Reaction Friday: Addition of Grignard Reagents to Ketones

by James

in Alcohols, Ketones, Organic Chemistry 2, Organic Reactions


Grignard reagents are very useful carbon-based nucleophiles and will readily form carbon-carbon bonds with carbonyl compounds. Here the reaction of Grignard reagents with ketones is described, along with several examples and a detailed mechanism.

Have a great weekend!

Related Posts:

{ 6 comments… read them below or add one }

Megan

Thanks for the video! Question – what if you add the grignard reagent to a molecule with two carbonyl groups? Will it add the alkyl group to both or just one?

Reply

Megan

What I mean to say is what happens if you add the grignard to an acid anhydride?

Reply

James

It will add twice to at least one side. The other side will remain a carboxylic acid, and Grignards do not add to carboxylic acids.

Reply

Megan

Ok thank you!

Reply

Dion

In the example at 2:00 the Grignard adds to a substrate that looks a lot like diisopropyl ketone, which I understood eliminates.
http://pubs.acs.org/doi/pdf/10.1021/ja01258a001

What governs whether the majority product will be elimination or 1,2-addition? Where do we draw the line, even if a fuzzy one?

Reply

James

It’s not actually “elimination”, in that paper, it’s “enolization”. The conjugate base of a ketone is an “enolate”. What that paper is saying is that the Grignard reagent acts as a base, deprotonating the carbon adjacent to the ketone, resulting in an enolate. This happens in the case of bulky Grignard reagents.

There isn’t a line, per se. If you see the paper, it’s more like a continuum. Think of it like turning a knob: as you increase the bulkiness of the Grignard reagent, you’ll start to increase deprotonation. Same goes for increasing the bulkiness of the ketone. When you have both a bulky Grignard and bulky ketone, reduction and/or deprotonation will predominate.

As a proxy for bulkiness the categories, “methyl, primary, secondary, and tertiary” are useful.

There are ways around this tendency – by using a strong Lewis acid that is compatible with Grignards (Cerium chloride is a common example) you can bias the reaction more towards addition.

Reply

Leave a Comment