Cu‐Catalyzed [4+1] Annulation toward Indolo[2,1‐a]isoquinolines through Oxidative C(sp³)/C(sp²)−H Bond Bifunctionalization

Abstract

A Cu‐catalyzed [4+1] annulation of N‐aryl‐1,2,3,4‐tetrahydroisoquinolines (N‐aryl THIQs) with α‐diazoketones has been established under oxidative conditions, leading to the construction of a series of indolo[2,1‐a]isoquinolines with generally good yields. The reaction enables dediazotized dicarbonylation of α‐diazoketones, creating direct C(sp3)/C(sp2)−H bond bifunctionalization to access tetracyclic aza‐heterocyclic skeletons.

Application of N-Alkyl Amines as Versatile Building Blocks in Oxidative Coupling Reactions

“…In 2019, this group [65] further reported another reaction of THIQ with diazo compounds for preparing indolo[2,1a]isoquinolines. The reation proceeded through a Cu-…”

Synthesis of indolo[2,1‐a]isoquinolines by CF3COOH‐induced cyclization

“…[ 1–5 ] Some of them have been shown to exhibit interesting biological activities [ 6‐12 ] including antileukemic and antitumor activities, [ 6‐8 ] nonsteroidal antiestrogen, [ 10 ] and anti‐tubulin activity. [ 11 ] Most of the reported methods for the synthesis of such alkaloids and related indolo[2,1‐ a ]isoquinolines [ 6‐59 ] involve the procedures ending up with the formation of the fused indole ring, such as benzyne method, [ 6–11 , 13–26 ] oxidative coupling, [ 27‐30 ] Bischler‐Napieralski cyclization, [ 31 ] photocyclization, [ 32 ] anionic cyclization, [ 33,34 ] radical cyclization, [ 34‐36 ] Pschorr cyclization, [ 37,38 ] Ni or Pd‐catalyzed intramolecular amination, [ 39,40 ] other metal‐catalyzed cycloaddition, [ 41‐50 ] and other methods. [ 12,51‐59 ] .…”

Three-component synthesis of arylsulfonyl-substituted indolo[2,1-a]isoquinolinones and benzimidazo-[2,1-a]isoquinolin-6(5H)-ones by SO2insertion and radical cascade cyclization

“…1 As a result, considerable efforts have been devoted to the construction of such indolo[2,1- a ]isoquinoline structures, especially under transition-metal-catalyzed conditions. 2 In contrast, the synthesis of indolo[2,1- a ]isoquinolin-6(5 H )-one derivatives catalyzed by transition metals was less reported. 3 In 2015, Nevado reported the synthesis of CF 3 − , SCF 3 − , Ph 2 (O)P − , and N 3 -substituted indolo[2,1- a ]isoquinolin-6(5 H )-ones from N -[(2-ethynyl)arylsulfonyl]acrylamides via cascade cyclization/aryl migration/desulfonylation processes.…”