One-Pot Palladium-Catalyzed Ligand- and Metal-Oxidant-Free Aerobic Oxidative Isocyanide Insertion Leading to 2-Amino-substituted-4(3H)-quinazolinones

Abstract

An efficient, ligand-and metal-oxidant-free, one-pot, cascade aerobic oxidative, palladium-catalyzed, multicomponent reaction has been developed through isocyanide insertion of less active secondary amide and aromatic amine, which leads to 2-aminosubstituted-4(3H)-quinazolinones. This approach proves to be one of the simplest methods for the synthesis of this class of valuable bioactive heterocyclic scaffolds.

Isocyanide-based multicomponent reactions in the synthesis of heterocycles

“…The organic segment is connected to the isocyanide group via the nitrogen atom, not via the carbon. They are used as privileged synthons for the synthesis of other organic compounds in particular various heterocycles [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] , frequently via multicomponent reactions (MCRs) namely isocyanide multicomponent reactions (IMCRs) 25,[38][39][40][41][42][43][44][45][46][47][48][49] . Noticeably isocyanides are susceptible to polymerization 50 .…”

Synthesis of heterocycles via aerobic oxidation

“…Here the authors employed isatoic anhydrides 40 as starting materials, which undergo decarboxylation-amination and isocyanide insertion in a one-pot fashion, to provide 2-amino-4-quinazolinones 28 (Scheme 7C). 28 The use of molecular sieves was essential for obtaining good yields. The same transformation was achieved using Ag2CO3 as oxidant by Cai.…”

Mo (CO)6‐assisted Pd‐supported magnetic graphene oxide‐catalyzed carbonylation‐cyclization as an efficient way for the synthesis of 4(3H)‐quinazolinones

“…Therefore, several synthetic approaches have been reported for the preparation of 4(3 H )‐quinazolinones. Palladium‐catalyzed oxidative insertion reaction of isocyanide with anthranilamide, carboxylic acids and amines, the carboxylation of ortho C–H bonds in anilides leading to N ‐acyl anthranilic acids and then treatment with anilines in the presence of PCl 3 , and the reaction of nitriles with lithiated anthranilamides are reported for the preparation of this class or compounds. In addition, other methods including microwave‐assisted condensation of anthranilic acids, oxidative reaction between benzyl halides, isatoic anhydride and primary amines, and the condensation of imidates with anthranilic acids, are reported for this purpose.…”

“…In addition, other methods including microwave‐assisted condensation of anthranilic acids, oxidative reaction between benzyl halides, isatoic anhydride and primary amines, and the condensation of imidates with anthranilic acids, are reported for this purpose. Amine‐induced thermal rearrangement of iminobenzoxazines, phosphine‐catalyzed intramolecular aza‐Wittig reaction, copper iodide‐catalyzed reaction between anthranilamide, and terminal alkynes and azides have also been used for the synthesis of 4(3 H )‐quinazolinone. Palladium‐catalyzed carbonylative cyclization of 2‐bromoanilines, trimethyl orthoformate and amines, and the condensation of aldehydes and anthranilamide or its derivatives in the presence of CuCl 2 are other reported methods, which are applied for the preparation of these compounds.…”