Rhodium(I)-Catalyzed Annulation of Bicyclo[1.1.0]butyl-Substituted Dihydroquinolines and Dihydropyridines

• DOI: 10.1021/jacs.4c04081
• Publication Date: 2024-05-20T13:51:46Z
• Authors: Matteo Borgini; Qi-Nan Huang; Pan-Pan Chen; Steven J. Geib; K. N. Houk; Peter Wipf
• Keywords: Annulation; Reactivity; Cyclopropane; Butane; Alkene; Iminium; Nucleophilic Addition; Methylene

Bicyclo[1.1.0]butane-containing compounds feature a unique chemical reactivity, trigger "strain-release" reaction cascades, and provide novel scaffolds with considerable utility in the drug discovery field. We report synthesis of new bicyclo[1.1.0]butane-linked heterocycles by nucleophilic addition bicyclo[1.1.0]butyl anions to 8-isocyanatoquinoline, or, alternatively, iminium cations derived from quinolines pyridines. The resulting bicyclo[1.1.0]butanes are converted high regioselectivity unprecedented bridged rhodium(I)-catalyzed annulative rearrangement. addition/rearrangement process tolerates surprisingly large range functional groups. Subsequent chemo- stereoselective synthetic transformations urea, alkene, cyclopropane, aniline moieties 1-methylene-5-azacyclopropa[cd]indene several additional heterocyclic building blocks. X-ray structure-validated quantum mechanical DFT calculations pathway indicate intermediacy rhodium carbenoid metallocyclobutane species.