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

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.