Читать книгу Catalytic Asymmetric Synthesis - Группа авторов - Страница 17

Some secondary amine catalysts, such as diphenylprolinol silyl ether, are effective catalysts in Michael reactions using an aldehyde as a Michael donor (see Scheme 1.1), but these catalysts are not effective in Michael reactions using a ketone as a Michael donor because generation of an enamine from a ketone using diphenylprolinol silyl ether is hindered by its steric bulk. On the other hand, a primary amine can easily generate an enamine from a ketone. Primary amine catalysts derived from cinchona alkaloids have enabled the stereoselective functionalization of a variety of sterically hindered carbonyl compounds, which cannot be realized by secondary amine catalysts (Scheme 1.1) [10]. Moreover, primary amine catalysts can activate structurally substituted substrates such as α‐branched substituted aldehydes and ketones. They also activate α‐substituted α,β‐unsaturated aldehydes and ketones. The reactions of these substrates using chiral cyclic secondary amine catalysts are difficult.

Scheme 1.1. Reactions of cinchona alkaloid catalysts.

Source: Based on [10].

Cinchona alkaloid catalysts act as efficient bifunctional catalysts. They possess a primary amine moiety that can react with aldehydes, ketones, and α,β‐unsaturated carbonyl compounds to generate enamines and imines. The catalysts have a basic quinuclidine moiety, which acts as a base, and a hydroxy or alkoxy group on C9, which can make a hydrogen‐bonding interaction. Thus, they can simultaneously activate both electrophilic and nucleophilic reagents in a reaction.