Organic Chemistry

Direct alpha-Amination of Amides and Lactams Enabled by the (3+2) Vinyl Azide-Enolate Cycloaddition Manifold

Authors

Abstract

Direct alpha-amination of carbonyl compounds remains an important yet synthetically challenging transformation. Here we report a solution for direct alpha-amination of amides and lactams, identified through fundamental exploration of (3+2) vinyl azide-enolate cycloaddition chemistry. Initial cycloadducts undergo rearrangement via 1,2-N-migration to afford imine intermediates that are readily converted to the target alpha-amino amides or lactams. The sequence requires no pre-functionalisation, can be performed on a range of substrates, including compound classes unsuccessful using reported methods, and delivers primary or secondary alpha-amines. This work highlights the diversity and synthetic potential of the rapidly expanding (3+2) azide-enolate cycloaddition manifold.

Version notes

In Scheme 1A, Ref 57 was specified

Content

Thumbnail image of Direct Amination 2022 - Manuscript .pdf

Supplementary material

Thumbnail image of Direct Amination 2022 - SI.pdf
Supporting Information
Experimental procedures, additional reaction optimisation data, unsuccessful substrates, NMR spectra and computational information.