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

在一个基于羧酸盐作为落叶导向基团的新概念框架内，我们打算开发从苯甲酸开始的区域选择性合成二取代芳烃的新方法。根据这一概念，羧酸盐最初通过引导第一取代基进入邻位而起到导向基团的作用，从而导致区域选择性的碳氢化合物功能化。这触发了一个脱羧的步骤，在这个步骤中，落叶的COOH基团被丢弃。所产生的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，羧酸盐在控制C-H功能化的区域选择性所需的时间内保持在原位，但在催化循环中无痕迹地脱落，从而排除了任何不需要的邻位和邻位双功能化。这种前所未有的反应模式的有效性已经在前期工作中得到了验证。提出的研究的关键目标是澄清芳基金属中间体的性质，并引导反应向第二次芳烃功能化而不是质子分解，以最大限度地提高可获得产品的多样性。

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.