瑞士洛桑联邦理工学院祝介平团队的一项最新研究发现，钯催化的应变释放双移重排：亚甲基环丁烷的扩环酰胺氟化反应。2025年3月2日，国际知名学术期刊《美国化学会杂志》发表了这一成果。

研究组在此报道了一个前所未有的Pd（II）催化氧化多米诺反应，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-氮杂环[3.2.1]辛烷。该转化在温和条件下，通过多米诺骨牌序列构建了三个化学键[Pd(hfacac)₂ (5.0 mol %), selectfluv (2.0 equiv), MeCN, 60°C， 10 min]，涉及5-外三角酰胺化/Pd（II）氧化/化学选择性异向重排/C -F键形成还原消除。值得注意的是，在这些条件下，环化模式仍然独立于N保护基团。

此外，不同的官能团可以在双环化合物的桥头堡位置通过一个明显的抗Bredt桥头堡铝中间体引入。

据了解，在Pd(II)/Pd（IV）催化循环下，根据N保护基团的不同，戊-4-烯-1-胺衍生物的环化通常产生吡咯烷或哌啶。

附：英文原文

Title: Pd-Catalyzed Strain-Releasing Dyotropic Rearrangement: Ring-Expanding Amidofluorination of Methylenecyclobutanes

Author: Baochao Yang, Guoqiang Yang, Qian Wang, Jieping Zhu

Issue&Volume: March 2, 2025

Abstract: 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)₂ (5.0 mol %), Selectfluor (2.0 equiv), MeCN, 60 °C, 10 min] through a domino sequence involving 5-exo-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 anti-Bredt bridgehead iminium intermediate.

DOI: 10.1021/jacs.5c01108

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c01108