Modular Synthesis of Functionalized Butenolides by Oxidative Furan Fragmentation

The development of new chemical transformations to simplify the synthesis of valuable building blocks is a challenging task in organic chemistry and has been the focus of considerable research effort. Here we report a chemical transformation that enables the facile and modular synthesis of synthetically challenging yet biologically important functionalized butenolides from easily accessible furans. Specifically, Diels-Alder reactions between furans and singlet oxygen generate versatile hydroperoxide intermediates, which undergo iron(II)-mediated radical fragmentation in the presence of Cu(OAc)(2) or various radical trapping reagents to afford butenolides bearing a wide variety of appended remote functional groups, including olefins, halides, azides, and aldehydes. The practical utility of this transformation is demonstrated by easy diversification of the products by means of cross-coupling reactions and, most importantly, by its ability to simplify the syntheses of known building blocks of eight biologically active natural products.