Application of 3-Alkyl-2-vinylindoles in Catalytic Asymmetric Dearomative (2+3) Cycloadditions

J Org Chem. 2021 Aug 6;86(15):10427-10439. doi: 10.1021/acs.joc.1c01105. Epub 2021 Jul 27.

Abstract

The first application of 3-alkyl-2-vinylindoles in catalytic asymmetric dearomative cycloadditions was established by chiral phosphoric acid (CPA)-catalyzed (2+3) cycloaddition with azoalkenes, leading to the generation of chiral pyrroloindolines bearing two tetrasubstituted stereogenic centers in good yields (61-96%) and excellent stereoselectivities (all >95:5 dr, 86-99% ee). This reaction has realized the first enantioselective dearomative cycloaddition of 3-alkyl-2-vinylindoles, which brings a new reactivity to this class of vinylindoles and will enrich the chemistry of 3-alkyl-2-vinylindoles. In addition, this approach has provided a useful strategy for the construction of enantioenriched pyrroloindoline skeletons bearing two tetrasubstituted stereogenic centers. More importantly, the bioassay of these chiral pyrroloindolines has revealed that some compounds exhibit strong anti-cancer activity against Hela and MCF-7 cell lines, which will be helpful for discovering anti-cancer drug candidates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Cycloaddition Reaction
  • Indoles*
  • Stereoisomerism

Substances

  • Indoles