Computational investigation of Rh-catalyzed three-component arylamidation of alkenes: mechanism, regioselectivity, and enantioselectivity

Abstract

The Rh-catalyzed three-component arylamidation of allylic sulfides was studied computationally to explore the mechanism, regioselectivity, and enantioselectivity. In one-pot multicomponent reactions, a significant challenge is that substrate promiscuity promotes competing two-component pathways. Our calculations indicate that the catalyst preferentially coordinates with arylboronic acid compared to alternative substrates. The calculated catalytic cycle comprises sequential stages: base-assisted transmetalation, 1,2-migratory insertion, CO₂ extrusion, nitrene migratory insertion, and HFIP-mediated protodemetalation. The regioselectivity-determining 1,2-migratory insertion that favors anti-Markovnikov pathways stems from reduced transition state distortion. For enantioselectivity, the (S)-thioether amide is preferentially formed, with NCI analysis revealing enhanced π–π stacking and C–H/π weak interactions between the chiral catalyst and substrates. These results provide valuable insights into the understanding of Rh-catalyzed multicomponent reactions for the synthesis of thioether amides.