High-Pressure-Mediated Thiourea-Organocatalyzed Asymmetric Michael Addition to (Hetero)aromatic Nitroolefins: Prediction of Reaction Parameters by PCP-SAFT Modelling.

Thiourea-organocatalyzed Michael additions of diethyl malonate to various heteroaromatic nitroolefins (13 examples) have been studied under high-pressure (up to 800 MPa) and ambient pressure conditions. High pressure was conducive to enhanced product yields by a factor of 2-12 at a given reaction time, high reaction rates (reaction times were decreased from 72-24 h down to 4-24 h) and high enantioselectivity. Elucidating the effects of solvents for maximizing reaction rates and yields has been carried out using the Perturbed-Chain Polar Statistical Associating Fluid Theory (PCP-SAFT), allowing for the first time a prediction of the kinetic profiles under high-hydrostatic-pressure conditions.