A practical synthesis of enantiopure N-carbobenzyloxy-N′-phthaloyl-cis-1,2-cyclohexanediamine by asymmetric reductive amination and the Curtius rearrangement

Enantiomerically pure N-carbobenzyloxy-N′-phthaloyl-cis-1,2-cyclohexanediamine was synthesized by the asymmetric reduction of a β-enamino ester formed from benzyl 2-oxocyclohexanecarboxylate and (R)-phenylethylamine, followed by hydrogenolysis, phthaloylation, and the Curtius rearrangement.

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(1S,2R)-2-Aminocyclohexanecarboxylic acidC7H13NO2Ee = >99%[α]D29=+20.2 (c 0.25, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(1S,2R)-2-Phthalimidocyclohexanecarboxylic acidC15H15NO4Ee = >99%[α]D28=+98.3 (c 1.00, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(1S,2R)-1-(N-Benzyloxycarbonylamino)-2-phthalimidocyclohexaneC22H22N2O4Ee = >99%[α]D29=+92.1 (c 0.10, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(1S,2R)-1-(N-Benzyloxycarbonylamino)-2-acetamidecyclohexaneC16H22N2O3Ee = >99%[α]D29=+33.6 (c 0.10, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)