Dipolar Cycloaddition Route to Diverse Analogues of Cocaine: The 6- and 7-Substituted 3-Phenyltropanes.
In our quest for an antagonist or partial agonist of cocaine, access to certain 6- and 7-substituted 3-phenyltropanes of type I was required. Starting from 3-hydroxy-1-methyl-4-phenylpyridinium iodide, we disclose a pyridinium betaine-based dipolar cycloaddition route to tropenones of type II. In turn, we show how this intermediate can be transformed to type I products either through the copper-catalyzed conjugate addition reaction of Grignard reagents to the enones 7-9 or by the copper(I)-catalyzed cross coupling reaction of the allylic acetates 15a and 16a with Grignard reagents.
Kozikowski
Alan P.
AP
Georgetown University Medical Center, Institute for Cognitive and Computational Sciences, 3970 Reservoir Road NW, Washington, DC 20007-2197, and Merck Sharp & Dohme Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065.
Araldi
Gian Luca
GL
Ball
Richard G.
RG