Selective Oxidative Cleavage of 3-Methylindoles with Primary Amines Affording Quinazolinones

Abstract

A selective functionalization of C–CC bonds toward N–CO bonds is realized by an n-Bu4NI-catalyzed reaction of 3-methylindoles with primary amines using TBHP as the unique oxidant. The systematic process involves oxygenation, nitrogenation, ring-opening, and recyclization, affording a broad range of quinazolinones in good to excellent yields.

Synthesis of Quinazolin-4-ones by Copper-Catalyzed Isocyanide Insertion

“…The quinazolin-4-one core can also be found in pharmaceuticals demonstrating hypnotic, antifungal, anticonvulsant, kinase inhibitory, or antimalarial activity (Figure ). Synthetic approaches, including methodology involving Pd-catalyzed isocyanide insertion, to access these high-valued heterocycles receive quite some attention . We envisioned a robust transformation that takes advantage of economically more viable copper­(II)-based catalytic systems combining isocyanobenzoates 1 and amines to access 3-substituted quinazolin-4-ones 3 (Scheme b).…”

Hypoiodite-Catalyzed Chemoselective Tandem Oxidation of Homotryptamines to Peroxy- and Epoxytetrahydropyridoindolenines

“…of the peroxy functionality of numerous pharmaceutical compounds, we have reported the dearomative peroxidation of electron-rich arenols with tert -butyl hydroperoxide (TBHP) as an oxidant and a coupling partner (Scheme a) . We envisioned that peroxyindolenines might be accessed from the oxidative dearomative coupling of indoles with alkyl hydroperoxides via a similar umpolung strategy of indoles. During our investigation of the oxidative dearomative coupling of indoles, , Zhong and colleagues reported the oxidative dearomative peroxycyclization of tryptamines 1 to peroxypyrroloindolenines 2 using a catalytic amount of n -tetrabutylammonium iodide (Bu 4 NI) in the presence of TBHP as an oxidant and coupling reagent (Scheme b) .…”

I2-Catalyzed Carbonylation of α-Methylene Ketones to Synthesize 1,2-Diaryl Diketones and Antiviral Quinoxalines in One Pot

“… 70 − 72 Subsequently, the generated tert -butoxyl radical ( t BuO • ) abstracted hydrogen atom from benzyl phenyl ketone 1a to afford the benzylic radical I , 73 , 74 and it was followed by the reaction of tert -butylperoxy radical ( t BuOO • ) with the intermediate I to generate the peroxide intermediate II . 75 , 76 Finally, the intermediate II underwent rapid oxidation or a Kornblum–DeLaMare rearrangement to give the desired product 2a with the elimination of tert -butyl alcohol. 70 , 77 − 79 …”

“…Based on the above control experiments and previous literature reports, a possible mechanism was proposed in Scheme . Initially, the tert -butoxyl and tert -butylperoxy radicals ( t BuO • and t BuOO • ) were formed via the redox cycle reaction of I 2 and TBHP. − Subsequently, the generated tert -butoxyl radical ( t BuO • ) abstracted hydrogen atom from benzyl phenyl ketone 1a to afford the benzylic radical I , , and it was followed by the reaction of tert -butylperoxy radical ( t BuOO • ) with the intermediate I to generate the peroxide intermediate II . , Finally, the intermediate II underwent rapid oxidation or a Kornblum–DeLaMare rearrangement to give the desired product 2a with the elimination of tert -butyl alcohol. ,− …”