A facile synthesis of enantiopure 7-benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carboxylic acid

An efficient procedure for the preparation of enantiopure 7-benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carboxylic acids is described.

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N-[(1S)-Phenylethyl]-(1S,2R,4R)-7-benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carboxamideC23H26N2O3[α]D25=-4.0 (c 1.0, CHCl3)Source of chirality: (S)-phenylethylamineAbsolute configuration: (1S,2R,4R,1′S)

N-[(1S)-Phenylethyl]-(1R,2S,4S)-7-benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carboxamideC23H26N2O3[α]D25=-23.5 (c 1.0, CHCl3)Source of chirality: (S)-phenylethylamineAbsolute configuration: (1R,2S,4S,1′S)

3-[(1R,2S,4S)-7-Benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carbonyl]-(4S)-(2-methylethyl)-2-oxazolidinoneC21H26N2O5[α]D25=+20.0 (c 1.0, CHCl3)Source of chirality: (S)-valineAbsolute configuration: (1R,2S,4S,4′S)

3-[(1S,2R,4R)-7-Benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carbonyl]-(4S)-(2-methylethyl)-2-oxazolidinoneC21H26N2O5[α]D25=+77.7 (c 1.0, CHCl3)Source of chirality: (S)-valineAbsolute configuration: (1S,2R,4R,4′S)

3-[(1R,2S,4S)-7-Benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carbonyl]-(4S)-methyl-2-oxazolidinoneC19H22N2O5[α]D25=+3.7 (c 1.0, CHCl3)Source of chirality: (S)-alanineAbsolute configuration: (1R,2S,4S,4′S)

3-[(1S,2R,4R)-7-Benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carbonyl]-(4S)-methyl-2-oxazolidinoneC19H22N2O5[α]D25=+66.2 (c 1.0, CHCl3)Source of chirality: (S)-alanineAbsolute configuration: (1S,2R,4R,4′S)

3-[(1R,2S,4S)-7-Benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carbonyl]-(4S)-(2-methylpropyl)-2-oxazolidinoneC22H28N2O5[α]D25=+27.3 (c 1.0, CHCl3)Source of chirality: (S)-leucineAbsolute configuration: (1R,2S,4S,4′S)

3-[(1S,2R,4R)-7-Benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carbonyl]-(4S)-(2-methylpropyl)-2-oxazolidinoneC22H28N2O5[α]D25=+72.2 (c 1.0, CHCl3)Source of chirality: (S)-leucineAbsolute configuration: (1S,2R,4R,4′S)

3-[(1R,2S,4S)-7-Benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carbonyl]-(4S)-[(1S)-methylpropyl]-2-oxazolidinoneC22H28N2O5[α]D25=+24.6 (c 1.0, CHCl3)Source of chirality: (S)-isoleucineAbsolute configuration: (1R,2S,4S,4′S,2″S)

3-[(1S,2R,4R)-7-Benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carbonyl]-(4S)-[(1S)-methylpropyl]-2-oxazolidinoneC(S)H22H28N2O5[α]D25=+74.2 (c 1.0, CHCl3)Source of chirality: (S)-isoleucineAbsolute configuration: (1S,2R,4R,4′S,2″S)

(1R,2S,4S)-7-Benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carboxylic acidC15H17NO4>99% ee (by HPLC)[α]D25=-8.6 (c 1.0, CHCl3)Source of chirality: chiral pool.Absolute configuration: (1R,2S,4S)