Lewis Base/Brønsted Acid Co‐Catalyzed Asymmetric Thiolation of Alkenes with Acid‐Controlled Divergent Regioselectivity

A divergent strategy for the facile preparation of various enantioenriched phenylthio‐substituted lactones was developed based on Lewis base/Brønsted acid co‐catalyzed thiolation of homoallylic acids. The acid‐controlled regiodivergent cyclization (6‐endo vs. 5‐exo) and acid‐mediated stereoselective rearrangement of phenylthio‐substituted lactones were explored. Experimental and computational studies were performed to clarify the origins of the regioselectivity and enantioselectivity. The calculation results suggest that C−O and C−S bond formation might occur simultaneously, without formation of a commonly supposed catalyst‐coordinated thiiranium ion intermediate and the potential π–π stacking between substrate and SPh as an important factor in the enantio‐determining step. Finally, this methodology was applied in the rapid syntheses of the bioactive natural products (+)‐ricciocarpin A and (R)‐dodecan‐4‐olide. The acid plays a decisive role: Various enantioenriched phenylthio‐substituted lactones were synthesized based on Lewis base/Brønsted acid co‐catalyzed thiolation of homoallylic acids. The acid‐controlled regiodivergent cyclization (6‐endo vs. 5‐exo) was explored and the developed method was applied in natural product synthesis.