TY - JOUR

T1 - Azirinyl-Substituted Nitrile Oxides: Generation and Use in the Synthesis of Isoxazole Containing Heterocyclic Hybrids

AU - Дудик, Александр Сергеевич

AU - Занахов, Тимур Олегович

AU - Галенко, Екатерина Евгениевна

AU - Новиков, Михаил Сергеевич

AU - Хлебников, Александр Феодосиевич

PY - 2025/7/2

Y1 - 2025/7/2

N2 - The procedure for the generation of azirinyl-substituted nitrile oxides by the reaction of 2-(diazoacetyl)-2H-azirines with tert-butyl nitrite while preserving the azirine ring has been developed. The [3+2] cycloaddition of azirinyl-substituted nitrile oxides to terminal acetylenes produced azirinyl(isoxazolyl)ketones with various substituents in position 3of azirine and position 5 of isoxazole fragments in a 51–91% yield at room temperature in DCM. DFT calculations and experimental data are consistent with the assumption that the formation of azirinyl-substituted nitrile oxides is accelerated by the acid catalyst. Cycloadducts of nitrile oxides with aryl/hetarylacetylenes and DMAD can be obtained by catalysis with boron trifluoride etherate, which significantly expands the scope of application of the reaction. Expansion of the azirine ring of the prepared cycloadducts allows obtaining a wide range of structurally diverse functionalized isoxazole-containing heterocyclic hybrids. LED light induces isomerization of the azirinecarbonyl moiety of the azirinyl(isoxazolyl)ketones, resulting in the formation of a set of 3,5’-biisoxazoles in a 40–71% yield, while the catalytic reaction of the azirine moiety with 1,3-diketones opens the way to pyrrole- and isoxazole-containing hybrids. 2-(Isoxazole-3-ylcarbonyl)-3-arylazirineswere also easily isomerized to 3-(oxazol-5-yl)isoxazoles in methanol in the presence of excess potassium carbonate at room temperature.

AB - The procedure for the generation of azirinyl-substituted nitrile oxides by the reaction of 2-(diazoacetyl)-2H-azirines with tert-butyl nitrite while preserving the azirine ring has been developed. The [3+2] cycloaddition of azirinyl-substituted nitrile oxides to terminal acetylenes produced azirinyl(isoxazolyl)ketones with various substituents in position 3of azirine and position 5 of isoxazole fragments in a 51–91% yield at room temperature in DCM. DFT calculations and experimental data are consistent with the assumption that the formation of azirinyl-substituted nitrile oxides is accelerated by the acid catalyst. Cycloadducts of nitrile oxides with aryl/hetarylacetylenes and DMAD can be obtained by catalysis with boron trifluoride etherate, which significantly expands the scope of application of the reaction. Expansion of the azirine ring of the prepared cycloadducts allows obtaining a wide range of structurally diverse functionalized isoxazole-containing heterocyclic hybrids. LED light induces isomerization of the azirinecarbonyl moiety of the azirinyl(isoxazolyl)ketones, resulting in the formation of a set of 3,5’-biisoxazoles in a 40–71% yield, while the catalytic reaction of the azirine moiety with 1,3-diketones opens the way to pyrrole- and isoxazole-containing hybrids. 2-(Isoxazole-3-ylcarbonyl)-3-arylazirineswere also easily isomerized to 3-(oxazol-5-yl)isoxazoles in methanol in the presence of excess potassium carbonate at room temperature.

KW - azirines

KW - diazo compounds

KW - heterocyclic hybrids

KW - isoxazoles

KW - nitrile oxides

KW - oxazoles

KW - pyrroles

UR - https://www.mendeley.com/catalogue/e293f66b-92c1-31a7-bb84-b85f605aca4b/

U2 - 10.3390/molecules30132834

DO - 10.3390/molecules30132834

M3 - Article

C2 - 40649348

VL - 30

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 13

M1 - 2834

ER -