Development of Chiral Bisphosphine Ligands with a Terminal Olefin Enables Asymmetric Orthogonal Auto‐Tandem Catalysis

Abstract Auto‐tandem catalysis (ATC) leverages the multiple roles of the catalyst, facilitating the direct synthesis of complex molecules from simple starting materials in a highly efficient and step‐economical manner. However, in conventional ATC, employing a single catalyst imposes significant limitations on the variety of catalyzed reactions. Herein, we present a novel catalysis strategy termed “orthogonal auto‐tandem catalysis (OATC)”, which provides the unique opportunity to develop more efficient chemical transformations that cannot be achieved with existing catalytic modes. An unprecedented tandem annulation process involving four different catalytic cycles via asymmetric OATC is demonstrated. The enantio‐determining step is a previously unrealized Pd(0)‐catalyzed asymmetric allylic lactonization. The key to the whole success lies in the development of a new class of chiral bisphosphine ligands with a terminal olefin (TOPhos) that addressed not only the racemization issue of allylic ester products in classic π‐allylmetal chemistry, but also the inherent compatibility challenges in transition‐metal/organo dual catalytic system. Density functional theory (DFT) calculations unveil the vital role of the terminal olefin in TOPhos, enabling the differentiation of competitive enantioselective pathways.