Photocatalysts

Photocatalysis has rapidly established itself as one of the most transformative developments in synthetic chemistry over the past two decades, and its integration into pharmaceutical research and medicinal chemistry has fundamentally expanded the range of chemical space accessible to drug discovery teams. Photocatalysts, compounds that absorb visible or ultraviolet light to generate electronically excited states capable of initiating single-electron transfer (SET), energy transfer, or hydrogen atom transfer (HAT) events, operate under conditions that are often mild, selective, and functionally tolerant in ways that classical thermal chemistry cannot match. The two principal classes of photocatalysts employed in pharmaceutical synthesis are polypyridyl transition-metal complexes, primarily iridium and ruthenium bis-terpyridyl and bis-phenylpyridyl complexes such as Ir(ppy)3, Ir[dF(CF3)ppy]2(dtbpy), and Ru(bpy)3, and organic photocatalysts including acridinium salts, 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene), and eosin Y. These catalysts, upon photoexcitation, become powerful single-electron oxidants or reductants that activate substrates via SET pathways that would be inaccessible under thermal conditions without high-energy or toxic reagents. In medicinal chemistry, the greatest impact of photoredox catalysis has been in the construction of sp3-rich C-C and C-heteroatom bonds, particularly at sp3 carbon centres adjacent to nitrogen, oxygen, and sulfur, providing direct access to the saturated, three-dimensionally diverse scaffolds that contemporary drug discovery prioritises over flat, aromatic systems. The marriage of photoredox catalysis with nickel or palladium cross-coupling, termed metallaphotoredox or dual catalysis, pioneered by MacMillan and others, has enabled C(sp3)-C(sp2) cross-couplings and C(sp3)-heteroatom bond formations from simple, abundant radical precursors including carboxylic acids, boronic acids, and alkyltrifluoroborates under mild, enantioselective conditions. Every major pharmaceutical company now deploys photoredox catalysis in its medicinal chemistry and process research workflows, and the field has moved from a niche academic methodology to an industrially viable platform supported by standardised photoreactors for both batch and continuous-flow operation.

Baloxavir marboxil (Xofluza, Shionogi/Roche), the first-in-class cap-dependent endonuclease (CEN) inhibitor for the treatment of influenza, approved by the FDA in 2018, has been the subject of a photoredox-enabled stereoselective synthesis developed by Shionogi's own process research chemists. The original commercial route to baloxavir marboxil relied on optical resolution, wasting up to 50% of material; the photocatalytic route, published in 2024, employs visible-light photoredox decarboxylation of L-serine as the key step to install the required chiral centre within the tricyclic triazinanone core, avoiding optical resolution entirely and delivering the target with high enantiopurity in fewer steps. Pregabalin (Lyrica, Pfizer), the first-in-class alpha-2-delta ligand approved for neuropathic pain and generalised anxiety disorder, has also been the subject of a published three-step photocatalytic synthesis, using a photoredox enantioselective desymmetrisation of a prochiral glutarate intermediate to install the required (S)-configured carbon centre, illustrating the value of photocatalysis in accessing chiral building blocks without classical resolution.

In organic synthesis, photocatalysts are central to a rapidly growing range of named and established reactions. The Giese radical addition, in which an alkyl radical adds to an electron-poor alkene, is now most commonly executed under photoredox conditions using redox-active ester precursors or carboxylic acids, providing mild and operationally simple access to C-C bonds that previously required toxic tin hydrides or harsh radical initiators. The Paternò-Büchi reaction, a [2+2] photocycloaddition between a carbonyl compound in its excited triplet state and an alkene, remains one of the most direct routes to strained oxetane rings, scaffolds of growing interest in medicinal chemistry for their three-dimensional character and favourable physicochemical properties. The Norrish type I and type II reactions exploit ketone photochemistry to cleave C-C bonds alpha to carbonyl groups or abstract gamma-hydrogen atoms, providing useful fragmentation and cyclisation pathways in total synthesis. The MacMillan alpha-arylation of aldehydes via photoredox/enamine co-catalysis was the foundational demonstration of asymmetric photoredox organocatalysis, and Minisci-type radical additions to heteroarenes under photoredox conditions have become standard tools for the late-stage diversification of drug-like heteroaromatic scaffolds. The Nicewicz anti-Markovnikov alkene hydrofunctionalisation, employing acridinium photocatalysts as potent single-electron oxidants, enables direct C-O, C-N, and C-S bond formation at alkene termini with complementary regioselectivity to classical acid-catalysed additions.

Our catalogue of photocatalysts and photocatalysis-compatible building blocks spans iridium and ruthenium polypyridyl complexes, organic photocatalysts, redox-active ester reagents, and a diverse range of radical precursors, to support medicinal chemistry programmes, late-stage diversification campaigns, and process research.