Synthesis and applications of exo N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)benzamides as NMR solvating agents for the chiral discrimination of 1,1′-binaphthyl-2,2′-diyl hydrogenphosphates and α-substituted acids

A series of exo N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)benzamides were prepared from (R)-isobornyl amine and screened as chiral solvating agents to discriminate the isomers of 1,1′-binaphthyl-2,2′-diyl hydrogenphosphates by 31P NMR analysis. A linear relationship between the experimental and calculated enantiomeric purity was established indicating the potential use of the system to determine the ee for samples of this acid of unknown enantiomeric purity. The amides were also screened for chiral discrimination of some α-substituted acids by 19F NMR analysis.

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N-((1R,2R,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-yl)benzamideC17H23NO[α]D28 = −70.8 (c 1.0, CHCl3)Source of chirality: (R)-iso-bornylamineAbsolute configuration: (1R,2R,4R)

4-Flouro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)benzamideC17H22FNO[α]D28 = −7.7 (c 1.0, CHCl3)Source of chirality: (R)-iso-bornylamineAbsolute configuration: (1R,2R,4R)

4-Nitro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)benzamideC17H22N2O3[α]D28 = −73.4 (c 1.0, CHCl3)Source of chirality: (R)-iso-bornylamineAbsolute configuration: (1R,2R,4R)

3,5-Dichloro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)benzamideC17H21Cl2NO[α]D28 = −16.4 (c 1.0, CHCl3)Source of chirality: (R)-iso-bornylamineAbsolute configuration: (1R,2R,4R)

3,5-Bis(triflouromethyl)-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)benzamideC19H21F6NO[α]D28 = −44.6 (c 1.0, CHCl3)Source of chirality: (R)-iso-bornylamineAbsolute configuration: (1R,2R,4R)

3,5-Dinitro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)benzamideC17H21N3O5[α]D28 = −62.8 (c 1.0, CHCl3)Source of chirality: (R)-iso-bornylamineAbsolute configuration: (1R,2R,4R)

4-Chloro-3,5-dinitro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)benzamideC17H20ClN3O5[α]D28 = −58.7 (c 1.0, CHCl3)Source of chirality: (R)-iso-bornylamineAbsolute configuration: (1R,2R,4R)

4-Trifluoromethyl-2-nitro-N-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)benzamideC18H21F3N2O3[α]D28 = −42.3 (c 1.0, CHCl3)Source of chirality: (R)-iso-bornylamineAbsolute configuration: (1R,2R,4R)