Key words
photoredox catalysis - deep red and near-infrared light - cross-coupling - reaction engineering - photodynamic therapy - photoaffinity labeling - proximity labeling - multiphoton excitation
Photoredox catalysis has emerged as a transformative tool in synthetic chemistry, carving out complementary pathways to established reactions as well as novel modes of substrate and catalyst activation for new chemistry. Indeed, photoredox catalysis has reinvigorated radical chemistry with its ability to access open-shell species under catalytic conditions. The merger of transition-metal-catalyzed cross-coupling with photoredox catalysis (‘metallaphotoredox catalysis’) has emerged as a powerful alternative for other cross-coupling-based technologies, with Ni catalysts featuring prominently. Metallaphotoredox catalysis has been especially transformative in how chemists approach C(sp2)–C(sp3) bond formation, where feedstock aliphatic coupling partners are used in place of organometallic nucleophiles. Furthermore, the ability to deliver energy in the form of light with pinpoint control defined by lasers has led to the patterning of materials using photoredox catalysts. Lastly, an emerging application uses photoredox catalysis to impact and probe biological systems.
The most commonly employed photoredox catalysts (PCs) absorb a photon of visible light, largely in the region of 380–450 nm (translating to approximately 63–70 kcal/mol), to access the singlet excited state. However, the high-energy light needed for photoredox catalysis can be problematic as several common functional groups can be directly photoexcited at these wavelengths. Indeed, control experiments sometimes indicate that the photoredox catalyst itself plays a minor role and that direct substrate excitation, or more commonly the intermediacy of electron donor–acceptor complexes, are responsible for the observed reactivity. Furthermore, catalytically generated intermediates may be directly photoexcited leading to productive chemistry or destructive side reactions.
With Ir- and Ru-derived photocatalysts, the singlet excited state initially accessed after excitation is extremely short-lived, decaying to the triplet within 10 ps via intersystem crossing (ISC). Triplet energies vary by catalyst structure: the Ir(ppy)3 singlet is 70 kcal/mol while the triplet is 60 kcal/mol. For Ru(bpy)3, those figures are 63 and 46 kcal/mol for the singlet and triplet excited states, respectively. From the triplet excited state, single-electron transfer (SET) and energy transfer (ET) steps can take place, which have largely defined the broad reactivity accessible within photoredox catalysis. Aside from the inherent waste associated with using 63 kcal/mol light (blue) to access a 46 kcal/mol excited state (red), the triplet energies matter for two interrelated fundamental reasons: they correspond to the energy potential that can be conveyed to the target molecule (ET steps), and they correlate with the oxidizing and reducing potential of the photocatalyst (SET steps), with numbers estimated from the Rehm–Weller equation. Thus, there has been emerging interest in developing technologies by which photoredox catalysis can use low energy deep red (DR) or near-infrared (NIR) light (specifically in the visible range of 660–730 nm) to access the same, or novel, excited state chemistry accessible with blue and purple light.
Employment of deep red or near-infrared light is extremely attractive. The relatively low energy associated with these wavelengths (35–40 kcal/mol) is unlikely to photoexcite any common functional groups. Red light also penetrates materials and tissues in ways that higher energy light does not. Indeed, the 600–800 nm window is known as the ‘phototherapeutic window.’ Emerging chemical biology applications of photoredox catalysis are more likely to benefit from lower wavelength excitation, avoiding cytotoxicity associated with high-energy light. For example, thymidine cross-links occur when cells are exposed to 400 nm light. Furthermore, within the context of photoaffinity labeling, the use of lower energy light mitigates background activation of organic molecules, thereby truly enabling spatiotemporal control in labeling only at the localized site of a red-light-absorbing photocatalyst.
Nevertheless, the successful translation of photoredox catalysis into regions of lower energy light is still nascent. The direct excitation of a photocatalyst from its singlet ground state (S0) to its triplet excited state (T1), a step mediated by spin-orbit coupling (SOC), would eliminate the wasteful energy loss associated with ISC (S1 → T1), enabling productive photocatalysis even with lower energy light. As such, our lab has identified a class of Os-based photocatalysts, as heavy atoms such as Os, Pd, and Pt are commonly incorporated to induce strong SOC and facilitate the spin-forbidden S0 → T1 excitation, that unlock DR and NIR photoredox catalysis. The development of new transition-metal-based photoredox catalysts, as well as red-light-absorbing organic dyes (e.g., methylene blue and fluorescein), will prove pivotal as the field shifts to red-light photoredox catalysis for applications such as batch-scale reactions and photoaffinity labeling. This review highlights the various approaches and fundamental photophysical concepts at play in red-shifting blue light photoredox catalysis.
Figure 1 Overview of photophysical principles of photoredox catalysis[1`]
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Figure 2 Overview of spin-forbidden excitation to access photoredox catalysis with NIR/DR light[1a]
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Figure 3 Selected metallaphotoredox applications of NIR/DR photocatalysis[2a]
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Figure 4 Engineering principles for scale-up[2a]
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Figure 5 Use of DR/NIR photoredox catalysis for biological applications[5`]
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Figure 6 Use of DR/NIR photoredox catalysis through multiphoton excitation[2c]
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Figure 7 Applications of DR/NIR photoredox catalysis for biological applications[2f]
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Figure 8 Overview of current triplet–triplet annihilation upconversion technology[8`]
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Figure 9 Applications of triplet–triplet annihilation upconversion to synthesis[8a]
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