Cyclopalladation and reactivity of amino esters through C - H bond activation: Experimental, kinetic, and density functional theory mechanistic studies

Eduardo Laga, Angel García-Montero, Francisco J. Sayago, Tatiana Soler, Salvador Moncho, Carlos Cativiela, Manuel Martínez, Esteban P. Urriolabeitia

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The orthopalladation, through C - H bond activation, of a large number of amino esters and amino phosphonates derived from phenylglycine, and having different substituents at the aryl ring and the C-α atom, as well as on the N-amine atom, has been studied. The experimental observations indicated an improvement in the yields of the orthopalladated compounds when the N-amine and/or the C-α atom are substituted, when compared with the unsubstituted methyl phenylglycinate derivatives. In contrast, substitutions at the aryl ring do not promote significant changes in the orthometalation results. Furthermore, the use of hydrochloride salts of the amino esters has also been shown to have a remarkably favorable effect on the process. All these observations have been fully quantified at different temperatures and pressures by a detailed kinetic study in solution in different solvents and in the presence and absence of added Brønsted acids and chloride anions. The data collected indicate relevant changes in the process depending on these conditions, as expected from the general background known for cyclopalladation reactions. An electronic mechanism of the orthopalladation has been proposed based on DFT calculations at the B3LYP level, and a very good agreement between the trends kinetically measured and the theoretically calculated activation barriers has been obtained. The reactivity of the new orthopalladated amino phosphonate derivatives has been tested and it was found that their halogenation, alkoxylation and carbonylation resulted in formation of the corresponding functionalized ortho- haloaminophosphonates, ortho-alkoxyaminophosphonates and oxoisoindolinylphosphonates. Remote control: The orthopalladation, through C - H bond activation, of substituted amino esters and amino phosphonates derived from phenylglycine has been studied (see scheme). Determination of the reaction rates indicated a clear acceleration of the C - H activation rate when the n-amine and/or the C-α atom are substituted. Substitutions at the aryl ring do not promote changes. The use of hydrochloride salts of the amino esters also has a strong accelerating effect on the process.

Original languageEnglish
Pages (from-to)17398-17412
Number of pages15
JournalChemistry - A European Journal
Volume19
Issue number51
DOIs
Publication statusPublished - 16 Dec 2013

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Keywords

  • C - H activation
  • amino acids
  • density functional calculations
  • kinetics
  • palladium

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Organic Chemistry

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