Mechanochemical Asymmetric Cross-Dehydrogenative Coupling Reaction: Liquid-Assisted Grinding Enables Reaction Acceleration and Enantioselectivity Control

We report here a mechanochemical protocol for asymmetric cross-dehydrogenative coupling (CDC) reaction of unreactive 3-arylmethyl indoles with 1,3-dicarbonyl by liquid-assisted grinding. Small drops of liquid additive n-butyl acetate (n-BuOAc) are key to achieve high yield and enantioselectivity in this transformation. The catalyst can be lowered to 5 mol% and reused for three times. Pharmaceutical useful chiral dihydrocoumarins are further achieved through one-pot tandem asymmetric CDC and cyclization with excellent enantioselectivities. Experimental and computational studies on the reaction mechanism suggest that n-BuOAc is participated to the catalytic cycle, forming a chiral metal species during the reaction process and thereby revealed the origin of stereoselectivity.