Molecular tools useful for the preparation of enantiopure compounds and simultaneous determination of their absolute configurations

Abstract

To obtain enantiopure compounds, the so-called chiral high performance liqui chromatography (HPLC) method, i.e., HPLC using a chiral stationary phase, is very useful as reviewed in the present Special Issue. On the other hand, normal HPLC (on silica gel separation of diastereomers is also useful for the preparation of enantiopure compounds an also for the simultaneous determination of their absolute configurations (ACs). The author an coworkers have developed some chiral molecular tools, e.g., camphorsultam dichlorophthalic aci (CSDP acid), 2-methoxy-2-(1-naphthyl)propionic acid (MΑNP acid), and others suitable for thi purpose. For example, a racemic alcohol is esterified with (S)-(+)-MΑNP acid, yielding diastereomeri esters, which are easily separable by HPLC on silica gel. The ACs of the obtained enantiopure MΑN esters can be determined by the 1H-NMR diamagnetic anisotropy method. In addition, MΑN or CSDP esters have a high probability of giving single crystals suitable for X-ray crystallography From the X-ray Oak Ridge thermal ellipsoid plot (ORTEP) drawing, the AC of the alcohol part ca be unambiguously determined because the AC of the acid part is already known. The hydrolysis o MΑNP or CSDP esters yields enantiopure alcohols with the established ACs. The mechanism an application examples of these methods are explained.