Anderson T E, Thamattoor Dasan M, Phillips David Lee
Department of Chemistry, Colby College, 5765 Mayflower Hill, Waterville, ME, 04901, USA.
Department of Chemistry, The University of Hong Kong, Pokfulam Road, 999077, Hong Kong, Hong Kong SAR PRC.
Nat Commun. 2024 Sep 27;15(1):8313. doi: 10.1038/s41467-024-52390-7.
Strained cycloalkynes are valuable building blocks in synthetic chemistry due to their high degree of reactivity and ability to form structurally complex scaffolds, common features of many pharmaceuticals and natural products. Alkylidene carbenes provide a pathway to the formation of strained cycloalkynes through Fritsch-Buttenberg-Wiechell rearrangements, but this strategy, like other methods of alkyne generation, is believed to depend upon a thermodynamic equilibrium that favors the alkyne over the carbene. Herein three highly strained, polycyclic alkynes, previously thought to be thermodynamically inaccessible, are generated under mild conditions and intercepted through Diels-Alder cycloaddition with a diene trapping agent. The use of a different trapping agent also allows for the interception of the alkylidene carbene, providing the first instance in which both an exocyclic alkylidene carbene and its cycloalkyne Fritsch-Buttenberg-Wiechell rearrangement product have been trapped.
由于其高反应活性以及形成结构复杂支架的能力，张力环炔烃是合成化学中有价值的构建单元，这是许多药物和天然产物的共同特征。亚烷基卡宾通过弗里茨希-布滕贝格-维歇尔重排反应提供了一条形成张力环炔烃的途径，但这种策略与其他生成炔烃的方法一样，被认为依赖于有利于炔烃而非卡宾的热力学平衡。在此，三种高度张力的多环炔烃在温和条件下生成，此前认为它们在热力学上无法获得，并且通过与二烯捕获剂的狄尔斯-阿尔德环加成反应进行截获。使用不同的捕获剂还能够截获亚烷基卡宾，这提供了首个外环亚烷基卡宾及其环炔烃弗里茨希-布滕贝格-维歇尔重排产物均被捕获的实例。
