Synthesis of furoquinolinones/pyranones/coumarins via a copper-catalyzed heteroannulation of oxime acetates and 1,3-cyclic dicarbonyls

A divergent copper-mediated cyclization between oxime acetates and distinct 1,3-cyclic dicarbonyl compounds such as 4-hydroxyquinolinones/pyranones/coumarins was developed. Using the same reaction conditions, an array of furan-fused heterocycles such as furoquinolinones/pyranones/coumarins were prepared in good to high yields. The products possess a less common substitution pattern than those in previous syntheses. The mildness of the protocol enables a broad scope without affecting sensitive functionalities such as azido, alcohol, terminal alkyne, alkyl ester, and alkyl halide groups. Mechanistic investigations infer a purely organometallic pathway, excluding the participation of radical intermediates. Ultimately, the heteroannulation was exploited as the key step in a short and high-yielding synthesis of the phytoestrogen coumestrol. • The reaction allows the synthesis of a wide array of furan-fused quinolinones, pyranones, and coumarins. • The reaction conditions tolerate sensitive functionalities. • The operative mechanistic pathway is distinct from previous similar reactions. • Natural product coumestrol was effectively assembled using this method as a key step.