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Topic: Oxidative Cleavage of 2-Allylphenol  (Read 321 times)

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Offline AlphaScent

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Oxidative Cleavage of 2-Allylphenol
« on: March 12, 2019, 05:18:28 PM »
So, How would you oxidatively cleave the terminal olefin in 2-allylphenol to give 2-hydroxyl-phenylacetic acid.

Because heres what does not work:

KMnO4 in 1M Sulfuric acid, Nope.
Ozonolysis is MeOH followed by hydrogen peroxide, Nope.

I am trying this right now: JACS 2002, 124, 3824.  0.01 eq potassium osmate, 4.0 eq oxone, done at 0.2 M in DMF.  Reaction is done at RT and ref gave now indication of an exothermic reaction....well it was.

My issue is the phenol.  I am oxidizing to the quinone, at least with KMnO4 I did.  Do we think I should just protect or do you fine chemists have another recommendation?

I was thinking Lemieux-Johnson followed by Pinnick to give acid if I really do not want to protect.

Anything helps! 

Cheers!
If you're not part of the solution, then you're part of the precipitate

Offline TheUnassuming

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Re: Oxidative Cleavage of 2-Allylphenol
« Reply #1 on: March 12, 2019, 08:54:27 PM »
My guess is you are going to have to 2-step it or protect, but protecting will add another step.

For the ozonolysis->H2O2 route, what did you see?  My first pass route would probably be ozonolysis->pinnick.
When in doubt, avoid the Stille coupling.

Offline AlphaScent

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Re: Oxidative Cleavage of 2-Allylphenol
« Reply #2 on: March 13, 2019, 02:27:48 PM »
Oddly enough it was a mixture of crap.  Was not clean so I did not proceed with a detailed analysis.  I am surprised given that ozonolysis is usually clean.

The OsO4 and oxone reaction has seemed to work.  NMR of crude looked ok. I am pumping on the bulk now and will get an NMR and yield tomorrow.

Ill let you know.

Cheers!
If you're not part of the solution, then you're part of the precipitate

Offline TheUnassuming

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Re: Oxidative Cleavage of 2-Allylphenol
« Reply #3 on: March 13, 2019, 02:33:13 PM »
Surprised your substrate is having such issues with O3, but it fits with what I've seen before.  Ozonolysis for me has always been an all or nothing reaction, I've never had a substrate that was middle of the road.

Good luck and stay safe with that OsO4 scale-up!
When in doubt, avoid the Stille coupling.

Offline AlphaScent

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Re: Oxidative Cleavage of 2-Allylphenol
« Reply #4 on: March 14, 2019, 01:07:54 PM »
I made about 660 mg of the 2-hydroxylphenylacetic acid.  58% yield.  I was hoping it would be an easy synthesis and I could just make it from the 500 g of 2-allylphenol I have; not so much. But then I looked at AK Scientific and it is $65 for 100 g of 2-hydroxylphenylacetic acid.  Path of least resistance.  I wont be scaling up.  I just bought it lol.

Cheers!
If you're not part of the solution, then you're part of the precipitate

Offline TheUnassuming

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Re: Oxidative Cleavage of 2-Allylphenol
« Reply #5 on: March 14, 2019, 09:04:18 PM »
Haha, I assumed the motif was part of a larger structure you were playing with!  Absolutely, just buy it!
When in doubt, avoid the Stille coupling.

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