[Altered State]

This is what I'm asked to explain:



As you can see, they give me 4 starting reagents and 1 final product, I'm supposed to explain that synthesis.


This is my attempt:



I think my route and mechanisms are OK, (please, check them), but as you can see, I don't even use one of those 4 starting compounds (the one that is an ester), and I introduce the extra carbon I need as Methyllithium.
Since this is going to be a graded exercise, I really need to know if there is another wayof obtaning the product using all the starting reagents. I don't see that way, specially when the sum of the carbons of those 4 reagents (without counting OEt, which would act as leaving group) is one more than there are in the final product (maybe lose of CO2? where?? and how???)

I also attempted using the ester:



But as you can see, in this case I don't see how can I add the Phenyl to the compound using the benzoic acid (which is one C more than I need). If it where bromobenzene, or benzene, I could simply add it as a grignard to the aldehyde -30ºC to obtain ketone... But is not the case.

I don't see other way more than the one I posted first, but I feel that's kinda "cheating", since I don't use one of the reagents and I use MeLi in exchange.


Any thoughts?

[orgopete]

Hint, start with a Claisen condensation. This will improve the remaining reactions retaining a similar strategy, but with better yields and fewer by-products.

[Altered State]

Hint, start with a Claisen condensation. This will improve the remaining reactions retaining a similar strategy, but with better yields and fewer by-products.

Mm, have a few questions

1) If I do a Claisen between two of the starting esters, now I have, not 1 but 3 more carbons more than I have in the final product using all of the four starting reagents.
I can't see what are your intentions by starting this way...

2) What do you mean by "similar strategy"? Similar to the first or to the second one I've posted?

3) In your opinion, what is the best way to add the phenyl group?

Thanks

[orgopete]

MeLi will add 2x with benzoyl chloride. The enolate of your ketone will give a lot of 1,2-addition rather than 1,4-addition. If you were using beta keto ester chemistry, this will not be true. I missed class, but I'm guessing this is the chemistry that might have been discussed as this problem is set up for its use. Obviously, I don't know this. It is just a guess.

[Altered State]

Let's say I use Me2CuLi at 0ºC, so I don't get 2x addition.

I've been taught beta leto ester chemistry, the thing is that I don't see how can I get to my final product using those 4 reagents and starting with a claisen between 2 molecules of the starting ester. I still have the three questions I mentioned in last post...
It's gotta be something I'm missing.


EDIT: I think I got it... You were talking about using acetoacetic synthesis? There we can "cut" some carbons out... Would make sense, I'll give it a try

[Altered State]

MeLi will add 2x with benzoyl chloride. The enolate of your ketone will give a lot of 1,2-addition rather than 1,4-addition. If you were using beta keto ester chemistry, this will not be true. I missed class, but I'm guessing this is the chemistry that might have been discussed as this problem is set up for its use. Obviously, I don't know this. It is just a guess.

Ok, I think I got it now, please tell me if you think it's correct this time:

[clarkstill]

I'd probably do the 1,4-addition before the decarboxylation; malonates/beta-keto esters are excellent nucleophiles for Michael additions, and then the product is quaternary and doesnt run the risk of doing multiple additions.  Also, do you really think the final elimination is a simple E1? 

The rest looks good.

[Altered State]

I'd probably do the 1,4-addition before the decarboxylation; malonates/beta-keto esters are excellent nucleophiles for Michael additions, and then the product is quaternary and doesnt run the risk of doing multiple additions.  Also, do you really think the final elimination is a simple E1? 

The rest looks good.

Thanks for the first point. I appreciate that kind of comments.

About elimination.. I don't know what you mean, you suggest it's E2? Or what?
The first thing that comes to my mind is that product won't be nicely yielded, because there is the possibility of forming a more substituted olefin...   

[clarkstill]

I don't think it'll be either E1 or E2; there's a particular elimination that operates when a leaving group is beta to an electron-withdrawing group called E1cb, where the reaction goes via a stable anionic intermediate...

[Altered State]

I don't think it'll be either E1 or E2; there's a particular elimination that operates when a leaving group is beta to an electron-withdrawing group called E1cb, where the reaction goes via a stable anionic intermediate...

Oh, didn't know that one, thank you.