Investigation of Reactive Intermediates and Reaction Pathways in the Coupling Agent Mediated Phosphonamidation Reaction
| Autor: | Mohamed Amedjkouh, Kim A. Fredriksen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
010405 organic chemistry
Organic Chemistry Reactive intermediate 010402 general chemistry 01 natural sciences Combinatorial chemistry Coupling reaction 0104 chemical sciences chemistry.chemical_compound PyBOP chemistry Acyl chloride Amide Hexafluorophosphate Organic chemistry Organic synthesis Physical and Theoretical Chemistry Carbodiimide |
| Zdroj: | European Journal of Organic Chemistry. 2016:474-482 |
| ISSN: | 1434-193X |
| DOI: | 10.1002/ejoc.201501244 |
| Popis: | The preparation of carboxamides through the coupling agent mediated reaction of carboxylic acids and amines is one of the most frequently employed reaction types of modern organic synthesis and has largely replaced older methods of amide formation based on reactive acyl chloride intermediates. However, the preparations of analogous phosphonamidates still rely on the use of phosphonochloridate intermediates – a method that is incompatible with sensitive functional groups. Herein, we present a comprehensive study in which different coupling agents are tested in the phosphonamidation reaction. The procedures, parallel to those typically applied to the preparation of carboxamides, were generally unsuccessful with regard to the coupling reactions of monoesters of phosphonic acids and amines, with the exception of those mediated by (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP). The implementation of a preactivation period in the absence of the amine coupling partner allowed for efficient phosphonamidate formation with coupling agents such as (1-cyano-2-ethyoxy-2-oxoethylideneaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (COMU), [ethyl cyano(hydroxyimino)acetato-O2]tri-1-pyrrolidinylphosphonium hexafluorophosphate (PyOxim), dicyclohexyl carbodiimide (DCC), N,N′-diisopropylcarbodiimide (DIC), and N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU). The reactive intermediates observed by 31P NMR analysis were individually synthesized and examined to understand their influence on the reaction. |
| Databáze: | OpenAIRE |
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