title: Tandem nucleophilic addition/oxy-2-azonia-Cope rearrangement for the formation of homoallylic amides and lactams: total synthesis and structural verification of motuporamine G.
abstract: In the presence of a Lewis acid, β,γ-unsaturated ketones and oximes or imines undergo nucleophilic addition to produce zwitterion intermediates, and subsequent oxy-2-azonia-Cope rearrangements give homoallylic amides. In the case of 2-vinylcycloalkanones, the process results in ring enlargement, providing a novel route to 9- to 16-membered lactams. The preparative significance of this protocol was evidenced by a short synthesis of macrocyclic alkaloid motuporamine G. The stereochemistry-defining step of this oxy-azonia-Cope rearrangement was further studied computationally. Despite a high-energy preequilibrium in the formation of zwitterionic intermediates, the [3,3]-sigmatropic step is the rate- and product-determining step. Chairlike transition states are generally preferred over boatlike ones.
authors.affiliation: Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Zou
authors.forename: Quanrui
authors.initials: Q
authors.lastname: Wang
authors.forename: Italo A
authors.initials: IA
authors.lastname: Sanhueza
authors.forename: Franziska
authors.initials: F
authors.lastname: Schoenebeck
authors.forename: Andreas
authors.initials: A
authors.lastname: Goeke
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D001391:Azo Compounds / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
chemical_list: D000470:Alkaloids; D000577:Amides; D001391:Azo Compounds; D007769:Lactams; C581438:motuporamine G