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

15 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.

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",

volume = "81",

journal = "Tetrahedron",

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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

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

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