silyl enol ether in baylis hillman reaction

[solak]

Hello yall,

a professor in an oral test asked me about reacting a silyl enol ether with a michael system and catalytic amounts of a tertiary amine. I was reminded of baylis hillman. He said that this was exactly right and wanted me to draw the product. Unfortunately i didn't understand how that was supposed to work with a silyl enol ether. He said that it would be the same product as with an aldehyde. I don't understand that. I've never seen a silyl enol ether as an electrophile. After some research on the net I couldn't find anything about it. What do you think? Is he wrong? Am I just confused?

Any response is appreciated!!

[hypervalent_iodine]

Your professor / instinct regarding the reaction is more or less correct. However, I think your professor may be a little wrong saying the product is the same as with the aldehyde, as the two would react ever so slightly differently. The main thing you'll need to think about here is how the silyl enol ether will feed into the traditional Bayliss Hillman mechanism and where the nucelophile is more likely to attack.

 

Looking at the general mechanism for the Bayliss Hillman (image taken from here because I couldn't be assed drawing it):

 

 

 

In this mechanism, you see that the stabilised nucleophillic anion on what was the reacting alkene attacks in at the most electropositive centre of the incoming aldehyde - i.e. the carbon in the carbonyl bond. The tertiary amine is then eliminated by either an intramolecular proton abstraction or base mediated proton abstraction. If we then feed a silyl enol ether into this, we see that the most electrophilic centre is more or less the same (the carbon bound to the oxygen), but there would be a slight difference in the way the reaction proceeds after the initial attack. I drew this for you, which should make some sense (hopefully):

 

 

 

 

There is a potential issue with condensation of the silyl ether with your amine, but I don't think it will be a problem since the resulting product from that would be very high energy and unstable.

 

Also, this is a super cool reaction; you could make all sorts of wacky conjugated dienes with it. I mentioned it to a friend who has a bit of a love hate relationship with the Bayliss Hillman reaction and he's decided he's going to give it a shot over summer as a bit of something to do. I'll let you know how he goes with it

 

Another thought I've had is that *maybe* the anion that forms after attack of the EWG nucleophile onto the enol is that you get an intramolecular reaction whereby the charge attacks the Si, causing the bond between the Si and the O to break. This would then undergo the same reaction as in the aldehyde version, with the exception of the Si being substituted alpha to the alcohol. Don't know how likely it is, but it's an idea.

Edited October 28, 2011 by hypervalent_iodine

[solak]

Thank you so much for your reply. Is your second mechanism is more or less a good guess or have you ever seen a silyl enol ether do that? I've also thought about the carbanion doing what the base normally does so that the product would have a protected alcohol instead of an alcohol in the normal reaction. Another question for me is: How likely would the carbanion be formed if R3 and R4 were methyl groups?

The reason why this is is driving me nuts is because I was asked that question in an oral test. He showed me the two compounds with the addition of TiCl4 and I knew that it's Mukaiyama. Then he replaced the Lewis Acid with the Amine and asked me what would happen now. That's when I became totally confused and lost my concentration for the rest of the test. So I'm wondering if someone who's starting his master's thesis should have known what happens....

[hypervalent_iodine]

I suppose it's just a good guess. The friend I told you about found two papers with similar reactions, but I didn't manage to get copies or names from him. I'll ask him to send them to me if you'd like?

 

I had thought about that question regarding the anion and how stable it would be. It might be okay with methyl groups, but if I'm being honest I don't really know. Myself and my friend are both Ph.D. students and neither of us have seen silyl enol ethers used like this. The lack of literature precedence suggests it's not particularly well known, either. That being said, the way it could proceed seems fairly intuitive when you break it down as I did in the second mechanism. The nucelophile attacks the most electropositive centre, etc., etc.

[solak]

Papers would be great

 

One last thing: How reasonable would it be to let the TMS group be attacked? I've seen that with Fluorine, Amine, BuLi and similar reagents. Do you think that would be possible with the enolate? One advantage might be that the carboanion would not have to be formed.

[solak]

Papers would be great

 

One last thing: How reasonable would it be to let the TMS group be attacked? I've seen that with Fluorine, Amine, BuLi and similar reagents. Do you think that would be possible with the enolate? One advantage might be that the carboanion would not have to be formed.

[hypervalent_iodine]

Do you mean, what if the bond breaks between the C and O upon initial attack of the incoming anionic nucleophile? I thought about that as well and the short answer is yes, I suppose it's possible. I was actually going to include it in the mechanism I drew, but decided against it. The other option is that the carbanion forms very transiently and not as an isolatable intermediate.

 

I'll get onto said friend re. the paper.

[solak]

That's not exactly what I meant. I was thinking about a nucleophilic attack at the Si, releasing the enolate...Although it feels strange drawing it.

[hypervalent_iodine]

I suppose it could do. Sterically, the carbon centre is much more accessible on account of it being planar and I can't imagine the difference in electronegativity being all that great since the Si has a heap of electron donating Me groups hanging off of it; I wouldn't expect it to occur all that much, if at all.

[mississippichem]

I think that whether our not the silicon atoms gets bitten depends on the nuclephile. I think a small, sterically unhindered "hard nucleophile" might go for the Si atom. But, as hypervalentiodine said that planar electron deficient carbon atom is a very attractive target for a nuclephile. In this case I think the Si atom attack will happen minimally.

 

If the Si atom was surrounded by -OH groups and that carbon wasn't so electron deficient then I could maybe see it. I do a reaction in my work where I sub out a methyl ether for an ethyl ether on an electron rich Silicon atom though (yes electron rich, strange right?). We have to use a Dean Stark trap to drive the equilibrium though, and the reaction is quite slow for a terminal substitution. Reactions at silicon atoms can be quite counterintuitive as the electronegativity is similar to carbon but the orbital energies are not and the polarizability is not.