title: One-pot reductive coupling of N-acylcarbamates with activated alkenes: application to the asymmetric synthesis of pyrrolo[1,2-a]azepin-5-one ring system and (-)-xenovenine.
abstract: The one-pot reductive coupling of N-acylcarbamates with activated alkenes is described. The method is based on partial reduction of N-acylcarbamates with DIBAL-H, followed by N-acyliminium ion formation and SmI(2)-mediated radical coupling with activated alkenes. Both acyclic and cyclic N-acylcarbamates can be used as stable substrates, and a range of activated alkenes serve as effective radical receptors. The reductive coupling of l-N-acylcarbamates 12/13 gave 2,5-disubstituted pyrrolidine derivatives in high trans-diastereoselectivities. The reductive coupling with penta-2,4-dienoate proceeded exclusively in a 1,6-addition fashion, producing a single non-conjugated E-isomer. On the basis of this method, a three-step construction of pyrrolo[1,2-a]azepin-5-one 16, the skeleton of many stemona alkaloids and lehmizidine alkaloids, and a seven-step synthesis of (-)-xenovenine (pyrrolizidine cis-223H, ent-6), the unnatural enantiomer of the frog/ant venom alkaloid possessing potent inhibitory activity towards nAChR channel, were achieved starting from L-12.
authors.affiliation: Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, PR China.
authors.forename: Xue-Kui
authors.initials: XK
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Ruan
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Pei-Qiang
authors.initials: PQ
authors.lastname: Huang
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D001381:Azepines; D002219:Carbamates; D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids; C572231:pyrrolo(1,2-a)azepin-5-one; C545571:xenovenine