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-1. 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.

Overreact, an in silico lab: Automative quantum chemical microkinetic simulations for complex chemical reactions.

Today's demand for precisely predicting chemical reactions from first principles requires research to go beyond Gibbs' free energy diagrams and consider other effects such as concentrations and quantum tunneling. The present work introduces overreact, a novel Python package for propagating chemical reactions over time using data from computational chemistry only. The overreact code infers all differential equations and parameters from a simple input that consists of a set of chemical equations and quantum chemistry package outputs for each chemical species. We evaluate some applications from the literature: gas-phase eclipsed-staggered isomerization of ethane, gas-phase umbrella inversion of ammonia, gas-phase degradation of methane by chlorine radical, and three solvation-phase reactions. Furthermore, we comment on a simple solvation-phase acid-base equilibrium. We show how it is possible to achieve reaction profiles and information matching experiments.

Free energy profile and microkinetic modeling of base-catalyzed conjugate addition reaction of nitroalkanes to α,ß-unsaturated ketones in polar and apolar solvents.

Michael reactions involving nitroalkanes and enones are important carbon-carbon bond formation reactions. These reactions are base-catalyzed, and during the past 15 years, the asymmetric version using bifunctional amino-thiourea organocatalyst has been developed. In this work, the reaction of nitromethane and 4-phenyl-3-buten-2-one, catalyzed by the methoxide ion and piperidine as bases, was investigated by theoretical calculations. We obtained the theoretical free energy profile and did a microkinetic analysis of the catalytic cycle. The direct reaction of the CH2NO2- ion and the enone is very favorable, with a free energy of activation of 21.1 kcal mol-1 in methanol solvent. However, the generated MS2 product works like an inhibitor of the catalysis, and the effective barrier in the catalytic cycle becomes 25.5 kcal mol-1, leading to slow kinetics at room temperature. In the case of the reaction in apolar solvent (toluene), we found a pathway involving isomerization from the CH3NO2 reactant to the CH2NO2H species, and the latter makes a nucleophilic attack on the enone. Piperidine works like a bifunctional catalyst. In this case, the barrier is very high (32.5 kcal mol-1), indicating the importance of the polar environment to accelerate the reaction in the catalytic cycle. Graphical abstract Base-catalyzed conjugate addition reaction of nitroalkanes to α,ß-unsaturated ketones.