Ethylation of Pyrazines Using Alkylmetals, Such as Triethylaluminum, Diethylzinc, and Triethylborane

Abstract

Triethylaluminum, diethylzinc and triethylborane were Used for the ethylation of pyrazines.Among these reagents, triethylborane gave the best results.Recently, we reported that trimethylaluminum is a convenient reagent for cross-Coupling methylation of chloropyrazineslr2.Namely, the methylation occurred with good yields in the presence of palladium catalysts.We have further studied the alkylation of pyrazines using other alkylmetals and found that diethylzinc and triethylborane have also the ability to introduce the ethyl group into the pyrazine ring.In this report, the comparison of the ethylation ability among triethylaluminum, diethylzinc, and triethylborane will be presented.Under the same conditions as previously reported.several chloropyrazines were heated with triethylaluminum3 in dioxane in the presence of tetrakis(tripheny1phosphine)palladium.Although the desired products were obtained in moderate to good yields (Table 1). the formation of dechlorinated products was also observed in all cases.The products were purified by preparative HPLC.Next, the ethylation of pyrazines using diethylzinc4 was performed.2-Chloro-3.6-5diisobutylpyrazine (lc) was treated with diethylzinc under various conditions and the optimum condition (reflux in DMF, tetrakis(tripheny1phosphine)palladium as catalyst and potassium carbonate as base) was chosen.The results of the reaction of several chloropyrazines are shown in Table 2, and in all cases, the formation of dechlorinated products was unavoidable.In the case of chlorophenyl-