Stereoselective synthesis of E-shaped double helicene analogues via organocatalytic intermolecular cycloaddition

The catalytic asymmetric synthesis of multiple helicenes represents one of the most daunting challenges in organic synthesis owing to the significant difficulties associated with the precise construction of helical backbones and the control of stereoselectivity. While sporadic examples of enantiocontrolled synthesis of S-shaped double helicenes have been documented, the catalytic asymmetric synthesis of E-shaped double helicenes remains an unfulfilled endeavor. Herein, we report an organocatalyzed intermolecular cycloaddition of polycyclic phenols with 2-alkynylphenols, which enables efficient assembly of E-shaped double helicene analogues with excellent stereocontrol. The steric hindrance effect is instrumental in diverting the reaction from a traditional Friedel-Crafts-type pathway, thereby ensuring excellent chemoselectivity. Besides, the scalability of this method and the diverse transformations of the double helical products underscore its practical utility. Moreover, DFT calculations shed light on the configurational stability of the helical products and unveil the mechanistic basis for the precise chemo- and stereocontrol realized in this methodology. While sporadic examples of enantiocontrolled synthesis of S-shaped double helicenes have been documented, the catalytic asymmetric synthesis of E-shaped double helicenes remains an unmet challenge. Here the authors report an organocatalyzed intermolecular cycloaddition of polycyclic phenols with 2-alkynylphenols, which enables efficient assembly of E-shaped double helicene analogues, with excellent stereocontrol.