Chemoenzymatic Preparation of Optically Active trans‐Cyclohexane‐1,2‐diamine Derivatives: An Efficient Synthesis of the Analgesic U‐(−)‐50,488

• Published in: Chemistry – A European Journal
• Main Authors: González‐Sabín, Javier, Gotor, Vicente, Rebolledo, Francisca
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2004
• Subjects: Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/chem.200400607; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fchem.200400607; https://onlinelibrary.wiley.com/doi/full/10.1002/chem.200400607

Abstract Stereoespecific syntheses of (±)‐ trans ‐ N , N ‐cyclohexane‐1,2‐diamines ((±)‐ 4 a – g ) were carried out from the corresponding (±)‐ trans ‐ N , N ‐dialkylaminocyclohexanols by successive treatment with mesyl chloride and aqueous ammonia. The stereochemical outcome indicates the formation of a meso ‐aziridinium ion intermediate. Kinetic resolutions of diamines (±)‐ 4 were efficiently accomplished in aminolysis reactions catalyzed by lipase B from Candida antarctica with ethyl acetate as the solvent and acyl donor. Acetamides and the remaining diamines, isolated as the benzyloxycarbonyl derivatives, were obtained with very high ee values (92–99 %). One of the carbamates was used as a precursor of the analgesic U‐(−)‐50,488.