DACH-Based Chiral Sensing Platforms as Tunable Benzamide-Chiral Solvating Agents for NMR Enantioselective...

Chiral discrimination is an indispensable tool that has pivotal importance in the assignment of absolute configuration and determination of enantiomeric excess in chiral compounds. A series of enantiomerically pure trans-1,2-diaminocyclohexane (trans-DACH)-derived benzamides were first synthesized by simple chemical steps, and 14 variated derivatives 6a-6n have been assessed as NMR chiral solvating agents (CSAs) for discrimination of the signals of mandelic acid (MA) in ¹H NMR analysis. The highly efficient chiral recognition of CSA 6e on different substrates, including MAs, carboxylic acids, amino acid derivatives, and phosphoric acids (32 examples), was expanded via ¹H, ¹⁹F, and ³¹P NMR spectroscopy. The quality of enantiodiscrimination was evaluated by means of the enantioresolution parameter R_s. Single-crystal X-ray analysis of three derivatives 6c, 6e, and 6h helped to understand enantiomeric recognition for the promising NMR analysis. Interestingly, the NMR signals of nonequivalent protons between the R and S configurations were completely opposite in the presence of CSA 6e and its stereoisomer, which can be utilized to establish a straightforward method for the configuration assignment of diverse hydroxy acid substrates.