Facile Installation of 2‐Reverse Prenyl Functionality into Indoles by a Tandem N‐Alkylation–Aza‐Cope Rearrangement Reaction and Its Application in Synthesis |
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Authors: | Dr Xiaobei Chen Huaqiang Fan Prof?Dr Shilei Zhang Chenguang Yu Prof?Dr Wei Wang |
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Institution: | 1. School of Pharmacy, East China University of Science and Technology, 130 Mei‐Long Road, Shanghai 200237 (P. R. China);2. Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM 87131‐0001 (USA), Fax: (+1)505‐277‐2609;3. College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou 215123 (P.R. China) |
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Abstract: | An unprecedented tandem N‐alkylation–ionic aza‐Cope (or Claisen) rearrangement–hydrolysis reaction of readily available indolyl bromides with enamines is described. Due to the complicated nature of the two processes, an operationally simple N‐alkylation and subsequent microwave‐irradiated ionic aza‐Cope rearrangement–hydrolysis process has been uncovered. The tandem reaction serves as a powerful approach to the preparation of synthetically and biologically important, but challenging, 2‐reverse quaternary‐centered prenylated indoles with high efficiency. Notably, unusual nonaromatic 3‐methylene‐2,3‐dihydro‐1H‐indole architectures, instead of aromatic indoles, are produced. Furthermore, the aza‐Cope rearrangement reaction proceeds highly regioselectively to give the quaternary‐centered reverse prenyl functionality, which often produces a mixture of two regioisomers by reported methods. The synthetic value of the resulting nonaromatic 3‐methylene‐2,3‐dihydro‐1H‐indole architectures has been demonstrated as versatile building blocks in the efficient synthesis of structurally diverse 2‐reverse prenylated indoles, such as indolines, indole‐fused sultams and lactams, and the natural product bruceolline D. |
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Keywords: | alkaloids domino reactions natural products rearrangement synthesis design |
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