Chapter 18 - Novel chiral derivatizing agents powerful for enantioresolution and determination of absolute stereochemistry by X-ray crystallographic and 1H NMR anisotropy methods

Abstract

This chapter discusses the determination of the absolute configuration of chiral compounds by x-ray crystallography and the proton nuclear magnetic resonance (1H NMR) anisotropy method. Chiral carboxylic acids are novel molecular tools proven to be powerful for enantioresolution and simultaneous determination of absolute configuration of various alcohols by high-performance liquefied chromatography (HPLC) separation, determination of absolute configuration by X-ray crystallography and/or by 1H NMR anisotropy method. The X-ray crystallographic method using an internal reference is, of course, the best for determining absolute configuration. However, ideal single crystals are not always obtained. In such a case, the 1H NMR method using propionic acid (MαNP), which requires no crystallization, is effective. In enantioresolution, chiral camphorsultan dichlorophthalic acid (CSDP) and MαNP acid are thus useful as the complementary molecular tools. If the resolution with one chiral derivatizing agent (CDA) is unsuccessful, the use of the other is suggested. The methods described above are very powerful for the preparation of enantiomeric alcohols with 100% enantiopurity, and also for the simultaneous determination of their absolute configurations. Further application of these methods to various compounds and studies toward the mass production of enantiomers is now in progress.