DABCO‐Mediated [4+1] Cycloaddition of β,β‐Dihalo Peroxides with Sodium Azide toward Isoxazoles

Abstract

The isoxazole skeleton is one of key structural motifs, which displays widespread applications in drugs, agriculture, and synthetic intermediates. Herein, we disclose the DABCO‐mediated [4+1] cycloaddition of β,β‐dihalo peroxides and sodium azide for synthesis of multisubstituted isoxazoles. The cycloaddition proceeds through the formation of N−C and N−O bonds. This method shows excellent regioselectivity and good scalability.

Multiple-fold C–F bond functionalization for the synthesis of (hetero)cyclic compounds: fluorine as a detachable chemical handle

“…In 2020, Li et al reported a DABCO-mediated approach toward multisubstituted isoxazoles that proceeded via defluorination cycloaddition of β,β-difluoro peroxides with sodium azide (Scheme 29). 58 Compared to their precedent (Scheme 11) with cobalt catalysis under heating, these transformations were performed in a relatively mild fashion. In the products of this reaction, susceptible substituents including carbalkoxy, amide, benzoyl, phosphoryl, and heteroaryl groups could be installed at R 3 position.…”

Sodium Azide: An Inorganic Nitrogen Source for the Synthesis of Organic N‐Compounds

“…In 2020, the preparation of a wide range of multisubstituted isoxazoles 33 was reported with sodium azide 1 as nitrogen source by Li et al (Scheme 6) [26] A broad scope of β,β-dihalo peroxides 29 reacted with sodium azide 1 under catalysis of DABCO in acetonitrile at 80 °C. All products 33 were obtained in low to good yields (31-89 %) with excellent regioselectivity except two derivatives which showed very low yields (R 1 = Alkyl, R 2 = H, R 3 = CO 2 Et, 7 % yield and R 1 = Ph, R 2 = H, R 3 = C 3 H 7 , 13 % yield).…”