Construction of Cationic Azahelicenes: Regioselective Three‐Component Annulation Using In Situ Activation Strategy

Abstract

Described herein is a strategy to construct cationic azahelicenes through the three‐component annulation reaction of isoquinoline, indole, and 1,2‐dichloroethane (DCE), in which DCE serves as an in situ activating agent for C1−H activation of isoquinoline, a vinyl equivalent, and a solvent. This in situ activation annulation reaction features a facile one‐step synthesis and complete regioselectivity. The complete regioselectivity of C1 over C3 for the isoquinoline ring paves a path to the helical structure in a highly ordered sequence. One of the synthesized ionic [5]azahelicenium fluorophores exhibits the potential to serve as a mitochondria‐targeted biomarker with good photostability and low cytotoxicity.

Recent Advances of Three‐component Reactions of Simple Indoles

“…Imine salt intermediates are more electrophilic than aldehydes. The You group [32] used isoquinolines and 1,2‐dichloroethane as precursors of imine salts 24.1 to achieve one‐pot synthesis of cationic azahelicenes 24.4 . 1,2‐Dichloroethane commonly acted as the organic solvent, but was rarely used as a reagent in organic synthesis.…”

Copper-Catalyzed Oxidative C–H Annulation of Quinolines with Dichloroethane toward Benzoquinoliziniums Using an In Situ Activation Strategy

“…Recently, You reported the rhodium-catalyzed three-component annulation of simple pyridines, alkynes, and 1,2-dichloroethane (DCE) to construct ring-fused pyridiniums . More recently, You and co-workers disclosed a Cu/Ag-promoted three-component annulation of (iso)­quinolines, indoles, and DCE to prepare cationic azahelicenes . In these two works, DCE not only serves as a solvent and in situ activating agent for pyridine C2–H activation but also works as a vinyl equivalent to complete the ring-closing step with another unsaturated species (e.g., alkynes and indoles).…”

Vinylation of α-Aminoazoles with Triethylamine: A General Strategy to Construct Azolo[1,5-a]pyrimidines with a Nonsubstituted Ethylidene Fragment

“…In 2019, N -vinyl formamide as an acetylene surrogate was applied to form 3,4-unsubstituted isoquinolones by the Chen group . Furthermore, You realized a rhodium-catalyzed three-component approach to ring-fused pyridiniums, wherein 1,2-dichloroethane served as a vinyl equivalent to generate N -vinylpyridiniums . Most recently, Miura et al used vinylene carbonate as a vinylene transfer agent to achieve the assembly of a nonsubstituted vinylene-fused scaffold .…”