(R)-(4-(Benzyloxycarbonylphenyl)-3-hydroxy-4,4-dimethyl-2-pyrrolidinone) acrylate derivative as a chiral dienophile for the synthesis of enantiopure 2-aminocyclohexane carboxylic acids

An asymmetric Diels–Alder reaction between the enantiopure (R)-benzyl-4-(3-acryloyloxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)-benzoate (R)-2 and the N-Z-aminodiene 3 proceeded with total endo diastereoselectivity and was facially controlled in favour of the (3′R,1R,2S)-adduct. The two adducts obtained, 4 (the main compound) and 5, were isolated pure after column chromatography on silica gel. Their LiOH hydrolysis followed by palladium-catalyzed hydrogenation of the double bond concomitant with hydrogenolysis of the carbamate moiety yielded the enantiopure cis-2-aminocyclohexane carboxylic acids (1R,2S)-8 and (1S,2R)-8.

Figure optionsDownload as PowerPoint slide

[N-(4-Benzyloxycarbonylphenyl)-4,4-dimethyl-2-oxopyrrolidin-3-yl]-2-(benzyloxycarbonylamino)cyclohex-3-ene-l-carboxylateC35H36N2O7De >99%[α]D20=+65 (c 0.5, CH2Cl2)Source of chirality: (R)-benzyl-4-(3-acryloyloxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)-benzoateAbsolute configuration: (3′R,1R,2S)

[N-(4-Benzyloxycarbonylphenyl)-4,4-dimethyl-2-oxopyrrolidin-3-yl]-2-(benzyloxycarbonylamino)cyclohex-3-ene-l-carboxylateC35H36N2O7De >99%[α]D20=-35 (c 0.35,CH2Cl2)Source of chirality: (R)-benzyl-4-(3-acryloyloxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)-benzoateAbsolute configuration: (3′R,1S,2R)

2-(Benzyloxycarbonylamino)cyclohex-3-ene-1-benzylcarbamoyleC15H17NO4Ee >99%[α]D20=+112 (c 2.3, CH2Cl2)Source of chirality: (R)-benzyl-4-(3-acryloyloxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)-benzoateAbsolute configuration: (1R,2S)

2-(Benzyloxycarbonylamino)cyclohex-3-ene-1-benzylcarbamoyleC15H17NO4Ee >99%[α]D20=-129 (c 1.0, CH2Cl2)Source of chirality: (R)-benzyl-4-(3-acryloyloxy-4,4-dimethyl-2-oxopyrrolidin-1-yl)-benzoateAbsolute configuration: (1S,2R)