Diene Synthesis

[blazinfury]

I am sorry to be a pain, but I was doing some practice synthesis and stumbled upon a 1,3 diene synthesis. I am not sure of how to approach this sort of problem and my textbook did not have any practice problems on this topic at all. The problem is attached below with my approach of doing it. You had to start with a cyclohexanol with 4 carbons or less. I am not sure if my way is effective, because I got stuck at my last step. Any advice would be appreciated. Thanks so much.

synth.pdf

[UC]

Did you mean cyclohexanol and any other compound up to 4 carbons?

 

The monoprotection of only one aldehyde is not going to be a very clean reaction. You'll need a strong base though to make the enolate before adding the TMSCl. Triethylamine (TEA) is going to be way too weak.

 

The organolithium is probably way overkill. A grignard reagent will probably be fine. Count your carbons. You have added an extra one after the organolithium treatment. The enol in the last step is going to rearrange into an aldehyde. I reccomend a wolff-kishner reduction to get to your final product.

 

I have attached the shortest route I could come up with tonight. Contrary to popular belief, I am not a walking dictionary of organic reactions, so there are probably much shorter ways to do what I did. I am not sure if step 8 will jive with that halogen though, so it may need reworking. Reagents/reactions are as follows.

 

1: H2SO4, heat

2: N-bromosuccinimide, radical initiator (light, benzoyl peroxide, etc.)

3: dimethylamine, weak base (acid trap)

4: O3, Zn/CH3COOH (There are several other ways to cleave the bond to two aldehydes, but take more steps)

5: wolff-kishner reduction

6: Hofmann elimination

7: N-bromosuccinimide, radical initiator

8: Oxymercuration/demercuration

9: oxidation (wide choice of reagents)

10: Strong, non-nucleophilic base

11: Schlosser modified wittig reaction using 1-halopropane to make the wittig reagent

 

Of course, it is absurdly complex to start from cyclohexanol. The second to last step can be reached directly with an aldol condensation between acetone enolate and propionaldehyde.

Edited January 23, 2009 by UC

[blazinfury]

Yes a cyclohexanol and any other compound or compounds containing 4 Carbons or less.

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Dude you are awesomely awesome. Thank you. Thank you. Just a quick side-quest. I just want to clarify something, if lets say you have a diol hydrocarbon chain right and you react it with PBr3, all of the OH's will become Br's right? If you have a diol hydrocarbon chain and you react it with TMSCl, would both of the OHs become OTMS or just one. I am personally curious about this because such an issue comes up frequently for me in synthesis and I wanted to clarify these two point. Thanks once again.

[UC]

First point, I just learned something about silyl ether formation. Take back what I said about the TEA. It should work fine.

 

It's all about stoichiometry. I however, get the feeling that for efficient protection of an alcohol, you probably need to use an excess of TMSCl, which won't give you what you want. If you use a strong base instead and make a monoalkoxide out of the vic-diol, you may be able to get a cleaner reaction. Then again, stoichiometry is usually not a great route to monoprotection or bromination, since you'll get some where there is no protection/bromination and some di-protected/brominated that need to be removed.

 

A better route is by opening epoxides. Dry HX in an appropriate solvent should open epoxides to halohydrins. Use of alcoxide in dry alcohol (after addition of water or acid) will yield a mono-protected ether.

 

Just as a note, vic-diols, epoxides, and halohydrins are somewhat unstable with respect to rearrangement depending on what the R groups attached to them are. Look up pinacol rearrangement and semipinacol rearrangement to know what to avoid.

[blazinfury]

Thanks so much for clarifying that.