Division of Chemistry and Chemical Engineering , California Institute of Technology , Pasadena , California 91125 , United States.
Department of Chemistry , Stanford University , Stanford , California 94305 , United States.
J Org Chem. 2018 Mar 16;83(6):3023-3033. doi: 10.1021/acs.joc.7b03291. Epub 2018 Jan 31.
The desire for maximally efficient transformations in complex molecule synthesis has contributed to a surge of interest in C-H functionalization methods development in recent years. In contrast to the steady stream of methodological reports, however, there are noticeably fewer studies comparing the efficacies of different C-H functionalization protocols on a single structurally intricate substrate. Recognizing the importance of heteroatom incorporation in complex molecule synthesis, this report discloses a comparative examination of diverse strategies for C-O, C-N, and C-X bond formation through late-stage C-H oxidation of the tricyclic cyanthiwigin natural product core. Methods for allylic C-H acetoxylation, tertiary C-H hydroxylation, tertiary C-H amination, tertiary C-H azidation, and secondary C-H halogenation are explored. These efforts highlight the robustness and selectivities of many well-established protocols for C-H oxidation when applied to a complex molecular framework, and the findings are relevant to chemists aiming to employ such strategies in the context of chemical synthesis.
近年来，对复杂分子合成中最大效率转化的渴望推动了 C-H 功能化方法发展的兴趣激增。然而，与不断涌现的方法学报告相比，在单一结构复杂的底物上比较不同 C-H 功能化方案的效率的研究明显较少。鉴于杂原子在复杂分子合成中的重要性，本报告披露了通过三环苍术甙天然产物核心的晚期 C-H 氧化对 C-O、C-N 和 C-X 键形成的多种策略的比较研究。探索了烯丙基 C-H 乙酰氧基化、叔 C-H 羟基化、叔 C-H 胺化、叔 C-H 叠氮化和仲 C-H 卤化的方法。这些努力突出了许多成熟的 C-H 氧化方法在应用于复杂分子骨架时的稳健性和选择性，并且这些发现与旨在在化学合成中采用此类策略的化学家相关。
