A Route to Alkenyl-Substituted 4-Hydroxypyridine and Pyrimidine Derivatives via Three-Component Access to β-Alkoxy-β-ketoenamides

Abstract

β-Alkoxy-β-ketoenamides with an alkenylated side arm were prepared by three-component reaction of lithiated methoxy-allene, nitriles, and α,β-unsaturated carboxylic acids. Their subsequent treatment with trimethylsilyl triflate and base provided 6-alkenyl-4-hydroxypyridine derivatives that were converted into the corresponding nonaflates. Alternatively, condensation of β-alkoxy-β-ketoenamides with an ammonium salt led to the smooth formation of alkenyl-substituted pyrimidine derivatives. The alkenyl group in pyridine or pyrimidine derivatives allows a wide scope of functional group modification. Moreover, the pyridin-4-yl nonaflates are excellent candidates for palladium-catalyzed coupling reactions and the 6-methyl group of the pyrimidine derivatives could also be employed for the introduction of functional groups and subsequent reactions. A variety of highly substituted pyridine and pyrimidine derivatives are available by this modular route to heterocycles.