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

We report a simple photocatalytic protocol for the direct synthesis of gamma-amino phosphonates via the alpha-C-H alkylation of unprotected, aliphatic primary amines with diethyl vinylphosphonate. These motifs are valuable bioisosteres of gamma-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 alpha-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). (C) 2020 Elsevier Ltd. All rights reserved.