Issue 28, 2015 - New progress has been made in the research of indole heterocyclic synthesis catalyzed by Dalian Chemicals

Recently, Wan Boshun, Wang Chunxiang and others of the heterocyclic synthesis research group catalyzed by Dalian Chemical Institute have successfully achieved the selective synthesis
of asymmetric 2,3-diaryl indole.

Indole building blocks are widely found in natural products, pharmaceuticals and pesticide chemicals, so the efficient and selective synthesis of indole and its derivatives has received more and more attention
from organic synthetic chemists.
Among them, the highly selective introduction of substituents at the 2,3-position of indole compound has been a difficult point
in research.
Reported studies usually achieve the synthesis of asymmetric 2,3-diaryl substituted indole through pre-functionalized raw materials or multi-step reactions, but the steps are relatively cumbersome and the atomic economy is poor
.
A more direct approach is to react aniline derivatives with asymmetric alkynes, but the regional selectivity of the reaction is difficult to control, and mixtures of two regional isomers are usually obtained and difficult to separate
.
The results show that the electronic effect of aryl substituents on asymmetric diarynes substituted alkynes has a much greater effect on the selectivity of the reaction region than the steric hindrance effect, so it is difficult to control the regional selectivity
of the reaction when using asymmetric diaryl substituted alkynes as reaction raw materials.

In recent years, Wan Boshun's team has been committed to developing new methods and strategies for catalyzing heterocyclic synthesis, and has successfully realized the selective synthesis
of pyridine and pyrrole.
The team discovered in situ generated Rh(III) intermediates in the study of the [2+2+5] cycloaddition reaction of alkynes and nitrogenone, and realized the synthesis of oxygen-bridged octa-nitrogen-containing heterocycles and the activation of C–H bonds on nitrogen N-aryl groups for the first time
.
In order to solve the selectivity problem involved in indole synthesis, the research group continued to do systematic and in-depth research, using symmetric diaryl substituted alkynes instead of asymmetric diaryl substituted alkynes, and introducing them into the indole unit (3-position substituent)
as a C1 synthesizer.
The aryl substituents at the indole 2-position are derived from the C-aryl groups of nitrotestosterone, and the introduction of two different aryl substituents at the indole 2,3-position is successfully realized through the "shear-splicing" strategy, and the reaction is highly specific.

This study provides new ideas
for the selective synthesis of indole and the further construction and development of other heterocyclic compounds.
(Work)