Skip to Content
Merck
  • Regioselective synthesis of heterocycles containing nitrogen neighboring an aromatic ring by reductive ring expansion using diisobutylaluminum hydride and studies on the reaction mechanism.

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

The Journal of organic chemistry (2009-12-31)
Hidetsura Cho, Yusuke Iwama, Kenji Sugimoto, Seiji Mori, Hidetoshi Tokuyama
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Diisobutylaluminum hydride solution, 25 wt. % in toluene
Sigma-Aldrich
Diisobutylaluminum hydride solution, 1.0 M in toluene
Sigma-Aldrich
Diisobutylaluminum hydride solution, 1.0 M in cyclohexane
Sigma-Aldrich
Diisobutylaluminum hydride solution, 1.0 M in methylene chloride
Sigma-Aldrich
Diisobutylaluminum hydride solution, 1.0 M in THF
Sigma-Aldrich
Diisobutylaluminum hydride, reagent grade
Sigma-Aldrich
Diisobutylaluminum hydride solution, 1.0 M in hexanes
Sigma-Aldrich
Diisobutylaluminum hydride solution, 1.0 M in heptane