ORGN 631 |
| A highly diastereoselective synthesis of Lamisil, an antifungal agent is developed. Two methods are explored based on the hydroboration and Suzuki coupling reactions. In the first method, the starting propargylamine containing a naphthylmethyl group is hydroborated with dichloroborane-dioxane complex followed by treatment with 1,3-propanediol. The resulting (E)-alkenylboronate ester is coupled with 1-bromo-3,3-dimethyl-1-butyne in the presence of Pd(0) catalyst and sodium methoxide in methanol to provide Lamisil in 72% isolated yield. The second method involves the hydroboration of propargyl chloride with dichloroborane-dioxane complex followed by a reaction with 1,3-propanediol. It is then converted into an “ate” complex with lithium isopropoxide. The resulting “ate” complex is reacted with lithiated methyl naphthylmethyl amine to undergo a substitution product containing an (E)-double bond and a boronate moiety. It is then subjected to Suzuki coupling using a Pd(0) catalyst, a base, and 1-bromo-3,3-dimethyl-1-butyne to provide Lamisil in 74% isolated yield. In both methods, the reaction proceeds to yield Lamisil in high stereochemical purity. |
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Materials, Devices and Switches, Metal-Mediated Reactions, Asymmetric Reactions, Total Synthesis, Biologically-Related Molecules and Processes
7:00 PM-9:00 PM, Wednesday, April 9, 2008 Morial Convention Center -- La Louisiane, Blrm. C, Poster
Division of Organic Chemistry |