C–H Bond Activation and Functionalization in Organometallic Systems

C–H bonds represent the most abundant linkages in organic molecules but are traditionally regarded as inert under standard reaction conditions. Organometallic chemistry has transformed this perspective by harnessing transition-metal catalysts to cleave and functionalise C–H bonds directly, bypassing the need for prefunctionalised substrates. Key strategies include oxidative addition, σ-bond metathesis and concerted metalation–deprotonation pathways, each enabled by carefully designed ligands that tune the metal’s reactivity and selectivity. Directing groups are often installed to guide activation to specific C–H bonds, while emerging approaches exploit transient interactions or weak coordination to achieve meta and para selectivity without permanent modification. Advances in earth-abundant metals and mild reaction media, including aqueous and electrochemical systems, have broadened the accessibility and sustainability of C–H functionalisation. These methods permit rapid construction of C–C, C–N, C–O and C–X bonds, streamlining the synthesis of pharmaceuticals, agrochemicals and materials. Late-stage functionalisation of complex molecules illustrates the power of these techniques to introduce diversity without de novo synthesis, while mechanistic studies continue to illuminate the interplay between catalyst design, reaction kinetics and substrate scope.

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C–H Bond Activation and Functionalization in Organometallic Systems publication trend

The graph below shows the total number of articles in c–h bond activation and functionalization in organometallic systems across all publications each year (not limited to Nature Index journals).

Technical terms

C–H activation: The cleavage of a carbon–hydrogen bond by a metal centre to form a metal–carbon bond, enabling subsequent functionalisation.

Directing group: A substituent temporarily attached to a substrate that coordinates the catalyst and directs C–H bond cleavage to a specific position.

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

Concerted metalation–deprotonation (CMD): A pathway in which metalation of a C–H bond and proton removal occur in a single, concerted step facilitated by a base or ligand.

Heterogenisation: The process of anchoring a molecular catalyst onto a solid support to combine advantages of homogeneous and heterogeneous catalysis.

References

1. Improving the sustainability of the ruthenium-catalysed N -directed C–H arylation of arenes with aryl halides. Green Chemistry (2023).
2. Electrochemical ruthenium-catalysed C–H activation in water through heterogenization of a molecular catalyst. Catalysis Science & Technology (2022).
3. Recent Advances in C–H Bond Functionalization with Ruthenium-Based Catalysts. Catalysts (2019).