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The Application of Metallated Enamines to the Synthesis of Morphine Alkaloids


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.


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.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Chemistry
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Grubbs, Robert H.
Thesis Committee:
  • Evans, David A. (chair)
  • Dervan, Peter B.
  • Goddard, William A., III
  • Grubbs, Robert H.
Defense Date:24 May 1982
Record Number:CaltechTHESIS:05162018-103306929
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10897
Deposited By: Mel Ray
Deposited On:29 Jun 2018 19:58
Last Modified:19 Apr 2021 22:27

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