Scientists from the ZIOC have proposed a method for the synthesis of 1,2-oxazine derivatives

1,2-Oxazines are an important class of N,O-heterocyclic compounds in both organic and medicinal chemistry. 1,2-Oxazines derivatives are marine metabolites of trichodermamides, exhibiting anticancer and antimicrobial activity, and synthetic structures based on 1,2-oxazines have high anti-inflammatory and anticancer activity. 1,2-Oxazines are also used in organic synthesis as intermediates on the way to 1,4-aminoalcohols and polysubstituted pyrroles, pyrrolidines, and tetrahydrofurans. However, there are still no versatile methods for the preparation of various 1,2-oxazines from available starting compounds.

Researchers from the Laboratory of Organic and Metal-Organic Nitrogen-Oxygen Systems of the ZIOC developed a method for the synthesis of 1,2-oxazine derivatives based on a previously unknown reaction of cyclic nitronates with aryne precursors. The process goes as a [3+2]-cycloaddition followed by fragmentation of the nitrosoacetal fragment, which was confirmed by the isolation of intermediate cycloadducts. The synthetic use of the obtained structures was demonstrated by the example of their stereoselective reduction to 1,4-aminoalcohols and reductive contraction of the 1,2-oxazine ring to tetrahydrofuran derivatives.

Source:

Alexander A. Lukoyanov, Andrey A. Tabolin, Yulia V. Nelyubina, Sema L. Ioffe, Alexey Yu. Sukhorukov Deoxygenative Arylation of 5,6-Dihydro‑4H‑1,2-oxazine‑N‑oxides with Arynes J. Org. Chem. 2022, 87, 6838–6851. DOI: 10.1021/acs.joc.2c00515.