A 10‐Year Journey Into Diverse Arylsulfonium Salts: Versatile Reagents for Organic Synthesis

Abstract

As an important class of organosulfur reagents for many chemical transformations, arylsulfonium salts have featured obvious advantages such as good thermal stability, easy preparation, high structural diversity, and rich reactivity, showing the broader substrate scopes and better selectivity than other aryl pseudohalides. Over the past decade, our group has pioneered the arylsulfonium salt chemistry. Starting from Pd‐catalyzed reactions with Yagupolskii–Umemoto reagents, we have established an array of arylation platforms with different types of arylsulfonium salts through transition‐metal‐mediated cross‐couplings, catalyst‐free reactions, and photoredox transformations. These reactions accommodate a wide range of carbon‐ and heteroatom‐centered coupling partners, showing excellent functional group tolerance, and prove effective in the late‐stage modification of structurally complex molecules. This account summarizes our efforts on the synthetic applications of arylsulfonium salts, demonstrating their great potential in modern organic synthesis.

This review summarizes our works in the synthetic applications of arylsulfonium salts, which is divided into the transition‐metal‐catalyzed, catalyst‐free, and photoinduced reactions of acyclic or cyclic arylsulfonium salts with diverse cross‐coupling partners, yielding a variety of high‐value products. The reactivity changes brought about by the subtle structural variation of arylsulfonium salts are also discussed in this review.

1. Introduction

In recent decades, the growing demand for efficient synthesis of chemical entities for drug discovery, natural product synthesis, and functional materials development has fueled significant methodological innovations in organic chemistry [1, 2, 3, 4]. A paramount requirement for the development of useful methodologies lies in the availability of reagents that enable diverse bond‐forming reactions under mild conditions, avoiding lengthy de novo syntheses especially for complex molecular scaffolds. Beyond their prevalence in the skeletons of pharmaceuticals [5], natural products [6], and advanced materials [7, 8], organosulfur compounds have been emerging as vital synthetic reagents. In particular, S(IV) arylsulfonium salts have been widely recognized as powerful and indispensable reagents in modern organic synthesis due to their unique structural and reactivity traits [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]. The recent years have witnessed the rapid development of arylsulfonium salts as highly efficient cross‐coupling partners in numerous chemical reactions [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]. To date, the Procter, Ritter, Alcarazo, Yorimitsu, our, and other research groups have made great contributions in this field and have systematically reviewed the synthesis and applications of various arylsulfonium salts from different aspects [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]. The advanced strategies such as earth‐abundant transition‐metal catalysis, photoredox catalysis, and electrocatalysis have been successfully utilized in the transformations of arylsulfonium salts, attracting more chemists to engage in this field.

Arylsulfonium salts can be classified into three categories according to the number of aryl groups attached to the sulfur center: cyclic/acyclic dialkylarylsulfonium salts, cyclic/acyclic alkyldiarylsulfonium salts, and cyclic/acyclic triarylsulfonium salts (Figure 1a–c). These salts possess a positive charge on sulfur atom and adopt a trigonal pyramidal geometry, exhibiting isoelectronic similarity to arylphosphines but with very different reactivity (Figure 1) [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]. The positively charged sulfur center creates a strong electron‐withdrawing effect: it restricts the sulfur's lone pair from coordination and enables deprotonation of α‐hydrogens on S‐alkyl groups of alkylarylsulfonium salts to form sulfur ylides (Figure 1d) [25, 26, 27]. The electron‐deficient nature of arylsulfonium cations underpins broad reactivity. Their low‐lying LUMO supports useful chalcogen bond interactions in organocatalysis (Figure 1e) [28, 29]. Notably, arylsulfonium salts can be activated under light irradiation with or without photocatalysts or through electron donor–acceptor (EDA) complexation, triggering the selective cleavage of C—S bonds and generation of carbon‐centered radicals (Figure 1f). Recent advances in the field of visible‐light photocatalysis have further enhanced this reactivity of arylsulfonium salts, enabling the formation of various aryl radicals under mild conditions [30, 31, 32, 33, 34, 35]. The electron‐deficient sulfur centers also facilitate oxidative addition of low‐valent metals into C—S bonds of tri(hetero)aryl‐, alkylaryl‐, and alkenylarylsulfonium salts for the facile synthesis of complicated compounds (Figure 1g) [36, 37, 38, 39, 40, 41, 42, 43]. Moreover, arylsulfonium salts can undergo straightforward substitution with diverse nucleophiles under catalyst‐free conditions for the construction of a multitude of carbon–carbon and carbon–heteroatom bonds through aryne intermediates, S_NAr mechanisms, or sulfurane pathways (Figure 1h) [44, 45, 46].

FIGURE 1.

Categories and synthetic applications of arylsulfonium salts.

The synthetic routes to arylsulfonium salts have been well established (Figure 2a–f), which mainly comprise the alkylation of aryl sulfides with alkyl halides and silver salts [47, 48], the arylation of thioethers with aryliodonium salts, arynes, arylboronic acids or their esters, and arylcarboxylic acids [49, 50, 51, 52], the sulfenylation of organometallic reagents, arylboronic acids, and aryl trifluoroborates with sulfoxides and activators [53, 54, 55], the C—H functionalization of arenes with sulfoxides or sulfonates in the presence of anhydrides and/or acids [56, 57, 58], the arylation of alkoxysulfoniums with aryl bromides in the presence of Grignard reagent, and so on [59]. These synthetic breakthroughs have greatly expanded the structural diversity of arylsulfonium salts, facilitating their widespread applications across various fields. Since arylsulfonium salts have merits of good thermal stability, simple preparation, easy handling, and diverse reactivity, yielding neutral sulfide leaving groups that are less harmful to catalysts than anionic thiolates, they have been considered as excellent aryl transfer reagents for a large number of synthetic practices [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 60, 61, 62, 63]. Despite their notable success in organic synthesis, the pursuit of milder and more sustainable methodologies continues to drive exploration into the new structures, properties, and reactivities of arylsulfonium salts.

FIGURE 2.

Representative synthetic methods for arylsulfonium salts.

Beginning with the Pd‐catalyzed arylations using Yagupolskii–Umemoto reagents, we have developed a series of efficient transformations with different types of arylsulfonium salts over the past decade [9]. This account summarizes our achievements in the domain and is divided into three parts, which include the transition‐metal‐catalyzed, catalyst‐free, and photoinduced reactions of acyclic or cyclic arylsulfonium salts with aryl(alkenyl)boronic acids, arenes, alkenes, alkynes, amines, alcohols, nitriles, fluorine‐containing reagents, and others, yielding a variety of high‐value cross‐coupling products. The reactivity changes brought about by the subtle structural variation of arylsulfonium salts are also discussed in this review, which is helpful for the interested readers to better understand the essence and potential of arylsulfonium salts in organic chemistry. The use of cyclic arylsulfonium salts (e.g., thianthrenium, phenothiazinium, phenoxathiinium, or dibenzothiophenium triflates) in some cases could further enhance the synthetic utility by directing reactions to exocyclic S—C bonds, which are very critical for the selective late‐stage functionalization of bioactive molecules in drug discovery [17, 60, 61, 62, 63]. It should be noted that the modifiable architecture of arylsulfonium salts can serve as a powerful guarantee for advanced complex synthesis, providing a robust platform to invent new reaction modes. These reactions usually proceed in different ways depending on the variable structures of arylsulfonium salts and the types of nucleophiles or reagents used. We hope that the examples presented in this article will offer some inspiration to the followers.

2. Transition‐Metal‐Mediated Reactions of Arylsulfonium Salts

Since Liebeskind's pioneering work on transition‐metal‐catalyzed cross‐couplings with sulfonium salts in 1990s, there had been almost no progress for nearly 20 years [36, 37, 38, 39]. This field began to expand rapidly only in the last decade, spurred by the later seminal works from Yorimitsu, Lewis, Ritter, Procter, Wang, our group, and others [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 60, 61, 62, 63]. To date, significant achievements have been made in the transition‐metal‐mediated synthetic applications of arylsulfonium salts. Our endeavors in this area stemmed from the transition‐metal‐mediated trifluoromethylation with the Yagupolskii–Umemoto reagent ([Ph₂SCF₃][OTf]) [64, 65, 66, 67]. While the cyclic Umemoto reagent has been widely used in transition‐metal‐mediated trifluoromethylation reactions, the similar application of the acyclic Yagupolskii–Umemoto reagents as trifluoromethyl sources remained relatively scarce (Figure 3) [64, 65, 66, 67, 68, 69, 70, 71, 72, 73]. To verify whether the Yagupolskii—Umemoto reagent can oxidize low‐valent transition metal other than copper to form a metal–CF₃ species, we studied the reactions between [Ph₂SCF₃][OTf] and palladium catalysts and found that both aryl–Pd complex and CF₃—Pd species were formed (Figure 3) [74]. Among them, the reaction of [Ph₂SCF₃][OTf] with Pd[P(t‐Bu)₃]₂ exhibited good chemoselectivity, where cleavage of the Ph—S bond to form an aryl–Pd complex is predominant over the CF₃—S bond cleavage for a CF₃—Pd species. These results indicated that, in addition to acting as a trifluoromethylation reagent, [Ph₂SCF₃][OTf] can serve as an aryl transfer reagent, which is completely different from the cyclic Umemoto reagent [74]. The reaction of [Ph₂SCF₃][OTf] in the presence of palladium catalysts is also in sharp difference from that in the presence of copper catalysts as the latter lead to only the CF₃—S bond cleavage (Figure 3) [64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74]. This intriguing discovery promoted us to further investigate the reactions of [Ph₂SCF₃][OTf] with different coupling partners under Pd catalysis. Meanwhile, other fluoroalkyl arylsulfonium salts were also synthesized [75] to investigate the influence of fluoroalkyl groups of sulfonium salts on the arylation reactions.

FIGURE 3.

Different activation pattern between the cyclic Umemoto reagent and the acyclic Yaguposkii–Umemoto reagent using low‐valent transition metals.

2.1. [Ph₂SCF₃][OTf] and the Other Acyclic Arylsulfonium Salts as Aryl Transfer Reagents

In 2015, we reported the first Pd‐catalyzed Suzuki cross‐coupling reaction between the Yagupolskii–Umemoto reagents ([Ar¹Ar²SCF₃][OTf], 1) and aryl(alkenyl)boronic acids (2) (Scheme 1) [74]. Various symmetric sulfonium salts [Ar₂SCF₃][OTf] reacted with boronic acids to afford the corresponding arylated products (3) in moderate to excellent yields. For asymmetric arylsulfonium salts [Ar¹Ar²SCF₃][OTf], the arylated products on both Ar¹/Ar² sides (3‐I and 3‐II) were obtained and the ratio of 3‐I and 3‐II varied depending upon the electronic nature of aryl groups (Ar¹/Ar²) on [Ar¹Ar²SCF₃][OTf]. The results indicated that transfer of electron‐deficient aromatic rings from sulfonium salts to metal center is easier than the electron‐rich ones. Mechanistically, arylsulfonium salt (1) first undergoes a selective oxidative addition with Pd(0) to form an Ar–Pd(II)–OTf intermediate (4), which goes through transmetalation with boronic acid in the presence of base to generate intermediate Ar–Pd(II)–R (5). Then, reductive elimination of 5 yields the final product (3). Short after, we investigated the influence of S‐substituents of arylsulfonium salts (6) on the Pd‐catalyzed Suzuki reaction, including structurally diversified fluoroalkyldiphenyl‐, alkyldiphenyl‐, dialkylphenyl‐, and triphenylsulfonium salts (Scheme 2) [76]. The study confirmed that, in contrast to the Yagupolskii–Umemoto reagents (1), perfluoroalkyldiphenylsulfonium salts (6a‐6c) and polyfluoroalkyldiphenylsulfonium salts (6e‐6g) are much less effective in the Pd‐catalyzed Suzuki reaction with arylboronic acid (7a) and gave the phenylated product (8a) in trace to 23% yields, which is probably attributed to their preferable S—R_fn bond cleavage or deprotonation/β‐F elimination under the reaction conditions. Notably, trifluoroethyldiphenylsulfonium salt (6d) appeared to be optimal phenyl transfer agent and exhibited better reactivity toward boronic acid than the Yagupolskii–Umemoto reagent (1a) (Scheme 2) [76]. Nonfluorinated alkyldiphenylsulfonium salts (6h and 6i), dialkylphenylsulfonium salts (6k and 6l), and triphenylsulfonium salt (6j) were also demonstrated to be effective phenylation reagents in this reaction. Later, the Ritter group disclosed a similar Pd‐catalyzed Suzuki cross‐coupling between arylthianthrenium salts and boronic acids, resolving the problematic C—S bond cleavage selectivity associated with the asymmetric triarylsulfonium salts [19, 77]. Recently, they achieved again the Pd‐catalyzed Suzuki reaction of arylthianthrenium salts with aryl halides in the presence of hypoboric acid by in situ generating arylboronic acids from arylthianthrenium salts [78].

SCHEME 1.

Pd‐catalyzed Suzuki arylation of aryl(alkenyl)boronic acids with the Yagupolskii–Umemoto reagents.

SCHEME 2.

Pd‐catalyzed phenylation of arylboronic acids with [Ph₂SR][OTf] and [PhSR¹R²][OTf].

Trifluoromethyl‐ and trifluoroethyldiphenylsulfonium salts (1a and 6d) are also the validated arylation reagents in the Pd‐catalyzed Mizoroki–Heck reaction [48]. Specifically, in the presence of Pd[P(t‐Bu)₃]₂ and TsOH, 1a and 6d underwent coupling with an array of alkenes (9) at low temperatures to afford the corresponding phenylated products (10) in good to excellent yields (Scheme 3). Phenylsulfonium salts bearing diverse S‐substituents were also examined in this reaction. It was interesting to find that 1) the reaction efficiency of polyfluoroalkyldiphenylsulfonium salts decreased with the increase in the degree of fluorine substitution on the alkyl groups; 2) the nonfluorinated alkyldiphenylsulfonium salts and triphenylsulfonium salt afforded the Heck‐coupled product in moderate to excellent yields; and 3) dialkylphenylsulfonium salts exhibited much poor reaction performance [48]. Notably, this protocol deviates from conventional Mizoroki‐Heck reaction paradigms: the use of a base drastically suppresses the cross‐coupling of fluoroalkyldiphenylsulfonium salts with alkenes, whereas TsOH can serve as an effective promoter. This divergent behavior can be rationalized by the inherent nature of sulfonium salts, which tend to decompose under basic conditions. Later, the cyclic arylthianthrenium salt was also applied in the Pd‐catalyzed Mizoroki–Heck reaction by the Ritter group [19]. Very recently, the Wang group synthesized a series of dihydrosiloles via the Pd‐catalyzed Heck‐type reactions of arylthianthrenium salts with 2,5‐dihydro‐1H‐siloles [79].

SCHEME 3.

Pd‐catalyzed Mizoroki–Heck‐type reactions of alkenes with [Ph₂SR_fn][OTf].

In 2017, we developed the first Pd/Cu‐catalyzed Sonogashira cross‐couplings of arylsulfonium salts (11) with terminal alkynes (12), expanding the cross‐coupling partners of the famous Sonogashira reaction (Scheme 4) [80]. The structures of arylsulfonium salts also exert a significant influence on the reaction [80]. Trifluoroethyldiphenylsulfonium salt, nonfluorinated alkyldiphenylsulfonium salts, phenyltetrahydrothiophenium salt, and triarylsulfonium salts exhibited excellent reactivity, affording the arylated products (13) in up to nearly quantitative yield. Dialkylphenylsulfonium salts showed slightly inferior reaction efficiency. Pentafluoroethyldiphenylsulfonium triflate and 2,2‐difluoroethyldiphenylsulfonium triflate gave much lower yields (less than 20%), probably due to their poor tolerance to the basic conditions. Additionally, asymmetric arylsulfonium salts (11) exhibited the similar chemoselectivity pattern in this Sonogashira reaction as observed in our previously reported Suzuki reaction (Scheme 4), wherein the electron‐deficient aryl groups undergo preferential transfer [80]. Likewise, the Ritter group successfully used the cyclic arylthianthrenium salt as aryl transfer source in the Pd/Cu‐catalyzed Sonogashira reaction with alkyne in 2019 [19]. In addition, the Liang and Niu group reported a photoinduced copper‐catalyzed Sonogashira‐type cross‐coupling of arylthianthrenium salts with alkynes [81]. The Wu group employed arylthianthrenium salts as building blocks for the Pd‐catalyzed carbonylative Sonogashira coupling of aliphatic terminal alkynes with CO to yield alkynones and furanones [82].

SCHEME 4.

Pd/Cu‐catalyzed Sonogashira reaction of alkynes with nonfluorinated arylsulfonium salts.

Different from the exclusive N‐alkylation that occurs between alkylarylsulfonium salts and amines under basic conditions [83], we have achieved the selective N‐arylation of amines (15) with alkylarylsulfonium salts in the Pd/Cu‐cocatalyzed Ullmann‐type reaction (Scheme 5) [84]. Alkylarylsulfonium salts (14‐I) bearing long‐chain S‐alkyl groups exhibited superior aryl transfer ability compared to those with short‐chain S‐alkyl groups [84]. This trend is obviously reflected in both alkyldiphenylsulfonium salts and dialkylphenylsulfonium salts: the arylation yield of S‐methyl phenylsulfonium salts in the Ullmann reaction is much lower than that of S‐butyl phenylsulfonium salts. Further studies indicated that the palladium catalyst is very essential for the selective N‐phenylation and that the copper salt benefits the transformation probably by both enhancing the N‐phenylation and suppressing the N‐alkylation. Since the chemoselectivity for cleavage of the aromatic C—S bonds of asymmetric diarylsulfonium salts is poor, we have developed a useful strategy for the selective breakage of the C—S bonds of asymmetric arylsulfonium salts [84]. This is accomplished by introducing a mesityl group at the sulfur center of alkyldiarylsulfonium salts, which exploits both electronic effect and steric hindrance to selectively render one of the aromatic C—S bonds inert during the reaction. For instance, the asymmetric butyldiarylsulfonium salts (14‐II) with Ar²= mesityl exhibited excellent aromatic C—S bond selectivity and proved to be superior selective aryl transfer agents (Scheme 5). Almost simultaneously, the Ritter group reported the Pd‐catalyzed or photoredox Cu(I)‐mediated cross‐coupling of arylthianthrenium salts with amines, achieving conversion of a wider range of N‐nucleophiles and the late‐stage functionalization of complex drug‐like molecules [85].

SCHEME 5.

The selective Ullmann‐type N‐arylation of anilines with alkylarylsulfonium salts.

2.2. Cyclic Arylsulfonium Salts as Aryl Transfer Reagents

The utilization of acyclic alkylaryl and triarylsulfonium salts as aryl transfer reagents represents our preliminary exploration into the reactivity of arylsulfonium salts and has enabled promotion of valuable reaction patterns for other types of arylsulfonium salts [9, 10, 11, 12, 13, 14, 15, 16]. However, the selective cleavage of aromatic C—S bonds of acyclic arylsulfonium salts remains a challenge, hindering their broader applications in arylation reactions. Encouragingly, the cyclic arylsulfonium salts such as arylthianthrenium salts, arylphenoxathiinium salts, arylphenothiazinium salts, and aryldibenzothiophenium salts, readily synthesized from the site‐selective C—H sulfenylations of arenes with the corresponding thianthrene 5‐oxide, phenoxathiine 10‐oxide, 10‐methyl‐10H‐phenothiazine 5‐oxide, and dibenzothiophene 5‐oxide, have shown excellent aromatic C—S bonds cleavage selectivity [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 60, 61, 62, 63]. These arylsulfonium salts have wider substrate scopes and can work as versatile platforms for the late‐stage functionalization of complex molecules [9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 60, 61, 62, 63].

In 2021, we established a Pd/Cu‐catalyzed formal C—H/C—H cross‐coupling of azoles (18) with (hetero)arenes via sulfonium intermediates (Scheme 6) [86]. In this reaction, both triphenylsulfonium salt (6j) and the cyclic arylthianthrenium salts (17) serve as powerful arylation reagents, affording the desired products (19) in good to excellent yields (Scheme 6), which are significantly superior to acyclic dialkylarylsulfonium salts and alkyldiarylsulfonium salts that generally provided inferior yields [86]. This method smoothly furnished a variety of 2‐(hetero)arylated azoles and enabled the facile late‐stage functionalization of structurally complex molecules, including the synthesis and modification of pharmaceuticals [86]. It should be mentioned that the photoredox‐catalyzed cross‐coupling of aryldibenzothiophenium salts with arenes developed by the Procter group was not applicable to the azole systems [87]. Our transition‐metal‐catalyzed reaction addressed this gap, offering a robust and broadly applicable strategy for C—H arylation across a wide range of azoles [86].

SCHEME 6.

Pd/Cu‐catalyzed cross‐coupling of azoles with triphenylsulfonium salt and arylthianthrenium salts.

Installation of deuterium atom(s) into the metabolically active sites of drug molecules has become a standard practice to gain better therapeutics in medicinal chemistry. In 2022, we successfully accomplished the Pd‐catalyzed deuteration of arylthianthrenium salts (20) with deuterated solvent (CD₃OD) for the convenient synthesis of deuterated arenes (21) [88]. CD₃OD is a very cheap deuterium source in comparison with the deuterium gas that was used by the Ritter group in their Pd‐catalyzed deuteration reaction [89]. Different types of arylsulfonium salts were evaluated in the Pd‐catalyzed hydrogenation [88]. Aryl(tetrafluoro)thianthrenium salt and arylphenoxathiinium salt exhibited slightly inferior reactivity compared to arylthianthrenium salts. Both substituted and unsubstituted aryldibenzothiophenium salts afforded low hydrogenation yields, while acyclic triarylsulfonium salt and dialkylarylsulfonium salts displayed extremely poor reactivity with yields less than 20%. Finally, arylthianthrenium salt (20) was chosen as the optimal platform for aromatic deuterium labeling [88]. By running the reaction with Cs₂CO₃ in the presence of Pd[P(t‐Bu)₃]₂, we achieved the selective deuteration of 22 arenes, including drug molecules, in CD₃OD with excellent deuterium incorporation ratios (Scheme 7) [88].

SCHEME 7.

Pd‐catalyzed deuteration of arylthianthrenium salts in CD₃OD.

In 2024, we disclosed the Pd‐catalyzed Heck remote functionalization of alkenyl alcohols (23) using triphenylsulfonium salt (6j) and cyclic arylphenoxathiinium salts (22) (Scheme 8) [90]. The standard Heck reaction of arylsulfonium salt and alkene was employed to trigger “chain walking,” leading to the facile convention of various alkenyl alcohols (23) to the corresponding aryl alkyl ketones (24‐I/24‐II) in excellent yields and with good functional group tolerance. Mechanistically, oxidative addition of arylsulfonium salt (6j or 22) to Pd(0) first forms an aryl–Pd complex (25), which undergoes insertion into the carbon–carbon double bond to afford intermediate 28a or 28b via two directions (Scheme 8). Then, β‐hydride elimination of 28a/28b through a coplanar configuration produces a Pd‐coordinated alkene (29a/29b), which undergoes a reversible chain‐walking process by repeated insertion of the in situ formed Pd—H species and β‐hydride elimination, followed by isomerization of the enol intermediate, to provide the carbonyl product (24‐I/24‐II). Finally, reductive elimination of the dissociated L _n Pd—H with a base regenerates the Pd(0) catalyst. No regioisomers were observed in the reactions of allylic alcohols, while minor branched isomers (24‐II) were obtained in the reactions of nonallylic alcohols, which were generated from an opposite‐direction insertion of Ar‐Pd(II) into the carbon–carbon double bond [90]. Other cyclic arylsulfonium salts such as aryldibenzothiophenium triflate, arylthianthrenium triflate, and arylphenothiazinium triflate were also efficient aryl transfer reagents in this relay Heck reaction, affording the desired product in comparable yields [90].

SCHEME 8.

Pd‐catalyzed relay Heck arylation of alkenyl alcohols with arylsulfonium salts.

Aryl ketones are often employed as versatile building blocks in the construction of bioactive molecules, and the development of efficient protocols for the synthesis of aryl ketones is of significant importance. In 2025, we uncovered a nickel‐catalyzed acylation reaction between arylsulfonium salts (30) and nitriles (31) for the preparation of aryl ketones (32) (Scheme 9) [91]. The cyclic arylthianthrenium salts were identified as optimal coupling reagents for this acylation, affording high yields of the products. Arylphenoxathiinium salt, aryldibenzothiophenium salt, and arylphenothiazinium salt were less effective in the reaction, providing moderate yields, while the use of dialkylarylsulfonium salts resulted in much lower yields of the product [27]. This protocol offered a practical synthetic route for synthesizing a wide variety of aryl ketones and enabled the selective coupling of arylsulfonium salts with retaining other functionalizable handles. When the easily available deuterated acetonitrile was employed as a nitrile source, the reaction allowed for construction of deuterated methyl aryl ketones in good yields with up to 99% deuterated form, permitting effective modification of complex drug molecules [91]. The reaction is likely initiated by the reduction of a Ni(II) complex with zinc powder to yield the active Ni(0) species, which undergoes oxidative addition with arylsulfonium salt (30) to form an aryl–Ni(II) species (33) (Scheme 9). Then, coordination of 33 with nitrile (31) generates intermediate 34, of which the aryl–Ni(II) bond inserts into the C≡N of nitrile to yield intermediate 35. Protonation of 35 with water affords a Ni(II) intermediate (36) and an imine; the latter is hydrolyzed to provide the target product (32). Intermediate 36 is further reduced by zinc to yield Ni(0) species, maintaining the catalytic cycle [91].

SCHEME 9.

Ni‐catalyzed synthesis of aryl ketones from arylthianthrenium salts and nitriles.

2.3. Alkylarylsulfonium Salts as Alkyl/Alkenyl/Allyl Transfer Reagents

Alkylarlysulfonium salts have drawn increasing attention because they can serve as alkylation reagents and sulfur ylide precursors to offer simple and effective access to target structures [13, 92, 93, 94, 95, 96]. Perfluoroalkyldiarylsulfonium salts, the fluorinated version of alkyldiarylsulfonium salts, are well‐known electrophilic perfluoroalkylation agents (e.g., the Yagupolskii–Umemoto reagents), exhibiting high reactivity for introducing perfluoroalkyl groups into a large number of organic compounds [64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 97, 98, 99]. In 2017, we accomplished a Cu‐mediated trifluoromethylation of α‐diazo esters (37) using the Yagupolskiii–Umemoto reagents (Scheme 10) [100]. Under the action of CuCl, various aromatic α‐diazo esters bearing either electron‐donating or electron‐withdrawing substituents on the aryl groups were smoothly converted with trifluoromethyldiphenylsulfonium triflate (1a) to afford α‐trifluoromethyl arylacetates (38) in up to 93% yield. The acyclic Yagupolskii–Umemoto reagent (1a) exhibited higher reaction efficiency than the cyclic Umemoto reagent in this reaction. The reaction may proceed through a reductive trifluoromethylation mechanism (Scheme 10) [67, 100]. First, 1a is reduced by Cu(I) salt via single‐electron transfer (SET) to form an unstable radical (40), which rapidly decomposes to produce a •CF₃ radical. The •CF₃ radical is further reduced by Cu(I) salt and combines with another equivalent of Cu(I) salt to generate a CuCF₃ species. Then, the CuCF₃ species inserts into α‐diazo ester (37) to form intermediate 41, which is finally protonated to yield α‐trifluoromethylated product (38). When perfluoroalkyldiphenylsulfonium salts (6) were used in the same reaction, followed by treatment with a base, the α‐perfluoroalkenylated products (39) were obtained in good yields via the sequential reductive perfluoroalkylation and defluorination [100].

SCHEME 10.

Cu‐mediated fluoroalkylation of α‐diazo esters with the Yagupolskii–Umemoto reagents.

1,3‐Enynes are prevalent structural motifs in natural products, pharmaceutical agents, and other functional molecules, and their conjugated carbon–carbon double and triple bonds can be selectively or concurrently transformed for the convenient synthesis of useful scaffolds such as aromatic systems, heterocycles, allenes, and 1,2‐/1,4‐addition products. In 2021, we developed a Pd/Cu‐cocatalyzed vinylation of terminal alkynes (43) with 2‐bromoethyldiphenylsulfonium salt (42) (Scheme 11) [101]. Mechanistically, 42 first undergoes HBr‐elimination to in situ generate a vinyl sulfonium salt (44), which then readily engages in the Pd/Cu‐cocatalyzed Sonogashira cross‐coupling with terminal alkynes to afford the expected 1,3‐enynes (45). The isolated vinyldiphenylsulfonium salt (44) could also favorably provide the 1,3‐enyne products under mild conditions (Scheme 11). While 44 exhibited enhanced reactivity, its liquid physical state and relatively poor stability make its precursor (the crystalline stable 2‐bromoethyldiphenylsulfonium salt, 42) to be the more preferable vinylation reagent in this Pd/Cu‐catalyzed preparation of unsubstituted 1,3‐enynes [101]. Furthermore, (2‐chloroethyl)diphenylsulfonium salts, (2‐iodoethyl)diphenylsulfonium salts, and 2‐bromoethyltetrahydrothiophenium salt were identified as ineffective vinylation reagents in this reaction due to their instability, affording only trace yields of the vinylated products [101]. Similarly, treatment of (2‐fluoroethyl)diphenylsulfonium, 2‐(tosyloxy)ethyldiphenylsulfonium, and (2‐bromoethyl)thianthrenium triflates under the standard conditions provided the vinylated product in moderated yields, indicating them as the less effective CH=CH₂ transfer sources [101].

SCHEME 11.

Pd/Cu‐cocatalyzed vinylation of terminal alkynes with (2‐bromoethyl)/vinyl diphenylsulfonium salts.

Cyclopropyldiphenylsulfonium salt has been widely employed as a ylide precursor for the efficient synthesis of spiro compounds and cyclic ketones and has made significant contributions to the sulfur ylide chemistry [102, 103, 104, 105]. Nevertheless, application of cyclopropyldiphenylsulfonium salt in other reactions has been rarely investigated. In 2022, we circumvented this limitation and uncovered a Cu‐catalyzed N‐allylation of amines (47) with cyclopropyldiphenylsulfonium salt (46) (Scheme 12) [106]. Under the standard reaction conditions used for the Pd/Cu‐catalyzed Ullmann coupling with alkylarylsulfonium salts [84], the cyclopropyldiphenylsulfonium salt (46) could only act as a phenyl transfer reagent for amine. In contrast, when the reaction was performed with copper(I) salt in the absence of Pd catalyst, the allylation of amine with 46 occurred. Moreover, addition of a bisoxazoline (BOX) ligand to the reaction system could significantly boost the allylation process [106]. This transformation is presumably initiated by the single‐electron reduction of 46 with LCu(I), generating an unstable sulfur radical (49) and a LCu(II) species (Scheme 12). Subsequently, the selective homolytic cleavage of the C—S bond of 49 produces a cyclopropyl radical, which undergoes ring‐opening in the presence of Cu(II) to form an allyl–Cu(III) intermediate (50). Finally, reaction of 50 with amine (47) via ligand exchange and reductive elimination yields the allylated product (48), with simultaneous regeneration of the LCu(I) catalyst for the next reaction cycle [106].

SCHEME 12.

Cu‐catalyzed allylation of amines with cyclopropyldiphenylsulfonium salt.

3. Transition‐Metal‐Free Electrophilic Transformations of Arylsulfonium Salts

Arylsulfonium salts have emerged as versatile electrophilic reagents, showing unique electronic/structural features, and have enabled numerous chemical transformations without catalysts. The transition‐metal‐free reactions of arylsulfonium salts with different nucleophiles could provide a variety of important arylated compounds [44, 45, 46, 107, 108, 109], demonstrating the great usefulness of arylsulfonium salts in catalyst‐free formation of carbon–carbon and carbon–heteroatom bonds. It was found that the base‐mediated reactions of triarylsulfonium salts with nucleophilic coupling agents gave the arylated products through aromatic nucleophilic substitution, aryne intermediates, sulfurane intermediates, or radical processes, which is dependent upon the nature of the bases and the structures of arysulfonium salts.

Although transition‐metal‐free reactions of amines with diaryliodonium salts under alkaline conditions have been reported to produce various arylamines, the interactions between triarylsulfonium salts and amines or their derivatives are rarely known [110]. In 2018, we reported the first transition‐metal‐free N‐arylation reaction between triarylsulfonium salts (6j/51) and amines (52) under basic conditions (Scheme 13) [110]. Triphenylsulfonium salt (6j) reacted with various aryl or alkyl amines in the presence of tBuOK or KOH to afford the corresponding N‐arylated products (53‐I) in good yields, including bioactive molecules. Increasing the equivalent of 6j allowed the bis(N‐arylation) of primary amines (53‐II) (Scheme 13). Moreover, the reactions with substituted triarylsulfonium salts (51) gave regioisomers of N‐arylated products [110]. The presence of regioisomeric products in these reactions implied that the N‐phenylation might proceed via an aryne intermediate [110]. The formation of high ratio of ortho‐H form of the deuterophenylated product in the reaction with tris(phenyl‐d₅)sulfonium triflate also suggested a predominant N—H addition process to benzyne intermediate [110]. Analogously, Zhang, Ding, and co‐workers recently disclosed a base‐mediated C—N bond formation between arylthianthrenium salts and amines, which also involves an aryne mechanism [44].

SCHEME 13.

Transition‐metal‐free N‐arylation of amines with acyclic triarylsulfonium salts.

The decomposition of triarylsulfonium salts under basic conditions can proceed via different pathways [111, 112, 113]. In 2019, we found that a transition‐metal‐free, base‐mediated O‐arylation of alcohols and phenols (55) with triarylsulfonium salts (54) allowed the facile synthesis of various aryl ethers (56) by aromatic nucleophilic substitution in excellent yields with a broad substrate scope (Scheme 14) [114]. We also attempted the use of cyclic arylthianthrenium salt to introduce the complex arenes onto the oxygen atoms of alcohols, but unfortunately, the sulfonium salt tends to undergo ring‐opening in this base‐mediated reaction [114]. Mechanistic studies revealed that alcohol or phenol is first deprotonated with base to form an oxyanion, which then undergoes nucleophilic attack at the carbon atom of the C—S bond in triarylsulfonium salt (54) to generate the O‐arylated product (56) (Scheme 14 ). Furthermore, the detection of small amounts of benzene and aldehyde as byproducts in these reactions suggested that the basic decomposition of triarylsulfonium cations by the nucleophilic attack of alkoxide ions at the sulfur center followed by elimination is also involved [114]. Later, Morofuji and Kano developed a similar transition‐metal‐free O‐arylation of alcohols and phenols with arylphenothiazinium salts, which can effectively avoid the ring‐opening side reactions of cyclic arylsulfonium salts under basic conditions and enable the introduction of complex aryl moieties onto oxygen atoms [45].

SCHEME 14.

Base‐mediated O‐arylation of alcohols and phenols with triarylsulfonium salts.

In 2024, we presented a base‐mediated preparation of aryl enol ethers from allylic alcohols and arylsulfonium salts (5j/59), wherein various α‐aryl allylic alcohols (57) including terminal and internal ones were favorably transformed to afford the corresponding aryl enol ethers (58‐I/58‐II) in good yields (Scheme 15) [115]. Both acyclic triphenylsulfonium salt (6j) and cyclic arylphenothiazinium salts (59) proved to be effective arylation reagents for the chemoselective O‐arylation and alkene‐isomerization of α‐aryl allylic alcohols [115]. Unfortunately, arylthianthrenium salt, arylphenoxathiinium salt, and aryldibenzothiophenium salt predominantly afforded the ring‐opening byproducts, and alkylarylsulfonium salts failed to produce the product [115]. Arylphenothiazinium salts bearing strong electron‐donating groups on the phenyl rings yielded the ring‐opening aryl enol ether products as well, due to the much electron‐rich feature of the aryl group over that of the phenothiazine moiety [115]. A plausible aromatic nucleophilic substitution mechanism is suggested as follows (Scheme 15): 1) allylic alcohol (57) first undergoes deprotonation with NaOH to form an alkoxide anion, which nucleophilically attacks the aryl ring of arylsulfonium salt (6j or 59) at the ipso position to generate an aryl allyl ether (60); 2) the aryl allyl ether (60) is further deprotonated by NaOH to form a carbanion (61); and 3) eventually, the thermodynamically favorable arrangement of the carbon–carbon double bond of 61, followed by protonation with trace amount of water or the solvent (HX), yields the isomerized product (58). This protocol offered a concise method for the synthesis of aryl enol ethers, enabling a valuable base‐mediated alkene‐isomerization under transition‐metal‐free conditions.

SCHEME 15.

Base‐mediated arylation of α‐aryl allylic alcohols with arylsulfonium salts for the facile synthesis of aryl enol ethers.

The difluoromethyl group (CF₂H) can be used as a bioisostere for thiol, hydroxyl, carbonyl, methyl, methoxy, and amino groups in bioactive molecules, behaving as a weak hydrogen bond donor with comparable steric and electrostatic parameters, and is capable of modulating their physicochemical and biological characteristics [116, 117, 118, 119, 120]. Much effort has been devoted to the development of efficient difluoromethylation strategies for the direct introduction of CF₂H group into target molecules [116, 117, 118, 119, 120]. Among an array of the known CF₂H reagents, difluoromethyltrimethylsilane (TMSCF₂H) functions as a highly efficient CF₂H source for nucleophilic difluoromethylation reactions, but the catalyst‐free difluoromethylation of aromatic systems with this reagent remains much underexplored [121, 122, 123, 124, 125]. Very recently, we developed a catalyst‐free difluoromethylation reaction between arylsulfonium salts (62) and TMSCF₂H (63), offering a practical and efficient strategy for the facile synthesis of difluoromethylated arenes (64) (Scheme 16) [126]. In this reaction, the cyclic arylthianthrenium salt and aryldibenzothiophenium salt were prone to undergo ring‐opening difluoromethylation, affording the desired difluoromethylated product in a very low yield; alkylarylsulfonium salts such as aryltetrahydrothiophenium triflate and aryldimethylsulfonium triflate failed to deliver the HCF₂‐product even though they were nearly completely decomposed [126]. Both arylphenothiazinium salts and arylphenoxathiinium salts (62) were demonstrated to be suitable aryl transfer platforms for the catalyst‐free difluoromethylation, due to their electronic features of the sulfur frameworks. This protocol enabled the formal C—H difluoromethylation of a broad scope of arenes, including pharmaceutically relevant molecules [126]. A plausible reaction mechanism is proposed as below (Scheme 16): 1) first, activation of TMSCF₂H with CsF in DMF yields a relatively stable intermediate (65), which behaves as a reservoir of the ⁻CF₂H anion via the fast addition of the ⁻CF₂H anion to the carbonyl group of DMF; 2) then, a reversible transfer of the ⁻CF₂H anion to the sulfur center of arylsulfonium salt (62) forms a sulfurane intermediate (66); and 3) this unstable intermediate (66) undergoes rapid and selective ligand coupling to form the difluoromethylated product (64) with release of 10‐methyl‐10H‐phenothiazine [126].

SCHEME 16.

Catalyst‐free difluoromethylation of arylsulfonium salts with TMSCF₂H.

4. Photoinduced Reactions of Arylsulfonium Salts

The photoredox catalysis has been extensively utilized as a potent and sustainable driving force to conduct various chemical transformations of arylsulfonium salts in recent years [9, 10, 11, 12, 13, 14, 15, 16, 17, 30, 31, 32, 33, 34, 35]. It has expanded the synthetic applications of arylsulfonium salts and has provided a promising avenue for the efficient generation of aryl radicals in modern organic chemistry. As a complement to the palladium‐catalyzed deuteration of arylsulfonium salts with CD₃OD, we simultaneously developed a photoinduced deuteration of arylsulfonium salts in a mixture of deuterated solvents (Scheme 17) [88]. The reaction required no photocatalyst, wherein various arylthianthrenium salts (20) were readily transformed in deuterated solvents under visible‐light irradiation. The photocatalytic hydrogenation of 20 was superior to that of aryldibenzothiophenium salt, arylphenoxathiinium salt, acyclic triarylsulfonium salt, and alkylarylsulfonium salt under the same conditions [88]. In some cases, the efficiency of photoinduced reaction was higher than that of the Pd‐catalyzed reaction. These two methods complemented each other and allowed the convenient synthesis of deuterated arenes in good yields [88].

SCHEME 17.

Photoinduced deuteration of arylthianthrenium salts.

Thanks to the unique electronic and lipophilic properties, the trifluoromethylselenyl (SeCF₃) group holds enormous potential in medicinal chemistry [127, 128, 129, 130]. Our group has devoted numerous efforts to the development of novel trifluoromethylselenolation reactions with [Me₄N][SeCF₃] [131, 132, 133, 134, 135, 136, 137]. The catalyst‐ and additive‐free reactions of arylaryldibenzothiophenium salts (67, as examples of efficient aryl transfer platforms) with [Me₄N][SeCF₃] (68) under visible‐light irradiation furnished the corresponding aryl trifluoromethyl selenides (69) in good yields, allowing the late‐stage selective trifluoromethylselenolation of arenes, which offers a precise and convenient synthetic route to SeCF₃‐containing drug‐like molecules (Scheme 18) [138]. Further investigation showed that aryldibenzothiophenium platform was a better aryl transfer agent than the thianthrenium and acyclic diphenylsulfonium salts for this photoinduced reaction [138]. Mechanistic studies revealed that the reaction may start from the formation of an electron donor–acceptor complex (70) between arylsulfonium cation and ^–SeCF₃ anion (Scheme 18) [138]. Subsequently, a intramolecular SET in 70 occurs under visible‐light irradiation to form a sulfur radical intermediate (71) and a •SeCF₃ radical, which undergoes rapid decomposition to yield an aryl radical and homocoupling to yield CF₃SeSeCF₃, respectively (path A). Finally, cross‐coupling of the aryl radical with CF₃SeSeCF₃ affords complex 72 that decomposes to provide the trifluoromethylselenylated product (69). It is also possible that complex 70 generates a sulfurane intermediate (73) under visible‐light irradiation, which then undergoes ligand coupling (reductive elimination), to afford the target product (path B) [138].

SCHEME 18.

Photoinduced trifluoromethylselenolation of arylsulfonium salts with [Me₄N][SeCF₃].

As a congener of oxygen‐, sulfur‐, and selenium‐containing chemical entities, the trifluoromethyltelluryl (TeCF₃)‐containing molecules also have substantial application potentials; however, their synthetic methods are particularly scarce [139, 140, 141]. In 2025, we reported a green‐light‐induced trifluoromethyltelluration with [Me₄N][TeCF₃] (75), allowing the conversion of a variety of arylsulfonium salts (74) bearing diverse substituents on the aryl moieties to the corresponding aryl trifluoromethyl tellurides (76) in good yields (Scheme 19) [142]. This catalyst‐free protocol is distinguished by its mild reaction conditions, simple operation, and broad substrate scope, enabling functionalization of complex pharmaceutically relevant molecules. Unlike the above trifluoromethylselenylation, arylthianthrenium salts exhibited optimal reactivity in the trifluoromethyltelluration [142]. Arylphenoxathiinium salt and aryldibenzothiophenium salt could afford the trifluoromethyltellurylated product in comparable yields, while acyclic triarylsulfonium salt provided a moderate yield. The reaction was postulated to proceed through an electron donor–acceptor (EDA) complex (Scheme 19): first, arylsulfonium salt (74) and [Me₄N][TeCF₃] (75) reversibly forms an EDA complex (77); subsequently, an intramolecular SET occurs upon photoirradiation to generate a sulfur radical (78) and a •TeCF₃ radical; and finally, decomposition of 78 yields an aryl radical which undergo cross‐coupling with the •TeCF₃ radical to furnish the trifluoromethyltellurylated products (76) [142]. Moreover, the MTT assays using different tumor cell lines uncovered that some of those synthesized TeCF₃‐containing compounds have excellent anticancer activity, implying the great application potentials of TeCF₃ motif in life science [142].

SCHEME 19.

Photoinduced trifluoromethyltelluration of arylsulfonium salts with [Me₄N][TeCF₃].

O‐Aryl esters represent an important family of renewable feedstocks and serve as effective arylation or acylation reagents for the synthesis of high‐value molecules [143]. These compounds have also been widely found in the backbones of pharmaceuticals, agrochemicals, natural products, and functional materials. Recently, we accomplished a convenient preparation of O‐aryl esters (81) from arylsulfonium salts (79) and carboxylic acids (80) via photoredox catalysis by combining an Ir‐catalyst with a copper salt, overcoming the poor nucleophilicity of carboxylic acids (Scheme 20) [143]. Among all types of arylsulfonium salts tested, arylthianthrenium salts were identified as the optimal aryl transfer reagents; arylphenoxathiinium salts afforded good yields of O‐aryl esters; aryldibenzothiophenium salt and arylphenothiazinium salt gave the lower yields of product; and alkylarylsulfonium salt was ineffective for esterification, leading to no desired product [143]. By this method, various structurally complex O‐aryl esters were readily synthesized in high yields with excellent functional group tolerance, including ligation of two drug molecules [143]. Mechanistically, the reaction is initiated by the photoexcitation of Ir(ppy)₃ to Ir(III)*, which reduces arylsulfonium salt (79) via SET to generate an aryl radical and an Ir(IV) species (Scheme 20). Meanwhile, Cu(MeCN)₄PF₆ undergoes ligand exchange with carboxylic acid (80) in the presence of NaHCO₃ to form a Cu(I)‐OCOR species (82), which is further oxidized with Ir(IV) to form a Cu(II)–OCOR complex (83). Subsequent addition of the aryl radical to 83 yields an Ar–Cu(III)–OCOR intermediate (84), which undergoes reductive elimination to afford the final product (81) [143].

SCHEME 20.

Visible‐light‐induced esterification of carboxylic acids with arylsulfonium salts.

Short after, we extended this photoredox/copper dual catalytic system to the direct difluoroalkylation of arylsulfonium salts [144]. In the presence of an Ir‐photocatalyst and copper agents, arylthianthrenium salts (85) underwent efficient green‐light‐irradiated difluoroalkylation with XCF₂COR (86, X = Br, I, TMS) to furnish the difluoroalkylated arenes (87) in good yields (Scheme 21). Arylphenoxathiinium salt, aryldibenzothiophenium salt, and arylphenothiazinium salt were also the available aryl coupling partners in the reaction, affording relatively lower yields, whereas dialkylarylsulfonium salt gave no desired product under the standard conditions [144]. This protocol featured mild reaction conditions, simple operation, a broad substrate scope, and excellent regioselectivity. Mechanistic studies revealed that this photoinduced copper‐mediated difluoroalkylation may involve a radical mechanism (Scheme 21) [144]. First, Ir(ppy)₃ is activated under visible‐light irradiation to form an excited state (Ir(III)*). The excited Ir(III)* is reduced by Cu(I) salt to yield an Ir(II) species, which readily reduces arylsulfonium salt (85) via SET to form an aryl radical and regenerate the Ir(III) catalyst (path A). Alternatively, the excited Ir(III)* directly reduces arylsulfonium salt (85) via SET to afford an aryl radical and Ir(IV) species (path B), which is reduced by Cu(I) salt to regenerate the Ir(III) catalyst. Meantime, the single‐electron reduction of BrCF₂COR with a mixture of Cu(I) salt/Cu powder generates a •CF₂COR radical (88), which is combined with the Cu(I) salt to give a Cu(II)‐CF₂COR intermediate (89). Association of 89 with the aryl radical furnishes an Ar–Cu(III)–CF₂COR complex (90), which undergoes reductive elimination to afford the difluoroalkylated product (87) [144].

SCHEME 21.

Photoinduced copper‐mediated difluoroalkylation of arylthianthrenium salts with XCF₂COR.

The copper‐mediated visible‐light‐induced trifluoromethylation of arylsulfonium salts was achieved with using Yagupolskii–Umemoto reagent as the CF₃ transfer source [145]. The reaction proceeded smoothly at ambient temperature under 380–385 nm LED irradiation and enabled the efficient conversion of a variety of arylthianthrenium salts (91) to the corresponding trifluoromethylated arenes (92) in good yields (Scheme 22), showing excellent selectivity and functional group tolerance. This protocol represents the first cross‐coupling of two electrophilic sulfonium‐based reagents and allows the late‐stage modification of bioactive molecules, supplying a practical approach for the synthesis of drug‐like CF₃ arenes [145]. In addition, arylphenoxathiinium salt, aryldibenzothiophenium salt, arylphenothiazinium salt, and triphenylsulfonium salt reacted similarly with the Yagupolskii–Umemoto reagent (1a) to give the desired product in close or relatively low yields [145]. Unfortunately, aryltetrahydrothiophenium salt and aryldimethylsulfonium salt did not form the CF₃‐product. A brief survey of reaction mechanism revealed that Cu(I)CF₃ is possibly formed as a key intermediate (Scheme 22), and a mixture of pyridine and copper agents may play a synergetic role in accelerating the decomposition of the two sulfonium salts [145]. Under visible‐light irradiation, the copper powder first reduces the Yagupolskii–Umemoto reagent (1a) through SET to generate a •CF₃ radical, facilitated by pyridine. The •CF₃ radical is further reduced by copper powder to form a Cu(I)CF₃ species. Subsequently, SET between arylthianthrenium salt (91) and Cu(I)CF₃ under visible light irradiation in the presence of pyridine produces an aryl radical and a Cu(II)CF₃ intermediate (93), which combine to afford an Ar–Cu(III)–CF₃ complex (94). Finally, reductive elimination of 94 provides the trifluoromethylated product (92) [145].

SCHEME 22.

Copper‐mediated photoinduced trifluoromethylation of arylthianthrenium salts with Yagupolskii–Umemoto reagent.

Heptafluoroisopropylated arenes have been recognized as promising candidates for drug discovery [146], as excellent catalysts for chiral synthesis [147], and as potent agents for agricultural pest control [148, 149], due to the unique characteristics of CF(CF₃)₂ group such as high lipophilicity, strong electron‐withdrawing ability (similar to that of the CF₃ group), and the much steric bulk. Consequently, the development of efficient synthetic methods for heptafluoroisopropylated arenes is very sought after [150]. Very recently, we disclosed a photoinduced Cu‐promoted heptafluoroisopropylation of arylsulfonium salts (95) with AgCF(CF₃)₂ (96) under 420 nm LED irradiation (Scheme 23) [150]. The reaction successfully tamed the light‐sensitive AgCF(CF₃)₂ reagent and enabled the conversion of different types of arylsulfonium salts to the corresponding heptafluoroisopropylarenes (97) in good yields. This protocol was also feasible for the late‐stage heptafluoroisopropylation of drug molecules, showing advantages of good functional group tolerance and excellent chemoselectivity [150]. Arylthianthrenium salt, arylphenoxathiinium salt, arylphenothiazinium salt, and aryldibenzothiophenium salt were all the suitable aryl coupling partners for this photocatalytic copper‐mediated heptafluoropropylation, with arylthianthrenium salts exhibiting relatively higher reaction efficiency. Alkylarylsulfonium salt was found to be incompatible and showed no reactivity with AgCF(CF₃)₂. The reaction may begin with the rapid transmetalation of AgCF(CF₃)₂ (96) with copper(I) to form a stable Cu(I)CF(CF₃)₂ complex (98) (Scheme 23) [150]. On the other hand, single‐electron reduction of arylsulfonium salt (95) with the excited Ir(III)* species (that is generated in situ from photoactivation of Ir(ppy)₃) to generate an aryl radical and a Ir(IV) species. The Cu(I)CF(CF₃)₂ complex (98) is subsequently oxidized with Ir(IV) to yield a Cu(II)CF(CF₃)₂ species (99), which combines with the aryl radical to form an Ar–Cu(III)–CF(CF₃)₂ intermediate (100). Eventually, reductive elimination of 100 affords the heptafluoroisopropylated product (97).

SCHEME 23.

Photocatalytic copper‐promoted heptafluoroisopropylation of arylthianthrenium salts with AgCF(CF₃)₂.

5. Conclusion

The need for efficient and selective synthetic methods for drugs, natural products, and advanced materials has significantly spurred chemists to continuously develop novel reagents and reaction paradigms. In this personal account, we summarized our group's decade‐long efforts in the synthetic application of arylsulfonium salts, covering three reaction systems: transition‐metal‐mediated cross‐couplings, catalyst‐free reactions, and photoinduced transformations. By taking advantages of the structural versatility of sulfonium salts from Yagupolskii–Umemoto reagents, alkylarylsulfonium salts to triarylsulfonium salts and from acyclic to cyclic arylsulfonium frameworks, we have developed a series of efficient coupling strategies for the convenient formation of carbon–carbon and carbon–heteroatom bonds and for the late‐stage functionalization of complex bioactive molecules. It was found that different reaction types usually prefer different kinds of arylsulfonium salts as the optimal aryl transfer platforms. The selective C—S bond cleavage and functionalization of arylsulfonium salts can be successfully tuned by modulating the electronic and steric features of arylsulfonium salts, the catalytic systems used, and the possible reaction mechanisms involved. The reasonable choice of sulfonium frameworks, catalytic systems, and reaction pathways (e.g., transition‐metal‐mediated coupling, aromatic electrophilic substitution, aryne formation/functionalization, and photoinduced transformation) is conductive to improve the reaction efficiency and selectivity, addressing the long‐standing challenges in the traditional cross‐coupling methods.

Looking ahead, the synthetic utilization of arylsulfonium salts holds great potential for further expansion [151, 152, 153]. Future research will continue exploring untapped reactivity of arylsulfonium salts, leveraging the structural innovations to unlock new reaction modes and functional groups installation. Considerable efforts will also focus on the deep mechanistic understanding of sulfonium‐mediated reactions, which will in turn guide the rational design of more efficient reagents and catalytic systems. Additionally, extensive application of arylsulfonium salts in complex molecular synthesis, including natural product total synthesis and pharmaceutical development, will become another important research field. This trend has been implicated by recent studies from the Ritter group applying vinylthianthrenium salts for cellular cysteine/protein labeling [154] and from the Mascareñas group using arylthianthrenium salts as prodrugs [155]. It is anticipated that a growing number of reaction paradigms with the known or newly designed arylsulfonium salts will be reported for advanced synthesis in the near future, contributing prominently to the development of the more sustainable, efficient, and selective synthetic toolkits.

Author Contributions

J.‐W. S. and X. H. collected the literature, analyzed the data, and wrote the paper. C.‐P. Z. conceived this work, and wrote and revised the paper.

Funding

This study was supported by the Natural Science Foundation of Hubei Province (2024DJC038).

Conflicts of Interest

The authors declare no conflicts of interest.

Biographies

Jia‐Wei Song is a second‐year Ph.D. student in the research group of Prof. Cheng‐Pan Zhang at Wuhan University of Technology (WHUT). He obtained his master's degree in pharmacy from WHUT in 2024. His research interests are the synthesis and applications of arylsulfonium salts.

Xue Han is a third‐year master student in the research group of Prof. Cheng‐Pan Zhang at Wuhan University of Technology. She obtained her bachelor's degree in pharmacy from Hubei University of Chinese Medicine in 2023. Her research interests mainly focus on the trifluoromethylselenolation reactions using BnSeCF₃ reagent.

Cheng‐Pan Zhang obtained his bachelor's degree in pharmacy from Chongqing Medical University in 2005. He received his Ph.D. degree from Shanghai Institute of Organic Chemistry in 2011 under the supervision of Prof. Ji‐Chang Xiao. He was a postdoctoral fellow in Prof. David A. Vicic's group at the University of Hawai’i from 2011 to 2012. Then, he worked with Prof. John A. Gladysz in Texas A&M University. In 2014, he joined Wuhan University of Technology as a full professor. His current research interests are the reactions of arylsulfonium salts and the development of novel fluoroalkylation methodologies.