title: Synthesis of indolo[2,1-a]isoquinolines via a triazene-directed C-H annulation cascade.
abstract: Indole-containing polyaromatic scaffolds are widely found in natural products, pharmaceutical agents, and π-conjugated functional materials. Often, the synthesis of these highly valuable molecules requires a multistep sequence. Therefore, a simple, one-step protocol to access libraries of polyaromatic indole scaffolds is highly desirable. Herein we describe the direct synthesis of polysubstituted indolo[2,1-a]isoquinoline analogues via a double C-H annulation cascade using triazene as an internally cleavable directing group. Evidence from HRMS and theoretical calculations suggests that an unprecedented 1,2-alkyl migration might be responsible for the in situ cleavage of the directing group. Both kinetic isotope effects and DFT calculations suggested that the alkyne insertion step is rate-limiting for the second C,N annulation reaction.
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School , Shenzhen 518055, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Sun
authors.forename: Chengming
authors.initials: C
authors.lastname: Wang
authors.forename: Yun-Fang
authors.initials: YF
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Wu
authors.forename: Xinhao
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
mesh_terms: D002384:Catalysis; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D014226:Triazenes / Q000737:chemistry*
chemical_list: D007211:Indoles; D007546:Isoquinolines; D014226:Triazenes