Developing efficient methods for preparing privileged chiral ligands is an important endeavor in synthetic chemistry. Herein, we develop an effective, modular method for the synthesis of tertiary amine-derived C₂-symmetric chiral pyridine-N,N′-dioxides (Py-2NO) from optically pure L-prolinamides/hydroxylprolinamides in operationally simple two steps and up to 62% overall yield. The key to the preparation of these chiral Py-2NO ligands was the regioselective N-oxidation of their corresponding chiral intermediate bis(pyrroloimidazolone)pyridines with m-CPBA. To the best of our knowledge, our work is the first report showing that the amine oxide is trans to the adjacent carboxyamide in chiral N-oxides and is also an unprecedented example of the synthesis of tertiary amine-derived C₂-symmetric chiral pyridine-N,N′-dioxide ligands, expanding the chemical space of chiral N-oxides. The catalytic activity of these novel Py-2NO ligands was evaluated in the asymmetric Friedel–Crafts alkylation reaction of indoles. The desired products were obtained with up to 92% yield and 99% ee with a low loading % of the Py-2NO-Ni(II) complex.

中文翻译：

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新型叔胺衍生的C2-对称手性吡啶-N,N'-二氧化物配体及其在不对称催化中的应用

开发制备特权手性配体的有效方法是合成化学中的一项重要工作。在此，我们开发了一种有效的模块化方法，用于从光学纯的L-脯氨酰胺/羟脯氨酸酰胺合成叔胺衍生的C ₂ -对称手性吡啶-N，N'-二氧化物 (Py-2NO) ，操作简单，只需两步以上到 62% 的总产率。制备这些手性 Py-2NO 配体的关键是它们相应的手性中间体双（吡咯并咪唑啉）吡啶与m -CPBA的区域选择性N氧化。据我们所知，我们的工作是第一份表明氧化胺是反式的报告到手性N-氧化物中相邻的羧酰胺，也是合成叔胺衍生的C ₂ -对称手性吡啶-N，N'-二氧化物配体的前所未有的例子，扩大了手性N-氧化物的化学空间。这些新型 Py-2NO 配体的催化活性在吲哚的不对称 Friedel-Crafts 烷基化反应中进行了评估。以高达 92% 的收率和 99% 的 ee 获得所需的产品，Py-2NO-Ni( II ) 配合物的负载百分比低。