[stevet]

I am trying to epoxidise a double bond using Sharpless methodology, though the first two times I tried (reaction left for 3 days), i got a 1:1:1 ratio of starting material:epoxide on 1 face :epoxide on the other face. So really ot appears that the reaction doesn't want to work. Currently I am trying to do the reaction with the opposite  diethyltartrate, with DIPT and with no tartrate. Any other ideas of how i could maybe pusuade this uncooperative reaction to work?

[sjb]

I'm surprised you don't seem to be getting any diastereoselectivity - you are using enantiomerically enriched (or pure) tartrate, aren't you? What happens during the 3 days of leaving the reaction - are you seeing formation of both enantiomers straight away, or does one form, then the other? Can you post the structure of your allylic alcohol, just in case there's something funny going on? How's your t-butyl hydroperoxide?

[stevet]

My suervisor is stumped as well...
I am using 98% SS-DET, so that shouldnt be the problem, and NMR of the t-butylhydroperoxide shows that its pure, so i don't think thats it either. The probplem with monitoring the reaction during the 3 days is that the allylic alcohol and both epoxides are inseparable by TLC, and NMR is of no use, due to the complexity of the mixture, as well as the formation of the tartrate esters, but i am assuming this. It is also worrying though that there is still starting material present, which means even if the desired epoxide were forming, to stop the reaction before the formation of the other epoxide would mean very low yields.

Reaction I am after is as follows:

[azmanam]

are you distilling the Ti(OiPr)4 before use?  You may want to get a rotation on the DET if it's old... It theoretically has epimerizable protons which could theoretically destroy the optical purity of the DET.

You might take a closer look at monitoring by NMR... You don't need to identify every peak in the mixture, but you can watch for the disappearance of the alkene protons.  it doesn't seem like there should be much in that region.

[sjb]

Hmmm, are you sure that diasteromer will form preferentially - it's been a while since I looked at SAEs, but it seems that the methyl group is blocking formation of your desired. Is the allylic alcohol enantiomerically pure? If you can't separate the compounds by TLC (have you tried a completely different system, so if it's ethyl acetate / ether at the mo', why not DCM / MeOH etc) and you say the NMR is difficult, how are you monitoring the reaction (can you check for disappearance of the olefinics relative to the methyl)? Can you change the TBS for something else?

[azmanam]

you could also try shi's epoxidation method if SAE just doesn't work for you.

[kiwi]

Hmmm, are you sure that diasteromer will form preferentially - it's been a while since I looked at SAEs, but it seems that the methyl group is blocking formation of your desired.

That's what I see as well. You've got mismatched stereoinduction - if you think about the transition state, the Sharpless catalyst is trying to place the oxygen on the top face of the double bond, but the allylic methyl group is also on this face and is sterically repealing the approach of the catalyst. So you are getting slow non-stereoselective epoxidation instead. Can you find any literature precedent for epoxidation cis to an allylic group?

[sjb]

Hmmm, are you sure that diasteromer will form preferentially - it's been a while since I looked at SAEs, but it seems that the methyl group is blocking formation of your desired.

That's what I see as well. You've got mismatched stereoinduction...

I guess if this is the case, reaction with the opposite tartrate ought to be fairly facile (to get the diasteromer, though). How are you setting that chirality up?

[stevet]

Thanks for all the comments. Strangely enough, after working up the three other experiments, namely the epoxidation with no tartrate, with RR-DET and with the SS-DIPT, the results are as follows:

No Tartrate: No epoxidation at all
RR-DET: A 1:1 ratio of the two epoxides agiain, and after the reaction was allowed to proceed for 5 days, still a significant amount of starting material left in the reaction mixture
SS-DIPT: SUCCESS! a 9:1 ratio of the desired epoxide to the undesired epoxide, which i am pretty happy about. There was also no starting material left in the reaction mixture at all.

I think the mismatch is still a problem, explaning why we still see some of the other diastereomer, however the added bulk of the DIPT sems to be able to force the desired reaction.

So quite an interesting result...

[sjb]

Glad things are starting to work the right way!

I return to my previous query on how you are monitoring the reaction? How are you sure your major isomer is your desired? A quick fiddle in ChemDraw (albeit an old version) does not show any significant difference between the two sets of CH peaks in terms of multiplicity or actual delta.

[stevet]

The only way I have to monitor the reaction is by proton NMR. I also checked the predicted shifts in Chemdraw, but they are slightly differentin practice. The signals appear at about 3ppm, and there are 4 distinct signals present, (2 x triplet of doublets and 2 x  double doublet) each slightly separated, but they dont overlap. The two outer signals are for the syn epoxide(1 x triplet of doublets and 1 x  double doublet), and the two inner ones for the anti epoxide. Theis isn;t set in stone, though from the NMR of the SS-DIPT, the outer set of signals was much stronger, with the inner signals there but much smaller, so it is an 'educated guess' that the desired epoxide is forming. Any suggestion as to how to check  this for certain?

[kiwi]

Something about this doesn't add up; i think you have misassigned the products.

Think about the initial example, 1:1 ratio of epoxides (regardless of NMR assignment). Due to the slow reaction rate, and poor selectivity, this is assigned as a case of mismatched stereoinduction between the catalyst and allylic methyl.
So, changing from the (R,R)-tartrate to the (S,S)-tartrate gives a vast increase in rate and selectivity. Which you expect if you now had matched stereoinduction, with both the catalyst and the allylic methyl group giving the same sense of stereoinduction. Which would occur if the major product was the undesired isomer. So i think you probably have your assignments backward.
You could investigate this by running the reaction with (R,R)-DIPT, to see if you get another mismatch ie. slow reactivity and poor selectivity. If you do, you assignments are probably backward. Alternatively you could try to induce crystallisation of the separated major isomer. You'll struggle to get crystals with that TBS group, my instinct would be to knock the TBS group off and try to introduce a crystallising group (tosyl or m,m-dinitrobenzoate ester are a good start). Truck your crystals off to the nearest friendly crystallographer and hopefully they can tell you for sure.

PS. a stupid question, but all the best ones are - you are certain you have the (E)-alkene?