Nickel‐Catalyzed C(Aryl)−O Bond Activation/Cross‐Coupling Reaction of Carbazoles with Methyl Grignard: Synthesis of Ellipticine

Abstract

An ickel-catalyzed cross-couplingr eaction between methoxy-substitutedc arbazoles and MeMgBr has been developed.T his protocolf or the cleavage of the C(aryl)ÀOMe was used to efficiently assemble various methyl-substitutedc arbazoles and successfully appliedt o the total synthesis of the antitumor agent ellipticine.

Photophysical Tuning of σ-SiH Copper-Carbazolide Complexes To Give Deep-Blue Emission

“…1-Methylcarbazole and 1,3-di­(trifluoromethyl)­carbazole were prepared by modified literature with 3-bromo-2-nitrotoluene, phenylboronic acid, and 1-bromo-2-nitrobenzene,3,5-bis­(trifluoromethyl)­phenylboronic acid, respectively . NMR spectra for 1-methylcarbazole and 1,3-di­(trifluoromethyl)­carbazole were consistent with NMR spectra reported in the literature. , …”

“…18 NMR spectra for 1-methylcarbazole and 1,3-di(trifluoromethyl)carbazole were consistent with NMR spectra reported in the literature. 41,42 Synthesis of (Si H P 2 )Cu(3,6-dichlorocarbazolide) (2). Potassium bis(trimethylsilyl)amide (1 M in THF, 500 μL, 500 μmol) was added dropwise to a solution of 3,6-dichlorocarbazole (118 mg, 500 μmol) in 5 mL of THF at −30 °C and stirred for 30 min at RT.…”

Recent synthesis of ellipticine and its derivatives

“…An efficient and simple Ni-catalyzed C(aryl)-OMe bond cleavage and subsequent C(aryl)-Me bond formation by treating carbazoles with MeMgBr has been developed in 2016 by Das et al 42 This protocol was successfully applied to the synthesis of the natural product ellipticine from readily available starting materials. They used commercially available 2,5-dimethoxybenzaldehyde 102 as the starting material and introduced the methyl group through a Ni-catalyzed Kumada-type coupling reactions at a late stage of the synthesis.…”

Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol

“…The B-ring can be constructed from an aryl triazene 5,6 with a Pd-catalyzed cross-dehydrogenative coupling reaction. 7 Much efforts has been devoted to the formation of the C-ring of ellipticine through a Diels-Alder reaction between furo [3,4-b]indole and 3,4-pyridyne 8,9 or between pyrano [3,4-b] indol-3-one and pyridyltriazene. 10 The lateral D-ring can be built from 3-formyl-1,4-dimethylcarbazole by a Pomeranz-Fritsch isoquinoline synthesis.…”