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Topic: Mesylation trouble  (Read 28684 times)

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Offline OC pro

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Re: Mesylation trouble
« Reply #15 on: June 11, 2012, 04:50:35 AM »
Do you have more than one OH groups free? If so I would assume you will get epoxide by-products.

Offline discodermolide

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Re: Mesylation trouble
« Reply #16 on: June 11, 2012, 05:10:27 AM »
You may be getting CH2=SO2 formed which then polymerizes, the idea of using the anhydride will prevent this.
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Offline sjb

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Re: Mesylation trouble
« Reply #17 on: June 11, 2012, 06:24:45 AM »
There is also more than one sort of OH in conduritols - see http://en.wikipedia.org/wiki/Conduritol . Is it possible you are mesylating one or the other with little chemoselectivity?

Offline sudi

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Re: Mesylation trouble
« Reply #18 on: June 11, 2012, 10:40:07 AM »
All the other -OH's are protected with -OBn. There is only one -OH available, the conjugated one. It seems that I am getting both epimers of the mesylated product because if I add water to the mixture I get my starting conduritol and its epimer (which originally was absent in the reaction). But assuming the mechanism is SN2 type, I don't know how I am getting the other epimer.
Any ideas?

Offline sudi

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Re: Mesylation trouble
« Reply #19 on: June 11, 2012, 10:57:20 AM »
My starting material is F conduritol referring to http://en.wikipedia.org/wiki/Conduritol. The top -OH is the only one available to react. The rest are benzyl protected.

Offline Doc Oc

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Re: Mesylation trouble
« Reply #20 on: June 11, 2012, 01:53:41 PM »
Maybe you're seeing a Baylis-Hillman type elimination, where the triethylamine is adding to the alkene and causing elimination of the mesylated alcohol.  That is obviously very reversible, hence the reason you're seeing both epimers.

Offline sudi

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Re: Mesylation trouble
« Reply #21 on: June 13, 2012, 12:34:15 AM »
Any idea on how to prevent it?
Does anyone know if Mesyl anhydride is sensitive to water? I read in this thread that MsCl is not water sensitive. How about Ms2O?

Offline Dan

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Re: Mesylation trouble
« Reply #22 on: June 13, 2012, 02:44:06 AM »
Any idea on how to prevent it?

If a Baylis-Hillman-like reaction is operating, switching to a less nucleophilic base (e.g. DIPEA) should stop/reduce it.

Quote
if I add water to the mixture I get my starting conduritol and its epimer

Why are you adding water? Is this in the workup? MsCl and Ms2O are both water sensitive, nobody claimed they weren't.

Another explanation is SN1 and/or SN2' possibly involving neighbouring group participation by a benzyl ether. It might be useful to know the relative stereochemistry of the four centres if you can provide it.

In that case it might be better to switch to a tosylate as it's not as good a leaving group, so SN1 pathways will be reduced. Not sure if that's really the cause though.

If you purify and take the mesylate on to the next reaction (which I assume is a displacement, can you tell us?) do you get complete inversion of configuration?

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Offline Babcock_Hall

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Re: Mesylation trouble
« Reply #23 on: June 13, 2012, 09:50:04 AM »
Rory, Is your starting material in the keto-form or the hemiketal form?

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