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Unmasked Primary Amines as C-Nucleophiles for Catalytic C–C Bond-Formation

preprint
submitted on 12.02.2020 and posted on 12.02.2020 by 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.

Funding

Royal Society University Research Fellowship (UF150533)

Engineering and Physical Sciences Research Council (EP/L016354/1)

History

Email Address of Submitting Author

a.j.cresswell@bath.ac.uk

Institution

University of Bath

Country

United Kingdom

ORCID For Submitting Author

0000-0003-4060-9657

Declaration of Conflict of Interest

The authors declare no competing interests.

Version Notes

Version 1.0

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