Regioselective alpha-Addition of Deconjugated Butenolides: Enantioselective Synthesis of Dihydrocoumarins

The enantioselective alpha-addition of deconjugated butenolides has rarely been exploited, in contrast to the well-studied gamma-addition of deconjugated butenolides. In this study, an unprecedented asymmetric alpha-addition/transesterification of deconjugated butenolides with ortho-quinone methides generated in situ afforded a series of functionalized 3,4-dihydrocoumarins containing two contiguous stereogenic centers with excellent diastereo- and enantioselectivity. DFT calculations suggested that the rarely observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic dienolate and the electrophilic ortho-quinone methide