Catalytic Indole Synthesis through Aza-Nazarov Rearrangement of a-Hydroxy Oxime Ethers. Atropselective Synthesis of Axially Chiral 3-Arylindoles

我们打算广泛研究并充分建立一种新的吲哚合成方法，该方法是基于酸催化的易于接近的a-羟基肟醚的aza-Nazarov重排。通过它们的酸催化脱水形成1-氮杂烯基苯基阳离子，并经历向吲哚骨架的快速4p电环化，然后再芳构化。已经成功地开发了两种强大的催化过程，每一种都使用5mol %的强Lewis酸或Brønsted酸。它们都将在广泛的a-羟基肟醚中进行研究，以提供大量不同取代的n -甲氧基吲哚。随后的氢解将定量地释放游离的nh -吲哚。根据反应的机理，吲哚-2-和吲哚-3取代基的位置将被明确定义，这是目前已知的其他吲哚合成的优势。此外，将这一概念扩展到机械上类似的吡咯合成将被研究。最后，通过手性、高酸性和限制性IDPI-Brønsted酸，对轴手性3-芳基吲哚的缩选择性合成进行了广泛的研究。与其他3芳基吲哚合成相比，不仅手性轴，而且整个杂环骨架将在一次操作中建立，大大简化了整个合成。

We intend to broadly study and fully establish a novel indole synthesis which is based upon the acid-catalyzed aza-Nazarov rearrangement of easily accessible a-hydroxy oxime ethers. Through their acid-catalyzed dehydration benzylic 1-azaallylic cations are formed which undergo a rapid 4p-elektrocyclization towards the indole skeleton followed by rearomatization. Two powerful catalytic processes have been successfully developed which each employ 5 mol% of either a very strong Lewis acid or Brønsted acid. Both of them will be studied across a broad range of a-hydroxy oxime ethers to furnish a multitude of differently substituted N-methoxy indoles. Subsequent hydrogenolysis will then deliver the free NH-indoles quantitatively. Based upon the mechanism of the reaction the position of indole-2- and indole-3-substituents will be clearly defined which constitutes an advantage to other currently known indole syntheses. Moreover, the extension of this concept towards a mechanistically similar pyrrole synthesis will be investigated. Finally, by using chiral, highly acidic and confined IDPI-Brønsted acids an atropselective synthesis of axially chiral 3-aryl indoles will be studied broadly. In contrast to other 3 aryl indole syntheses not only the chiral axis, but the entire heterocyclic skeleton will be established in a single operation significantly streamlining the overall synthesis.