Thiyl Radicals: Versatile Reactive Intermediates for Cyclization of Unsaturated Substrates

Abstract

<jats:p>Sulfur centered radicals are widely employed in chemical synthesis, in particular for alkene and alkyne hydrothiolation towards thioether bioconjugates. The steadfast radical chain process that enables efficient hydrothiolation has been explored in the context of cascade reactions to furnish complex molecular architectures. The use of thiyl radicals offers a much cheaper and less toxic alternative to the archetypal organotin-based radical methods. This review outlines the development of thiyl radicals as reactive intermediates for initiating carbocyclization cascades. Key developments in cascade cyclization methodology are presented and applications for natural product synthesis are discussed. The review provides a chronological account of the field, beginning in the early seventies up to very recent examples; a span of almost 50 years.</jats:p>

PhICl2-Mediated Regioselective and Electrophilic Oxythio/Selenocyanation of o-(1-Alkynyl)benzoates: Access to Biologically Active S/SeCN-Containing Isocoumarins

“…Then the reaction of thiocyanate with thiocyanogen chloride provides (SCN) 2 , which further reacts with the oxidative PhICl 2 to give thiocyanogen chloride ( Tao et al, 2021 ). Next, electrophilic addition between the reactive thiocyanogen chloride with substrate 1a gave rise to intermediate B ( Xing et al, 2019a ; An et al, 2020 ; Hellwig et al, 2020 ; Lynch and Scanlan, 2020 ; Sun et al, 2020 ; Jurinic et al, 2021 ; Slivka and Onysko, 2021 ). Due to the presence of the adjacent electron-withdrawing methoxycarbonyl group which makes the C (sp 2 ) connecting with the Ph substituent more electron-deficient, a favored intramolecular 6-exo cyclization occurred in intermediate B , leading to formation of the cyclic intermediate C .…”

Recent Advances in Visible-Light Photoredox Catalysis for the Thiol-Ene/Yne Reactions

“…Ranitidine, a well-known drug which is widely used in the treatment of duodenal and gastric ulceration, also contains the typical carbon-sulfur bond [ 9 ]. Moreover, thioethers are valuable synthetic intermediates and important building blocks to access more functionalized sulfur-containing molecules such as sulfoxides and sulphones, consequently, they play an important role in synthetic chemistry and material science [ 10 , 11 , 12 , 13 , 14 ]. Due to the importance of thioethers, the development of methodologies for the synthesis of thioethers are of particular significance, and tremendous efforts have been made.…”

Light-Induced Single-Electron Transfer Processes involving Sulfur Anions as Catalysts

“…In visible-light photocatalysis, thiolates are readily oxidized by an excited photoredox catalyst to generate thiyl radicals, which are employed for the construction of organosulfur molecules, and used as hydrogen atom transfer agents (Scheme A,B) . Additionally, thiyl radicals are produced from photolysis of disulfides, which have been utilized in a variety of chemical transformations in a catalytic manner (Scheme C). , Excited sulfur-based anions are potent electron donors as a photocatalyst and can be used for inert bond activation. Moreover, upon photoinduced electron transfer between sulfur anions and substrates, the resulting sulfur-centered radicals and substrate radical anions are valuable intermediates in subsequent reaction steps.…”

“…11 Additionally, thiyl radicals are produced from photolysis of disulfides, which have been utilized in a variety of chemical transformations in a catalytic manner (Scheme 1C). 12,13 Excited sulfur-based anions are potent electron donors as a photocatalyst and can be used for inert bond activation. Moreover, upon photoinduced electron transfer between sulfur anions and substrates, the resulting sulfur-centered radicals and substrate radical anions are valuable intermediates in subsequent reaction steps.…”