Regioselective synthesis of fused oxa-heterocycles via iodine-mediated annulation of cyclic 1,3-dicarbonyl compounds with propargylic alcohols

Functionalized oxa-heterocycles are basic structural units in various natural products and bioactive molecules. Synthetic methodologies to obtain fused oxa-heterocycles from propargylic precursors have received increasing interest. In particular, iodine-mediated cascade electrophilic cyclizations of propargylic compounds readily lead to numerous novel cyclic scaffolds. However, the oxygen atom of the aliphatic carbonyl acting as the nucleophile in the iodocyclization of alkynyl-tethered compounds has not been reported. Herein, we describe an efficient regioselective synthesis of fused oxa-heterocycles through iodine-mediated annulation of propargylic alcohols with cyclic 1,3-dicarbonyl compounds. Using this methodology, one-pot regioselective syntheses of 2-acylated dihydrobenzofuranones and pyrano[2,3-b]chromenones from propargylic alcohols were readily achieved.

Automated summary

Functionalized oxa-heterocycles, basic structural units in natural products and bioactive molecules, can be efficiently synthesized through iodine-mediated annulation of propargylic alcohols with cyclic 1,3-dicarbonyl compounds, leading to novel cyclic scaffolds with high regioselectivity.