Nonlinear effects in asymmetric synthesis and stereoselective reactions: Ten years of investigation

Abstract

The first preoccupation of organic chemists was to develop their ability to reproduce the organization of atoms in natural products. This incursion in nature's laboratory gave rise to numerous techniques to transform matter but led to the discovery of her subtle way of producing substances with chirality and the preference of one enantiomer over the other in the living matter gave a lesson in perfection. The development of asymmetric synthesis gave the opportunity to elaborate methods, reagents, and reactions in order to prepare enantiomerically pure compounds. But this journey is far from being over, and there is a lot of surprises left. No chemist would have thought that an enantiomerically impure chiral auxiliary or ligand could give a stereoselection higher than its own and even equivalent to the pure one. Molecules can behave in numerous ways in solution; aggregation or organization can occur depending on the nature of the molecule or its environment. These phenomena give rise to modification of the anticipated enantiomeric excess (ee) of the reaction product. The relation between the ee value of the auxiliary or ligand and the ee value of the product deviates from linearity to give what we now call nonlinear effects (NLEs). The nonlinear effects in asymmetric synthesis and stereoselective reactions reflect molecular interactions and complexity in reaction mechanisms. They can be used to generate products with high ee's from an enantiomerically impure, and more economical to prepare, chiral auxiliary or ligand. Furthermore, the NLEs can also act as a probe to obtain information on the subtle mechanisms by which the enantioselectivity is generated.