Palladium‐Catalyzed Synthesis of Phenanthridine/Benzoxazine‐Fused Quinazolinones by Intramolecular CH Bond Activation

Abstract

A highly efficient synthesis of phenanthridine/benzoxazine-fused quinazolinones by ligand-free palladium-catalyzed intramolecular C-H bond activation under mild conditions has been developed. The C-C coupling provides the corresponding N-fused polycyclic heterocycles in good to excellent yields and with wide functional group tolerance.

Modular Synthesis of Quinazolinone-Fused Phenanthridinones by a Palladium-Catalyzed Cascade C–H/N–H Arylation Process

“…product in 52% yield (entry 18). The regioisomeric product 3-methyl-14H-quinazolino[3,2-f]phenanthridin-14-one (a known compound reported by Hajela 13 ), formed by a palladium-catalyzed tandem N-arylation/direct C-H arylation process, was not found in this reaction system. Moreover, no matter whether the substituent R 3 of the o-dihaloarenes was electron-donating (Me, 2e) or electron-withdrawing (Cl, 13 2f), both of them gave the regioselectively C-H/N-H arylated products in good yields (entries 18 and 19).…”

“…Yield: 47.1 mg (76%); white solid; mp 152-153 °C (Lit. 13 152-153 °C). 133.1, 131.2, 129.9, 128.2, 127.9, 127.4, 126.8, 126.3, 125.9, 124.7, 123.1, 122.9, 122.2, 121.9, 120.7, 22.0.…”

“…14H-quinazolino[3,2-f]phenanthridin-14-one (3ca) Yield: 47.3 mg (65%); white solid; mp 160-162 °C (Lit. 13 160-162 °C).…”

“…11 Chen and Wu 12 developed an efficient protocol for the synthesis of indazole-fused quinazolinone derivatives by palladium-catalyzed intramolecular aerobic oxidative C-H amination of 2aryl-3-(arylamino)quinazolinones. Hajela 13 reported a novel approach for the synthesis of phenanthridine/benzoxazine-fused quinazolinones through palladium-catalyzed intramolecular biaryl cross-coupling. More recently, Banerji 14 developed a new route for the synthesis of quinazolinone and phenanthridine-fused heterocycles through a palladium-catalyzed regioselective intramolecular oxidative C-H amidation with Cu(OAc) 2 as co-oxidant.…”

Pd-Catalyzed Regioselective Mono-Arylation: Quinazolinone as the Inherent Directing Group for C(sp2)–H Activation

“…Besson and co-workers reported regioselective arylation of (2 H )-quinazolin-4-ones . Pd-catalyzed syntheses of phenanthridine/benzoxazine-fused quinazolinones were reported by using three different approaches; intramolecular C–H activation with bromoarenes, intramolecular oxidative C–H amination, and cascade C–H/N–H arylation . A few other metal catalysts were utilized in the quinazolinone/quinazoline functionalization, such as rhodium-catalyzed regioselective direct C–H amidation, copper-catalyzed cascade amination, and Ru/Rh-catalyzed annulation reactions .…”