Computational study on the asymmetric aminocatalysed Michael addition reaction of cyclohexanone to trans–β–nitrostyrene

Asymmetric organocatalysed reactions are one of the most fascinating synthetic strategies which one can adopt in order to induct a desired chirality into a reaction product. From all the possible practical applications of small organic molecules in catalytic reaction, amine–based catalysis has attracted a lot of attention during the past two decades. The high interest in asymmetric aminocatalytic pathways is to account to the huge variety of carbonyl compounds that can be functionalized by many different reactions of their corresponding chiral–enamine or –iminium ion as activated nucleophile and electrophile, respectively. Starting from the employment of L–Proline, many useful substrates have been proposed in order to further enhance the catalytic performances of these reaction in terms of enantiomeric excess values, yield, conversion of the substrate and turnover number. In particular, in the last decade the use of chiral and quasi–enantiomeric primary amine species has got a lot of attention in the field. Contemporaneously, many studies have been carried out in order to highlight the mechanism through which these kinds of substrates induct chirality into the desired products. In this scenario, computational chemistry has played a crucial role due to the possibility of simulating and studying any kind of reaction and the transition state structures involved. In the present work the transition state geometries of primary amine–catalysed Michael addition reaction of cyclohexanone to trans–β–nitrostyrene with different organic acid cocatalysts has been studied through different computational techniques such as density functional theory based quantum mechanics calculation and force–field directed molecular simulations.

Computational investigation of a stereoselective synthesis of atropisomeric hydrazides possessing an N–N stereogenic axis

Axially chiral substrates are an interesting and widely studied class of compounds as they can be found in bioactive natural products and are employed as functional materials or as ligands in asymmetric catalytic processes. One branch of this family is the well-known world of the atropisomers. Among them, atropisomeric compounds possessing an N–N stereogenic axis are one truthfully fascinating system but not completely understood yet. In this thesis, we computationally investigated the mechanism of the diastereoselective formation of the N – N chiral axis of a hydrazide under asymmetric phase transfer catalytic conditions. Moreover, during this study, torsional barriers have been calculated for both the reagent and the product at the density functional theory (DFT). These values turned out to suitably match the experimental values and observations. Finally, Electronic Circular Dichroism (ECD) spectra have been simulated in order to assign the chiral absolute configuration to the products.