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

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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.