The Merger of Transition Metal and Photocatalysis: Recent Advances and Prospects in Asymmetric Intermolecular 1,2-Difunctionalization of Alkenes

Abstract

Unsaturated carbon–carbon bonds are fundamental building blocks in organic compounds. The difunctionalization of olefins allows for the rapid construction of drugs and complex molecular architectures. This transformation, which simultaneously installs two distinct functional groups across a carbon–carbon double bond, has therefore emerged as prominent research frontier in organic chemistry. In recent years, the synergy between photoredox and transition metal catalysis has emerged as a powerful and sustainable platform for constructing C-X bonds. This review covers advances since 2018 in the asymmetric difunctionalization of olefins enabled by synergistic visible light photoredox and transition metal catalysis, encompassing the construction of both carbon–carbon and carbon–heteroatom bonds. It systematically summarizes the reaction conditions, substrate scope, mechanisms, and merits and limitations of these catalytic systems, aiming to provide a useful reference for researchers in this field.

1. Introduction

Olefins are inexpensive and readily accessible chemical feedstocks with broad applications in pharmaceuticals, agrochemicals, and materials science [1,2,3,4]. Their intermolecular difunctionalization provides atom and step economy while enabling the rapid generation of molecular diversity, aligning with the principles of green chemistry [5,6,7,8]. Consequently, alkene difunctionalization has emerged as a cornerstone in modern organic synthesis, enabling the precise construction of two distinct functional groups across a carbon–carbon double bond with stereochemical control. Over the past decade, transition metal-catalyzed alkene difunctionalization has attracted widespread attention and is now established as a powerful methodology for building diverse carbon–carbon and carbon–heteroatom bonds [9,10,11,12,13,14,15,16]. However, thermochemical reactions often rely on organometallic reagents, require elevated temperatures, and employ expensive ligands, presenting substantial challenges for further development [17,18].

In recent years, visible light-mediated photoredox catalysis has emerged as a valuable concept in organic synthesis. Photocatalytic olefin difunctionalization employs photocatalysts for single-electron transfer (SET) activation of olefins under mild conditions, enabling the efficient and highly selective incorporation of two distinct functional groups [19,20]. Compared to conventional methodologies relying on transition metal catalysis or stoichiometric redox systems, photocatalytic approaches generally exhibit superior functional group tolerance, milder reaction conditions, and enhanced atom and step economy [10]. Visible light-driven catalytic asymmetric difunctionalization of alkenes has thus become a highly attractive frontier in modern synthetic chemistry, as it allows for the simultaneous introduction of two functional groups and the precise construction of stereogenic centers in a single step under mild conditions. However, a core challenge lies in the high reactivity and instability of the short-lived radical intermediates generated, which renders enantioselective control over the newly formed stereocenters particularly difficult. To address this selectivity challenge, the metallaphotoredox cooperative catalysis strategy has been developed and has become a major research focus [21,22,23,24].

The merger of photoredox and transition metal catalysis has rapidly advanced alkene difunctionalization, establishing it as a mild and efficient route to complex molecular architectures. Representative developments include Shu and colleagues’ systematic review on the visible light-mediated nickel-catalyzed asymmetric bifunctionalization of alkenes, which highlights cross-electrophile three-component reactions under both redox-neutral and reductive conditions, along with detailed mechanistic insights [25]. Subsequently, Xiao’s group summarized their advances in visible light-mediated copper-catalyzed asymmetric multicomponent radical cross-coupling of olefins, elucidating the pivotal role of photocatalysis in promoting enantioselective transformations and offering valuable insights for this rapidly evolving field [26]. However, a comprehensive and comparative review focusing specifically on the asymmetric 1,2-difunctionalization of alkenes enabled by visible light and transition metal cooperative catalysis—with an emphasis on the distinct mechanistic paradigms across different metals—remains conspicuously absent. Prior accounts have largely been organized by reaction type or limited to a single metal, leaving a critical gap in understanding how the choice of metal (Cu, Ni, Pd, Co) dictates the stereoelectronic control model, radical capture pathway, and ultimately the substrate scope and limitations. To fill this critical gap, this review aims to provide a consolidated and mechanistic-oriented survey of this vibrant area. We will organize the discussion by transition metals (Cu, Ni, Pd, Co), analyze representative catalytic cycles and substrate scope, and outline future directions to inspire further innovation in the field.

The following figure represents the ligands and photocatalyst discussed in this review (Figure 1 and Figure 2).

2. Visible Light-Mediated Copper-Catalyzed Asymmetric Difunctionalizations of Alkenes

Copper, an abundant and low-toxicity transition metal, serves as an important catalyst in organic synthesis. The merger of copper catalysis with photoredox processes leverages light energy to generate highly reactive intermediates or radicals that are often inaccessible under thermal conditions [27,28]. This synergy provides a powerful strategy for achieving enantioselective difunctionalization of olefins. Two possible mechanisms are proposed in Scheme 1. The first involves excitation of the photocatalyst by visible light. The resulting excited-state species undergoes SET to form a nucleophilic radical (R^•). This radical combines with the alkene to form a new alkyl radical intermediate. Then, copper stereoselectively captures the intermediate to form a high-valent alkyl-L/Cu intermediate. Finally, reductive elimination affords the target compound. The second mechanism involves rapid ligand exchange between L/Cu and R¹-X to deliver photoactive L/Cu^I-R¹ species. This complex can be irradiated to its reducing excited-state [L/Cu^I-R¹]*. Subsequently, [L/Cu-R¹]* undergoes SET with R²-X to generate an L/Cu^II intermediate and R² radical. The R² radical then rapidly attacks the alkene to give a benzyl radical, which is captured by the L/Cu^II intermediate to form a chiral L/Cu^III species. Finally, this L/Cu^III species undergoes enantioselective reductive elimination to afford the final product. Using this approach, a variety of functional groups, including cyano, aryl, and ester groups, have been successfully incorporated via enantioselective copper catalysis.

2.1. Enantioselective C–CN Difunctionalization

The cyano group is a key functional group in drug synthesis, high-performance materials and organic synthesis. In 2018, Han and Mei et al. reported a protocol for photoredox and copper-catalyzed asymmetric cyanoalkylation of alkenes with alkyl N-hydroxyphthalimide esters [29]. Under an atmosphere of argon, compound 4 was obtained in moderate yields and enantioselectivities in the presence of 1 (4.0 equiv), 2 (0.2 mmol), 3 (1.1 equiv), CuBr (1.0 mol%) as the metal catalyst, ligand L1 (1.2 mol%) as the chiral ligand, fac-Ir(ppy)₃ PC1 (0.5 mol%) as the photocatalyst in a mixed solvent of NMP and PhCl at room temperature for 24 h. This protocol provides a valuable new approach to asymmetric cyanoalkylation of alkenes, particularly relevant to pharmaceutical and natural product chemistry. Both electron-donating and electron-withdrawing groups at the para-position of the styrene derivatives are well tolerated. Furthermore, reactions with meta- and ortho-substituted styrene derivatives also proceeded smoothly. Unfortunately, the inactive alkene shows poor reactivity. In addition, a wide range of primary, secondary, and tertiary alkyl-substituted esters are also well tolerated in this reaction. A possible mechanism is proposed in Scheme 2. Firstly, the photoredox catalyst Ir^III PC1 is excited to the activated state Ir^III*, which then undergoes SET with N-hydroxyphthalimide esters to generate a radical anion and photocatalyst intermediate Ir^IV. Secondly, the radical anion releases CO₂ to form the alkyl radical that adds to styrene to produce a benzylic radical. At the same time, the Ir^IV oxidizes the L/Cu^I catalyst to generate L/Cu^II species. Next, the L/Cu^II complex is oxidized by the benzylic radical and then captures TMSCN 3 to generate L/Cu^III intermediate. Finally, the L/Cu^III intermediate undergoes reductive elimination to afford the desired product with high enantioselectivities and regenerate the L/Cu^I catalyst to close the catalytic cycle.

In 2019, Xu and Wang et al. developed a visible light-induced Cu-catalyzed enantioselective cyanofluoroalkylation of alkenes that proceeds without an external oxidant [30]. Treatment of alkenes 5, fluoroalkyl iodides 6 and TMSCN 3 with CuI (10 mol%), bisoxazoline ligand L2 (20 mol%), N,N-dimethylbenzylamine (1.5 equiv) and H₂O (2.0 equiv) in MeCN at room temperature for 4 h under argon atmosphere enabled the synthesis of the desired cyanofluoroalkylation products 7 in good yields (up to 93%) with excellent enantioselectivities (up to 96%). Different fluoroalkyl iodides reacted smoothly to provide products with uniformly good yields and enantioselectivities. However, the conjugated dienes and styrene substrates with strong electron-withdrawing groups showed limited reactivity. Notably, the cyanofluoroalkylation product could be further converted to fluoroalkylated carboxylic acid and amine. While this method offers a direct route to enantioenriched cyanofluoroalkylated compounds, the reliance on a high loading (12 mol%) of the chiral ligand raises concerns regarding its practicality and sustainability. At such a high loading, the ligand—often the most synthetically complex and expensive component—effectively becomes a stoichiometric additive rather than a true catalyst, which severely undermines the atom economy of the transformation. A possible mechanism is proposed in Scheme 3. The catalytic cycle is initiated by rapid ligand exchange between TMSCN and [L/Cu^IX] species to give [L/Cu^ICN] species. Upon irradiation, the [L/Cu^ICN]* state is oxidatively quenched, generating the fluoroalkyl radical and L/Cu^II(CN)₂ intermediate. The fluoroalkyl radical then adds to the alkene to form benzyl radical intermediate, which subsequently reacts with the [L/Cu^II(CN)₂] complex to form the chiral L/Cu^III(CN)₂ species. Finally, reductive elimination of [L/Cu^III(CN)₂] species delivers the final product with high enantioselectivities.

In 2021, Chen and Xiao et al. developed an efficient intermolecular three-component asymmetric dicarbofunctionalization of alkenes 5 by photoredox and copper dual catalysis (Scheme 4) [31]. This transformation, employing precious metal fac-Ir(ppy)₃ PC1 (0.8 mol%) as the photocatalyst, Cu(CH₃CN)₄PF₆ (1.5 mol%) as the catalyst and chiral Box-type ligand L2 as the ligand in DMA at room temperature for 24 h under argon could obtain a wide range of styrenes with electron-donating (such as Me, tBu, and Ph) or electron-withdrawing (such as F and OAc) in moderate to good yields and excellent enantioselectivities (up to 93%). Notably, styrenes derived from dihydroartemisinin and gibberellic acid could also participate in the reaction with good stereoselectivity. A possible mechanism is proposed in Scheme 4. Upon light irradiation, the photoredox catalyst fac-Ir(ppy)₃ PC1 is excited to the activated state, which then proceeds with SET with the esters 8 to give iminyl radicals. Cleavage of these iminyl radicals generated a radical species, followed by radical addition to the styrene derivative to form the relatively stable benzyl radical. Then, the L/Cu^ICN complex could be oxidized by the photocatalyst radical cations via a SET process to obtain ground-state photocatalyst and the L/Cu^II(CN)₂ complex. Subsequently, the L/Cu^II(CN)₂ complex adds to radical 10 to produce L/Cu^III(CN)₂ species and then reductive elimination of L/Cu^III(CN)₂ species to deliver the final product with high enantioselectivities and regenerate L/Cu^ICN species to complete the catalytic cycle. Although the catalytic system employs relatively inexpensive copper salts, the photocatalyst remains a precious iridium complex. It is worth noting that while this system exhibits excellent compatibility with simple styrenes and their derivatives, it is not applicable to unactivated alkenes. This work provides an important methodological foundation for asymmetric radical difunctionalization; however, to evolve into a truly general synthetic tool, further breakthroughs are still required in catalyst sustainability, substrate universality, and in-depth mechanistic analysis.

In 2021, Xiao et al. developed a visible light/copper dual-catalyzed strategy for asymmetric carbocyanation of 1,3-dienes 11 (3.0 equiv) with carboxylic acid derivatives 12 (1.0 equiv) and TMSCN 3 (3.0 equiv) (Scheme 5) [32]. NHP esters with different substitution patterns as well as cyclic or linear alkylcarboxylic acids and 1,3-dienes with different substituents were compatible in the reaction. Notably, this success was successfully expanded to 1,3-enynes; however, internal acyclic dienes were unsuccessful under the current conditions. Although the system successfully avoids the use of precious metal photocatalysts and ultimately employs white LEDs as the light source, which enhances the sustainability of the protocol to some extent, the extended reaction time—requiring up to 36 h under low concentration and specific wavelength irradiation—poses significant challenges to space–time yield and process scale-up in practical production. A possible mechanism is proposed (Scheme 5). The photocatalyst perylene PC2 is irradiated to afford its excited state under visible light excitation. The excited-state PC2 reduces NHP ester 12 in a SET to generate PC2 radical cations and 12 radical anion, which subsequently releases CO₂ to form radical 14. Then, the alkyl radical 14 adds to 1,3-diene to give allyl radical. In addition, the complex L/Cu^I(CN) is oxidized by the radical cations PC2 via a SET process to obtain ground-state photocatalyst and the L/Cu^II(CN) complex. Next, the L/Cu^II(CN) complex adds to allyl radical to produce L/Cu^III(CN) species. Finally, reductive elimination of this L/Cu^III(CN) species delivers the final chiral allyl cyanide product and regenerates the L/Cu^I(CN) catalyst.

In 2021, Lu et al. developed a chemodivergent asymmetric strategy by tuning the metal-to-ligand ratio in an organometallic catalytic system. This transformation utilized N-(aroyloxy)phthalimide esters (NHP esters) as precursors to generate either oxygen-centered aroyloxy or nitrogen-centered phthalimidyl radicals, yielding a series of products (Scheme 6) [33]. The optimized conditions for this reaction were as follows: 3DPA2FBN PC3 as the photocatalyst, Cu(CH₃CN)₄BF₄ as the catalyst and L3 as the chiral ligand in MeCN at 5 °C for 12 h with irradiation of blue LED. Importantly, this chemodivergent asymmetric synthesis was achieved by tuning the metal-to-ligand ratio. Moreover, this reaction was amenable to electron-rich or electron-deficient substituents at the para-position or meta-position of styrene. The reaction was also applicable to heteroarenes, vinylcyclopropanes and bioactive molecules, including estrone and dehydrocholic acid. Notably, the effectiveness of the reaction was demonstrated by the transformation of the products through later functionalization to generate 1,3-diamines, amino alcohols, and aldehydes, which are fragments widely found in natural products and many useful compounds.

In 2025, Lu, Li and Chen et al. developed a switchable divergent radical platform for olefin difunctionalization using N-(acyloxy)phthalimides as tunable radical precursors (Scheme 7) [34]. The reaction can be directed toward either 1,2-alkylcyanation or 1,2-aminocyanation with high enantioselectivity and broad functional group tolerance. This methodology exhibits broad substrate compatibility, successfully achieving highly selective transformations of typically challenging NHPI esters bearing electron-withdrawing groups such as α-cyano, ester, polyfluoroalkyl, and halogens, while also accommodating a wide range of aryl, heteroaryl, and even complex natural product-derived alkenes. The resulting bifunctional products demonstrate remarkable synthetic utility, allowing for diverse derivatizations via cyano and halogen groups to efficiently construct key intermediates such as chiral amines, esters, lactams, and β-ketoesters. The successful gram-scale preparation and subsequent tandem transformations further underscore the robustness and practicality of this platform for the rapid assembly of structurally complex and functionally dense molecules.

In 2023, Nicewicz et al. developed an interesting photocatalytic protocol for the enantioselective amino and oxycyanation of alkenes via organic photoredox and copper catalysis [35]. They utilized olefins 18, carbamate nucleophiles 19 and TMSCN 3 to synthesize a series of the amino- and oxycyanation products, which were obtained in the presence of Cu(OTf)₂ (5 mol%), sBOX(iPr) L4 (7.5 mol%), Mes-Acr-BF₄ PC4 (5 mol%), TBHP (2.0 equiv) in MeCN at 5 °C under blue LED irradiation for 16 h (Scheme 8). Importantly, this protocol can be considered an effective method to synthesize the β-amino nitrile moiety and its derivatives, important building blocks for natural products and pharmaceuticals. Both terminal and internal styrene derivatives were well tolerated under the standard reaction conditions. Unfortunately, diastereoselectivity could not be achieved with alkenes bearing two prochiral carbon centers. It is worth noting that the group conducted cyclic voltammetry studies. The experiments showed that the oxidation potential of acrylic acid was more compatible with that of the corresponding β-methylstyrene, indicating that the oxidation occurred in the olefinic part rather than the carboxylic acid part. The mechanism begins with the excitation of the PC4 catalyst by blue LED light, generating an excited-state PC4 that oxidizes the alkene to form a radical cation. Subsequently, this radical cation is intercepted by a nucleophile to afford an intermediate, and then the alkyl radical adds to L/Cu^IICN species to give L/Cu^III(CN) intermediate. Reductive elimination from the L/Cu^III(CN) intermediate releases the desired product (Scheme 8).

In 2023, Zhu et al. reported an efficient strategy for the 1,2-amidocyanation of 1,3-dienes 21 using N-Boc-amidopyridinium 22 salts and TMSCN 3 under visible light irradiation (Scheme 9) [36]. The highlights of this protocol include mild reaction conditions and broad substrate scope. The reaction of 21 (0.1 mmol) with N-Boc-amidopyridinium salts 22 (1.0 equiv) and TMSCN 3 (2.0 equiv) employed fac-Ir(ppy)₃ PC1 (1 mol%), Cu(OTf)₂(H₂O)_x (20 mol%) as the catalyst and L2 as the ligand in CHCl₃ at room temperature under blue LED irradiation, affording the desired 1,2-amidocyanation products. Notably, electron-withdrawing substitution (F, Cl, Br, COOMe, and CF₃) at various positions of 1,3-dienes was well tolerated, affording the required products in good yields and excellent ee values. Similarly, electron-donating alkyl substitution (Me, OMe) at various positions of 1,3-dienes was reacted smoothly and delivered the expected products in good yields. Importantly, the reaction was also applicable to N-amidopyridinium salts, and both N-Boc and N-Cbz derivatives were applicable. The group demonstrated the existence of an allylic radical intermediate through radical clock experiments, and further unequivocally confirmed the inner-sphere cyanide transfer mechanism by characterizing the L/CuCN complex by X-ray crystallography. A possible mechanism is proposed in Scheme 9. Firstly, the excited-state photocatalyst fac-Ir(ppy)₃ can be oxidized by N-amidopyridinium salt 22 to provide photocatalyst Ir^IV and radical 24. Then, the radical undergoes fragmentation to generate 2,4,6-collidine and ^●NHBoc. Subsequently, 1,3-diene adds to ^●NHBoc to form an allylic radical, followed by oxidation with L/Cu(CN)₂ to generate the allylic L/Cu^III complex. Next, reductive elimination of L/Cu^III complex affords the final product and L/CuCN. Finally, oxidation of L/CuCN to L/Cu(CN)₂ in the presence of TMSCN by Ir^IV would close the catalytic cycle, regenerating the Ir^III PC1.

In 2024, Xiao and Chen et al. reported an organic photoredox-catalyzed reductive functionalization of aromatic alkenes for the synthesis of hydrocyanation, deuterocyanation, and cyanocarboxylation products by employing TMSCN 3 as the cyanide source (Scheme 10) [37]. The reaction proceeded via the generation of alkene radical anions, which were orthogonally functionalized with a cyanide source, enabling highly regio- and enantioselective hydrocyanation, deuterocyanation, and cyanocarboxylation. Under an atmosphere of argon, compound 29 was obtained in high yields and enantioselectivities in the presence of 25 (1.0 equiv), 3 (1.5 equiv), either H₂O (1.0 equiv), D₂O (20.0 equiv), CO₂ (5 atm), 10-phenylphenothiazine PC5 (PTH-1, 10 mol%), CuTc (2 mol%) and bisoxazoline L2 (2.4 mol%) in DMA at room temperature for 2–48 h. Notably, electron-rich and electron-poor styrene derivatives, internal alkenes and those with alkynyl groups as well as other vinylarenes are both applicable to the reaction conditions. A possible mechanism is proposed in Scheme 10. Firstly, upon visible light irradiation, the excited-state photocatalyst PC5* oxidizes the alkene* to generate the alkene radical anion and the PC5 radical cation. Next, the radical anion is protonated by H₂O or HCN to obtain the benzyl radical. At the same time, the [L/Cu^ICN] complex is oxidized by the radical cation PC5 via a SET process to generate the [L/Cu^II(CN)₂] complex after trapping another cyanide anion from TMSCN. Finally, the [L/Cu^II(CN)₂] complex reacts with prochiral benzylic radicals to form product through a high-valent L/Cu^III complex and reductive elimination.

In 2025, Yuan et al. reported a catalytic electron donor–acceptor (EDA) complex in cooperation with copper catalysis. In this protocol, NaI was used as a catalytic donor to achieve copper-catalyzed radical asymmetric carbocyanation (Scheme 11) [38]. They selected NHPI ester 30 (2.0 equiv), alkene 31 (0.2 mmol), and TMSCN 3 (2.0 equiv) as model substrates to optimize the reaction conditions, employing NaI/PCy₃ (20 mol%) as the donor catalyst, CuBr (20 mol%) and ligand L2 (12 mol%) as the chiral copper catalytic system under blue LED irradiation to afford the desired products. Notably, alkene substrates, styrene and its derivatives with different substituents at the para-, meta-, and ortho-positions, as well as 2-vinylnaphthalene, could react smoothly with high yields and enantioselectivities. A possible mechanism is proposed in Scheme 11. Photoexcitation of the EDA complex triggers SET to generate an alkyl radical and an R₃P-I^● intermediate, and then the alkyl radical adds to styrene to form a benzyl radical intermediate. Subsequently, the catalyst L/Cu^II(CN) complex further reacts with TMSCN 3 to generate the L/Cu^II(CN)₂ intermediate. Then, the benzyl radical is captured by the L/Cu^II(CN)₂ complex to produce the L/Cu^III complex, which subsequently undergoes reductive elimination to furnish the final product and regenerate L/Cu^I(CN) catalyst. This protocol features a broad scope of alkyl radical precursors, paving the way for applying catalytic EDA complex photochemistry. Although this strategy circumvents the use of precious metal photocatalysts by employing NaI/PCy₃ as a catalytic donor, the system still requires 20 mol% of copper salt and 12 mol% of the chiral bisoxazoline ligand. The high loading of the chiral ligand presents non-negligible environmental and economic costs. Moreover, its applicability to electron-deficient alkenes, unactivated alkenes, and internal alkenes has not yet been demonstrated, indicating that the generality of this method remains limited to substrates with specific electronic properties and configurations. Overall, this work provides an important proof-of-concept for EDA/metal cooperative catalysis, but further breakthroughs in catalyst design and substrate universality are still required.

In 2025, Zhang and Fang et al. developed an enantioselective cyanoalkylation of styrenes using a cooperative photoredox and copper catalysis system, proceeding via deoxygenation of alkoxyl radicals with organophosphorus compounds (Scheme 12) [39]. This protocol employed PC1 (1 mol%) as the photocatalyst, Cu(CH₃CN)₄PF₆ (2 mol%) as the copper catalyst, and chiral bisoxazoline ligand L2 (3 mol%) as the ligand, triethyl phosphite as the additive in DCM at room temperature for 12 h. A variety of styrene derivatives and some naphthalene-derived substrates could afford the desired chiral alkyl nitrile products in good yields (54–83%) with excellent enantioselectivities (60–95%). Some alkyl N-hydroxyphthalimide ethers also reacted well, providing products in good yields (50–75%) and high enantioselectivities (82–93% ee). The model reaction was successfully scaled up to 3 mmol without any erosion in yield or enantioselectivity. In addition, the resulting alkyl nitriles served as versatile synthetic intermediates, allowing for their straightforward conversion into various chiral carboxylic acids, amides, and esters, thereby highlighting the method’s synthetic utility. A possible mechanism is proposed in Scheme 12. The mechanism begins with the excitation of the photocatalyst PC1 by blue LED light, generating an activated state photocatalyst Ir^III*, which donates an electron to the alkyl N-hydroxyphthalimide ether to form an alkoxyl radical and Ir^IV. The alkoxyl radical reacts with P(OEt)₃ to generate a phosphorus radical, which then releases PO(OEt)₃ to form an alkyl radical, and then the alkyl radical adds to the alkene to generate a benzylic radical intermediate. Meanwhile, L/Cu^II(CN) species reacts with TMSCN to generate the active L/Cu^II(CN)₂ species. Finally, L/Cu^II(CN)₂ species enantioselectively traps the benzylic radical intermediate, obtains the final chiral alkyl nitrile product and after reductive elimination, regenerates L/Cu^I(CN) for the next catalytic cycle.

In 2025, Wu and Chen et al. reported a photoredox and copper dual-catalyzed asymmetric alkoxycarbonyl-cyanation of styrenes, providing a mild and practical approach for the efficient synthesis of chiral β-cyanoesters (Scheme 13) [40]. Employing PC1 as the photocatalyst, CuBr as the catalyst, chiral bisoxazoline L24 as the ligand, this protocol enables the 1,2-difunctionalization of styrenes under blue light irradiation using N-phthalimidoyl oxalates as alkoxycarbonyl radical precursors and TMSCN as the cyanide source. The reaction is compatible not only with a variety of styrene derivatives bearing electron-donating or electron-withdrawing groups (such as halogens, cyano, trifluoromethyl, aldehyde), including ortho-, meta-, para-substituted and poly-substituted styrenes, but also compatible with alkoxycarbonyl precursors derived from methanol to various cyclic alcohols and even chiral alcohols. The target products are obtained in moderate to good yields with high enantioselectivity.

In 2025, Chen et al. reported a photoinduced copper-catalyzed asymmetric radical sulfonylcyanation of vinylarenes using sulfonyl cyanides as bifunctional reagents under mild conditions, employing CuTc (5 mol%) as the copper catalyst, chiral bisoxazoline ligand L2 (6 mol%), and phenothiazine-based photocatalyst PC5 (5 mol%) in MeCN under irradiation with purple LED at room temperature under an argon atmosphere [41]. The protocol demonstrates broad substrate scope, accommodating a wide range of styrene derivatives bearing diverse electronic and steric properties, as well as various aryl- and alkyl-substituted sulfonyl cyanides, delivering chiral β-sulfonyl nitriles in high yields (up to 98%) and enantioselectivities (up to 95% ee). The synthetic utility of this method is further demonstrated by transformations such as conversion of the nitrile product into ester and Boc-protected amine derivatives without significant loss of enantiopurity, underscoring the method’s potential for preparing valuable enantiomerically enriched building blocks in medicinal and synthetic chemistry (Scheme 14).

2.2. Enantioselective Dual Carbofunctionalization

In 2020, Zhang et al. developed a copper-catalyzed photoinduced enantioselective dual carbofunctionalization of alkenes, employing CuI (10 mol%) as the catalyst, bisoxazoline diphenylamine L6 (tBu-BOPA, 20 mol%) as the chiral ligand and K₃PO₄ (3.0 equiv) as the base in MeCN under blue LED irradiation at 0 °C for 24 h [42]. The reaction proceeded with moderate to good yields and excellent enantioselectivities (up to 98%), with fluorinated propargylic compounds providing particular synthetic value. Although the reaction was applicable to ortho-substituted styrenes, their yields diminished due to steric hindrance, and disubstituted alkenes were unreactive. In addition, the successful gram-scale synthesis and downstream transformations confirmed its practical utility. The group demonstrated the involvement of radical intermediates through radical trapping experiments. UV-vis absorption spectroscopy revealed that the BOPA–copper–alkyne complex is the actual photoactive species. Additionally, cyclic voltammetry and Stern–Volmer fluorescence quenching experiments were conducted. Unfortunately, the isolation and crystallographic characterization of key intermediates were not mentioned in the article. A possible mechanism is proposed in Scheme 15. The [L/Cu^I(C≡CR)] complex undergoes photoexcitation to generate the excited-state [L/Cu^I(C≡CR)]* species. This excited-state complex then reduces an alkyl iodide via SET, generating an alkyl radical and [L/Cu^II(C≡CR)] species. Then, the alkyl radical adds to styrene to form a benzylic radical, which reacts with [L/Cu^II(C≡CR)] to form a L/Cu^III complex that undergoes reductive elimination to provide the chiral propargylic product.

In 2024, Xiao et al. developed a versatile copper-bisoxazoline catalytic system for the asymmetric three-component arylative radical cross-coupling of benzylic, propargylic or allenylic radicals with oxime carbonates and aryl boronic acids (Scheme 16) [43]. This methodology enables access to chiral 1,1-diarylalkanes, benzylic alkynes, and allenyl-substituted allenes with high enantioselectivities, employing copper salts in combination with chiral ligands for catalysis, with the transformation proceeding in a mixed solvent system at 0 °C. Although this methodology successfully constructs a diverse array of chiral allenes under mild conditions with excellent enantioselectivity, sterically hindered 1,1- and 1,2-disubstituted styrenes are incompatible with this system, underscoring the high sensitivity of the radical addition step to substrate steric hindrance. Furthermore, the method relies on specifically designed bisoxazoline ligands, with the optimal ligand structure requiring switching based on the radical type, highlighting the current lack of a truly universal ligand solution.

In 2024, Liu et al. developed a protocol for the synthesis of cyanoalkylalkynylation compounds of alkenes (0.1 mmol), terminal alkynes 43 (3.0 equiv) and oximes 44 (3.0 equiv) in PX/DCM (v/v = 7/3) in the presence of CuOTf (10 mol%) as the catalyst, G-TqPy L5 (12 mol%) as the ligand, Cs₂CO₃ as base at 5 °C under blue LED irradiation for 44 h (Scheme 17) [44]. Substrate scope studies disclosed that various substituted ethynylbenzenes such as different positions and electronic nature reacted smoothly with 2-vinyl-naphthalene and cyclobutanone oxime yielding the corresponding products in moderate yields and high enantioselectivities. Unfortunately, the bicyclo [4.2.0]octa-1(6),2,4-trien-7-one oxime ester and 2,2,4,4-tetramethylcyclobutane-1,3-dione oxime ester gave the desired product in poor yields and enantioselectivities, probably due to steric hindrance resulting in decreased reactivity of the cyclobutanone oxime ester. A possible mechanism is proposed in Scheme 17. A chiral anionic guanidine-amide Cu^I acetylide complex absorbs visible light to form the triplet state, which then performs a SET process with oxime ester 44 to generate the Cu^II complex and an iminyl radical, and then the iminyl radical transforms into cyanoalkyl radical via carbon–carbon cleavage and the alkyl radical adds to alkene to give allyl radical 46. Subsequently, Cu^II complex and radical 46 undergo corresponding selective coupling to obtain Cu^III species, and then reductive elimination of Cu^III species affords the desired product.

In 2025, Guo and Zhang et al. reported a photoinduced copper-catalyzed enantioselective three-component alkylalkynylation of alkenes (Scheme 18) [45]. This method employs more economical and readily available acetonitrile as the cyano source. The reaction system is applicable for late-stage modification of various complex molecules, such as estrone, naproxen, menthol, and glucose derivatives, affording the target products in moderate to good yields. Furthermore, the resulting products can be further transformed into a wide range of functional groups, including amides, ketones, aldehydes, alcohols, carboxylic acids, and alkenes, demonstrating the broad applicability and synthetic versatility of this methodology. Although this method exhibits good compatibility with a wide range of C(sp³)-H precursors (including acetonitrile, ketones, esters, amides, ethers, and amines), selective functionalization at the α-sulfur site was observed for substrates containing both α-oxygen and α-sulfur atoms. However, whether this selectivity—presumably governed by polarity matching—possesses universal predictive power requires validation through further case studies. Furthermore, the complex ligand L10 is employed at a loading as high as 12 mol%. Further breakthroughs are still required in subsequent substrate universality validation and catalyst economy optimization.

2.3. Enantioselective C-O Difunctionalization

In 2022, Chen, Xiao and Guan et al. disclosed a visible light-induced, copper-catalyzed asymmetric three-component coupling reaction for the C−O bond formation using alkenes, oxime esters, and carboxylic acids [46]. The optimized conditions employed Cu(CH₃CN)₄PF₆ (5.0 mol%) as the catalyst with L10 (6.0 mol%) as the chiral ligand in DCE under an argon atmosphere at 0 °C. The protocol demonstrated its utility by facilitating the late-stage modification of various pharmaceuticals and natural products. A possible mechanism is proposed in Scheme 19. The L/Cu^I species is excited to its excited-state [L/Cu^I]* species under purple light irradiation. Then, the reaction proceeds through a photoinduced SET from the [L/Cu^I]* species to the oxime ester to generate an iminyl radical and a L/Cu^II species. Subsequently, the iminyl radical undergoes ring-opening to form cyanoalkyl radical, which then adds to an alkene to generate a benzylic-type radical. Finally, L/Cu^II species coordinates with benzylic-type radical to form L/Cu^III complex and undergoes reductive elimination to form the final product.

At the same time, Chen and Xiao et al. disclosed a Cu-catalyzed three-component radical 1,2-carbon-oxygen bifunctionalization of 1,3-dienes to afford a series of corresponding products [47]. The reaction was performed under an argon atmosphere using Cu(CH₃CN)₄PF₆ (2.0 mol%) as the catalyst, L11 (2.4 mol%) as the ligand and DCM as the solvent at room temperature under purple LED irradiation for 4 to 8 h (Scheme 20). The group synthesized a series of chiral aryl-substituted 1,3-dienes, a range of styrenes bearing weak electron-donating groups (such as Me, tBu and OMe) at the para-, meta-, or ortho-positions worked well and delivered the corresponding products in good yields and enantioselectivities (up to 96%). Moreover, the reaction can accommodate a variety of carboxylic acids, aromatic carboxylic acids with different substituents, heteroaromatic carboxylic acids, aliphatic carboxylic acids, furnishing the diversified products. A plausible mechanism is proposed in Scheme 20. Firstly, catalytic cycle begins with the excited-state [L/Cu^I]* complex by purple light irradiation upon L/Cu^I. Then, the reaction proceeds through a photoinduced SET from the [L/Cu^I]* complex to the oxime ester to generate an iminyl radical and a L/Cu^II species. Next, the iminyl radical adds to the 1,3-diene to form an allylic radical, which is trapped by L/Cu^II species to form allyl L/Cu^III complex and undergoes enantioselective reductive elimination to furnish the desired product.

In 2024, Chen et al. developed a Cu-catalyzed three-component radical 1,2-azidooxygenation of 1,3-dienes to afford a series of corresponding products (Scheme 21) [48]. Under an atmosphere of argon, the products were obtained with excellent yields and enantioselectivities (up to 98%) in the presence of Cu(CH₃CN)₄PF₆ (2.0 mol%) as the catalyst, (S,S)-L12 (2.4 mol%) as the ligand and DCM as the solvent at room temperature for 24 h. The group synthesized a series of chiral aryl-substituted 1,3-dienes, a range of styrenes bearing weak electron-donating groups at the para-, meta-, or ortho-positions worked well and delivered practical and efficient approach for the synthesis of valuable azidated chiral allylic esters. Unfortunately, electron-withdrawing groups result in moderate yields. A possible mechanism is proposed in Scheme 21. Firstly, catalytic cycle begins with the excited-state [L/Cu^I]* species by purple light irradiation upon L/Cu^I species, then, the [L/Cu^I]* species to facilitate SET to generate an azidyl radical and L/Cu^II species and release of an amidyl anion. Next, the azidyl radical adds to the 1,3-diene to form an allylic radical, which is trapped by L/Cu^II species to form an allyl L/Cu^III complex and undergoes enantioselective reductive elimination to furnish the desired product.

In 2023, Chen et al. developed a photoinduced copper-catalyzed asymmetric radical three-component cross-coupling of 1,3-enynes with oxime esters and carboxylic acids (Scheme 22) [49]. The initial reaction was performed using 1,3-enyne 61, oxime ester 62, and para-ester-substituted benzoic acid 63 as the model substrates. The optimal conditions were Cu(CH₃CN)₄PF₆ (2.0 mol%) and ligand (S,S)-L12 (2.4 mol%) in DCE at room temperature for 24 h under purple LED irradiation. Moreover, the reaction could be conducted on a gram scale. Notably, under the optimized conditions, various 1,3-enynes, 3-aryl-substituted 1,3-enyne derivatives, 1,3-enynes with functional groups at the meta- or ortho-position, 1,3-enynes with a naphthyl or thiophenyl substituent, and alkyl-substituted 1,3-enynes were found to deliver the corresponding products in high yields and excellent enantioselectivities. Most products exhibited ee values above 90%, with some reaching up to 99%, demonstrating excellent chiral control. Although a large number of substrates were tested, most of the 1,3-enynes employed were aryl-substituted, with alkyl-substituted enynes being scarcely explored. Additionally, while the authors demonstrated the modification of drug molecules, no catalyst recovery experiments were conducted, leaving the assessment of practical application potential insufficient. A possible mechanism is proposed in Scheme 22.

3. Visible Light-Mediated Nickel-Catalyzed Asymmetric Difunctionalizations of Alkenes

Nickel, as a common and abundant transition metal catalyst, has been extensively employed in organic synthesis due to its rich redox chemistry, broad applicability, and high catalytic efficiency [50,51]. Furthermore, the integration of nickel catalysis with photoredox processes utilizes light energy to drive distinctive SET pathways, thereby facilitating the generation of transient nickel intermediates or radical species that are typically inaccessible under conventional thermal conditions. This synergistic catalytic strategy significantly expands the design space for enantioselective difunctionalization of olefins, opening new avenues for the development of green and efficient synthetic methodologies [25]. The common cooperative catalytic mechanisms are illustrated below (Scheme 23).

3.1. Enantioselective Alkylarylation of Alkene

In 2020, Chu et al. reported nickel-catalyzed enantioselective three-component fluoroalkylarylation strategy for the synthesis of products from unactivated alkenes 66 with aryl halides and perfluoroalkyl iodides [52]. A variety of 5-bromopyrimidines bearing electron-withdrawing and electron-donating groups all worked well. In 2020, Chu and Gutierrez et al. reported the first asymmetric dual photoredox/nickel-catalyzed three-component alkylarylation of alkenes, enabling the construction of chiral α-aryl carbonyls under redox-neutral and mild visible light conditions (Scheme 24) [53]. The protocol accommodates a wide range of aryl bromides, including electron-rich, electron-deficient, and heteroaryl systems, with excellent chemoselectivity for bromides over chlorides. The method enables concise, enantioselective synthesis of pharmaceutically relevant compounds, including Flurbiprofen analogs and the lead compound for a glucokinase activator piragliatin. Although significant progress has been made in this study, there is still room for improvement in certain aspects. For example, primary alkyltrifluoroborates such as methyl and benzyl derivatives performed poorly under the standard conditions, predominantly generating two-component aryl-alkyl cross-coupling byproducts. Additionally, the method relies on an iridium-based photocatalyst, and the modification of drug-derived substrates was not demonstrated on a gram-scale, leaving the practical applicability of this method questionable.

In 2021, Mao and Walsh et al. developed a visible light-promoted nickel/photoredox-catalyzed enantioselective reductive alkylarylation of acrylates 66 with alkyl bromides 67 and aryl bromides 68 (Scheme 25) [54]. The reaction employed 4CzIPN PC7 (10 mol%) as the organic photocatalyst, NiBr₂ (10 mol%) as the catalyst and chiral bimidazoline BiIM ligand L14 (11 mol%) as the chiral ligand, Hantzsch ester (3.0 equiv) as the organic reductant and Cy₂NMe (3.0 equiv) as the base in DMA (0.33 M) at room temperature under blue LED irradiation for 24 h. In the protocol, Hantzsch ester replaces organometallic reagents and stoichiometric metal reductants. This reaction can be compatible with various aryl bromides and alkyl bromides including electron-withdrawing, neutral, and electron-donating groups, providing corresponding products in good yields and enantioselectivities. In addition, the active molecules ibuprofen and geraniol derivatives were employed in this three-component reaction, achieving excellent enantiocontrol (89%, 88%) during the synthesis process. A possible mechanism is proposed in Scheme 25. Initially, the photoredox catalyst PC7 is irradiated to the activated state and HEH or Cy₂NMe donates an electron to form a radical anion. The resulting PC7 radical anion is oxidized by the L/Ni^II complex to generate PC7 and an L/Ni⁰ species, which adds to the aryl bromide to form a L/Ni^II-(Ar)Br complex. At the same time, the tertiary radical adds to the acrylate to form the α-carbonyl radical, which is subsequently captured by L/Ni^III species. Finally, the resulting L/Ni^III species then undergoes rapid reductive elimination to give the product. In 2025, Wang et al. reported a boron removal cross-coupling reaction catalyzed by nickel photoredox catalysis [55]. When a chiral biimidazoline was used, this method could be extended to the three-component carbonylation/carbonarylation reaction of alkenes, and seven enantioenriched α-aryl carbonyl compounds were successfully prepared (Scheme 26).

In 2024, an efficient visible light-driven nickel/photoredox complex-mediated three-component cross-electrophile coupling methodology for the alkylarylation of vinyl phosphonates to afford a series of α-aryl phosphonates products 74 was developed by Mao, Walsh and Xu et al. (Scheme 27) [56]. The optimal conditions were NiBr₂·DME (10 mol%) as the catalyst, PC7 (1 mol%) as the photocatalyst, L15 (11 mol%) as the ligand, Cy₂NMe (3.0 equiv) as the base, HEH (2.0 equiv) as reductant and THF as solvent under blue LED irradiation for 24 h. The desired products were obtained by various aryl halides 72 and alkyl bromides 73 in good to excellent enantioselectivities and moderate to good yields. This method avoids the use of brominated phosphorus reagents and organometallic reagents, and does not involve metal reductants. A possible mechanism is proposed in Scheme 27. The catalytic cycle begins with the PC7 photocatalyst absorbing blue light to reach its excited-state PC7* and then undergoes SET with HEH to generate a radical anion. At the same time, the active L/Ni⁰ catalyst precursor undergoes oxidative addition with aryl halides to deliver a L/Ni^II species, which then could undergo spin crossover to give a triplet tetrahedral species. Moreover, the alkyl radical generated from the reaction of the tert-butyl group with the alkene is captured by the triplet state tetrahedron to give an L/Ni^III intermediate. Finally, the L/Ni^III intermediate undergoes enantioselective reductive elimination to release the α-aryl phosphonate product and regenerate L/Ni^I complex. The resulting L/Ni^I complex abstracts a bromine atom from tert-butyl bromide to generate a L/Ni^II complex 75 and an alkyl radical. Subsequently, the complex 75 undergoes a SET reaction with radical anion 4CzIPN to regenerate L/Ni⁰ and completes the catalytic cycle.

In 2024, Nevado et al. disclosed a visible light-induced, nickel-catalyzed photoredox enantioselective alkene dicarbofunctionalization by photochemical aliphatic C–H bond activation to afford a series of high-value chiral products, including α-aryl/alkenyl carbonyls, phosphonates, 1,1-diarylalkanes, ether and alcohol feedstocks (Scheme 28) [57]. The standard reaction conditions proved compatible with a broad range of substrates, including both electron-deficient and electron-rich (hetero)aryl bromides, various cycloalkanes, and diverse alkenes such as acrylates, styrenes, and enones. Importantly, this protocol can be considered an effective method to synthesize biologically active molecules, such as estrone and cholesterol derivatives, which gave the corresponding products in moderate yields. A possible mechanism is proposed in Scheme 28. It begins with the generation of excited-state tetrabutylammonium decatungstate 80 by violet-light irradiation and abstracts a hydrogen atom from nucleophiles to generate a carbon radical and reduced decatungstate 81. Disproportionation of 81 provides doubly reduced decatungstate and regenerates ground-state TBADT PC8. Subsequently, the generated alkyl radical adds to alkene to form stabilized benzylic radical intermediates and the intermediates are captured by ligated L/Ni⁰ species to give L/Ni^I-alkyl intermediate. Then, the L/Ni^I-alkyl complex conducts oxidative addition with aryl bromides to deliver L/Ni^III-aryl intermediate. Next, this intermediate undergoes reductive elimination to release the product and regenerate L/Ni^I species to finish the catalytic cycle.

In 2024, Xiao and Shi et al. developed a dual photoredox/nickel-catalyzed enantioselective multicomponent cross-coupling reaction for the synthesis of chiral benzylic boronic esters (Scheme 29) [58]. This reaction features mild conditions, NiBr₂·diglyme (10 mol%) as the catalyst, Ir[dF(CF₃)ppy]₂(bpy)PF₆ PC10 (2 mol%) as the photocatalyst and chiral biimidazoline L18 (12 mol%) as the ligand in DME at 20 °C for 24 h. Under the optimized conditions, the reaction tolerated a variety of aryl bromides with diverse electronic and steric substituents (46 examples), including polycyclic, heterocyclic, bioactive motifs as well as tertiary alkyltrifluoroborates with good to high yields and high enantioselectivities (up to 98:2 er). However, this method still has limitations in the following aspects. First, when secondary alkyltrifluoroborates participated in the reaction, their enantioselectivity control was generally inferior to that of tertiary alkyl precursors, indicating that the stereorecognition ability of the current chiral ligand system for secondary radical intermediates still needs improvement. Second, although the authors demonstrated the potential of this method for the late-stage modification of complex natural products and drug molecules, the low yields of some substrates may limit its practical application in medicinal chemistry. Third, in terms of reaction scale-up, the yield of the gram-scale experiment (1.0 mmol) decreased significantly, and the enantioselectivity was also slightly reduced. A possible mechanism is proposed in Scheme 29. Upon irradiation with blue LED, photocatalyst PC10 is excited to its excited-state PC10* and then undergoes SET with the alkyltrifluoroborate to form the alkyl radical and the reduced Ir^II. Subsequently, the alkyl radical adds to the vinyl boronate 86 to give a new radical, which is rapidly captured by L/Ni⁰ species to furnish L/Ni^I species. Oxidative addition of aryl halide to L/Ni^I adduct gives L/Ni^III intermediate, which then undergoes facile reductive elimination to deliver the final product and regenerates L/Ni^I species.

In 2024, Mao et al. developed a nickel/photoredox dual-catalyzed enantioselective three-component cross-coupling reaction to access enantioenriched 1,1-diaryl(heteroaryl)alkanes (Scheme 30) [59]. This protocol employs Ni(acac)₂ (10 mol%) as the nickel catalyst, bisnitrogen L19 (11 mol%) as the chiral ligand, PC7 (8 mol%) as the photocatalyst, HEH (3.0 equiv) as the reductant and Cy₂NMe (3.0 equiv) as the base in DME/iPr₂O under blue light irradiation for 24 h. Notably, the reaction avoids the use of air- and moisture-sensitive organometallic reagents and stoichiometric metal reducing agents, successfully constructing 1,1-diaryl(heteroaryl)alkanes in good yields (up to 88%) and enantioselectivities (up to 99%). A possible mechanism is proposed in Scheme 30. Firstly, it begins with the generation of excited-state PC7* by blue light irradiation and undergoes SET with HEH to generate reduced 4CzIPN^•−. Secondly, the L/Ni⁰ catalyst undergoes the oxidative addition with aryl bromide to deliver the L/Ni^II species. Next, the alkyl bromide undergoes SET to generate alkyl radical, which undergoes a radical addition to the vinylarenes to give a new carbon radical. Then, the carbon radical is trapped by the L/Ni^II species to form a L/Ni^III species intermediate. After reductive elimination, L/Ni^III species intermediate affords the target 1,1-diarylalkane product and releases L/Ni^I species. The L/Ni^I species is oxidized by alkyl bromide to regenerate the L/Ni^II complex, which is reduced to regenerate the L/Ni⁰ catalyst via photoredox catalysis, thus closing the catalytic cycle.

In 2025, Yang and coworkers developed a photoredox/Ni dual-catalyzed enantioselective three-component 1,2-arylaminoalkylation of acrylates 87 with heteroaryl iodides 85 and α-silyl alkylamines 86 [60]. The protocol employs PC7 (2.5 mol%) as the photocatalyst, NiBr₂·diglyme (7.5 mol%) as the catalyst, bisimidazoline ligand L17 (12 mol%) as the chiral ligand in NMP/AC under blue LED irradiation at 30 °C for 12 h, allowing rapid access to enantioenriched α-aryl-substituted γ-amino esters in good yields with moderate to good enantioselectivities. Both electron-deficient and electron-rich aryl iodides—bearing substituents such as trifluoromethyl, ester, and aldehyde groups, as well as fluorine—were compatible with this protocol. Moreover, heteroaromatic iodides and structurally complex drug-derived substrates were also compatible. The synthetic utility of this strategy is highlighted by the diversification of complex biologically active compounds and concise synthesis of functional molecule intermediates. A possible mechanism is proposed in Scheme 31. The α-amino radical adds to the acrylate to deliver a β-aminoalkyl radical, which can be intercepted by L/Ni⁰ species to furnish L/Ni^I-alkyl intermediate. The resulting complex L/Ni^I intermediate oxidatively adds the aryl iodide to give the L/Ni^III-aryl-alkyl intermediate. Lastly, the intermediate undergoes rapid reductive elimination to give the product and L/Ni^I species. The group employed a variety of methods to thoroughly investigate the reaction mechanism, demonstrating the involvement of radical intermediates and the initial photoredox step. Unfortunately, the isolation and crystallographic characterization of key intermediates were not achieved, nor were DFT calculations performed to verify the enantiodetermining step.

In 2024, Chu et al. described a highly enantioselective visible light-induced three-component 1,2-alkylarylation reaction with vinyl boronates 89, (hetero)aryl bromides 90 and alkyl redox-active esters 91 (Scheme 32) [61]. The optimal reaction conditions were determined, using Ir[dF(CF₃)ppy]₂(dtbbpy)(PF₆) PC11 (1.0 mol%) as the photocatalyst, NiBr₂·DME (10 mol%) as the catalyst, chiral biimidazoline L20 (13 mol %) as the ligand, HE (2.0 equiv) as reductant and Me₂NBn (3.0 equiv) as additive in DMA/AC at −10 °C for 12 h under blue LED irradiation. A wide range of β-alkyl-α-aryl boronates with diverse substitution patterns and electronic properties were well tolerated, affording the corresponding products in moderate to good yields with excellent enantioselectivities. This reaction requires no metal reductants or alkyl halides, demonstrating broad substrate scope and good functional compatibility under mild conditions. A possible mechanism is proposed in Scheme 32. Firstly, the photocatalyst Ir^III PC11 is excited to its excited-state PC11* upon blue light exposure and the excited photocatalyst undergoes reductive quenching with HE to give the reduced Ir^II and a HE radical cation. In addition, a SET occurs between Ir^II and the NHP ester to release alkyl radical, which then adds to the vinyl boronate to generate the α-boryl radical. Meanwhile, the L/Ni⁰ complex undergoes oxidative addition with aryl bromides to give a L/Ni^II-Ar intermediate, which then combines with α-boryl radical to generate a L/Ni^III complex. Finally, the L/Ni^III complex undergoes reductive elimination to deliver the final product and L/Ni^I species.

3.2. Enantioselective Sulfonylalkenylation

In 2023, Shu et al. developed a visible light- and nickel-catalyzed enantioselective sulfonylalkenylation of alkenes, enabling rapid synthesis of β-chiral sulfones via a three-component strategy (Scheme 33) [62]. The reaction employed PC12 (1.0 mol %) as the photocatalyst, NiBr₂ (10 mol %) as the catalyst, ligand L2 (12 mol %) with NaOAc (1.0 equiv) and Na₃PO₄ (2.0 equiv) as additives in DMSO (0.1 M) under irradiation with a 3 W blue LED at room temperature to achieve chemoselective radical addition and asymmetric Csp³–Csp² coupling. Notably, the protocol features a wide substrate scope and good functional group tolerance. The synthesized β-chiral sulfones served as versatile intermediates for late-stage diversification such as hydrogenation and epoxidation, retaining stereochemical integrity. A possible mechanism is proposed in Scheme 33. At the beginning, the photocatalyst PC12 is irradiated to the activated state, which abstracts an electron from the sulfinate to form a photocatalyst radical anion and a sulfonyl radical and then the sulfonyl radicals add to styrene to generate the key intermediate benzyl radical. Next, the L/Ni⁰ species reacts with alkenyl halide to yield the L/Ni^II-alkenyl intermediate. Eventually, the key benzylic radical intermediate is enantioselectively trapped by L/Ni^II-alkenyl intermediate to give final product through reductive elimination and regenerates L/Ni^I species for the next catalytic cycle. Meanwhile, the photocatalyst radical anion reduces the L/Ni^I species to form the L/Ni⁰ species and release photocatalyst PC12.

In 2023, Nevado et al. developed a three-component strategy enabled by visible light- and Ni-catalyzed carbosulfonylation for the synthesis of enantioenriched β-aryl and β-alkenyl sulfones. (Scheme 34) [63]. The reaction employed L17-NiBr₂ (10 mol%) as the catalyst, PC7 (1 mol%) as the photocatalyst and crown ethers (9.0 equiv) as additive in DME at 0 °C for 48 h. With the optimized reaction conditions, a range of aryl iodides bearing electron-rich or electron-poor substituents and various heteroaryl, alkenyl bromides served as appropriate substrates to give the enantioenriched β-aryl and β-alkenyl sulfones in moderate yields with moderate to excellent enantioselectivities. A possible mechanism is proposed in Scheme 34. Firstly, the photocatalyst PC7 was excited to PC7* under violet-light irradiation, which oxidizes sodium benzenesulfinate to afford the radical anion of the photocatalyst and sulfonyl radical selectively adds to styrenes to generate benzylic radicals. Secondly, the benzylic radical is captured by the L/Ni⁰ complex to afford the L/Ni^I species and then undergoes oxidative addition of aryl halides to generate the L/Ni^III species. The L/Ni^III species undergoes reductive elimination to afford the carbosulfonylation product and the L/Ni^I species. Finally, the L/Ni^I species is reduced by the photocatalyst to regenerate L/Ni⁰ catalyst to close catalytic cycles.

3.3. Enantioselective Silylarylation

In 2025, Zhang et al. reported a novel photoredox/nickel dual catalytic system for the asymmetric three-component silylarylation of terminal alkenes under mild and environmentally friendly conditions (Scheme 35) [64]. Employing PC10 (10 mol%) as the photoredox catalyst, Ni(Py)₄Cl₂ (10 mol%) as the catalyst, L19 (13 mol%) as the ligand, morpholine as the promoter in DME at room temperature for 36 h with irradiation of blue LED, the method enables the efficient construction of chiral β-silyl-α-aryl propionates with high yields and excellent enantioselectivity (up to 96% ee). Although over 30 examples of substrate scope were demonstrated in this work, the applicability of alkenes remains limited. While electron-deficient alkenes exhibited good reactivity and enantioselectivity, electron-rich alkenes generally suffered from low yields and poor enantiocontrol; unactivated alkenes were completely ineffective. This limitation significantly restricts the generality of this method for the late-stage modification of complex molecules. Synthetic applications highlight its utility through subsequent transformations such as hydrolysis, reduction, and intramolecular Friedel–Crafts acylation, leading to pharmacologically relevant chiral structures including tropic acid analogs and sila-isoflavanones.

4. Visible Light-Mediated Palladium-Catalyzed Asymmetric Difunctionalizations of Alkenes

Palladium stands as a cornerstone in transition metal catalysis, playing an indispensable role in modern organic synthesis [65,66]. The integration of palladium catalysis with emerging strategies such as photoredox or electrochemical processes has further transcended the limitations inherent in conventional thermal reactions. This synergistic effect facilitates the generation of highly reactive palladium intermediates or radical species through SET pathways, establishing a novel and powerful platform for challenging transformations [67].

4.1. Enantioselective Aminoalkylation

An efficient visible light-driven hydrogen atom transfer (HAT) methodology for Pd-catalyzed enantioselective three-component carboamination of aryl-substituted 1,3-dienes to afford a series of corresponding allylic amines products was developed by Gong and Han et al. (Scheme 36) [68]. This reaction tolerated a wide variety of dienes, aliphatic C–H partners, and primary/secondary amines. Moreover, the group successfully transformed chiral allylic amine products, further demonstrating the high versatility of this protocol. Unfortunately, cyclohexyl-substituted dienes afforded only 52% yield and 55% ee, indicating the limited compatibility of this method with non-conjugated or sterically hindered dienes. Optimizing ligand structures or adjusting reaction conditions could improve the tolerance for unactivated dienes. Additionally, the use of excess toluene in the reaction results in low atom economy; introducing alternative directing group strategies may help reduce the substrate loading. A possible mechanism is proposed in Scheme 36. Upon blue light irradiation, the L/Pd⁰ catalyst is photoexcited to produce excited-state L/Pd⁰*, which reduces excess aryl bromide via SET to generate an aryl radical and L/Pd^I species. Then, the aryl radical undergoes hydrogen atom transfer with the C-H partner to generate an alkyl radical and an aryl byproduct. Afterwards, the radical selectively adds to diene to form a stabilized allyl radical intermediate. The radical recombines with the L/Pd^I species to form the L/Pd^II complex, and the amine attacks this L/Pd^II complex to generate the chiral allylamine product and regenerate the L/Pd⁰ catalyst.

In 2024, Yang and Xiang et al. reported visible light-driven palladium-catalyzed enantioselective 1,2-carboamination of 1,3-dienes using NHP esters and 1,3-dienes in the presence of K₂CO₃ as base, Pd(PPh₃)₄ (20 mol%) as the catalyst and (R)-BINAP L22 (30 mol%) as the ligand at 0 °C for 48 h (Scheme 37) [69]. This protocol offers operational simplicity, photocatalyst-free conditions, and broad functional group tolerance. Under the optimum conditions, aryl-substituted dienes bearing both electron-donating and electron- withdrawing groups, heteroarenes, naphthyl and 1,2-disubstituted dienes were well tolerated and delivered the products in moderate yields and good enantioselectivities. Unfortunately, in this reaction system, the use of Pd(PPh₃)₄ at a loading of 20 mol% and the ligand at 30 mol% is unfavorable for large-scale applications. Efforts should be made to explore supported catalysts or develop low-loading, high-efficiency catalytic systems. Furthermore, unactivated alkenes (such as aliphatic dienes) were completely incompatible with this reaction. A possible mechanism is proposed in Scheme 37. Initially, the photoexcited L/Pd⁰ reduces the alkyl NHP ester via SET to produce hybrid alkyl palladium radical species, which is accompanied by the release of NHP anion and CO₂. Then, the alkyl radical adds to the terminal carbon of the 1,3-diene to produce the allyl radical complex, which then undergoes a radical recombination to generate a π-allylpalladium complex. Finally, the NHP anion nucleophilically attacks the π-allylpalladium complex to afford the target 1,2-carboamination product and regenerates the palladium catalyst.

4.2. Enantioselective Alkylsulfonylation

Yang and Xiang et al. reported a visible light-driven palladium-catalyzed enantioselective 1,2-alkylsulfonylation of 1,3-dienes from readily available alkyl bromides 118, 1,3-dienes 116, and sodium sulfinates 117 (Scheme 38) [70]. The reaction employed Pd(PPh₃)₄ (10 mol%), (S)-tol-BINAP L23 (15 mol%) in 1,4-dioxane at 10 °C for 48 h under irradiation by blue LEDs. The protocol was successfully applied to the late-stage functionalization of drug-derived molecules such as sildenafil and glibenclamide, and could be scaled up to gram-scale synthesis. However, the reaction was incompatible with tertiary alkyl bromides. It is noteworthy that DFT calculations were employed to support multiple key steps in this work, such as verifying the stereoselectivity-determining step involving the allyl-Pd intermediate. Furthermore, a variety of experimental techniques were systematically utilized to validate the radical pathway and a palladium catalytic cycle. A possible mechanism is proposed in Scheme 38. Under blue light irradiation, L/Pd⁰ catalyst is photoexcited, which undergoes SET with alkyl bromides to generate alkyl radicals and a L/Pd^I-Br intermediate. Then, the alkyl radical preferentially adds to the terminal position of the 1,3-diene to form an allylic palladium radical complex. This radical then rearranges into the more stable π-allylpalladium intermediate, which is attacked by the sulfinate anion to give the target product and regenerate the L/Pd⁰ catalyst.

5. Visible Light-Mediated Cobalt-Catalyzed Asymmetric Difunctionalizations of Alkenes

Cobalt is relatively low-cost, making it crucial for industrial-scale applications and green chemistry. It commonly exists in Co⁰, Co^I, Co^II, and Co^III oxidation states. This diversity enables participation in SET processes, which are essential for initiating radical reactions [71]. The integration of photocatalysis with cobalt catalysis to construct a synergistic catalytic system demonstrates unique advantages that are insurmountable for single catalytic modes. The core of this strategy lies in utilizing the reactive species generated by the photosensitizer under photoexcitation to couple with the cobalt catalytic cycle, thereby overcoming thermodynamic or kinetic reaction barriers [72].

Enantioselective Hydroamination

In 2025, Zhang et al. reported a dual photoredox and chiral cobalt catalysis strategy that enables the intermolecular enantioselective hydroamination of unactivated alkenes with simple amines [73]. The success of this reaction hinges on the synergistic combination of a chiral Salen cobalt catalyst and the photocatalyst PC13 under irradiation with blue LEDs. Employing collidinium triflate as a proton source in THF solvent under mild conditions, this system efficiently constructs α-chiral tertiary amines. The protocol exhibits a broad substrate scope, demonstrating excellent compatibility with a range of diaryl-substituted unactivated terminal alkenes and N-alkyl anilines bearing diverse electronic properties, affording the desired products in high yields and with high enantioselectivities. Nevertheless, enantiocontrol remains a challenge for aliphatic alkenes. A possible mechanism is proposed in Scheme 39. Cobalt-hydride-mediated hydrogen atom transfer to generate an alkyl radical, enantioselective trapping of this radical by the chiral cobalt catalyst, photoinduced single-electron oxidation to form a highly reactive alkyl-cobalt intermediate, and final C–N bond formation via nucleophilic substitution by the amine.

6. Conclusions

The strategy combining photocatalysis with transition metal catalysis has opened new avenues for asymmetric alkene difunctionalization reactions. This dual catalytic system combines highly reactive radical species generated through photoexcitation with the precise stereochemical control of transition metal catalysts, achieving chemoselectivity and stereoselectivity that traditional methods struggle to attain. In these synergistic systems, the stereoelectronic control models for the four metals—copper, nickel, palladium and cobalt—each have their own distinct characteristics. Copper catalysis typically relies on photoinduced π-allyl-Cu^III complexes, where the stereodetermining step is the reductive elimination, with chiral bisoxazoline ligands being key. Nickel catalysis often follows a Ni⁰/Ni^II/Ni^III cycle, with stereochemistry dictated by the enantioselective capture of an alkyl radical at the Ni^II center, where chiral bisoxazoline and biimidazoline ligands excel. Palladium catalysis proceeds via a π-allyl-palladium intermediate under photoexcitation, and its stereodetermining step is the nucleophilic attack on the π-allylpalladium complex to form the C–N bond, with chiral bisphosphine ligands, exemplified by BINAP, playing a crucial role. Cobalt catalysis operates through a Co^III-H-mediated hydrogen atom transfer process, where stereochemistry is established during the addition of an alkyl radical to form the C-Co bond; the chiral Salen ligands play an important role. From the perspective of applicable scenarios, the copper catalytic system excels in the construction of C–O and C–N bonds, and is particularly suitable for the transformation of electron-deficient alkenes and 1,3-enynes. The nickel catalytic system, leveraging its flexible oxidation states and compatibility with a wide range of radical precursors, has emerged as the dominant platform for three-component carboarylation reactions. Palladium catalysis, built upon π-allyl chemistry, achieves direct functionalization of C(sp³)–H bonds through photoexcitation, thereby significantly expanding the pool of accessible alkyl sources. Cobalt catalysis, operating via HAT-mediated hydrofunctionalization of alkenes, exhibits unique regioselectivity and potential for engaging unactivated alkenes (

Table 1. Comparative summary of catalytic cycle mechanisms for four transition metals. The table outlines key features including typical oxidation states, preferred ligand types, favored alkene substrates, and typical bond formations. Photocatalyst compatibility, mechanistic steps governing stereoselectivity, and the primary strengths and limitations of each metal system are also compared. Representative references are provided for each catalytic system.

	Copper	Nickel	Palladium	Cobalt
Typical oxidation states	CuI/CuII/CuIII	Ni0/NiII/NiIII	Pd0/PdII	CoII/CoIII
Preferred ligand types	Bisoxazoline	Bisoxazoline; Biimidazoline	Bisphosphine	Salen
Stereoselectivity step	Reductive elimination from CuIII	Enantioselective radical capture at NiII	Nucleophilic attack on π-allyl-Pd complex	C–Co bond formation via radical addition
Preferred alkene substrates	Electron-deficient alkenes, 1,3-enynes	styrenes, acrylates, vinyl phosphonates	1,3-Dienes	Unactivated alkenes
Typical bond formations	C–C, C–O, C–N	C–C, C–S, C–Si	C–N, C–S	C–N
Photocatalyst compatibility	Organic PC, Cu-excited (no external PC)	PC1, PC7	Pd-excited (no external PC)	Salen-Co with organic PC
strengths	Versatile for C–O/C–N bonds; well-developed Box ligands	Flexible oxidation states; broad radical precursor compatibility	Direct C(sp3)–H functionalization; π-allyl chemistry	HAT-mediated functionalization of unactivated alkenes
limitations	Limited to activated alkenes	High ligand loading	High catalyst loading; limited to conjugated dienes	Limited substrate scope; emerging field
Representative references	[29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49]	[52,53,54,55,56,57,58,59,60,61,62,63,64]	[68,69,70]	[73]

). This diversity of catalytic modes enables synthetic chemists to select the optimal catalytic system based on the structural features of the target molecule.

The selection of a photocatalyst is not a unidimensional choice but a dynamic decision-making process that necessitates a comprehensive consideration of transition metal catalyst compatibility, the activation difficulty of the radical precursor, and the overall economy of the reaction system. From the perspective of compatibility with the metal catalyst, organic dyes represented by 4CzIPN have become ideal partners in nickel/photoredox synergistic catalysis due to the excellent match of their redox potentials with the Ni⁰/Ni^II cycle. When considering the activation demands of the radical precursor, classical Ir complexes demonstrate robust initiation efficiency for moderately active precursors like alkyltrifluoroborates. However, for substrates that are extremely difficult to reduce, such as NHP esters or unactivated alkenes, it is necessary to utilize highly reducing organic dyes like PTH and PAZ, or even EDA catalytic strategies. In scenarios pursuing atom economy and extreme system simplification, EDA complex catalysis leverages in situ interactions between substrates and additives to avoid potential interference from exogenous photocatalysts, showcasing unique potential. In mechanistic studies, photoredox catalysts generate radical intermediates through SET processes, which engage in unique interactions with transition metal species, including radical addition, oxidative addition, and reductive elimination elementary steps. This synergistic catalytic mode not only expands the diversity of reaction types but also significantly enhances atom economy and step economy of reactions. The high enantioselective transformations achieved under mild conditions particularly demonstrate the advantages of this strategy in green chemistry and sustainable development.

Despite significant advances, this field still faces numerous challenges. Unactivated terminal and internal alkenes remain the most challenging substrate class. Unlike activated olefins, unactivated alkenes exhibit low reactivity due to their inability to stabilize the nascent radical intermediates generated during the reaction, compounded by significant steric hindrance. In addition, challenges such as prolonged reaction times, dependence on specific light sources, and difficulties in achieving industrial-scale synthesis remain to be addressed. Therefore, developing novel visible light photocatalysts, designing multifunctional chiral ligands, and establishing continuous flow reaction technologies will drive the field forward. For future industrial applications, this field still faces three core challenges. First, catalyst loading remains excessively high, with most current systems requiring 5–20 mol% of precious metal catalysts and 10–30 mol% of chiral ligands, far from meeting the demands of industrial catalysis. Second, the sensitivity of reaction conditions, including stringent requirements for light intensity, solvent, oxygen, and moisture, limits their stability during scale-up in continuous flow. Third, the substrate scope is fragmented, as individual catalytic systems are often effective only for specific types of alkenes or radical precursors, lacking general applicability. For industrial application, the most promising path is to combine the green chemistry principles of organic photocatalysis with the engineering advantages of continuous flow. This synergy directly addresses the three key criteria: it lowers material costs, simplifies operation by avoiding precious metals and solids handling, and achieves high productivity with low catalyst loadings. A notable gap in the current literature is the lack of sustainability metrics, including photocatalyst turnover numbers, quantum yields, and light energy efficiency. Although such data are rarely reported in the primary studies discussed herein, we emphasize that these parameters are crucial for assessing the practical utility and environmental footprint of metallaphotoredox catalysis. Future work should aim to routinely include these measurements to enable more meaningful comparisons and to guide the development of greener, more efficient synthetic protocols.

Currently, for photocatalytic and transition metal-catalyzed asymmetric difunctionalization of alkenes, commonly employed transition metals include copper and nickel, with a limited number of reports on palladium and cobalt. However, the use of other metals such as iron or rhodium has not yet been reported as of now. The abundance of metals such as iron and manganese may stem from their unique electronic structure, complex spin-state behavior, and the challenge of stereoscopic control over free radical intermediates. These might become the main obstacles in developing new reactions. The main strategies to overcome these obstacles might involve the cavity effect of chiral macrocyclic ligands, bimetallic catalysis, and the participation and regulation of alkali metal cations. The integration and development of these strategies will open up new paths for the application of abundant metal catalysts in future industrial settings. Therefore, the development of synergistic catalytic systems based on other inexpensive metals remains an important goal for researchers. As research continues to advance, asymmetric alkene difunctionalization via photo/transition metal dual catalysis will play an increasingly important role in drug synthesis, agrochemical development, and functional material preparation, providing more efficient and green synthetic strategies for constructing structurally diverse chiral molecular libraries.