Researchers of the Zelinsky Institute discovered a new tandem reaction of cyclic nitronates

Tandem reactions are a powerful tool for rapid increasing molecular complexity in an efficient and cost-effective manner. Of particular interest are tandem processes based on a combination of pericyclic reactions, since the formation of bonds and stereogenic centers in such transformations proceeds regio- and stereoselectively. Currently, tandem reactions with the participation of nitroalkenes are being actively studied: the sequence of cycloaddition processes with their participation leads to the formation of a number of nitrogen-containing heterocycles, such as pyrrolizidines, indolizidines, and 1,2-oxazines, which are found in many bioactive natural compounds.

Scientists of the Laboratory of Organic and Organometallic Nitrogen-Oxygen Systems of the ZIOC have developed a method for the synthesis of previously unknown saturated oxazolo[3,2-b][1,2]oxazines containing up to four adjacent stereogenic centers in their structure. In the first stage, [4+2]-cycloaddition takes place between nitroalkenes and olefins with the formation of cyclic nitronates. The subsequent tandem reaction of [3+2] cycloaddition/formal [1,3]-rearrangement between cyclic nitronates and disubstituted ketenes leads to the final products. The obtained compounds can be used as precursors of other condensed derivatives of 1,2-oxazines, in particular, 1,2-oxazino-1,2,4-triazin-3-ones.

Source:

Roman S. Malykhin, Ivan S. Golovanov, Yulia V. Nelyubina, Sema L. Ioffe, Alexey Yu. Sukhorukov Construction of Saturated Oxazolo[3,2‑b][1,2]oxazines via Tandem [3+2]-Cycloaddition/[1,3]-Rearrangement of Cyclic Nitronates and Ketenes J. Org. Chem.2021, 86, 16337−16348. DOI: 10.1021/acs.joc.1c01744.