Effective Formation of New C(sp²)−S Bonds via Photoactivation of Alkylamine‐based Electron Donor‐Acceptor Complexes

Abstract

A novel visible light promoted formation of C Aryl-S bonds through electron donor-acceptor (EDA) complexes of alkylamines with 5-and 6-membered (hetero)arene halides is presented. This represents the first EDA-based thiolation method not relying on π-π or a thiolate-anion-π interactions and provides a facile access to heteroarene radicals, which can be suitably trapped by disulfide derivatives to form the corresponding versatile arylsulfides. Mechanistic investigations on the aspects of the whole process were conducted by spectroscopic measurements, demonstrating the hypothesized EDA complex formation. Moreover, the strength of this method has been proven by a gram-scale synthesis of thiolated products and the late-stage derivatization of an anticoagulant drug.

Visible-light-mediated synthesis of non-anomericS-aryl glycosidesviaa photoactive electron-donor–acceptor complex

“…The glycosyl radical C is attacked by the disulfide 2i to give a trivalent sulfur radical D . Based on previous data, 17 systems close to trivalent sulfur radical D were found to act as reducing agents to promote electron transfer to DIPEA˙ + . So the trivalent sulfur radical D is oxidized by the DIPEA˙ + to give rise to DIPEA and intermediate E , which finally generates the final product 3i and by-product F in the presence of a large excess of DMSO (solvent).…”

Visible Light Induced Photocatalyst‐Free C−X (X=B, C, O, P,S, Se) Bond Formation of Aryl Halides

“…In 2022, Pérez-Ruiz and co-workers et al disclosed a photocatalyst-free cross-coupling reaction for construction of aryl thioethers 31 from disulfides 30 and aryl halides 29 (Scheme 15). [23] An array of thiophenols with various aryl chlorides as well as aryl bromides produced aryl thioethers in good to excellent yields. The protocol could engage a wide range of aryl halides with excellent functional group compatibility.…”

Assembly of (hetero)aryl thioethers via simple nucleophilic aromatic substitution and Cu-catalyzed coupling reactions with (hetero)aryl chlorides and bromides under mild conditions

“…During the past two decades, great efforts have been directed to the development of catalytic systems for coupling of (hetero)aryl halides with thiols and their equivalents 1–15 to assemble (hetero)aryl thioethers of high prevalence in bioactive molecules 16 and synthetic intermediates. 17 Because of their abundance, relatively low cost but low reactivity, the utilization of (hetero)aryl chlorides as coupling partners has become a reference point to assess the efficiency of newly developed catalytic systems.…”

“…11 Meanwhile, room temperature arylation of thiols under the action of a photocatalyst [ fac -Ir(ppy) 3 ] was described in 2016, 12 a while Miyake's group observed that visible-light promoted cross-coupling reactions between aromatic thiols and aryl halides took place at RT through an electron donor–acceptor (EDA) complex mechanism. 13 Interestingly, most successful coupling reactions have resulted from electron-deficient (hetero)aryl halides except for those in Fu's and Oderinde's studies. 9,10 The same reactivity trend was also observed in Baran's studies on DEL synthesis via Ni-catalyzed C–S bond formation 14 and Lipshutz's Ni-catalyzed migita-like C–S cross-coupling in recyclable water 15 that were disclosed very recently (Fig.…”

“…18 f These reactions were believed to go through an S N Ar mechanism and require a strong electron-withdrawing group in the substrate to proceed under mild conditions. The requirement of relatively harsh reaction conditions for less reactive electron-deficient aryl halides triggered intensive studies on the assembly of (hetero)aryl thioethers via metal- and photo-catalyzed coupling of thiols and aryl halides, 1–15 as well as S N Ar reactions using more reactive electrophiles, 19 through microwave irradiation 20 or in some special solvents. 21…”