Mechanochemical Stereoselective Povarov Reaction via Brønsted Acid Organocatalysis

Abstract

Mechanochemically-assisted multicomponent Povarov reaction catalyzed by chiral BINOL-derived TRIP organocatalyst enabled the stereoselective synthesis of various tetrahydroquinolines in good yields and high enantiomeric purities. This represents a new example for the thus far less explored stereoselective transformations under mechanochemical conditions utilizing noncovalent asymmetric organocatalysis. A series of conventional and alternative solvents was tested for the liquid-assisted grinding. The solvent additive has a considerable influence on the stereocontrol of the reaction. The mechanochemical reaction setup offers better mass intensity values than the solution-based variant. The isolation of the addition intermediate and significant effect of solvent polarity suggests a stepwise polar mechanism. DFT calculation provided insights into the stereoinduction of the reaction.