Catalytic Enantioselective Synthesis of α‐Difunctionalized Cyclic Sulfones

Bowen, Eleanor and Laidlaw, Gillian and Atkinson, Bethany and McArdle-Ismaguilov, Timur and Franckevicius, Vilius (2022) Catalytic Enantioselective Synthesis of α‐Difunctionalized Cyclic Sulfones. The Journal of Organic Chemistry. 10256–10276.

Abstract

As saturated heterocyclic building blocks become increasingly popular in medicinal chemistry and drug discovery programs, expansion of the synthetic toolkit to novel stereofunctionalized heterocycles is a priority. Herein, we report the development of a palladium-catalyzed decarboxylative asymmetric allylic alkylation reaction to access a broad range of enantioenriched α-difunctionalized 5- and 6-membered sulfones from easily accessible racemic starting materials. The allylic alkylation step was found to occur with high levels of enantioselectivity as a result of a palladium-mediated dynamic kinetic resolution of E/Z enolate intermediates. This methodology paves the way to hitherto unexplored stereodefined cyclic sulfones for medicinal chemistry applications.