| Palladium-catalyzed three component coupling is a unique, very interesting, and useful method in organic synthesis, especially for making long chain hydrocarbons bearing two functional groups at remote ends of the carbon chain.;We have successfully developed the palladium-catalyzed coupling of aryl iodides, nonconjugated dienes and several different types of nucleophiles, such as phenylmetallics, amines, sulfonamides, azides, etc. Generally, these coupling reactions proceed under mild conditions and provide good yields of the desired products. Although there are usually two to four isomers present in the products, the regioselectivity can be controlled somewhat by the choice of the aryl iodide. For example, sterically hindered aryl groups, such as ortho-substituted aryl iodides have provided very high regioselectivity.;This methodology has been successfully applied to the synthesis of naturally-occurring, biologically active pyridine alkaloids, such as theonelladins C and D. The palladium-catalyzed coupling of 3-iodopyridine, nonconjugated dienes and nitrogen nucleophiles is used as a key step, followed by hydrogenation and deprotection to afford the natural products in good overall yields.;Our palladium-catalyzed coupling process has also provided an efficient way for preparing a variety of C-5 substituted pyrimidine nucleosides which may exhibit potent antiviral activities. Interestingly, in the case of the coupling of 5-iodo-2'-deoxyuridine, nonconjugated dienes and amine nucleophiles, we have found that the use of a Lewis acid, such as ZnCl2, remarkably increases the yield of the desired product. |
