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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: Nescafe on September 23, 2014, 12:04:35 PM

Title: Oxetane, what happened?
Post by: Nescafe on September 23, 2014, 12:04:35 PM

Hello,

I was trying to globally deprotect two acid labile protecting groups and by NMR they are gone but it seems as though my octane ring has opened up my conditions were Dioxane/MeoH/4.0M HCl.

Not sure what happened, is anyone familiar with oxetane chemistry?

Thanks,

Nescafe.

Title: Re: Oxetane, what happened?
Post by: discodermolide on September 23, 2014, 12:25:38 PM

Would you not expect this to happen under acidic conditions? Release of ring strain.
Why use acid labile protecting groups?

Title: Re: Oxetane, what happened?
Post by: Nescafe on September 23, 2014, 12:31:22 PM

It was the shortest number of steps to reach a point to generate a library have to restructure the path.

I opened up the ring and basically made HO-CH2-C(R,R)-CH2-Cl based on LCMS and NMR

I will have to utilize protecting groups that are removed under basic conditions. I think Oxetane is stable to Pd/C so I might benzyl protect

Title: Re: Oxetane, what happened?
Post by: discodermolide on September 23, 2014, 12:35:46 PM

You may need to be careful with the conditions.
Why not use silyl?

Sometimes the shortest is actually the longest:)

Title: Re: Oxetane, what happened?
Post by: Nescafe on September 23, 2014, 12:36:54 PM

I have an amine and an acid on the molecule that need protecting :|

I dont think the oxetane is base sensitive, the previous step I had lots of Cesium carbonate and it remained intact

Title: Re: Oxetane, what happened?
Post by: discodermolide on September 23, 2014, 12:42:37 PM

I meant the conditions of the hydrogenation.
But base labile groups should be ok.

Title: Re: Oxetane, what happened?
Post by: TheUnassuming on September 27, 2014, 04:24:34 PM

Hey disco, what do you think will happen to the oxetane with the Pd reduction conditions?

Title: Re: Oxetane, what happened?
Post by: discodermolide on September 28, 2014, 11:15:05 AM

Ring opening, depending upon the conditions?

Title: Re: Oxetane, what happened?
Post by: TheUnassuming on September 29, 2014, 06:07:41 PM

haha... yes.  I was trying to come up with a mechanism for it but wasn't coming up with anything. 
I'm proposing to use an oxetane in a few analogues and was thinking of using allyl and benz protecting groups in the synthesis.  If this is a known problem I'll propose a different route. :)

Title: Re: Oxetane, what happened?
Post by: Dan on September 30, 2014, 03:39:32 AM

Quote from: discodermolide on September 28, 2014, 11:15:05 AM

Ring opening, depending upon the conditions?

This can certainly happen with azetedines, so I wouldn't be surprised to see it as a side reaction with oxetanes.

Title: Re: Oxetane, what happened?
Post by: Nescafe on September 30, 2014, 04:13:12 PM

Well, I can tell you that it opened up like a baaast**d under pd/c in MeOH. Apparently a way around it is using water/ethanol which I will try next. Interestingly, it looked like a 50:50 but when performing the celite filtration and using MeOH to flush the product through it converted to 100% fully opened ring.