Scientists of the Zelinsky Institute continue to study the chemistry of cyclic nitronates

Cyclic nitronates are convenient intermediates in the stereoselective synthesis of complex carbo- and heterocycles, including those that are structural fragments of natural compounds and active pharmaceutical ingredients. Over the past few years, researchers at the Laboratory of Organic and Organometallic Nitrogen-Oxygen Systems of the Zelinsky Institute have been actively studying the chemistry of cyclic nitronates. In one of their latest works, the scientists realized [3 + 2]-cycloaddition between cyclic nitronates and arynes, resulting in tricyclic benzannelated nitrosoacetals. The process was regio- and stereoselective in most cases and provided the target products in good to high yields. In the course of the study, the chemistry of the obtained tricyclic products was also studied using the reductive and acid-catalyzed cleavage of the nitrosoacetal fragment as an example. During catalytic hydrogenation on Raney nickel, the cycloadducts were converted into valuable polysubstituted amino diols containing up to four adjacent stereogenic centers. Under acidic conditions, an unusual fragmentation of the cyclic nitrosoacetal moiety was observed via heterolytic N–O bond cleavage followed by a Beckmann-type reaction. Thus, the developed synthetic method based on [3 + 2]-cycloaddition between cyclic nitronates and arynes made it possible to obtain several classes of polyfunctional nitrogen-containing structures at once for further use in organic synthesis and medicinal chemistry.
 

Source:

Alexander A. Lukoyanov, Andrey A. Tabolin, Yulia V. Nelyubina, Svetlana A. Aksenova, Alexey Yu. Sukhorukov Nitronate-aryne cycloaddition as a concise route to stereochemically complex fused benzisoxazolines and amino alcohols // Org. Biomol. Chem., 2023, 21, 3871-3880. DOI: 10.1039/d3ob00235g.