美国埃默里大学Huw M. L. Davies研究团队报道了，CH功能化实现的(-)-cylindrocyclophane A的全合成。相关研究成果发表在2024年11月8日出版的《科学》。

(-)-Cylindrocyclophane A是一种22元C2对称[7.7]对环烷，具有双间苯二酚官能团和六个立体中心。

研究人员报告了一种使用10个CH官能化反应的(-)-cylindrocyclophane A的合成策略，该策略具有高对映选择性和效率的简化路线（17个步骤）。

手性四羧酸二氢铑的催化实现了伯位和仲位的C-H官能化，并辅以钯催化的C（sp²）-C（sp²）交叉偶联，从而快速形成大环核心和所有具有高区域、非对映和对映选择性的立体中心。使用后续钯催化的四重C（sp²）-H乙酰氧基化安装了双间苯二酚部分。

该项研究展示了多实验室合作，如何实现复杂全合成工作的实质性现代化。

附：英文原文

Title: Total synthesis of (-)-cylindrocyclophane A facilitated by CH functionalization

Author: Aaron T. Bosse, Liam R. Hunt, Camila A. Suarez, Tyler D. Casselman, Elizabeth L. Goldstein, Austin C. Wright, Hojoon Park, Scott C. Virgil, Jin-Quan Yu, Brian M. Stoltz, Huw M. L. Davies

Issue&Volume: 2024-11-08

Abstract: ()-Cylindrocyclophane A is a 22-membered C2-symmetric [7.7]paracyclophane that bears bis-resorcinol functionality and six stereocenters. We report a synthetic strategy for ()-cylindrocyclophane A that uses 10 CH functionalization reactions, resulting in a streamlined route with high enantioselectivity and efficiency (17 steps). The use of chiral dirhodium tetracarboxylate catalysis enabled the C–H functionalization of primary and secondary positions, which was complemented by palladium-catalyzed C(sp2)–C(sp2) cross-couplings, resulting in the rapid formation of the macrocyclic core and all stereocenters with high regio-, diastereo-, and enantioselectivity. The use of a late-stage palladium-catalyzed fourfold C(sp2)–H acetoxylation installed the bis-resorcinol moieties. This research exemplifies how multilaboratory collaborations can produce substantial modernizations of complex total synthesis endeavors.

DOI: adp2425

Source: https://www.science.org/doi/10.1126/science.adp2425