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Catalytic Enantioselective Synthesis of α-Difunctionalized Cyclic Sulfones.

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.

SUBMITTER: Bowen E

PROVIDER: S-EPMC9490805 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Catalytic Enantioselective Synthesis of α-Difunctionalized Cyclic Sulfones.

Bowen Eleanor E Laidlaw Gillian G Atkinson Bethany C BC McArdle-Ismaguilov Timur A TA Franckevičius Vilius V

The Journal of organic chemistry 20220708 15

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 ...[more]

PMID: 35801657

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