2024-11-08 カリフォルニア工科大学(Caltech)
A 3-D X-ray diffraction image of cylindrocyclophane A. The bonds highlighted in blue were prepared using catalytic C–H bond functionalization reactions.Credit: Camila Suarez
＜関連情報＞
- https://www.caltech.edu/about/news/breaking-carbonhydrogen-bonds-to-make-complex-molecules
- https://www.science.org/doi/10.1126/science.adp2425
C-H官能基化を利用した(-)-シリンドロシクロファンAの全合成に成功 Total synthesis of (−)-cylindrocyclophane A facilitated by C−H functionalization
Aaron T. Bosse, Liam R. Hunt, Camila A. Suarez, Tyler D. Casselman, […], and Huw M. L. Davies
Science Published:7 Nov 2024
DOI:https://doi.org/10.1126/science.adp2425
Editor’s summary
C−H bonds abound in the sorts of molecules used as precursors in drug synthesis, but they are conventionally the most inert. Over the past two decades, multiple advances in catalysis have enabled the direct functionalization of C−H bonds. Bosse et al. now showcase some of these advances in an asymmetric synthesis of the natural product (−)-cylindrocyclophane A, specifically relying on rhodium and palladium catalysis to achieve 10 C−H functionalization reactions for the formation of C−C and C−O bonds. —Jake S. Yeston
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.
