Synthesis of Indolequinones from Bromoquinones and Enamines Mediated by Cu(OAc)₂·H₂O

Abstract

A Cu(II)-mediated synthesis of indolequinones from the corresponding bromoquinones and enamines is reported. The key oxidative cyclization proceeds in good yield for a broad range of substrates and can be performed on a multigram scale, allowing access to biologically interesting structures.

Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells

“…In order to address this problem, we have recently developed a new route to indolequinones based on the regioselective reaction of bromoquinones with enamines. 22, 23 Thus, reaction of bromo-5-methoxy-1,4-benzoquinone 26a with methyl 3-methylaminoacrylate 27a gave the indolequinone ester 28a in 40% yield (Scheme 2). Use of the isomeric 2-bromo-6-methoxy-1,4-benzoquinone 26b with the same enamine gave the corresponding 6-methoxyindolequinone 28b in 64% yield.…”

Copper(II)‐Mediated Synthesis of Indolequinones from Bromoquinones and Enamines

“…In our search for methods to synthesize indolequinones, we were attracted by the convergent nature of this reaction and the ready availability of the requisite starting materials. Hence, we sought to develop a set of reaction conditions that would give reliably good yields for a wide range of substrates 20,21…”

Quinones

“…A broad range of substrates could be used and a multigram scale promises access to interesting structures. The key oxidative cyclization leading to 1H-Indole-3-carboxylic acid, 4, 7-dihydro-6-methoxy-1-methyl-4, 7-dioxo-, methyl ester (98) [1240194- takes place in good yield and is typical of the process (174). …”