[Kysi]

Hello there,
Could anyone explain me mechanism of this reaction, please.
I thought Dess Martin periodinane would just oxidize the free hydroxyl group, but the article (Synthesis of Chamobtusin A, Org. lett. 2010, 4709-4711) says that acetic acid generated in situ might promote eliminative epoxide opening and acetalization. So, how the cyclization proceeds?



Thanks in advance for your answers.

[azmanam]

two questions to help guide you:

1) what happens to epoxides in acid?

2) Note the double bond.  Can you see how its movement can help you open the epoxide?

[Kysi]

1) Protonisation

And then the double bond moves?
Does it proceed like this?



Couldn't think of anything better  

[azmanam]

that's what I was envisioning:)

2 notes:  after the first two structures on the second line are resonance structures, and you should use the resonance arrow (alternatively, in the last structure on the top line, draw one more arrow from the OMe oxygen to form the C=O double bond and you can go the the second structure on the second line straight away.

in the very last step, you have the OH oxygen attacking the C=O carbon atom.  You need one more arrow pushing electrons on to the OMe oxygen to complete this step (and is that line above the OH oxygen indicating a lone pair of electrons or is it a negative charge?)

Good work

[Kysi]

and is that line above the OH oxygen indicating a lone pair of electrons or is it a negative charge?

It should be a lone pair, the hydrogen is still bonded to the oxygen atom, right?
So the acetalization proceeds like this:


Thank you for your help

[azmanam]

yup, that's how it works.

now, do you know the mechanism of the D/M oxidation?

[Kysi]

Sorry, I didn't reply earlier. I just needed to find out the mechanism of that cyclisation and keep on revising for a test.

I should know the Dess-Martin oxidation mechanism. At least I've heard it in school..
So if I remember it correctly, it proceeds like this:

[azmanam]

Yup.  Just checking

I love the DMP oxidation.  Fast, easy, don't have to flame-dry glassware (I even found it worked better if I used DCM out of my wash bottle as the solvent), no smelly dimethylsulfide byproduct.  Definitely my alcohol->aldehyde oxidation of choice!

You don't have to answer my follow up questions if you dont want to, but we are a teaching forum  

Do you know the oxidation state of iodine before and after the reaction?

[Doc Oc]

Do you know the oxidation state of iodine before and after the reaction?

Ha ha!  This got asked during my qualifying exam.  I had the mechanism all ready to go, and instead my committee chair asked me the change in oxidation state of the iodine.  I'm so glad that's over with.

[nox]

I love the DMP oxidation.  Fast, easy, don't have to flame-dry glassware (I even found it worked better if I used DCM out of my wash bottle as the solvent), no smelly dimethylsulfide byproduct.  Definitely my alcohol->aldehyde oxidation of choice!

Well as they say, all good things in life come with a price.

(Of course you could make your own, especially since there's an OrgSyn prep for it, but the point still stands)

[Dan]

Yup.  Just checking

I love the DMP oxidation.  Fast, easy, don't have to flame-dry glassware (I even found it worked better if I used DCM out of my wash bottle as the solvent), no smelly dimethylsulfide byproduct.  Definitely my alcohol->aldehyde oxidation of choice!

I can't agree more! I seem to remember you actually need a trace of water to get this to go - I think under strictly anhydrous conditions the reaction is very slow. Apparently this was first noticed when DMP oxidations proceeded more efficiently in humid months - but this may be a lab legend.

The alternative I used before we started making DMP in the old lab was PCC - now that's a workup from the depths of hell I tell you (works well though).

[azmanam]

we do make our own DMP.  Everyone always cringes about having to go through IBX, but we think the rumors of its sensitivity are mildly overstated.

[nox]

^wikipedia states the explosiveness is actually due to residual sodium bromate and not IBX itself, not sure how accurate that is though

Never used PCC myself, though I've hears stories. MnO₂ works well for allylic and propargylic systems, but filtering off >10g of manganese gunk at the end when doing large scale reactions is quite something. And trying to get a TLC is a b$*%(.

[azmanam]

For whatever reason, when I tried oxidizing a benzylic alcohol to the ketone, MnO₂ never worked well for me.  This was while trying to synthesize the aromatic fragment from hell.  I graduated without ever making that fragment...

[Doc Oc]

we do make our own DMP.  Everyone always cringes about having to go through IBX, but we think the rumors of its sensitivity are mildly overstated.

I think Nicolaou's JACS paper on IBX addresses the issue of the explosiveness of it.  Actually, now I can't remember if it was Nicolaou or if he references another group of authors who figured it out (I think it's the latter), but apparently the new method for synthesizing IBX is a lot safer and it's not as susceptible to explosion.