Heterazolium salts

Apart form a great number of chiral NHC carbenes that have been used as ligands in enantioselective transition-metal catalysis (Gade and Bellemin-Laponnanz 2007), some less usual heterazolium salts have been tested in organocatalytic transformations. A planar-chiral thia-zolium salt (Pesch et al. 2004) and a rotaxane-derived precatalyst were reported (Tachibana et al. 2004), as well as catalytically active peptides containing an unnatural thiazolium-substituted alanine amino acid (Fig. 3 Mennen et al. 2005a,b). 

Heterazolium salts such as thiazolium salts (12.86) and triazohum salts " are able to catalyse the conversion of benzaldehyde (12.87) into benzoin (12.88). The mechanism involves deprotonation of the thiazolium salt to give the true catalytic species (12.89), which acts as a nucleophile towards benzaldehyde, and subsequently promotes the formation of benzoin. 

In the benzoin condensation, a new stereogenic center is formed, as the product is an a-hydroxy ketone. Consequently, many chemists aspired to develop heterazolium-catalyzed asymmetric benzoin condensations and, later, other nucleophilic acylation reactions [9]. For example, Sheehan et al. presented the first asymmetric benzoin condensation in 1966, with the chiral thiazolium salt 7 (Fig. 9.2) as catalyst precursor [10]. 

In general, the three most common, major classes of NHC carbenes can be accessed by deprotonation of their corresponding heterazolium precursors2, i.e. thiazolium, imidazol(in)ium and triazolium salts, which comprise differences in both the electronic and steric nature for the respective carbenes. 

The first investigations in the field of heterazolium-catalyzed asymmetric nucleophilic acylation go back to Sheehan et al. (Scheme 2) [24], who tried to devise an asymmetric variant of the benzoin reaction, which was known to be catalyzed by thiazolium salts from the work of Ukai et al. [25,26] and of Mizuhara et al. 

The first attempts to develop a heterazolium-catalyzed asymmetric variant of the Stetter reaction were carried out by our group [44,45,46], employing the chiral thiazolium salt 9 to catalyze the addition of butanal to chalcone. The resultant 1,4-dicarbonyl compound 10 was obtained in 29% yield with enantiomeric excesses up to 30% (Scheme 6). 

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