Department of Chemistry, Building 201, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Org Biomol Chem. 2010 Dec 21;8(24):5576-82. doi: 10.1039/c0ob00106f. Epub 2010 Oct 20.
A straightforward and atom-economical method is described for the synthesis of 2,3-disubstituted indoles. Anilines and 1,2-diols are condensed under neat conditions with catalytic amounts of either Cp*IrCl(2)/MsOH or RuCl(3)·xH(2)O/phosphine (phosphine = PPh(3) or xantphos). The reaction does not require any stoichiometric additives and only produces water and dihydrogen as byproducts. Anilines containing methyl, methoxy, chloro and fluoro substituents can participate in the cyclocondensation. Meta-substituted anilines give good regioselectivity for 6-substituted indoles, while unsymmetrical diols afford excellent regioselectivity for the indole isomer with an aryl or large alkyl group in the 2-position. The mechanism for the cyclocondensation presumably involves initial formation of the α-hydroxyketone from the diol. The ketone subsequently reacts with aniline to generate the α-hydroxyimine which rearranges to the corresponding α-aminoketone. Acid- or metal-catalysed electrophilic ring-closure with the release of water then furnishes the indole product.
一种直接且原子经济性的方法被用来合成 2,3-取代的吲哚。苯胺和 1,2-二醇在均相条件下，催化量的Cp*IrCl(2)/MsOH 或 RuCl(3)·xH(2)O/膦（膦=PPh(3)或 xantphos）反应，不需要任何化学计量添加剂，只生成水和氢气作为副产物。含甲基、甲氧基、氯和氟取代基的苯胺可以参与环缩合。间位取代的苯胺对 6-取代的吲哚具有很好的区域选择性，而不对称二醇则对 2-位有芳基或大烷基的吲哚异构体具有极好的区域选择性。环缩合的机理可能涉及二醇首先形成α-羟基酮。酮随后与苯胺反应生成α-羟基亚胺，该亚胺重排得到相应的α-氨基酮。然后，酸或金属催化的亲电环化反应伴随着水的释放，生成吲哚产物。
