The first regioselective metalation and functionalization of unprotected 4-halobenzoic acids

  • J Org Chem. 2005 Feb 18;70(4):1501-4. doi: 10.1021/jo0483365.
Frédéric Gohier  1 ,  Anne-Sophie Castanet ,  Jacques Mortier
Affiliations
  • 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: 15704996 DOI: 10.1021/jo0483365
Abstract

[reaction: see text] By treatment with s-BuLi, s-BuLi/TMEDA, or t-BuLi at approximately -78 degrees C, 4-fluoro- and 4-chlorobenzoic acids (1a,b) are metalated preferentially in the position adjacent to the carboxylate. A complete reversal in regioselectivity is observed for 1a when treated with LTMP; a sequential process involving a rapid intraaggregate lithiation through a quasi dianion complex "QUADAC" is postulated to explain the unusual reactivity of Me(2)S(2) and I(2).

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