Amino-heterocycles are present in a broad range of active pharmaceutical ingredients and natural products. Among the top 200 best-selling pharmaceuticals in 2019, there are about 50 drugs containing amino-heterocyclic motif. Particularly, in living organisms, DNA and RNA also bear such important skeletons. Consequently, their efficient synthesis has always been a fundamental theme in chemistry community.
Ynamides are unique alkynes with carbon-carbon triple bond directly attached to the nitrogen atom bearing an electron-withdrawing group. Accordingly, ynamide is endowed with both nucleophilic and electrophilic properties. Nowadays, catalytic intermolecular annulation of ynamides, featuring high step- and atom-economy, has emerged as a versatile tool for the assembly of diverse amino-heterocycles.
Recently, a team led by Prof. CHEN Qing-An and Prof. WAN Bo-Shun from Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) provided a comprehensive summary on this special topic.
Catalytic intermolecular annulations of ynamides. (Image by HU Yan-Cheng)
The review covers the advances achieved over the past decade and is organized by the catalytic systems. A variety of annulation paradigms have been discussed with transition-metal and acid catalysis.
Moreover, the intermolecular annulations of the ynamide analogs including ynol ethers and thioalkynes were also summarized, which can provide insights into the reactivity difference caused by the heteroatoms.
The study was published in Chemical Society Reviews.
It was supported by National Natural Science Foundation of China. (Text by HU Yan-Cheng)