Chromone-Thiocoumarin Transmutation Enabled by Lawesson's Reagent.

Selective editing of molecular skeletons at specific atomic sites is a core strategy for lead compound discovery in medicinal chemistry. Herein, we report an efficient protocol for the skeletal transmutation of chromone derivatives to thiocoumarins, which are biologically privileged scaffolds, using Lawesson's reagent. A series of thiocoumarins were obtained from chromone derivatives with Lawesson's reagent by heating in toluene, involving a cascade of ring opening, rearrangement, and cyclization. The synthetic utility of this skeleton remodeling strategy is validated by gram-scale synthesis and late-stage modification of the estrone. Mechanistic studies using 18O-labeled substrates confirm that the oxygen atom attached to the silicon moiety in the thiocoumarin product originates from the carbonyl group of the chromone precursor.