Department of Chemistry, Indian Institute of Technology Patna, Bihta 801106, Bihar, India.
Org Biomol Chem. 2019 Jul 17;17(28):6809-6820. doi: 10.1039/c9ob01082c.
In the present study, we report the palladium(ii)-catalyzed regioselective ortho-C-H bromination/iodination of challenging arylacetamide derivatives using N-halosuccinimides as halogenating agents. Diverse arylacetamides underwent the regioselective ortho-bromination and iodination of aromatic C-H bonds in the presence of a reactive benzylic C(sp3)-H bond without installing any bulky auxiliaries via unfavorable six-membered metallacycles. Weak coordination, the use of ubiquitous primary amides for challenging C-H functionalization, the simple catalytic system and the wide substrate scope are the key features of this transformation. Further, the halogenated amide derivatives were transformed into a variety of valuable synthons. Detailed mechanistic studies revealed some interesting aspects concerning the reaction pathway. We present for the first time strong evidence for the formation of imidic acid (in situ) from primary amides under Brønsted acid conditions that eventually aids in the stabilization of palladacycles of amide derivatives and drives regioselective C-X bond formation.
在本研究中，我们报告了使用 N-卤代琥珀酰亚胺作为卤化剂，钯（ii）催化的具有挑战性的芳基乙酰胺衍生物的区域选择性邻位 C-H 溴化/碘化。在存在反应性苄基 C(sp3)-H 键的情况下，各种芳基乙酰胺通过不利的六元金属环化反应，无需安装任何庞大的辅助基团，经历了芳香族 C-H 键的区域选择性邻位溴化和碘化。弱配位、使用普遍存在的伯酰胺进行具有挑战性的 C-H 官能化、简单的催化体系和广泛的底物范围是这种转化的关键特征。此外，卤代酰胺衍生物被转化为多种有价值的合成子。详细的机理研究揭示了反应途径的一些有趣方面。我们首次提出了在 Brønsted 酸条件下，伯酰胺形成亚氨酸（原位）的有力证据，这最终有助于酰胺衍生物的钯配合物的稳定，并驱动区域选择性 C-X 键形成。
