Reformatsky Reaction

In 1887, Russian chemist Sergey Reformatsky discovered that the ethyl ester of iodoacetic acid reacted with acetone in the presence of metallic zinc to form 3-hydroxy-3-methylbutyric acid ethyl ester. Since then, the zinc-activated reaction between an alpha-halo ester and an aldehyde or ketone has become known as the Reformatsky reaction.

The reaction proceeds by a two-step process: the zinc metal initially inserts into the carbon-halogen bond to form the zinc enolate Reformatsky reagent, which then reacts with the carbonyl compound in an aldol reaction. In addition to aldehydes and ketones, Reformatsky reagents can also react with esters, acid chlorides, epoxides, nitrones, aziridines, imines, and nitriles, the latter transformation being known as the Blaise reaction.

The scope of the Reformatsky reaction was further expanded by activating the zinc prior to use. Activated zinc metal can be formed by removal of the deactivating zinc oxide layer through use of reagents such as iodine or 1,2-dibromoethane, or by the reduction of zinc halides in solution using various reducing agents (e.g. Rieke zinc compounds).