Cyanomethylative cyclization of unactivated alkenes with nitriles for the synthesis of cyano-containing ring-fused quinazolin-4(3H)-ones

Abstract

The synthesis of cyano-containing ring-fused quinazolin-4(3H)-one derivatives was developed under metal-free conditions. This reaction undergoes radical C(sp3)-H functionalization of alkyl nitriles, cascade radical addition/cyclization with N-alkylated quinazolinones to deliver the...

Metal-Free Photoinduced Hydrocyclization of Unactivated Alkenes toward Ring-Fused Quinazolin-4(3H)-ones via Intermolecular Hydrogen Atom Transfer

“…8 Among them, N-cyanamide alkenes have been developed for the construction of functionalized ring-fused quinazolinones with the formation of two rings in a one-pot procedure. 9 Recently, utilizing the N-alkenetethered quinazolinones as the substrates, various functionalized ring-fused quinazolinone derivatives were obtained via radical cyclization developed by Jin, 10 our group, 11 and others 12 under photoinduced, electrochemical, or peroxideinitiated conditions. Mechanistically, in those reactions, radicals that were in situ generated from different radical precursors were first added to the more reactive double bonds in alkenes to form the carbon-centered secondary/tertiary radicals.…”

Advances in the Application of Acetonitrile in Organic Synthesis since 2018

“…The metal-free catalyzed functionalization of unsaturated hydrocarbons involving acetonitrile is another application of cyanomethylation. Several interesting methods have been developed to provide nitrile-containing products, including the hydrofunctionalization of alkynes [38], cascade radical cyclization of alkynes [39,40], cascade radical cyclization of alkenes [41], etc. A free radical addition of acetonitrile to alkynes was developed by Liu's group in 2019 (Scheme 7) [38].…”

Recent advances in the synthesis of 2,3-fused quinazolinones

“…21 Recently, Pan et al synthesized a series of cyanoalkylated pyrrolo- and piperidino-quinazolin-4(3 H )-ones 29 using N -alkylated quinazolinones 27 and alkyl nitriles 28 as the substrates via a radical cyclization strategy (Scheme 14). 22 Di- tert -butyl peroxide (DTBP) was used as oxidant in this reaction. The electronic effects of substituents on the aryl ring of N -alkylated quinazolinones had little impact on the yields of the products.…”