Regio- and Enantioselective α,γ-Dialkylation of α,β-Unsaturated Aldehydes Through Cascade Organocatalysis

The first regio- and enantioselective organocatalytic cascade alpha,gamma-dialkylation of alpha,beta-unsaturated aldehydes is achieved. Substrates scope is demonstrated with a variety of alpha,beta-unsaturated aldehydes and alkylating agents. The absolute configuration of the alpha,gamma-dialkylated product is confirmed using single-crystal X-ray analysis of its carbamate derivative. The practicality of this methodology is showcased by the gram-scale synthesis. Further application of this methodology for the regio- and enantioselective alpha,gamma-difunctionalization of alpha,beta-unsaturated aldehydes using other electrophiles are currently underway in our laboratory.