Dienamine-Mediated Inverse-Electron-Demand Hetero-Diels-Alder Reaction by Using an Enantioselective H-Bond-Directing Strategy

The first H-bond-directed inverse-electrondemand hetero-Diels-Alder reaction proceeding via a dienamine intermediate was developed. Under optimized reaction conditions, the corresponding dienamine species underwent regio- and stereoselective functionalization at the remote double bond, five bonds away from the stereogenic center of the catalyst, to give dihydropyran derivatives bearing three contiguous stereogenic centers. High stereoselectivities were obtained by employing a bifunctional squaramide-containing aminocatalyst, and the rationalization for the stereochemical outcome of the reaction was provided. Furthermore, the possibility to employ the introduced chiral framework for the synthesis of tetrahydropyrans as well as polycyclic compounds was demonstrated. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.