Formal Synthesis of (+/-) Morphine via an Oxy-cope/Claisen/Ene Reaction Cascade

Title: Formal Synthesis of (+/-) Morphine via an Oxy-cope/Claisen/Ene Reaction Cascade
Authors: Marcotte, Joel
Date: 2012
Abstract: For years now, opium alkaloids and morphinans have been attractive synthetic targets for numerous organic chemists due to their important biological activity and interesting molecular architecture. Morphine is one of the most potent analgesic drugs used to alleviate severe pain. Our research group maintains a longstanding interest in tandem pericyclic reactions such as the oxy-Cope/Claisen/ene reaction cascade and their application to the total synthesis of complex natural products. Herein we report the ventures towards the formal synthesis of (+/-)-morphine based on the novel tandem oxy- Cope/Claisen/ene reaction developed in our laboratory. These three highly stereoselective pericyclic reactions occurring in a domino fashion generate the morphinan core structure after only 7 steps from commercially available material. The formal synthesis culminated in the production of a formal intermediate after a total of 18 linear steps, with an overall yield of 1.0%, successfully intersecting two previous syntheses of the alkaloids, namely the ones of Taber (2002) and Magnus (2009).
CollectionThèses, 2011 - // Theses, 2011 -