hydroamination

Hydroamination is the chemical reaction that forms a carbon–nitrogen bond by adding an N–H bond across an unsaturated carbon–carbon bond, most commonly an alkene or an alkyne, to give amines. It is valued for atom economy because it uses simple nitrogen sources and directly converts alkenes or alkynes into amines without stoichiometric byproducts.

Substrates and scope: Hydroamination can be intramolecular, producing cyclic amines such as pyrrolidines and piperidines, or intermolecular, where an amine adds to a separate unsaturated substrate. Regioselectivity depends on substrate and catalyst; anti-Markovnikov addition to simple alkenes is often desirable but challenging. Enantioselective hydroamination has been demonstrated with chiral catalysts, enabling the synthesis of chiral amines.

Catalysis and mechanisms: A wide range of catalysts has been developed, including late transition metals (e.g., Rh, Ir, Pd, Cu), early metals, and some organocatalytic or radical approaches. Most catalytic cycles involve activation of the N–H bond and subsequent addition of the nitrogen to the carbon–carbon bond, either via a metal–nitrogen species that inserts into the alkene or via ammonium-type radical pathways. Mechanistic details vary with substrate and catalyst; some systems proceed through metal–nitrogen migratory insertion, others through radical mechanisms.

Applications and challenges: Hydroamination provides direct access to primary, secondary, and tertiary amines, including heterocycles, from simple starting materials. Challenges include achieving broad substrate scope, high regio- and stereoselectivity, and practical reaction conditions for unactivated alkenes.