Free carbene from deprotonation

Abstract The manuscript describes the methods that are most often used in the preparation of N-heterocyclic carbene (NHC) complexes. These methods include (1) insertion of a metal into the C = C bond of bis(imidazolidin-2-ylidene) olefins (2) use of carbene adducts or protected forms of free NHC carbenes (3) use of preformed, isolated free carbenes (4) deprotonation of an azolium salt with a base (5) transmetallation from an Ag-NHC complex prepared from direct reaction of an imidazolium precursor and Ag20 and (6) oxidative addition via activation of the C2 - X (X = Me, halogen, H) of an imidazolium cation. 

The commonest route goes via the free NHC, 11.16, formed via deprotonation of the parent imidazohum salt with a strong base, such as BuLi (Eq. 11.38). Bulky R groups such as mesityl prevent the free carbene from dimerizing to 11.19, but the need for BuLi forbids the presence of functional groups with labile protons in the NHC structure. These limitations have led to the development of milder routes that avoid the free carbene. 

Utilizing prochiral a,a-disubstituted Michael acceptors, the Stetter reaction catalyzed by 76a has proven to be both enantio- and diastereoselective, allowing control of the formation of contiguous stereocenters Eq. 8 [73]. It is noteworthy that a substantial increase in diastereoselectivity is observed, from 3 1 to 15 1, when HMDS, the conjugate acid formed upon pre-catalyst deprotonation, is removed from the reaction vessel. Reproducible results and comparable enantioselectivities are observed with free carbenes for example, free carbene 95 provides 94 in 15 1 diastereoselectivity. The reaction scope is quite general and tolerates both aromatic and aliphatic aldehydes (Table 9). 

Togni s synthetic route to a planar chiral (trimethylsilyl group on ferrocene) and central chiral (asymmetric carbon in the NHC-Cp alkyl linker) carbene ligand starts from a central chiral aminomethyl ferrocene (see Figure 5.29) [9]. Lithiation and subsequent reaction with trimethylsilyl chloride introduces planar chirality on ferrocene. Quartemisation of the dimethylamino group with methyl iodide enables reaction with imidazole to the double Fc substituted imidazolium salt which can then be deprotonated to the free carbene with potassium rerf-butylate. 

Rhodium complexes such as 16 with A-heterocyclic carbenes can be prepared in one step proceeding from commercially available precursors (e. g. [( /" -1,5-COD)RhCl]2 (eq. (20)) or Wilkinson s complex [RhCl(PPh3)3] and the free carbene, which is generated from the storable imidazolium salt by deprotonation [47 9]. For more details, see Section 3.1.10. 

An important type of Fischer carbene is the A/-heterocyclic carbene or NHC. The classic example, J1.6, is derived from an A/,AT -disubstituted imidazolium salt by deprotonating the acidic hydrogen at C-2. The resulting free carbene is sufliciently stable to be isolated if the R groups are bulky (e.g., adamantyl). 

Weak bases can be used to liberate free carbenes in situ from the imidazolium salt, instead of using a strong base e.g. NaH, KOt-Bu, KHMDS). Despite the fact that the pK of azolium salts is ca. 15-25, this only measures the equilibrium position and not the rate of the deprotonation, which can occur quite quickly. " This is exploited in organocatalysis, where the NHC catalyst is typically added as the corresponding azolium salt, with only a weak base present to deprotonate it. This approach has been used in the synthesis of a number of NHC-metal complexes which do not possess a basic ligand or the ability to oxidatively add the C2-H of the azolium salt. 

On the basis of these results, a mechanism (Scheme 8.10) involving the intermediacy of a silver-carbene 54 was proposed in which the insertion product arises from the formation of the halonium ylide 55, followed by a 1,2 shift (55 —> 26, or 51 or 52). Alternatively, if the substrate and thus the halonium ylide 56 contain a (3-hydrogen, this could be removed by an intramolecular deprotonation with concomitant loss of halide resulting in formation of the olefin 57 and the a-haloacetate 53. At this stage, no independent evidence has been obtained to support this pathway thus this mechanism is purely speculative (see text below). Indeed, although the pathway has been depicted as involving metal-free intermediates, it is quite likely that this is not the case, but this awaits independent experimental verification. 

The carbene complexes [Os(P Bu2Me)2 =G(OR)Me HGl] form rapidly at low temperatures upon addition of vinyl ethers to [Os(P Bu2Me)2H3Gl], via the intermediacy of 77 -alkene complexes. While the carbene complexes generally decompose upon warming to form a mixture of products, changing the phosphine to P Pt3 allows the clean formation of the carbyne complex [Os(P Pr3)2(=GMe)HGl] (R = Ph) from H2G=GH(OPh), but the vinylidene [Os(P Pr3)2(=G=GH2)HGl] with H2G=GH(OEt). This difference in reactivity arises from the better stability of PhO compared to EtO as a free nucleophile, and the Bronsted basicity of the ethoxide anion that allows it to deprotonate a Os=GMe to afford the vinylidene product. ... 

Aldono-1,4-lactone iV-tosyl- or iV-naphthalene-2-sulfonylhydrazone derivatives such as 77 were prepared from the corresponding free sugars (e.g. 76), and shown to act as glycofuranosylidene carbene precursors on deprotonation and photolysis (Scheme 14). The carbenes could be trapped with alkenes to give adducts such as 78, or phenols to give glycosides e.g. 79. ... 

NHCs are most commonly derived from A,A -disubstituted imidazo-lium salts (4.16) by deprotonation at C2 to give the free NHC, 4.15. This acts as a very powerful 2e donor, binding to a variety of ML fragments to give NHC complexes (4.17). These are often seen represented in one of two ways depending on whether we want to emphasize the carbene character of the product (4.17a) or else the alternative picture of a metal substituted arenium ring (4.17b). 

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