SYNTHETIC AND MODEL COMPUTATIONAL STUDIES OF MOLAR ROTATION ADDITIVITY FOR INTERACTING CHIRAL CENTERS - A REINVESTIGATION OF VANT-HOFF PRINCIPLE

When plane-polarized light impinges on a solution of optically active molecules, the polarization of the light that emerges is rotated. This simple phenomenon arises from the interaction of light with matter an d is well understood, in principle. van't Hoff's rule of optical super position correlates the molar rotation with the individual contributio ns to optical activity of isolated centers of asymmetry. This straight forward empirical additivity rule is rarely used for structure elucida tion nowadays because of its limitations in the assessment of conforma tionally restricted or interacting chiral centers. However, additivity can be used successfully to assign the configuration of complex natur al products such as hennoxazole A if appropriate synthetic partial str uctures are available. Therefore, van't Hoff's principle is a powerful stereochemical complement to natural products' total synthesis. The q uest for reliable quantitative methods to calculate the angle of rotat ion a priori has been underway for a long time. Both classical and qua ntum methods for calculating molar rotation have been developed. Of pa rticular practical importance for determining the absolute structure o f molecules by calculation is the manner in which interactions between multiple chiral centers in a single molecule are included, leading to additive or non-additive optical rotation angles. This problem is add ressed here using semi-empirical electronic structure models and the R osenfeld equation. (C) 1997 Wiley-Liss, Inc.