Regioselective synthesis of heterocycles containing nitrogen neighboring an aromatic ring by reductive ring expansion using diisobutylaluminum hydride and studies on the reaction mechanism

Hidetsura Cho, Yusuke Iwama, Kenji Sugimoto, Seiji Mori, Hidetoshi Tokuyama

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

(Chemical Equation Presented) A systematic investigation of the reductive ring-expansion reaction of cyclic ketoximes fused to aromatic ringswith 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 twomaxima (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 ketoximeswere examined to investigate preference of migrating group. It was found that themore electron-rich group migrated preferentially to give the corresponding secondary amines.

Original languageEnglish
Pages (from-to)627-636
Number of pages10
JournalJournal of Organic Chemistry
Volume75
Issue number3
DOIs
Publication statusPublished - 2010 Feb 5

ASJC Scopus subject areas

  • Organic Chemistry

Fingerprint Dive into the research topics of 'Regioselective synthesis of heterocycles containing nitrogen neighboring an aromatic ring by reductive ring expansion using diisobutylaluminum hydride and studies on the reaction mechanism'. Together they form a unique fingerprint.

Cite this