Scientists Realize Cobalt-Catalyzed Direct Aminocarbonylation of Ethers
Ethers are widely present in biomass, chemical feedstocks, and fine chemicals, which are key motifs for the production of value-added fuels and biomass-derived chemicals.
Since ether motifs can greatly modify the pharmacological properties of the parent molecules, thus they are indispensable in biology, pharmaceuticals, and agrochemicals.
Recently, a research team led by Prof. WU Xiaofeng from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) realized cobalt-catalyzed direct aminocarbonylation of ethers, and accessed α-amide substituted ether derivatives.
Their findings were published in Angewandte Chemie International Edition on Mar. 23.
"The neighbored oxygen atom of the ether can be relatively easy oxidized by the radical intermediates via either intermolecular or intramolecular pathways, so the carbonylation of ethers is challenging," said Prof. WU.
"There are two main challenges for exploring cobalt catalyst in carbonylation chemistry, one is that the carbon monoxide trends to coordinate with cobalt metal tightly to give stable cobalt carbonyl complexes, and the other is that the catalytic activities of cobalt are insensitive with the ligands added for their reactivity tuning," said Prof. WU.
To solve the above challenges, the researchers developed a novel strategy. They used inert ethers as carbonylation substrates, and cheap metal cobalts as catalysts to realize the carbonylation of ethers in the presence of di-tert-butyl peroxide.
Based on this strategy, they synthesized a wide variety of α-carbonylated ethers, including crown ether derivative and various drug related molecules, with good functional group compatibility and efficiency.
Moreover, this strategy can obtain the commercially available drug alfuzosin in moderate yields.
The above work was supported by the K. C. Wong Education Foundation. (Text by WANG Lecheng)
