Copper(I)-Mediated Cascade Annulation via Dual C–H/C–H Activation: Access to Benzo[a]carbazolic AEEgens

Abstract

A Cu­(I)-mediated cascade cyclization/annulation of unprotected o-alkynylanilines with maleimides in one pot is developed. The protocol offers sequential formation of one C–N and two C–C bonds to deliver fused benzo­[a]­carbazoles having free NH skeletons. The annulated products display fluorescence emission in the range of 485–502 nm with a large Stokes shift and fluorescence lifetime of ∼17 ns. The annulated 3aa displays AEE behavior in the ethanol/hexane system and possesses marigold-flower-like morphology at the aggregated state. Cell viability assays enumerate biocompatible AEEgens, while their high intracellular fluorescence depicts cell imaging applicability.

Recent Advances in N-Heterocyclic Small Molecules for Synthesis and Application in Direct Fluorescence Cell Imaging

“…In 2021, Patel et al synthesized a series of maleimide derivatives with bright fluorescence [ 61 ]. These compounds were obtained through the tandem intra- and inter-molecular cyclization of o -alkynylanilines with maleimides ( Scheme 20 ).…”

Metal‐ and Solvent‐Free Synthesis of Maleimide Fused Carbazoles from (Indol‐3‐Yl)cyclohexanones and Maleimides

“…In the same year, the Yan group disclosed an efficient synthesis of maleimide‐fused carbazoles via NH 4 I promoted three‐component reaction [9] . In 2021, Patel and co‐workers developed Cu(I)‐mediated cascade annulation of o ‐alkynylanilines with maleimides to generate maleimide‐fused benzocarbazoles (Scheme 1, c) [10] . In spite of the utility of these procedures, they require to use expensive transition metal catalysts and stoichiometric amount of metallic oxidant, which will increase the reaction cost and lead to metal contamination.…”

“…[9] In 2021, Patel and co-workers developed Cu(I)-mediated cascade annulation of o-alkynylanilines with maleimides to generate maleimide-fused benzocarbazoles (Scheme 1, c). [10] In spite of the utility of these procedures, they require to use expensive transition metal catalysts and stoichiometric amount of metallic oxidant, which will increase the reaction cost and lead to metal contamination. Metal contamination remains an important issue to be solved urgently, especially in medicine and materials.…”

Copper-catalyzed switchable cyclization of alkyne-tethered α-bromocarbonyls: selective access to quinolin-2-ones and quinoline-2,4-diones

“…10 In 2021, the Patel group developed a dual cyclization protocol of o-alkynylanilines with maleimides using a vinyl-Cu II intermediate under a N 2 atmosphere (Scheme 1a). 11 In 2017, Hwang and co-workers disclosed a direct oxidative coupling between phenols and terminal alkynes via an oxidative cleavage of the vinyl-Cu II intermediate (Scheme 1b). 12 Although great progress has been made in these approaches, a switchable strategy for cyclization and oxidative cleavage of the vinyl- Cu II intermediate has not yet been reported, mainly due to difficulties caused by the high reactivity of the vinyl-Cu II intermediate.…”

“…Next, the CuC triple bond in complex B undergoes a formal anti-carborhodation to afford the key vinyl-Cu II intermediate C. 13 The intermediate C and maleimide 2a undergo coordination/migratory insertion to generate intermediate D. 14 Subsequently, Cu II gets inserted into the C-H bond of the phenyl ring and further oxidation takes place to produce a seven-membered cupracycle E, and then the reductive elimination of the intermediate E delivers intermediate F, followed by oxidation to construct quinolin-2one 3a. 11,13,15 Moreover, the vinyl-Cu II intermediate C is readily oxidized to yield a peroxide intermediate G under an air atmosphere. 16 Then, the intramolecular addition of the intermediate G leads to a four-membered ring H, which is cleaved to furnish quinoline-2,4-dione 4a and acid (it has be detected by GC-MS, see the ESI †) with the help of O 2 and H 2 O.…”