Computational studies of organic reactions

A selective reaction is one where, of multiple possible reaction pathways, one pathway dominates. Each pathway is associated with a transition state, however some transition states are more favourable and lower in energy than others. The lowest energy transition state corresponds to the most favourable reaction pathway and hence leads to the major product of a selective reaction.

Selective reactions, whether regio-, enantio- or diastereoselective, are of the significant interest in chemistry due to their widespread implications in both industry, research and on the environment. For example, asymmetric catalysis allows the highly selective formation of purely the desired enantiomer of a particular compound. This is often cheaper, and allows for much better yields, than corresponding unselective methods. Hence the amount of waste can be reduced while the efficiency and ease of selective chemical syntheses and processes can be improved.

Understanding the selectivity behind a reaction relies on a knowledge of the reaction mechanism and relevant transition states, as well as the underlying factors that determine the energy of each transition state. Such insights into reaction mechanisms may be obtained by a thorough exploration of their potential energy surfaces, a mathematical function that gives the energy of the system as a function of the positions of all the atoms within it. The ground state species of a reaction, i.e. reactants, intermediates, or products, are represented by minima on the potential energy surface, whilst transition states are represented by saddle points. A variety of computational methods exist that can be used to explore the potential energy surface of a reaction, for example density functional theory (DFT), an ab initio, quantum mechanical method which derives the energy of a system based only on its electron density, and molecular mechanics, which uses classical mechanics to describe molecules.

Hence quantum mechanical calculations, such as those carried out using DFT, can be used to locate and determine the energy of transitions states and hence elucidate reaction mechanisms. Such detailed insights enables the rational design of improved selective catalysts, the application of existing catalysts to new selective reactions, and the tuning of existing selective processes to improve yield and efficiency.

The basis of this research involves the use of computational methods, such as DFT and molecular mechanics, to investigate the mechanistic details of a variety of selective reactions. Transition-metal catalysed selective C-H borylation of arenes and organocatalyzed enantioselective aldol condensations are two such examples of reactions of interest.