Catalytic Hydroamination of Alkenes and Alkynes

Catalytic hydroamination—the direct addition of an N–H bond across carbon–carbon multiple bonds—has emerged as a cornerstone transformation for the construction of valuable amine derivatives from simple feedstocks. Alkenes and alkynes, abundant and structurally diverse, serve as the unsaturated substrates in this process. Key challenges lie in controlling regioselectivity (Markovnikov versus anti-Markovnikov addition), chemoselectivity and enantioselectivity under mild conditions. A variety of homogeneous catalysts based on late-transition metals (platinum, palladium, nickel, copper) and, more recently, earth-abundant 3d elements (iron, cobalt, manganese) have been developed. Mechanistic studies reveal pathways involving metal–alkene or metal–alkyne coordination, proton- or hydride-transfer steps and, in some instances, ligand dissociation/re-association events that govern reactivity and selectivity. Emerging approaches include metal-free radical-mediated hydroaminations, redox-enabled intramolecular cyclisations and photocatalytic variants. Collectively, these advances underscore the broad synthetic potential of hydroamination for pharmaceutical lead synthesis, agrochemical production and the assembly of nitrogen-containing heterocycles.

Research from Nature Portfolio

Recent work has unveiled “donor–acceptor” platinum complexes that catalyse hydroamination of unactivated alkenes with unprecedented efficiency and substrate scope. These catalysts accommodate mono-, di- and tri-substituted alkenes under mild temperatures and display high turnover numbers. Detailed mechanistic investigations indicate a reversible dissociation of an electron-deficient ligand to generate an alkene-bound intermediate, which facilitates N–H insertion with low energy barriers. These insights have laid the groundwork for the rational design of chiral variants, opening pathways to enantioselective hydrofunctionalization and the synthesis of optically active amines without the need for stoichiometric additives.

Catalytic Hydroamination of Alkenes and Alkynes publication trend

The graph below shows the total number of articles in catalytic hydroamination of alkenes and alkynes across all publications each year (not limited to Nature Index journals).

Technical terms

Hydroamination: Catalytic addition of an N–H bond across a carbon–carbon multiple bond to form a C–N single bond.

Alkene: An unsaturated hydrocarbon containing at least one carbon–carbon double bond.

Alkyne: An unsaturated hydrocarbon containing at least one carbon–carbon triple bond.

Regioselectivity: Preference for bond formation at one position over another on an unsymmetrical substrate.

Anti-Markovnikov: Addition pattern in which the incoming group attaches to the less substituted carbon of a multiple bond.

References

1. Development of highly efficient platinum catalysts for hydroalkoxylation and hydroamination of unactivated alkenes. Nature Communications (2021).
2. Anti-Markovnikov Intermolecular Hydroamination of Alkenes and Alkynes: A Mechanistic View. Chemical Reviews (2023).
3. NiH-catalyzed C–N bond formation: insights and advancements in hydroamination of unsaturated hydrocarbons. Chemical Science (2024).
4. Earth-Abundant 3d Transition Metal Catalysts for Hydroalkoxylation and Hydroamination of Unactivated Alkenes. Catalysts (2021).
5. A redox-enabled strategy for intramolecular hydroamination. Chemical Science (2022).
6. Synthesis of β‐Diamine Building Blocks by Photocatalytic Hydroamination of Enecarbamates with Amines, Ammonia and N−H Heterocycles. Chemistry - A European Journal (2020).