Origins of Stereoselectivity in Chiral Aminoalcohol Catalysis of Oxyallyl Cation-Indole Reactions.

The enantioselective coupling of indoles with racemic α-tosyloxy ketones mediated by a chiral amino alcohol catalyst is studied with density functional theory (DFT) calculations. The addition of indole to an oxyallyl cation intrinsically favors the (S,S) and (R,R) stereoisomeric products through electrostatic interactions in the transition state. Our model shows that the enantioselectivity is controlled by the cyclohexane moiety of the catalyst; selectivity diminishes upon removal of the cyclohexane ring. Substitution to enhance the enantioselectivity of this reaction is proposed.