Disulfonimide-Catalyzed Asymmetric Vinylogous and Bisvinylogous Mukaiyama Aldol Reactions

摘要

The term vinylogy, which describes a unique property of π systems where the electron density and reactivity is amplified along conjugated bonds, was proposed 75 years ago by Fuson. The principle becomes particularly relevant in the context of the aldol reaction: While metal dienolates often furnish mixtures of α- and γ-addition products, the corresponding dienolsilanes react with high selectivity at the remote y position. Asymmetric vinylogous Mukaiyama aldol reactions furnish structural subunits commonly occurring in natural products, as illustrated by the research groups of Carreira, Denmark, Kalesse, and others. Several catalytic, asymmetric versions have been developed over the last few years. However, general and highly stereoselective methods that tolerate a wide range of unactivated substrates are still needed. Moreover, bisvinylogous aldol additions, potentially furnishing α,β,γ,δ-unsaturated esters in a single step, have to our knowledge not been successfully developed to date. Herein we report asymmetric vinylogous aldol additions, catalyzed by our recently introduced pre-Lewis acidic disul-fonimide catalysts 1. We also describe the unprecedented extension of the Mukaiyama aldol addition towards a bisvinylogous ε-selective and highly enantioselective variant.