Studies toward the oxidative and reductive activation of CeS bonds in 20-S-aryl-2ʹ-thiouridine derivatives

Studies directed toward the oxidative and reductive desulfurization of readily available 20-S-aryl-20thiouridine derivatives were investigated with the prospect to functionalize the C20-position of nucleosides. The oxidative desulfurization-difluorination strategy was successful on 2-(arylthio)alkanoate surrogates, while extension of the combination of oxidants and fluoride sources was not an efficient fluorination protocol when applied to 20-S-aryl-20-thiouridine derivatives, resulting mainly in C5halogenation of the pyrimidine ring and C20-monofluorination without desulfurization. Cyclic voltammetry of 20-arylsulfonyl-20-deoxyuridines and their 20-fluorinated analogues showed that cleavage of the arylsulfone moiety could occur, although at relatively high cathodic potentials. While reductivedesulfonylation of 20-arylsulfonyl-20-deoxyuridines with organic electron donors (OEDs) gave predominantly base-induced furan type products, chemical (OED) and electrochemical reductivedesulfonylation of the a-fluorosulfone derivatives yielded the 20-deoxy-20-fluorouridine and 20,30-didehydro-20 ,30-dideoxy-20-fluorouridine derivatives. These results provided good evidence of the generation of a C20-anion through carbon-sulfur bond cleavage, opening new horizons for the reductivefunctionalization approaches in nucleosides. 2016 Elsevier Ltd. All rights reserved.