Directed ortho-metalation of unprotected benzoic acids. Methodology and regioselective synthesis of useful contiguously 3- and 6-substituted 2-methoxybenzoic acid building blocks.
[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.
Nguyen
Thi-Huu
TH
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.
Castanet
Anne-Sophie
AS
Mortier
Jacques
J
D006131:Growth Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D035926:Hepatophyta / Q000737:chemistry; D015394:Molecular Structure; D012459:Salicylates / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry
D006131:Growth Inhibitors; D012459:Salicylates; D013267:Stilbenes; C067452:lunularic acid