Diastereoselective synthesis of cyclopropyl sulfoxides <i>via</i> hydrosulfenation.

ABSTRACT: Cyclopropyl sulfoxides, merging two privileged motifs in medicinal chemistry, remain synthetically challenging despite their pharmaceutical potential. Herein, we report a mild, metal-free hydrosulfenation strategy that enables their direct synthesis, achieving exceptional diastereoselectivity (dr up to > 20 : 1) in systems with up to eight possible diastereomers. Chiral sulfoxides with 4 to 7 stereogenic centers were also synthesized in high dr. The methodology provides direct access to medicinally relevant architectures, including cyclopropyl sulfones, sulfoximines, and drug-conjugated hybrids. Mechanistic studies reveal stereochemical control via collective spatial factors including endo/exo, facial and side selectivities during the cycloaddition step.

SUBMITTER: Yuwen L 

PROVIDER: S-EPMC12706915 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature