Propargyl-Substituted Phosphonocarboxylates: Efficient Synthesis and Application to Click Chemistry

An efficient pathway for the selective preparation of monopropargyl-substituted phosphonocarboxylate (PC) has been developed via the addition of sodium acetylenide to ethylidenephosphonate. The reaction works perfectly on multi-gram scales. The synthesis of the corresponding methyl(propargyl)-, trifluoro­methyl(propargyl)-, and dipropargyl-substituted derivatives was elaborated based on direct alkylation of either the correspondingly substituted phosphonocarboxylates or methylene phosphonocarboxylate with excess of propargyl bromide. A series of novel potentially biologically active 1,2,3-triazole-containing phosphono­-carboxylates were synthesized using copper(I)-catalysed 1,3-dipolar cycloaddition of organic azides with propargyl-substituted phosphonocarboxylates.