Asymmetric Multi-Atom Insertion of Esters via Rh-Catalyzed Ring Opening of Oxabicyclic Alkenes

Precise skeletal manipulation involving insertion, deletion, and replacement has garnered considerable attention within the synthetic chemistry community. Among these processes, multi-atom insertion reactions in acyclic compounds remain a formidable challenge, primarily due to the low efficiency of fragment recapture after cleavage, which results from the lack of substrate-specific proximity during the reconstruction stage. Here, we report an asymmetric multi-atom insertion reaction of esters via Rh-catalyzed ring opening of oxabicyclic alkenes, achieving excellent regio-, diastereo-, and enantioselectivity. This approach enables the efficient and rapid construction of a molecular library of esters with a chiral hydroxy-dihydronaphthalene scaffold, showcasing an atom-efficient reaction. Detailed density functional theory calculations reveal key mechanistic features and the stereoselectivity-determining model of this transformation.