α-Heteroarylation of Thioethers via Photoredox and Weak Brønsted Base Catalysis

Abstract

We report the C−H activation of thioethers to α-thio alkyl radicals and their addition to N-methoxyheteroarenium salts for the redoxneutral synthesis of α-heteroaromatic thioethers. Studies are consistent with a two-step activation mechanism, where oxidation of thioethers to sulfide radical cations by a photoredox catalyst is followed by α-C−H deprotonation by a weak Brønsted base catalyst to afford α-thio alkyl radicals. Further, N-methoxyheteroarenium salts play additional roles as a source of methoxyl radical that contributes to α-thio alkyl radical generation and a sacrificial oxidant that regenerates the photoredox catalytic cycle.

Radical chain monoalkylation of pyridines

“… 30,31 Recently, related processes involving radical generation via hydrogen atom transfer were reported by Shen et al , 32 Lakhdar and co-workers 33 and by Alfonzo and Hande. 34 These examples extended the scope of Mitchell's strategy, and the desired alkyl radicals were generated by hydrogen atom transfer to the highly reactive alkoxyl radical released in the rearomatization process. Chemo- and regioselective control of this approach is very challenging and is usually limited to precursors presenting electron-rich weak C–H bonds positioned alpha to a heteroatom ( O , N , S ).…”

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

“…In future applications of 1,4-dithiane or -dithiin building blocks, the recently described zincation protocol by Knochel and co-workers could offer more opportunities here ( Scheme 7 ) [ 43 – 44 ]. Furthermore, some recently reported photoredox-catalyzed thioether (C–H) alkylation and heteroarylation reactions developed by Alfonzo and Hande have demonstrated the use of 1,4-dithianes as viable substrates in such attractive bond-formation processes ( Scheme 12 ) [ 82 – 83 ]. These recently obtained results indicate that a sulfur-stabilized carbon radical derived from 1,4-dithiane ( 1 ) is a viable reaction intermediate, opening up the use of 1,4-dithianes in various free radical-type cross-couplings.…”

Advanced Synthesis Using Photocatalysis Involved Dual Catalytic System

“…Mes-Acr + was excited by visible light to generate Mes-Acr + *, and then quenched by sulfide reduction to generate Mes-Acr• and sulfide radical cations (scheme 51). [193] The sulfide radical cations were deprotonated by CF 3 CO 2 to generate α-thioalkyl free radicals.…”