Reductive Carbonylation of Nitro Compounds

Reductive carbonylation of nitro compounds constitutes a versatile and atom-efficient approach to the synthesis of diverse nitrogen-containing functional groups, including amides, carbamates and N-heterocycles. By combining in situ reduction of nitro moieties with carbon monoxide insertion, this methodology permits direct access to structurally complex targets in a single operation. Historically, applications have relied upon transition-metal catalysts such as palladium, ruthenium and iron under high-pressure CO conditions, often requiring specialised equipment. Recent advances have focused on mechanistic clarifications of nitro-to-intermediate conversion pathways, the development of heterogeneous catalysts for robust recycling, and—critically—the use of CO surrogates to obviate the need for pressurised gas. These innovations have expanded substrate scope to include o-nitrochalcones, β-nitrostyrenes and nitroarenes, fostering applications in the construction of pharmaceutically relevant scaffolds such as quinolones and indoles. The growing emphasis on safe, scalable and sustainable protocols underscores the global significance of reductive carbonylation for industrial and academic synthesis, linking fundamental organometallic chemistry with practical process design.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Reductive Carbonylation of Nitro Compounds publication trend

The graph below shows the total number of articles in reductive carbonylation of nitro compounds across all publications each year (not limited to Nature Index journals).

Technical terms

Reductive carbonylation: Simultaneous reduction and incorporation of carbon monoxide into a substrate bearing a nitro group to form amides, carbamates or heterocycles.

Carbon monoxide surrogate: A reagent that releases CO under reaction conditions, eliminating the need for pressurised gaseous CO.

Nitroarene: An aromatic compound containing one or more nitro (–NO₂) substituents, which serve as precursors for reductive transformations.

Reductive cyclization: Intramolecular ring formation driven by simultaneous reduction and carbonylation steps, often yielding heterocyclic frameworks.

N-heterocycle: A cyclic organic molecule in which one or more ring atoms are nitrogen, common in pharmaceuticals and materials.

References

1. Effective Synthesis of 4-Quinolones by Reductive Cyclization of 2′-Nitrochalcones Using Formic Acid as a CO Surrogate. Molecules (2023).
2. Phenyl Formate as a CO Surrogate for the Reductive Cyclization of Organic Nitro Compounds to Yield Different N-Heterocycles: No Need for Autoclaves and Pressurized Carbon Monoxide †. Catalysts (2023).
3. Formic Acid as Carbon Monoxide Source in the Palladium-Catalyzed N‑Heterocyclization of o‑Nitrostyrenes to Indoles. The Journal of Organic Chemistry (2023).