Synthesis of new 2-substituted 3-amino-4-hydroxymethylthiophenes through intramolecular nitrile oxide cycloaddition processes and N,O-bond cleavage

A synthesis of new 2-substituted 3-amino-4-hydroxymethylthiophenes 7 is reported as a useful alternative to the long known oximation of oxothiophenes 8, followed by treatment with gaseous hydrochloric acid in a polar solvent. The synthesis consists of an INOC process of unsaturated sulfide nitrile oxides, obtained from the condensation of corresponding nitroalkenes and allylmercaptan and then dehydration, which leads to tetrahydrothieno[3,4-c]isoxazoline 4. N,O-Bond cleavage of 4 upon hydride reduction affords to thiophenes 7 of biological interest