A General Route to Bicyclo[1.1.1]pentanes through Photoredox Catalysis
A General Route to Bicyclo[1.1.1]pentanes through Photoredox Catalysis
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DOI：
10.1021/acscatal.9b03190
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发表时间：
2019-10-01
期刊：
影响因子：
12.9
通讯作者：
Anderson, Edward A.
中科院分区：
文献类型：
--
作者：
Nugent, Jeremy;Arroniz, Carlos;Anderson, Edward A.
光氧化还原催化改变了自由基合成化学的面貌。通过光氧化还原催化产生的自由基与碳-碳π键的加成已被广泛接受；然而，这种方法尚未应用于碳-碳α-键的功能化。在这里，我们首次报道了利用光氧化还原催化来促进有机卤化物加成到碳环[1.1.1]丙烷中；产品双环[1.1.1]戊烷 (BCP) 是制药工业和材料化学中非常重要的基序。该方法显示出广泛的底物范围和官能团耐受性，首次实现了 sp(2) 碳-卤素键双环戊基化以获得（杂）芳基化 BCP，以及不稳定 sp(3) 自由基的官能化。含有烯烃受体的底物允许通过前所未有的原子转移自由基环化级联一步构建多环双环戊烷产物，同时通过天然产物类和药物类分子的后期双环戊基化证明了加速药物发现的潜力。机理研究证明了光催化剂在该化学中的重要性，并提供了对反应循环中自由基稳定性和应力消除的平衡的深入了解。
Photoredox catalysis has transformed the land-scape of radical-based synthetic chemistry. Additions of radicals generated through photoredox catalysis to carbon-carbon pi-bonds are well-established; however, this approach has yet to be applied to the functionalization of carbon-carbon a-bonds. Here, we report the first such use of photoredox catalysis to promote the addition of organic halides to the carbocycle [1.1.1]propellane; the product bicyclo[1.1.1]pentanes (BCPs) are motifs of high importance in the pharmaceutical industry and in materials chemistry. Showing broad substrate scope and functional group tolerance, this methodology results in the first examples of bicyclopentylation of sp(2) carbon-halogen bonds to access (hetero)arylated BCPs, as well as the functionalization of nonstabilized sp(3) radicals. Substrates containing alkene acceptors allow the single-step construction of polycyclic bicyclopentane products through unprecedented atom transfer radical cyclization cascades, while the potential to accelerate drug discovery is demonstrated through late-stage bicyclopentylations of natural productlike and druglike molecules. Mechanistic investigations demonstrate the importance of the photocatalyst in this chemistry and provide insight into the balance of radical stability and strain relief in the reaction cycle.