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

23 March 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

A catalytic protio-semipinacol ring-expansion reaction has been developed for the highly enantioselective conversion of ter-tiary vinyl cyclopropanols into cyclobutanone products bearing alpha-quaternary stereogenic centers. The method relies on the co-catalytic effect of a chiral dual-hydrogen-bond donor (HBD) with hydrogen chloride. Experimental and computational evidence is provided for a stepwise mechanism proceeding through an enantiodetermining, HBD-promoted protonation of the alkene to generate a discrete carbocationic intermediate. This short-lived (20 ps), high-energy carbocation is generated in a chiral conformation in the presence of HBD catalyst and undergoes subsequent stereospecific C–C bond migration to the enantioenriched product. This research applies strong acid/chiral HBD co-catalysis to weakly basic olefinic substrates and lays the foundation for further investigations of enantioselective reactions involving high-energy cationic intermediates.

Supplementary materials

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Title
Supporting Information for Dual-Hydrogen-Bond Donor and Brønsted Acid Co-Catalysis Enables Highly Enantioselective Protio-Semipinacol Rearrangement Reactions
Description
Experimental procedures, spectral data, additional kinetic data, and information regarding the DFT calculations.
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