Quinolizidine Synthesis via Intramolecular Immonium Ion Based Diels-Alder Reactions: Total Syntheses of (+/-)-Lupinine, (+/-)-Epilupinine, (+/-)-Cryptopleurine, and (+/-)-Julandine

Article abstract of DOI:10.1021/jo00249a036

Total syntheses of (+/-)-julandine (1), (+/-)-cryptopleurine (2), (+/-)-lupinine (3), and (+/-)-epilupinine (4) have been developed that feature intramolecular immonium ion based Diels-Alder reactions.Amines 6 and 14, prepared from stilbene ester 5 in a straightforward manner, gave rise to, upon treatment with aqueous formaldehyde solution, the corresponding immonium salts, which undergo intramolecular cyclocondensation, leading to isojulandine (11) and cryptopleurine (2), respectively, in good yield.Exposure of 11 to acid afforded (+/-)-julandine.Intramolecular <4 + 2> cycloaddition of immonium ion 18 derived from amine 17 provided Diels-Alder adducts 19 and 20, which are rationalized on the basis of transition states 22 and 23, respectively.Reduction of 19 and 20 gave (+/-)-epilupinine (4) and (+/-)-lupinine (3), respectively.