Ru-catalyzed room-temperature alkylation and late-stage alkylation of arenes with primary alkyl bromides
Ru-catalyzed room-temperature alkylation and late-stage alkylation of arenes with primary alkyl bromides
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DOI：
10.1016/j.checat.2021.05.008
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
M. Wheatley;Michael T Findlay;Rocío López-Rodríguez;Diego M Cannas;Marco Simonetti;Igor Larrosa
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文献类型：
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作者：
M. Wheatley;Michael T Findlay;Rocío López-Rodríguez;Diego M Cannas;Marco Simonetti;Igor Larrosa
芳烃与N-基导向基团的C-H烷基化通常需要高温和/或苛刻的反应条件，这传统上降低了其官能团相容性和后期官能化的适用性。我们报告，环化钌配合物是能够进行C-H烷基化芳烃轴承各种N-导向基团与伯烷基溴在室温下，在温和的反应条件下。我们证明了这一点与扩展的底物范围，其中包括几个例子的后期阶段的烷基化药物分子，从而展示了“现实世界”的能力，这种方法。机理研究表明，与以前的机理建议相反，反应通过双环化Ru中间体进行，然后通过SN 2型氧化加成。
The C–H alkylation of arenes with N-based directing groups typically requires high temperatures and/or harsh reaction conditions, which has traditionally reduced its functional group compatibility and applicability for late-stage functionalization. We report that a cyclometallated Ru complex is able to perform the C–H alkylation of arenes bearing a variety of N-directing groups with primary alkyl bromides at room temperature and under mild reaction conditions. We demonstrate this with an extended substrate scope, which includes several examples of late-stage alkylation of drug molecules, thus showcasing the "real-world" capabilities of this method. Mechanistic studies show that, in contrast to previous mechanistic proposals, the reaction proceeds via a bis-cyclometallated Ru intermediate, followed by an SN2-type oxidative addition.