Novel oxoisochromene synthesis via chemoselective O–H insertion of 1,3-dicarbonyl compounds and subsequent Pd-catalyzed intramolecular arylation reaction

Abstract

Chemoselective O-alkylation of 1,3-diketones is a formidable synthetic challenge due to the competing C-alkylation reaction. In this report, N-triftosylhydrazones derived from 2-bromo(hetero)arylaldehydes are utilized for the O-alkylation of cyclic 1,3-diketones under base-mediated transition-metal-free conditions to generate vinyl ethers in good to high yields. The key to the success of the highly chemoselective O-alkylation reaction is the use of potassium enolate of 1,3-diketones as the base as well as the nucleophile in a highly polar-aprotic solvent at moderate temperature. These vinyl ethers are subsequently converted into novel oxoisochromene derivatives via Pd-catalyzed intramolecular arylation reaction. A plausible mechanism of the chemoselective O-alkylation reaction is outlined.