Yi Liang, Kong Deshen, Prabhakar Kale Ajit, Alshehri Rawan, Yue Huifeng, Gizatullin Amir, Maity Bholanath, Kancherla Rajesh, Cavallo Luigi, Rueping Magnus
KAUST Catalysis Center (KCC), King Abdullah University of Science and Technology (KAUST), 23955-6900, Thuwal, Saudi Arabia.
Key Laboratory of Molecule Synthesis and Function Discovery, Fujian Province University), College of Chemistry, Fuzhou University, 350108, Fuzhou, China.
Angew Chem Int Ed Engl. 2024 Dec 16;63(51):e202411961. doi: 10.1002/anie.202411961. Epub 2024 Oct 30.
Bicyclo[1.1.1]pentane (BCP), recognized as a bioisostere for para-disubstituted benzene, has gained widespread interest in drug development due to its ability to enhance the physicochemical properties of pharmaceuticals. In this work, we introduce a photoinduced, halogen bonding-initiated, metal-free strategy for synthesizing various BCP derivatives. This method involves the generation of nucleophilic α-aminoalkyl radicals via halogen-bonding adducts. These undergo selective radical addition to [1.1.1]propellane, yielding electrophilic BCP radicals that subsequently participate in polarity-matched additions, culminating in the difunctionalization of bicyclopentane. The versatility and practicality of this metal-free approach are underscored by its broad substrate scope, which includes late-stage functionalization and a series of valuable transformations, all conducted under mild reaction conditions.
双环[1.1.1]戊烷（BCP）被认为是对二取代苯的生物电子等排体，由于其能够改善药物的物理化学性质，在药物开发中受到了广泛关注。在这项工作中，我们介绍了一种光诱导、卤键引发的无金属策略，用于合成各种BCP衍生物。该方法涉及通过卤键加合物生成亲核α-氨基烷基自由基。这些自由基对[1.1.1]丙烷进行选择性自由基加成，生成亲电BCP自由基，随后亲电BCP自由基参与极性匹配的加成反应，最终实现双环戊烷的双官能化。这种无金属方法的通用性和实用性体现在其广泛的底物范围，包括后期官能化和一系列有价值的转化反应，所有反应均在温和的反应条件下进行。
