The intramolecular cycloizomerization of 2-alkynyl-3-nitrothiophenes was catalyzed by AuCl 3 or CF 3 CO 2 Ag to produce the corresponding thieno [3,2-c]isoxazoles bearing carbonyl functionality in position 3 instead of expected 5-substituted 6H-thieno[3,2-b]pyrrol-6-one 4-oxides.The cyclization of alkynes containing proximate nucleophilic centers is currently of great interest and developing into a most effective strategy for heterocyclic ring construction. This chemistry provides a straightforward approach to the synthesis of functionalized carbo-and heterocycles through the regio-and stereoselective addition of a nucleophile and an unsaturated carbon unit across the carbon-carbon triple bond. 1 Thus a variety of transition-metal or electrophile-induced 5-exo-dig or 6-endo-dig cyclization reactions have been reported. 2 The ortho-alkynyl nitrobenzenes are well known as precursors for the preparation of isatogens (Scheme 1). The classical cycloisomerizations of starting compounds can be initiated by pyridine, 3a-e nitrosobenzene, 3e,f concentrated sulfuric acid, 3g,h tetrabutylammonium fluoride (TBAF), 3c and UV light. 3i-k Usually these reactions take long times and require high temperatures. However, few years ago, it was shown that the presence of transition-metal salts such as gold(III) bromide 4a or silver (I) nitrate 4b initiates smooth cyclization reaction.
Scheme 1 Literature resultsOn the other hand, recently, we have developed a novel, concise, and high-yielding formation of pyrrolo[3,2-d]-pyrimidin-7-one 5-oxides via smooth cycloisomerization of 2,4-disubstituted 6-arylethynyl-5-nitropyrimidines in the presence of pyridine. We have shown that the triple bond of the starting compounds is electron poor, so the cycloisomerization reaction takes only a few minutes and does not require transition-metal catalysts. 5 Encouraged by knowledge from literature and our previous results, we envisioned that cycloizomerization of all aromatic and heteroaromatic compounds, bearing triple bond and nitro group in close proximity to each other, would always lead to the formation of pyrolone N-oxide ring containing compounds. However, to our great surprise, we observed different regioselectivity in cycloisomerization of 2-alkynyl-3-nitrothiophenes, so herein we would like to report on these unexpected results.The starting compounds 1 were synthesized by wellknown Sonagashira reaction 6 from 2-bromo-3-nitrothiophene (Scheme 2). 7 First of all, it should be noted that classical pyridine initiated cycloisomerization of the title compounds was not successful. During the long heating of 3-nitro-2-phenylethynylthiophene 1a in dry pyridine, no changes of the starting material were observed by TLC. This result can be easily explained by the fact that triple bonds in starting compounds are electron-rich due to neighboring electron-donating thiophene ring, so nucleophilic activation becomes impossible. So we decided to take advantages of transition-metal salts catalytic potency. When we added 5 mol% of gold(III) chloride to the sol...
