Amine Transaminase-Catalyzed Enantioselective Synthesis of Cyclohexylidene-Based Axially Chiral Amines

We report an unprecedented amine transaminase-catalyzed asymmetric transamination of 4-alkylidene cyclohexanones, affording various axially chiral alkylidene cyclohexane amines in high conversions (up to 99%) and excellent stereoselectivities (mostly between 96% and 99% ee). The synthetic prospect was underscored further by efficient preparative-scale synthesis (67-83% isolated yields) and downstream product derivatization. Molecular dynamics simulations and related mutational studies were conducted to gain insights into effective catalysis, including the rationale for the superb observed enantioselectivity.