The origin for highly enantioselective induction of 1-naphthol to isatin-derived N-Boc ketimines catalyzed by quinine thiourea catalyst: an experimental and computational study

Abstract

An enantioselective aza-Friedel–Crafts reaction of 1-naphthol with isatin derived N-Boc ketimines by cinchona based bifunctional thiourea as organo-catalyst is reported. In general the derivatives of Betti base are formed in excellent enantioselectivities (95–99%) with high yields (<99%). The combination of experimental and computational studies have revealed the origin of the stereoselectivity of the aza-Friedel–Crafts reaction of 1-naphthol with isatin derived N-Boc ketimines by cinchona based bifunctional thiourea as organo-catalyst. The attractive electrostatic interactions in the Re face transition state and the deleterious lone-pair⋯π interactions in the Si face transition state governed the formation of Re-face as a major product in this aza Friedel–Crafts reaction. The NMR studies performed to examine the formation of the complex with 1-naphthol, isatin derived N-Boc ketimines and cinchona based bifunctional thiourea catalyst has corroborated the calculated complex geometry employed in the study.