YAMADA Coupling reagent

The use of diethyl phosphoryl cyanide (diethyl cyanophosphonate) for the activation of carboxylic acids. 

Yokoyama, Y. Shioiri, T. Yamada, S. Chem. Pharm. Bull. 1977, 25, 2423. 

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YAMADA Coupling reagent 430 YAMAGUCHILactonizalion reagent 431 YAMAZAKI Cyanoandine synthesis 432 Yamamoto 177... 

Yamada s coupling reagent (diethylcyanophosphonate, DEPC) is representative of phosphorous based activators, including diphenylphosphoryl azide. 

Diphenyl phosphoryl azide in dimethylformamide followed by triethylamine added at or below 0° to a soln. of N-carbobenzoxy-L-leucyl-L-leucine and L-valyl-L-phenylalanine methyl ester hydrochloride in the same solvent, stirred several hrs. at the above temp, and overnight at room temp. -> product. Y 87%. - Practically no racemization occurred. F. e., also direct prepn. of urethans from carboxylic acids (cf. Synth. Meth. 17, 393) by a simplified Curtius degradation, s. T. Shioiri, K. Ninomiya, and S. Yamada, Am. Soc. 94, 6203 (1972) Tetrah. Let. 1973, 2343 synthesis of N-subst. carboxylic acid amides and peptides with diethyl phosphoryl cyanide s. Tetrah. Let. 1973, 1595 coupling reagents in peptide synthesis, review, s. Y. S. Klausner and M. Bodansky, Synthesis 1972, 453 review of peptide synthesis s. J. Meienhofer, Chem. Technol. 3, 242 (1973). 

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