Mechanism of alkoxy groups substitution by Grignard reagents on aromatic rings and experimental verification of theoretical predictions of anomalous reactions

  1. Jiménez-Osés, G. 2
  2. Brockway, A.J. 1
  3. Shaw, J.T. 1
  4. Houk, K.N. 2
  1. 1 University of California, Davis
    info

    University of California, Davis

    Davis, Estados Unidos

    ROR https://ror.org/05rrcem69

  2. 2 University of California Los Angeles
    info

    University of California Los Angeles

    Los Ángeles, Estados Unidos

    ROR https://ror.org/046rm7j60

Revista:
Journal of the American Chemical Society

ISSN: 0002-7863

Año de publicación: 2013

Volumen: 135

Número: 17

Páginas: 6633-6642

Tipo: Artículo

DOI: 10.1021/JA4015937 PMID: 23601086 SCOPUS: 2-s2.0-84877049847 WoS: WOS:000318469100040 GOOGLE SCHOLAR

Otras publicaciones en: Journal of the American Chemical Society

Resumen

The mechanism of direct displacement of alkoxy groups in vinylogous and aromatic esters by Grignard reagents, a reaction that is not observed with expectedly better tosyloxy leaving groups, is elucidated computationally. The mechanism of this reaction has been determined to proceed through the inner-sphere attack of nucleophilic alkyl groups from magnesium to the reacting carbons via a metalaoxetane transition state. The formation of a strong magnesium chelate with the reacting alkoxy and carbonyl groups dictates the observed reactivity and selectivity. The influence of ester, ketone, and aldehyde substituents was investigated. In some cases, the calculations predicted the formation of products different than those previously reported; these predictions were then verified experimentally. The importance of studying the actual system, and not simplified models as computational systems, is demonstrated. © 2013 American Chemical Society.