1,4-addition of enolates to enones (“The Michael Reaction”)

by James

Description:

Enolates of carbonyl compounds will add to an α,β-unsaturated carbonyl compounds to give 1,5-dicarbonyl compounds. This is called the Michael reaction.

Notes: 

Enolates are excellent nucleophiles; although a second resonance form is present with the negative charge on oxygen, the resonance form with the negative charge on carbon tends to be more important for determining reactivity.

Examples:

Notes: Note that in each case a carbon-carbon bond is being formed

Mechanism:

Removal of a proton from the ketone with strong base (Step 1, arrows A and B) results in an enolate, which then performs a 1,4-addition on the α,β-unsaturated carbonyl compound (Step 2, arrows C and D), which is then protonated (Step 3, arrows E and F).

Notes:

Sodium here isn’t specifically important, it just balances out the negative charge.

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{ 10 comments… read them below or add one }

Daniel

Thanks for the numbering part James. It was driving me mad.
Plus, your tip of always making sure to count my Carbons really helps as well.

Reply

james

It makes a big difference! Mistakes are really easy to make.

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Vicki

Thank you this is easy to follow. I actually understand what is going on.

Reply

Smriti

Thanks for numbering and this makes so much more sense!!!

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Fiona Liang

Hey James! Quick question:I read in Klein’s book that Michael donors have to be an enolate from a di-carbonyl compound (because it’s more stable and less reactive, etc) in order to be selective to strictly undergo 1,4-addition. Is steric hinderance the reason why 1,4-addition prefer to occur in this case?

Many thanks!

Reply

Jon Harwell

Hi Fiona,

Here’s a link to James’ explanation of conjugate addition:

https://www.masterorganicchemistry.com/tips/conjugate-addition/

I’m just a student, but anytime I have a conjugated ketone, I have to make a decision between 1,2 direct addition and 1,4 conjugate addition. The direct addition is the kinetic product and the conjugate addition is the more stable thermodynamic product.

1,2 direct addition is only accomplished by “super hero” amazing nucleophiles. These would be nucleophiles like Grignard reagents (MgBr), Hydrides, or ylides like Wittig reagents (PPh3). I’m sure there are more, but in my O-Chem class, those are the only three we have to worry about. If it’s not one of those, it is going to add 1,4.

Enolates are great nucleophiles, but they are not “super hero” nucleophiles. So, they will readily add 1,4.

Hope that helps.

Reply

Naga veera

Usually more substituted alpha C of michael donar is involved in the addition. Even bulky base using. Is it right?

Reply

HagiAzo

thank you James, the mechanism makes sense now, and the numbering is creally helpful…

Reply

Neha

If 1,4- addition and 1,2- addition pathways are both possible, how do we decide which one the reaction actually goes through?

Reply

Jon Harwell

Hi Neha,

I just commented on the same question above, so I’ll tell you how I remember it, as well.

Here’s a link to James’ explanation of conjugate addition:

https://www.masterorganicchemistry.com/tips/conjugate-addition/

I’m just a student, but anytime I have a conjugated ketone, I have to make a decision between 1,2 direct addition and 1,4 conjugate addition. The direct addition is the kinetic product and the conjugate addition is the more stable thermodynamic product.

1,2 direct addition is only accomplished by “super hero” amazing nucleophiles. These would be nucleophiles like Grignard reagents (MgBr), Hydrides, or ylides like Wittig reagents (PPh3). I’m sure there are more, but in my O-Chem class, those are the only three we have to worry about. If it’s not one of those, it is going to add 1,4.

Enolates are great nucleophiles, but they are not “super hero” nucleophiles. So, they will readily add 1,4.

Hope that helps.

Reply

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