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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: Telamond on March 24, 2011, 04:25:33 AM

Title: Suggesting reagents
Post by: Telamond on March 24, 2011, 04:25:33 AM

Having some troubles suggesting reagents for these transformation.

1b is an epoxide opening followed by an oxidation to form the ketone, but I don't know anyways to open the epoxide on the most substituted position using a hydride...

1c, for this I suggested a Sonogashira, but I don't know a synthesis that would add the ethyl group on the triple bond like the and give that stereoisomer of the double bond. (not to mention about the selectivity troubles one would get by adding the conjugated ester first...)

A friend that's a ph d suggested a carbometalation, I checked it up on wiki, and didn't recognize it, and none of my lecture notes mention it... does anyone have any other ideas on how to synthesize it?

Any tips/hints would be helpful.

Title: Re: Suggesting reagents
Post by: jake.n on March 24, 2011, 08:37:52 AM

I don't know of any way to selectively open that epoxide with hydride as you suggested.  However, you open the ring with water, then dehydrate to the corresponding enol as shown in this paper:

http://lib.mdpu.org.ua/load/Chemistry/Organic%20chemistry/Organic%20syntheses/English%20edition/diol2ketone.zni2

I don't know about that second one, though

Title: Re: Suggesting reagents
Post by: Honclbrif on March 24, 2011, 12:15:35 PM

For the second: I'm thinking organocopper reagents and conjugate addition.

Title: Re: Suggesting reagents
Post by: Telamond on March 24, 2011, 02:46:24 PM

jake.n : Formation of the enol wouldn't give the methyl enantioselectivity.

Was wondering if you were to use the BF3 as suggested in your paper, a carbocation intermediate would open up. A hydride shift from the top face would then push the methyl group down, no? Are these hydride shifts plausible at all? Are there any reagents that would help such a shift?


Honclbrif : I checked the wiki-page on organocuprates, and it does mention something about Normant's reaction adding to terminal alkynes. Would like to know if you/anyone knows how they look like and how they are synthesized, don't have access to Tet Lett at home (and the article seems to be in french as well)...

Title: Re: Suggesting reagents
Post by: nox on March 24, 2011, 10:37:50 PM

Not sure if this will work, but this is what I have for 1c:

1. Deprotonate propyne with BuLi, then quench with formaldehyde
2. Oxidize to make ynal
3. Do a copper catalyzed conjugate addition to the ynal using ethylboronic acid to make the enal (ref: ChemComm, 2008, 2010-2012, they only tried adding aryl boronic acids to alkyne esters, so not sure if alkyl boronic acids or ynals would work)
4. Horner-Wadsworth-Emmons on the enal to make the final product

Title: Re: Suggesting reagents
Post by: Honclbrif on March 25, 2011, 09:07:59 AM

I was thinking propyne + lithium diethylcuprate, oxidize the cuprous product to a bromide or iodide. Add Mg, conjugate addition to ethyl propynoate.

Or propyne + DIBAL, then Pd catalyzed coupling of the aluminum product with ethyl 3-bromopropenoate.