Photoredox catalytic asymmetric dearomative [3 + 2] cycloaddition of isoquinolines with enones

Asymmetric dearomative photocycloaddition has emerged as a transformative strategy for the enantioselective construction of complex three-dimensional molecular architectures from simple planar aromatic precursors. While significant progress has been made in this field, the scope has largely been confined to electron-rich and electron-neutral aromatic systems. Herein, we present a breakthrough with the development of the direct asymmetric dearomative photocycloaddition involving electron-deficient isoquinolines. Our approach employs a quaternary carbon formation strategy to effectively suppress potential aromatization pathways. By establishing a synergistic photoredox and chiral hydrogen-bonding catalysis system, we achieve highly regioselective reactions between various acyclic and cyclic terminal enones and internal enones with the azaaryl ring of isoquinolines. This methodology facilitates the efficient synthesis of pharmaceutically relevant complex benzotropane derivatives, yielding satisfactory results in terms of yield, ee, and dr. Notably, this system demonstrates remarkable versatility in constructing three or four consecutive stereocenters, including challenging all-carbon quaternary stereocenters.