Heterocyclization of electrophilic alkenes with tetranitromethane revisited: regiochemistry and the mechanism of nitroisoxazole formation

Synthesis of 3,4,5‐Trisubstituted Isoxazoles from Morita–Baylis–Hillman Acetates by an NaNO2/I2‐Mediated Domino Reaction

“…[8] But later, based on the X-ray analysis,t hese products turned out to be 5-nitroisoxazoles. [9] Therefore ageneral approach to substituted 3-nitroisoxazoles utilizing readily available starting materials is desired. Herein, we report av ersatile route to new alkyl 3-nitro-5-(aryl/ alkyl)isoxazole-4-carboxylatesf rom ar eaction between Morita-Baylis-Hillman (MBH) acetates and NaNO 2 in the presence of I 2 /DMSO at room temperature in short reaction time.T he process not only represents an ovel cascade transformation but provides preparative access to useful 3,4,5-trisubstituted isoxazoles.F urthermore,t hese products are exemplified to be apposite precursors to arange of novel isoxazoles by nucleophilic aromatic substitution (S N Ar) reactions and new 3,3-diamino-2-benzoylacrylatest hrough hydrogenolysis.…”

A Facile Approach to Bis(isoxazoles), Promising Ligands of the AMPA Receptor

“…Surprisingly, we failed to involve the hydroquinone derivative, diene 2i with isolated double bonds, in the heterocyclization as only bis(4,4,4-trinitrobutanoic ester) 5a was isolated as the main product (Scheme 2). Trinitro-substituted adduct formation is an alternative pathway for the reaction of electrophilic alkenes with the TNM-TEA complex according to the previously suggested mechanism [36,38]. To affirm whether this route is general for the aryl acrylic esters, we obtained alkene 2j and employed it in the reaction with TNM-TEA, which also afforded only Michael adduct 5b under various conditions (Scheme 2).…”

“…In particular, the structures containing the phenylene-based linkers and aminoisoxazole moieties were identified among the most promising potential PAMs. Recently, we have elaborated a novel preparative method for the synthesis of 3-EWG-5-nitroisoxazoles, based on the heterocyclization of electrophilic alkenes via treatment with the tetranitromethane-triethylamine (TNM-TEA) complex [36][37][38][39]. Until now, this method has been used to produce polysubstituted isoxazoles containing one heterocyclic fragment in a molecule.…”

Synthesis of 3,4,5‐Trisubstituted Isoxazoles from Morita–Baylis–Hillman Acetates by an NaNO2/I2‐Mediated Domino Reaction

“…As a consequence, a new route to 3‐nitroisoxazoles by reacting tetranitromethane with electrophilic alkenes was developed 8. But later, based on the X‐ray analysis, these products turned out to be 5‐nitroisoxazoles 9. Therefore a general approach to substituted 3‐nitroisoxazoles utilizing readily available starting materials is desired.…”