Synthesis of NHCs

After some minutes of reaction time, the carbene can be isolated with excellent yield. In another approach suggested by Kuhn and Kratz, the carbene is prepared by desulfurization of the corresponding cyclic thiourea with stoichiometric amounts of metallic potassium in refluxing THF for 4h to give the carbene in a yield of 90% [31]. 

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In many cases the synthesis of NHC complexes starts from iV,A/ -disubstituted azolium salts. Imidazolium salts as precursors for imidazolin-2-ylidenes are generally accessible by two ways complementing each other (i) nucleophilic substitution at the imidazole heterocycle or (ii) a multicomponent reaction building up the heterocycle with the appropriate substituents in a one-pot reaction. 

Alternative precursors for the synthesis of NHCs are thiourea derivatives of type 3. The preparation of such thiones with a symmetrical substitution pattern is achieved by the reaction of a-hydroxyketones like 3-hydroxy-2-butanone with suitable 2-thiones (Fig. 3d) [31] or by reaction of a diamine with thiophosgene [32, 33]. Unsymmetrically substituted thiones 4 possessing a saturated heterocycle have also been described (Fig. 3e) [34, 35]. 

The carbene transfer reaction from silver NHC complexes has developed into a standard procedure for the synthesis of NHC complexes. This versatile procedure was introduced by Lin et al. in 1998 [102]. It is based on the preparation of silver NHC complexes which are obtained in good yield by the in situ deprotonation of azolium salts with silver oxide (Fig. 9). Depending on the counter ions present in the azolium salt and the steric demand of the N,N -substituents, complexes 25a-25c... 

Recently the synthesis of NHC complexes by a base catalyzed tautomeric rearrangement has been introduced. Af-Phenylimidazole coordinates via the unsubstituted nitrogen atom to Mn to give complex 82 (Fig. 26a) [198]. Subsequent attempts to deprotonate the C2 carbon atom in complex 82 led to the intermediate... 

Even though the oxidative addition pathway of imidazolium salts has been shown to be possible at certain metal complexes under special circumstances, it is far from being generally applicable to the synthesis of NHC complexes [60-67]. 

Widely applicable is the last pathway shown in Scheme 4, the transmet-allation reaction . Although other reagents have been proposed [68], the use of Ag20 as introduced by Lin [69,70] is currently the most important pathway for the synthesis of NHC metal complexes. The imidazofiiun halide forms a silverhafide-NHC complex which then transfers the carbene ligand to the metal precursor. Scheme 4 shows a general representation of possible pathways for the synthesis of transition metal NHC complexes. 

Although arguably the most popular route to NHC is via the azolium salt, there are many other options for their synthesis. An excellent and comprehensive overview of the synthesis of NHC and some of their complexes can be found in Hahn [34]. An interesting route to tri- and tetracarbenes is provided by the template controlled cyclisation of isocyanides, a method pionered by Lappert and coworkers [35,36] (see Fignre 1.2). 

Figure 5.2 Synthesis of NHC with central chirality in the wingtip groups.

Scheme 4 Synthesis of NHC-metal complexes from carboxylate-NHC adduct...

On the other hand, reaction of Pd(OAc)2 with free NHC in toluene at room temperature afforded the monomer (41) [(NHC)Pd(OAc)(A -(9,(9-Ac)]. It is worth noting that the mode of formation of the NHC (in situ generated or isolated) led to different products. Recently, Organ reported a procedure for the synthesis of NHC-Pd(II) complexes from PdCl2. PdCl2 and NHC-HCl were heated in neat 3-chloropyridine in the presence of K2CO3. The reaction yielded [PdCl2(NHC)(3-ClPy)] (42) in quantitative yields. 

Since the synthesis of NHC TM complexes was initially achieved by in situ formation of NHC from azolium salt in the presence of base followed by coordination to a metal center, a simpler procedure would be useful. In 1996, Arduengo reported the synthesis of Hg(IDM)2 (128) from Hg(OAc)2 and IDM HCl salt. The mechanism of this reaction is depicted in Scheme 21. Dissociation of one acetate ligand generates [Hg(OAc)]+ (126) and the mildly basic acetate anion drives the deprotonation of the imidazohum salt. Thus, the newly formed NHC coordinated promptly (126) and led to [(IDM)Hg(OAc)]+ (127). 

NHC transmetallation can be mediated by different TMs however, only Ag-NHC complexes are commonly used for TM-complex synthesisd The straightforward synthesis of NHC-Ag complexes, their high stability, and their tolerance to functional groups explain the success of this procedure. Other TM-mediated transmetallation are presented in Section 3.1.4. 

The transmetallation process was found competent for several metals - for instance, Crabtree and coworkers reported the transmetallation of [Ag(NHC)2](AgCl2) to Rh(I) and Ir(i) 155 Owing to its mild reaction conditions, this procedure for the synthesis of NHC-containing complexes has found... 

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