Novel NMR chiral solvating agents derived from (1R,2R)-diaminocyclohexane: synthesis and enantiodiscrimination for chiral carboxylic acids

A series of new compounds, (1R,2R)-1-(1′,8′-naphthalimide)-2-aminocyclohexane 1 and its 4′-derivatives 2 and 3 derived from (1R,2R)-1,2-diaminocyclohexane have been synthesized conveniently and efficiently. 1H NMR spectroscopy was employed to investigate their enantiodiscriminating ability. Compared with α-phenylethylamine, a commercially available chiral solvating agent (CSA), these compounds exhibited better enantiodiscriminating ability toward the chiral carboxylic acids we had chosen, distinguishing them as promising and practical CSAs.

Graphical abstract(1R,2R)-1-(1′,8′-Naphthalimide)-2-aminocyclohexane and its 4′-derivatives derived from (1R,2R)-diaminocyclohexane are efficient NMR chiral solvating agents for chiral carboxylic acids leading to large separation (ΔΔδ up to 104.1 Hz) of the proton signals of the enantiomers.Figure optionsDownload full-size imageDownload as PowerPoint slide

(1R,2R)-1-(1′,8′-Naphthalimide)-2-aminocyclohexaneC18H18N2O2Ee 100%[α]D20=+2.3 (c 2.50, CHCl3)Source of chirality: (1R,2R)-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R)

(1R,2R)-1-(4′-Bromo-1′,8′-naphthalimide)-2-aminocyclohexaneC18H17BrN2O2Ee 100%[α]D20=-12.8 (c 0.065, CHCl3)Source of chirality: (1R,2R)-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R)

(1R,2R)-1-(4′-Dimethylamino-1′,8′-naphthalimide)-2-aminocyclohexaneC20H23N3O2Ee 100%[α]D20=-16.0 (c 0.025, CHCl3)Source of chirality: (1R,2R)-1,2-diaminocyclohexaneAbsolute configuration: (1R,2R)