Iridium(III)-Catalyzed Alkynylation of 2-(Hetero)arylquinazolin-4-one Scaffolds via C–H Bond Activation

Abstract

The directed C–H alkynylation of 2-(hetero)­arylquinazolin-4-ones has been explored with the ethynylbenziodoxolone reagent TIPS-EBX employing an Ir­(III) catalyst. Complementary conditions for either monoalkynylation or dialkynylation have been developed. Also demonstrated is the broad scope of this reaction and the compatibility of various functional groups such as −F, −Cl, −Br, −CF3, −OMe, −NO2, and alkyl, etc.

Ru(II)‐Catalyzed Selective C—H Alkynylation of Isoquinolones, Quinazolones and Phthalazinones with Bromoalkynes

“…[ 11 ] In 2019, a Ir(III)‐catalyzed C—H alkynylation of quinazolones with the same EBX alkynylation reagent was established (Scheme 1b). [ 12 ] Therefore, there is a high demand for developing efficient and general strategies that employ lower cost transition metals and readily accessible alkynylation reagents beyond the alkynylated hypervalent iodine reagents to allow selective C—H alkynylation of isoquinolones, quinazolones and phthalazinones.…”

Recent progress in alkynylation with hypervalent iodine reagents

“… 95 Rohokale and coworkers developed an iridium-catalyzed ortho alkynylation of (hetero)aryls using TIPS-EBX (4a) and arylquinazolin-4-ones as directing groups ( Scheme 22 ). 96 Interestingly, switching the solvent for DCE and increasing the temperature to 70 °C allowed to access dialkynylated compounds in moderate to excellent yields.…”

Halogenative Annulation Reactions of Alkyne-Tethered N- and O-Containing Arenes: Methods for Accessing Aryl-Fused Halogenated N- and O-Heterocycles

“…Halogenative cyclization using bromine as the electrophilic reagent was demonstrated as an example by using a quinazolinone substrate tethered with an alkyne, which, in turn, was prepared by iridium(III)-catalyzed alkynylation. 24 The quinazolinone product was embedded with a brominated isoquinoline ring (Scheme 18 ). However, this was the only example of a brominative annulation of an alkyne-tethered substrate to give this type of brominated quinoline product.…”