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

我们打算广泛地研究并完全建立一种新的吲哚合成方法，该方法基于酸催化的易得的α-羟基肟醚的氮杂-纳扎罗夫重排反应。通过它们的酸催化脱水，生成了苄基1-氮烯丙基阳离子，这些阳离子经过快速的4P-电环向吲哚骨架，然后再芳构化。已经成功地开发了两个强大的催化过程，每个过程都使用了5mol%的非常强的Lewis酸或Brnsted酸。这两种化合物都将通过广泛的α-羟基肟醚进行研究，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提供游离的NH-吲哚。基于反应机理，吲哚-2-和吲哚-3-取代基的位置将被明确定义，这与目前已知的其他吲哚合成相比具有优势。此外，这一概念的扩展，以机械相似的吡咯合成将被研究。最后，通过使用手性、高酸性和受限的IDPI-Brnsted酸，我们将广泛地研究轴向手性3-芳基吲哚的反式选择性合成。与其他3个芳基吲哚的合成相比，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过程。

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.