Highly Enantio‐ and Diastereoselective Synthesis of Tetrahydrofuran Frameworks via Chiral Lewis Acid‐Catalyzed Formal [3+2] Cycloaddition of Allylsilanes

Abstract

ABSTRACT A formal [3+2] cycloaddition via cyclization/1,2‐hydride shift initiated by nucleophilic attack of allylsilanes has been developed for the enantioselective synthesis of cis ‐2,5‐disubstituted tetrahydrofuran‐3‐ones. In the presence of chiral oxazaborolidinium ion (COBI) catalyst, the reaction proceeded in high yields (up to 88%) with excellent stereoselectivity (up to 99% ee, > 20:1 dr). Key advantages of this approach are its unprecedented ability to forge THF scaffolds asymmetrically without inherent chirality, its high stereoselectivity including cis ‐selectivity, and its capability to control four stereocenters in a single transformation.