An expeditious and efficient bromomethylation of thiols: enabling bromomethyl sulfides as useful building blocks

Abstract

A new method for the bromomethylation of thiols using paraformaldehyde and HBr/AcOH, minimizes the generation of toxic byproducts. Synthetic utility of α-bromomethyl sulfides was demonstrated through umpolung and free radical chemistry.

A Simple Method for the Formation of α‐Thioalkyl Radicals and the Promotion of Carbon‐Carbon Bond Formation by Photoirradiation of Electron Donor‐Acceptor Complexes

“…As part of this endeavor, the generation of α‐thioalkyl radicals, known for their pronounced nucleophilicity, for use in carbon‐carbon bond‐forming reactions has been explored. α‐thioalkyl radicals can be yielded through the one‐electron oxidation of thioethers that bear α‐electrofuge groups, such as trimethylsilyl, carboxylic acid, and trifluoroborate, which subsequently dissociate to produce α‐thioalkyl radicals (Scheme 1a) [2–7] …”

“…α-thioalkyl radicals can be yielded through the one-electron oxidation of thioethers that bear α-electrofuge groups, such as trimethylsilyl, carboxylic acid, and trifluoroborate, which subsequently dissociate to produce α-thioalkyl radicals (Scheme 1a). [2][3][4][5][6][7] In a seminal study conducted in 2017, MacMillan and his team proficiently executed the α-C(sp 3 )À H alkylation of thioethers with alkyl bromides using a confluence of photoredox catalysts, nickel catalysts, and hydrogen atom transfer catalysts. [8][9] Additionally, Alfonzo and Hande demonstrated the generation of α-thioalkyl radicals via the CÀ H activation of thioethers, enabled by photoredox catalysts and weak base catalysts, which then interacted with electron-deficient olefins (Scheme 1b), [10] and N-methoxyheteroarenium salts.…”

Photoredox and Weak Brønsted Base Dual Catalysis: Alkylation of α-Thio Alkyl Radicals

“…α-Thio alkyl radicals have been previously generated from single electron transfer (SET) oxidation and fragmentation of thioethers comprising an α-electrofuge group (Scheme B) . In this vein, Mariano’s studies first demonstrated that α-silyl thioethers can undergo fragmentation through oxidation with a photoredox catalyst, and work since has shown that other functional groups, like carboxylic acids and trifluoroborates, are also viable. − MacMillan and co-workers demonstrated that α-thio alkyl radicals could be generated from thioethers using a hydrogen atom transfer (HAT) catalyst, which were then leveraged in a nickel-mediated cross-coupling reaction …”

“…With established reaction conditions, the olefin scope was evaluated with three structurally different thioethers (Table 2A). Acrylates containing methyl (5), 1,1,1,3,3,3-hexafluoroisopropyl (8), 2,2,2-trifluoroethyl (9), propargyl (10), allyl (11), and amide groups (12) reacted in good yields with thioanisole. Example 8 was synthesized on a 1 g scale, and the reaction showed an improved outcome (87% vs 71%).…”

Stereoselective synthesis of vinyl nitriles through a Ramberg–Bäcklund approach

“…As part of our interest in synthetic methodologies based on sulfur functional groups for advanced synthetic applications, 23 including the generation of olefinic blocks for materials, 24 we aimed to develop a robust method for the synthesis of vinyl nitriles using the RBR (Fig. 1d).…”