The most frequent SET process in photoredox reactions usually entails the photocatalyst’s gain or loss of an electron. The production of active radical intermediates is facilitated by this mechanism (Prier et al., 2013; Romero and Nicewicz, 2016). Studies reveal that radicals like CF₃CO₂• or CF₃CO• undergo a quick decarbonylation process. The CF₃• radicals is produced as a result of the removal of CO₂ or CO during this process (Sawada et al., 1990; Zhong et al., 2015). The mechanistic understanding of CF₃• radical generation via decarboxylation or decarbonylation laid the foundation for developing photocatalytic trifluoromethylation strategies. A key milestone was achieved in 1993 when Mallouk’s group pioneered the photocatalytic trifluoromethylation of aromatic C-H bonds using CF₃CO₂Ag as the CF₃ source and TiO₂ as the catalyst under 500 W Hg lamp irradiation (Scheme 2A; Lai and Mallouk, 1993). This work marked the first demonstration of light-induced trifluoroacetate decarboxylative trifluoromethylation. However, the system suffered from metallic Ag deposition-induced catalyst deactivation, requiring excess TiO₂ to sustain reactivity, and exhibited limited regioselectivity for substituted arenes, resulting in mixed isomer products. Mechanistic investigations, including hexafluoroethane detection and radical trapping experiments, conclusively identified CF₃• radicals as the pivotal intermediates.

Subsequent advances addressing these challenges expanded both mechanistic understanding and substrate applicability. In 2017, Su and Li developed a Rh@TiO₂-mediated photocatalytic system for C–H trifluoromethylation of (hetero)arenes using TFA as a CF₃ source under 365 nm UV light. Their mechanistic studies revealed that hole-induced TFA oxidation generated CF₃• radicals, which coupled with arenes to form intermediates subsequently oxidized to final products, concurrent with H₂ evolution at the conduction band (Scheme 2B; Lin et al., 2017). Complementing this approach, Hosseini-Sarvari’s group employed CF₃CO₂Na and blue LED irradiation to achieve Au@ZnO-catalyzed trifluoromethylation of diverse C–X (X = I, Br, B) and C–H bonds (Bazyar and Hosseini-Sarvari, 2019). They proposed a dual radical pathway involving conduction band reduction-triggered aryl radical formation and valence band oxidation of CF₃CO₂ ⁻ to CF₃•, followed by selective radical coupling (Scheme 2C).

The field’s progression toward visible-light compatibility culminated in Jin’s 2020 work employing Ru(bpy)₃Cl₂ and stoichiometric (4-ClPh)₂SO to drive TFA decarboxylative trifluoromethylation under visible light (Scheme 2D). Mechanistic evidence suggested (4-ClPh)₂SO facilitates light-induced CF₃• generation via TFA decarboxylation, with subsequent dearomative addition to (hetero)arenes forming trifluoromethylated products. Nevertheless, the precise redox synergy between TFA and (4-ClPh)₂SO remained unresolved. While these innovations validated TFA-based CF₃• generation, persistent limitations—catalyst deactivation, erratic regioselectivity, and UV dependency—underscored the necessity for visible-light systems with enhanced control. This imperative catalyzed the emergence of photoelectrocatalytic paradigms that integrate optical and electrical fields to manipulate radical dynamics, offering new precision in trifluoromethylation strategies.

For instance, the Wu group reported a photoelectrocatalytic platform for direct (hetero)arene C-H trifluoromethylation using TFA, employing a graphite-Pt dual-electrode system under 5 mA current and 390 nm LED irradiation (Qi et al., 2023). This system addressed the scalability challenge by enabling continuous operation without catalyst degradation. Although effective for electron-deficient aromatics, regioselectivity limitations arose from radical-mediated pathways. Mechanistic studies revealed that photoinduced electron-hole pairs at the graphite anode selectively oxidize CF₃CO₂ ⁻ through electrostatic interactions, preserving neutral arenes. The generated CF₃• radicals undergo dearomative addition to form cyclohexadienyl intermediates, which are subsequently oxidized and deprotonated to regenerate aromaticity, with concurrent H₂ evolution at the Pt cathode ensuring charge balance (Scheme 3A). This dual-functional design not only resolved catalyst deactivation but also facilitated late-stage fluorofunctionalization of pharmaceuticals and natural products, demonstrating versatile synthetic applicability.

Building on this, Mo and Xuan introduced an ion-shielded photoelectrocatalytic strategy to address thermodynamic bottlenecks in C–H trifluoromethylation (Chen et al., 2024). Utilizing a Mo-doped WO₃ photoanode under 390 nm irradiation with a 2 V bias, CF₃CO₂ ⁻ anions formed an electrostatic shielding layer on the anode surface. This layer selectively blocked substrate access to photogenerated holes while promoting preferential oxidation of CF₃CO₂ ⁻ to CF₃• radicals. These radicals engaged (hetero)arenes via sequential oxidation-dearomatization-deprotonation cascades (Scheme 3B). This study elucidates the mechanistic paradigm for enabling selective electron transfer under extreme anodic polarization while establishing an operationally scalable platform for trifluoromethylation processes.

While photoelectrocatalysis has opened new mechanistic avenues for trifluoromethylation, conventional photocatalytic approaches have simultaneously advanced through systematic engineering of reaction systems. The foundations for these developments were established by early photoredox studies, particularly the seminal 1986 report by Barton and coworkers, who achieved the trifluoromethylation of 1-hydroxypyridine-2-thione using TFAA as the CF₃ source (Scheme 4A; Barton et al., 1986). This transformation, which proceeds via light-induced decarboxylation and rearrangement, represented a pioneering example of radical-mediated C–CF₃ bond formation. Building upon these fundamental insights, contemporary researchers have developed more sophisticated photocatalytic systems. The Pan group recently demonstrated an efficient, additive-free photoredox protocol utilizing TFAA for the trifluoromethylation of (hetero)aromatics and polarized alkenes (Song et al., 2023). This method exhibits remarkable substrate scope, accommodating natural product derivatives and pharmaceutical scaffolds, while mechanistic studies confirmed the generation of CF₃• radicals through visible-light-driven activation of TFAA.

Expanding the synthetic utility of this approach, Fan and Xu group developed a visible-light-mediated tandem trifluoromethylation/cyclization of quinazolinone-tethered alkenes (Zou et al., 2024). Employing fac-Ir(ppy)₃ irradiation at 457 nm, this transformation proceeds without strong oxidants to construct tri- and tetracyclic quinazolinones with excellent functional group tolerance. Detailed mechanistic investigations revealed a sequence involving: (i) photoinduced single-electron transfer to TFAA, generating a radical anion that fragments to form CF₃CO₂•; (ii) decarbonylation to CF₃• radicals; and (iii) radical addition followed by cyclization through deprotonation, hydrogen migration, and aromatization steps (Scheme 4B).

These seminal works on TFAA activation exemplify the remarkable progress in photocatalytic trifluoromethylation, yet the field continues to evolve through innovative system design and mechanistic understanding. A prime example of such advancement emerged from the Qing group’s 2018 work, which demonstrated visible-light-driven C–H trifluoromethylation of electron-deficient arenes using Ru(bpy)₃(PF₆)₂ and FPIFA (Yang et al., 2018). The protocol operated under mild conditions, delivering moderate-to-good yields albeit with limited regioselectivity. Mechanistic studies revealed that oxidative quenching of the photoexcited Ru(II)* species by FPIFA generated Ru(III) and a hypervalent iodine intermediate, which subsequently decomposed to release CF₃• radicals. These radicals underwent dearomatization with the arene substrate, forming a cyclohexadienyl radical intermediate. This intermediate followed dual oxidation pathways (mediated by Ru(III) or FPIFA) and subsequent deprotonation to yield the trifluoromethylated product (Scheme 5A). Further expanding the reaction scope, Wang, Liang and Wu subsequently developed a hydrotrifluoromethylation protocol for unactivated alkenes using NHBC as a radical precursor (Scheme 5B; Zhang et al., 2019). The proposed mechanism involves oxidative quenching of the photoexcited Ir(III) photocatalyst by NHBC, generating a CF₃CO₂• that undergoes decarboxylation to produce CF₃• radicals. These radicals add to alkenes, followed by HAT-mediated hydrogen abstraction to afford the final hydrotrifluoromethylated product.

While SET processes have dominated photoredox trifluoromethylation strategies, recent advances have unveiled the complementary potential of ET mechanisms in radical generation. This paradigm shift is exemplified by the Molander group’s innovative work employing benzophenone-mediated triplet-triplet energy transfer to activate trifluoroacetyl oxime esters (TFAOx) (Majhi et al., 2022). In contrast to conventional SET pathways that rely on redox potentials, this ET approach operates through direct photoexcitation of the oxime ester to its triplet state, triggering N–O bond homolysis and subsequent decarboxylation to generate both CF₃• and persistent iminyl radicals. The CF₃• radicals undergo kinetically favorable, irreversible and regioselective addition to terminal alkene positions, while the iminyl radicals propagate a chain cycle through interaction with additional oxime ester molecules, ultimately enabling synergistic C–C/C–N bond formation (Scheme 6).

EDA complexes, formed through non-covalent interactions between electron-rich donors (D) and electron-deficient acceptors (A), enable directional electron transfer under photoexcitation to generate solvent-caged radical ion pairs, which drive diverse reaction pathways such as radical recombination and polarity inversion (Lee and Kochi, 1992; Lima et al., 2016). This mechanism underpins versatile applications in organic synthesis, including catalytic alkylation of carbonyl compounds and stereoselective construction of complex architectures. The EDA paradigm exemplifies a sustainable strategy for achieving spatiotemporal control over reactivity, offering transformative potential for green synthesis of high-value molecules.

The Stephenson group pioneered this approach in 2015, reporting the trifluoromethylation of (hetero)arene C–H bonds using TFAA as the CF₃ source, Ru(bpy)₃Cl₂·6H₂O as the photocatalyst, and pyridine N-oxide as the oxidant, with pyridine generated in situ as the base (Beatty et al., 2015). This catalytic system exhibited operational simplicity and scalability to gram-scale synthesis, albeit with moderate regioselectivity and yields. In 2016, the same group expanded on this work, elucidating the mechanism and broadening the substrate scope to include complex (hetero)aromatics, highlighting its potential for pharmaceutical synthesis. Mechanistic studies revealed the formation of a 4-phenyl-1-(trifluoroacetoxy)pyridinium intermediate (I) from TFAA and 4-phenylpyridine N-oxide. Intermediate I generates CF₃• radicals through three distinct pathways: (i) EDA complex formation with 4-phenylpyridine N-oxide or aromatic substrates, followed by photoinduced electron transfer to yield radical intermediate II and subsequent release of 4-phenylpyridine and CO₂ (Scheme 7, Paths I and II); (ii) Intermediate I oxidizes Ru(II)* via a SET process, forming intermediate II and Ru(III) while releasing 4-phenylpyridine and CO₂ simultaneously (Scheme 7, Path III). The resulting CF₃• radicals undergo dearomatization via addition to arenes, forming cyclohexadienyl intermediates that re-aromatize upon oxidation to afford the final products (Beatty et al., 2016).

Building on these foundations, the Leibfarth group adapted the system in 2019 for the trifluoromethylation of industrial plastic waste and commercial plastics (Scheme 8A; Lewis et al., 2019). This work extended the synthetic utility of photocatalytic C–H trifluoromethylation to polymer functionalization, offering a potential strategy for upcycling plastic materials. Concurrently, Zhong and Tong developed a photocatalytic system for the tandem trifluoromethylation and cyclization of secondary benzylamines using TFAA/pyridine N-oxide/Ru(bpy)₃Cl₂ (Scheme 8B). Mechanistic studies proposed that photoinduced generation of CF₃• radicals—via EDA complex-mediated or SET pathways—initiated the transformation. This method demonstrated precise control over regioselectivity in complex heterocycle synthesis (Qi et al., 2019).

In 2020, the Stephenson group redesigned their EDA platform to mitigate back-electron transfer in homogeneous photocatalysis (Scheme 8C; Mcclain et al., 2020). By replacing Ru(bpy)₃Cl₂ with a dual-component EDA system (2-methoxynaphthalene donor + in situ-generated acylated 4-ethoxycarbonylpyridine N-oxide acceptor from CF₃COCl/TFAA), they achieved photosensitizer-free CF₃• radicals generation. EDA complex photoexcitation triggered charge transfer, yielding a 2-methoxynaphthalene radical cation and releasing CF₃• radicals via acceptor decarboxylation. The radicals engaged in Minisci-type C–H trifluoromethylation of (hetero)arenes, forming a dearomatized intermediate rearomatized by the radical cation to close the catalytic cycle. This strategy achieved moderate yields while eliminating traditional photosensitizers, though catalytic electron donor quantities remained essential. The work demonstrates charge-transfer system engineering to suppress parasitic electron loss, advancing practical late-stage aromatic C–H trifluoromethylation. Furthermore, the Rovis and Joe’s group developed a catalytic system for the trifluoromethylation of 1-methylpyridine-2(1H)-one to synthesize 1-methyl-3-(trifluoromethyl)pyridine-2(1H)-one, employing TFAA/pyridine N-oxide and Os(tpy)₂(PF₆)₂ as the photocatalyst (Scheme 8D). The Os(tpy)₂(PF₆)₂ complex uniquely harnesses near-infrared (NIR) and deep-red (DR) light with minimal energy loss, addressing the ∼25% energy dissipation observed in conventional Ru/Ir-based systems during excited-state quenching (Ravetz et al., 2020).

In 2022, Xu, Hu, et al. developed a photoinduced radical tandem trifluoromethylation/cyclization strategy using TFAA activated by pyridine N-oxide (Scheme 8E; Hu et al., 2022). This methodology leverages an EDA process to generate CF₃• radicals, which are captured by N-cyanamide olefins, yielding diverse trifluoromethylated quinazolinones with high efficiency and broad functional group tolerance. While photocatalytic trifluoromethylation strategies exploiting EDA complex mechanisms enable precise C–H activation and heterocycle construction under mild conditions—advancing sustainable fluorofunctionalization for pharmaceutical late-stage modification and complex molecule synthesis—their applicability remains constrained by inherent substrate scope limitations of EDA-mediated processes.

The LMCT process involves electron transfer from ligand orbitals to empty metal center orbitals, facilitating electron migration from the ligand to the metal center (Juliá, 2022). This process typically occurs in complexes with electrophilic, high-valent metal centers (e.g., Fe(III), Ag(II)) due to the reduced energy barrier for electron transfer. Electron-rich σ- or σ/π-hybridized ligands are more prone to LMCT transitions as they act as intrinsic electron donors (Juliá, 2022). This unique electron transfer mode has opened new pathways for chemical transformations under mild conditions and has been utilized in the trifluoromethylation of organic molecules via TFA decarboxylation (Liu et al., 2024). Mechanistically, a metal catalyst forms a complex with CF₃CO₂ ⁻, which undergoes the LMCT process under visible light to generate CF₃CO₂•. These radicals drive β-bond cleavage and subsequent transformations, underscoring the potential of LMCT in catalyzing decarboxylative trifluoromethylation of TFA and its salts.

The Juliá-Hernández group developed a visible-light-driven trifluoromethylation of (hetero)arenes using CF₃CO₂Na as the CF₃ source and an Fe(OTf)₂/4,4′-dimethoxy-2,2′-bipyridine/K₂S₂O₈ system under 405 nm irradiation (Scheme 9A; Fernandez-Garcia et al., 2024). Mechanistic studies revealed a LMCT mechanism: Fe-ligand complexes underwent photoinduced O–Fe bond homolysis, generating CF₃CO₂• radicals that decarboxylated to CF₃• radicals. These radicals participated in Minisci-type addition to electron-rich (hetero)aromatics, forming intermediates oxidized to final products. The protocol demonstrated broad substrate tolerance, including pyrroles, indoles, and bioactive molecules, with moderate to good yields. However, regioselectivity remained limited for polyfunctional substrates, reflecting inherent challenges in controlling radical pathways in complex systems.

The West group developed a redox-neutral hydrofluoroalkylation of alkenes under mild conditions, employing TFA as the CF₃ source, Fe(OAc)₂ as the catalyst, aryl thiols (ArSH) or disulfides (ArSSAr) as HAT mediators, Na₂CO₃ as the base, and 390 nm light irradiation (Bian et al., 2023). This dual catalytic system synergizes LMCT and HAT pathways through four key stages: (i) photolytic cleavage of the O–Fe bond in the Fe(II)–TFA coordination complex generates CF₃CO₂• concurrent with reduction of Fe(III) to Fe(II); (ii) decarboxylation of CF₃CO₂• produces CF₃• radicals; (iii) radical addition to alkenes forms transient carbon-centered radical intermediates; (iv) HAT from ArSH to the intermediate delivers hydrofluoroalkylated products (Scheme 9B). This mechanistically integrated platform enables late-stage installation of C–CF₃ bonds in structurally complex bioactive molecules, demonstrating compatibility with over twenty functional groups including electrophilic and protic moieties.

The Nocera group developed a dual-mode catalytic strategy for arene trifluoromethylation using Ag(bpy)₂(OTf)₂ and CF₃CO₂Na under visible light irradiation. The reaction proceeds via a LMCT mechanism: photoexcitation of the electrophilic Ag(II) center in the Ag(II)–CF₃CO₂ ⁻ coordination complex induces O–Ag bond homolysis, generating CF₃• radicals. Two distinct operational modes were engineered—(i) a stoichiometric photocatalytic system (2.0 equiv Ag) to offset incomplete Ag(I)-to-Ag(II) reoxidation, and (ii) a catalytic photoelectrochemical system (2.5 mol% Ag) leveraging anodic oxidation to regenerate Ag(II) from Ag(I), enabling sustained turnover. The CF₃• radicals engage in dearomatizing addition to arenes, followed by Ag(II)-mediated rearomatization to furnish trifluoromethylated aromatic products (Scheme 10A; Campbell et al., 2024). This LMCT-driven platform exhibits broad functional group tolerance under mild conditions, enabling scalable synthesis of pharmaceuticals and advanced materials. Notably, the photoelectrochemical variant circumvents high catalyst loadings typical of conventional photoredox systems, showcasing a synergistic integration of light- and electricity-driven processes for energy-efficient bond activation.

Niu, Li, and Lan recently reported a visible-light-driven photocatalytic fluorotrifluoromethylation of unactivated olefins using Fe(acac)₃ as the catalyst, TFAA as the CF₃ source, and Selectfluor as the fluorine donor (Scheme 10B). Mechanistic studies revealed that the active species is an in situ-formed Fe(III) complex with CF₃CO₂ ⁻, H⁺, and acetonitrile, where Brønsted acids enhance LMCT efficiency via hydrogen-bonding interactions. Upon visible-light irradiation, LMCT excitation triggers decarboxylation of the Fe(III) complex, generating CF₃• radicals and reducing Fe(III) to Fe(II). The CF₃• radicals add to unactivated olefins, forming a carbon-centered radical intermediate, which abstracts a fluorine atom from Selectfluor to yield fluorotrifluoromethylated products. The catalytic cycle is sustained through two pathways: direct Fe(II) reoxidation by intermediate II (Path B) or via a diaryl ether-derived cation radical generated by intermediate II-mediated oxidation (Path A) (Jiang et al., 2024).

LMCT catalysis has emerged as a powerful strategy for trifluoromethylation under mild conditions, leveraging high-valent metal complexes (e.g., Fe(III), Ag(II)) to generate reactive CF₃CO₂• radicals via photoinduced O–M bond cleavage. These systems exhibit broad substrate scope and operational simplicity, bridging the gap between photoredox and transition-metal catalysis. While challenges in regioselectivity control and catalytic turnover efficiency persist, their ability to enable sustainable transformations underscores LMCT’s potential for mechanistic innovation. This progress highlights LMCT’s transformative role in radical chemistry, prompting further exploration of scalability and selectivity in next-generation synthetic methodologies.