Transition Metal-Catalyzed Carbon-Carbon Bond Activation

Transition metal-catalysed carbon–carbon (C–C) bond activation has emerged as a powerful strategy for the selective cleavage and reorganisation of otherwise inert C–C σ-bonds. By exploiting the ability of metals such as rhodium, manganese, zinc and palladium to undergo oxidative addition into C–C frameworks, chemists can effect ring openings, rearrangements and fragment couplings under mild conditions. Strained substrates (for example cyclobutanones and benzocyclobutenones) often serve as privileged starting materials, with ring strain lowering the energy barrier for metal insertion. Complementary approaches employ radical mediators or single-atom heterogeneous catalysts on nitrogen-doped carbon supports to achieve aerobic oxidative cleavages. These methodologies afford streamlined access to complex molecular architectures—bridged and fused rings, chiral centres and elaborated heterocycles—offering sustainable routes to pharmaceuticals, agrochemicals and advanced materials. Recent advances integrate C–C activation with cross-coupling, carbonylation and sigmatropic rearrangements, thereby enriching the toolbox for deconstructive and reconstructive synthetic design.

Research from Nature Portfolio

Recent studies have demonstrated a manganese-catalysed sigmatropic rearrangement of β,γ-unsaturated alcohols via selective C–C σ-bond activation, enabling in situ 1,2- and 1,3-rearrangements to furnish complex arylethyl and arylvinyl carbonyl compounds under remarkably simple conditions. Zinc single-atom catalysts on microporous nitrogen-doped carbon have also been shown to mediate aerobic oxidative cleavage of C(CO)–C bonds, converting a broad array of ketones into esters with high yields at moderate temperatures; mechanistic insights reveal the critical role of Zn–N coordination and the microporous matrix. In another advance, radical-mediated activation of unstrained cycloketones under mild conditions affords 3-coumaranones and indanones, with density functional theory studies elucidating the unusual regioselectivity of side-chain aryl radicals in driving easy C–C bond cleavage.

Transition Metal-Catalyzed Carbon-Carbon Bond Activation publication trend

The graph below shows the total number of articles in transition metal-catalyzed carbon-carbon bond activation across all publications each year (not limited to Nature Index journals).

Technical terms

C–C σ-bond activation: The process by which a transition metal inserts into an unactivated carbon–carbon bond, breaking it to form two metal–carbon bonds.

Metallacycle: A cyclic organometallic complex in which carbon atoms of an organic substrate and a transition metal form part of the ring.

Cyclobutanone: A four-membered cyclic ketone whose ring strain facilitates transition metal insertion into a C–C bond.

Benzocyclobutenone: A strained bicyclic ketone containing a benzene ring fused to a cyclobutanone, often used as a substrate for cut-and-sew chemistry.

Desymmetrisation: An enantioselective process in which a symmetrical substrate is converted into a chiral product by selective activation of one of two equivalent bonds.

Cut-and-sew reaction: A deconstructive strategy involving oxidative addition of a metal into a cyclic C–C bond followed by intramolecular insertion of an unsaturated unit to forge new ring systems.

References

1. Mn(I)-catalyzed sigmatropic rearrangement of β, γ-unsaturated alcohols. Nature Communications (2023).
2. Zn-Nx sites on N-doped carbon for aerobic oxidative cleavage and esterification of C(CO)-C bonds. Nature Communications (2021).
3. Radical-mediated C-C cleavage of unstrained cycloketones and DFT study for unusual regioselectivity. Nature Communications (2020).
4. Deconstructive Synthesis of Bridged and Fused Rings via Transition-Metal-Catalyzed “Cut-and-Sew” Reactions of Benzocyclobutenones and Cyclobutanones. Accounts of Chemical Research (2022).
5. Enantioselective Desymmetrization of Cyclobutanones: A Speedway to Molecular Complexity. Angewandte Chemie International Edition (2020).
6. Synthesis and applications of rhodacyclopentanones derived from C–C bond activation. Chemical Communications (2016).