Limitations of Trifluoromethylbenzoimidazolylbenzoic Acid as a Chiral Derivatizing Agent to Assign Absolute Configuration for beta-Chiral Aminoalcohols

Abstract

Axially chiral 2-(2-(trifluoromethyl)-1H-benzo[d]-imidazole-1-yl)benzoic acid (TBBA) was used as a chiral derivatizing agent to evaluate the limits of absolute configuration assignment for beta-chiral aminoalcohols. Seven Boc-aminoalcohols and eight variously N-substituted (S)-phenylglycinols were prepared, and their TBBA esters were analyzed by NMR spectroscopy. Diverse substitution at the beta-position was employed to demonstrate the effect of structure on the general conformational model and reliability of the absolute configuration assignment. It was concluded that hydrogen bond formation and steric hindrance were the main factors affecting the correct assignment for Boc-aminoalcohols.