Direct Site-Specific and Highly Enantioselective γ-Functionalization of Linear α,β-Unsaturated Ketones: Bifunctional Catalytic Strategy

摘要

The direct asymmetric y functionalization of simple unmodified carbonyl compounds has emerged as a powerful, distinct, and atom-economical method offering an efficient entry into functionalized building blocks having high levels of structural complexity. Since the pioneering studies carried out by the groups of Jorgensen, Chen, Melchiorre, and others, different types of vinylogous processes initiated by dienamine intermediates have been studied extensively. However, while there is an ever growing number of documents involving catalytic γ-selective activation of enals, the corresponding reaction embracing enones as γ-type nucleophiles remain comparatively rare. To date, the only example of enantioselective γ functionalization of cyclic enones has been reported by Melchiorre and co-workers who use cyclohex-enone derivatives as nucleophilic substrates.Nevertheless, for the γ-site-specific functionalization of linear α,β-unsatu-rated ketones, which usually act as electrophiles in Michael additions (Figure 1 a) or prefer to selectively direct the reaction toward a alkylation (Figure 1 b), still represents a longstanding challenge (Figure 1c).