[camptzak]

"Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group"

Syntheses of each of the following compounds has been reported in the Chemical literature. Using the identical starting material and any necessary organic or inorganic reagents, describe the short sequences of reactions that would be appropriate for each transformation.

I cant figure out how to do this one
I have tried hydride reduction followed by organo-metallic substitution of the hydroxy group. I cannot make an organic group for the second reduction that fits into making the target molecule.

Ive tried the wittig using different types of substituents.
I have tried a few different Diels alder reactions.

I was thinking that the double bond conjugated with the aldehyde may be subject to attack by a nucleophile creating a carbanion. The carbanion could be protonated and the aldehyde could then be reduced intermolecularly...

cant make it work..

I dont have Chem draw, so I apologize about the bad artwork. I do not know the nomenclature for these compounds.

[Dan]

Can you think of any direct, general methods for forming unsaturated 6-membered rings?

[AlphaScent]

Dan,

    Upon first glance I thought it was a birch reduction type question.  Then I thought Diels-Alder, then Alder(ene) die to the oxygen being present.  But the oxygen is lost during this synthesis.  The double bond made from that functional group has to come from dehydration.  Still thinking about this problem.  Any more thoughts from you camp, or dan??

[AlphaScent]

but the dehydration doesnt follow zaitsevs rule...

[fledarmus]

What if you take the oxygen out first? I see a possible start using a Wittig reaction...

[AlphaScent]

That was my next assumption, it does work for that bond.  But what ylid to use?  Is something like that vicinal vinyl diester available??? I dont believe it is a one step reaction and besides, it's from a chapter about nucleopilic addition to a carbonyl group

[orgopete]

Just to keep this moving in the right direction. The target is not the product of a Diels-Alder reaction. However, a Diels-Alder reaction looks like a good precursor which could give the target after a bond migration. If that were the case, what Diels-Alder reaction will give the carbon-carbon connectivity of the target molecule?

[AlphaScent]

Orgopete,

My stump in the road has been the double bond between the esters.  I figure maleic anhydride diels-alder will get you get closer once you remove the aldehyde by wittig to produce the diene.  Which reacts with the maleic anhydride (dienophile.  But only one double bond is produced. 

Hydrolysis of the anhydride and esterification would be the final step.  Its that double bond that is a problem for me.

[Dan]

Hint: It is not only alkenes that can react with dienes in Diels-Alder reactions...

[AlphaScent]

Dan,

I know alkynes can react also to perform a [4+2] cycloaddition.  So the answer to the question would be:

1) Wittig reaction with methyl triphenylphosphonium bromide to yield diene

2) Diels-Alder reaction with alkyne  (maleic anhydride type followed by hydrolysis and esterification)
    2*) Most likely one would use ethyl-1,4-but-2-ynenoate
3) Bond Migration to yield conjugated olefins and final product....dont know the conditions here...maybe KOH and heat, but that would hydrolyze the ester...I guess we are almost there...

[Dan]

Yeah, that's the approach I'd put on paper

Most likely one would use ethyl-1,4-but-2-ynenoate

Do you mean 1,4-diethyl but-2-ynedioate?

3) Bond Migration to yield conjugated olefins and final product....dont know the conditions here...maybe KOH and heat, but that would hydrolyze the ester...I guess we are almost there...

Base catalysed alkene isomerisation looks like it would work to me. KOH will cause problems with the esters - this is quite a general problem with esters, and there is a general solution. If you need a base with a similar basicity to hydroxide, but that will not give a net reaction with an ester, what do you normally use? Example: why don't you use KOH for the Claisen self-condensation of ethyl acetate? What do you use instead and why?

[AlphaScent]

Dan,

You are indeed correct.  My nomenclature is my weakest area.  Yes, 1,4-diethyl-but-2-ynedioate is the reagent to use in this synthesis.

You would sodium ethoxide during a self condensation of ethyl acetate.  It is catalytic in nature and is regenerated when it is kicked out after the nucleophilic addition of the enolate. 

[fledarmus]

KOH will cause problems with the esters - this is quite a general problem with esters, and there is a general solution. If you need a base with a similar basicity to hydroxide, but that will not give a net reaction with an ester, what do you normally use? Example: why don't you use KOH for the Claisen self-condensation of ethyl acetate? What do you use instead and why?

My compliments Dan - I think this is one of the most instructive hints I've seen on this forum!

[camptzak]

wow, Im sorry i missed the chase on this one.
Thanks for the answer, Im arrow pushng through it right now. this question was driving me crazy.

[Dan]

i didnt know maleic anhydride in an alkyne form could exist.. then again, theres lots I dont know, so i guess that shouldnt suprise me.

It can't. Read the thread more carefully, the alkyne suggested was 1,4-diethyl but-2-ynedioate.