Stereoselective Two-Carbon Ring Expansion of Allylic Amines via Electronic Control of Palladium-Promoted Equilibria

22 March 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Despite their potential value within drug discovery, general methodologies enabling the two-carbon homologation of pyrrolidine and piperidine systems have yet to be developed. Herein we report that palladium-catalysed allylic amine rearrangements enable efficient two-carbon ring expansion of 2-vinyl pyrrolidine and piperidines to their azepane and azocane counterparts. Conditions are mild, tolerant of a range of functional groups and the process can occur with a high degree of enantio-retention. The products formed undergo a range of orthogonal transformations, making them ideal scaffolds for the creation of compound libraries.


Allylic amine
Medicinal chemistry

Supplementary materials

Full supporting information
Supplementary data, including procedures and spectra.


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