Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, 34141, Republic of Korea.
Angew Chem Int Ed Engl. 2021 Mar 29;60(14):7873-7879. doi: 10.1002/anie.202016156. Epub 2021 Mar 1.
Through the formation of an electron donor-acceptor (EDA) complex, strain-release aminopyridylation of [1.1.1]propellane with N-aminopyridinium salts as bifunctional reagents enabled the direct installation of amino and pyridyl groups onto bicyclo[1.1.1]pentane (BCP) frameworks in the absence of an external photocatalyst. The robustness of this method to synthesize 1,3-aminopyridylated BCPs under mild and metal-free conditions is highlighted by the late-stage modification of structurally complex biorelevant molecules. Moreover, the strategy was extended to P-centered and CF radicals for the unprecedented incorporation of such functional groups with pyridine across the BCP core in a three-component coupling. This practical method lays the foundation for the straightforward construction of new valuable C4-pyridine-functionalized BCP chemical entities, thus significantly expanding the range of accessibility of BCP-type bioisosteres for applications in drug discovery.
通过形成电子给体-受体（EDA）复合物，[1.1.1]三叶烷与 N-氨吡啶盐作为双功能试剂的应变释放氨吡啶化反应，在没有外部光催化剂的情况下，能够将氨基和吡啶基直接安装到双环[1.1.1]戊烷（BCP）骨架上。该方法在温和无金属条件下合成 1,3-氨吡啶基化 BCP 的稳健性，通过对结构复杂的生物相关分子的后期修饰得到了突出体现。此外，该策略还扩展到 P 中心和 CF 自由基，用于在三组分偶联中以前所未有的方式将此类功能基团与吡啶基团引入 BCP 核中。这种实用的方法为直接构建新的有价值的 C4-吡啶功能化 BCP 化学实体奠定了基础，从而显著扩展了 BCP 型生物等排体在药物发现中的应用范围。
