First General, Direct, and Regioselective Synthesis of Substituted Methoxybenzoic Acids by Ortho Metalation

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• 作者：Thi-Huu Nguyen ; Nguyet Trang Thanh Chau ; Anne-Sophie Castanet ; Kim Phi Phung Nguyen ; Jacques Mortier
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：April 27, 2007
• 年：2007
• 卷：72
• 期：9
• 页码：3419 - 3429
• 全文大小：171K
• 年卷期：v.72,no.9(April 27, 2007)
• ISSN：1520-6904

文摘

New general methodology of value in aromatic chemistry based on ortho-metalation sites in o-, m-, andp-anisic acids (1-3) (Scheme 1) is described. The metalation can be selectively directed to either of theortho positions by varying the base, metalation temperature, and exposure times. Metalation of o-anisicacid (1) with s-BuLi/TMEDA in THF at -78 C occurs exclusively in the position adjacente to thecarboxylate. On the other hand, a reversal of regioselectivity is observed with n-BuLi/t-BuOK. WithLTMP at 0 C, the two directors of m-anisic acid (2) function in concert to direct introduction of themetal between them while n-BuLi/t-BuOK removes preferentially the proton located ortho to the methoxyand para to the carboxylate (H-4). s-BuLi/TMEDA reacts with p-anisic acid (3) exclusively in the vicinityof the carboxylate. According to these methodologies, routes to very simple methoxybenzoic acids witha variety of functionalities that are not easily accessible by other means have been developed (Table 1).