Guangzhou Health Center has made new progress in the synthesis of chiral pyridinolinspircene

Recently, the research group of Zhu Qiang of the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, etc.
, completed the asymmetric synthesis of chiral pyridine spironicene molecules with high enantioselectivity, and explored the optical activity of some products
.
The research results were recently published under the title Palladium-Catalyzed Modular Synthesis of Enantioenriched Pyridohelicenes through Double Imidoylative Cyclization ACS Catal.
on
.

Chiral pyridylspilicene is an important member of the nitrogen-heterospilicene family and has a wide range of important uses, such as: as a chiral emitter, metal complex, catalyst, chiral auxiliary, etc
.
Therefore, the asymmetric synthesis of chiral pyridintospiene molecules has received more and more attention
from organic chemists.
At present, the single configuration isomers of chiral pyridinylspilicene molecules mainly rely on chiral resolution of racemates or separation by HPLC chiral columns
.
The currently reported asymmetric synthesis of pyridinnospilene analogues generally has the following limitations
.
For example: 1) catalysts are expensive and have a large loading capacity (up to 60 mol%); 2) The preparation steps of reaction raw materials are cumbersome, and the linear strategy also limits the diversity of products; 3) The product requires additional conversion to obtain pyridintospircene derivatives; 4) The product structure is special and not easy to expand
.
Therefore, the development of a new synthesis method of aggregated asymmetric chiral pyridine spironicene with low catalyst dosage, easy substrate synthesis and diversification is of great significance
for promoting the in-depth research of such helical chiral compounds.

In this study, on the basis of the previous work, Zhu Qiang's team cleverly designed biaryl isonitrile C containing two isonitrile groups, realized a two-step iminocyclization reaction through "one-pot transformation", and constructed two pyridine rings at the same time to construct bispyridine spironicene
in one step.
The innovation of this reaction is mainly reflected in the following three aspects: 1) the synthesis of bisisonitrile ring closure precursors is relatively simple, and the aryl iodide that initiates the ring is cheap and easy to obtain, and such a bimolecular convergence reaction mode provides the possibility for the diversification and rapid construction of products; 2) The catalyst dosage is low, the bonding efficiency is high, 4 C-C bonds are generated in one step, and 2 pyridine rings are constructed at the same time; 3) Through the change of the central mother nucleus and the regulation of controlling the successive closing of isonitrile rings, not only the enantioselective selectivity and selectivity of different substituted [6] spilicene can be synthesized, but also the common furan ring can be hybridized with pyridine into spilicene, It greatly enriches the types
of chiral pyridinolinspireene.

At the same time, the study also completed the characterization
of the optical activity of some pyridinolene compounds.
The results show that such chiral pyridinolone spironicene compounds have good CPL activity
.

In short, this study can not only solve the many drawbacks of the current chiral pyridine spirone asymmetric synthesis, but also make it possible to quickly construct structures and replace diverse chiral pyridinolene molecules, which is of great significance
for studying their optoelectronic properties and applications in asymmetric synthesis.

The first author of the paper is Yu Ting
, a doctoral student at Guangzhou Health Institute.
Researcher Zhu Qiang and Associate Professor Luo Shuang of Guangzhou Health Institute, and researcher Zhong Yuwu, Institute of Chemistry, Chinese Academy of Sciences are co-corresponding authors
.
The research was supported
by the National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province.

Palladium-catalyzed diiminocyclization with high enantioselectivity to construct pyridinolene

Some compounds and their optical properties are studied

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