14.15:
Acid Halides to Ketones: Gilman Reagent
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°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.
14.15:
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 −78 °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–oxygen double bond with the loss of a halide ion as the leaving group to give a ketone as the final product.
The electronegativity of copper is closer to the electronegativity of carbon as compared to magnesium. Therefore, the carbon–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.