γ-Amino phosphonates via the photocatalytic α-C–H alkylation of primary amines

James D. Grayson; Alexander J. Cresswell

doi:10.1016/j.tet.2020.131896

γ-Amino phosphonates via the photocatalytic α-C–H alkylation of primary amines

James D. Grayson, Alexander J. Cresswell

Department of Chemistry

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

19 Citations (SciVal)

Abstract

We report a simple photocatalytic protocol for the direct synthesis of γ-amino phosphonates via the α-C–H alkylation of unprotected, aliphatic primary amines with diethyl vinylphosphonate. These motifs are valuable bioisosteres of γ-amino acids and O-phosphorylated amino alcohols. Visible-light photoredox catalysis in combination with hydrogen atom transfer (HAT) catalysis is used to access the necessary α-amino radical intermediates for C–C bond formation. The procedure is also demonstrated on gram-scale in continuous flow for the synthesis of a racemic, protected derivative of the mGlu agonist 2-amino-4-phosphonobutyric acid (AP4).

Original language	English
Article number	131896
Journal	Tetrahedron
Volume	81
Early online date	23 Dec 2020
DOIs	https://doi.org/10.1016/j.tet.2020.131896
Publication status	Published - 12 Feb 2021

Bibliographical note

Funding Information:
The authors would like to acknowledge Anna Kinsella for obtaining preliminary results. This work was supported by the Engineering and Physical Sciences Research Council EP/R020752/1 . A.J.C. thanks the Royal Society for a University Research Fellowship ( UF150533 ) and the University of Bath for generous financial support.

Publisher Copyright:
© 2020 Elsevier Ltd

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Funding

The authors would like to acknowledge Anna Kinsella for obtaining preliminary results. This work was supported by the Engineering and Physical Sciences Research Council EP/R020752/1 . A.J.C. thanks the Royal Society for a University Research Fellowship ( UF150533 ) and the University of Bath for generous financial support.

Keywords

Bioisosteres
C–H functionalisation
Photoredox catalysis
γ-Aminophosphonates

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tet.2020.131896

Cite this

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title = "γ-Amino phosphonates via the photocatalytic α-C–H alkylation of primary amines",

abstract = "We report a simple photocatalytic protocol for the direct synthesis of γ-amino phosphonates via the α-C–H alkylation of unprotected, aliphatic primary amines with diethyl vinylphosphonate. These motifs are valuable bioisosteres of γ-amino acids and O-phosphorylated amino alcohols. Visible-light photoredox catalysis in combination with hydrogen atom transfer (HAT) catalysis is used to access the necessary α-amino radical intermediates for C–C bond formation. The procedure is also demonstrated on gram-scale in continuous flow for the synthesis of a racemic, protected derivative of the mGlu agonist 2-amino-4-phosphonobutyric acid (AP4).",

keywords = "Bioisosteres, C–H functionalisation, Photoredox catalysis, γ-Aminophosphonates",

author = "Grayson, {James D.} and Cresswell, {Alexander J.}",

note = "Funding Information: The authors would like to acknowledge Anna Kinsella for obtaining preliminary results. This work was supported by the Engineering and Physical Sciences Research Council EP/R020752/1 . A.J.C. thanks the Royal Society for a University Research Fellowship ( UF150533 ) and the University of Bath for generous financial support. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

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language = "English",

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AU - Grayson, James D.

AU - Cresswell, Alexander J.

N1 - Funding Information: The authors would like to acknowledge Anna Kinsella for obtaining preliminary results. This work was supported by the Engineering and Physical Sciences Research Council EP/R020752/1 . A.J.C. thanks the Royal Society for a University Research Fellowship ( UF150533 ) and the University of Bath for generous financial support. Publisher Copyright: © 2020 Elsevier Ltd Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/2/12

Y1 - 2021/2/12

N2 - We report a simple photocatalytic protocol for the direct synthesis of γ-amino phosphonates via the α-C–H alkylation of unprotected, aliphatic primary amines with diethyl vinylphosphonate. These motifs are valuable bioisosteres of γ-amino acids and O-phosphorylated amino alcohols. Visible-light photoredox catalysis in combination with hydrogen atom transfer (HAT) catalysis is used to access the necessary α-amino radical intermediates for C–C bond formation. The procedure is also demonstrated on gram-scale in continuous flow for the synthesis of a racemic, protected derivative of the mGlu agonist 2-amino-4-phosphonobutyric acid (AP4).

AB - We report a simple photocatalytic protocol for the direct synthesis of γ-amino phosphonates via the α-C–H alkylation of unprotected, aliphatic primary amines with diethyl vinylphosphonate. These motifs are valuable bioisosteres of γ-amino acids and O-phosphorylated amino alcohols. Visible-light photoredox catalysis in combination with hydrogen atom transfer (HAT) catalysis is used to access the necessary α-amino radical intermediates for C–C bond formation. The procedure is also demonstrated on gram-scale in continuous flow for the synthesis of a racemic, protected derivative of the mGlu agonist 2-amino-4-phosphonobutyric acid (AP4).

KW - Bioisosteres

KW - C–H functionalisation

KW - Photoredox catalysis

KW - γ-Aminophosphonates

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DO - 10.1016/j.tet.2020.131896

M3 - Article

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SN - 0040-4020

VL - 81

JO - Tetrahedron

JF - Tetrahedron

M1 - 131896

ER -

γ-Amino phosphonates via the photocatalytic α-C–H alkylation of primary amines

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

A Radical Approach to C-H Alkylation

Nucleophilic alkaline earth boryls: from conception and theory to application

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

Avance III 400 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (9West)

Cite this

γ-Amino phosphonates via the photocatalytic α-C–H alkylation of primary amines

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

A Radical Approach to C-H Alkylation

Nucleophilic alkaline earth boryls: from conception and theory to application

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

Equipment

Avance III 400 MHz Nuclear Magnetic Resonance (NMR) Spectrometer (9West)

Cite this