[beheada]

I have been tasked with coming up with a theoretical synthesis from a diethyl ester to a benzyl ether. The only difference in the the two esters is that one is a secondary ester attached to an alcohol and the other is a primary ester.

The starting materials is D-(+)-Malic Acid diethyl ester. <BR>
<A HREF="http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=W237418|ALDRICH&N5=SEARCH_CONCAT_PNO|BRAND_KEY&F=SPEC">Starting Material</A><BR><BR>

I wish it was simple enough to protect the alcohol with TBS, then reduce the ester and use a williamson to add on the required benzyl group, but I have TWO esters. I've looked up papers on selective reduction of esters but the only helpful one is a selective reduction, but the rate of reaction is faster in this order 1 > 2 > 3 which means it won't be helpful. I also found a journal article that's japanese which states it will reduce an ester to a diol if it is already attached to an alcohol group, but I can't get the article because its japanese!!!

I'm running out of ideas on how to get from my starting material to the benzyl ether (left side from ester to benzyl ether)... aside from finding a way to protect the primary ester then reduce the secondary.

Any ideas would help greatly.

[Squirmy]

Can you provide a structure for the desired product?

[beheada]

Well, I have made the images on chemsketch but am unfortunately I am illiterate as far as computer technology goes. I have the pictures saved as gif formats, but can't figure out how to place them into my posts. Copy and paste won't work and when I click the insert image all I get are img prompts (like its HTML).

Regardless, the product I'm looking for is the benzyl ether instead of the ester on the side with the diol, and I have to keep the stereochemistry of the alcohol group. So the on the product, the ester needs to be replaced with a benzyl ether. My idea was:

Protect the alcohol
Selectively reduce (if this is possible with two esters) the ester
Williamson Ether Synthesis with Benzylbromide/chloride
Deprotect the alcohol

My problem is working with the di-ester. I'm not familiar with any selective protecting groups for esters (if there are any?). Anyway, I'll be up all night trying to figure out a possible route, so let me know if you have any ideas.

Thanks
(Also if you could tell me how to post gif format files I can place pictures on this post of the various structures)

[Borek]

When answering, click on Additional Options below edit field, then on choose button.

[beheada]

The attachment is of the b-hydroxy ester which is to be synthesized. I finally found the article on scifinder after learning to use the lock position button. If anyone is interested in the method, it was a selective reduction using BH3.DMS, to reduce the ester to the diol and then dibutyltin oxide and TBAI/benzylbromide to convert the primary alcohol to the appropriate ester. Figuring out the mechanisms for these guys was a little tricky for me, but after 3 hours of sitting in my prof's office, I got'em!
Thanks for the help with the pictures.

[sjb]

How about epichlorohydrin, reacted with benzyl alcohol. I think this attacks the epoxide preferentially, but not sure and don't have access to the literature at the minute  Trap the alkoxide with something like TES-Cl, then either form a grignard (or equivalent) and chuck in CO₂ to form the acid; or cyanide displacement which you can then hydrolyse again to the acid, then esterify and deprotect (are there non-acidic sources of fluoride?)

[Squirmy]

How about epichlorohydrin, reacted with benzyl alcohol. I think this attacks the epoxide preferentially, but not sure and don't have access to the literature at the minute  Trap the alkoxide with something like TES-Cl,

It's often difficult to get good selectivity when treating epichlorohydrin with nucleophiles, and if it does add to the epoxide, the alkoxide is often "trapped" by simply kicking out the chloride. This gives an epoxide with opposite stereochem than what you'd get from direct substitution of the chloride. Not to say it couldn't be done, but it's not trivial.

then either form a grignard (or equivalent) and chuck in CO₂ to form the acid; or cyanide displacement

This Grignard would be prone to elimination.

which you can then hydrolyse again to the acid, then esterify and deprotect (are there non-acidic sources of fluoride?)

Hydrolysis in the presence of the TES ether might be a concern. For non-acidic sources of fluoride, there's TBAF. If you want to get fancy, there's also TBAT.