Rational development of regioselective difunctionalizations of arenes using carboxylates as deciduous directing groups

使用羧酸盐作为落叶导向基团的芳烃区域选择性双官能化的合理发展

• 批准号: 323224092
• 负责人: Professor Dr. Lukas J. Gooßen
• 金额: --
• 依托单位: Lehrstuhl für Organische Chemie I (AG Gooßen)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/323224092?language=en
• 关键词: Rational; development; regioselective; difunctionalizations; arenes

Within a novel conceptual framework based on the use of carboxylates as deciduous directing groups, we intend to develop new methods for the regioselective synthesis of disubstituted arenes starting from benzoic acids. According to this concept, the carboxylate initially acts as a directing group by guiding a first substituent into its ortho position, leading to a regioselective C-H functionalization. This triggers a decarboxylation step in which the deciduous COOH group is discarded. The resulting organometallic intermediate is trapped by an electrophile, leading to the regioselective formation of a second C-C or C-heteroatom bond. The carboxylate thus stays in place as long as it is needed to control the regioselectivity of the C-H functionalization, but is shed tracelessly within the catalytic cycle, precluding any unwanted ortho,ortho-difunctionalization. The validity of this unprecedented reaction mode has been demonstrated in preliminary work. The key targets of the proposed research are to clarify the nature of the aryl-metal intermediate and to steer the reaction towards a second arene functionalization rather than protonolysis in order to maximize the diversity of obtainable products.

在一个新的概念框架的基础上使用的羧酸酯作为落叶导向基团，我们打算开发新的方法，从苯甲酸开始的二取代芳烃的区域选择性合成。根据该概念，羧酸酯最初通过将第一取代基引导至其邻位而充当导向基团，导致区域选择性C-H官能化。这引发了脱羧步骤，其中脱落的COOH基团被丢弃。所得有机金属中间体被亲电试剂捕获，导致第二个C-C或C-杂原子键的区域选择性形成。因此，只要需要控制C-H官能化的区域选择性，羧酸酯就保持在原位，但在催化循环内无痕迹地脱落，从而排除任何不需要的邻位、邻位-二官能化。这种前所未有的反应模式的有效性已在初步工作中得到证明。所提出的研究的关键目标是澄清芳基金属中间体的性质，并将反应转向第二芳烃官能化而不是质子化，以最大限度地提高可获得的产品的多样性。