[bmilla35]

Hello everyone!

Here I am again, lying on bended knee begging for advice. I worked on it for 3 hours and have a whole pile of eraser markings and a blank paper to show. I think it's the whole NaOH AND H30+ that's throwing me off. I don't recall doing this other than with esters...does this just prepare it for the second addition?

Just so everyone is clear, it's the top problem. Thanks for any input. I REALLY appreciate it.

[discodermolide]

Form the enolate of the ketone (removal of one
Of the H atoms in the methyl group) and react this enolate with your ketone and see what you get after acidification.

[bmilla35]

Form the enolate of the ketone (removal of one
Of the H atoms in the methyl group) and react this enolate with your ketone and see what you get after acidification.

Once again, thanks for your help. So I add the second equivalent before I treat with acid? If so I don't know what the second step would be

Edit: Is this remotely correct? I reacted the enolate with the ketone and treated with acid....if this is right, what is the next step asking to do?

[discodermolide]

Yes you add the 2nd equivalent of methyl ketone before the acid.
That structure is correct.
The acid is there as a work-up to re-protonate things and neutralize the NaOH.

[bmilla35]

Yes you add the 2nd equivalent of methyl ketone before the acid.
That structure is correct.
The acid is there as a work-up to re-protonate things and neutralize the NaOH.

My goodness..I guess miracles cannnn happen

Now..for the second part? Do I just repeat the process?

[Arctic-Nation]

You can form an enolate again, but then an elimination reaction follows.

[bmilla35]

You can form an enolate again, but then an elimination reaction follows.

Is there no second equivalent then? I don't understand why it isn't stated. I hate assuming things lol

Thank you for the *delete me*

[Arctic-Nation]

There's no second equivalent of acetylcyclohexane. Acidic workup means that the reaction is stopped and the product isolated.

[bmilla35]

There's no second equivalent of acetylcyclohexane. Acidic workup means that the reaction is stopped and the product isolated.

Makes sense. You people are incredible..its a great online resource. I'm sure ill be back soon (like hours).

[bmilla35]

-Here we go..last question. I tried the NaOH and acid method, which gets me close if i'm doing it right. You should see where i'm stuck.

[discodermolide]

In your proposed product you have a 5 valent carbon atom!
This looks like a two step reaction to me and you are almost there with your reasoning.

[orgopete]

-Here we go..last question. I tried the NaOH and acid method, which gets me close if i'm doing it right. You should see where i'm stuck.

To me, this problem looks like an error in its formulation if it was intended to follow the precedent of the other problem.

NaOH would only hydrolyze the ester.
Phenoxide cannot catalyze a Claisen condensation.
If you did use LDA, I still think it would catalyze a Claisen condensation as phenoxide is a good leaving group, but I don't see how you would add a phenyl group to the ketone because the acidic hydrogen would quench your Grignard reagent.

It seems more likely that the starting material should have been a phenyl ketone.

[discodermolide]

Here is a suggestion for a retro-synthesis and some reagents for the forward direction.

[orgopete]

I just thought that was an unusual Claisen reaction, one in which a phenyl ester was used. Therefore you cannot use the phenoxide because it is too acidic. Okay, use LDA. Does that really work? I know LDA doesn't attack a carbonyl group, but if you have a phenyl ester, does that still hold? If you took isopropylamine and phenyl acetate and there is no reaction? No matter, I'll concede the Claisen.

I just didn't think you could add a Grignard to a beta-keto ester. If you have a beta-keto ester and treat it with the corresponding alkoxide, it forms the alcohol and the enolate because a beta-keto ester is more acidic. I didn't think you could add a Grignard to a carbonyl group in alcohol. Even though alcohols are less acidic than a beta-keto ester, I thought they would react faster than a ketone, especially a phenyl ketone. There is a reaction sequence of reacting the methyl ether from cyclohexane-1,3-dione with a Grignard, hydrolyze, and eliminate to get a beta substituted cyclohexenone. Why make an ether if you can add directly?

There is still an alternate route, make the phenyl ketone from the phenyl ester and do a Claisen with that. This still looks convoluted. I just thought there could have been an error.

[discodermolide]

If you used a co-ordinating metal do you think the phenyl group would still add or would it enhance the enolisation?
I was thinking of some of Knöchel's work here.