[Guitarmaniac86]

Dear Organic forum,

I couldnt do this in the exam because I froze. Im doing a masters so I should find this easy, but for some reason I couldnt do it in the exam, so could someone check that I have this right... Organic is supposed to my strongest subject.

This is the retrosynthesis. I know, its really lazy but it takes ages to write out in chemdraw:



And here is the synthesis, again lazy. I know what the reagents are supposed to be but I didnt write them in.

[orgopete]

The cyclohex-4-ene-1,3-dione is actually resorcinol, and commercially available.

[OrgoTutor]

Hi Guitarmaniac86, I'm no expert but I have a few questions about the forward synthesis.

In steps 3 (and 7), where you react the substrate with acetaldehyde (in both cases), I would have expected the base to deprotonate the active methylene carbon between the 1,3-dicarbonyls given that those hydrogens are more acidic, in which case you would get a Knoevenagel condensation-type reaction, right?

In step 8 (labelled "Oxidise"), focussing on the two ring carbonyl groups, how did the carbonyls go from a 1,3 relationship to a 1,2 relationship?

In step 11 (the protection step), how do you selectively protect only the specific carbonyls you have drawn, i.e. why would the unprotected carbonyl remain unprotected rather than react with the glycol?

[Fluorine]

In step 11 (the protection step), how do you selectively protect only the specific carbonyls you have drawn, i.e. why would the unprotected carbonyl remain unprotected rather than react with the glycol?

I was wondering the same question, thanks for asking.

If I may give a guess, would it be because of carbocation stabilization? It's not much to go on but by unfavorable induction from both sides and minimal hyperconjugation the center (resulting) carbocation should be the least stabilized, thus least likely to proceed/react. If that's true add on possible steric interference from the protecting groups once attached to the more reactive sites. It seems to be correct when I drew it out but I'm prone to overlooking things. Is this the right idea or am I off?

[Guitarmaniac86]

Hi Guitarmaniac86, I'm no expert but I have a few questions about the forward synthesis.

In steps 3 (and 7), where you react the substrate with acetaldehyde (in both cases), I would have expected the base to deprotonate the active methylene carbon between the 1,3-dicarbonyls given that those hydrogens are more acidic, in which case you would get a Knoevenagel condensation-type reaction, right?

I would agree with you. I done the mechanism this way to justify the formation of the ring.

In step 8 (labelled "Oxidise"), focussing on the two ring carbonyl groups, how did the carbonyls go from a 1,3 relationship to a 1,2 relationship?

Genuine mistake in the synthesis, I need to revise it.

In step 11 (the protection step), how do you selectively protect only the specific carbonyls you have drawn, i.e. why would the unprotected carbonyl remain unprotected rather than react with the glycol?

I was going to do them in separate steps but I didnt think it would work because deprotection occurs with acid. I dont know how it would be selective for the ones I protected, in fact it wouldnt be.

[PKI_InformatixTS]

This is the retrosynthesis. I know, its really lazy but it takes ages to write out in chemdraw:

Hi,

Perhaps some tips and tricks could help you create such schemes much faster.  For example, using Name to Structure may help you create structures faster.  Using copy and paste may help you paste arrows/catalysts faster.  You could also potentially use templates for anything you know you are going to use frequently.  The ChemDraw Help menu will provide many more details on these suggestions in case you are interested.  Hope this helps!