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Manuscript.pdf (1.08 MB)
Unmasked Primary Amines as C-Nucleophiles for Catalytic C–C Bond-Formation
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 12.02.2020 and posted on 12.02.2020by Alison Ryder, William Cunningham, George Ballantyne, Tom Mules, Anna Kinsella, Jacob Turner-Dore, Catherine Alder, Lee Edwards, Blandine McKay, Matthew Grayson, Alex Cresswell
A practical, catalytic entry
to α,α,α‑trisubstituted (α‑tertiary) primary amines by
C–H functionalisation has long been recognised as a critical gap in the
synthetic toolbox. We report a simple and scalable solution
to this problem that does not require any in
situ protection of the amino group and proceeds with 100% atom-economy. Our
strategy, which uses an organic photocatalyst in combination with azide ion as
a hydrogen atom transfer (HAT) catalyst, provides a direct synthesis of C-alkylated amines or γ‑lactams, including
valuable azaspirocycles. We anticipate that this methodology will inspire new
retrosynthetic disconnections for substituted amine derivatives in organic
synthesis, and particularly for challenging α‑tertiary primary amines.