Concentration Effect in the Asymmetric Michael Addition of Acetone to β-Nitrostyrenes Catalyzed by Primary Amine Thioureas

Abstract

Bifunctional primary amine thiourea (PAT) organocatalysts show remarkable improvement in enantioselectivity and catalytic activity (turnover frequency) in the asymmetric Michael addition of acetone to β-nitrostyrenes upon dilution. Mechanistic investigations indicate that this behavior corresponds to the inhibition of off-cycle catalyst deactivation at low concentration, rather than to the operation of aggregation phenomena at high concentration. Reaction at low concentration (≤0.2 M in β-nitrostyrene) leads to the minimization of catalyst deactivation and, thus, to the optimization of yield and ee of the Michael­ addition products.