Recent Advances in Photoredox-Catalyzed Difunctionalization of Alkenes

Abstract

Alkenes and their related analogs are ideal starting materials for organic synthesis, and the selective difunctionalization of alkenes, which allows the simultaneous introduction of two neighboring bonds, has gained considerable attention in recent years. In particular, the photoredox-catalyzed difunctionalization of alkenes has also been accomplished, which has been regarded as an increasingly powerful tool for the synthesis of miscellaneous interesting molecular scaffolds in an environmentally benign and economical manner. Several exquisite strategies have been developed to facilitate this transformation, such as photosensitizer-catalyzed redox reactions, electron donor-acceptor (EDA) complexes-mediated photoreactions, and atom transfer radical addition (ATRA) reactions. This literature review briefly describes the most recent key progress on the photoredox-catalyzed 1,2-difunctionalization of various structurally diverse alkenes, including 1,2-dicarbofunctionalization, 1,2-carboheterofunctionalization, and 1,2-diheterofunctionalization, with a special emphasis on the mechanistic details.

1. Introduction

Alkenes and their related analogs are a class of ideal starting materials for the construction of complex molecules, because they are readily available in bulk quantities from renewable resources and petrochemical feedstocks [1]. They are also considered to be the most cost-effective and widely used raw material for organic synthesis, and due to the diversity of functional groups, they are used very frequently in different chemical industries. As basic functionalities, the exploration of efficient methods for the selective functionalization of alkenes has been a continuous pursuit throughout the history of organic chemistry. Thanks to the tireless efforts of chemists, various important advances in this field have been achieved, and a series of excellent approaches have already been applied in industry [2]. Scientists in the field have explored photoredox-catalyzed alkenes with regard to the study of catalysts, such as the catalyst-free functionalization of alkenes 1,2-dicarbon, the organic photocatalytic actualization of alkenes 1,2-dicarbon, the catalysis of alkene 1,2-dicarbon functionalization by COF photocatalyst, photocatalysts of transition metals (such as copper, iridium, palladium, rhodium) to catalyze the functionalization of alkenes 1,2-dicarbon, alkene 1,2-dicarbon functionalization reactions under double catalysis, the photocatalysis of 1,2-dicarbon functionalized alkenes using nanomaterials, etc. However, the research on photoredox-catalyzed alkenes still needs to be continuously explored, so researchers have done a lot of work on this basis. Among the many efforts toward alkene derivatization, the selective 1,2-difunctionalization of alkenes, allowing the simultaneous introduction of two new neighboring bonds on alkene skeletons, has gained considerable attention from the synthetic community [3]. In this scenario, a variety of chemical transformations, such as 1,2-dicarbofunctionalization, 1,2-carboheterofunctionalization, and 1,2-diheterofunctionalization, are particularly fascinating due to the construction of versatile significant complex molecules, which are ubiquitously encountered as core structural units in many bioactive natural products, synthetic drugs, and materials [4,5,6]. A number of heteroatoms, such as nitrogen, halogen, oxygen, sulfur, as well as selenium, could be efficiently decorated on the olefinic carbon atoms via such 1,2-difunctionalization, thus bringing new opportunities for the fabrication of uncommon bonds [7].

In recent years, visible light-driven photoredox transformations have been being regarded as an increasingly powerful instrument in synthetic chemistry for the synthesis of miscellaneous interesting molecular scaffolds in an environmentally benign and economical manner, since this replaces energy-consuming thermal chemical transformations [8]. Generally, in a photoredox transformation, the absorption of light by a specific organic compound leads to the formation of an excited state, and further results in the formation of highly reactive intermediates that promote the reaction, such as ions, radicals, or radical ions. Consequently, the reaction could proceed smoothly with stable and inactive substrates, thus simplifying the operation procedure [9]. In particular, the photoredox difunctionalization of alkenes has also been achieved [10]. Several exquisite strategies have been developed to facilitate this transformation under mild conditions to broaden its application scope in both academia and industry, such as the photosensitizer-catalyzed redox reactions, electron donor-acceptor (EDA) complexe-mediated photoreactions, and atom transfer radical addition (ATRA) reactions [11,12,13]. A few excellent reviews on photoredox catalysis and the functionalization of alkenes have already been published [14,15]. Considering the rapid development of photoredox chemistry, a comprehensive and timely overview on the photoredox-catalyzed difunctionalization of alkenes is highly desirable. Therefore, the information collected in this literature review briefly describes the most recent key progress on photoredox-catalyzed 1,2-difunctionalization of alkenes, giving mechanistic insights and their synthetic applications. Other related works on the functionalization of alkenes involving heterogeneous catalysis are not included.

2. Photoredox-Catalyzed Difunctionalization of Alkenes

2.1. Iridium-Catalyzed Difunctionalization of Alkenes

2.1.1. 1,2-Dicarbofunctionalization of Alkenes

In 2019, Glorius and co-workers [16] disclosed an elegant method of the 1,2-dicarbofunctionalization of aryl alkenes with Katritzky pyridinium salts as the radical precursors and electron-rich indoles as the coupling partners. With a catalytic amount of [Ir(dtbbpy)(ppy)₂](PF₆), a number of densely functionalized 1,1-diarylalkanes could be obtained in 25–95% yields (Scheme 1). Notably, pyridine-containing products, thioether-functionalized products, ester-containing products, Boc-protected amino-functionalized products and all-carbon quarternary centers are successfully produced in this system. Dipeptide-derived Katritzky pyridinium salt is also amenable in this transformation. Further, mechanistic studies suggest that the reaction began with the reduction of Katritzky salt by excited photocatalyst to afford the corresponding radical, which was captured by the aryl alkenes to give the arylmethyl radical intermediate. This intermediate could be oxidized to produce an arylmethyl carbocation intermediate, which was trapped by the nucleophilic aromatic compound to furnish the target product.

Subsequently, the Molander group [17] adopted another kind of radical progenitor alkyl N-(acyloxy)phthalimide ester to trigger the 1,2-dicarbofunctionalization of electron-rich aryl and heteraryl substituted olefins with organotrifluoroborates as the carbon-centered nucleophiles (Scheme 2). This protocol provides a robust implement for the carbo-alkynylation, -arylation, -allylation, or -alkenylation of alkenes by simply altering the structure of organotrifluoroborates. The author suggested that this reaction proceeds through photochemical radical/polar oxidation to afford a key carbocation species 1 with the extrusion of carbon dioxide and Phth from alkyl N-(acyloxy)phthalimide esters. This carbocation species then underwent subsequent coupling with organoboron nucleophiles to produce the desired product. Notably, the strained cyclobutane subunit, the Boc-protected amine, halogens, heterocyclic moiety, the bridged bicycle and acyclic moieties were all tolerated in this reaction. Furthermore, a substrate derived from estrone was also viable and delivering the corresponding steroid derivative in good yield [18].

Recently, Huang and co-workers [19] addressed the (Ir[dF(CF₃)ppy]₂(dtbpy))PF₆ catalyzed difunctionalization of alkenyl ketones for the synthesis of tetralones and cyclopropane compounds with α-carbonyl alkyl bromide as the radical source (Scheme 3). With the irradiation of visible light, the Ir complex could promote the reduction of α-carbonyl alkyl bromides to deliver the corresponding radical species. Subsequently, this radical was trapped by the alkenyl group of the substrate to produce the secondary alkyl radical intermediate, which preceded a further cyclization process to obtain the product. Interestingly, with gem-dimethyl substituted alkenes as the substrate, intramolecular cyclization occurred between the aryl group and secondary alkyl radical section, followed by oxidization with the Ir-complex to afford the six-membered cyclic product tetralones. However, when β,γ-unsaturated arylketones were introduced, the cyclopropane derivatives could be achieved through the loss of a proton and intramolecular three-membered cyclization.

In 2022, Mao and co-workers [20] developed another radical progenitor [Ph₃PCF₂H]⁺Br⁻triggered, visible light-mediated tandem difluoromethylation/cyclization reaction with alkenyl aldehydes as the starting material (Scheme 4). By utilizing fac-Ir(ppy)₃ as the catalyst, a range of CF₂H-substituted chroman-4-one skeletons could be achieved in moderate to good yields, and good chemoselectivity under mild reaction conditions. In this transformation, the fac-Ir(ppy)₃ could be activated to generate the excited-state fac-Ir^III(ppy)₃* under irradiation with a 5 W blue LED, which then reduced [Ph₃PCF₂H]⁺Br⁻ to produce the vital •CF₂H radical through a single-electron transfer (SET) process to promote the further intramolecular cyclization. In addition, substrates derived from phenolphthalein and coumarin were also viable, generating the corresponding products in good yields.

With the same catalyst, Dolbier and co-workers [21] realized the photoredox-catalyzed addition of difluoromethyl radical to trimethylsilyloxy-substituted alkenes, allowing the construction of a diverse series of difluoromethyl ketones via neophyl-like aryl and heteroaryl migrations (Scheme 5). With the irradiation of 390–780 nm LEDs, both 1,2- and 1,4-functional group migrations could be achieved, delivering the corresponding product with 32–96% yields. The reaction was initiated by the photoexcited fac-Ir(ppy)₃ catalyst to reduce CF₂HSO₂Cl via SET with the release of chloride and SO₂, generating the vital •CF₂H radical. This radical was then captured by the alkenyl group and further underwent aryl ipso-migration to deliver an arylmethyl radical, which was subsequently oxidized by the high-valent Ir catalyst and underwent the loss of the trimethylsilyl group to furnish the final product.

The CF₃ group is one of the most important functional groups for drug research, and numerous efforts have been devoted to the incorporation of this group into specific molecules [22]. In this regard, Kim et al. [23] developed a (Ir[dF(CF₃)ppy]₂(dtbpy))PF_6-catalzyed functionalization of 2-vinylphenols with 1,3-diketones as the coupling partner and the famous Umemoto’s reagent as the trifluoromethylating reagent (Scheme 6). This reaction resulted in the capture of in situ-generated trifluoromethylated ortho-quinone methides from 2-vinyl phenols, followed by conjugate addition and deacetylation. With 2,2,2-trifluoroethanol (TFE) as the solvent, a variety of γ-trifluoromethylated ketones could be generated in 51–92% yields under the irradiation of 5 W blue LEDs (λmax = 455 nm). In addition, the trifluoromethylated ketone products could be successfully cyclized to 4-(2,2,2-trifluoroethyl)-4H-chromenes in good yields with an equivalent amount of Sc(OTf)₃.

2.1.2. Carbon-Hetero Bond Formation

In 2022, Chen’s group [24] developed a visible light-induced fac-Ir(ppy)₃, catalyzed three-component Ritter reaction with alkenes, nitriles, and α-bromo nitriles/esters as the substrates, delivering various structurally diverse γ-amino nitriles/acids (Scheme 7). The authors disclosed that the acetonitrile radical or ester group-containing radical could be generated through the metalla-photoredox catalyst fac-Ir(ppy)_3-promoted SET process from α-bromo nitriles or α-bromoesters, respectively. Importantly, the introduction of KF is critical for the generation of the acetimidoyl fluoride intermediate, which undergoes the Ritter reaction, thus delivering the amino-alkylation product.

Molander’s group [25] reported the amidoarylation of the amide group containing alkenes by merging photoredox proton-coupled electron transfer (PCET) with nickel catalysis for the synthesis of five-membered heterocyclics with aryl halides (Scheme 8). In this protocol, the [Ir-photocatalyst] (3 mol%) was utilized as the photocatalyst and Ni-(dMeObpy)(H₂O)₂Br₂ (6 mol%) was the catalyst for the radical-mediated coupling process. This strategy has granted access to an array of complicated molecules bearing a pyrrolidinone core from readily available alkenyl amides and aryl- or heteroaryl-halides. Additionally, this transformation is not limited to amides, as carbamates and ureas were also viable. Disappointingly, the reaction failed for substrates bearing protic functional groups. Mechanistic studies, including hydrogen-bond affinity constants, control experiments and cyclic voltammetry studies, have confirmed that the reaction followed a proton-coupled electron transfer (PCET) procedure. Initially, the formation of an amidyl radical 2 via PCET occurred, which was followed by fast 5-exo-trig cyclization to generate the alkyl radical 3. Subsequently, combination with the nickel catalyst formed a Ni(I)-complex 4, which underwent oxidative addition with aryl halides, resulting in the Ni-intermediate 5. The reductive elimination of 5 generated the desired product 6 and the Ni(I)-halide complex 7 to facilitate the next catalytic cycle.

Bromodifluoromethanephosphonates represents another kind of difluoromethylation reagent, and the use of such reagents could not only introduce the CF₂ group, but also introduced a phosphate functional group [26]. The photocatalyzed intermolecular aminodifluoromethylphosphonation of aryl alkenes was successfully developed by Yang’s group [27] for the synthesis of α,α-difluoro-γ-aminophosphonates (Scheme 9). In this protocol, fac-[Ir(ppy)₃] was employed as the photocatalyst and arylamines as the nucleophilic reagent. The diethyl or diisopropyl bromodifluoromethylphosphate was tolerated in this transformation; however, (bromodifluoromethyl)diphenylphosphine oxide failed to give the desired product. Moreover, this reaction could be applied to the modification of complex chiral arylamines, such as (R)-BINAM ((R)-(+)-2,2′-diamino-1,1′-binaphthalene).

α-Difluoroacetates is a class of efficient difluoroacetylation reagent, and it could also be introduced to the difunctionalization of alkenes [28]. In 2022, Xi’s group [29] developed the photoredox-catalyzed hydroxydifluoroacetylation of aryl alkenes with FSO₂CF₂CO₂Me and H₂O as the coupling partners (Scheme 10). The -CF₂CO₂Me and -OH groups could be simultaneously introduced into the molecules with fac-[Ir(ppy)₃] as the photocatalyst in good to high yields with high regioselectivity. Interestingly, when disubstituted alkenes were used in the reaction, the difluorolactone compound was only isolated after a general work-up due to the congestion effect of the substituents. Subsequently, the same group disclosed the fluorodifluoroacetylation of aromatic alkenes with this difluoroacetylation reagent. In this reaction, the Et₃N·3HF was introduced as the nucleophilic reagent, and an array of γ-functionalized difluoroacetates could be obtained with 60–84% yields [30].

In 2020, Shen’s group [31] developed a reactive electrophilic selenium ylide-based trifluoromethylating reagent and realized the difunctionalization of aryl alkenes using an array of nucleophiles, such as amines, azides, alcohols, water, as well as electron-rich arenes. The Lewis acid Sc(OTf)₃ and photoredox catalyst fac-Ir(ppy)₃ were selected for use in the synergistic catalyst system to promote the 1,2-difunctionalization of olefins, providing a unified route to functionalized trifluoromethylated compounds with good to excellent yields (Scheme 11). Mechanistic studies have demonstrated that the Lewis acid Sc(OTf)₃ could activate this trifluoromethylating process via generating the complex Sc(OTf)₃•3(8) through Lewis acid–Lewis base interaction. It is worth mentioning that the radical addition/cyclization sequence occurred smoothly when tosyl-protected allylamine was used as the substrate [32].

Recently, trifluoromethylthiomoiety (SCF₃) has attracted increasing attention due to its high Hansch’s hydrophobicity parameter, and numerous methods for its preparation have been described in the literature [33]. As regards the difunctionalization of olefins, Magnier and co-workers [34] accomplished the carbotrifluoromethylthiolation of acrylamides or aryl alkenes with N-trifluoromethylthiosaccharin as the source of the SCF₃ radical (Scheme 12). With fac-[Ir(ppy)₃] as the photocatalyst, a series of N-aryl acrylamides andstyrenes could be difunctionalized in both an intramolecular and an intermolecular manner, providing the corresponding products in good to excellent yields. Additionally, the author demonstrated that the vital •SCF₃ radical was generated by the photoexcited Ir-catalyzed reduction of N-trifluoromethylthiosaccharin through spin trapping/electron paramagnetic resonance (ST/EPR) experiments.

In 2021, Zhang and co-workers [35] developed a synergistic photoredox and Cu(II)-catalyzed fluoroalkylphosphorothiolation of inactivated alkenes via a radical process. In this catalysis, the fluoroalkyl halides (R_fX) was introduced as the radical precursor, and the phosphorus compound P(O)SH or P(S)SH was selected as the coupling partner (Scheme 13). A wide range of S-alkyl phosphorothioates and phosphorodithioates bearing β-monofluoroalkyl, -difluoroalkyl, -trifluoromethyl, or -perfluoroalkyl substitutes could be easily fabricated with good yields and moderated to good diastereoselectivity. Importantly, this transformation could be applied to the late-stage functionalization of bioactive molecules [36]. Through mechanistic studies, the authors proposed a possible mechanism. Firstly, the catalyst Ir^III could be excited to generate the Ir^III* with blue light irradiation, and this highly active species reduces BrCF₂COOEt to produce an ethyl difluoroacetate radical through the SET process. Then, the in situ-formed ethyl difluoroacetate radical is captured by the C=C bond of styrene, generating the alkyl radical intermediate. Simultaneously, the phosphorothiolation compound (EtO)₂P(O)SH reacts with the Cu(II)-catalyst, yielding the corresponding active (EtO)₂P(O)S-Cu(I) intermediate, which further produces a (EtO)₂P(O)S-Cu(II) complex 9 via oxidation with the high-valent Ir(IV) species, releasing the iridium (Ir) to finish the photo-redox cycle. This complex 9 can cooperate with alkyl radical 10 to produce a Cu(III) species 11, which undergoes reductive elimination to regenerate the Cu(I) species to close the Cu-catalysis cycle.

In the same year, Glorius’ group [37] developed an elegant [Ir(dtbbpy)(ppy)₂](PF₆)-catalyzed difunctionalization of alkenes via a base-controlled reincorporation/release of SO₂ strategy (Scheme 14). With this chemo-divergent strategy, various valuable γ-trifluoromethylated ketones and trifluoromethylated sulfonyl ketones could be constructed from the same starting materials. This catalysis exhibited high chemoselectivity with a broad substrate scope. Simple alkenes, such as propene, ethylene, 1-hexene, decene and allylcyclohexane, were amenable. Multi-substituted alkenes, including 1,2-disubstituted, α-methyl substituted, trisubstituted, and tetrasubstituted alkenes, were proved as suitable substrates. Various functional groups including ester, ether, ketone, succinimide, phosphate ester, and polyfluoroalkyl groups are well tolerated. Notably, this protocol could be scaled up and applied in the construction of complicated molecules. Furthermore, one-pot synthesis with alkenes, ketones, and sulfonic anhydride as the starting materials was also viable. Through systematic mechanistic studies, the author proposed a radical chain mechanism for this transformation. Firstly, the •CF₃ radical was generated from the enol triflate substrate via SET catalysis, which was followed by the attack of alkenes to produce a carbon-centered radical. Then, this radical underwent two different transformations with the presence of different bases. In catalytic cycle A, intermediate 12 can react with enol triflate and then undergo further fragmentation to finish the desired product by the release of the SO₂. In this process, the excess KOH could consume the generated SO₂ and facilitate this transformation. However, when introducing K₂CO₃ as the base, the intermediate K₂S₂O could be generated and react with 12 to deliver 13, which could add to the enol triflate substrate to selectively produce the trifluoromethylated sulfonyl ketones [38].

Fluoroalkanesulfinate salts ((R_FSO₂)_nM), such as the Langlois reagent CF₃SO₂Na, could also be utilized as dual fluoroalkyl (R_F) and sulfur dioxide (SO₂) sources by the action of photoredox catalysis [39,40]. In 2020, Akita and co-workers [41] found that the Ir-complex [Ir{dF(CF₃)ppy}₂(bpy)](PF₆) could promote the photoredox catalyzed fluoroalkyl-sulfonylation of alkenes with CF₃SO₂Na, (CF₂HSO₂)₂Zn, MeCF₂SO₂Na, and 4-BrC₆H₄CH₂CF₂SO₂Na as the radical precursors. Under visible light irradiation (425 nm), the reaction of fluoroalkanesulfinate salts with alkenes generated a trifluoromethyl-sulfonylated product, which could be transformed to a more stable methanesulfonylated product via the treatment of the reaction mixture with MeI (Scheme 15). Besides substituted styrenes, other alkenes including aliphatic alkenes, allylamine derivatives and pyridyl substituted alkenes were compatible with this present reaction, delivering the corresponding products in 23–69% yields.

Shortly afterwards, Yi and co-workers [42] found that the same catalyst promoted the trifluoromethyl-thiotrifluoromethylation of alkenes by using CF₃SO₂Na as both CF₃ and SCF₃ source (Scheme 16). This photocatalysis strategy provided a facile method to a variety of vicinal trifluoromethylthio-trifluoromethylated compounds with 31–91% yields. In addition, an array of mechanistic investigations demonstrated that the reaction occurred through a photocatalyzed dual-oxidative process. Firstly, a long-lived triplet excited-state species Ir^III* was generated through the SET pathway. Then, another SET between such species and CF₃SO₂Na resulted in the trifluoromethyl radical •CF₃ and Ir^II species. The in situ-formed •CF₃ radical then reacted with alkenes to generate a carbon-centered radical intermediate 14. Meanwhile, CuSCF₃ could be generated in situ from CuI and CF₃SO₂Na with the assistance of PPh₃, which was followed by oxidation to deliver a Cu^II species via SET. Subsequently, the intermediate 14 underwent single-electron oxidative addition to Cu^II-SCF₃ to form species 15, a formally Cu^III intermediate. Lastly, reductive elimination from intermediate 15 would yield the desired product by regenerating the corresponding Cu^I species.

Recently, the N-Ts-protected 1-aminopyridine salt was developed as a N-radical progenitor in photoredox catalytic reactions [43]. The subjection of this compound to the mixture of olefins with a suitable nucleophilic reactant provided a chance for the construction of olefin-difunctionalized products. In this regard, Xu and co-workers [44] disclosed the Ir-catalyzed three-component aminofluorination or aminochlorination of styrenes with this shelf-stable nitrogen-radical precursor, and hydrogen fluoride-pyridine (py•9HF) or pyridine hydrochloride (py•HCl) as the nucleophilic halogen source. An array of styrenes were converted to the corresponding fluorosulfonamides or chlorosulfonamides in yields ranging from 34% to 86%, with the diastereoselectivities ranging from 1.2:1 to 4:1 in favor of the trans diastereomers (Scheme 17).

With Umemoto’s reagent as the trifluoromethylating reagent, Akita and co-workers [45] accomplished the three-component intermolecular oxytrifluoromethylation of alkenes with oxygenic nucleophiles. The introduction of a CF₃ group and various oxygenic functional groups, including hydroxy, alkoxy, as well as carboxy groups, to C=C bonds has been realized by employing fac-Ir(ppy)₃ as the photoredox catalysis under irradiation with blue LEDs or sunlight (Scheme 18) [46]. Notably, this reaction could be applied to styrenes with halogen atoms or ester groups, such as AcO and Bpin. For internal alkenes, the reaction occurred smoothly, with the diastereoselectivity ranging from 1:1 to 1:10. Notably, the electron-rich alkene 3,4-dihydro-2H-pyran also provided a suitable substrate in this photocatalytic system.

Xiao and co-workers [47] found that the exposure of 2-vinylphenols to the mixture of Umemoto’s reagent and sulfur ylides under photoredox catalysis with fac-Ir(4′-CF₃ppy)₃ enabled a multicomponent cyclization reaction, providing access to trifluoromethylated 2,3-dihydrobenzofurans (Scheme 19). The substrate scope of sulfur ylides proved to be broad, and substrates bearing furan- and thiophene- substituents were amenable. Importantly, the sulfonium bromide could be used directly, producing the desired product with good yield. The reaction with 2-vinyl phenols bearing several functional groups such as halogen and nitro groups worked well to furnish the vinyl difunctionalized products. Interestingly, the cyanoalkylated 2,3-dihydrobenzofuran could be obtained in a 70% yield, when using iodoacetonitrile instead of Umemoto’s reagent as the radical source and Ru(bpy)₃Cl₂•6H₂O as the photocatalyst. Notably, the use of (R)-BINOL-derived sulfur ylide under standard conditions resulted in the corresponding product in an 18% yield with 25% ee. On the basis of the mechanistic studies, the author proposed a plausible mechanism. First, the relatively stable benzyl radical was generated through the SET process, which was followed by further oxidization by the oxidizing state Ir^IV via the SET process, forming a benzylic cation. Subsequently, this benzylic cation intermediate underwent deprotonation to produce a reactive o-QM intermediate, which participated in a formal [4+1] annulation with the sulfur ylide to obtain the desired product.

Subsequently, the same group found that a light-drivenα-carbonyl alkyl radical could be formed via the SET-reduction of sulfur ylides, and this process can be coupled with the difunctionalization of aryl alkenes under the Ir-catalyzed photoredox reaction [48]. Notably, this transformation presented a broad substrate scope with high functional group tolerance for both sulfur ylides and alkenes, affording a practical method to achieve structurally diverse γ-hydroxy carbonyl compounds with up to 99% yield. The authors also proposed a possible mechanism, as outlined in Scheme 20. Initially, the sulfur ylide 16 could undergo the reaction with 2,2,2-trifluoroethanol and Et₃N•3HF to produce the corresponding sulfonium salt, which was transformed to the α-carbonyl carbon radical via SET-reduction with the irradiation of the LEDs. Then, the in situ-generated α-carbonyl carbon radical was trapped by the alkenes, producing a benzylic radical intermediate 17, which was oxidize to the corresponding carboncation intermediate 18 by another SET, thus finishing the photocatalytic cycle. The intermediate 18 was then captured by a small amount of water to achieve the desired product. The authors also claim that the Cu(II) salt acted as an oxidant and nucleophile reagent carrier [49].

Huo and co-workers [50] found that the aromatic carboxylic acid oxime esters could be employed as bifunctional agents for the difunctionalization of aryl alkenes with (Ir[dF(CF₃)ppy]₂(dtbpy))PF₆ as the catalyst (Scheme 21). Both O-centered radicals and N-centered radicals were generated in the meantime through the photosensitized Energy Transfer Catalysis (EnT) strategy-promoted O–N bond homolysis event [51]. With this strategy, a series of complex vicinal amino alcohols were facilely fabricated in one-step synthesis through the EnT-promoted 1,2-bifunctionalization of alkenes to decorate both C–N and C–O bonds synchronously. The substrate scope of this reaction proved to be broad, and an array of oxyaminated products were constructed in 40–79% yield. In addition, the synthetic utility of this transformation was further extended to the late-stage modification of complicated alkenes, such as the functionalization of several drug-related molecules and bioactive natural products.

2.2. Rutheniumo-Catalyzed Difunctionalization of Alkenes

2.2.1. 1,2-Dicarbofunctionalization of Alkenes

In 2019, Wu and co-workers [52] found that the photo-catalytic 1,2-difunctionalization of ethylene could be achieved by the incorporation of Ru-photoredox catalysis and Ni-catalysis sequences (Scheme 22). With a catalytic amount of Ru(bpy)₃Cl₂•6H₂O and NiCl₂•glyme, various 1,2-diarylethanes could be furnished in 55–91% yields. Mechanistic studies demonstrated that this reaction was initiated by Ru-promoted Ni(I) formation under visible light irradiation. Subsequently, the aryl-Ni(III) species 19 was formed through the oxidative addition of Ni(I) with aryl halides, which was followed by the migration insertion of ethylene into the intermediate 19 along with the halide dissociation event, delivering a cationic alkyl Ni-species 20. Subsequently, the transmetallation between 20 and the aryl-Ni(III) species 19 occurred, and gave an aryl alkyl Ni(III) intermediate, which further caused a reductive elimination event, producing the desired product with the formation of the active catalyst Ni(I) species. Notably, the transmetallation between 20 and the aryl-Ni(III) species 19 would also give a cationic Ni(III) intermediate, which could be reduced and regenerate the reactive Ni(I) species through the SET [53].

For the synthesis of CF₂-containing compounds, Ryu’s group [54] developed the Ru-catalyzed difunctionalization of 1-octene and methyl acrylate with α-gem-difluorinated halides and allyl sulfones as the coupling partners under visible light irradiation (Scheme 23). With this strategy—the subjection of a catalytic amount of Ru(bpy)₃Cl₂ to the mixture of Hantzsch ester (HEH), terminal alkenes and diisopropylethylamine—the difunctionalization reaction was finished within 2 h to give the corresponding 6,6-difluoroalkenes in 32–82% yields. The HEH and/or amine served as the reductant to activate the Ru(II) catalyst, and facilitated the generation of difluoroalkyl radicals from gem-difluorinated halides [55].

With Togni’s reagent as the radical precursor, the intramolecular trifluoromethylation/arylation of N-aryl acrylamides could also be accomplished by Ru-photoredox catalyst [Ru(phen)₃]Cl₂ (Scheme 24) [56,57]. Under visible light irradiation, an array of CF₃-containing oxindoles with a quaternary carbon center was obtained in 51–91% yields. However, the use of a secondary aryl amide failed to produce the desired product, and the regioselectivity was poor for aryl meso-substituted N-aryl acrylamides.

2.2.2. Carbon-Hetero Bond Formation

In 2019, Masson [58] developed an efficient four-component photoredox-catalyzed azidoalkoxy-trifluoromethylation reaction by employing [Ru(bpy)₃(PF₆)₂] as the catalyst in the presence of Umemoto’s reagent, a carbonyl compound, and TMSN₃. With the irradiation of blue LEDs, a variety of carbonyl compounds could be coupled with various terminal or internal alkenes to obtain several structurally diverse trifluoromethylated products with up to 77% yield. For the internal alkenes, the diastereomeric ratios ranged from 52:48 to 92:8. In addition, the TMSCN reagent could be introduced instead of TMSN₃, and this generated the corresponding cyanoalkoxy-trifluoromethylation product at a moderate yield. A plausible reaction mechanism has been proposed and outlined in Scheme 25. Initially, the SET process generated a reactive •CF₃ from Umemoto’s reagent, which was followed by the regioselective addition of electrophilic •CF₃ to alkenes and formed the carbon-centered radical species. Subsequently, this carbon-centered radical species was oxidized into a carbon cation intermediate by SET from Ru(bpy)₃³⁺. Finally, the corresponding cation intermediate was trapped by the TMSN₃-induced nucleophilic attack of the carbonyl compound tandem, coupling with the assistance of tetrafluoroborate counteranion to produce the desired product, and this finished the catalytic cycle.

By employing aryl diazonium salts as the radical precursor, and ammonium thiocyanate or potassium selenocyanate as the nucleophilic reagent, Maity and co-workers [59,60] achieved the intermolecular arylthiocyanation/arylselenocyanation of alkenes under the irradiation of visible light (Scheme 26). Both terminal and internal alkenes were accommodated in this protocol. Several functional groups, including ester, benzyl chloride, acrylate, and nitryl, were tolerated in 42–87% yields. For conjugated dienes, the reaction occurred regioselectively at the terminal double bond. However, alkyl-substituted alkenes failed to deliver the desired products.

The Ru-photoredox catalysis intermolecular aminotrifluoromethylation of alkenes with Umemoto’s reagent was developed by Akita and co-workers [61]. This photocatalytic strategy enabled a robust one-step facial route to various valuable 1,1,1-trifluoro-3-acetylaminopropane derivatives. This reaction featured a broad substrate scope with 28 examples in 53–91% yield. A plausible reaction mechanism is shown in Scheme 27. First, the •CF₃ was generated via the SET processes, which was followed by the addition of •CF₃ to the C=C bond of alkenes to give the corresponding carbon-centered radical intermediate. This intermediate could be oxidized to carbon cations by [Ru(bpy)₃]³⁺ through the SET event (path a). Additionally, this cation intermediate would also be furnished through the radical propagation process (path b). Lastly, this intermediate underwent the further attack process with RCN and hydrolysis with water sequences (Ritter type amination), affording the desired aminotrifluoromethylated products [62].

In 2019, She and co-workers [63] developed a four-component intermolecular trifluoromethylation-acyloxylation of arylalkenes with Ru(bpy)₃(PF₆)₂ as the photoredox catalyst under mild reaction conditions (Scheme 28). In this protocol, a new Umemoto’s reagent was developed and employed as the trifluoromethyl radical source to facilitate the difunctionalization of styrenes. Under optimized conditions, this photoredox reaction exhibits good functional group tolerance for aryl olefins, with yields up to 91%. Based on control, deuterium and O¹⁸-labeling experiments, the authors proposed a conceivable mechanism involving an acyloxyl process, with the mixture of N,N-dimethylformamide (DMF)/N,N-dimethylacetamide (DMAc) with H₂O as the acyloxyl source. First, the reaction formed a reactive Ru^II(bpy)₃(PF₆)₂ species under irradiation with white LEDs, which was followed by the single-electron reduction of 21 to generate the electrophilic •CF₃ radical. The following combination with arylalkene 22 generated the stable benzyl radical 23, which was further oxidized by the reactive Ru(III) species to deliver the corresponding benzyl carbocation 24 via another SET event. This intermediate 24 was then trapped by the nucleophilic attack with DMF or DMAc to produce the imine intermediate 25, which was hydrolyzed, yielding the desired difunctionalized product 26.

The intermolecular atomic transfer thiosulfonylation reaction of alkenes could also be achieved by using Ru(bpy)₃Cl₂ as the photoredox catalyst, with IPrAuCl as the co-catalysts (Scheme 29) [64]. In this protocol, the trifluoromethylthio group (SCF₃), sulfonyl group and other functionalized thio-groups could be regioselectively decorated into the C=C bond of alkenes in an environmentally benign fashion. Through mechanistic studies, the authors demonstrated that this transformation occurred through synergistic catalysis with the incorporation of a Au-based catalyst and a Ru-based photoredox catalyst [65]. The irradiation of the Ru-catalyst produced a photoexcited Ru-species, which underwent an SET process with the cationic Au-catalyst to trigger the catalytic cycle. Subsequently, a benzenesulfonyl radical PhSO₂• occurred through the promotion of the in situ-generated reactive IPrAu(I) species, and formed the IPrAu(I)SCF₃ intermediate. Then, the PhSO₂• radical was attacked by styrenes to afford the corresponding alkyl radical, followed by the interaction with the former generated IPrAu(I)SCF₃ to produce the vital Au(II) intermediate, which was further oxidized to the Au(III) intermediate through another SET. Finally, the corresponding Au(III) intermediate was decomposed to furnish the desired product, regenerating the [IPrAu(I)]⁺ species to complete the catalytic cycle.

2.3. Visible Light-Promoted Copper-Catalyzed Reactions

Hu et al. reported the chlorosulfonation of alkenes by employing a Cu photocatalyst to afford a series of organic sulfones with sulfonyl chlorides under the irradiation of 40 W LED (Scheme 30) [66]. This chlorosulfonation of alkene transformation could tolerate a variety of functional groups, including esters, nitriles, halogens, thiophenes, and amines in the sulfonyl chloride moiety, as well as esters, F, Cl, and Br functional groups in the alkene substrates. Internal styrenes also worked, delivering the corresponding product with 1:1 diastereoselectivity. In addition, a complicated Estrone-derived alkene substrate could also be transformed to the 1,2-difunctionalized product in 66% yield. The author demonstrated that the light source, photoredox catalyst, and N₂ atmosphere were all necessary, and other Ru, Ir or organic photocatalysts failed to produce this transformation [67].

In 2019, Zhang developed a photoinduced Cu-catalyzed three-component reaction with carbohalides, alkenes and amines, resulting in various valuable fluoroalkyl-bearing amines with or without ligands (Scheme 31) [68]. This method involved employing the in situ-generated Cu-complex as the photoredox and coupling catalyst without introducing any other reagents. A variety of terminal alkenes, as well as 1,3-dienes and aliphatic alkenes, could work well in this method. In addition, 1,3-dienes were transformed to the 1,4-fucntionalized products. Besides 1,1-difluoro-2-iodoethane, other halides, such as (2-bromo-2,2-difluoroethoxy)-tert-butyldimethylsilane, iodoperfluoroalkanes, and nonfluoro-substituted alkyl halides, performed well and produced the desired products. In addition, the simple dichloromethane also proved a suitable substrate, delivering the corresponding monochlorinated product in a moderate yield. Based on mechanistic studies, the author outlined a plausible reaction mechanism. First, the copper salts undergo ligand exchange to generate the reactive LnCu(I)Nu, which could be activated to the excited-state adduct by irradiation with blue LEDs, and this might result from the viability of the photoexcitation of the π systemof the Cu-complex. As to the simple amines, the Cu(I)-binaphtholate complex 27 was supposed to be the photosensitive complex. Subsequently, the excited-state complex 28 interacted with the halides to produce the alkyl radical R• through electron transfer. The alkyl radical R• than further added to the styrenes to form an internal radical, which underwent bond formation with the nucleophile bound Cu-complex to generate the compound 29 or 30. Finally, the following reductive elimination (path a), or SET process (path b), occurred to furnish the desired products and regenerate the Cu(I) species to fulfill the catalytic cycle.

In 2020, Reiser’s group successfully achieved a visible light-mediated Cu-catalyzed carboiodination of terminal alkenes by utilizing the easily available iodoform as the sole functionalization reagent (Scheme 32) [69]. In this reaction, [Cu(dap)₂]Cl (dap = 2,9-di(p-anisyl)-1,10-phenanthroline) was introduced as the photocatalyst to facilitate the transformation of alkenes via the atom transfer radical addition (ATRA) process. An array of styrene analogs bearing electron withdrawing substituents or alkyl substituents on the benzene ring were well tolerated. Notably, α,β-unsaturated substrates and vinyl pyridines were amenable substrates, whereas electron-rich five-membered heterocycles resulted in the formation of a MeO-substituted product. Furthermore, the synthetic application of the reaction was further demonstrated upon gram-scale synthesis, as well as plenty of transformations of the obtained products. The mechanistic studies have shown that the Cu-catalyst could generate an excited-state species to facilitate radical formation and promote the following radical-involved ATRA process [70].

Peters and co-workers [71] found that the functionalized alkyl halides and the trifluoromethylthiolate nucleophile NMe₄SCF₃ could combine with an array of alkenes in the presence of a CuI/binap catalyst (Scheme 33). A wide variety of substituted alkenes, including styrenes and electron-poor olefins, were viable in this transformation. Other nucleophiles, such as bromide, cyanide, and azide-containing nucleophiles, served as suitable substrates, providing the corresponding trifluoromehylthiolation products in good yields. Mechanistic studies demonstrated that the photoexcited Cu(I)/binap/SCF₃ complex was regarded as a reductant to facilitate the formation of alkyl radical from the alkyl halide substrate, and the alkyl radical reacted with the alkenes and the reactive Cu(II)/SCF₃ complex furnishing the desired coupling products.

2.4. Visible-Light Promoted Metal Free Reactions

2.4.1. Organic Dyestuff-Promoted Difunctionalization of Alkenes

With Eosin Y (EY) as the photosensitizer, Hong’s group developed an elegant site-selective trifluoromethylative pyridylation of unactivated alkenes using the in situ-generated N-triflylpyridinium salts from pyridines and triflic anhydride (Tf₂O) (Scheme 34) [72]. In this reaction, the N-triflylpyridinium salts served as bifunctional reagents to incorporate both trifluoromethyl and pyridyl groups across the C=C of terminal alkenes with excellent selectivity on the C4-position of the pyridine core. A wide variety of functional groups, such as furanyl, thiophenyl, methoxy, ketone, tosylate, amide, and ester groups, were well tolerated in furnishing the desired products with 32–68% yields. Notably, this strategy could be expended to the late-stage diversification of structurally diverse, biologically relevant molecules, including eugenol-, lithocholic acid-, and nicotinyl alcohol-derived substrates.

In 2020, Hong and co-workers [73] developed an Eosin Y-catalyzed trifluoromethylative pyridylation of functionalized alkenes through the migration of the pyridyl ring on the terminalalkenes scaffold to selectively generate a new C–C bond with the ortho-site (Scheme 35). This transformation was initiated through •CF₃ radical-triggered addition to the alkene moiety to produce a nucleophilic alkyl radical intermediate, which underwent intramolecular endo addition to the ortho-site of the pyridinium moiety to provide the final product. This transformation is applicable to a wide variety of substrates to construct various important C2-fluoroalkyl-functionalized pyridines. As regards the alkene moiety, both disubstituted and trisubstituted substrates were tolerated, providing trifluoromethylative pyridylation products with exclusive selectivity on the C2 position of the pyridinium unit. Furthermore, the diarylphosphine oxides also proved suitable substrates in this transformation, and generated the corresponding products with good yields. The in situ generation of P-centered radicals via the SET was conceived as the key step in this case. In addition, a series of pyridinium salts bearing various functional groups, such as ester, 3-bromophenyl, and 4-trifluoromethylphenyl, were viable to provide the corresponding functionalized products with up to 66% yields [74].

In 2019, Ouyang and co-workers [75] developed an efficient dialkylation of terminal alkenes with simple alkanes and 1,3-dicarbonyl compounds through the combination of a photoredox catalysis system with an Ir-catalysis system to construct a series of difunctionalized complicated 1,3-dicarbonyl derivatives (Scheme 36). In this strategy, the C(sp³)-H bond of cycloalkanes, linear alkanes, or ethers could be split in a hemolytic manner to fabricate the vital alkyl radicals, facilitating the following transformation. Based on mechanistic studies, the author proposed a reasonable mechanism. Initially, the ^tBuOO^tBu (DTBP) substrate could be transformed to the ^tBuO• radical under this photo- and Ir-co-catalysis (the Fenton chemistry), which was followed by the interaction with cyclohexane to achieve the crucial alkyl radical intermediate 31 [76]. Subsequently, the addition of intermediate 31 across the C=C moiety of 1-methoxy-4-vinylbenzene substrate afforded the intermediate 32. Lastly, intermediate 32 underwent iron-promoted single-electron oxidation to give the carbocation intermediate 33, which was snatched by the nucleophilic reagent ethyl 3-oxo-3-phenylpropanoate to access 34. Besides this, the homocoupling of intermediate 34 and the dehydrogenolefinization of 35 would lead to the undesired side products.

With rhodamine B as the organic photoredox catalyst, Singh et al. developed a mild photocatalyzed 1,2-difunctionalization of styrenes to provide diverse β-keto dithiocarbamates with CS₂ and amines as the functionalization reagents [77]. With 2 equiv of TBHP as the oxidant, various styrenes contacting both electron-donating and electron-withdrawing substituents could be transformed to the corresponding products in moderate to good yields. Notably, 2-vinylnaphthalene also delivered the desired products in good yields. A broad variety of amines including pyrrolidine, piperidine, dipropylamine, morpholine, dicyclohexylamine, and tertbutyl piperazine-1-carboxylate reacted effectively to produce the corresponding dithiocarbamates in good yields. However, the reaction was ineffective with aniline, 2-aminopyridine, n-butylamine, 2-phenylethylamine and diphenylamine. Based on control experiments, the authors suggested a plausible mechanism, outlined in Scheme 37. Initially, the amine easily reacts with carbon disulfide to form the dithiocarbamic acid 35, which underwent the SET process to form the radical cation 36 with the photosensitizer rhodamine B under the irradiation of blue LEDs. In the meantime, TBHP could be converted into ^tBuO• and a hydroxide ion via the SET event, which was followed by the formation of reactive ^tBuOO• species through oxidation by another molecular of TBHP. Subsequently, the deprotonated product 37 attacked the C=C bond of styrenes, offering a benzylic radical 38, which could be converted to the final product in two different pathways. In path A, the radical 38 was trapped by dioxygen (air) delivering the peroxy radical 39, and the following reaction with ^tBuOO• afforded the reactive intermediate 40, which participated in Russell fragmentation to furnish the desired product 41. In path B, the intermediate 38 was directly incorporated with the in situ-generated ^tBuOO•, resulting in the peroxy intermediate 42, which could be transformed to the final product via Kornbium–DeLaMare rearrangement.

The tandem radical cyclization of N,N-dimethylanilines could be achieved by introducing Rose Bengal as the photoredox catalyst with 2-benzylidenemalononitriles as the alkene substrate (Scheme 38). Guan and co-workers [78] found that this cyclization process could be promoted with an equivalent amount of trifluoroacetic acid (TFA) as the additive and a 23 W compact fluorescent lamp (CFL) as the light source. Under the optimized conditions, an array of tetrahydroquinoline derivatives was obtained in 38–74% yields.

2.4.2. Organic Photosensitizer Promoted Difunctionalization of Alkenes

In 2022, Hong and co-workers [79] developed an elegant photocatalytic tandem trifluoromethylative 1,2-difunctionalization of simple alkenes with Q1 as the photosensitizer. This operationally simple method features a broad substrate scope, including derivatives of flavones, coumarins, estrones, nalidixic acids, L-tyrosines, and ciprofibrates. Alkenes containing alkyl, phenyl, silyl, and hydroxyl groups were well tolerated in this process. Based on mechanistic investigations, the authors proposed a catalytic cycle, as depicted in Scheme 39. Initially, the alkyl N-amidopyridinium salts 43 were transformed to the amidyl radical 44, along with the formation of the vital radical cation Q1^•+ intermediate through the SET event. Subsequently, the generated Q1^•+ underwent the single-electron oxidation of NaSO₂CF₃ to provide the corresponding trifluoromethyl radical via the release of SO₂. The •CF₃ was then added to the alkene moiety to produce the alkyl radical 45, which was associated with SO₂ in solution to form β-CF₃ alkylsulfonyl radical 46. The radical 46 was then trapped by the in situ-generated dihydropyridine from the dehydrogenation of the alkyl N-amidopyridinium salt substrate to furnish the radical intermediate 47. Finally, the homolytic N–N bond cleavage of 47 could give the final product with the byproduct 44, which could be further transformed to the corresponding sulfamides via another SET process.

In 2019, Akita and co-workers [80] found that the monofluoromethyl radical (•CH₂F) could be facilely obtained from the sulfoximine-based precursor via metal-free photoredox catalysis with 1,4-bis(diphenylamino)naphthalene as the photosensitizer. The generated radical could interact with the oxy-monofluoromethylation of alkenes amenable to γ-fluoroalcohol scaffolds with water as the hydroxyl source (Scheme 40). Several functional groups were tolerated, including NO₂, pyridyl, and thienyl groups. The late-stage functionalization of potentially bioactive molecules is also viable, such as steroid and flavonoid. In addition, the gram-scale synthesis was performed without loss of reactivity, demonstrating the scalability of this organic photocatalytic system.

By employing 4CzIPN as the photocatalyst, Zhang and co-workers [81] disclosed an organic photosensitizer-catalyzed acetalation-pyridylation of arylalkenes with diethoxyacetic acids and cyanopyridines as the coupling partners (Scheme 41). In this protocol, the diethoxyacetic acids were employed as the radical progenitor, which underwent a radical addition to alkenes, followed by the capture of cyanopyridines, reduction, and cyanide anion elimination to deliver the desired acetal-protected 3-aryl-3-(pyridin-4-yl)propanals products. Significantly, this protocol could be employed in the fabrication of various important functionalized pyridines and the late-stage modification of complex bioactive molecules. In addition, the acetal group on the produced compounds could be easily transformed to the aldehyde group, which can be further converted to many other derivatives by simple operations [82].

In 2021, Ohmiya and co-workers [83] developed the photoredox catalyzed 1,2-difunctionalization of arylalkenes with various heteroatom nucleophiles, and aliphatic acid-derived esters with a catalytic amount of PTH. Various heteroatom nucleophiles, including oxygen, nitrogen, and halogen nucleophiles, were applicable without an excess amount required. The water-induced difunctionalization of styrene proceeded well to afford the alkylhydroxylation product in good yield. Carboxylic acids, cyclic amides, carbamates, fluoride and chloride anions were also applicable in providing the corresponding products smoothly. Based on the mechanistic studies, the authors proposed a mechanism, as presented in Scheme 42. This reaction proceeded with the formation of EDA complex 48 from the PTH and r aliphatic acid-derived esters. The decomposition of 48 would provide the radical cation 49 and radical anion 50, which underwent disruption to furnish the radical intermediate 51 and phthalimide anion with the extrusion of CO₂. The radical 51 added to alkenes 52, resulting in another radical 53, which was incorporated with intermediate 49 to produce the benzylsulfonium intermediate 54 via the SET event. Lastly, 54 could be intercepted by the suitable nucleophiles to deliver the corresponding difunctionalized products and regenerate 55 to promote another catalytic cycle [84].

In 2022, Sureshkumar and co-workers [85] developed the acridinium photocatalyst Ph-Acr-Mes⁺BF₄^--triggered difunctionalization of activated alkenes to construct a series of high substituted amides bearing a trifluoromethionyl group (Scheme 43). This protocol realized the direct C(sp³)-H activation/alkylationand trifluoromethylthiolation sequences in a one-step transformation using a bench-stable trifluoromethylthiolating reagent [86]. The reaction strategy was compatible with a wide variety of functional groups, including nitro, ester and heterocycle groups. Besides N,N-dimethylformamide, other H donors were also viable, such as N,N-dimethylpropionamide and its analogues, 2-chloro-N,N-dimethylacetamide, N,N-dimethylbenzenesulfonamide, N,N-dimethylaniline, tetrahydrofuran and dioxane. Mechanistic studies have demonstrated that the photocatalyst-promoted radical formation from H donors was the key process in this transformation.

In 2022, Park and co-workers [87] developed a –Mes-2,7-diMe-AcrPhBF₄-catalyzed difunctionalization of aryl alkenes to prepare various β-hydroxysulfides. The reaction is applicable in converting a wide scope of substrates to the corresponding β-hydroxysulfides products (45 examples, 25–88% yield), including various aryl alkenes (from simple styrene to complex bioactive compounds) and structurally diverse aryl thiols (from diverse heteroaromatic thiols to nonheteroaromatic thiols). The author proposed a plausible mechanism, as depicted in Scheme 44. Initially, thiol 56 is deprotonated to thiolate 57 by interaction with K₂CO₃. Thiolate 57 is then switched to the thiyl radical 58 via the SET process, which is followed by the radical addition to alkenes, delivering the benzylic radical 59 [88]. Meanwhile, the SET process could also facilitate the generation of the hydroperoxyl radical under irradiation with blue LEDs. Product 59 then reacts with this ·OOHradical to give hydroperoxide 60, which could be reduced by thiolate 57 to yield product 61 and sulfonate 62. Here, the hydroperoxyl is either derived from superoxide, which is generated via another SET event between PC· and O₂, or spontaneously generated via photoirradiation. The reduction of hydroperoxide 60 is suggested as the most difficult step to activate in the proposed catalytic cycle.

The N-methyl-9-mesityl acridinium (Mes-Acr⁺) photoredox-catalyzed chloro-, bromo- and trifluoromethylthiotrifluoromethylation of unactivated alkenes was realized using the easy-to-handle Langlois reagent (CF₃SO₂Na), N-halophthalimide or N-trifluoromethylthiosaccharin as the functional reagent (Scheme 45) [89]. With TFA as the additive and white LEDs as the light source, a broad range of unactivated alkenes were converted to the corresponding products in 41–88% yields via a radical process.

Wu’s group found that the photocatalyst 4CzIPN could promote the silacarboxylation and carbocarboxylation of terminal alkenes with CO₂ and active Si-H or C(sp³)-H-containing substrates via synergistic catalysis incorporated with hydrogen atom transfer (HAT) catalysis [90]. With quinuclidin-3-yl acetate as the HAT catalyst, various significant compounds, including β-silacarboxylic acids and acids bearing a γ-heteroatom, could be facilely constructed under mild conditions. In addition, this transformation could be scaled up with higher yields using continuous-flow technology. A plausible mechanism was proposed following controlled experiments (Scheme 46). First, the quinuclidin-3-yl acetate could be activated to radical cation 63 via the SET process, which was followed by the interception with Si(C)-H substrate to produce the corresponding radical intermediate R₃Si(C)•. Subsequently, the radical addition of R₃Si(C)• to alkenes generated the carbon radical 65, which was reduced to deliver an anion intermediate 66 via another SET event [91]. The carbon anion intermediate 66 underwent subsequent nucleophilic addition to CO₂ and protonation with the quinuclidinium cation 64 to afford the final difunctionalized product.

With Ph-PTZ as the photosensitizer, Chen’s group successfully achieved the cyanoalkylfluorination of aryl alkenes under the irradiation of 40 W purple LEDs [92]. In this protocol, the oxime esters and Et₃N•3HF were employed as the cyanoalkylation and fluorination reagents, respectively, giving diverse cyanoalkylfluorinated products with good to excellent yields. Various functional groups were tolerated, including ester, benzyloxy, 2-naphthyl, and heterocycles. Notably, the estrone-derived alkene was also viable in this three-component transformation, affording the functionalization of the product in a 56% yield with 1:1 dr. Through mechanistic investigations, the author described a catalytic cycle as shown in Scheme 47. Similar to most photoredox catalysis processes, the organic photosensitizer Ph-PTZ could be activated to its excited state Ph-PTZ*, and participate in the subsequent SET process. The oxime ester 67 was converted to cyclic iminyl radical 68 via SET reduction with the release of ArCO₂⁻. The β-C−C bond cleavage of 68 delivered the cyanoalkyl radical 69, which could be trapped by alkenes, providing intermediate 70. The oxidation of 70 gave the carbocation 71 via the SET process along with the Ph-PTZ to promote the next catalytic cycle. Finally, 71 was captured by the nucleophilic fluoride ion, generating the desired product 72.

Fang and co-workers [93] disclosed a facile method to produce various pyrrolidin-2-ones through the photoredox three-component cyclization of arylalkenes, tertiary α-bromoalkyl esters and primary amines in a micro channel reactor with 5,10-diaryl-5,10-dihydrophenazines as the photosensitizer (Scheme 48). Substrate-scope studies have disclosed that anilines bearing alkyl, trifluoromethyl, aryl, and halogen were smoothly coupled with arylalkenes and ethyl 2-bromoisobutyrates to yield an array of corresponding cyclized products in 42–96% yields. Through radical scavenger studies, the authors demonstrated that the reaction process occurs through a radical pathway, and the tertiary α-bromoalkyl esters were regarded as the radical precursor to promote this transformation.

Glorius et al. disclosed an elegant photoredox protocol for the introduction of both nitrogen- and oxygen-containing functional groups to various alkene moieties in one step (Scheme 49) [94]. In this approach, the oxime carbonate was employed as the bifunctional source for generating both oxygen- and nitrogen-centered radicals to add across the C=C bond with complementary regioselectivity. With thioxanthone as a cheap and readily available organo-photosensitizer, a battery of 2-amino-1-alcohol derivatives could be obtained in good to excellent yields. In addition, this method could be successfully applied to the construction of various value-added complex molecules for materials and drug research. Unactivated terminal alkenes, 1,2-disubstituted alkenes, and various cyclic alkenes were all tolerated in this transformation, whereas tetrasubstituted alkenes failed to deliver the desired product. Furthermore, mechanistic experiments confirmed that the oxime carbonate could be transformed to alkoxycarbonyloxyl and iminyl radicals via the homolytic cleavage of the N–O bond under the photoredox catalysis system.

With 4CzIPN as the photosensitizer, Studer’s group accomplished the 1,2-amidoalkynylation of alkenes to produce a series of β-amido alkynes (Scheme 50) [95]. In this methodology, Troc-protected α-amino-oxy acids (Troc = 2,2,2-trichloroethoxycarbonyl) acted as amidyl radical precursors, and ethynylbenziodoxolone (EBX) was employed as the suitable alkylation reagent with blue LEDs as the light source. Notably, other N-protected α-amino-oxy acids, including the benzoyl- phenyloxycarbonyl- and phthaloyl-protected substrates, failed to produce the desired product. Various EBX reagents were viable in this protocol, such as substitutional arylalkynyliodoxolone, β-styryl-benziodoxolone, and cyanobenziodoxolone. Under optimized conditions, various unactivated alkenes including mono-, di- and trisubstituted alkenes, vinylethers, vinylesters and vinylamides are efficiently 1,2-difunctionalized to generate the correspondingβ-alkynylated Troc-amides in moderate to good yields. Based on mechanistic studies, the author suggested a plausible mechanism. The catalytic cycle initialized with the excitation of 4CzIPN to produce the excited-state 4CzIPN*, further promoting the following SET processes. Then, the deprotonated carboxylate 73 was transformed to the carboxyl radical 74 and the 4CzIPN*⁻ via SET. Subsequently, the intermediate 74 decomposed to deliver the amidyl radical 75 via the release of CO₂ and acetone. The radical addition to the C=C double bond as occurred following the interception of amidyl radical 75 with alkene to generate the intermediate 76, which was trapped by the EBX reagent to produce the final product 77 and the intermediate 78 to finish the catalytic cycle.

Subsequently, the same group developed the trifluoromethyl-alkenylation of unactivated alkenes to construct a series of trifluoromethylated aromatic alkenes under a visible light environment (Scheme 51) [96]. This transformation employed the bench-stable Langlois reagent (CF₃SO₂Na) as the CF₃ source and β-nitrostyrenes as the alkenyl source, providing a wide variety of CF₃-substituted alkenes in moderate to good yields. With the 9-mesityl-10-methylacridinium per chlorate (MesAcrMe⁺) as the photocatalyst, the •CF₃ radical could be derived from the Langlois reagent and added to the corresponding alkenes to furnish the vital alkyl radical intermediate, which could be incorporated with β-nitrostyrenes to produce the desired trifluoromethyl-alkylated alkenes via the extrusion of the nitro group. In addition, this reaction could be introduced to the further late-stage modification of complex bioactive intermediates.

In 2022, Roy and co-workers [97] developed a difunctionalization of various styrenes with quinoxalin-2(1H)-ones and aryl disulfides as the coupling partners mediated by visible light (Scheme 52). Arylalkenes with both electron-donating and electron-withdrawing substituents could be converted to thioalkylated products with good to excellent yields. Aryl disulfides containing a series of functional groups, such as Me, OMe, Cl, and naphthyl, were well compatible in this reaction. Disulfide-bearing heterocyclic units, such as 2-pyridine group, afforded the corresponding products in 61% yield. An array of N-alkyl quinoxalin-2-ones with various alkyl groups was tolerated to provide the corresponding products with no impediment. Mechanistic studies have demonstrated that the quinoxalin-2(1H)-ones or aryl disulfides might serve as the photosensitizer to promote the following two pathways to afford the desired product. In Path-a, the excited quinoxalin-2(1H)-ones react with aryl disulfide to generate the radical cation intermediate 79 along with the ArS⁻ and S-centered radical ArS• through a photoinduced electron transfer (PET) process. Further, this ArS• adds to the aryl alkene derivatives to produce a relatively stable radical 80, which is captured by the former generated 79 to furnish the cation intermediate 81, which could be transformed to the desired product 82 via interaction with the anion ArS⁻. Alternatively, Path-b describes another possibility for the generation of the ArS• intermediate, which could be converted to 80. In this pathway, the generated 80 could be intercepted by substrate 83 to produce the intermediate 84, which is followed by ArS•-involved aromatization to give the final thioalkylated product via the HAT event.

The aryl radical-involved Meerwein arylations provided a supplementary method for accessing arylations, in addition to the transition metal-mediated cross-coupling reactions from aryl halides [98]. However, Meerwein arylations require thermally unstable or even explosive aryldiazonium or iodonium salts to generate the vital aryl radicals [99]. Recently, Ritter and co-workers [100] developed an elegant photocatalyzed Meerwein-type bromoarylation of terminal alkenes with stable arylthianthrenium salts as the aryl radical precursors, N-phenyl-benzo[b]phenothiazine (PTH) as the photocatalyst, and tetrabutylammonium bromide (TBAB) as the bromide source. The initial reaction was performed using arylthianthrenium salt, TBAB, and methyl acrylate with white LEDs in acetonitrile at −20 °C (Scheme 53). Arylthianthrenium salts bearing electron-deficient, -neutral and -rich arenes were all viable in coupling with methyl acrylate, affording the corresponding bromoarylation products in moderate to good yields. A series of functional groups were tolerable, such as alkyl- or aryl-halides, aldehyde, ethers, ketones, esters, amides, nitro groups, nitriles, heteroaromatics, and protic groups. Various Michael acceptors are tolerated, such as acrylonitrile, vinyl sulfone, methyl vinyl ketone, vinyl phosphate, fluoroacrylate, methacrolein α-methylene lactone, and acrylamide. Several terminal alkenes, including monosubstituted styrenes and non-activated 4-bromo-1-butene, are also compatible. In addition, this protocol was applicable to the late-stage modification of several biomolecules that are difficult to fabricate by other methods.

With 4CzIPN as the photocatalyst, Yu’s group successfully developed an elegant strategy for the construction of dicarboxylic acids through the dicarboxylation of alkenes with the incorporation of two CO₂ molecules with high chemo- and diastereoselectivities (Scheme 54) [101]. The optimized conditions were ⁱPr₂NEt as the reductant and Cs₂CO₃ as the base in DMF under a CO₂ atmosphere. This metal-free photoredox catalysis could be applied to the transformation of a wide variety of styrenes bearing different kinds of functionalities to the corresponding dicarboxylated products with good to excellent yields. In addition, reactions with α-alkyl styrenes, β-substituted styrenes and heteroarenes were all feasible. Notably, the reaction with acrylate esters also happened mildly, delivering the corresponding product at a 59% yield. Based on mechanistic investigations, the author proposed a plausible mechanism. Firstly, the organic photocatalyst 4CzIPN was excited to the excited-state species 4CzIPN*, which could be converted to the strong reductant anion radical 4CzIPN^•− with ⁱPr₂NEt via a SET process. Then, 4CzIPN^•− attacked the alkene 86 to afford another radical anion 85, followed by the interaction with CO₂ to produce the intermediate 87 (path a). Subsequently, the 87 underwent the SET with another molecule of 4CzIPN^•−to generate the vital benzylic anion 88, followed by the capture of another molecule of CO₂ and protonation to furnish the final product 89. It should be mentioned that electron transfer (ET) from 85 to CO₂ to form the intermediate 87 could not be excluded (path b).

2.4.3. Others

Photoredox reactions mediated by EDA complexes have been recognized as unique and green approaches to trigger light-assisted synthesis without external photocatalysts [102]. In 2021, Guo’s group successfully realized the fluoroalkylthiocyanation of alkenes via the EDA complex-mediated intermolecular electron transfer [103]. The combination of perfluoroalkyl iodide reagents (R_f-I) and K₃PO₄ led to the formation of a photoactive EDA complex. A variety of fluoroalkylthiocyanationalized products could be achieved under LED light irradiation, with TMSNCS as the thiocyanation reagent and CuCl as the Lewis acid catalyst. Various terminal alkenes, internal alkenes, and estrone-derived alkenes were amenable in this reaction. Interestingly, iodoperfluoroalkylation products were obtained in the case of aliphatic alkenes through the atom transfer radical additions (ATRAs) pathway, and this result might be caused by the distinct properties of the benzyl and non-benzyl radical intermediates. A plausible mechanism has been proposed and depicted in Scheme 55. First, the colored EDA complex was generated, followed by visible light-promoted SET to generate the fluoroalkyl radical •R_f via the reductive cleavage of the C–I bond. Then, the electrophilic radical •R_f was intercepted by the alkenes to provide the benzylic intermediate 90, which could be oxidized by the PO₄ ²⁻ anion to produce a carbocation intermediate 91. Finally, the carbocation intermediate 91 coupled with the nucleophilic SCN^- to yield the fluoroalkylthiocyanation product.

In 2021, Reiser’s group developed an EDA complex-mediated protocol enabling the iodoamination of miscellaneous olefins using sulfonamides and N-Iodosuccinimide (NIS) as the N-source and iodo-source, respectively (Scheme 56) [104]. This protocol featured a broad substrate scope (over 60 examples, yields up to 99%) with high functional group tolerance, utilizing dimethyl carbonate (DMC) as a green and biodegradable solvent. In addition, this protocol is suitable for the late-stage modification of bioactive drugs and can be scaled up without a loss of efficiency. Based on mechanistic investigations, they proposed a reasonable reaction mechanism. First, the halogen bond complex 92 absorbs the visible light, resulting in the ion–radical complex via visible light-induced homolysis. The following charge and proton transfer of this complex delivers the iodine radical I• and the nitrogen-centered radical 93, which adds to the alkene 94 to generate the intermediate 95. Finally, the intermediate can react with the halogen bond complex 92, which delivers the iodoamination product and regenerates the nitrogen-centered radical 93.

Recently, Chen developed a visible light-induced intermolecular alkylpyridylation of arylalkenes to afford various alkylated pyridines with Hantzsch ester (HE) under the irradiation of a 90 W blue LED (Scheme 57) [105]. In this protocol, the HE was found to be crucial to trigger the reductive radical coupling reaction as a photoreductant. N-(acyloxy)phthalimide esters (NMP) and 4-cyanopyridine were employed as the alkylation and pyridylation reagents, respectively. Notably, no product formation was observed under an aerobic atmosphere, and the removal of HE or LED light would totally shut down the transformation. According to the authors, this reaction may involve the following mechanism. The excited-state Hantzsch ester HE^* reacted with the NHP ester to produce the decarboxylative product alkyl radical through the extrusion of CO₂. Then, the alkyl radical was intercepted by aryl alkenes to produce the intermediate 96. Meanwhile, the 4-cyanopyridine underwent reduction by HE^* to form a radical anion intermediate 97, which was trapped by the in situ-generated 96, furnishing the desired alkylpyridine product with the extrusion of cyanide.

Li’s group disclosed another EDA complex strategy for the photoredox iodosulfonylation of various alkenes in water to fabricate an array of β-iodo-substituted sulfone derivatives at room temperature (Scheme 58) [106]. The EDA complex was generated with an iodine ion as the electron donor and sulfonyl chloride as the electron acceptor under the promotion of the surfactant CTAB. In this protocol, under the optimum conditions, various styrenes and alkyl-substituted alkenes can be smoothly transformed to the corresponding iodosulfonylation products in good to excellent yields. However, the aryl moiety bearing strong electron-withdrawing substituents cannot provide the desired products due to the low reactivity. As to aryl sulfonyl chlorides, both electron-rich and electron-poor substituents on the aryl group are well tolerated to produce the corresponding products in moderate to good yields. The reaction is also amenable to heteroaromatic sulfonyl chloride.

In 2021, Xie’s group developed a pothoredox oxysulfonylation of styrenes with easily available sulfonic acids as the radical precursor and air as the oxidant to afford a wide variety of β-ketosulfones in CH₃CN and water as the solvent (Scheme 59) [107]. The reaction was tolerant for various vinylbenzenes with valuable functional groups, including methoxy, phenoxy, halide, trifluoromethyl, ester, and nitro groups. Besides this, cyclic olefins could also give the desired product in good yields. Unfortunately, aliphatic alkenes failed to give the desired products. Interestingly, this strategy was also applicable to various heteroaryl and aliphatic sulfonic acids, delivering the oxysulfonylation products in good to excellent yields. The radical scavenger experiments demonstrated that the reaction proceeded through a radical pathway. Initially, under visible light irradiation, the oxygen could be transformed to singlet oxygen ¹O₂ under irradiation with a blue LED. Following the generation of this active ¹O₂, it rapidly reacted with sulfonic acid 98 via a hydrogen atom transfer (HAT) event to deliver a sulfonyl radical R²SO₃• and another active hydroperoxy radical HO₂• [108]. Then, the addition of the R²SO₃• to alkene 99 gave the carbon-centered radical 100, which could be transformed to the peroxy radical 101 through the incorporation of dioxygen. Lastly, the radical 101 was trapped by the generated HO₂•, providing the tetroxide intermediate 102, which underwent Russel fragmentation to furnish the desired product 103, along with the extrusion of O₂ and water.

With Umemoto reagent II as the CF₃ source and ammonium thiocyanate or potassium selenocyanate as the nucleophilic reagent, Akondi’s group developed an effective method for the trifluoromethyl-thiocyanation and trifluoromethyl-selenocyanation of both aryl and alkyl alkenes under irradiation with a blue LED (450 nm) (Scheme 60) [109]. The substrate scope proved to be broad with good functionalities and tolerance, affording difunctionalized alkenes with good to excellent yields. For the trifluoromethyl-thiocyanation reaction, various functionalized styrenes and unactivated alkenes were tolerated, delivering the corresponding products in good to excellent yields. Similarly, the trifluoromethyl-selenocyanation of styrenes and even acrylates was also viable under the same reaction conditions with potassium selenocyanate as the coupling partner. The author demonstrated that this transformation was initiated by the homolytic cleavage of Umemoto reagent II with the aid of visible light to produce the radical cation 108 and radical •CF₃, which was trapped by alkene 104 to generate the intermediate 105. The interaction between 108 and 105 through the single-electron transfer process produced the carbocation 107 and regenerated the •CF₃, along with the byproduct 106. The 107 trapped by the anion nucleophilic reagent would provide the final product. In another reaction pathway, the ammonium thiocyanate or potassium selenocyanate could be transformed to the corresponding •SCN radical and •SeCN radical with the aid of radical cation 108 or Umemoto reagent II. Finally, the adducted radical 105 combined with the •SCN or •SeCN could produce the desired product [110].

This section mainly introduces the difunctional grouping of olefins catalyzed by photoredox. Starting from the four aspects of the iridium-catalyzed difunctionalization of olefins, the ruthenium-catalyzed difunctionalization of olefins, the visible light-promoted copper-catalyzed reaction, and the visible light-promoted metal-free reaction, the research methods of photooxidation-catalyzed olefins in this field are briefly reviewed. Classification is given according to the catalyst used for conversion. It also covers different important aspects of these conversions [111].

3. Conclusions

In organic synthesis, we must follow the concept of green chemistry and advocate sustainable development, and the use of visible light catalytic reactions corresponds to this. In recent years, the creation of novel functional molecules from alkenes has become the focus of organic chemists, and the search for mild reaction conditions has also become the focus of the scientific community. Scientists use the advantages of photocatalysis to carry out various functionalization reactions of alkenes at room temperature and pressure, and synthesize a variety of molecules.

To sum up, we have summarized the most recent key progress on the photoredox-catalyzed 1,2-difunctionalization of alkenes, including 1,2-dicarbofunctionalization, 1,2-carboheterofunctionalization, and 1,2-diheterofunctionalization (Scheme 61). Some unique reaction methods with the advantages of the easy availability of raw materials, mild reaction conditions, high yield, strong regional selectivity and complex molecular structures of products, are summarized. Further, we have also discussed several exquisite strategies to facilitate these transformations, such as photosensitizer-catalyzed redox reactions, photoreactions mediated by EDA complexes and ATRA reactions. We found that due to incomplete mechanism information, catalysts are scarce and precious, and the reaction times are long, resulting in low reaction efficiency. After reviewing the relevant literature, it was found that modern techniques, such as processes and batch methods, can be used to effectively solve problems with long reaction times. Despite much progress having been achieved, there remain great opportunities for progress in this research field. The life of organic compounds is short, so in the development of this research field, the self-quenching of organic compounds is a challenge, which requires researchers to develop new photo-catalysts and propose new methods to deal with them on the basis of the existing ones. As there is a great diversity of alkenes, a vast number of alkenes with structurally diverse substituent groups are still unexplored, and the photoredox-catalyzed functionalization of these compounds is full of challenges, for example, the issues of alkenes containing free hydroxyl, amido, or other electron-deficiency functional groups. In addition, the photoredox enantioselective difunctionalization of alkenes to fabricate chiral compounds is still in its infancy. Nevertheless, in view of the rapid development of new catalysts and novel synthetic strategies, we believe that there will be more breakthroughs in this research area. Finally, we hope that this review will be helpful to researchers in this field.