title: Facile Installation of 2-Reverse Prenyl Functionality into Indoles by a Tandem N-Alkylation-Aza-Cope Rearrangement Reaction and Its Application in Synthesis.
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.
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Mei-Long Road, Shanghai 200237 (P. R. China). xiaobei@ecust.edu.cn, xiaobei@ecust.edu.cn.|Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM 87131-0001 (USA), Fax: (+1)505-277-2609. xiaobei@ecust.edu.cn, xiaobei@ecust.edu.cn.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Mei-Long Road, Shanghai 200237 (P. R. China).
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM 87131-0001 (USA), Fax: (+1)505-277-2609.|College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou 215123 (P.R. China).
authors.forename: Shilei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM 87131-0001 (USA), Fax: (+1)505-277-2609.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Yu
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Mei-Long Road, Shanghai 200237 (P. R. China). wwang@unm.edu, wwang@unm.edu.|Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM 87131-0001 (USA), Fax: (+1)505-277-2609. wwang@unm.edu, wwang@unm.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
keywords: alkaloids; domino reactions; natural products; rearrangement; synthesis design