Posted by: Mark Foreman | July 31, 2015

Reactions of Grignard reagents

Dear Reader,

I was recently asked on Quora about a reaction of a Grignard reagent with a ketone which instead of forming the alkoxide of a tertiary alcohol it forms the alkoxide from a secondary alcohol. In short the Grignard acts as a reducing agent which is a hydride donor rather than as a carbon nucleophile, we need to consider why.

The example I was asked about was a very hindered ketone which was reacting with a Grignard which had beta hydrogens. Now before those of you who have taken an organometallics class such as the second / third year ones which Tony Hill and David Widdowson gave to me about 20 years ago start to mention the beta hydride elimination, I have to say that I do not think that a magnesium hydride is responsible for this chemistry.

What is much more reasonable is the formation of an alkene from the Grignard and the nucelophilic attack of a hydrogen atom on the ketone. Here is the reaction with the curved arrows shown.

Reduction of a ketone by a Grignard reagent

Reduction of a ketone by a Grignard reagent

This reaction can be explained with steric effects, consider the steric repulsion between the isopropyl groups in 3-isopropyl-2,4-dimethylpentan-3-ol. I calculated this molecule in MM to have an energy of 26.5930 kCal per mole. When the same calculation is done for a molecule of propylene and a molecule of 2,4-dimethylpentan-3-ol then we get only 4.5838 kCal per mole. If the transition states for the two reactions are similar in energy to the products then this could explain why the Grignard acted as a reducing agent instead of as a carbon nucleophile.

Another reaction to watch out for is the Grignard acting as a base on a ketone to form an enolate. This is much more simple reaction. Here is the reaction with the curved arrows.

Grignard forming an enolate

Grignard forming an enolate

 

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