Metallaphotoredox Catalysis in Organic Synthesis

Metallaphotoredox catalysis merges the complementary strengths of transition-metal and photoredox catalysis to enable novel pathways for bond formation under mild, sustainable conditions. In such dual catalytic schemes, a photoredox catalyst harvests visible light to generate reactive excited states or radical species, which in turn modulate the oxidation state of a metal centre. This synergy permits access to catalytic cycles involving high-energy intermediates—such as Ni(I)/Ni(III) or Cu(III) species—that are challenging to generate thermally. The approach has revolutionised carbon–carbon and carbon–heteroatom cross-couplings, facilitating C–O, C–N, C–S and C–P bond constructions with broad substrate scope and functional-group tolerance. Moreover, the development of heterogeneous and semi-heterogeneous platforms based on carbon nitride, poly(heptazine imide) or microporous polymers has advanced catalyst recyclability and lowered operational costs. Collectively, metallaphotoredox catalysis delivers unprecedented control over reactivity and selectivity, offering a versatile toolkit for pharmaceutical synthesis, agrochemical production and late-stage functionalisation of complex molecules.

Research from Nature Portfolio

Recent studies have addressed long-standing limitations in the field by unlocking electron-rich substrates and reducing catalyst loadings. A 2024 investigation demonstrated nickel-catalysed C–heteroatom bond formation from arylthianthrenium salts under light irradiation, enabling amination, oxygenation, sulfuration and halogenation of highly electron-rich aryl donors with a simple NiCl₂ system. In 2023, the integration of bipyridyl Ni complexes into crystalline potassium poly(heptazine imide) afforded heterogeneous catalysts that combine site isolation with photo/Ni cooperativity, achieving exceptionally low loadings and high turnover numbers in C–P, C–S, C–O and C–N cross-couplings. A complementary 2022 report introduced a copper-mediated etherification strategy in which photoinduced energy transfer generates aryl radicals from triplet states, bypassing energetically demanding oxidative addition and expanding C–O, C–N and C–F bond formation to aryl chlorides and a variety of nucleophiles.

Metallaphotoredox Catalysis in Organic Synthesis publication trend

The graph below shows the total number of articles in metallaphotoredox catalysis in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Metallaphotoredox catalysis: A dual-catalytic approach combining metal and photoredox cycles to access radical or ionic intermediates under visible light.

Oxidative addition: A step in which a metal centre inserts into a covalent bond, increasing its oxidation state by two units.

Reductive elimination: The reverse of oxidative addition, where two ligands on a metal combine to form a new bond, lowering the metal’s oxidation state.

Single-electron transfer (SET): The transfer of one electron between species, often initiated by an excited-state photocatalyst.

Heterogeneous catalysis: Catalysis in which the catalyst is in a different phase (usually solid) from the reactants, enabling separation and reuse.

Turnover number (TON): The number of substrate molecules converted per catalyst molecule before deactivation.

References

1. C–heteroatom coupling with electron-rich aryls enabled by nickel catalysis and light. Nature Catalysis (2024).
2. Poly(heptazine imide) ligand exchange enables remarkable low catalyst loadings in heterogeneous metallaphotocatalysis. Nature Communications (2023).
3. Copper-mediated etherification via aryl radicals generated from triplet states. Nature Synthesis (2022).
4. Visible‐Light Promoted C–O Bond Formation with an Integrated Carbon Nitride–Nickel Heterogeneous Photocatalyst. Angewandte Chemie International Edition (2021).
5. An Integrated Carbon Nitride‐Nickel Photocatalyst for the Amination of Aryl Halides Using Sodium Azide. Angewandte Chemie International Edition (2022).