title: Asymmetric synthesis and applications of beta-amino Weinreb amides: asymmetric synthesis of (S)-coniine.
abstract: Conjugate addition of lithium (S)-N-benzyl-N-alpha-methylbenzylamide to a range of alpha, beta-unsaturated Weinreb amides proceeds with high levels of diastereoselectivity (>95% de). The beta-amino Weinreb amide products may be transformed into beta-amino ketones via reactions with Grignard reagents, while treatment with DIBAL-H furnishes beta-amino aldehydes. Trapping of the aldehyde via Wadsworth-Emmons reaction and subsequent manipulation offers an efficient route to homochiral delta-amino acid derivatives and 2-substituted piperidines. The application of this methodology for the synthesis of (S)-coniine is demonstrated.
authors.affiliation: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, UK OX1 3TA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Burke
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: A Christopher
authors.initials: AC
authors.lastname: Garner
authors.forename: Tom D
authors.initials: TD
authors.lastname: McCarthy
authors.forename: Paul M
authors.initials: PM
authors.lastname: Roberts
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.forename: Humberto
authors.initials: H
authors.lastname: Rodriguez-Solla
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Vickers
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis; D000470:Alkaloids / Q000138:chemical synthesis*; D000577:Amides / Q000138:chemical synthesis*; D007659:Ketones / Q000138:chemical synthesis; D018020:Lithium Compounds / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis*
chemical_list: D000447:Aldehydes; D000470:Alkaloids; D000577:Amides; D007659:Ketones; D018020:Lithium Compounds; D010880:Piperidines; C007112:coniine