DFT-Guided Mechanistic Insights into Chemodivergence: A Mixed Explicit-Implicit Solvent Description to Dictate the Chemoselectivity.

Herein we report a density functional theory (DFT)-guided mechanistic investigation of the nitrile reduction reaction, which exhibits a solvent-dependent chemodivergence. This study reveals an interesting mechanistic picture, highlighting the exact role of a protic solvent, isopropanol, in regulating the reaction outcome. The explicit solvent effect involving polar protic isopropanol favors imine metathesis by proton hopping through stepwise addition and elimination steps and thus produces a secondary amine as the final product. In contrast, the nonpolar solvent -hexane is incapable of facilitating the proton migration and stops the solvent-assisted imine metathesis. As a result, only primary amines are obtained as the final product. This DFT study provides a recipe for the choice of solvents that can dictate chemoselectivity in product formation.