Halide Bond Assisted Double Desymmetrization of <i>Meso</i> ‐Dicarboxylic Acids with Symmetrical Olefins via Asymmetric Halogenation

The efficient synthesis of complex chiral molecules from achiral precursors is essential for sustainable pharmaceutical development. Among available strategies, the desymmetrization of meso compounds provides a powerful route to construct multiple stereocenters in a single step. Although meso-dicarboxylic acids are promising feedstocks, their catalytic asymmetric desymmetrization remains a significant challenge. Herein we report a catalytic asymmetric halolactonization of meso-dicarboxylic acids with electronically unbiased olefins, achieving simultaneous desymmetrization of both the meso-dicarboxylic acid and haliranium intermediate. This method efficiently constructs chiral caged polycyclic lactones bearing six stereocenters in a single operation. Furthermore, the reaction is extended to exocyclic olefins, granting access to valuable terpenoid scaffolds. Its synthetic utility is highlighted by the enantioselective formal synthesis of (-)-longifolene, establishing a versatile platform for accessing norbornane-based natural products. Mechanistic studies reveal that the brominated amino-urea catalyst operates as a biomimetic hydrogen-bonding activator. Unexpectedly, the bromine substituent on the catalysts functions as an unconventional Brønsted base to stabilize a key intermediate via halide bond instead of a typical halogen bond. This work marks a substantial advancement in terpenoid synthesis, merging operational simplicity with the efficient generation of multiple stereocenters in a single transformation.