Enantioselective Tail-to-Head Cyclizations Catalyzed by Dual-Hydrogen-Bond Donors

Chiral urea derivatives are shown
to catalyze enantioselective
tail-to-head cyclization reactions of neryl chloride analogues. Experimental
data are consistent with a mechanism in which π-participation
by the nucleophilic olefin facilitates chloride ionization and thereby
circumvents simple elimination pathways. Kinetic and computational
studies support a cooperative mode of catalysis wherein two molecules
of the urea catalyst engage the substrate and induce enantioselectivity
through selective transition state stabilization.