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

Abstract

As one of the most important structural units in pharmaceuticals and medicinal chemistry, quinazolinone and its derivatives exhibit a wide range of biological and pharmacological activities, including anti-inflammatory, antitubercular, antiviral,...

Synthesis of 2,3-Fused Quinazolinones via the Radical Cascade Pathway and Reaction Mechanistic Studies by DFT Calculations

“…Hence, ring-fused quinazolinones play vital roles in the field of medicinal chemistry, and it is meaningful to afford efficient strategies for the synthesis of polycyclic quinazolinone derivatives. Typically, it was reviewed to synthesize 2,3-fused quinazolinones in a number of ways, including difunctionalization of alkenes, ring opening of easily available small rings, dehydrogenative cross-coupling reactions, transition-metal-catalyzed cyclizations, 4 + 2 or 4 + 1 cycloadditions, and other cascade reactions . In these methods, difunctionalization of olefins is usually initiated by free radicals through photoinduction or oxidation, followed by radical tandem addition and cyclization .…”

“…It is of great significance in modern organic synthesis that the C−H bond is converted into a C−C bond 11 by activating C(sp 3 )−H of commercially available and low-cost ethers, alcohols, and cycloalkanes. Nonetheless, to the best of our knowledge, it has not been reported yet to obtain 2,3-fused quinazolinones via C(sp 3 )−H functionalization of inert ethers up to now.…”

“…It is of great significance in modern organic synthesis that the C−H bond is converted into a C−C bond 11 by activating C(sp 3 )−H of commercially available and low-cost ethers, alcohols, and cycloalkanes. Nonetheless, to the best of our knowledge, it has not been reported yet to obtain 2,3-fused quinazolinones via C(sp 3 )−H functionalization of inert ethers up to now. In addition, although the addition cyclization of quinazolones with alkanes 4a and alcohols 4g has been reported, there are disadvantages such as a long reaction time and the need for phase transfer agents and bases, which need to be further optimized.…”

“…In addition, although the addition cyclization of quinazolones with alkanes 4a and alcohols 4g has been reported, there are disadvantages such as a long reaction time and the need for phase transfer agents and bases, which need to be further optimized. Herein, we develop an approach for the C(sp 3 )−H functionalization of inert ethers using etheryl radicals for an efficient synthesis of valuable polycyclic quinazolinones via radical cyclization of alkene substituted quinazolinones (Scheme 1). The method reported here can enable the addition cyclization of quinazolones with simple ethers, alkanes, and alcohols with the prominent advantages of high atomic economy, metal-free, base-free, and wide substrate adaptability.…”

Dicarbofunctionalization of unactivated alkenes via organo-photoredox catalysis in water: access to cyanoalkylated fused quinazolinones

“…4 As a result, chemists have devoted a great deal of effort in developing novel methods for synthesizing the valuable derivatives of quinazolinones. 5 In particular, in recent years, various radical-triggered addition/cyclization cascade strategies have been developed to construct polycyclic quinazolinone derivatives. 6 All these strategies involve a radical addition/cyclization cascade of either N -cyanamide alkenes or alkene-tethered quinazolinones for the synthesis of polycyclic quinazolinones (Scheme 1a).…”