C-Glycosylation of Substituted Heterocycles Under Friedel-Crafts Conditions (II): Ribosylation of Multi-Functionalized Thiophenes and Furans for the Synthesis of Purine-Like C-Nucleosides

Abstract

In our continuing studies of the Friedel-Crafts glycosylation of preformed heterocycles, we have observed that while the SnCl₄ catalyzed glycosylation of methyl 4-(formylamino)thiophene-3-carboxylate (5) gives readily the C-nucleosides 7b and 7a, the corresponding Et₂AlCl catalyzed reaction gives exclusively the N-nucleoside 11. These nucleosides can be further elaborated into the bicyclic thieno[3,4-d]-pyrimidine system. Similarly, methyl 4-(formylamino)furan-3-carboxylate (19) gave the expected C-nucleosides 2Ob and 2Oa upon glycosylation in the presence of SnCl₄. However, these nucleosides could not be converted into the furo[3,4-d]pyrimidine system. Interestingly, several of the N-formamido compounds exhibit pronounced rotational isomerism, which was demonstrated by ¹H NMR spectroscopy