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

Mickael Belaud-Rotureau; Anne-Sophie Castanet; Thi Huu Nguyen; Jacques Mortier

doi:10.1071/CH15398

RESEARCH ARTICLE

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

Abstract

References

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