Gold(III)-catalyzed one-pot synthesis of isoxazoles fron terminal alkynes and nitric acid

Terminal alkynes react smoothly with nitric acid, in nitromethane/water (1:1, vol./vol.) and in the presence of catalytic amt. of tetrabutylammonium tetrachloroaurate (TBA+ AuCl4-) to give 3,5-disubstituted isoxazoles (I, R = Ph, Bu, BzOCH2CH2, etc.). The reaction, of the hitherto unknown (2 + 2 + 1) type (according to the no. of isoxazole ring atoms in each component synthon), takes place with any type of R group (alkyl, aryl, alkoxy, carboxylate, etc.) and gives the product I in 35-50% isolable yield. The role of the catalyst has been investigated. Attack on the triple bond of an electrophile (AuCl3 or H+) and of a nucleophile (NO2-) leads to the formation of a vinyl nitrite which is converted to a nitrile oxide either at the expense of gold(III) or of nitric acid. Subsequent 1,3-dipolar cycloaddn. of a second mol. of alkyne leads to formation of the isoxazole. Nitromethane/water has proved to be a unique biphasic system for promoting this reaction.