Catalytic Asymmetric Inverse-Electron-Demand Oxa-Diels-Alder Reaction of In Situ Generated ortho-Quinone Methides with 3-Methyl-2-Vinylindoles

The first catalytic asymmetric inverse-electrondemand (IED) oxa-Diels-Alder reaction of ortho-quinone methides, generated in situ from ortho-hydroxybenzyl alcohols, has been established. By selecting 3-methyl-2-vinylindoles as a class of competent dienophiles, this approach provides an efficient strategy to construct an enantioenriched chroman framework with three adjacent stereogenic centers in high yields and excellent stereoselectivities (up to 99% yield, > 95: 5 d. r., 99.5: 0.5 e. r.). The utilization of ortho-hydroxybenzyl alcohols as precursors of dienes and 3-methyl-2-vinylindoles as dienophiles, as well as the hydrogen-bonding activation mode of the substrates met the challenges of a catalytic asymmetric IED oxa-Diels-Alder reaction.