Lewis acid-catalyzed diastereoselective formal ene reaction of thioindolinones/thiolactams with bicyclobutanes

Abstract

Bicyclo[1.1.0]butanes (BCBs), featuring two fused cyclopropane rings, have found widespread application in organic synthesis. Their versatile reactivity towards radicals, nucleophiles, cations, and carbenes makes them suitable for various reactions, including ring-opening and annulation strategies. Despite this versatility, their potential as enophiles in an ene reaction remains underexplored. Considering this and given the challenges of achieving diastereoselectivity in ring-opening reactions of BCBs, herein, we present a unique method utilizing BCBs as enophiles in a mild and diastereoselective Sc(OTf)₃-catalyzed formal ene reaction with thioindolinones/thiolactams, delivering 1,3-disubstituted cyclobutane derivatives in high yields and excellent regio- and diastereoselectivity. Notably, structurally different thiolactam derivatives underwent diastereoselective addition to BCBs, affording the corresponding cyclobutanes. The synthesized thioindole-substituted cyclobutanes could serve as a versatile tool for subsequent functional group manipulations.