[bcorgo]

Hi,

I am trying to separate the E Z isomers of the compound whose image is attached.

I have them in a 3:1 E:Z ratio and I need only the E isomer. I need to do this on a large scale for a total synthesis so silver impregnated column chrom. is not an ideal solution. Also regular fractional distillation won't work because the BPs are too similar. Does anyone know of any other techniques?

I was trying to find some literature on Z selective dihydroxylation or epoxidation in order to selectively oxidize the Z isomer so that I can then easily separate the unreacted E isomer. I didn't really find any helpful articles. Does anyone know of any such selective reactions?

thanks,

A

[Dan]

How much experimentation with solvent systems for chromatography have you done? Different systems can give quite varied separation. My starting points are usually hexane/EtOAc, toluene/acetone, DCM/MeOH.

If I was in your position I'd try and carry the mixture through to the next step and see if the separation improves, or recrystallisation becomes an option.

Failing that you could try to derivatise the aldehyde to allow crystallisation. This is really old-school but maybe Brady's reagent will allow you to recrystallise the major isomer cleanly. Or maybe there's a crystalline acetal derivative?

[bcorgo]

hi,

thanks so much for the suggestions. I'll definitely look into them. The problem with carrying the mixture through to the next step is that I am coupling it with a compound that's valuable and I don't want to waste a bunch of it by separating after this next step.
I'll definitely look into your other suggestions. Again, thanks so much! I am a first year grad student working on a total synthesis so its definitely challenging, but I am learning lots of new chemistry quickly which is great.

A

[Doc Oc]

1) I think you could separate this by column chromatography.  I've successfully separated E/Z isomers many times this way.

2) Is the alkene a functionality that carries through the entire synthesis or are you doing something to it later?  If you do something like an epoxidation or hydroxylation, you'll have diastereomers due to that other chiral center alpha to the aldehyde.  Those often separate very nicely by column.

3) I like Dan's suggestion to try and crystallize it.  I don't know enough about crystallization to help you, but I think it's worth looking into.

[discodermolide]

Hi,

I am trying to separate the E Z isomers of the compound whose image is attached.

I have them in a 3:1 E:Z ratio and I need only the E isomer. I need to do this on a large scale for a total synthesis so silver impregnated column chrom. is not an ideal solution. Also regular fractional distillation won't work because the BPs are too similar. Does anyone know of any other techniques?

I was trying to find some literature on Z selective dihydroxylation or epoxidation in order to selectively oxidize the Z isomer so that I can then easily separate the unreacted E isomer. I didn't really find any helpful articles. Does anyone know of any such selective reactions?

thanks,

A

They are relatively volatile, use a spinning band distillation to achieve the separation;  http://en.wikipedia.org/wiki/Spinning_band_distillation

[orgopete]

We haven't been given much to go on with this problem, so we are limited in what we can suggest. Is this a mixture of the four isomers? I doubt you can crystalize this from the mixture. I think you might find it difficult to crystalize if you had a pure single compound (racemic or one isomer).

Almost any reaction is potentially selective. Because I don't know what you planned to react the aldehyde with, it is difficult to predict its selectivity, but if it were my problem, I'd give it a try. Given that is the case, I'd be a little selective in how I tried it. Since you have a 3:1 mixture, try a reaction with a 0.25 mol ratio of a similar reagent. What is the ratio of the products and recovered starting material? Is it totally non-selective? Does your reagent react faster with the E or the Z isomer? How low of a temperature can you run the reaction?

I agree with discodermolide. A spinning band distillation column may separate the isomers. However, I don't know whether a spinning band column is available to you. I also don't know how widely separated these isomers are on a boiling point gas chromatography column.

Derivatization: It's an aldehyde, can you do the coupling from an imine? Can you make an imine with something that might increase the selectivity? If your starting material is readily available, you could convert it to the carboxylic acid. There, you should be able to make a crystalline derivative, including separating into the R and S isomers (if not already separated). I'm sure we could go on and on about derivatives, …

Synthesis: Just make the desired compound by another route so you have a single isomer. That looks like it might be the easier route.