Kim Changha, Kim Yuhyun, Hong Sungwoo
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, Korea.
Nat Commun. 2024 Jul 17;15(1):5993. doi: 10.1038/s41467-024-50356-3.
Current methodologies for the functionalization of [1.1.1]propellane primarily focus on achieving 1, 3-difunctionalized bicyclo[1.1.1]pentane or ring-opened cyclobutane moiety. Herein, we report an innovative approach for the 1, 3-difunctionalization of [1.1.1]propellane, enabling access to a diverse range of highly functionalized cyclobutanes via nucleophilic attack followed by ring opening and iron-hydride hydrogen atom transfer. To enable this method, we developed an efficient iron-catalyzed hydropyridylation of various alkenes for C - H alkylation of pyridines at the C4 position, eliminating the need for stoichiometric quantities of oxidants or reductants. Mechanistic investigations reveal that the resulting N-centered radical serves as an effective oxidizing agent, facilitating single-electron transfer oxidation of the reduced iron catalyst. This process efficiently sustains the catalytic cycle, offering significant advantages for substrates with oxidatively sensitive functionalities that are generally incompatible with alternative approaches. The strategy presented herein is not only mechanistically compelling but also demonstrates broad versatility, highlighting its potential for late-stage functionalization.
目前用于[1.1.1]丙搭烯官能化的方法主要集中于实现1,3-双官能化的双环[1.1.1]戊烷或开环环丁烷部分。在此，我们报道了一种用于[1.1.1]丙搭烯1,3-双官能化的创新方法，该方法通过亲核进攻、开环以及铁氢化物氢原子转移，能够得到多种高度官能化的环丁烷。为实现此方法，我们开发了一种高效的铁催化各种烯烃的氢吡啶化反应，用于吡啶在C4位的C-H烷基化反应，无需化学计量的氧化剂或还原剂。机理研究表明，生成的以氮为中心的自由基作为一种有效的氧化剂，促进还原态铁催化剂的单电子转移氧化。该过程有效地维持了催化循环，对于具有氧化敏感官能团的底物具有显著优势，这些底物通常与其他方法不相容。本文提出的策略不仅在机理上令人信服，而且具有广泛的通用性，突出了其在后期官能化中的潜力。
