title: First general, direct, and regioselective synthesis of substituted methoxybenzoic acids by ortho metalation.
abstract: New general methodology of value in aromatic chemistry based on ortho-metalation sites in o-, m-, and p-anisic acids (1-3) (Scheme 1) is described. The metalation can be selectively directed to either of the ortho positions by varying the base, metalation temperature, and exposure times. Metalation of o-anisic acid (1) with s-BuLi/TMEDA in THF at -78 degrees C occurs exclusively in the position adjacente to the carboxylate. On the other hand, a reversal of regioselectivity is observed with n-BuLi/t-BuOK. With LTMP at 0 degrees C, the two directors of m-anisic acid (2) function in concert to direct introduction of the metal between them while n-BuLi/t-BuOK removes preferentially the proton located ortho to the methoxy and para to the carboxylate (H-4). s-BuLi/TMEDA reacts with p-anisic acid (3) exclusively in the vicinity of the carboxylate. According to these methodologies, routes to very simple methoxybenzoic acids with a variety of functionalities that are not easily accessible by other means have been developed (Table 1).
authors: 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.
authors: Thi-Huu
authors: TH
authors: Nguyen
authors: Nguyet Trang Thanh
authors: NT
authors: Chau
authors: Anne-Sophie
authors: AS
authors: Castanet
authors: Kim Phi Phung
authors: KP
authors: Nguyen
authors: Jacques
authors: J
authors: Mortier