Progress in Radical Fluorosulfonyl Reagents

Abstract

Sulfur(VI) fluoride exchange (SuFEx) chemistry that relies on the unique reactivity–stability balance of high valent organosulfur has emerged as a promising topic for the next-generation click reaction. Sulfonyl fluorides are the most widely used connective hubs of the SuFEx click reaction with widespread applications in the fields of chemical biology, drug discovery, and materials science. Compared with current methods, direct fluorosulfonylation with fluorosulfonyl radicals has emerged as a concise and efficient approach for the production of sulfonyl fluorides. The highly active SO₂F radical was an unstable and inaccessible precursor until it was observed in the decomposition of fluorosulfonyl azide, which inspired efforts towards the production of fluorosulfonyl radical precursors for direct radical fluorosulfonylation processes. This review presents and discusses current breakthroughs in the generation of fluorosulfonyl radicals from various radical precursors, as well as their application in the synthesis of diverse functionalized sulfonyl fluorides.

1 Introduction

2 FSO₂Cl as a Radical Precursor

3 Benzimidazolium Fluorosulfonates as Radical Precursors

4 Alk-1-ynylsulfonyl Fluorides as Radical Precursors

5 (Diarylmethylene)sulfamoyl Fluorides as Radical Precursors

6 Vinyl Fluorosulfates as Radical Precursors

7 Conclusion and Outlook

Key words

SuFEx - sulfonyl fluoride - fluorosulfonyl radicals - radical fluorosulfonylation - fluorosulfonyl radical precursors

1

Introduction

A promising area for the next-generation click reaction is sulfur(VI) fluoride exchange (SuFEx) chemistry, which is based on the special reactivity–stability balance of high valent organosulfur.[1] Sulfonyl fluorides are the most popular connective hubs of the SuFEx click reaction, and as such they have garnered interest and are widely applied in the domains of chemical biology,[2] [3] [4] [5] [6] drug development,[7] [8] [9] [10] [11] and materials science (Figure [1]).[12] [13] [14] [15] [16] Presently, numerous methods exist for synthesizing sulfonyl fluoride compounds, including the chloride–fluoride exchange of sulfonyl chlorides,[17] [18] [19] SO₂ insertion/fluorination,[20] [21] [22] [23] electrophilic fluorination of thiols,[24] [25] and anodic oxidative fluorination of thiols.[26] [27] Another method for synthesizing sulfonyl fluoride compounds is to use synthetic building blocks containing a sulfonyl fluoride group[28] [29] [30] to complete the direct fluorosulfonylation process to construct the corresponding products. Compared with the above mentioned S–F bond formation, direct fluorosulfonylation using a fluorosulfonyl radical is more challenging and in high demand.[31] [32] [33] [34] [35]

Yi Wang obtained his B.S. degree in 2005 at Nanjing University (China). He continued to study organic chemistry at the University of Edinburgh, where he received his Ph.D. in 2010 with Prof. Hon Wai Lam. He then pursued postdoctoral studies in the group of Prof. David O’Hagan (University of St Andrews, UK) as an ERC Research Fellow. In 2013, he joined the faculty at the School of Chemistry and Chemical Engineering, Nanjing University as an associate professor. Since 2020, he has been a professor at School of Chemistry and Chemical Engineering at Nanjing University. His research group is interested in fluorine chemistry, photocatalytic synthetic chemistry, and electrochemical synthesis. Heyin Li obtained his B.S. degree in 2020 at LiaoNing Petrochemical University (China). He has been a graduate student in Prof. Wang Yi’s group at Nanjing University, where he focuses on activation and utilization of inert fluorine sources.

The highly active SO₂F radical was recognized as an unstable and inaccessible reagent until the observation of this species from the decomposition of fluorosulfonyl azide.[36] This observation inspired efforts to develop suitable fluorosulfonyl radical precursors for direct radical fluorosulfonylation reactions. In this review, we focus on the most recent advances in the fluorosulfonyl radical involved transformations, with emphasis on the synthesis of sulfonyl fluorides.

Scheme 1 Radical fluorosulfonylation of alkenes by using FSO₂Cl as a radical precursor and proposed mechanism

Figure 1 Examples of biologically active SO₂F-containing compounds

2

FSO₂Cl as a Radical Precursor

Scheme 2 Radical chloro-fluorosulfonylation of alkynes

Scheme 3 Electrochemical oxo-fluorosulfonylation of alkynes under air

Due to the complicated preparation process and its volatility at room temperature, sulfuryl chloride fluoride (FSO₂Cl) has not been widely used by researchers in the past. However, since the homolytic bond dissociation energy of the S–F bond (84 ± 10 kcal mol^–1) is higher than that of the S–Cl bond (43 ± 10 kcal mol^–1), it was used as a fluorosulfonyl radical source for the first time by Liao and co-workers in 2020 (Scheme [1]).[37] This method can be used to construct a series of diverse sulfonyl fluoride compounds. A possible reaction mechanism has been proposed as follows: the fluorosulfonyl radical is produced when electrons are transferred from the excited iridium catalyst to FSO₂Cl. Then the radicals can react with unsaturated hydrocarbons to form the intermediate A. Intermediate A initiates the chain pathway by attacking FSO₂Cl, leading to the formation of intermediate C. Subsequently, intermediate C undergoes HCl elimination to yield sulfonyl fluoride compounds. Additionally, a redox mechanism involving the oxidation of A to B by Ir^IV, followed by deprotonation, likely contributes to this process.

Scheme 4 Radical fluorosulfonylation of vinyl triflates

Scheme 5 Electroreductive hydroxy-fluorosulfonylation of alkenes

In 2021, the same group developed a radical chloro-fluorosulfonyl difunctionalization reaction using FSO₂Cl and successfully synthesized a series of 2-chloroalk-1-enylsulfonyl fluorides (BCASF) as new sulfonyl fluoride building blocks that can serve as efficient synthetic intermediates (Scheme [2]).[38] The proposed mechanism is shown in Scheme [2]. Initially, the fluorosulfonyl radical is produced by electron transfer from the excited iridium catalyst to FSO₂Cl. The SO₂F radical subsequently combines with the C≡C bond of the alkyne to form intermediate A. Then the intermediate A attacks FSO₂Cl, generating the 2-chloroalk-1-enylsulfonyl fluoride product and initiating the chain pathway. Furthermore, intermediate A undergoes a hydrogen-atom transfer process (HAT) that can promote the generation of B. α-Chlorinated diethyl ether E is produced when Ir^IV oxidizes the ether-derived radical C to the cationic intermediate D and then adds the chloride anions.

Electrochemical synthesis plays an increasingly important role in organic synthesis. In 2021, Huang, Liao, and co-workers developed an electrochemical strategy that can achieve the transformation of FSO₂Cl into fluorosulfonyl radicals under electrocatalytic conditions.[39] This approach can smoothly synthesize a rich variety of β-keto sulfonyl fluorides (BKSF) via oxo-fluorosulfonylation of alkynes with air as an oxidant (Scheme [3]). In the proposed mechanism (Scheme [3]) the process starts with the cathodic reduction of FSO₂Cl, which creates a FSO₂ radical. The SO₂F radical then adds to the alkyne generating vinyl radical A, which can be trapped by O₂ to produce peroxy radical B. Then the Russell mechanism transforms B into radical intermediate C, followed by a cathodic reduction of C to make enolate D, which is protonated to produce the β-keto sulfonyl fluoride. Remarkably, α-chloro-β-keto sulfonyl fluorides could be formed by electrophilic chlorination of the in situ produced MgCl₂ and FSO₂Cl in THF.[39]

The same group discovered a method in 2022 for electrochemically radical fluorosulfonylation of vinyl triflates by using FSO₂Cl as the SO₂F radical source, allowing for quick synthesis of several β-keto sulfonyl fluorides (Scheme [4]).[40] In the proposed mechanism (Scheme [4]) the SO₂F radical is produced during cathodic reduction of FSO₂Cl, which subsequently adds to the vinyl triflate yielding intermediate A. Then A undergoes β-fragmentation to afford the β-keto sulfonyl fluoride product.

Scheme 6 Fluorosulfonylvinylation of unactivated C(sp³)–H via electron donor–acceptor photoactivation

In 2023, Huang and co-workers successfully developed an electroreductive 1,2-hydroxy-fluorosulfonylation of alkenes producing various β-hydroxy sulfonyl fluorides (Scheme [5]).[41] In the proposed reaction path (Scheme [5]) for this electroreductive mechanism, the process begins with the production of a SO₂F radical through cathodic reduction of FSO₂Cl. The SO₂F radical then combines with styrene to form benzylic radical intermediate A that predominantly reacts with O₂ to yield benzyl peroxy radical B. A HAT process between Et₃SiH and B produces hydroperoxide C that is reduced by B₂(OH)₄ to provide borate D, which is hydrolyzed to give the β-hydroxy sulfonyl fluoride product. Simultaneously, the SO₂F radical is renewed by halogen atom transfer (XAT) of the triethylsilyl radical with FSO₂Cl. Other rival reaction routes, especially in the absence of B₂(OH)₄ and Et₃SiH, are also feasible in the interim.[41]

In 2023, Huang and co-workers developed a novel electron donor–acceptor (EDA) complex mediated radical fluorosulfonylation processes for the synthesis of diverse 6-keto alkenylsulfonyl fluorides (Scheme [6]).[42] [43] In addition, tetrahydropyridine can also be generated by condensation of 6-keto-enesulfonyl fluorides with aniline followed by an intramolecular aza-Michael addition. The mechanism is shown in Scheme [6]. First, the EDA complex generates the SO₂F radical through the SET pathway under light irradiation, which subsequently react with alkynes to give vinyl radical A. Subsequently, radical B is generated after a 1,5-HAT process, which undergoes a 5-exo-trig cyclization to afford the radical C. Following that, the successful migration of a fluorosulfonylvinyl group leads to the generation of ketyl radical D. The subsequent SET process of D with FSO₂Cl produces intermediate E, while the SO₂F radical is regenerated. Finally, the corresponding 6-keto alkenylsulfonyl fluoride is smoothly generated after cation E loses a proton. This product can condense with aniline and then undergoes intramolecular aza-Michael addition to give the tetrahydropyridine product (Scheme [6]).[42] [43]

Scheme 7 Radical hydro-fluorosulfonylation of propargylic alcohols

Scheme 8 Fluorosulfonyl arylation of alkynes

The same research group achieved a simple synthesis of γ-hydroxy (E)-alkenylsulfonyl fluorides in 2024 by developing a radical hydro-fluorosulfonylation process of propargyl alcohols with FSO₂Cl (Scheme [7]).[44] In the proposed reaction pathway (Scheme [7]), a SET process of the EDA complex formed between propargyl alcohol 2 and FSO₂Cl upon visible light irradiation generates the fluorosulfonyl radical, which then combines with the alkyne to generate vinyl radical A. Notably, thermodynamic control leads to a configurational inversion and generates vinyl radical B. The subsequent HAT process releases the product and the alkyl radical C, and the halogen atom transfer (XAT) between C and FSO₂Cl provides the SO₂F radical.[44]

Huang and co-workers designed a novel approach for fluorosulfonyl-arylation of alkynes with FSO₂Cl in 2024, allowing for the rapid assembly of benzo-fused carbocyclic and heterocyclic compounds containing the fluorosulfonyl group (Scheme [8]).[45] The proposed mechanism is shown in Scheme [8]. Under light irradiation, the EDA complex produces the SO₂F radical and radical cation C, the SO₂F radical subsequently couples with alkyne 3 to form vinyl radical A, which undergoes intramolecular cyclization to afford the intermediate B. Product 4 is produced smoothly together with the regeneration of SO₂F radical when intermediate B is oxidized by FSO₂Cl. In addition, the SO₂F radical may also react with C to generate intermediate D that undergoes a cyclization reaction to give intermediate E; oxidative aromatization of intermediate E smoothly gives product 4.[45]

In 2024, Huang and co-workers also developed a novel protocol for the radical ring-opening fluorosulfonylation of methylenecyclobutanol with FSO₂Cl; this method rapidly generates various FSO₂-functionalized γ,δ-unsaturated carbonyls (Scheme [9]).[46]

Scheme 9 Radical ring-opening fluorosulfonylation of methylenecyclobutanols

3

Benzimidazolium Fluorosulfonates as Radical Precursors

Since FSO₂Cl is volatile at room temperature and the preparation process is complicated, there is a high demand for the development of new radical fluorosulfonylation reagents. To solve these difficulties, in 2022, independent work by Wang and co-workers[47] and Liao and co-workers[49] developed 2-aryl-1-(fluorosulfonyl)-3-methylbenzimidazolium salts that they named IMSF and FABI, respectively.

Wang and co-workers successfully developed a series of new radical fluorosulfonylation reagents by activating sulfuryl fluoride (SO₂F₂).[47] The resulting imidazolium fluorosulfonate reagents (IMSF) are practical and air-stable crystalline salts that can be utilized for a sequential radical stereoselective fluorosulfonylation to produce diverse functionalized sulfonyl fluoride compounds (Scheme [10]).[47] The proposed mechanism for the photocatalytic formation of alkenylsulfonyl fluorides is shown in Scheme [10]. Following the oxidation of the excited state of 4CzIPN* by 1-(fluorosulfonyl)-3-methyl-2-(4-(trifluoromethyl)phenyl)benz­imidazolium triflate (2b), the 4CzIPN⁺ species is generated alongside imidazole B and fluorosulfonyl radical A. The fluorosulfonyl radical subsequently participates in an addition reaction with alkene 1, leading to the formation of intermediate C. Subsequently, intermediate C is oxidized by 4CzIPN⁺ to yield intermediate D and regenerate 4CzIPN. Intermediate D then undergoes hydrogen elimination to form E-alkenylsulfonyl fluoride 3 in the presence of a weak base. Under photocatalytic conditions, product 3 undergoes isomerization to yield the (Z)-alkenylsulfonyl fluoride product 4.[47]

Scheme 10 A novel imidazolium-based SO₂F radical reagent (IMSF) for radical stereoselective fluorosulfonylation

Furthermore, the same group broadened the scope of this radical fluorosulfonylation process to the hydro-fluorosulfonylation and migratory SO₂F-difunctionalization of alkenes using fluorosulfonyl-benzimidazolium salts 2a and 2b to give various functionalized sulfonyl fluoride compounds (Scheme [11]).[47] [48] The proposed mechanism is shown in Scheme [11]. The oxidation of the excited state of iridium catalyst *Ir^III by 1-(fluorosulfonyl)-2-methyl-3-phenylbenzimidazolium triflate (2a) generates an Ir^IV species together with imidazole F and fluorosulfonyl radical A. The addition of the SO₂F radical to the alkene affords intermediate G followed by hydrogen atom transfer with cyclohexa-1,4-diene H to furnish the alkylsulfonyl fluoride. The Ir^IV species was reduced by intermediate I to regenerate the Ir^III catalyst and to give compound J. The mechanism for photocatalytic migration fluorosulfonylation is also shown in Scheme [11]. Initially, the oxidation of the *Ir^III by fluorosulfonyl-benzimidazolium salt 2a gives an Ir^IV species and sulfonyl fluoride radical A. The addition of the SO₂F radical and 1-aryl-1-benzothiazol-2-ylpent-4-en-1-ol afforded the carbon radical intermediate K, which rapidly attacks the heteroarene to generate cyclic nitrogen radical intermediate L. Fast ring opening followed by radical β-cleavage furnishes a stabilized radical intermediate M, which is oxidized by Ir^IV to carbocation intermediate N. Finally, deprotonation of intermediate N affords the heteroaryl-migrated product.[47] [48]

Scheme 11 A novel fluorosulfonyl-benzimidazolium salt radical reagent for radical hydro-fluorosulfonylation and migratory SO₂F-difunctionalization of alkenes

Liao and co-workers independently developed the same, or similar 1-(fluorosulfonyl)-2-arylbenzimidazolium triflate salts, named FABI, as fluorosulfonyl radical reagents for the radical fluorosulfonylation reactions of alkenes. The radical fluorosulfonylation of various alkenes under photoredox conditions using 1-(fluorosulfonyl)-3-methyl-2-(4-(trifluoromethyl)phenyl)benzimidazolium triflate (2b) gave a series of functionalized sulfonyl fluoride compounds (Scheme [12]).[49]

Scheme 12 Radical fluorosulfonylation of alkenes enabled by a bench-stable redox-active fluorosulfonyl-benzimidazolium salt

Laio and co-workers successfully achieved the radical hydro-fluorosulfonylation of unactivated alkenes and alkynes under photocatalytic conditions by using fluorosulfonyl-benzimidazolium salt 2b as a source of the fluorosulfonyl radical to give a series of aliphatic sulfonyl fluoride compounds (Scheme [13]).[50] This method was used for the hydro-fluorosulfonylation of bioactive molecules.[50]

Scheme 13 Radical hydro-fluorosulfonylation of unactivated alkenes and alkynes by a fluorosulfonyl-benzimidazolium salt

Liao and co-workers also developed a photo-organocatalytic radical fluorosulfonylation of vinyl acetates with fluorosulfonyl-benzimidazolium salt 2b as the fluorosulfonyl radical precursor under visible light irradiation. This radical fluorosulfonylation strategy allows facile access to various β-keto sulfonyl fluorides (Scheme [14]).[51]

Scheme 14 Radical fluorosulfonylation of vinyl acetates

A radical fluorosulfonylation-initiated 1,2-fluorosulfonyl-arylation of alkenes to access of FSO₂-functionalized chromanes was furthermore developed by Liao and co-workers (Scheme [15]). The proposed mechanism is given in Scheme [15]. First, the excited state ODA* is oxidized by fluorosulfonyl-benzimidazolium salt 2b to generate a fluorosulfonyl radical, which then adds to the alkene to generate intermediate A. Subsequently, intermediate A is oxidized by ODA⁺ and loses a proton to give the chromane product.[52]

Scheme 15 Radical fluorosulfonyl arylation of alkenes

In 2023, Liao and co-workers developed a type of alkene radical 1-fluorosulfonyl-2-heteroaromatization reaction, which can efficiently introduce the sulfonyl fluoride group into the quinoxalinone skeleton. In addition, they devised a three-component radical-polar crossover reaction involving two distinct alkenes, employing fluorosulfonyl-benzimidazolium salt 2b as the source of SO₂F radicals. This approach enables a convenient access to alk-3-enylsulfonyl fluorides (Scheme [16]).[53] [54]

Scheme 16 Radical fluorosulfonyl heteroarylation of unactivated alkenes and FSO₂ radical-initiated tandem addition reaction of two different alkenes

Although many building blocks containing sulfonyl fluoride groups have been developed previously, the development of molecules containing both boronate and sulfonyl fluoride groups has been largely neglected. To solve this problem, in 2023, Wang and co-workers successfully developed the first fluorosulfonyl-borylation of alkenes and alkynes by using fluorosulfonyl-benzimidazolium salt 2b as a difunctional reagent under photocatalytic conditions. This method can utilize the imidazole residue generated by the single electron transfer process of the fluorosulfonyl-benzimidazolium salt reagent to in situ activate the B–B bond, thereby efficiently constructing a series of bifunctionalized products vicinal fluorosulfonyl borides (VFSBs) (Scheme [17]).[55]

Scheme 17 Photoredox-catalyzed stereo- and regioselective vicinal fluorosulfonyl-borylation of unsaturated hydrocarbons

The possible mechanism of the reaction is shown in Scheme [17]. The radical fluorosulfonyl-benzimidazolium salt 2b can be reduced by PC* under photocatalytic conditions to produce the SO₂F radical and imidazole residue II. The SO₂F radical then regioselectively adds to the alkene to produce vinylic radical intermediate III, which is then combined with B₂Cat₂ to produce Z-vinyl diboron radical species IV. The steric repulsion between the fluorosulfonyl group and the boronates leads to excellent stereoselectivity of the product. Subsequently, the in situ generated imidazole residue II efficiently activates the diboron reagent (as confirmed by ¹¹B NMR experiments) to form a highly active reaction intermediate V, which can then rapidly give the product and the radical intermediate VI. Finally, the intermediate VI is oxidized by PC⁺ followed by coupling with ^–OTf to obtain the boryl imidazolium salt VII, and the PC is regenerated to complete the photocatalytic cycle.[55]

Scheme 18 FSO₂ radical initiated photoredox cyclization of 4-enoic acids

In 2023, Liao and colleagues used fluorosulfonyl-benzimidazolium salt 2b as a fluorosulfonyl radical precursor and developed a tandem radical fluorosulfonylation/intramolecular lactonization method for the conversion of 4-enoic acids into γ-lactones containing sulfonyl groups (Scheme [18]).[56]

4

Alk-1-ynylsulfonyl Fluorides as Radical Precursors

Scheme 19 Radical 1-fluorosulfonyl-2-alkynylation of unactivated alkenes

Scheme 20 EnT-mediated N–S bond homolysis of a bifunctional reagent leading to aliphatic sulfonyl fluorides

2-Substituted alk-1-ynylsulfonyl fluorides (SASF) were usually used as connective hubs for click-cycloaddition reactions.[30] In 2022, Studer and co-workers first developed a method that using SASFs as C-radical traps and at the same time as SO₂F radical precursors. This protocol utilizes a novel radical alkene 1,2-difunctionalization pathway that allows the efficient preparation of various β-alk-1-ynyl fluorosulfonylalkanes (BAFSAs) (Scheme [19]).[57] In the proposed mechanism it is hypothesized that the reaction begins with AIBN initiating the formation of an AIBN-derived cyanopropyl radical. This radical subsequently adds to alkyne 2, leading to radical cleavage and the generation of a fluorosulfonyl radical. The fluorosulfonyl radical then adds to alkene 1 forming intermediate A. Radical intermediate A is trapped with alk-1-ynylsulfonyl fluoride 2 to give vinyl radical B that undergoes β-fragmentation to yield β-alkynyl fluorosulfonylalkane 3, thereby regenerating the fluorosulfonyl radical.[57]

Scheme 21 Three-component photochemical 1,2,5-trifunctionalizations of alkenes

Scheme 22 Photocatalytic access to aromatic keto sulfonyl fluorides from vinyl fluorosulfates

5

(Diarylmethylene)sulfamoyl Fluorides as Radical Precursors

The simultaneous incorporation of two functional groups onto alkene feedstocks in a single synthetic step represents an attractive strategy. In this context, in 2023, Glorius and co-workers reported the use of (diphenylmethylene)sulfamoyl fluoride as a potent bifunctional reagent for generating diverse aliphatic β-imino sulfonyl fluorides via EnT catalysis (Scheme [20]).[58]

The proposed mechanism is depicted in Scheme [20]. First, The PC* activates (diphenylmethylene)sulfamoyl fluoride (1) causing homolysis of the N–S σ-bond forming the fluorosulfonyl radical that rapidly adds to alkene 2 generating carbon-centered radical intermediate I. The carbon-centered radical intermediate I has the potential to engage in either radical recombination with the persistent iminyl radical II or undergo hydrogen atom transfer in the presence of a hydrogen atom donor, thereby forming aliphatic sulfonyl fluoride products 3 or 4 via chemodivergent pathways.[58]

In 2023, the same group achieved a three-component 1,2,5-trifunctionalization reaction catalyzed by energy transfer, which involved two different alkenes and utilized diverse bifunctional reagents. Notably, employing (diphenylmethylene)sulfamoyl fluoride yielded the desired products effectively. (Scheme [21]).[59]

6

Vinyl Fluorosulfates as Radical Precursors

In 2022, Li and co-workers reported the development of a photocatalytic method for synthesizing β-keto sulfonyl fluorides. This process involves radical fragmentation and recombination of vinyl fluorosulfates (Scheme [22]).[60] In the mechanism there are two proposed pathways (Scheme [22]). In Path A, upon energy transfer from PC*, vinyl fluorosulfate 1 undergoes homolytic decomposition, yielding the enol radical and the fluorosulfonyl radical. Subsequent radical recombination of these intermediates leads to the formation of product 2. Alternatively in Path B, 1 is reduced to the radical anion I by PC*, and then radical fragmentation/reconstruction gives intermediate III that is oxidized by PC⁺ to give the product 2.[60]

Scheme 23 Switchable carbo-fluorosulfonylation and hydro-fluorosulfonylation of alkenes enabled by bifunctional fluorosulfonyl radical precursors

Given that enol-derived fluorosulfonates could only undergo intramolecular radical fluorosulfonylation in previous reports, in 2023, Weng and co-workers developed a method for intermolecular radical fluorosulfonylation using enol-derived fluorosulfonates that can achieve the simultaneous installation of fluorosulfonyl and ketone functional groups onto alkenes. Furthermore, under this scheme, a radical hydro-fluorosulfonylation protocol can also be simultaneously achieved by adding appropriate hydrogen atom transfer reagents. This novel radical fluorosulfonylation strategy provides a facile method for the rapid assembly of various aliphatic δ-keto sulfonyl fluorides and their derivatives (Scheme [23]).[61] Mechanistically, first, the PC* activates radical fluorosulfonylating reagent 3 to promote the cleavage of the weak S–O σ-bond and form fluorosulfonyl radical I and O-radical II simultaneously. The fluorosulfonyl radical subsequently reacts with the alkene to form radical III. Radical recombination between radical III and α-keto-stabilized alkyl radical IV, which arises from the isomerization of intermediate II, yields the carbo-fluorosulfonylation product 5. Alternatively, HAT in the presence of a hydrogen atom donor leads to the hydro-fluorosulfonylation product 4.[61]

7

Conclusion and Outlook

The strategy involving fluorosulfonyl radicals for direct fluorosulfonylation has become an appealing approach for the straightforward synthesis of sulfonyl fluorides. This short review discusses recent progress in the field of direct fluorosulfonylation using various precursors of fluorosulfonyl radicals, highlighting five types of radical fluorosulfonylating reagents: FSO₂Cl, benzimidazolium fluorosulfonates, alk-1-ynylsulfonyl fluorides, (diarylmethylene)sulfamoyl fluorides, and vinyl fluorosulfates. These advancements have enabled the efficient synthesis of a broad array of functionalized sulfonyl fluorides, promising new opportunities for SuFEx click chemistry.

However, several challenges persist in this area. Firstly, the range of substrates applicable in the aforementioned reactions is relatively narrow, primarily confined to alkenes and alkynes. Secondly, the variety of available fluorosulfonyl radical precursors remains limited, currently comprising only five types. Therefore, there is a pressing need to innovate and expand the repertoire of fluorosulfonyl radical precursors. Lastly, the development of enantioselective radical fluorosulfonylation utilizing the SO₂F radical to produce chiral sulfonyl fluorides has yet to be achieved. Thus, the exploration of enantioselective radical fluorosulfonylation is in high demand. Considering the ongoing advancements and obstacles, there is potential for significant future progress in the utilization of fluorosulfonyl radicals.

Conflict of Interest

The authors declare no conflict of interest.

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Publication History

Received: 22 July 2024

Accepted after revision: 21 October 2024

Article published online:
11 November 2024