Claisen rearrangement is a powerful reaction that generates carbon-carbon bonds from carbon-oxygen bonds with chirality transfer. However, applications of this reaction to the generation of a quaternary carbon in the cyclohexane ring system possessing a sterically hindered ortho-substituted phenyl group, and reports on its cascade-version are limited. In this paper, we report the total synthesis of (+)-galanthamine (1) and formal total synthesis of (-)-morphine (2) starting from carbohydrates in which the key stereoselective generation of the quaternary carbons was achieved by the Claisen rearrangement. In the synthesis of an Amaryllidaceae alkaloid galanthamine (1), it was found 2-nitrophenol-catalyzed Johnson-Claisen rearrangement of cyclohexenol 5 possessing o-substituted phenyl group, prepared from D-glucose using Ferrier's carbocyclization, afforded the rearranged product 3 in high yield. The dibenzofuran skeleton was effectively constructed by the Br^+ mediated cyclization. After introduction of an endo olefin, the Pictet-Spengler type cyclization, followed by reduction of the amide function completed the chiral and non-biomimetic synthesis of 1. In the morphine (2) synthesis, D-glucal was converted into cyclohexene diol 12 possessing a cathecol moiety using the Ferrier's carbocyclization and Suzuki-Miyaura coupling. The cascade Claisen rearrangement of 12 in the presence of 2-nitrophenol successfully provided the double-rearranged product 11 in moderate yield. The epoxide-mediated dibenzofuran formation, followed by intramolecular Friedel-Crafts reaction and Birch reduction provided (-)-dihydroisocodeine (23), representing the formal synthesis of 2.
