Directed ortho-metalation of unprotected benzoic acids. Methodology and regioselective synthesis of useful contiguously 3- and 6-substituted 2-methoxybenzoic acid building blocks

Thi-Huu Nguyen; Anne-Sophie Castanet; Jacques Mortier

doi:10.1021/ol0530427

Directed ortho-metalation of unprotected benzoic acids. Methodology and regioselective synthesis of useful contiguously 3- and 6-substituted 2-methoxybenzoic acid building blocks

Org Lett. 2006 Feb 16;8(4):765-8. doi: 10.1021/ol0530427.

Authors

Thi-Huu Nguyen¹, Anne-Sophie Castanet, Jacques Mortier

Affiliation

¹ Université du Maine and CNRS, Unité de Chimie Organique Moléculaire et Macromoléculaire (UMR 6011), Faculté des Sciences, avenue Olivier Messiaen, 72085 Le Mans Cedex 9, France.

PMID: 16468762
DOI: 10.1021/ol0530427

Abstract

[reaction: see text] By treatment with s-BuLi/TMEDA at -78 degrees C, unprotected 2-methoxybenzoic acid is deprotonated exclusively in the position ortho to the carboxylate. A reversal of regioselectivity is observed when the acid is treated with n-BuLi/t-BuOK. These results are of general utility for the one-pot preparation of a variety of very simple 3- and 6-substituted 2-methoxybenzoic acids that are not easily accessible by conventional means. The potential usefulness of the method is demonstrated by the expedient synthesis of lunularic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Growth Inhibitors / chemical synthesis*
Growth Inhibitors / chemistry
Hepatophyta / chemistry
Molecular Structure
Salicylates / chemical synthesis*
Salicylates / chemistry
Stereoisomerism
Stilbenes / chemical synthesis*
Stilbenes / chemistry

Substances

Growth Inhibitors
Salicylates
Stilbenes
lunularic acid