Atroposelective Synthesis of Ultrarigid Chiral Styrenes via Pd‐Catalyzed Unconventional 5‐exo‐dig Cyclization/Carbonylation of 1,5‐Enynes

Abstract Axially chiral styrenes represent a promising class of atropisomers with broad potential in asymmetric catalysis, drug discovery, and materials science. However, their catalytic asymmetric synthesis remains underdeveloped due to the conformational flexibility and inherently low rotational barriers. Herein, we report a Pd‐catalyzed cyclization/carbonylation of 1,5‐enynes that enables efficient access to a series of configurationally ultrastable axially chiral styrenes in good to high yields (up to 88%) with excellent enantioselectivities (up to 99.5/0.5 er). Key to success is the strategic design of an ortho ‐alkyne‐substituted styrene substrate that favors olefin‐first Pd–hydride insertion, followed by unconventional 5‐exo‐dig cyclization and carbonylation. This protocol exhibits broad nucleophile compatibility, including alcohols, water, and amines, enabling the modular synthesis of diverse chiral styrene‐based esters, carboxylic acids, and amides. The resulting conformationally rigid product was further transformed into an axially chiral monophosphine ligand, which demonstrated high efficiency in asymmetric catalysis. Mechanistic investigations support a Pd–hydride insertion–cyclization–carbonylation sequence. This transformation provides a powerful platform for the asymmetric synthesis and application of axially chiral styrenes.