A Benzannulation Strategy for Rapid Access to Quinazoline-2,4-diones via Oxidative N-Heterocyclic Carbene Catalysis

Abstract

N-Heterocyclic carbene-catalyzed formal [4+2] benzannulation of enals with suitably substituted pyrimidine-2,4diones allowing the mild and facile synthesis of functionalized quinazoline-2,4-diones is presented. This oxidative transformation proceeds via the simultaneous generation of dienolates and α,β-unsaturated acylazoliums and follows a vinylogous Michael/aldol/βlactonization/decarboxylation/oxidation sequence to afford quinazoline-2,4-diones, including axially chiral ones with suitable substitutions, in an operationally simple procedure. In addition, substituted coumarins as dienolate precursors afforded benzochromen-6-one derivatives.

N-Heterocyclic Carbene-Catalyzed Enantioselective Synthesis of Carbocycle-Fused Uracils via Formal [4 + 2] Annulation/Lactone Formation/Decarboxylation Cascade

“…Herein, we report a new strategy to access a series of novel six-membered carbocycle-fused uracils in a highly enantioselective manner. It is noteworthy that during submission of the present work related NHC-catalyzed [4 + 2] annulations between enals and o QDM species derived from 5-arylcarbonyl-5-methyluracils were reported that gave benzannulated quinazolidione products …”

“…Since the remotely enolizable 6-methyluracil-5-carbaldehydes 1 could be deprotonated to generate the highly reactive o-quinodimethane (oQDM) dienolates I, we envision [4 + 2] annulations between enals and oQDM species derived from 5arylcarbonyl-5-methyluracils were reported that gave benzannulated quinazolidione products. 9 We commenced our study of the model reaction of 6methyluracil-5-carbaldehyde 1a with 2-bromo-3-phenyl enal 2a using Cs 2 CO 3 as a base in DCM in the presence of several chiral NHC precatalysts (Table 1, entries 1−5). It was found that precatalysts A−C gave the desired product 3a with ee values lower than 70%, while precatalysts D and E afforded 3a with 72% ee and 80% ee, respectively.…”

Oxidative N‐Heterocyclic Carbene Catalysis

“…Very recently, vinylogous Michael addition to alkenyl acyl azoliums at the hands of dienolates engendered from pyrimidine‐2,4‐diones has been envisioned as the entry point of a cascade transformation foreseeing intramolecular aldol reaction and lactonization as successive stages. [104] This strategy provided access to β‐lactone intermediates, suitable precursors of quinazoline‐2,4‐diones (Scheme 71 ).…”

Synthesis of Pincer type carbene and their Ag(I)-NHC complexes, and their Antimicrobial activities

“…Additionally, they may be stabilized as ligands in different transition-metal complexes [9], and the synthesis of these pNHC complexes received interest and were prepared by many applications [10]. One feasible route for the adjustment of complexes with protic pNHC ligands is the oxidative supplementation of [11] N-alkyl halogen azoles [12] or unsubstituted azoles to different kind low-valent transition metals, such as Ni, Pd, and Pt. As a proton resource, this reaction gives pNHC complexes of type I, as an example [13].…”