Application of the amino-claisen rearrangement to the synthesis of isoquinoline alkaloids

Abstract

An investigation of novel and general approaches to the syntheses of hydroisoquinolines and hydrophenanthridines is described. These approaches employ amino-Claisen and related rearrangements of N-vinylisoquinuclidenones, N-vinylisoquinuclidenes, and N-vinylisoquinuclidenium salts. The N-vinylisoquinuclidenones were prepared by the Diels-Alder eraction of l-vinyl-2-pyridones with suitable dienophiles. When methyl vinyl ketone was employed as the dienophile, a mixture of stereo-and-regio-isomers was obtained. The ratio of these products was in good agreement with the results predicted by first-order molecular orbital methods. N-Dimedonylisoquinuclidenones prepared in this manner were observed to undergo either low yielding acid catalyzed amino-Claisen rearrangement to the corresponding hydrophenanthridinone or fragmentation to an N-dimedonyl benzamide, depending on the temperature of the reaction. Alternatively, cyclohexenonylisoquinuclidenes underwent efficient acid catalyzed rearrangement to the corresponding hydrophenanthridine. ...