Variations on the Blaise Reaction: Synthesis of 3,5-Dioxopentanoates and 3-Amino-5-oxopent-3-enoates

We have achieved a facile and convenient synthesis of a variety of 3,5-dioxopentanoates (3,5-diketo esters) and 3-amino-5-oxopent-3-enoates by a zinc-mediated condensation of readily available 3-oxopropanenitriles (α-cyano ketones) with ethyl bromoacetate. The reaction is a variation on the classical Blaise reaction, tuned to the synthesis of trifunctional compounds having 3,5-diketo ester or 3-enamino 5-keto ester functional groups. Our studies revealed that the Blaise reaction on the nitrile occurs in preference to the Reformatsky reaction on the neighboring ketone when the two functional groups are in a geminal relationship, as found in α-cyano ketones, possibly due to zinc complexation leading to increased electrophilicity of the nitrile.