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

• DOI: 10.1016/j.tet.2020.131896
• Publication Date: 2020-12-23T07:48:43Z
• Authors: James D. Grayson; Alexander J. Cres...
• Keywords: 01 natural sciences; 0104 chemical sciences

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).