Bifunctional iminophosphorane organocatalyst with additional hydrogen bonding: Calculations predict enhanced catalytic performance in a michael addition reaction.

A new iminophosphorane-thiourea superbase was rationally designed and investigated as an organocatalyst for the enantioselective Michael addition reaction of nitromethane to 4-phenylbut-3-en-2-one. Starting from an iminophosphorane-thiourea organocatalyst structure already known, we have used theoretical calculations to determine the structures of transition states involved in the carbon-carbon bond formation step and carried out structural modifications to accelerate the reaction rate and to increase the enantioselectivity. The effective structural modification was adding a rigid hydroxyl group able to make an additional hydrogen bond to the transition state, producing a substantial decrease of the ΔG by 7 kcal mol. The enantiomeric excess is predicted to be above of 97% using the reliable M06-2X and ωB97M - V functionals. The determination of the complete reaction mechanism and free energy profile was followed by a detailed microkinetic analysis. The present study points out a new direction for structural modifications on this kind of organocatalyst.