Catalytic Insertion Reactions of Diazo Compounds

Diazo compounds, bearing the characteristic –N₂ moiety, serve as versatile precursors to metal- or main-group-stabilised carbenes that undergo insertion into diverse X–H and C–H bonds. These catalytic insertion processes enable formation of C–C, C–N, C–O and C–H linkages with high atom economy and minimal waste, meeting modern sustainability demands. Transition-metal catalysts such as rhodium, copper, silver and gold have historically dominated the field, delivering remarkable reactivity and selectivity in intramolecular and intermolecular insertions. More recently, main-group systems—triarylboranes and boranes—alongside visible-light-promoted and metal-free protocols, have expanded the scope to delicate substrates and sensitive functional groups. Contemporary methods achieve chemo-, regio- and enantioselective insertion into unactivated alkanes, amines and phenols, often under ambient conditions. The global significance of these reactions spans late-stage functionalisation of pharmaceuticals, agrochemical synthesis, polymer modification and complex natural product assembly. Advances in mechanistic understanding, bolstered by computational studies, guide rational catalyst design. Ongoing efforts focus on diverse diazo precursors, mild activation strategies and precise site-selective transformations, underlining the enduring impact of diazo insertion chemistry on synthetic innovation.

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Catalytic Insertion Reactions of Diazo Compounds publication trend

The graph below shows the total number of articles in catalytic insertion reactions of diazo compounds across all publications each year (not limited to Nature Index journals).

Technical terms

Diazo compound: An organic molecule bearing the –N₂ group, precursors to reactive carbene intermediates.

Carbene: A neutral species with a divalent carbon atom possessing two nonbonded electrons, key intermediate in insertion reactions.

Insertion reaction: Formal incorporation of a carbene fragment into an X–H or C–H bond, yielding a new sigma bond framework.

Donor–acceptor diazo compound: A diazo substrate bearing electron-donating and electron-withdrawing substituents that stabilise the resultant carbene.

Chemo-selectivity: The preferential reaction of a reagent with one functional group in the presence of others.

Visible-light activation: Use of ambient light wavelengths to promote carbene generation without thermal or metal catalysts.

References

1. A visible-light-promoted metal-free approach for N–H insertions by using donor/donor diazo precursors. Green Chemistry (2024).
2. Borane-Catalyzed Stereoselective C–H Insertion, Cyclopropanation, and Ring-Opening Reactions. Chem (2020).
3. Site-Selective C–H Benzylation of Alkanes with N-Triftosylhydrazones Leading to Alkyl Aromatics. Chem (2020).