Radical Polychloromethylation/Cyclization of Unactivated Alkenes: Access to Polychloromethyl‐Substituted Ring‐Fused Quinazolinones

Abstract

A radical di‐ and trichloromethylation/cyclization of unactivated alkenes was developed with commercially available dichloromethane and chloroform as di‐and trichloromethyl radical sources under metal‐free conditions. Variously substituted di‐ and trichloromethylated pyrrolo‐ and piperidino‐quinazolinones were obtained in 47–94% yields. Additionally, dibromomethylation/cyclization was also achieved under standard conditions when CH2Br2 was utilized. Moreover, the obtained dichloromethylated product can be transformed into 1′H‐spiro[cyclopropane‐1,3′‐pyrrolo[2,1‐b]quinazolin]‐9′(2′H)‐one after treating by KOH.

Transition-metal-free radical difluorobenzylation/cyclization of unactivated alkenes: access to ArCF2-substituted ring-fused quinazolinones

“…More recently, remarkable achievements have been made in radical addition/cyclization of unactivated alkenes to furnish polycyclic quinazolinone derivatives. Representative studies include the alkylation/cyclization, 7 acylation, 8 sulfonylation, 9 phosphorylation/cyclization of unactivated alkenes. 10 Despite the development of these methods, it is still highly desirable to develop practical and mild synthetic methods for construction of biologically important ring-fused quinazolinones bearing other bioactive functional groups or pharmacophores.…”

Designing, Synthesis, and Anti‐Breast Cancer Activity of a Series of New Quinazolin‐4(1H)‐one Derivatives

“…In this context, testing several derivatives of quinazolin‐4(1 H )‐one by molecular docking studies appears to be a logical strategy. Since most of the synthetic and natural quinazolinones [22–30] exhibited a remarkable broad spectrum in biological activities including anti‐microbial, [31] anti‐cancer, [32] anti‐convulsant, [33] anti‐bacterial, [34] and anti‐tumor [35] . Several synthetic routes have been reported so far for synthesizing quinazolin‐4(1 H )‐one derivatives using some of the starting materials like isatoic anhydride, ammonium acetate and aldehyde with (AS) as a catalyst, [36,37] anthranilic acid, amine and orthoester in the presence of aluminum nitrate, [38] carbonyl compounds, and 2‐aminobenzonitrile/2‐aminobenzamide in water with a surfactant combined base catalyst, [PEG‐TEA]OH [39] as well as [(4‐SO 3 H)BMIM]HSO 4 as a catalyst [40] .…”

Organic photoredox catalytic radical sulfonamidation/cyclization of unactivated alkenes towards polycyclic quinazolinones

“…Radical difunctionalization of alkenes can install two functional groups on both sides of the carbon–carbon bond, and thus can dramatically improve the molecular complexity. 9 Recently, this cascade radical strategy was applied to construct polycyclic quinazolinones, 10–13 which are privileged cores in pharmaceuticals and natural products (Scheme 1). 14 In this area, Jin, Wu and He developed a photo-induced cascade radical carbonization/cyclization of quinazolinones bearing unactivated alkenes for the synthesis of polyfluoromethylated and acylated quinazolinones.…”