title: Regioselective synthesis of heterocycles containing nitrogen neighboring an aromatic ring by reductive ring expansion using diisobutylaluminum hydride and studies on the reaction mechanism.
abstract: A systematic investigation of the reductive ring-expansion reaction of cyclic ketoximes fused to aromatic rings with diisobutylaluminum hydride (DIBALH) is described. This reaction regioselectively afforded a variety of five- to eight-membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen neighboring an aromatic ring, including indoline, 1,2,3,4,5,6-hexahydrobenz[b]azocine, 3,4-dihydro-2H-benzo[b][1,4]oxazine, 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine, 1,2,3,4,5,6-hexahydroazepino[3,2-b]indole, 2,3,4,5-tetrahydro-1H-benzothieno[2,3-b]azepine, 2,3,4,5-tetrahydro-1H-benzothieno[3,2-b]azepine, 5,6-dihydrophenanthridine, and 5,6,11,12-tetrahydrodibenz[b, f]azocine. The reaction mechanism leading to the rearrangement was investigated on the basis of the restricted Becke three-parameter plus Lee-Yang-Parr (B3LYP) density functional theory (DFT) with the 6-31G (d) basis set. It was found that the reaction proceeds through a three-centered transition state via a stepwise mechanism because the potential energy curve along the intrinsic reaction coordinate (IRC) had two maxima (saddle points; TS1 and TS2) and the partial phenonium cation intermediate C. In addition to cyclic ketoximes fused to aromatic rings, the reactions of various cyclic and acyclic ketoximes were examined to investigate preference of migrating group. It was found that the more electron-rich group migrated preferentially to give the corresponding secondary amines.
authors.affiliation: Graduate School of Science, Tohoku University,6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. hcho@mail.pharm.tohoku.ac.jp
authors.forename: Hidetsura
authors.initials: H
authors.lastname: Cho
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Iwama
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Mori
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tokuyama
mesh_terms: D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009589:Nitrogen Oxides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D006571:Heterocyclic Compounds; D009589:Nitrogen Oxides; D009942:Organometallic Compounds; D010091:Oximes; C015388:nitrones; C035719:diisobutylaluminum