Irreversible endo ‐Selective Diels–Alder Reactions of Substituted Alkoxyfurans: A General Synthesis of endo ‐Cantharimides

The [4+2] cycloaddition of 3‐alkoxyfurans with N‐substituted maleimides provides the first general route for preparing endo ‐cantharimides. Unlike the corresponding reaction with 3 H furans, the reaction can tolerate a broad range of 2‐substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead‐like properties for medicinal chemistry programs. Furthermore, the electron‐rich furans are shown to react with a variety of alternative dienophiles to generate 7‐oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT calculations have been performed to rationalize the activation effect of the 3‐alkoxy group on a furan Diels–Alder reaction.