Bosse Aaron T, Hunt Liam R, Suarez Camila A, Casselman Tyler D, Goldstein Elizabeth L, Wright Austin C, Park Hojoon, Virgil Scott C, Yu Jin-Quan, Stoltz Brian M, Davies Huw M L
Department of Chemistry, Emory University, Atlanta, GA 30322, USA.
Warren and Katherine Schlinger Laboratory of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Science. 2024 Nov 8;386(6722):641-646. doi: 10.1126/science.adp2425. Epub 2024 Nov 7.
(-)-Cylindrocyclophane A is a 22-membered C-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(sp)-C(sp) 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(sp)-H acetoxylation installed the bis-resorcinol moieties. This research exemplifies how multilaboratory collaborations can produce substantial modernizations of complex total synthesis endeavors.
（-）-圆柱环戊烷A是一种含有双间苯二酚官能团和六个立体中心的22元C对称[7.7]对环芳烷。我们报道了一种用于（-）-圆柱环戊烷A的合成策略，该策略使用了10次C-H官能化反应，从而得到了一条具有高对映选择性和效率的简化路线（17步）。使用手性四羧酸二铑催化实现了伯位和仲位的C-H官能化，这通过钯催化的C(sp)-C(sp)交叉偶联得到补充，从而以高区域选择性、非对映选择性和对映选择性快速形成大环核心和所有立体中心。后期使用钯催化的四重C(sp)-H乙酰氧基化反应引入了双间苯二酚部分。这项研究例证了多实验室合作如何能够实现复杂全合成努力的实质性现代化。
