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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Uncatalyzed CO2Li-Mediated SNAr Reaction of Unprotected Benzoic Acids via Silicon Trickery

Mickael Belaud-Rotureau A , Anne-Sophie Castanet A , Thi Huu Nguyen A and Jacques Mortier A B
+ Author Affiliations
- Author Affiliations

A Université du Maine and CNRS UMR 6283, Institut des Molécules et Matériaux du Mans, Faculté des Sciences et Techniques, Avenue Olivier Messiaen, 72085 Le Mans Cedex 9, France.

B Corresponding author. Email: jacques.mortier@univ-lemans.fr

Australian Journal of Chemistry 69(3) 307-313 https://doi.org/10.1071/CH15398
Submitted: 2 July 2015  Accepted: 31 July 2015   Published: 15 September 2015

Abstract

The alkyl and aryllithium nucleophilic aromatic substitution (SNAr) displacement of a fluoro or methoxy group from unprotected 2-fluoro/methoxybenzoic acids is discussed. It was discovered that a TMS group located at the C6-position ortho to the carboxyl group shields effectively the carboxylate against nucleophilic attack, thus reducing dramatically ketone formation, and reorients nucleophilic substitution to the C2-position. The reactions with fluoro-substituted substrate 7 proceed efficiently; in contrast, the use of methoxy-functionalized benzoic acid 8 only affords moderate yields with s-BuLi and PhLi. This uncatalyzed coupling reaction, which provides a direct access to biaryl compounds, presumably proceeds by an addition–elimination sequence via intermediate formation of a resonance-stabilized pentavalent silalactone-Meisenheimer complex.


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