Electroauxiliary-Assisted C-C Bond Formations in Lithium Perchlorate / Nitromethane Solution

Abstract

C-nucleosides have C-C bonds between ribosyl moiety and nucleobase at anomeric carbon. This substitution of covalent bond gives hydrolysis resistance to C-nucleosides. Therefore, C-nucleosides are good candidates for antiviral or antitumor drugs as mimic building blocks of oligonucleotide.To synthesize nucleosides, cation intermediate is used for installing nucleobase on ribosyl moiety. When it comes to generation of cation intermediate, electrochemical methodology is one of the useful tools. In electrochemical method, 1’-arylthioriboses are used as glycosyl donors. They have thioether group as electroauxiliary at anomeric carbon forging O,S-acetal that are activated with anodic oxidation to generate corresponding cation intermediate. Since electrochemically generated cation intermediates have high reactivity enough to react with carbon nucleophiles, this method can be adopted to C-nucleoside synthesis.Previously, electrochemical nucleoside synthesis was reported using cation pool method in combination with electroauxiliary. To avoid undesired oxidation of nucleophile, it is important to pool the cation and/or to lower the oxidation potential of ribose. The low temperature condition such as -78 ~ -50 oC is necessary to pool cation intermediates.In this research, we aimed to achieve electrochemical C-C bond formation at anomeric carbon with ambient temperature condition. In this strategy, we use glycosyl donors with lowered oxidation potential to avoid competitive oxidation with carbon nucleophiles. We also adapt lithium perchlorate/nitromethane system for electrolysis. Figure 1