Dearomative Photocatalytic Construction of Bridged 1,3-Diazepanes
Dearomative Photocatalytic Construction of Bridged 1,3-Diazepanes
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DOI：
10.1002/anie.201914390
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发表时间：
2020-01-27
影响因子：
16.6
通讯作者：
Dixon, Darren J.
中科院分区：
文献类型：
--
作者：
Leitch, Jamie A.;Rogova, Tatiana;Dixon, Darren J.
构建多种富含sp（3）的骨架环系统对于药物发现和天然产物合成具有重要意义。在此，我们报告了通过Minisci反应的还原转向来光催化构建2，7-二氮杂双环[3.2.1]辛烷（桥连1，3-二氮杂环庚烷）。提出稠合三环产物通过自由基加成至4-取代的喹啉底物的C4位置形成，随后Hantzsch酯促进还原为二氢吡啶中间体，其经历原位双电子环闭合以形成桥接的二氮杂环庚烷结构。广泛的N-芳基亚胺和喹啉衍生物被证明和良好的效率，观察到在空间拥挤的全碳季中心的建设。计算和实验机制的研究提供了深入的反应机理和观察到的区域选择性/非对映选择性。
The construction of diverse sp(3)-rich skeletal ring systems is of importance to drug discovery programmes and natural product synthesis. Herein, we report the photocatalytic construction of 2,7-diazabicyclo[3.2.1]octanes (bridged 1,3-diazepanes) via a reductive diversion of the Minisci reaction. The fused tricyclic product is proposed to form via radical addition to the C4 position of 4-substituted quinoline substrates, with subsequent Hantzsch ester-promoted reduction to a dihydropyridine intermediate which undergoes in situ two-electron ring closure to form the bridged diazepane architecture. A wide scope of N-arylimine and quinoline derivatives was demonstrated and good efficiency was observed in the construction of sterically congested all-carbon quaternary centers. Computational and experimental mechanistic studies provided insights into the reaction mechanism and observed regioselectivity/diastereoselectivity.