Modified Kagan's amide: synthesis and application as a chiral solvating agent for hydrogen-bonding based chiral discrimination in NMR

Abstract

A modified Kagan's amide, N-((S)-1-(3,5-bis(trifluoromethyl)phenyl)ethyl)-3,5-dinitrobenzamide [(S)-2] has been designed, synthesized and screened as a Chiral Solvating Agent (CSA) for discrimination of optically active substrates. The proposed mode of action for recognition of chiral isomers of analytes by CSA is based on hydrogen-bonding. The ¹H NMR signals of the two isomers of chiral amides, sulfoxides, α-substituted acids, α-hydroxy ketone, epoxy ketone and N-protected amino acids with (S)-2 were well resolved for practical applications of determination of optical purity. The CSA was also screened for detection of separation of signals in ¹⁹F NMR.