Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania19104-6323, United States.
Medicinal Chemistry Department, Neuroscience Discovery Research, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen67061, Germany.
J Am Chem Soc. 2022 Jul 20;144(28):12961-12969. doi: 10.1021/jacs.2c05304. Epub 2022 Jul 6.
Bicyclo[1.1.1]pentane (BCP) motifs as para-disubstituted aryl bioisosteres are playing an emerging role in pharmaceutical, agrochemical, and materials chemistry. The vast majority of these structures is obtained from a BCP electrophile or nucleophile, which are themselves derived from [1.1.1]propellane via cleavage of the internal C-C bond through the addition of either radicals or metal-based nucleophiles. Compared with the current stepwise approaches, a multicomponent reaction that provides direct access to complex and diverse disubstituted BCP products would be more attractive. Herein, we report a single-step, multicomponent approach to synthetically versatile arylated BCP products via nickel/photoredox catalysis. Importantly, this three-component process allows two C-C bonds to be formed in a single step and sets three quaternary centers, unprecedented in any previously reported methods. The method has been demonstrated to allow access to complex BCP architectures from aryl halide and radical precursor substrates.
双环[1.1.1]戊烷（BCP）作为对位取代的芳基生物等排体，在药物、农用化学品和材料化学中发挥着越来越重要的作用。这些结构中的绝大多数是由 BCP 亲电试剂或亲核试剂衍生而来的，而这些亲电试剂或亲核试剂本身又是通过自由基或基于金属的亲核试剂的加成，从[1.1.1]莰烷中切断内部 C-C 键得到的。与当前的逐步方法相比，多组分反应可直接提供复杂多样的双取代 BCP 产物，更具吸引力。本文报道了一种镍/光氧化还原催化的、合成多功能芳基 BCP 产物的一步多组分方法。重要的是，该三组分反应可在一步中形成两个 C-C 键，并设置三个季碳原子，这在以前报道的任何方法中都是前所未有的。该方法已被证明可从芳基卤化物和自由基前体底物中获得复杂的 BCP 结构。
