Enantioselective Thia-Wolff Rearrangement via Cooperative Catalysis of Rhodium/Chiral Brønsted Acid: A Facile Access to Enantioenriched α-Sulfenylated Amides

Abstract

Although significant advances have been accomplished in the synthesis of α-chiral carboxylic acid derivatives through Wolff rearrangement of α-diazo ketones via different asymmetric catalytic mode including transition metal/photocatalysis, chiral Lewis base/photocatalysis, chiral SPA/photocatalysis and chiral NHC/photocatalysis, to the best of our knowledge, the construction of chiral carbon-heteroatom bond through Wolff rearrangement remains underdeveloped. In this paper, the first catalytic asymmetric thia-Wolff rearrangement between α-aryl α-diazothioesters and amines has been successfully achieved under cooperative rhodium/chiral phosphoric acid catalysis, which provides efficient access to synthetically valuable chiral α-sulfenylated amide architectures. This protocol features mild reaction conditions, high efficiency, excellent stereoselectivity, a broad substrate scope, scalable synthesis and versatile product functionalization, highlighting its practical value in constructing various chiral sulfur-containing compounds. Additionally, this study significantly expand the utility of diazo compounds in Wolff rearrangement for asymmetric synthesis of sulfur-containing compounds and carbene transfer reactions.

Keywords

Wolff rearrangement / α-Sulfenylated amides / Chiral Brønsted acid / Diazothioesters / Carbene / Coperative catalysis / Rhodium / Enantioselectivity

RIGHTS & PERMISSIONS

2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH