Department of Chemistry, South University of Science and Technology of China, Shenzhen 518055, China.
Nat Chem. 2018 Jan;10(1):58-64. doi: 10.1038/nchem.2866. Epub 2017 Oct 2.
Arylation is a fundamental reaction that can be mostly fulfilled by electrophilic aromatic substitution and transition-metal-catalysed aryl functionalization. Although the azo group has been used as a directing group for many transformations via transition-metal-catalysed aryl carbon-hydrogen (C-H) bond activation, there remain significant unmet challenges in organocatalytic arylation. Here, we show that the azo group can effectively act as both a directing and activating group for organocatalytic asymmetric arylation of indoles via formal nucleophilic aromatic substitution of azobenzene derivatives. Thus, a wide range of axially chiral arylindoles have been achieved in good yields with excellent enantioselectivities by utilizing chiral phosphoric acid as catalyst. Furthermore, highly enantioenriched pyrroloindoles bearing two contiguous quaternary chiral centres have also been obtained via a cascade enantioselective formal nucleophilic aromatic substitution-cyclization process. This strategy should be useful in other related research fields and will open new avenues for organocatalytic asymmetric aryl functionalization.
芳基化反应是一种基本反应，主要通过亲电芳香取代和过渡金属催化的芳基官能团化来实现。尽管偶氮基团已被用于通过过渡金属催化的芳基碳-氢键（C-H）键活化来实现许多转化，但在有机催化芳基化反应中仍然存在重大的未满足的挑战。在这里，我们证明偶氮基团可以有效地作为导向和活化基团，通过偶氮苯衍生物的形式亲核芳香取代，实现吲哚的有机催化不对称芳基化反应。因此，利用手性磷酸作为催化剂，可以以良好的收率和优异的对映选择性获得广泛的轴手性芳基吲哚。此外，通过级联对映选择性形式亲核芳香取代-环化反应，还获得了具有两个相邻季碳手性中心的高对映富集的吡咯并吲哚。该策略在其他相关研究领域应该是有用的，并将为有机催化不对称芳基官能团化开辟新的途径。
