2-Trimethylsilylethyl Sulfides in the von Braun Cyanogen Bromide Reaction:  Selective Preparation of Thiocyanates and Application to Nucleoside Chemistry

• Published in: Journal of organic chemistry Vol. 67; no. 6; pp. 1898 - 1904
• Main Authors: Chambert, Stéphane, Thomasson, François, Décout, Jean-Luc
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 22.03.2002; Amer Chemical Soc
• Subjects: Bromine - chemistry; Carbohydrates. Nucleosides and nucleotides; Catalysis; Chemistry; Chemistry, Organic; Chemistry, Organic - methods; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Exact sciences and technology; Magnetic Resonance Spectroscopy; Methanol - chemistry; Molecular Structure; Nucleosides - chemistry; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Silanes - chemical synthesis; Silanes - chemistry; Sulfides - chemical synthesis; Sulfides - chemistry; Thiocyanates - chemistry; INACTIVATION; ACID RELATED-COMPOUNDS; SELF-ASSEMBLED MONOLAYERS; L-HOMOCYSTEINE HYDROLASE; 2-(TRIMETHYLSILYL)ETHYL SULFIDES; ALKYL THIOCYANATES; ANALOGS; MECHANISM-BASED INHIBITORS; DERIVATIVES; S-ADENOSYLHOMOCYSTEINE HYDROLASE; Adenine derivatives; Solvent effect; Organic thiocyanate; Purine nucleoside; Chemoselectivity; Organic silane; Bromine Cyanides; Organic sulfide; Dideoxynucleoside; Thioglycoside; Dichloromethane; Aromatic compound; Chemical synthesis; Pyrimidine nucleoside; Methanol
• DOI: 10.1021/jo016200q
• ISSN: 0022-3263

Mixed 2-(trimethylsilyl)ethyl sulfides were synthesized and used in the von Braun cyanogen bromide reaction for preparing selectively thiocyanates in high yield. We show here that this cleavage reaction is highly selective in methanol in comparison with the reaction of the corresponding non-silyl sulfide analogues. This reaction was applied to the synthesis of nucleosidic thiocyanates such as the new nucleosides 14 and 18 in the search for mechanism-based inhibitors of ribonucleoside diphosphate reductase and bioactive molecules. The selective cleavage is possible for sulfides bearing hydroxyl functions and aromatic rings. The reactions of cyanogen bromide as cyanating and brominating agent were observed for the first time under the same conditions with the naphthoxyhexyl 2-trimethylsilylethyl sulfide 7, which, treated with cyanogen bromide in dichloromethane, led selectively to the p-bromonaphthoxyhexyl thiocyanate 10 in 89% yield. Another reaction induced by cyanogen bromide was observed in dichloromethane with the 2-(trimethylsilylethyl)thio nucleoside 13, which gives the corresponding symmetrical disulfide 21 in good yield.