Synthesis of N-Protected 1-Aminoalkylphosphonium Salts from Amides, Carbamates, Lactams, or Imides.

Jakub Adamek, Paulina Zieleźny, Karol Erfurt

The Journal of organic chemistry 2021 Apr 16

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This report describes the development and optimization of the one-pot method for the synthesis of N-protected 1-aminoalkylphosphonium salts based on the three-component coupling of aldehydes and either amides, carbamates, lactams, imides, or urea in the presence of triarylphosphonium salts. The proposed strategy is very efficient and easy to carry out even on a larger scale (20 g) in any typical laboratory. Most reactions occur at temperatures between 50 and 100 °C in a short time (1-2 h) without requiring any catalyst, and simple workup procedures afford good to excellent yields. The exceptions are condensations with imides, which require much higher temperatures (150-170 °C) and longer reaction times (even 30 h). The possibility of carrying out the synthesis under solvent-free conditions (neat reactions) is also demonstrated. It is especially important for less reactive substrates (imides), and reactions required high temperature (or generally harsher conditions). Finally, we prove the developed one-pot methodology can be successfully applied for the synthesis of structurally diverse N-protected 1-aminoalkylphosphonium salts. Mechanistic studies showed the intermediate products of described couplings are 1-hydroxyalkylphosphonium salts, not N-hydroxyalkylamides, -imides, etc., as initially expected.

Citation

Jakub Adamek, Paulina Zieleźny, Karol Erfurt. Synthesis of N-Protected 1-Aminoalkylphosphonium Salts from Amides, Carbamates, Lactams, or Imides. The Journal of organic chemistry. 2021 Apr 16;86(8):5852-5862