Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104-6323, USA.
Medicinal Chemistry Department, Neuroscience Discovery Research, AbbVie Deutschland GmbH & Co. KG, 67061, Ludwigshafen, Germany.
Angew Chem Int Ed Engl. 2023 Jun 12;62(24):e202302223. doi: 10.1002/anie.202302223. Epub 2023 May 4.
1-Aryl-substituted bicyclo[1.1.1]pentanes (BCPs) are an important class of BCP derivatives with widespread application in drug development. Most syntheses of these materials require multiple chemical steps via BCP electrophiles or nucleophiles derived from [1.1.1]propellane. Although one-step, multicomponent radical cross-coupling reactions could provide a more sustainable and rapid route to access diverse heteroarylated BCPs, current approaches are limited to tertiary alkyl radicals, leading to a decrease in their practical value. In this study, a conceptually different approach enabled by a radical multicomponent heteroarylation of [1.1.1]propellane to access functionalized heteroarylated BCPs is described. Importantly, this protocol is compatible with primary-, secondary-, and tertiary aliphatic radicals, as well as various fluoroalkyl radical sources, thus enabling rapid library generation of sought-after BCP derivatives for drug development.
1-芳基取代的双环[1.1.1]戊烷（BCPs）是一类重要的 BCP 衍生物，在药物开发中有广泛的应用。这些材料的大多数合成需要通过[1.1.1]莰烯衍生的 BCP 亲电试剂或亲核试剂进行多步化学合成。尽管一步多组分自由基交叉偶联反应可以提供一种更可持续和快速的方法来获得各种杂芳基化的 BCP，但目前的方法仅限于叔烷基自由基，从而降低了它们的实际价值。在这项研究中，描述了一种通过[1.1.1]莰烯的自由基多组分杂芳基化来获得功能化的杂芳基化 BCP 的新概念方法。重要的是，该方案与伯、仲和叔脂肪族自由基以及各种氟烷基自由基源兼容，从而能够快速生成用于药物开发的所需 BCP 衍生物文库。
