Stereodivergent Ruthenium/Copper Relay Catalysis for Modular Access to δ-Lactones with Two Nonadjacent Carbon Stereocenters

The stereodivergent synthesis of δ-lactones, which are prevalent in natural product frameworks, from simple starting materials via a single transformation remains a significant challenge. Herein, we report an enantio- and diastereodivergent cascade reaction for the modular synthesis of chiral δ-lactones bearing two nonadjacent quaternary and tertiary carbon stereocenters. This approach employs bimetallic Ru/Cu relay catalysis between allylic alcohols and azaaryl acetates. This method integrates Ru-catalyzed asymmetric borrowing hydrogen reaction, Cu-catalyzed asymmetric Michael addition, and rapid lactonization into a one-pot process, with all catalysts and substrates introduced at the outset. By orthogonal permutation of two chiral metal catalysts, precise control over the relative and absolute configurations of the newly formed nonadjacent stereocenters is achieved, allowing selective access to all stereoisomers of the δ-lactone products in a predictable and efficient manner.