Amide-Type Substrates in the Synthesis of N-Protected 1-Aminomethylphosphonium Salts

Herein we describe the development and optimization of a two-step procedure for synthesis N-protected 1-aminomethylphosphonium salts from imides, amides, carbamates, or lactams. Our “step-by-step” methodology involves transformation amide-type substrates to corresponding hydroxymethyl derivatives, followed by substitution hydroxyl group with phosphonium moiety. The first step described was conducted based on well-known protocols hydroxymethylation formaldehyde paraformaldehyde. In turn, second (substitution) stage required studies. general, reactions amide, carbamate, lactam derivatives occurred at temperature 70 °C in relatively short time (1 h). On other hand, N-hydroxymethylimides reacted triarylphosphonium much higher (135 °C) over longer reaction times (as as 30 However, proposed strategy is very efficient, especially when NaBr used catalyst. Moreover, simple work-up involving only crystallization afforded good excellent yields (up 99%).