Radhoff Niklas, Daniliuc Constantin G, Studer Armido
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstraße 40, 48149, Münster, Germany.
Angew Chem Int Ed Engl. 2023 Aug 21;62(34):e202304771. doi: 10.1002/anie.202304771. Epub 2023 Jun 20.
Design, synthesis and application of benzene bioisosteres have attracted a lot of attention in the past 20 years. Recently, bicyclo[2.1.1]hexanes have emerged as highly attractive bioisosteres for ortho- and meta-substituted benzenes. Herein we report a mild, scalable and transition-metal-free protocol for the construction of highly substituted bicyclo[2.1.1]hexan-2-ones through Lewis acid catalyzed (3+2)-cycloaddition of bicyclo[1.1.0]-butane ketones with disubstituted ketenes. The reaction shows high functional group tolerance as documented by the successful preparation of various 3-alkyl-3-aryl as well as 3,3-bisalkyl bicyclo[2.1.1]hexan-2-ones (26 examples, up to 89 % yield). Postfunctionalization of the exocyclic ketone moiety is also demonstrated.
在过去20年中，苯生物电子等排体的设计、合成及应用备受关注。最近，双环[2.1.1]己烷已成为邻位和间位取代苯极具吸引力的生物电子等排体。在此，我们报道了一种温和、可扩展且无过渡金属的方法，通过双环[1.1.0] - 丁烷酮与二取代烯酮的路易斯酸催化（3 + 2）环加成反应来构建高度取代的双环[2.1.1]己烷 - 2 - 酮。该反应显示出高官能团耐受性，成功制备了各种3 - 烷基 - 3 - 芳基以及3,3 - 双烷基双环[2.1.1]己烷 - 2 - 酮（26个实例，产率高达89%），同时还展示了环外酮部分的后期官能团化。
