title: An asymmetric synthesis of (2S,5S)-5-substituted azepane-2-carboxylate derivatives.
abstract: To facilitate a drug discovery project, we needed to develop a robust asymmetric synthesis of (2S,5S)-5-substituted-azepane-2-carboxylate derivatives. Two key requirements for the synthesis were flexibility for elaboration at C5 and suitability for large scale preparation. To this end we have successfully developed a scalable asymmetric synthesis of these derivatives that starts with known hydroxy-ketone 8. The key step features an oxidative cleavage of aza-bicyclo[3.2.2]nonene 14, which simultaneously generates the C2 and C5 substituents in a stereoselective manner.
authors.affiliation: Pfizer Worldwide Research and Development, Eastern Point Rd., Groton, Connecticut 06340, USA. donn.g.wishka@pfizer.com
authors.forename: Donn G
authors.initials: DG
authors.lastname: Wishka
authors.forename: Marion
authors.initials: M
authors.lastname: Bédard
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Brighty
authors.forename: Richard A
authors.initials: RA
authors.lastname: Buzon
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Farley
authors.forename: Michael W
authors.initials: MW
authors.lastname: Fichtner
authors.forename: Goss S
authors.initials: GS
authors.lastname: Kauffman
authors.forename: Jaap
authors.initials: J
authors.lastname: Kooistra
authors.forename: Jason G
authors.initials: JG
authors.lastname: Lewis
authors.forename: Hardwin
authors.initials: H
authors.lastname: O'Dowd
authors.forename: Ivan J
authors.initials: IJ
authors.lastname: Samardjiev
authors.forename: Brian
authors.initials: B
authors.lastname: Samas
authors.forename: Geeta
authors.initials: G
authors.lastname: Yalamanchi
authors.forename: Mark C
authors.initials: MC
authors.lastname: Noe
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D055808:Drug Discovery; D007659:Ketones / Q000737:chemistry
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002264:Carboxylic Acids; D007659:Ketones