Catalyst-Controlled C–H Allylation and Annulation of 2-Aryl Quinazolinones with 2-Methylidene Cyclic Carbonate

Abstract

The site-selective modification of quinazolinone as a privileged bicyclic N-heterocycle is an attractive topic in medicinal chemistry and material science. We herein report the ruthenium(II)catalyzed C−H allylation of 2-aryl quinazolinones with 2-methylidene cyclic carbonate. In addition, tandem C−H allylation and annulation are achieved under rhodium(III) catalysis, resulting in the formation of tetracyclic quinazolinones including a tertiary carbon center. Posttransformations of the synthesized products demonstrate the potential of the developed methodology. A series of mechanistic investigations were also performed.

Efficient Synthesis of Highly Fused Quinazolinone Derivatives via Multiple C−C Bond Formations and 1,4‐Palladium Migration

“…[9] In 2023, Kim group achieved a tandem CÀ H allylation and annulations led to tetracyclic quinazolinones. [10] Peng and co-workers recently developed Rh(III)-catalyzed CÀ H activation/cyclization of 2arylquinazolinones with elemental sulfur. [11] So far, the functionalization and annulation of 2-arylquinazolinones are well known in the literature.…”

Tandem annulation and dipolar cycloaddition of azomethine imines in catalytic C(sp2)–H functionalization

“…Cyclic carbonates with exo‐olefin moieties, such as 2‐methylidenetrimethylene carbonate, have been intensively used in catalytic C–H allylation reactions 65–69 . In 2022, Kim's group highlighted the ruthenium(II)‐catalyzed tandem C–H allylation and intramolecular dipolar cycloaddition between azomethine imines and 2‐methylidenetrimethylene carbonate (Scheme 30).…”

Alkoxycarbonylation-triggered nitrile insertion/remote C(sp2)–H and C(sp3)–H functionalization to access esterified quinazolinones and amidines

“…2 Accordingly, numerous synthetic strategies have been developed to construct these skeletons. 3 For example, Kim and coworkers 4 described the Ru( ii )-catalyzed C–H functionalization and subsequent annulation of 2-aryl quinazolinones with activated aldehydes and 2-methylidene cyclic carbonate to afford tetracyclic isoindoloquinazolinones. Most of the previous strategies rely on the pre-synthesis of 4(3 H )-quinazolinones bearing hydroxyl, 5 iodine, 6 or alkene groups, 7–9 and result in formation of only one new ring (Scheme 1a).…”