Synthesis of N-Fused Triazole–Piperazine–Quinazolinones via One-Pot Tandem Click Reaction and Cross-Dehydrogenative Coupling

Abstract

Herein, a one-pot protocol to synthesize tetracyclic triazole−piperazine−quinazolinone-fused N-heterocyclic scaffolds is reported. In this strategy, a tandem approach of two highly efficient synthetic reactions, click and cross-dehydrogentive coupling reactions, with high atom economy were employed to obtain the target N-fused scaffolds. Being highly functional group tolerable, this method has broad substrate scope. Interestingly, some of these derivatives showed strong white solid-state fluorescence.

Synthesis of Hydroxylated Polycyclic Pyrrolo/Indolo[1,2-a]quinoxaline-Fused Lactam Derivatives via PhI(OAc)2-Promoted 1,2-Bond Migration and Solvent Insertion

“…Various intermolecular condensations are found in the literature for the effective generation of diversified axially chiral biaryl-bridged seven-membered fused azepinones . Synthesis of several polyheterocycle-fused isoquinolinone and quinazolinone derivatives, mostly through transition-metal-catalyzed cyclization reactions are also reported . However, generation of fused heterocycles through the ring expansion of carbocyclic scaffolds by 1,2-migration of C–C σ-bond is limited due to difficulties in the cleavage of C–C bond .…”

Synthesis of fused bis-indazoles/indazoles via a one-pot sequential strategy

“…The fabrication of polycyclic heterocycles can be achieved via metal-catalyzed intramolecular cross-dehydrogenative coupling reactions between heterocycles and heterocycle-linked arenes/heteroarenes. 7–9 Although synthetically very attractive, this protocol suffers from the disadvantage of step-wise construction of both heterocycles linked with an aliphatic chain. 7,8 Additionally, the intermolecular 9 dehydrogenative cross-coupling has been well studied to date, and intramolecular variants have remained limited.…”

Dihydropyrazinoquinazolinones via SN2 Sulfamidate Ring-Opening and a Sequential Quinazolinone–Amidine Rearrangement Strategy (SQuAReS)

“…2 Fewer cases exist in which the α-position is occupied by an alternative to the carbonyl group (e.g., ardeemin 5 10 and evodiamine analog 6 11 ), though synthetic method development is more frequently producing these modified frameworks to explore potential pharmacology, as seen with scaffold 7. 12 Recently, we reported a route to diastereomeric pyrrolopyrazinoquinazolinones (Figure 2a). 13 In that work, a Ugi−Mumm/aza-Wittig protocol generated densely functionalized quinazolinones that underwent a tandem quinazolinone rearrangement/intramolecular amidine ring closure.…”

“…Dihydropyrazino-[2,1- b ]-quinazolinones, which feature a 4­(3 H )-quinazolinone fused to a piperidine ring (Figure , highlighted core), are a ubiquitous subclass of fungal metabolites in which the piperidinyl nitrogen atom is often flanked by a carbonyl and at least one alkyl appendage on the α- and α′-carbons, respectively ( 1 – 4 , Figure ). Fewer cases exist in which the α-position is occupied by an alternative to the carbonyl group (e.g., ardeemin 5 and evodiamine analog 6 ), though synthetic method development is more frequently producing these modified frameworks to explore potential pharmacology, as seen with scaffold 7 …”