In April 2022, Professor Yan Hailong group at the School of Pharmaceutical Science of Chongqing University has published an article on Journal of the American Chemical Society entitled "Organocatalytic Asymmetric Dearomatizing Hetero-Diels-Alder Reaction of Nonactivated Arenes".

Nonactivated arenes, such as benzene derivatives, are chemically inert due to their intrinsic aromaticity and low polarity. The catalytic asymmetric dearomatization (CADA) of the benzene derivatives represents a formidable challenge. Although sporadic examples through enzyme catalysis and transition metal catalysis have been reported to achieve this goal, organocatalytic alternatives are still unknown. This report stands to be the first to utilize the benzene derivatives as a 2p component in catalytic asymmetric [4+2] cycloadditions rather than as a 4p component.

Furthermore, Yan group's understanding of the reaction is enhanced by the mechanistic studies. An extreme reactive chiral tetra-substituted vinylidene ortho-quinone methide (VQM) intermediate, derived from a dearomatization process, was considered crucial to compensate the loss of aromaticity of benzene derivatives with concomitant chirality transfer.

Related link: https://doi.org/10.1021/jacs.2c01106