Chengdu Biotechnology Institute has made important progress in palladium-catalyzed asymmetric carbonylation research

 Palladium-catalyzed carbonylation is an important reaction widely concerned by academia and industry, and has a wide range of applications in the construction of a variety of practical molecules, through the introduction of carbon monoxide (carbonylation process), bulk chemical raw materials, such as olefins, alkyl or aryl halide compounds, can be converted into high-value products
such as aldehydes, alcohols and carboxylic acid derivatives.
However, classical palladium-catalyzed (zero-valent/divalent palladium-catalyzed cycle) carbonylation still faces great challenges
in achieving high yield, high chemical selectivity, high regional selectivity, and enantioselectivity.

The team of researcher Liao Jian of the Drug Design and Synthesis Project Group of Chengdu Institute of Biology, Chinese Academy of Sciences has developed a new strategy
for asymmetric amine carbonylation using chiral sulfoxide/palladium complex as catalyst and high-valent palladium catalytic pathway.
Through this strategy, under mild conditions, the carbonylation reaction with high yield, excellent chemoselectivity, regional selectivity and enantioselectivity was achieved, and a series of shaftal chiral a-ketoamide/amide compounds with high optical purity were synthesized, which showed good IL-1β inhibitory activity and very low cytotoxicity.
It is expected to be developed as a small molecule drug candidate for the treatment of gout
.
In addition, the mechanism
of high-valent palladium-catalyzed carbonylation was analyzed from the perspective of experimental and theoretical calculation.
The research results have laid an important research foundation
for the application of high-valent palladium catalysis in carbonylation and other important directions.
The study, "Enantioselective double carbonylation enabled by high-valent palladium catalysis," was published in the Journal of the American Chemical Society, doctoral student Han Jian is the first author, researcher Liao Jian and academician Wu Yundong of Peking University Shenzhen Research Institute (responsible for theoretical calculation) are co-corresponding authors
.
This research was supported
by the National Natural Science Foundation of China (22171258 and 21933004).