Grignard Reaction

In 1900, French chemist Victor Grignard discovered that when treating an alkyl halide with magnesium metal in diethyl ether, a cloudy solution of an organomagnesium compound was formed. This substance would subsequently react with aldehydes and ketones to produce secondary and tertiary alcohols, respectively.

These organomagnesium compounds became known as Grignard reagents, and their addition across carbon–heteroatom multiple bonds is now called the Grignard reaction. Very shortly after this discovery, the Grignard reaction became one of the best known and most versatile carbon–carbon bond forming reactions.

Grignard reagents are typically prepared by reacting alkyl, aryl, or vinyl halides with magnesium metal in aprotic nucleophilic solvents such as ethers. The carbon magnesium bond is highly polar, making Grignard reagents excellent carbon nucleophiles. As a result, the subsequent carbon–carbon bond-forming step is straightforward.

Grignard reagents have been used in the synthesis of several natural products, including the total synthesis of (±)-lepadiformine and several natural and modified cyclotetrapeptide trapoxins.