Evans DA,
*,
Mitch CH.
California Institute of Technology, Pasadena, USA
Studies Directed Towards the Total Synthesis of Morphine Alkaloids.
Tetrahedron Lett. 1982;
23: 285-288
DOI:
10.1016/S0040-4039(00)86810-0
Key words
morphine - opioids - kinetic protonation - iminium aziridination - Kornblum oxidation - Lemieux–Johnson reaction
Significance
In 1982, Evans and Mitch disclosed an elegant route to access the core of morphine alkaloids. Their synthetic route provides access to an intermediate from Gates’ seminal morphine synthesis (J. Am. Chem. Soc.
1956, 78, 1380). Evans’ formal synthesis, which features an unusual Kornblum oxidation as its centerpiece, accesses known tetracycle J, which can be transformed into the natural product in nine additional steps.
Comment
Metalation and double alkylation of C affords enamine E which is, under kinetic conditions, transformed into the cis-configured iminium F. A subsequent aziridination and Kornblum oxidation sequence gives rise to α-amino aldehyde H. A Friedel–Crafts-type reaction of H affords tetracycle I, which is then elaborated into known intermediate J, thereby completing the formal synthesis of (±)-morphine.
