Base-Controlled Selectivity in the Synthesis of Linear and Angular Fused Quinazolinones by a Palladium-Catalyzed Carbonylation/Nucleophilic Aromatic Substitution Sequence

• Published in: Angewandte Chemie (International ed.) Vol. 53; no. 29; pp. 7579 - 7583
• Main Authors: Chen, Jianbin, Natte, Kishore, Spannenberg, Anke, Neumann, Helfried, Langer, Peter, Beller, Matthias, Wu, Xiao-Feng
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 14.07.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: carbonylation; Carbonyls; Catalysis; Chemistry; Chemistry, Multidisciplinary; Crystallography, X-Ray; Derivatives; Diels-Alder reactions; domino reactions; Formations; Isomerism; Isomers; Joining; Models, Molecular; Modulators; nucleophilic aromatic substitution; Palladium - chemistry; palladium catalysts; Physical Sciences; Quinazolinones; Quinazolinones - chemistry; Science & Technology; Synthesis; ULLMANN CONDENSATION; PYRIDOQUINAZOLONES; ONE-POT SYNTHESIS; 4(3H)-QUINAZOLINONES; NUCLEOPHILES; CYCLOADDITION; palladium catalysts; HETEROCYCLES; domino reactions; RUTAECARPINE; nucleophilic aromatic substitution; carbonylation; quinazolinones; DERIVATIVES
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201402779

A new approach for the facile synthesis of fused quinazolinone scaffolds through a palladium‐catalyzed carbonylative coupling followed by an intramolecular nucleophilic aromatic substitution is described. The base serves as the key modulator: Whereas DBU gives rise to the linear isomers, Et3N promotes the preferential formation of angular products. Interestingly, a light‐induced 4+4 reaction of the product was also observed. First base, second base…︁ home run! A base‐controlled palladium‐catalyzed carbonylation/intramolecular nucleophilic aromatic substitution reaction gave linear and angular fused pyridoquinazolones: 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene (DBU) yielded the linear products, whereas NEt3 gave the angular derivatives (see scheme; Ad=adamantyl, DMA=dimethylacetamide). A light‐induced Diels–Alder reaction of the product was also observed.