Catalytic Enantioselective Synthesis of α-Difunctionalized Cyclic Sulfones.

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.

Citation

Eleanor Bowen, Gillian Laidlaw, Bethany C Atkinson, Timur A McArdle-Ismaguilov, Vilius Franckevičius. Catalytic Enantioselective Synthesis of α-Difunctionalized Cyclic Sulfones. The Journal of organic chemistry. 2022 Aug 05;87(15):10256-10276

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PMID: 35801657

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