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

Abstract

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.

Regiodivergent Organocatalytic Reactions

“…Controlling the selectivity of the reactions is one of the popular fields of the research area in synthetic organic chemistry. Organocatalysts have made it possible to develop a large number of reactions to synthesize stereoselective [19][20][21][22][23][24][25][26][27][28][29], regioselective [30][31][32][33][34][35][36][37][38][39][40], and chemo-selective [41][42][43][44][45][46][47][48] products. Regiodivergent synthesis reactions, which enable two or more regioisomeric products to be synthesized from the same starting material, are controlled by various reaction parameters such as catalysts, additives, solvents, temperatures, ligands, and functional groups [49,50].…”