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.
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.
Thi-Huu
TH
Nguyen
Anne-Sophie
AS
Castanet
Jacques
J
Mortier
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