title: Asymmetric Schmidt reaction of hydroxyalkyl azides with ketones.
abstract: An asymmetric equivalent of the Schmidt reaction permits stereocontrol in ring expansions of symmetrical cyclohexanones. The procedure involves the reaction of chiral 1,2- and 1,3-hydroxyalkyl azides with ketones under acid catalysis; the initial reaction affords an iminium ether that can be subsequently opened with base. A systematic study of this reaction is reported, in which ketone substrates, chiral hydroxyalkyl azides, and reaction conditions are varied. Selectivities as high as ca. 98:2 are possible for the synthesis of substituted caprolactams, with up to 1,7-stereoselection involved in the overall process. The fact that either possible migrating carbon is electronically identical provides an unusual opportunity to study a ring-expansion reaction controlled entirely by stereoelectronic factors. The mechanism of the reaction and the source of its stereoselectivity are also discussed.
authors.affiliation: Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott Hall, Room 4070, University of Kansas, Lawrence, KS 66045-2506, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Sahasrabudhe
authors.forename: Vijaya
authors.initials: V
authors.lastname: Gracias
authors.forename: Kelly
authors.initials: K
authors.lastname: Furness
authors.forename: Brenton T
authors.initials: BT
authors.lastname: Smith
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Katz
authors.forename: D Srinivasa
authors.initials: DS
authors.lastname: Reddy
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
mesh_terms: D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry*; D003512:Cyclohexanones / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D013237:Stereoisomerism
chemical_list: D001386:Azides; D003512:Cyclohexanones; D007659:Ketones; D007769:Lactams