Aza-Michael Addition of Aliphatic Amines to Weakly Polarised Alkenes via Organobase Catalysis
Year: 2026
Type: preprint
Abstract: The direct addition of aliphatic amines to alkenes offers an atom-economical route to valuable N-alkyl amines, but remains challenging for weakly polarised alkenes. This is because C–N bond formation is poorly driven thermodynamically and difficult to achieve without strongly activating the alkene or generating more reactive nitrogen species. Here we report an organobase-catalysed strategy that enables anti-Markovnikov addition of secondary aliphatic amines to weakly polarised (hetero)aryl alkenes. Kinetic studies and calculations support a mechanism in which the organobase promotes C–N bond formation through hydrogen bonding and noncovalent stabilisation of the addition transition state, followed by rapid deprotonation of the addition complex. The developed conditions were also applicable to challenging C–C bond forming Michael addition reactions with enolate nucleophiles. These findings demonstrate that organobase catalysis can overcome the intrinsic kinetic and thermodynamic challenges associated with closed-shell additions to weakly activated alkenes.
Source: ChemRxiv
Institutions: University of Manchester, AstraZeneca (United Kingdom)
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7221106164