Name: gilman reagent: stop at the ketone
Uploaded: 2025-05-22T09:05:37.000Z
Duration: 1 min 14 s
Channel: JoVE

Grignard reagents reduce acid halides to alcohols, whereas reduction with lithium dialkyl cuprate, also known as the Gilman reagent, yields ketones.
This reaction is carried out in an ether solution at -78&#176;C to obtain ketones in good yields.
The mechanism proceeds in two steps. In the first step, one of the alkyl groups of the organocuprate acts as a nucleophile and attacks the carbonyl carbon, forming a tetrahedral intermediate.
Next, the carbonyl is re-formed with the departure of a halide ion, giving ketone as the final product.
However, unlike the Grignard reduction, why does this reaction stop at the ketone? The answer lies in the reactivity of the reagents.
Copper is more electronegative than magnesium, but closer to the electronegativity of carbon. So, the carbon-copper bond is less polarized than the carbon-magnesium bond.
Consequently, the alkyl carbon in the Gilman reagent is weakly nucleophilic and less reactive than the Grignard reagent, preventing further reduction of ketones to alcohols.

acid halides to ketones: gilman reagent

Acid Halides to Ketones: Gilman Reagent

Lithium dialkyl cuprate, also known as Gilman reagents, selectively reduces acid halides to ketones. The acid chloride is treated with Gilman reagent at &#8722;78 &#176;C in the presence of ether solution to produce a ketone in good yield.
As shown below, the mechanism proceeds in two steps. First, one of the alkyl groups of the reagent acts as a nucleophile and attacks the acyl carbon of the acid chloride to form a tetrahedral intermediate. This is followed by the reformation of the carbon&#8211;oxygen double bond with the loss of a halide ion as the leaving group to give a ketone as the final product.
<img alt="Grignard reaction mechanism diagram, chemical process with reagents and intermediates." src="/files/ftp_upload/12365/12365_PT_Figure_1.svg" style="text-align: center; height: 125px;" data-altupdatedat="1754904545000" data-alt="Organocuprate reaction mechanism; arrows, formulas; organic chemistry diagram; nucleophilic substitution." />
The electronegativity of copper is closer to the electronegativity of carbon as compared to magnesium. Therefore, the carbon&#8211;copper bond in the Gilman reagent is less polarized, which makes the alkyl carbon weakly nucleophilic and less reactive. Consequently, the reaction stops at the ketone intermediate and prevents further reduction of a ketone to an alcohol.

Lithium dialkyl cuprate, also known as Gilman reagents, selectively reduces acid halides to ketones. The acid chloride is treated with Gilman reagent at ...

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Organic Chemistry

Unit 1

Carboxylic Acid Derivatives

KEY TERMS AND CONCEPTS

gilman reagent: stop at the ketone

Gilman reagent lets an acid chloride stop at the ketone stage. Lithium dialkyl cuprate reacts with acid halides and gives ketones in good yield. For this reaction, the acid chloride is treated with the reagent at −78 °C in ether solution.

The reaction happens in two steps. First, one alkyl group on the Gilman reagent acts as a nucleophile, meaning it donates a pair of electrons. It attacks the acyl carbon of the acid chloride and forms a tetrahedral intermediate.

Next, the carbon–oxygen double bond forms again. At the same time, a halide ion leaves. This step produces the ketone as the final product.

The reagent stops at the ketone because of the carbon–copper bond. Copper has an electronegativity closer to carbon than magnesium does, so the bond is less polarized. That makes the alkyl carbon only weakly nucleophilic and less reactive, which helps prevent the ketone from being reduced further to an alcohol.

Gilman Reagent: Stop at the Ketone

carboxylic acid derivatives: overview

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Water Attack on Acid Halides

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Gilman reagent lets an acid chloride stop at the ketone stage. Lithium dialkyl cuprate reacts with acid halides and gives ketones in good yield. For this reaction, the acid chloride is treated with the reagent at −78 °C in ether solution. The reaction happens in two steps. First, one alkyl group on the Gilman reagent acts as a nucleophile, meaning it donates a pair of electrons. It attacks the acyl carbon of the acid chloride and forms a tetrahedral intermediate. Next, the carbon–oxygen...

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Acid Anhydride Reactions and Products

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esters to carboxylic acids: saponification

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Saponification and Soap-Making from Esters

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esters to carboxylic acids: acid-catalyzed hydrolysis

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How Acid Speeds Ester Hydrolysis

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Grignard Reagents in Ester Alcohol Synthesis

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preparation of amides

Amide Formation from Carboxylic Acids

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amides to carboxylic acids: hydrolysis

Amide Hydrolysis Under Acid and Base

Amide hydrolysis breaks an amide into a carboxylic acid using either acidic or basic conditions. The reaction is a nucleophilic acyl substitution, which means a nucleophile attacks the carbonyl carbon and the acyl group is changed. Both pathways need strong conditions and heat because amides are slow to react. In acid-catalyzed hydrolysis, the acid first protonates the carbonyl oxygen. This makes the amide carbonyl carbon more electrophilic, or more likely to be attacked by a nucleophile.

amides to amines: lialh4 reduction

How LiAlH4 Turns Amides into Amines

Lithium aluminum hydride, or LiAlH4, reduces amides to amines through nucleophilic acyl substitution. In this reaction, a strong reducing agent supplies hydride ions, which can add to the carbonyl group. Primary, secondary, and tertiary amides give primary, secondary, and tertiary amines, respectively. The reduction starts when a hydride ion attacks the carbonyl carbon. This forms a tetrahedral intermediate. Next, the carbonyl oxygen bonds to aluminum hydride, creating an oxygen-aluminum bond.<br...

preparation of nitriles

Making Nitriles from Amides and Halides

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nitriles to carboxylic acids: hydrolysis

Turning Nitriles into Carboxylic Acids

Nitriles can be converted into carboxylic acids by hydrolysis. This reaction can happen under acidic conditions or basic conditions. In both cases, the change goes through an amide intermediate before the final carboxylic acid forms. In acid-catalyzed hydrolysis, the nitrogen atom is protonated first. This makes the nitrile carbon more open to attack. Water then attacks the nitrile carbon. After deprotonation, the product becomes a tautomeric form of an amide. Protonation of nitrogen then...

nitriles to ketones: grignard reaction

Grignard Reagent Forms Ketones from Nitriles

Grignard reagents can turn nitriles into ketones by forming a new carbon-carbon bond. This reaction follows a nucleophilic acyl substitution pathway, which means a nucleophile attacks a carbonyl-related carbon and then the product changes in later steps. Organomagnesium halides are commonly called Grignard reagents. Their alkyl-magnesium bond is highly polar, so the alkyl carbon has carbanionic character and acts as the nucleophile. First, it attacks the nitrile carbon and forms an anion, also...

nitriles to amines: lialh4 reduction

Reducing Nitriles with LiAlH4

The mechanism occurs in three steps. First, a hydride ion acts as a nucleophile and attacks the nitrile carbon to form an anion. Then a second hydride ion attacks that anion to give a dianion. Water then protonates the dianion and produces a primary amine as the final product.

key terms and concepts

See how lithium dialkyl cuprate converts acid chlorides to ketones at low temperature. Learn the two-step mechanism and why the reaction stops there.

Gilman Reagent: Stop at the Ketone | JoVE K12

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Gilman Reagent: Stop at the Ketone

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