Department of Chemistry, Aarhus University, Aarhus, 8000 Aarhus C, Denmark.
Chemistry. 2022 Oct 26;28(60):e202202395. doi: 10.1002/chem.202202395. Epub 2022 Aug 23.
The first atroposelective aminocatalytic methodology for the construction of C-N atropisomers is presented. The synthesis of this class of axially chiral molecules typically encompasses substrates in which the C-N bond is pre-formed. In contrast, this work presents the direct coupling of indole-2-carboxaldehydes to ortho-quinones, to form the stereogenic C-N axis in an atroposelective way. Application of typical secondary amine catalysts furnished the desired product, however, in low yields and as a complex mixture arising from poor regiocontrol among the C - and N -sites of the indole core. A new aminocatalyst was designed and synthesized with increased outer-sphere steric bulk to address these challenges thereby providing good levels of regio- and enantioselectivity. A novel library of functionalized and enantioenriched C-N atropisomers was obtained and their synthetic utility was demonstrated by various transformations.
本文首次报道了一种手性氨基催化方法，用于构建 C-N 轴手性化合物。这类轴手性分子的合成通常包含预先形成 C-N 键的底物。相比之下，这项工作直接将吲哚-2-甲醛与邻醌偶联，以非对映选择性方式形成手性 C-N 轴。应用典型的仲胺催化剂可以得到所需产物，但产率较低，且由于吲哚核的 C-和 N-位之间的区域控制不佳，产物是复杂的混合物。设计并合成了一种新型手性氨基催化剂，增加了外部空间位阻，从而解决了这些挑战，提供了良好的区域和对映选择性。获得了一系列功能化和对映体富集的 C-N 轴手性化合物，并通过各种转化证明了它们的合成实用性。
