Transition‐Metal‐Free Radical Cyclization of 2‐Arylbenzoimidazoles with Unactivated AlkanesviaC(sp³)−H Functionalizations in Aqueous Media

Abstract

Here we present a transition-metal-free radical cyclization of 2-arylbenzoimidazoles with unactivated alkanes. By using di-tert-butyl peroxide (DTBP) to promote the C(sp 3 )À H bond functionalization, this approach enables assembly of various benzimidazo[2,1-a]isoquinolin-6(5H)-ones in aqueous media. This strategy can not only well tolerate a wide range of cyclic alkanes, straight-chain alkanes, toluene derivatives, as well as pharmaceutical molecule eudesmol, but also provides an approach for the functionalization of unactivated C(sp 3 )À H bonds in aqueous media under transition-metal-free systems.

Pd-Catalyzed Photochemical Alkylative Functionalization of C═C and C═N Bonds

“…1 [4,5]imidazo[2,1a]isoquinolin-6(5H)-one (3i). 46 According to the general procedure, 3i was obtained after flash column chromatography (15% ethyl acetate in petroleum ether) as a colorless oil (36 mg, 56%). R f = 0.5 (15% ethyl acetate in petroleum ether).…”

“…1 5-(Cyclohexylmethyl)-2-methoxy-5-methylbenzo [4,5]imidazo-[2,1-a]isoquinolin-6(5H)-one and 5-(cyclohexylmethyl)-4-methoxy-5-methylbenzo [4,5]imidazo [2,1-a]isoquinolin-6(5H)-one (3d). 46 According to the general procedure, 3d was obtained after flash column chromatography (5% ethyl acetate in petroleum ether) as a colorless oil (50 mg, 78%). R f = 0.5 (20% ethyl acetate in petroleum ether).…”

“…Among the known methods, those that employ functionalized precursors to deliver an alkyl group are the most prevalent. Alkylboranes are widely used for alkylation assisted by transition metals or strong oxidants. , The N -hydroxy phthalimide esters are alternative alkylating reagents formed by the combination of NHPI and the corresponding carboxylic acids. − Other reagents include alkylated dihydropyridines (DHPs) − and Katritzky salts. − Decarboxylative alkylation with corresponding carboxylic acids − and decarbonylative alkylation − with aldehydes are also well-explored. The development of alkylation strategies that do not require pre-functionalized precursors, harsh oxidizing conditions, or expensive/highly engineered photocatalysts represents an advancement in this area.…”

Photoredox catalysis harvesting multiple photon or electrochemical energies

“…Naturally, these are not so atom economical and the use of non-prefunctionalized alkyl radical precursors would increase atom economy. Although a step in this direction has been taken by the group of Wei and co-workers [ 266 ], a potentially explosive peroxide radical was necessary. However, recently, Xu, Zeng and co-workers reported an interesting PEC cerium-catalyzed radical addition/cyclization process for the incorporation of unactivated alkanes 136 as radical precursors [ 267 ], by exploiting a PEC HAT to generate an alkyl radical directly from the unactivated alkane (as described previously by Xu, Ravelli and Lambert; Figures 56–59).…”

Visible-Light-Induced Synthesis of Alkylsulfonated Isoquinolinones from 2-Aryl Indoles/Benzimidazoles through Insertion of Sulfur Dioxide

“…Isoquinolinones play an important role in nitrogen-containing heterocycles as they are widely used in pharmaceuticals, natural products, and functional materials . One of the most simple and efficient ways to synthesize isoquinolinones is by radical-mediated cascade cyclization of 2-aryl indoles/benzimidazoles derivatives . As a mild and powerful tool, photochemical transformations have been broadly applied to organic radical chemistry .…”