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Dual-Hydrogen-Bond Donor and Brønsted Acid Cocatalysis Enables Highly Enantioselective Protio-Semipinacol Rearrangement Reactions

Melanie A. S. Blackburn, Corin C. Wagen, M. Raul Bodrogean, Pamela M. Tadross, Andrew J. Bendelsmith, Dennis A. Kutateladze and Eric N. Jacobsen*

*Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States, Email:

M. A. S. Blackburn, C. C. Wagen, M. R. Bodrogean, P. M. Tadross, A. J. Bendelsmith, D. A. Kutateladze, E. N. Jacobsen, J. Am. Chem. Soc., 2023, 145, 15036-15042.

DOI: 10.1021/jacs.3c02960

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A catalytic protio-semipinacol ring-expansion reaction for the highly enantioselective conversion of tertiary vinylic cyclopropyl alcohols into cyclobutanone products bearing α-quaternary stereogenic centers relies on the cocatalytic effect of a chiral dual-hydrogen-bond donor (HBD) with hydrogen chloride. In a stepwise mechanism, protonation of the alkene is followed by C-C bond migration.

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proposed reaction pathways

Key Words

cyclobutanones, pinacol rearrangement, organocatalysis

ID: J48-Y2023