Chiral Molecular Science: How were the absolute configurations of chiral molecules determined? "Experimental results and theories"

Abstract

Molecular chirality is a key concept in chemistry, bioscience, and molecular technology, like the invention of a light-powered chiral molecular motor explained in this review. Thus, the primary research subject is how to determine the absolute configuration (AC) of chiral compounds. This review article focuses on the principle, theory, and practice of the nonempirical methods for determining ACs of chiral compounds, i.e., the Bijvoet method in X-ray crystallography and the circular dichroism (CD) exciton chirality method, together with the historical aspects of AC determination. The theoretical equations of X-ray crystallography and exciton CD spectroscopy are explained in detail, and these equations are useful for readers to understand the principle and mechanism of these methods. This review also focuses on the relative methods, where the internal reference with known AC is used and the relative configuration is determined by X-ray crystallography and/or ¹ H nuclear magnetic resonance (NMR) diamagnetic anisotropy method. In these cases, CSDP acid and MαNP acid are useful for the chiral resolution of racemic alcohols, where their diastereomeric esters are easily separable by high-performance liquid chromatography (HPLC) on silica gel. Thus, these methods are useful for the preparation of enantiopure compounds and simultaneous determination of their ACs. In this review article, the above methods are explained mainly based on the author's own research results.

Keywords: 1H NMR diamagnetic anisotropy method; Bijvoet method; CD exciton chirality method; CSDP and MαNP acids; ORD and CD spectroscopy; X-ray crystallography.