Ruthenium(II)/chiral Brønsted acid co-catalyzed enantioselective four-component reaction/cascade aza-Michael addition for efficient construction of 1,3,4-tetrasubstituted tetrahydroisoquinolines

Abstract

An elegant synergistic catalytic system comprising a ruthenium complex with a chiral Brønsted acid was developed for a four-component Mannich/cascade aza-Michael reaction. The ruthenium-associated ammonium ylides successfully trapped with in situ generated imines indicates a stepwise process of proton transfer in the ruthenium-catalyzed carbenoid N-H insertion reaction. The different decomposition abilities of various ruthenium complexes towards diazo compounds were well explained by the calculated thermodynamic data. The transformation features a mild, rapid, and efficient method for the synthesis of enantiomerically pure 1,3,4-tetrasubstituted tetrahydroquinolines bearing a quaternary stereogenic carbon center from simple starting precursors in moderate yields with high diastereo- and enantioselectivity.

Keywords: Brønsted acid; multicomponent reactions; ruthenium; synergistic catalysis; tetrahydroisoquinolines.