The directing group (DG)-assisted approach has so far been the major route to achieve selective C-H activation at both proximal and distal positions. While rhodium catalysts are highly effective in DG-assisted ortho-C-H arylation, meta-C-H arylation with rhodium has not yet been reported. In this study, we present the first example of Rh-catalyzed meta-C-H arylation of arenes. We found that the 2-cyanophenyl-based directing group, in conjunction with aryl boronic acids, selectively promotes meta-arylation with complete mono-selectivity. Despite significant advancements in meta-C-H activation for substrates with shorter linkers, such as hydrocinnamic acids, benzyl alcohols/amines, etc., meta-C-H activation of substrates with longer alkyl chains remains challenging with limited literature examples. We demonstrated that arenes with varying chain lengths, including conformationally flexible and less rigid ones such as 4-phenylbutanoic acid, 5-phenyl valeric acid, 6-phenylcaproic acid, 3-phenylpropanol, and 4-phenylbutanol underwent meta-arylation with high levels of regiocontrol. From a synthetic perspective, this approach could be valuable as it allows for the production of biaryl derivatives of flexible arenes with native functional groups at the meta-position. The synthetic utility of this strategy is demonstrated through the total synthesis of CNBCA, a bioactive compound possessing promising potency against the SHP2 enzyme activity in vitro.

中文翻译：

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铑催化的具有不同接头长度的芳烃的 meta-C-H 芳基化反应：桥接催化选择性与结构多样性


迄今为止，指导组 （DG） 辅助方法一直是在近端和远端位置实现选择性 C-H 激活的主要途径。虽然铑催化剂在 DG 辅助的邻位 C-H 芳基化反应中非常有效，但尚未报道与铑的 meta-C-H 芳基化反应。在这项研究中，我们提出了芳烃 Rh 催化的 meta-C-H 芳基化的第一个例子。我们发现基于 2-氰基苯的定向基团与芳基硼酸结合，选择性地促进具有完全单选择性的间芳基化。尽管具有较短接头的底物（如氢肉桂酸、苯甲醇/胺等）的 meta-C-H 活化取得了重大进展，但具有较长烷基链的底物的 meta-C-H 活化仍然具有挑战性，文献实例有限。我们证明具有不同链长的芳烃，包括构象柔韧性和刚性较低的芳烃，如 4-苯基丁酸、5-苯基戊酸、6-苯基己酸、3-苯基丙醇和 4-苯基丁醇，经历了高水平的区域控制。从合成的角度来看，这种方法可能很有价值，因为它允许在变位位置产生具有天然官能团的柔性芳烃的联芳基衍生物。该策略的合成效用通过 CNBCA 的全合成得到证明，CNBCA 是一种生物活性化合物，在体外具有对抗 SHP2 酶活性的良好效力。