Stereoselective Synthesis of α-Aminophosphonates and Their Derivatives via Asymmetric α-Azidation of the...

Optically active α-aminophosphonic acids are unique analogues of α-amino acids, and numerous synthetic methods have been developed. Herein, we present a highly diastereoselective α-azidation approach to the CAMDOL-derived phosphonates, enabling ready access to 27 diverse α-azidophosphonates with defined chirality in up to 85% yield and more than 99:1 dr. Late-stage transformations through the Staudinger reaction or click reaction efficiently delivered the related pharmacological α-aminophosphonic acids or the unique α-triazolylphosphonate derivative, respectively. This CAMDOL-induced asymmetric architecture of the P-adjacent carbon chiral center exhibited comparable advantages over known induction methods with high stereoselectivity, easy manipulability, and broad compatibility.