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.

Functional changes of biomolecules and organocatalysts as a probe for pressure effects in solution.

High pressure acts as a mild and non-destructive activation mode for chemical reactions. However, in the context of organo-/biocatalysis, high pressure activation, has not been investigated systematically, although there are significant benefits such as rate acceleration, increased selectivity and the possibility of suppressing side product formation. The influence of hydrostatic pressure in solution on the catalytic performance of enzymes and small molecule organocatalysts such as amino acids, peptides, amines, cinchona alkaloids and thioureas is evaluated in this review, taking reactivity and selectivity as a probe to identify pressure effects on biomolecules.