound 126 (Scheme 1.16). Contrary to the activation of dihydrogen by electrophilic transition metals, the carbene acted primarily as a nucleophile, creating a hydride-like hydrogen, which subsequently bonded to the vacant p orbital of the positively polarized carbene carbon atom.²⁰¹  Importantly, this activation was not observed with the slightly less nucleophilic imidazol-2-ylidenes and imidazolin-2-ylidenes.

Pairs of Lewis acids and bases normally form stable donor–acceptor adducts. When steric effects prevent this adduct formation, frustrated Lewis-pairs (FLPs) are obtained instead. Such FLPs are promising reagents for the activation of small molecules.²⁰²  Tamm²⁰³  and Stephan²⁰⁴  combined an NHC with sterically demanding N,N′-substituents and tris(pentafluorophenyl)borane to form a non-quenching carbene-based FLP (Scheme 1.16). In toluene purged with dihydrogen the FLP reacted with the dihydrogen to form the imidazolium borate salt 127 in quantitative yield. The limitations of this FLP system became apparent when, in the absence of dihydrogen, the resulting solution lost its reactivity towards dihydrogen within one hour and the 1 : 1 zwitterionic carbene–borane adduct 128 was isolated instead.

The electron-donating ability of NHCs is determined by the mesomeric and inductive effects of the α-substituents (see Section 1.2).⁵²  While the electronegativity of the α-carbon atom in CAACs is lower than that of nitrogen in NHCs, the sp³-hybridized α-carbon atom in CAACs is certainly no π-donor. To enhance the π-donating ability of carbon atoms in α-position to the carbene center, amino(ylide)carbenes (AYCs) were developed. Similar compounds had been known for some time,²⁰⁵  but up to then had little impact compared to their diamino-stabilized relatives.

Kawashima and co-workers attempted to prepare the phosphorus ylide-stabilized AYC ligand 129 which could, however, not be isolated because of an intramolecular rearrangement giving 130. The intermediate formation of 129 was confirmed by its reaction with sulfur to give 131 and by the formation of the rhodium complexes 132 and 133 (Scheme 1.17).²⁰⁶  Infrared spectroscopy of the carbonyl complex 133 confirmed the superb donor properties of AYC 129. A palladium complex bearing the phosphorus ylide-stabilized NHC was also prepared.²⁰⁶  Fürstner et al. synthesized the analogous sulfur ylide-stabilized AYC which again could not be directly observed but was stabilized in the rhodium complex 134.²⁰⁷  Moving away from the indole scaffold, AYC 135 was prepared and characterized in solution [δ(C2) = 218 ppm, J_C,P = 51.2 Hz]. Finally, it was tested whether polarized C=C bonds also lend themselves to the stabilization of a vicinal carbene. The “carbon-ylide” stabilized AYC 136 was characterized by its reaction with sulfur. Compound 137 reacted with [Pd(acac)₂] (acac = acetylacetonato) with formation of a C(NHC)^N(pyridyl) chelate complex bearing a “carbon ylide” stabilized carbene ligand (Scheme 1.17).²⁰⁷ 

Yet another ylide/carbene combination exists in bidentate CAAC-phosphonium ylide and diaminocarbene-phosphonium ylide ligands prepared by Bertrand²⁰⁸  and by Canac et al.²⁰⁹  While the free carbenes were not isolated, they could be stabilized in palladium complexes 138–140 (Scheme 1.17).

Given that the stability of N-heterocyclic carbenes is based on the stabilizing effect of the α-nitrogen atoms, it is surprising that the heavier analogues of nitrogen, such as phosphorus, were initially disregarded for the stabilization of heterocyclic carbenes. Acyclic phosphorus-stabilized carbenes have been known since 1988.²¹  Experimental and theoretical studies revealed that the π-donor capability of the third-row elements was as large or even larger than those of their second-row counterparts.²¹⁰  Calculations also showed that the phosphorus atoms in a hypothetical P-heterocyclic carbene were expected to be pyramidalized²¹¹  and thus incapable of stabilizing the carbene center, while the nitrogen atoms in NHCs are trigonal-planar.⁵² 

The first complex with a P-heterocyclic carbene ligand, analogue of an imidazol-2-ylidene, was described by Le Floch and co-workers in 2004.²¹²  The free P-heterocyclic carbene (PHC) ligand, however, could not be isolated. Avoiding the pyramidalization of the phosphorus atoms by bulky P,P′-substituents, Bertrand isolated the first stable PHC 142 in 2005 (Scheme 1.18).²¹³  Since the phosphorus analogues of azolium salts were unknown, a new protocol for the preparation of cationic PHC precursors had to be developed. This involved the dehalogenation of a phosphaalkene with AgOTf or GaCl₃ followed by a [3 + 2] cycloaddition of the intermediate diphosphaallylic cation with acetonitrile as dipolarophile. Compounds 141 were then deprotonated with LiHMDS to give the stable PHC 142.

The molecular structures of 141b and 142 provided evidence that the use of the sterically demanding 2,4,6-tri-tert-butylphenyl substituents led to the desired planarization of the phosphorus atoms. The slight deviation from planarity and the resulting trans-arrangement of the aryl substituents at the phosphorus atoms led to chiral compounds in the solid state.

The ¹H and ¹³C NMR spectra of solutions of 142 exhibited only one resonance for the diastereotopic groups, even at low temperature (−100 °C), giving evidence for a rapid interconversion of the possible enantiomers in solution and a low inversion barrier at the phosphorus atoms. In addition, the ¹³C NMR resonance for the carbene carbon atom in PHC 142 (δ = 184 ppm) appeared highfield shifted relative to the chemical shift observed for NHC analogues. The structure analysis of 142 confirmed the donor character of the phosphorus atoms. The P–C_carbene distances [1.673(6) and 1.710(6) Å] are significantly shorter than P–C single bonds. Deprotonation of the PHC precursor caused the P–C–P angle to become more acute, from 106.2(5)° in 141b to 98.2(3)° in 142. This behavior is analogous to that of the azolium salts and the NHCs obtained from these by deprotonation. Ab initio calculations demonstrated that a decrease in the steric bulk of the P,P′-substituents led to a pyramidalization of the phosphorus atoms and a decrease of the singlet–triplet energy gap. Thereby destabilizing the P,P′-heterocyclic carbene.²¹⁴  Some derivatives of PHC 142 were prepared,^213b  as well as metal complexes.²¹³  Moreover, a report on the first persistent P,N-stabilized heterocyclic carbene also appeared.²¹⁵ 

Diverse NHCs containing Lewis-acidic boron atoms within the carbene ring have been described in the literature. Carbene 143, derived from a four-membered heterocycle (Figure 1.11),²¹⁶  showed several similarities with the previously discussed carbene 88b (see Scheme 1.11). Substitution of the phosphorus atom in 88b with a boron atom in 143 resulted in a shift of the ¹³C NMR resonance for the carbene carbon atom down to the lowest value observed so far for cyclic diaminocarbenes (δ = 312.6 ppm in C₆D₆). The four-membered carbene ring in 143 is planar and the exocyclic nitrogen atom is also surrounded in a trigonal-planar fashion. The lengths of the endocyclic C–N and B–N bonds indicated an efficient π-electron donation from the nitrogen atoms to the electron-poor carbon and boron atoms. The endocyclic N–C–N angle in 143 [94.0(2)°] represents the smallest value observed so far for NHCs.

The five-membered carbene ring in 144 (Figure 1.11) is nearly planar.²¹⁷  The resonance for the carbene carbon atom appeared downfield at δ = 304 ppm in the ¹³C NMR spectrum. A comparison of the geometrical parameters of 144 with imidazol-2-ylidenes 89 or imidazolin-2-ylidenes 97 revealed a relatively long B–B bond [1.731(2) Å] in 144 in addition to an enlarged value for the N–C–N angle [108.45(8)°]. The endocyclic B–N bonds were about 0.1 Å longer than the exocyclic ones, indicating that N → B π-delocalization is weak within the heterocycle and stronger involving the exocyclic amine substituents. A significant N → B π-interaction of the exocyclic amine groups was also confirmed by the observation of a hindered rotation around the B–NMe₂ bond in both the ¹H and ¹³C NMR spectra at room temperature. First experiments indicated that 144 might be a better σ-donor than its analogues 89 and 97 with a carbon backbone.²¹⁷ 

Heterocycles of type 145 are isoelectronic with the stable borazine. The carbene ring in 145c is nearly planar and the cyclohexyl groups are oriented to achieve a maximal steric protection of the carbene center.²¹⁸  The N–C–N angle in 145c is enlarged to 114.5(1)° in accordance with expectations for a six-membered ring. The resonances for the carbene carbon atoms in 145a–c fall in the narrow range of δ = 281.5–282.9 ppm in the ¹³C NMR spectra. The IR spectra of complexes [(145)RhCl(CO)₂] were used to demonstrate that the σ-donor strength of the carbenes 145 could be modulated by the exocyclic substituents at the boron atoms. The σ-donor strength of the carbene ligand decreased together with the donor strength of the exocyclic substituents at the boron atoms in the order 145a > 145b > 145c.²¹⁸ 

The anionic carbene 146 was isolated and characterized as lithium adduct.²¹⁹  Crystallographically determined molecular parameters of 146 are very similar to those found for the isoelectronic lithium terphenyl derivatives.²²⁰  DFT calculations suggested that 146 exhibited a σ-donor strength in between those of imidazol-2-ylidenes and terphenyl anions.²¹⁹ 

Aside from the ubiquitous NHCs featuring a five-membered heterocycle, significant advances have been achieved in the preparation of NHCs derived from larger heterocycles. The first stable NHC featuring a six-membered aliphatic heterocycle 147a was prepared in 1999,⁶⁴  followed by a number of differently N,N′-substituted derivatives.^68c,69  Aromatic derivatives such as 148a are also known (Figure 1.12).⁶⁵  The NHCs derived from six-membered heterocycles were obtained by deprotonation of the corresponding cyclic amidinium salts with sterically demanding bases because the use of alkali tert-butoxides often led to the formation of alcohol adducts. Carbenes with a saturated six-membered scaffold, such as 147a, showed no tendency to dimerize to the entetraamines. However, compounds of type 148a rapidly dimerized to the entetraamines if bearing aromatic or unsymmetrical N,N′-substituents.⁶⁵ 

NHCs featuring an aliphatic seven- or eight-membered membered ring scaffold of type 147b ^68c,69,221  or 147c ^68e  were also obtained by deprotonation of amidinium salts with sterically demanding bases. Contrary to this situation, the seven-membered ring NHC 148b with an aromatic backbone cannot be obtained by deprotonation. Only the in situ deprotonation and immediate coordination of the generated NHC to a metal center was successful.^66,222  Stahl et al. were able to synthesize carbene 148b by base induced α-elimination from the phenol adduct of the carbene.^66,222,223  The seven-membered NHCs 147b and 148b are not planar but adopted a twisted conformation instead. The anionic N-heterocyclic carbene 149 and its zwitterionic complexes were also prepared.²²⁴  In their search for NHCs, which allow tuning of the electronic properties by a redox reaction, Bielawski²²⁵  and Siemeling²²⁶  prepared the diaminocarbene[3]ferrocenophanes 150 (Figure 1.12) and their metal complexes. Yang et al. succeeded with the synthesis of the six-membered NHC 151, which possesses a spiro-fused backbone, and studied the reactivity and coordination chemistry of this carbene.²²⁷ 

The characteristic ¹³C NMR resonances for the carbene carbon atoms of the NHCs featuring six-membered heterocycles (147a, 148a) fall in the range δ = 235–245 ppm,^65,68c,69  similar to those of imidazolin-2-ylidenes 97, whereas the carbene resonances for 147b and 148b appeared more downfield (δ = 258–260 ppm).^68c  The resonances of the carbene carbon atom of eight-membered ring NHC 147c (δ = 245–253 ppm) are detected in between the chemical shifts of the six- and the seven-membered NHCs.^68e  The N–C–N angles in NHCs derived from six- and seven-membered heterocycles were larger than in their five-membered analogues (≈115° in 147a and 148a, 116.6° in 147b, 113.4° in 148b). The corresponding angle is even larger in the eight-membered heterocycle (≈120°). This situation causes the N-wingtip substituents to point more directly towards the metal atoms bonded to the NHC carbon atom. As a result of this steric crowding, the formation of complexes with low coordination numbers is preferred.²²⁸ 

Currently, a large number of NHCs featuring different ring sizes, ring-heteroatoms and substitution patterns are accessible. In spite of the large number of known derivatives, reports on new NHCs regularly appear in the literature. As diverse as the topology of NHCs are their stereochemical and electronic properties.²²⁹ 

Different, sometimes surprisingly facile, routes leading to stable NHCs or directly to their metal complexes have been developed. Particularly interesting new studies include the development of “remote”²³⁰  and “abnormal”^230b,231  NHCs (see Chapter 3 for further details) and the generation of unusual NHC ligands from biomolecules.²³²  Complexes featuring protic NHC ligands, an NHC type which cannot be isolated in the free form, offer the possibility of a functionalization of the NHC ligand after the coordination to a metal center.²³³  In addition, complexes bearing protic NHCs might be of interest in regioselective catalysis owing to the possibility of substrate recognition via formation of hydrogen bonds to the NH wingtips.²³⁴  Recently developed iron NHC complexes exhibited promising properties as catalysts for selected catalytic transformations, a field of high economic interest because it combines the superb donor properties of the NHCs with the cheap transition metal iron.²³⁵  NHC complexes are also used in OLEDs²³⁶  or as metallodrugs.²³⁷ 

NHCs have not only been used as ligands in transition metal chemistry but also as nucleophilic organocatalysts.^40,41  In an extension of this concept, the first organometallic transformation catalyzed by NHCs has been disclosed.²³⁸  These few examples nicely illustrate that, 25 years after Arduengo’s first report on an N-heterocyclic carbene, new NHCs as well as new applications for these interesting and versatile molecules are still emerging and these will for some time remain the subject of intensive research.