The Application of Metallated Enamines to the Synthesis of Morphine Alkaloids

Citation

Mitch, Charles Howard (1982) The Application of Metallated Enamines to the Synthesis of Morphine Alkaloids. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/vf0x-tn08. https://resolver.caltech.edu/CaltechTHESIS:05162018-103306929

Abstract

Metallated enamines have been used to prepare a number of morphine-based analgesics, including efficient entry to the 4a-phenylisoquinolines and morphinans. Stereocontrolled formation of both cis and trans-fused perhydroisoquinolines has been accomplished by either kinetic or thermodynamic protonation of the corresponding octahydroisoquinoline. Reaction of 4a-phenyloctahydroisoquinolinium perchlorates with diazomethane afforded the expected aziridinium perchlorate with a component of direct cyclization to the morphinan structure also observed. Kornbloom oxidation to the α-amino-aldehyde was accomplished on treatment of the aziridinium salts with dimethyl-sulfoxide. The aldehydes were cyclized to the morphinan structure on reaction with boron trifluoride etherate, providing ready access to intermediates used by Gates in his pioneering total synthesis of morphine.

Thesis Files