Iminium Ions as Dienophiles in Aza-Diels-Alder Reactions: A Closer Look

• Published in: Chemistry : a European journal 2012-10, Vol.18 (40), p.12554-12582
• Main Authors: Memeo, Misal Giuseppe, Quadrelli, Paolo
• Format: Article
• Language: English
• Subjects: Aldehydes; Aliphatic compounds; Amines; Aqueous solutions; asymmetric synthesis; Chemistry; cycloaddition; Diels-Alder reactions; Historic; iminium ions; Lewis acid; Lewis acids; mechanisms; Origins; State of the art; synthetic methods
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201201894

This review highlights the state of the art of the use of iminium ions as dienophiles in Aza‐Diels–Alder (ADA) cycloadditions. An historical survey spanning the very first discovery of the reaction to modern developments, mechanistic studies and synthetic applications of the iminium variant of the ADA (iADA) reaction are presented. The discussion is focused on the intermolecular and intramolecular versions of the iADA reactions that are conducted in aqueous solutions to generate, in situ, the reactive dienophile from an amine hydrochloride and either aliphatic or aromatic aldehydes in the presence of a variety of dienes. The retro‐ADA reaction is also presented as an interesting method for the protection of amines. The use of Lewis acid catalysis in these reactions was thoroughly studied by the reactions of different amines and aldehydes conducted in the presence of lanthanide(III) complexes. I′m in ()ium: A review of the origins, modern developments, mechanistic studies and synthetic applications of the iminium variant of the aza‐Diels–Alder (iADA) reaction is presented, and the inter‐ and intramolecular versions of the iADA reactions that are conducted in aqueous solutions to generate the reactive dienophile in situ are discussed (see scheme).