Synthesis of N-protected 1-aminoalkylphosphonium salts—a new perspective

Abstract

The current study presents two novel and efficient strategies for the synthesis of N-protected 1-aminoalkylphosphonium salts from readily available substrates. The first one is a one-pot methodology which is based on the three-component coupling reaction of aldehydes with amides, carbamates, lactams, imides, or urea in the presence of triarylphosphonium salt. This approach results in the production of a wide range of structurally diverse N-protected 1-aminoalkylphosphonium salts. The second one is a step-by-step procedure which results in the synthesis of N-protected 1-aminomethylphosphonium salts only, and hence has a limited scope of application. This method is performed in two steps: transformation of amide-type substrates to the corresponding hydroxymethyl derivatives and substitution of the hydroxyl group with triarylphosphine. Both protocols are promising alternatives and complement the hitherto described methodologies.

Graphical Abstract

Keywords:

• Phosphonium salts
• α-amidoalkylation
• α-amidoalkylating agents
• amides
• imides
• aldehydes