Copper-Catalyzed Synthesis of Triazolyl-α-CF₃-α-Aminophosphonates

Significance

Reported is the synthesis of acetylenic and propargylic α-CF₃-α-aminophosphonates 2 and 3 which are converted into corresponding triazoles 4 and 5 by copper-catalyzed click reactions. Compounds 2 and 3 are obtained in moderate yields from imine 1 by addition of sodium acetylide and Grignard reagent derived from propargyl bromide. The copper(I) species is generated in situ from CuSO₄ and sodium ascorbate. The reaction proceeds in moderate to good yields. For aminophosphates 3 the reaction is heated at 80 ˚C resulting in a shorter reaction time (2 h compared to 8-12 h for 2). Selective deprotection of Cbz and pivaloylmethyl groups in good yields as well as the acidolysis of the phosphonate group to the free aminophosphonic acid as a salt was also achieved.