Copper-Catalyzed Intramolecular α-C–H Amination via Ring-Opening Cyclization Strategy to Quinazolin-4-ones: Development and Application in Rutaecarpine Synthesis

Abstract

A copper-catalyzed intramolecular α-C–H amination has been developed for the synthesis of quinazolin-4(3H)-one derivatives from commercially available isatoic anhydride and primary and secondary benzylamines via ring-opening cyclization (ROC). This method shows good functional group tolerance and allows access to a range of 2-aryl, 2-alkyl, and spiroquinazolinone derivatives. However, 2-methylquinazolin-4(3H)-one was synthesized from 2-amino-N-isopropylbenzamide by C–C bond cleavage, and N-benzyl-2-(methylamino)benzamide afforded 1-methyl-2-phenylquinazolin-4(1H)-one along with 2-phenylquinazolin-4(3H)-one by N–C bond cleavage for aromatization. It is the first general method to construct the potentially useful 2-methylquinazolin-4(3H)-one by copper-catalyzed intramolecular C–H amination. Also this ROC strategy has been successfully applied to the synthesis of quinazolinone alkaloid rutaecarpine.

Photocatalytic Visible-Light-Induced Nitrogen Insertion via Dual C(sp3)–H and C(sp2)–H Bond Functionalization: Access to Privileged Imidazole-based Scaffolds

“…In the past few decades, C–H activation leading to C–N bond formation has emerged as a powerful tool for the synthesis of nitrogen-containing bioactive molecules and pharmaceutically important compounds. , Very recently, radical chemistry has gained importance due to its sustainable features, and, in particular, “N” radical species have gained importance in their applicability in C–N bond formation, specifically with photo/electrotechniques. Among them, iminyl radicals represent valuable synthons among N-centered radicals .…”

“One pot” synthesis of quinazolinone-[2,3]-fused polycyclic scaffolds in a three-step reaction sequence

“…5–9 In the past decade numerous efforts have been devoted to their construction, largely expanding the synthetic strategies towards quinazolinone-fused polycylic skeletons. These synthetic strategies include radical addition to inactivated alkenes installed on the parent quinazolinone and intramolecular annulation, 10 N -arylation of 2-aryl quinazolinones through C–H activation, 11 decarboxylative cyclization of isatins or their equivalents with heterocycles, 12 oxidative or reductive cyclization of o -nitrogen-containing benzaldehydes or their derivatives with heterocycles 13 and so on. 14–16 Despite being concise, green and efficient, these strategies could not meet the need for flexible access to diverse bioactive natural products possessing quinazolinone-[2,3]-fused polycyclic skeletons (Fig.…”

Acid/Base-Steered Cascade Cyclization: An Efficient One-Pot Access to Diverse Isobenzofuranone and Isoindolobenzoxazinone Derivatives

“…Isatoic anhydride is a cheap and commercially available compound that is a raw material for the synthesis of pharmaceuticals, agrochemicals and dyes, as well as an intermediate in the production of herbicide, Bentazone. The chemistry of isatoic anhydride and its reaction with amines has been investigated in detail [ 36 , 37 , 38 , 39 ]. We found that isatoic anhydride undergoes ring opening upon heating with various amines to produce 2-amino- N -alkylbenzamides, which can react with aldehydes [ 40 , 41 , 42 ] or orthoesters [ 43 , 44 , 45 , 46 ] and 2-formylbenzoic acid [ 47 , 48 , 49 ] to produce quinazolinones and isoindoloquinazolinones, respectively ( Scheme 1 a,b).…”