Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Nat Commun. 2020 Oct 19;11(1):5266. doi: 10.1038/s41467-020-19038-8.
Despite the fundamental importance of efficient and selective synthesis of widely useful alkylarenes, the direct catalytic C(sp)-H alkylation of unactivated arenes with a readily available alkyl halide remains elusive. Here, we report the catalytic C(sp)-H alkylation reactions of unactivated arenes with alkyl bromides via visible-light induced Pd catalysis. The reaction proceeds smoothly under mild conditions without any skeletal rearrangement of the alkyl groups. The direct syntheses of structurally diverse linear and branched alkylarenes, including the late-stage phenylation of biologically active molecules and an orthogonal one-pot sequential Pd-catalyzed C-C bond-forming reaction, are achieved with exclusive chemoselectivity and exceptional functional group tolerance. Comprehensive mechanistic investigations through a combination of experimental and computational methods reveal a distinguishable Pd(0)/Pd(I) redox catalytic cycle and the origin of the counter-intuitive reactivity differences among alkyl halides.
尽管高效和选择性合成广泛有用的烷基芳烃具有重要意义，但用易得的卤代烷烃直接催化 C(sp 3 )-H 烷基化未活化的芳烃仍然难以实现。在此，我们报告了通过可见光诱导 Pd 催化，未活化芳烃与烷基溴的 C(sp 3 )-H 烷基化反应。该反应在温和的条件下顺利进行，烷基基团没有任何骨架重排。通过直接合成结构多样的直链和支链烷基芳烃，包括生物活性分子的后期芳基化和正交一锅顺序 Pd 催化 C-C 键形成反应，实现了独特的化学选择性和出色的官能团耐受性。通过实验和计算方法的组合进行综合的机理研究揭示了一个可区分的 Pd(0)/Pd(I)氧化还原催化循环以及卤代烷烃之间反直觉反应性差异的起源。
