Pd-Catalyzed regioselective C–H halogenation of quinazolinones and benzoxazinones

Abstract

A Pd-catalyzed ortho-selective halogenation of benzoxazinone and quinazolinone scaffolds has been described employing N-halosuccinimide as both a halogen source and an oxidant reagent via C-H bond activation. This transformation shows high chemo- and regioselectivities and demonstrates a broad range of benzoxazinone and quinazolinone substrates with different functional groups and has been scaled up to the gram level.

Palladium Catalyzed Cross‐Dehydrogenative Coupling/Annulation Reaction: A Practical and Efficient Approach to Hydroxyisoindolo[1,2‐b]quinazolinone

“…[24] Other oxidants such as K 2 S 2 O 8 , H 2 O 2 , AgOAc and Cu(OAc) 2 did not promote the desired reaction (Table 1, entries 7- 10). Other catalysts including Cu(OAc) 2 , PdCl 2 , Ru(p-cymene)Cl 2 , Ru(COD)Cl 2 , and Co(OAc) 2 were also ineffective under the present conditions (Table 1, entries [15][16][17][18][19]. Additionally, the increase in the mount of TBHP to four equivalents has resulted in a yield increase of up to 52 % (Table 1, entry 12).…”

“…In the absence of either Pd(OAc) 2 or TBHP, no product was observed, indicating that Pd(OAc) 2 and TBHP are indispensable ingredients for the CDC/annulation reaction (Table 1, entries 6 and 14). Other catalysts including Cu(OAc) 2 , PdCl 2 , Ru(p-cymene)Cl 2 , Ru(COD)Cl 2 , and Co(OAc) 2 were also ineffective under the present conditions (Table 1, entries [15][16][17][18][19]. It was found that the yield could be remarkably improved by increasing the catalyst loading as an isolated yield of 71 % for the product was obtained in the presence of 10 mol-% of Pd(OAc) 2 (Table 1, entry 20).…”

“…Based on above introduction and also as part of our ongoing research studies on the C-H activation reactions and organic synthesis, [18][19][20][21][22][23] herein we present the tandem palladium-catalyzed CDC reaction followed by an intramolecular cyclization between arylquinazolinones and aldehydes under tert-butyl hydroperoxide (TBHP) as a convenient oxidant to afford hydroxyisoindolo [1,2-b]quinazolinone. To the best of our knowledge, this is the first report of CDC/annulation reaction for the formation of hydroxyisoindolo[1,2-b]quinazolinone polyheterocyclic frameworks (Scheme 1d).…”

Palladium‐Catalyzed Regioselective C‐H Bond ortho‐Acetylation and Oxidative Homocoupling of N‐Arylcarbamates

“…Substrates with electron‐donating substituent ( p ‐Me) or electron‐withdrawing substituents ( p ‐Cl and p ‐NO 2 ) afforded corresponding acyloxylated products in moderate to good yields (Table , entries 9–11). The electron‐donating substituent ( p ‐Me) led to the higher yield than electron‐withdrawing substituents ( p ‐Cl and p ‐NO 2 ) which could be ascribed to the electrophilic acyloxylation C–H activation to construct a carbon–palladium bond . Acetoxylation of N ‐arylcarbamate with a chloro at meta ‐position afforded product ( 3 l ) in good yield (Table , entry 12).…”

Acetoxylation and Halogenation of 2‐Arylbenzoxazinones via Palladium‐Catalyzed C(sp2)‐H Bond Oxidation

“…As the next diversification pathway, we set out to investigate C−H halogenation. There is a previous reported transition‐metal catalyzed ortho‐C–H halogenation of benzoxazinone scaffold, however it was limited to the acidic reaction medium which caused oxazinone ring hydrolysis to open, in addition the dihalogenated product was the major product in the chlorination and iodination of benzoxazinones, in any case, and it was not an ideal condition to challenge the instability of benzoxazinones. We report here that Pd(II)/AgNO 3 catalysts system in conjunction with electrophilic halogenating reagents N ‐halosuccinimides (NBS, NIS) promote the ligand‐directed conversion of arene C−H bonds into carbon‐halogen bonds.…”