Grignard reaction
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The Grignard reaction ({{#invoke:IPA|main}}) 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.<ref name=":1">Template:March6th</ref><ref>Chapter 19: Carboxylic Acids. Organic Chemistry 4e Carey. mhhe.com</ref><ref name=":12" /> This reaction is important for the formation of carbon–carbon bonds.<ref>Template:Cite journal</ref><ref>Template:Cite book</ref>
History and definitionsEdit
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.<ref name=":0">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> He was awarded the 1912 Nobel Prize in Chemistry for this work.<ref>Template:Cite journal</ref>
The reaction of an organic halide with magnesium is not a Grignard reaction, but provides a Grignard reagent.<ref name=":2">IUPAC. Compendium of Chemical Terminology, 2nd ed. (the "Gold Book"). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997). Template:ISBN. {{#invoke:doi|main}}.</ref>
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.<ref name=":1" /> However, some chemists understand the definition to mean all reactions of any electrophiles with Grignard reagents.<ref name=":3" /> 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."<ref name=":3">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.
Reaction mechanismEdit
Template:See also 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.<ref>Template:Cite journal</ref>
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.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>
ConditionsEdit
The Grignard reaction is conducted under anhydrous conditions.<ref name=":12">Template:Citation</ref> Otherwise, the reaction will fail because the Grignard reagent will act as a base rather than a nucleophile and pick up a labile proton rather than attacking the electrophilic site. This will result in no formation of the desired product as the R-group of the Grignard reagent will become protonated while the MgX portion will stabilize the deprotonated species.
To prevent this, Grignard reactions are completed in an inert atmosphere to remove all water from the reaction flask and ensure that the desired product is formed.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Additionally, if there are acidic protons in the starting material, as shown in the figure on the right, one can overcome this by protecting the acidic site of the reactant by turning it into an ether or a silyl ether to eliminate the labile proton from the solution prior to the Grignard reaction.
VariantsEdit
Other variations of the Grignard reagent have been discovered to improve the chemoselectivity of the Grignard reaction, which include but are not limited to: Turbo-Grignards, organocerium reagents, and organocuprate (Gilman) reagents.
Turbo-GrignardsEdit
Turbo-Grignards are Grignard reagents modified with lithium chloride. Compared to conventional Grignard reagents, Turbo-Grignards are more chemoselective; esters, amides, and nitriles do not react with the Turbo-Grignard reagent.<ref>Template:Cite journal</ref>
Heterometal-modified Grignard reagentsEdit
The behavior of Grignard reagents can be usefully modified in the present of other metals. Copper(I) salts give organocuprates that preferentially effect 1,4 addition.<ref name=":4">Template:Cite journal</ref> Cerium trichloride allows selective 1,2-additions to the same substrates. Nickel and palladium halides catalyze cross coupling reactions.
See alsoEdit
- Grignard reagent
- Wittig reaction
- Horner–Wadsworth–Emmons reaction
- Barbier reaction
- Bodroux–Chichibabin aldehyde synthesis
- Fujimoto–Belleau reaction
- Organolithium reagents
- Sakurai reaction
- Indium-mediated allylation
- Alkynylation