Total synthesis of (−)-cylindrocyclophane A facilitated by C−H functionalization

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2024-11-07 DOI:10.1126/science.adp2425

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

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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 C−H 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.

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通过 C-H 功能化促进 (-)-cylindrocyclophane A 的全合成

(-)-Cylindrocyclophane A 是一种 22 元 C 2 - 不对称 [7.7]paracyclophane，具有双间苯二酚官能团和六个立体中心。我们报告了一种 (-)-cylindrocyclophane A 的合成策略，该策略使用了 10 个 C-H 官能化反应，形成了一条具有高对映选择性和高效率（17 个步骤）的简化路线。使用手性四羧酸二氢铑催化实现了一级和二级位置的 C-H 功能化，再辅以钯催化的 C(sp 2 )-C(sp 2 ) 交叉耦合，从而以高区域、非对映和对映选择性快速形成了大环核心和所有立体中心。后期使用钯催化的四重 C(sp 2 )-H 乙酰氧基化反应安装了双间苯二酚分子。这项研究体现了多实验室合作如何使复杂的全合成工作实现实质性的现代化。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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