Intermolecular exo-selective Diels–Alder reaction catalysed by dual-functional Brønsted acid: conformational restriction of transition states by hydrogen bonds as the key interaction

Abstract

An exo-selective Diels–Alder (exo-DA) reaction in which the formed diastereomer is different from that formed in the conventional endo-selective Diels–Alder (endo-DA) reaction was developed, which involves a dual-functional Brønsted acid as a catalyst and not only a dienophile (vinylquinoline) but also an acyclic diene (dienylcarbamate) having a sterically less demanding substituent. Factors necessary for achieving the exo-DA reaction were extracted through an exhaustive computational search of the corresponding transition states, in which the relative orientation of the dienophile and the acyclic diene is firmly defined by hydrogen bonding interactions with a dual-functional Brønsted acid catalyst. It was experimentally verified that the combined use of the dual-functional acid catalyst, such as phosphoric acid, and the conformationally restricted diene (dienylcarbamate), which was realized by the introduction of a substituent at the 2-position of the diene unit, is the key to achieving the exo-DA reaction. A catalytic enantioselective exo-DA reaction was also attempted by using a chiral phosphoric acid catalyst, which gave rise to the corresponding exo-adduct with fairly good enantioselectivity.