Open AccessHomologation of Electron-Rich Benzyl Bromide Derivatives via Diazo C–C Bond Insertion
Author(s) -
A. Modak,
Juan V. AlegreRequena,
Louis de Lescure,
Kathryn J. Rynders,
Robert S. Paton,
Nicholas J. Race
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c11503
Subject(s) - chemistry , diazo , bromide , benzyl bromide , derivatization , combinatorial chemistry , alkyl , selectivity , lewis acids and bases , medicinal chemistry , organic chemistry , catalysis , high performance liquid chromatography
The ability to manipulate C-C bonds for selective chemical transformations is challenging and represents a growing area of research. Here, we report a formal insertion of diazo compounds into the "unactivated" C-C bond of benzyl bromide derivatives catalyzed by a simple Lewis acid. The homologation reaction proceeds via the intermediacy of a phenonium ion, and the products contain benzylic quaternary centers and an alkyl bromide amenable to further derivatization. Computational analysis provides critical insight into the reaction mechanism, in particular the key selectivity-determining step.