Help with the synthesis of solanesylacetone

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Ida Forgione - 27 Jan 2004 15:03 GMT

Doing solanesylacetone by condensing ethyl acetoacetate with solanesyl
bromide and subsequent decarboxylation at 80°C in the presence of aqueous
NaOH cause the formation of some unexpected stereoisomers. How can I do to
avoid this formation and to abtain steromerically pure Solanesylacetone?

Ida

Università La Sapienza - Roma

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Paul J. Franklin(moderator - sci.chem.organic.synthesis)
http://organicworldwide.net/sci.chem.organic.synthesis
Georgia State University <chepjf@panther.gsu.edu>
Atlanta, GA

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Uncle Al - 28 Jan 2004 20:35 GMT

> Doing solanesylacetone by condensing ethyl acetoacetate with solanesyl
> bromide and subsequent decarboxylation at 80°C in the presence of aqueous
> NaOH cause the formation of some unexpected stereoisomers. How can I do to
> avoid this formation and to abtain steromerically pure Solanesylacetone?

Solanesol is a C-45 9-isoprene unit primary alcohol. Was it
isomerically pure to start? Did you expose it to acid when making the
bromide? Uncle Al would make the tosylate from the alkoxide in cold
3:1 anhydrous THF/HMPA via butyl lithium titration (a few mg of Ph3CH
indicator) under argon and then purified (recrystallized from
distilled hexanes) tosyl chloride. Adding 10 mole-% NaI to the mix
before the displacement might be wonderfully catalytic. Why?

Your decarboxylation conditions are not gentle. What happens if you
take a long chain alkoxide as a model and displace bromoacetone
(slowly adding a solution of the alkoxide to the bromoketone in cold
THF/HMPA)?

It would be very elegant to saponify with a mole of basic hydrogen
peroxide. You would get the peracid anion intermediate that might -
given the molecule balled up in aqueous solvent - selectively
epoxidize the terminal olefin as you acidified to work up. You would
then be set up to stereoselectively cyclize the entire molecule as in
a William B. Johnson steroid synthesis.

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Uncle Al
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"Quis custodiet ipsos custodes?" The Net!
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Paul J. Franklin(moderator - sci.chem.organic.synthesis)
http://organicworldwide.net/sci.chem.organic.synthesis
Georgia State University <chepjf@panther.gsu.edu>
Atlanta, GA

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Muhammar - 06 Feb 2004 21:49 GMT

Solanesol is the waxy stuff from tobbaco. I have seen the crude stuff
as isolated from tobbaco and the nice crystalline purified one. There
is huge differece in these, I believe there are other minor oligomers
present in the plant too. To get them out, you need to do a couple of
crystallizations. That's why pure solanesol is so expensive. Make sure
your starting material is good.

Allylic bromide prep: we have done very similar compounds from
terpenic allylic alcohols using the MsCl/iPr2NEt/LiBr mix in THF at
-20 to 0, to avoid isomerisation. As Uncle said, make sure that the
allylic bromide you are taking into reaction is not an isomeric mix.

Also, you always have to expect some 3-allylic isomer formation and
cis/trans isomeration on allyl with these. Keep the temperature down,
get good starting material and find a very close precedent with
farnesyl, geranyl or geranylgeranyl acetone preparation.

Uncle Al <UncleAl0@hate.spam.net> wrote in message news:<bv96dn$l0f@panther.Gsu.EDU>...

> Ida Forgione wrote:

> > Doing solanesylacetone by condensing ethyl acetoacetate with solanesyl
> > bromide and subsequent decarboxylation at 80°C in the presence of aqueous
> > NaOH cause the formation of some unexpected stereoisomers. How can I do to
> > avoid this formation and to abtain steromerically pure Solanesylacetone?

> Solanesol is a C-45 9-isoprene unit primary alcohol. Was it
> isomerically pure to start? Did you expose it to acid when making the
[quoted text clipped - 3 lines]
> distilled hexanes) tosyl chloride. Adding 10 mole-% NaI to the mix
> before the displacement might be wonderfully catalytic. Why?

> Your decarboxylation conditions are not gentle. What happens if you
> take a long chain alkoxide as a model and displace bromoacetone
> (slowly adding a solution of the alkoxide to the bromoketone in cold
> THF/HMPA)?

> It would be very elegant to saponify with a mole of basic hydrogen
> peroxide. You would get the peracid anion intermediate that might -
> given the molecule balled up in aqueous solvent - selectively
> epoxidize the terminal olefin as you acidified to work up. You would
> then be set up to stereoselectively cyclize the entire molecule as in
> a William B. Johnson steroid synthesis.

Signature

Paul J. Franklin(moderator - sci.chem.organic.synthesis)
http://organicworldwide.net/sci.chem.organic.synthesis
Georgia State University <chepjf@panther.gsu.edu>
Atlanta, GA

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Natural Science Forum / Chemistry / Organic Synthesis / February 2004

Help with the synthesis of solanesylacetone