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

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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
Early online date23 Dec 2020
DOIs
Publication statusE-pub ahead of print - 23 Dec 2020

Keywords

  • Bioisosteres
  • C–H functionalisation
  • Photoredox catalysis
  • γ-Aminophosphonates

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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