Bronsted Acid-Catalyzed, Diastereo- and Enantioselective, Intramolecular Oxa-Diels-Alder Reaction of ortho-Quinone Methides and Unactivated Dienophiles

A stereoselective, phosphoric acid-catalyzed synthesis of dihydrochromenochromenes has been developed using transient ortho-quinone methides (o-QMs). Three contiguous stereogenic centers were formed with excellent yields, partially as single diastereomers and with moderate to excellent enantioselectivity. This intramolecular hetero-Diels-Alder reaction features unactivated dienophiles and o-QM precursors tethered by a simple phenoxy linker and furnishes cycloadducts with a prominent structural motif found in many natural products. Through an appropriate choice of dienophile configuration and backbone substitution either exo- or endo-stereoisomers were formed selectively with up to a 96:04 enantiomeric ratio.