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

被引：8

作者：

Bosse, Aaron T. ^{[1
]}

Hunt, Liam R. ^{[2
]}

Suarez, Camila A. ^{[1
,2
]}

Casselman, Tyler D. ^{[2
]}

Goldstein, Elizabeth L. ^{[2
]}

Wright, Austin C. ^{[2
]}

Park, Hojoon ^{[3
]}

Virgil, Scott C. ^{[2
]}

Yu, Jin-Quan ^{[3
]}

Stoltz, Brian M. ^{[2
]}

Davies, Huw M. L. ^{[1
]}

机构：

[1] Emory Univ, Dept Chem, Atlanta, GA 30322 USA

[2] CALTECH, Warren & Katherine Schlinger Lab Chem & Chem Engn, Pasadena, CA 91125 USA

[3] Scripps Res Inst, La Jolla, CA 92037 USA

来源：

SCIENCE | 2024年 / 386卷 / 6722期

基金：

美国国家科学基金会;

关键词：

ENANTIOSELECTIVE TOTAL-SYNTHESIS; TRANSITION-METAL CATALYSIS; CYLINDROCYCLOPHANES;

D O I：

10.1126/science.adp2425

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

(-)-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.

引用

页码：641 / 646

页数：6

共 42 条

[41] Syntheses of naturally occurring cytotoxic [7.7]paracyclophanes, (-)-cylindrocyclophane A and its enantiomer, and implications for biological activity [J].