Grignard reaction

The Grignard reaction (French: [ɡʁiɲaʁ]) is an organometallic chemical reaction in which, according to the classical definition, carbon alkyl, allyl, vinyl, or aryl magnesium halides (Grignard reagent) are added to the carbonyl groups of either an aldehyde or ketone under anhydrous conditions. This reaction is important for the formation of carbon–carbon bonds.

Grignard reactions and reagents were discovered by and are named after the French chemist François Auguste Victor Grignard (University of Nancy, France), who described them in 1900. He was awarded the 1912 Nobel Prize in Chemistry for this work.

The reaction of an organic halide with magnesium is not a Grignard reaction, but provides a Grignard reagent.

Classically, the Grignard reaction refers to the reaction between a ketone or aldehyde group with a Grignard reagent to form a primary or tertiary alcohol. However, some chemists understand the definition to mean all reactions of any electrophiles with Grignard reagents. Therefore, there is some dispute about the modern definition of the Grignard reaction. In the Merck Index, published online by the Royal Society of Chemistry, the classical definition is acknowledged, followed by "A more modern interpretation extends the scope of the reaction to include the addition of Grignard reagents to a wide variety of electrophilic substrates." This variety of definitions illustrates that there is some dispute within the chemistry community about the definition of a Grignard reaction.

Shown below are some reactions involving Grignard reagents, but they themselves are not classically understood as Grignard reactions.

Because carbon is more electronegative than magnesium, the carbon attached to magnesium acts as a nucleophile and attacks the electrophilic carbon atom in the polar bond of a carbonyl group. The addition of the Grignard reagent to the carbonyl group typically proceeds through a six-membered ring transition state, as shown below.

Consequently, when the Grignard reagent adds to an aldehyde or a prochiral ketone, the Felkin-Anh model or Cram's Rule can usually predict which stereoisomer will be formed.

Based on the detection of radical coupling side products, an alternative single electron transfer (SET) mechanism that involves the initial formation of a ketyl radical intermediate has also been proposed. A recent computational study suggests that the operative mechanism (polar vs. radical) is substrate-dependent, with the reduction potential of the carbonyl compound serving as a key parameter.