Synthesis of Unsymmetrical Thioethers Using an Uncommon Base-Triggered 1,5-Thiol Transfer Reaction of 1‑Bromo-2-alkylthiolcarbonates

• Published in: Journal of organic chemistry 2014-11, Vol.79 (22), p.10743-10751
• Main Authors: Taouai, Marwa, Abidi, Rym, Garcia, Julien, Siriwardena, Aloysius, Benazza, Mohammed
• Format: Article
• Language: English
• Subjects: Alkanes - chemistry; Azides - chemistry; Carbohydrates - chemistry; Catalysis; Cycloaddition Reaction; Hydrocarbons, Brominated - chemistry; Phenols - chemistry; Sulfhydryl Compounds - chemistry; Sulfides - chemical synthesis; Sulfides - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo5015504

Described herein is a convenient, odorless, metal-free, one-pot strategy for the synthesis of unsymmetrical thioethers. The key step in this new strategy is a base-catalyzed 1,5-thiol transfer reaction via a pseudointramolecular mechanism of a 1-bromo-2-alkylthiolcarbonate, which is itself obtained through a straightforward microwave-assisted thioalkylation of a 1,2-cyclic-thionocarbonate precursor with an appropriate alkyl bromide. The starting 1,2-cyclic-thionocarbonates are easily obtained from the corresponding diols. When a propargylthiolcarbonate constitutes the key alkylthiolcarbonate 1,5-shift precursor, a copper-mediated dipolar cycloaddition reaction (“click”) with azide partners is rendered possible. This increases the versatility of the approach, as a very large variety of complex triazole-tethered substrates can potentially be integrated into the target unsymmetrical thioether final products. As an example of the scope of the reaction, four 1,5-shift reactions have been triggered simultaneously from a sugar-derived tetrathiolcarbonate precursor using base catalysis, to allow four 6-thioglucose moieties to be installed (78% yield for each sugar unit) onto a 1,3-alternate thiacalix[4]arene scaffold in a one-pot transformation.