The Reaction of Grignard Reagents with Bunte Salts: A Thiol-Free Synthesis of Sulfides

Abstract

S-Alkyl, S-aryl, and S-vinyl thiosulfate sodium salts (Bunte salts) react with Grignard reagents to give sulfides in good yields. The S-alkyl Bunte salts are prepared from odorless sodium thiosulfate by an SN2 reaction with alkyl halides. A Cu-catalyzed coupling of sodium thiosulfate with aryl and vinyl halides was developed to access S-aryl and S-vinyl Bunte salts. The reaction is amenable to a broad structural array of Bunte salts and Grignard reagents. Importantly, this route to sulfides avoids the use of malodorous thiol starting materials or byproducts.

Evaluation of tert‐Butyl Isosteres: Case Studies of Physicochemical and Pharmacokinetic Properties, Efficacies, and Activities

“…Solubility was determined according to the lyophilization solubility assay (LYSA) [32] at pH 6.5. pH: stability of compounds in aqueous media was determined at pH 1, pH 4, pH 6.5, pH 8, and pH 10.…”

“…6. Solubility was determined according to the lyophilization solubility assay (LYSA) [32] at pH 6.5. 7.…”

Photochemical Dual‐Catalytic Synthesis of Alkynyl Sulfides

“…[4] The direct substitution of an alkyne by as ulfur provides af ascinating arrangement of functional groups,asthe electron-rich sulfur atom permits conjugation with its lone pair(s) to afford enhanced reactivity to the triple bond as well as ahandle for modulation of physical properties and desired applications. [6] Direct oxidative coupling of thiols and terminal alkynes is also possible via copper catalysis,b ut competing homocoupling of both the alkyne and the thiol can be problematic. [6] Direct oxidative coupling of thiols and terminal alkynes is also possible via copper catalysis,b ut competing homocoupling of both the alkyne and the thiol can be problematic.…”

“…Alkynyl sulfides can be obtained in chemoselective fashion through the use of Umpolung-type strategies:t he C À Sb ond can be formed through manipulation of al eaving group on sulfur,t ypically employing ac opper-o rarhodium-catalyzed coupling with disulfides [5] or by nucleophilic displacement of as ulfur-halogen functionality or Bunte salts ( Figure 1A). [6] Direct oxidative coupling of thiols and terminal alkynes is also possible via copper catalysis,b ut competing homocoupling of both the alkyne and the thiol can be problematic. [7] Consequently,n ovel routes to the alkynylation of thiols continue to be reported, such as ar ecent disclosure of at ransition-metal-free protocol using ethynyl benziodoxo-lone (EBX) reagents to promote the CÀSb ond formation ( Figure 1B).…”

Alkynylthioimidazolium Salts: Efficient Reagents for the Synthesis of Alkynyl Sulfides by Electrophilic Thioalkynylation

“…groups,w hich suffer the nucleophilic attack at the sp-hybridized carbon directly bonded to sulphur. [8] The robustness and applicabilityo ft he protocol we developed is highlighted especially by the successful preparation of an umber of structurally differentiated thioacetylenes containing alkyl (4)(5)(6)(7)(8)(9), aryl (10)(11)(12)(13)(14), vinyl (15)(16)(17)(18)(19), or even second alkynyl units (20-23)d irectly attached to the central sulfur atom (Scheme 3). The preparation of the last two groups of products is remarkable because their synthesis is challenging through other routes.…”