[addymarei06]

I need to do a retrosynthesis of 2-acetyl-3-hydroxy-2-cyclopenten-1-one from an acyclic precursor of 5 carbons or less. Which functional group would I add first to the precursor?

[Doc Oc]

I don't wanna give away too much, but I'm willing to bet you recently covered the topic of aldol additions.  Maybe it will help you visualize it if you tautomerize the enol into a ketone.

[addymarei06]

Ok. So I figured out how to get the ring with the double bond and the acetyl group in the right spot but now there is a methyl group where the hydroxy group should be. Is there a reaction that changes the methyl to an -OH group?

[Doc Oc]

Without seeing your work it's hard for me to give you proper guidance.  Maybe I can ask you a couple of questions that will give me an idea:

1) I'm assuming that I was correct that you did recently learn aldol additions.  Did you also learn Claisens?  Not the rearrangement, the condensation.  Mixed aldol additions?

2) What about oxidations and reductions?

3) Do you know acetal/ketal formation?

4) Can you tell me how you went about your synthesis?

[addymarei06]

Yes we've learned all of those reactions. I took octane-2,7-dione in KOH which gave me 2-acetyl-3-methyl-3-hydroxycyclopentane. That treated with heat gave 2-acetyl-3-methyl-2-cyclopentene (I found this reaction in my class notes). Now I've gotten stuck in both directions.

[Doc Oc]

I see.  Okay, you're on the right track.  First problem is that you're using forbidden starting material, you can't use anything more than 5 carbons long, right?  Your prof deliberately gave you a different material so you couldn't just copy the lecture notes.

I'll just point you in the direction towards the answer.  Tautomerize the enol into the ketone.  You should have the triketone at that point.  Break the ring next to either carbonyl, it doesn't matter because it's symmetric.  Then draw that structure and BE CAREFUL to count the carbons so you have the proper number for the linear precursor.  You're just breaking a bond so the number of carbons should be the same.  This will give you a linear compound with more than 5 carbons.  So you'll need to break it again.  How can you start with 5 carbons and build it to the proper length?  I gave hints earlier, this can all be achieved with aldol and Claisen reactions, although you can also do just aldols and oxidize since the products from aldol additions are alcohols and you need to end up with carbonyls.

Good luck!

[addymarei06]

Thanks for the help. That precursor that I found in the notes would have to be broken down further in order for me to use that one.

[addymarei06]

what would i use to break the ring into the triketone?

[Doc Oc]

You're not trying to break the ring open, you're trying to make it, remember?  So figure out a way that you can cyclize it with the linear precursor.  Remember my hint, you can use an aldol or a Claisen to do this if you have a linear tri-carbonyl compound.

[addymarei06]

ah. and I meant break in it in respect to the retrosynthesis

[Doc Oc]

When using retrosynthesis you don't need to actually come up with reagents to achieve those transformations, the retrosynthesis is just meant to show a logical thought process in disassembling the molecule.  Keep plugging away!

[addymarei06]

we get extra points if we show both the retrosyntheis and the actual synthesis with reagents... sorry, I should have mentioned that