Comparative Studies on the Amidoalkylating Properties of N-(1-Methoxyalkyl)Amides and 1-(N-Acylamino)Alkyltriphenylphosphonium Salts in the Michaelis–Arbuzov-Like Reaction: A New One-Pot Transformation of N-(1-Methoxyalkyl)Amides into Phosphonic or Phosphinic Analogs of N-Acyl-α-Amino Acids

Abstract

It was demonstrated that N-(1-methoxyalkyl)amides do not react with trimethyl phosphite under neutral or basic conditions. The treatment of N-(1-methoxyalkyl)amides with trialkyl phosphites or dialkyl phosphonites, triphenylphosphonium tetrafluoroborate, and Hünig's base caused immediate formation of the corresponding 1-(N-acylamino)-alkyltriphenylphosphonium tetrafluoroborates, followed by the slow Michaelis–Arbuzov-like reaction of phosphonium salt with phosphites or phosphonites to α-(N-acylamino)-alkanephosphonic or α-(N-acylamino)alkanephosphinic acid esters, respectively. A plausible mechanism of the considered transformations, assuming an equilibrium between N-(1-alkoxyalkyl)amide, triphenylphosphonium tetrafluoroborate, 1-(N-acylamino)alkyltriphenyl-phosphonium salt, N-acylimine, and N-acyliminium salts, is discussed.

GRAPHICAL ABSTRACT

Keywords:

• Amidoalkylating agents
• 1-(N-acylamino)alkyltriphenylphosphonium salts
• N-(1-methoxyalkyl)amides
• Michaelis–Arbuzov-like reaction
• phosphorus analogs of N-acyl-α-amino acids

Acknowledgments

The financial help of the Ministry of Science and Higher Education of Poland (Grant No. N N204 165636) is gratefully acknowledged.