Coupling rections of zinc amide enolates with nitriles: Preration of β-keto and β-amino amides

The promising results from our previous studies on the applications of highly active zinc intermediate led us to anticipate further applications of this active zinc intermediate. In this study, zinc amide enolates were prepared and used for the synthesis of β-keto and β-amino amides. Zinc enolates derived from α-haloamides were easily prepared by the reaction of readily available α-chloroacetamide and active zinc using the literature procedure. We demonstrated an alternative synthetic procedure for the preparation of β-keto amides and β-enamino amides. The reaction was accomplished by the direct addition of highly active zinc to N,N-disubstituted chloroacetamides and subsequent coupling reactions to diverse nitrile derivatives under mild conditions. Further studies to elucidate this methodology including the effect of TMEDA are currently underway in our laboratory.