title: Synthesis of enantiomerically enriched (R)-5-tert-butylazepan-2-one using a hydroxyalkyl azide mediated ring-expansion reaction.
abstract: A procedure for the conversion of a symmetrical ketone to an enantiomerically pure lactam is described. The technique described here involves a ring-expansion reaction of a 4-substituted cyclohexanone accomplished with a chiral 1,3-azidopropanol derivative. The procedure entails first a one-step preparation of (R)-1-phenyl-3-azidopropanol from a commercially available halide precursor, which is then reacted with the ketone using BF(3) x OEt(2) as a Lewis acid promoter. The resulting lactam is subsequently converted into a chiral lactam of high enantiopurity via the two-stage removal of the chiral nitrogen substituent. The present protocol carries out the diastereoselective ring-expansion reaction with higher selectivity than competing processes and is generally useful for the preparation of 5-substituted caprolactams.
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045-7582, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Ribelin
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
mesh_terms: D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D001386:Azides / Q000737:chemistry*; D002625:Chemistry, Organic / Q000379:methods; D013237:Stereoisomerism
chemical_list: C526594:5-tert-butylazepan-2-one; D001381:Azepines; D001386:Azides