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

The first regio- and enantioselective organocatalytic cascade α,γ-dialkylation of α,β-unsaturated aldehydes is achieved. Substrates scope is demonstrated with a variety of α,β-unsaturated aldehydes and alkylating agents. The absolute configuration of the α,γ-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 α,γ-difunctionalization of α,β-unsaturated aldehydes using other electrophiles are currently underway in our laboratory.