Photocatalytic α-Tertiary Amine Synthesis via C-H Alkylation of Unmasked Primary Amines

Alison S H Ryder; William B Cunningham; George Ballantyne; Tom Mules; Anna G Kinsella; Jacob Turner-Dore; Catherine M Alder; Lee J Edwards; Blandine S J McKay; Matthew N Grayson; Alexander J Cresswell

doi:10.1002/anie.202005294

Photocatalytic α-Tertiary Amine Synthesis via C-H Alkylation of Unmasked Primary Amines

Alison S H Ryder, William B Cunningham, George Ballantyne, Tom Mules, Anna G Kinsella, Jacob Turner-Dore, Catherine M Alder, Lee J Edwards, Blandine S J McKay, Matthew N Grayson, Alexander J Cresswell

Research output: Contribution to journal › Article › peer-review

69 Citations (SciVal)

Abstract

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 α-tertiary amines, or their corresponding γ-lactams. 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.

Original language	English
Pages (from-to)	14986-14991
Number of pages	6
Journal	Angewandte Chemie (International ed. in English)
Volume	59
Issue number	35
Early online date	11 Jun 2020
DOIs	https://doi.org/10.1002/anie.202005294
Publication status	Published - 24 Aug 2020

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10.1002/anie.202005294Licence: CC BY

A Radical Approach to C-H Alkylation
Cresswell, A.
Engineering and Physical Sciences Research Council
20/01/20 → 31/03/23
Project: Research council
UR Fellowship for Alex Cresswell - Better than Boron? Silicon-Mediated Aromatic Functionalisation
Cresswell, A.
The Royal Society
1/10/16 → 31/03/22
Project: Research council

Alex Cresswell
- A.J.Cresswellbath.acuk
- Department of Chemistry - Royal Society University Research Fellow
- Institute for Sustainability
Person: Research & Teaching, Core staff
Matthew Grayson
- M.N.Graysonbath.acuk
- Department of Chemistry - Senior Lecturer
- EPSRC Centre for Doctoral Training in Advanced Automotive Propulsion Systems (AAPS CDT)
Person: Research & Teaching, Affiliate staff

Balena High Performance Computing (HPC) System
Facility/equipment: Equipment

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Ryder, A. S. H., Cunningham, W. B., Ballantyne, G., Mules, T., Kinsella, A. G., Turner-Dore, J., Alder, C. M., Edwards, L. J., McKay, B. S. J., Grayson, M. N., & Cresswell, A. J. (2020). Photocatalytic α-Tertiary Amine Synthesis via C-H Alkylation of Unmasked Primary Amines. Angewandte Chemie (International ed. in English), 59(35), 14986-14991. https://doi.org/10.1002/anie.202005294

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title = "Photocatalytic α-Tertiary Amine Synthesis via C-H Alkylation of Unmasked Primary Amines",

abstract = "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 α-tertiary amines, or their corresponding γ-lactams. 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.",

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doi = "10.1002/anie.202005294",

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AU - Mules, Tom

AU - Kinsella, Anna G

AU - Turner-Dore, Jacob

AU - Alder, Catherine M

AU - Edwards, Lee J

AU - McKay, Blandine S J

AU - Grayson, Matthew N

AU - Cresswell, Alexander J

PY - 2020/8/24

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AB - 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 α-tertiary amines, or their corresponding γ-lactams. 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.

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DO - 10.1002/anie.202005294

M3 - Article

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Photocatalytic α-Tertiary Amine Synthesis via C-H Alkylation of Unmasked Primary Amines

Abstract

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Projects

A Radical Approach to C-H Alkylation

UR Fellowship for Alex Cresswell - Better than Boron? Silicon-Mediated Aromatic Functionalisation

Profiles

Alex Cresswell

Matthew Grayson

Equipment

Balena High Performance Computing (HPC) System

Cite this