Carbene derived from imidazolium salts

Scheme 1.5 General approach to free carbenes derived from imidazolium salts.

Chiral diaminocarbene complexes of copper were used in asymmetric conjugate addition of diethylzinc to Michael acceptors. Achiral copper carbene complexes derived from imidazolium salts were synthesized and characterized for the first time by Arduengo in 1993 [43]. In 2001, Woodward reported the use of such Arduengo-type carbene in copper-catalyzed conjugate addition and showed their strong accelerating effect [44]. The same year, Alex-... 

Ylides derived from imidazolium- and triazolium-substituted indole anions belong to the class of conjugated mesomeric betaines. Their tautomers are N-heterocyclic carbenes, which undergo trapping reactions with sulfur, selenium, and triethylborane, respectively. Deprotonation of the salts 45a—c with NaOH/EtOH produces the ylides 46a—c which are in tautomeric equihbrium with carbenes 47a—c (Scheme 36) (2014T8672). 

Only recently an additional, elegant access to unsymmetrically substituted imidazolium salts has been disclosed (Fiirstner et al. 2006). Unsymmetric bisaryl-substituted IV-heterocyclic carbenes (imidazolidinium derived) can be prepared from ethyl chlorooxoacetate (Waltman and Grubbs 2004). 

A third example comes from Clyne et al. [358] and concerns the axial chiral binaphthyl backbone [359,360], itself known from phosphorus chemistry [361]. The synthesis starts from the trifluoromethylsulfonato substituted binaphthyl with a Kumada coupling reaction [291,292] with methytmagnesiumbromide. Oxidation with NBS yields the methyl brominated derivative that can be attached to the imidazole ring. Subsequent methylation results in the bis-imidazolium salt that is deprotonated to the bis-carbene and coordinated to the transition metal halide (Pd, Ni), a rather straightforward reaction sequence (see Figure 3.113). The overall yield for the four-step reaction to the bis-imidazolium salt is surprisingly good (65%). 

The chemistry of transition metal carbene complexes with NHC derived from purines or xanthines has its roots in the synthesis of xanthinium betaines [75], the xanthine analogues of imidazolium salts. The synthesis is sttaightforward and involves the methylation of the xanthine with methyl tosylate (see Figure 6.32). 

Carbene ligands are usually derived from very hindered imidazoles and are strong donors, so also form powerful catalysts. The carbenes themselves are very unstable to air, so are often generated in situ by reaction of precursor imidazolium salts with base. Alternatively, additionally stabilized preformed complexes, such as the PEPPSF group (stabilized by the additional pyridine ligand) can be used. 

With the goal of exploring the efficiency of NHC-type ligands in this particular catalytic reaction, Ma and coworkers [12], in 2010, synthesized several planar chiral imidazolium salts derived from [2.2]paracyclophane (Figure 7.3). By using these imidazolium salts as carbene precursors, the rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes proceeded readily with low catalyst loadings (0.03-0.3 mol%) and afforded a variety of diarylmethanols in excellent yields but in low to moderate enantioselectivities (a maximum of 52% ee was achieved). 

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). 

Rourke and co-workers showed that the reaction of a simple A-aryl imi-dazolium ion with [Pd(OAc)2] in DMSO led to a Pd-carbene complex, but the presence of an aniline ligand derived from the initial imidazolium salt in the coordination sphere of the Pd implied the presence of a significant decomposition process. ... 

Bridging of two carbene precursor groups with the 1,1 -binaphthyl moiety led to ligand precursors with axial chirality. Bis(imidazolium) salt 67 and the analogous benzimidazolium derivative belong to this kind of ligand precursor, as well as the hydroxyl substituted mono(imidazolium) derivative 68. Additional examples for earbenes and earbene preeursors derived from ehirally modified N-heteroeyeles are presented in Sehemes 1.7 and 1.8. 

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