Chloride-Mediated Alkene Activation Drives Enantioselective Thiourea and Hydrogen Chloride Co-Catalyzed Prins Cyclizations.

ABSTRACT: The mechanism of chiral hydrogen-bond donor (HBD) and hydrogen chloride (HCl) co-catalyzed Prins cyclizations was analyzed through a combination of experimental and computational methods and revealed to involve an unexpected and previously unrecognized mode of alkene activation. Kinetic and spectroscopic studies support the participation of a catalytically active HCl·HBD complex that displays reduced Brønsted acidity relative to HCl alone. Nevertheless, rate acceleration relative to the HCl-catalyzed background reaction as well as high levels of enantioselectivity are achieved. This inverse Brønsted correlation is ascribed to chloride-mediated substrate activation in the rate-limiting and enantiodetermining cyclization transition state. Density functional theory (DFT) calculations, distort

SUBMITTER: Kutateladze DA 

PROVIDER: S-EPMC9437134 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature