Yang Baochao, Yang Guoqiang, Wang Qian, Zhu Jieping
Laboratory of Synthesis and Natural Products (LSPN), Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH5304, Lausanne CH-1015, Switzerland.
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
J Am Chem Soc. 2025 Mar 12;147(10):8969-8977. doi: 10.1021/jacs.5c01108. Epub 2025 Mar 2.
Under the Pd(II)/Pd(IV) catalytic cycle, the cyclization of pent-4-en-1-amine derivatives typically yields either pyrrolidines or piperidines depending on the N-protecting group. We report herein an unprecedented Pd(II)-catalyzed oxidative domino process that converts readily accessible N-protected 2-(2-amidoethyl)-1-methylenecyclobutane derivatives to 1-fluoro-2-azabicyclo[3.2.1]octanes. This transformation constructs three chemical bonds under mild conditions [Pd(hfacac) (5.0 mol %), Selectfluor (2.0 equiv), MeCN, 60 °C, 10 min] through a domino sequence involving 5--trig amidopalladation/Pd(II)-oxidation/chemoselective dyotropic rearrangement/C-F bond-forming reductive elimination. Notably, the cyclization mode remains independent of the N-protecting group under these conditions. Furthermore, diverse functional groups can be introduced at the bridgehead position of a bicyclic compound via an apparent -Bredt bridgehead iminium intermediate.
在钯（II）/钯（IV）催化循环下，取决于N-保护基，4-戊烯-1-胺衍生物的环化通常生成吡咯烷或哌啶。我们在此报告了一种前所未有的钯（II）催化的氧化多米诺过程，该过程将易于获得的N-保护的2-（2-氨基乙基）-1-亚甲基环丁烷衍生物转化为1-氟-2-氮杂双环[3.2.1]辛烷。这种转化在温和条件下[Pd（hfacac）（5.0 mol％），Selectfluor（2.0当量），乙腈，60°C，10分钟]通过涉及5-反式酰胺钯化/钯（II）氧化/化学选择性双环重排/C-F键形成还原消除的多米诺序列构建三个化学键。值得注意的是，在这些条件下，环化模式与N-保护基无关。此外，通过明显的布瑞德桥头亚胺鎓中间体，可以在双环化合物的桥头位置引入各种官能团。
