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, 2006/2/16;8(4):765-8.

Nguyen TH[1], Castanet AS, Mortier J

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PMID: 16468762

Impact factor: 6.072

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.
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