Organic Chemistry

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. From a synthetic perspective, it would be ideal if the natural reactivities of feedstock chemicals could be diverted to the production of high value-added compounds which are otherwise tedious to prepare. Here we report a chemical transformation that enables 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.


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Supplementary material

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Supporting Information