One-step synthesis of differently bis-functionalized isoxazoles by cycloaddition of carbamoylnitrile oxide with β-keto esters

Abstract

A new protocol for synthesizing different functionalized isoxazoles is provided. Carbamoylnitrile oxide generated from nitroisoxazolone underwent inverse electron-demand 1,3-dipolar cycloaddition with 1,3-dicarbonyl compounds in the presence of magnesium acetate that formed magnesium enolate in situ. Although electron-deficient trifluoroacetoacetate did not undergo this cycloaddition under the same 10 conditions, conversion to sodium enolate furnish the corresponding bis-functionalized trifluoromethylisoxazole. The DFT calculations using B3LYP 6-31G+(d,p) also supported the abovementioned reactivity.

One‐Pot Three‐Component Heteroannulation of β‐Oxo Dithioesters, Amines and Hydroxylamine: Regioselective, Facile and Straightforward Entry to 5‐Substituted 3‐Aminoisoxazoles

“…Their use as versatile intermediates in organic synthesis is well recognized due to the presence of two electrophilic and three nucleophilic reactive sites, which can be exploited in a regioselective manner 20,21. Although isoxazole derivatives have been synthesized from S,S‐/N,S‐acetals22a–22e and β‐oxo esters,22f so far, to the best of our knowledge, there is no report on the synthesis of isoxazoles from β‐oxo dithioesters. Therefore, we set out to explore the feasibility of β‐oxo dithioesters as 1,3‐dielectrophilic synthons to access isoxazoles.…”

Trisubstituted push-pull nitro alkenes

“…The first method A (Scheme 1) is the most exploited preparation of reviewed structures of nitroenolethers where ether alkyl is mostly lower alkyl (methyl, ethyl). 12,16,17,19,[25][26][27][28][29][30][31][32] The reaction of ethyl orthoformate and acetic anhydride with active methylene compounds was reported by Claisen 33 in 1893. The modification 28 for alkyl nitroacetates was first time reported in 1959.…”

“…12 Formed isoxazoline salt is used in further synthesis as a source of carbamoyl-substituted nitrile oxide for 1,3-dipolar cycloadditions. 30,56 Reaction F2 is an example from a set of reactions with hydrazine derivatives that results in pyrazole derivatives. 44 Generally, the reaction should be composed of two main steps.…”

Trifluoromethyl‐β‐dicarbonyls as Versatile Synthons in Synthesis of Heterocycles

“…Nishiwaki et al reported the synthesis of bis functionalized trifluoromethylisoxazole 273 which could have importance in medicine and material science by reacting nitroisoxazolone 272 with sodium enolate of ethyl trifluoroacetate 1 in tetrahydrofuran at room temperature (Scheme 91). [174] In this reaction, 1,3-dipolar cycloaddition of 1 with carbamoylnitrile oxide 272 A generated in situ from 272 could result in isoxazoles 273 having vicinal functionalities at the 3-and 4-positions.…”