Issue 15, 2022

Stannyl radical-mediated synthesis of 6H-1,3-oxazin-6-ones from 2-acyloxyazirines or whether free radicals can open the azirine ring?

Abstract

A fundamentally new radical cascade reaction of 2-acyloxyazirines provides an effective one-step method for the preparation of 5-hydroxy-6H-1,3-oxazin-6-ones from methyl 2-acyloxy-2H-azirine-2-carboxylates using a Bu3SnH/ACHN system as a source of stannyl radicals. The method provides high product yields from a variety of 2-aroyloxy-, 2-hetaroyloxy-, and 2-tert-alkylcarbonyloxy-substituted methyl azirine-2-carboxylates. The decreasing volume of the acyloxy substituent causes a side reaction leading to the formation of methyl oxazole-2-carboxylates. According to the DFT calculations, the switch between these reaction pathways occurs when changing the C1-substituent in the 2-azabuta-1,3-dien-4-oxyl intermediate, the volume of which controls further stabilization routes: radical–radical recombination or Z,E isomerization followed by recombination. The hydroxyl group in 5-hydroxy-6H-1,3-oxazin-6-ones can be easily replaced, through a triflation step, with aryl, pyridyl, alkenyl, alkynyl, and cyano groups by palladium-catalyzed cross-coupling reactions. 5-Hydroxy-6H-1,3-oxazin-6-ones were converted to pyridine-2,3(1H,4H)-diones in good yields via copper-catalyzed transannulation with 3-tolyl-2H-azirine. The key step of this new domino reaction is the copper-catalyzed pyrrolooxazine–oxazolopyridine isomerization, which, according to the DFT calculations, proceeds via a concerted mechanism.

Graphical abstract: Stannyl radical-mediated synthesis of 6H-1,3-oxazin-6-ones from 2-acyloxyazirines or whether free radicals can open the azirine ring?

Supplementary files

Article information

Article type
Research Article
Submitted
14 May 2022
Accepted
21 Jun 2022
First published
21 Jun 2022

Org. Chem. Front., 2022,9, 4118-4127

Stannyl radical-mediated synthesis of 6H-1,3-oxazin-6-ones from 2-acyloxyazirines or whether free radicals can open the azirine ring?

A. V. Agafonova, P. A. Sakharov, I. A. Smetanin, N. V. Rostovskii, A. F. Khlebnikov and M. S. Novikov, Org. Chem. Front., 2022, 9, 4118 DOI: 10.1039/D2QO00783E

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