Skeletal Reconstruction of 3-Alkylidenepyrrolidines to Azepines Enabled by Pd-Catalyzed C-N Bond Cleavage

Herein we report a Pd-catalyzed C-N bond cleavage strategy for the cycloaddition of pyrrolidines with azlactones or butenolides to construct the azepines. Leverage of the readily accessible 3-alkylidenepyrrolidine can serve as an effective precursor for zwitterionic salts. The in situ formation of an allyl-palladium intermediate through the cleavage of inert, cyclic C-N bonds leads to a cascade [5 + 2] cycloaddition, which allows for the diverse synthesis of azepine scaffolds with good functional group tolerance and 100% atom economy.

Automated summary

In this study, a new Pd-catalyzed strategy was reported for the construction of azepines through C-N bond cleavage reactions, showing good functional group tolerance and 100% atom economy. The use of 3-alkylidenepyrrolidine as a precursor for zwitterionic salts and the in situ formation of an allyl-palladium intermediate were key factors for the successful cascade [5 + 2] cycloaddition.