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

James D. Grayson, Alexander J. Cresswell

Research output: Contribution to journalArticlepeer-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 languageEnglish
Article number131896
JournalTetrahedron
Volume81
Early online date23 Dec 2020
DOIs
Publication statusPublished - 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

Fingerprint

Dive into the research topics of 'γ-Amino phosphonates via the photocatalytic α-C–H alkylation of primary amines'. Together they form a unique fingerprint.

Cite this