Grignard Reaction-百灵威

The Grignard reaction is one of the most versatile ways to form C-C bonds. Although its mechanism with carbonyl compounds is not fully understood, it is thought to take place either via a concerted process or a radical stepwise pathway. It was found that low electron affinity substrates tend to react in a concerted fashion, while sterically demanding substrates and bulky Grignard reagents tend to react through a radical pathway.

Reagents: Acid Work-up
Reactant: Grignard Reagent and Electrophile
Product: Various Products Dependent on the Electrophile
Type of Reaction: Nucleophilic Addition
Bond Formation: C-C

Lab Tips

Air and moisture sensitive conditions are required.
Acidic functional groups (i.e. alcohols, thiols, phenols, carboxylic acids, 1° or 2° amines, terminal alkynes) are incompatible with Grignard reagents.
Most electrophiles require only one equivalent of the Grignard reagent except for acid derivatives (esters, acyl halides), which require two equivalents.
The Grignard reagent can react with α-position protons present on the carbonyl compound, enolizing the substrate. Alkyllithiums are an alternative as they do not abstract α-protons.

Kürti, L., Czakó, B. (2005). Strategic Applications of Named Reactions in Organic Synthesis; Background and Detailed Mechanisms. Burlington, MA: Elsevier Academic Press.

Mechanism

Original Grignard Reaction Paper

Grignard, V. C. R. Acad. Sci. 1900, 130 (2), 1322–1324

Top Citations

The Samarium Grignard Reaction. In Situ Formation and Reactions of Primary and Secondary Alkylsamarium(III) Reagents. J. Am. Chem. Soc. 1992, 114 (15), 6050–6058

Design of Ionic Liquids as a Medium for the Grignard Reaction. Tetrahedron Letters. 2007, 48 (44), 7774-7777.

Mechanism of the Grignard Reaction. Reaction of Benzil. J. Am. Chem. Soc. 1986,108 (20), 6263-6270.

Related Reactions

Kumada Coupling

Nozaki-Hiyama Coupling

Reformatsky Reaction

Weinreb Ketone Synthesis

Related Compounds

Grignard Reagents