Catalytic Hydrogenation Processes in Organic Synthesis

Catalytic hydrogenation—the addition of molecular hydrogen to unsaturated bonds under the influence of a catalyst—constitutes a cornerstone of modern organic synthesis. By converting alkenes, alkynes, imines, ketones and aromatic rings into more saturated products, these processes enable the efficient assembly of pharmaceuticals, fine chemicals and bulk materials. Traditionally dominated by precious metals such as palladium, platinum and rhodium, the field has recently witnessed a marked shift towards earth‐abundant alternatives and atom‐efficient designs. Homogeneous systems employing well‐defined organometallic complexes offer exquisite control over regio‐ and stereoselectivity, while heterogeneous and single‐atom catalysts deliver ease of separation and enhanced robustness. Innovations in transfer hydrogenation and borrowing‐hydrogen strategies have expanded the repertoire of benign hydrogen donors, reducing reliance on high‐pressure H₂ and harsh conditions. Collectively, these advances underscore the dual aims of sustainability and performance: maximising turnover numbers and selectivities while minimising waste, energy consumption and reliance on scarce materials. Emerging mechanistic insights, aided by computational studies, continue to inform rational catalyst design, paving the way for increasingly sophisticated and green hydrogenation methodologies.

Research from Nature Portfolio

Recent studies have introduced single‐atom metal architectures to reconcile high activity with maximal metal utilisation. One report describes a ruthenium single‐atom catalyst supported on nitrogen‐doped carbon, which achieves exceptional turnover rates and selectivities in the reductive amination of aldehydes and ketones. Its uniform Ru–N₃ active sites confer both robustness under hydrotreating conditions and resistance to common poisons such as sulfur and carbon monoxide.

A separate investigation has demonstrated the direct hydrogenation of carbon dioxide to formate over a Schiff‐base‐modified gold nanocatalyst. This heterogeneous system surpasses previous benchmarks by engaging CO₂ through a carbamate zwitterion intermediate, achieving high turnover numbers at moderate temperatures without requiring alkaline media. The approach offers a promising route for CO₂ utilisation in fine‐chemical and energy contexts.

In the homogeneous realm, defined manganese PNP pincer complexes have been shown to catalyse the N-alkylation of amines with alcohols via borrowing‐hydrogen. Operating under mild conditions, these catalysts afford monoalkylated products with excellent chemoselectivity even in the presence of reducible functionalities, highlighting the potential of base‐metal systems to rival precious‐metal benchmarks in transfer‐hydrogenation processes.

Catalytic Hydrogenation Processes in Organic Synthesis publication trend

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

Technical terms

Catalytic hydrogenation: Addition of H₂ to unsaturated organic substrates in the presence of a catalyst to form saturated products.

Transfer hydrogenation: Hydrogenation in which a hydrogen donor (e.g. an alcohol or formate) replaces molecular hydrogen.

Single-atom catalyst (SAC): A heterogeneous catalyst in which individual metal atoms are dispersed on a support to maximise atom efficiency.

Pincer complex: A tridentate organometallic ligand system that binds a metal centre in a meridional fashion, imparting high stability and tunable reactivity.

Reductive amination: A two-step process involving condensation of an amine with a carbonyl compound to form an imine, followed by catalytic hydrogenation to yield an amine.

References

1. Highly selective and robust single-atom catalyst Ru1/NC for reductive amination of aldehydes/ketones. Nature Communications (2021).
2. Direct catalytic hydrogenation of CO2 to formate over a Schiff-base-mediated gold nanocatalyst. Nature Communications (2017).
3. Efficient and selective N-alkylation of amines with alcohols catalysed by manganese pincer complexes. Nature Communications (2016).
4. Asymmetric arene hydrogenation: towards sustainability and application. Chemical Society Reviews (2023).
5. Recent advances in homogeneous borrowing hydrogen catalysis using earth-abundant first row transition metals. Organic & Biomolecular Chemistry (2019).