Red light-driven electron sacrificial agents-free photoreduction of inert aryl halides via triplet-triplet annihilation

Selective photoactivation of inert aryl halides is crucial in organic synthesis. While red light offers advantages over blue light due to its superior penetration depth, its low energy presents a challenge for activating these inert substrates. Existing methods often rely on high-energy photons (UV and short-wavelength visible light) which suffer from shallow penetration depth, resulting in low yields and by-products, especially in large-scale reactions. Micro-flow reactors have been attempted to improve efficiency but remain inefficient and complex for large-scale industrial production. The development of red light-driven photoredox catalysis would significantly improve efficiency and scalability. However, the low energy of a single red photon (1.9 eV at 650 nm, compared to 2.8 eV for a 450 nm blue photon) makes it challenging to initiate the energy-demanding bond dissociation needed for aryl halide photoreduction. Recent attempts using stable radical anion-mediated multiphoton strategies and Z-scheme processes have shown promise, but these still require electron sacrificial agents, leading to side reactions and complex purification. Previously reported short-wavelength TTA systems also rely on sacrificial agents. While near-infrared (NIR) TTA-UC systems have been developed, their indirect energy transfer is inefficient for demanding reactions like inert aryl halide photoreduction. This study aims to overcome these limitations by developing a highly efficient, sacrificial agent-free, red light-driven photoreduction of inert aryl halides via a two-component TTA system.

The literature extensively documents the importance of photoredox catalysis in chemistry and materials science, particularly the activation of inert aryl halides. The use of short-wavelength visible light (<500nm) and UV light is common but suffers from drawbacks related to penetration depth and byproduct formation, especially at scale. Efforts to address these limitations include the use of microfluidic reactors and the exploration of alternative strategies like multiphoton excitation and Z-scheme processes. However, these approaches often introduce complexities, such as the requirement for sacrificial electron donors, which hinders scalability and sustainability. Triplet-triplet annihilation (TTA) upconversion has emerged as a promising technique for photoredox catalysis, but typically relies on short-wavelength excitation sources and/or sacrificial agents. The challenge of achieving efficient red-light-driven photoreduction of aryl halides without sacrificial agents has remained largely unsolved until now.

This study investigates a two-component TTA system for the red light-driven photoreduction of inert aryl halides. The system consists of a red light-absorbing photosensitizer, PdTPBP (meso-tetraphenyl-tetrabenzoporphine Palladium complex), and a perylene derivative (Py) acting as a metal-free photocatalyst. The authors discovered that perylene itself can efficiently catalyze the photoreduction of aryl halides without sacrificial agents, utilizing an oxidation quenching cycle. The PdTPBP photosensitizer absorbs red light (656 nm) and transfers its energy to the perylene derivative via a TTA process, generating a high-energy excited state of perylene capable of reducing aryl halides. The efficiency of this process is enhanced by modifying the perylene structure (Py1-Py4) to restrict the rotation of the phenyl moiety, suppressing triplet non-radiative decay. This modification increases the efficiency of singlet excited state generation via TTA. The researchers performed electrochemical analysis to determine the oxidation and reduction potentials, UV-Vis and fluorescence spectroscopy to characterize the photophysical properties, and density functional theory (DFT) calculations to study the electronic structure and excited states of the perylene derivatives. Various coupling reactions were conducted to demonstrate the versatility of the system, including reactions with different aryl halides, coupling partners (pyrrole derivatives, 1,3,5-trimethoxybenzene, indole, triethyl phosphite), and even late-stage modification of biologically active molecules. The effects of reaction volume (2 mL vs. 20 mL) were also studied to compare penetration depths of blue and red light. The mechanism was explored by calculating Gibbs free energy of electron transfer and reaction kinetics to confirm that singlet excited perylene, rather than the triplet state, participates in the photoreduction.

The authors successfully demonstrated red light-driven (656 nm) photoreduction of aryl halides without the need for electron sacrificial agents. Perylene derivatives were identified as efficient, metal-free photocatalysts. The introduction of PdTPBP as a photosensitizer enabled the utilization of red light, and the modification of perylene to restrict phenyl rotation significantly enhanced the TTA-mediated photoreduction. The TTA-UC efficiency was improved from 7% (PdTPBP/Py0) to 23% (PdTPBP/Py4) by introducing steric hindrance. This improvement translated into higher product yields and turnover numbers in the photoreduction of 4-bromoacetophenone with N-methylpyrrole. The optimized PdTPBP/Py4 system showed a 79.4% yield under 656 nm illumination, exceeding the 70.3% yield obtained with direct blue light excitation using Py4. The longer-lived singlet excited state (upconverted delayed fluorescence lifetime of 510.3 µs) generated by TTA was attributed to this enhanced performance. The red light-driven system also demonstrated superior performance in larger-scale reactions (20 mL) compared to blue light, showcasing the advantage of deeper light penetration. A range of coupling reactions with different aryl halides and trapping reagents confirmed the broad applicability of the method, with the optimized system achieving high yields in several instances. Mechanistic studies revealed that the singlet excited state of perylene derivatives is responsible for the photoreduction, consistent with thermodynamic and kinetic analyses.

This work addresses the significant challenge of developing efficient red-light-driven photoredox catalysis for the activation of inert aryl halides. The authors successfully developed a system that overcomes the limitations of previous approaches by combining a red light-absorbing photosensitizer with a highly efficient metal-free photocatalyst (perylene derivatives) and eliminating the need for environmentally unfriendly sacrificial agents. The improved performance in larger reaction volumes highlights the practical advantages of this method for industrial applications. The mechanistic insights provide a deeper understanding of the TTA-mediated photoreduction and the role of perylene derivatives. This study opens up new possibilities for sustainable and efficient organic synthesis.

This research successfully demonstrates a red light-driven, electron sacrificial agent-free photoreduction of inert aryl halides using a triplet-triplet annihilation strategy. The use of perylene as a metal-free photocatalyst and the optimization of perylene derivatives to enhance TTA efficiency have resulted in a highly efficient and scalable method for photochemical activation. The superior penetration of red light enables the method to be effectively used in large-scale reactions. Future research could focus on exploring other photosensitizers and photocatalysts to further extend the applicability of this approach to a wider range of substrates and reactions.

The study primarily focuses on electron-deficient aryl halides. The efficiency of the method may be reduced for substrates with different electronic properties. While the system shows promise for large-scale applications, further optimization and scale-up studies are necessary to fully realize its industrial potential. The mechanistic studies provide strong evidence for the proposed mechanism, but further investigations might be needed to fully elucidate all the reaction pathways and intermediates.