Asymmetric Barton-Zard Reaction To Access 3-Pyrrole-Containing Axially Chiral Skeletons
Asymmetric Barton-Zard Reaction To Access 3-Pyrrole-Containing Axially Chiral Skeletons
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不对称 Barton-Zard 反应获得含 3-吡咯的轴向手性骨架
DOI：
10.1021/acscatal.9b00767
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发表时间：
2019-05-01
期刊：
影响因子：
12.9
通讯作者：
Chen, Ying-Chun
中科院分区：
文献类型：
--
作者：
He, Xiao-Long;Zhao, Hui-Ru;Chen, Ying-Chun
开发一种有效和可靠的催化方法来获得阿托品异构体化合物，特别是那些含有具有较低旋转势垒的五元杂芳基结构的化合物，是一项具有挑战性的任务。在此，我们通过中心到轴向的手性转移策略，在Ag2O和金鸡纳衍生的膦配体的催化下，使用具有β-邻位取代(杂)芳基的α-取代的硝基烯烃和具有各种电子吸引基团的α-异氰基底物，通过中心到轴向的手性转移策略，揭示了一种史无前例的阿托品选择性的Barton-Zard反应，为构建具有实质性骨架和功能多样性的轴向手性3-(杂)芳基吡咯提供了一种可靠的方法。另一种不对称相转移催化方案也被证明对于直接构建轴向手性双膦氧化物是可行的。此外，合成的阿托品具有良好的构象稳定性，在立体选择性很高的形式[4+2]环加成反应中，它们作为有价值的有机催化剂得到了很好的应用。
Developing an efficient and reliable catalytic protocol to access atropisomeric compounds, especially those bearing five-membered heteroaryl structures with lower rotation barriers, is a challenging task. Here, we disclose an unprecedented atropenantioselective Barton-Zard reaction via a central-to-axial chirality transfer strategy, by employing alpha-substituted nitroolefins with a beta-ortho-substituted (hetero)aryl group and alpha-isocyano substrates with various electron-withdrawing groups, under the catalysis of Ag2O and a cinchona-derived phosphine ligand, providing a robust approach to construct axially chiral 3-(hetero)aryl pyrroles with a substantial skeleton and functionality versatility. An alternative asymmetric phase transfer catalysis protocol was also demonstrated to be practical for the direct construction of axially chiral bisphosphine dioxides. In addition, good conformational stability is generally observed for the obtained atropisomers, and their potential application as valuable organocatalysts has been well demonstrated in a highly stereoselective formal [4 + 2] cycloaddition reaction.