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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: azmanam on August 31, 2009, 09:52:48 AM

Title: Problem of the Week - 08/31/09
Post by: azmanam on August 31, 2009, 09:52:48 AM
So, after a brief hiatus, we're back with a vengeance.  Put on your conformational analysis hat, and dive right into this week's problem.

QUESTION: Provide a complete, arrow-pushing mechanism for the following transformation.  Bonus: name any named reactions involved.
Title: Re: Problem of the Week - 08/31/09
Post by: Ida Isotope on August 31, 2009, 10:02:51 AM
Reaction Mechanisms is my weakness! I'm glad you post this. Out of curiousity...is this considered an advanced organic chem question?
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on August 31, 2009, 10:45:41 AM
Yes, this is considered an advanced question... but don't be daunted.  The mechanism is quite doable.
Title: Re: Problem of the Week - 08/31/09
Post by: blind on August 31, 2009, 12:04:53 PM
Perhaps something like this?

Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on August 31, 2009, 12:08:40 PM
almost.  no acid in solution.
Title: Re: Problem of the Week - 08/31/09
Post by: blind on August 31, 2009, 12:14:04 PM
Hm...does it go through some zwitterion TS?
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on August 31, 2009, 12:20:36 PM
nope :)  and be more specific with one of your named reactions
Title: Re: Problem of the Week - 08/31/09
Post by: blind on August 31, 2009, 12:26:49 PM
First step - Oxy-Cope, Second step - Claisen?

Not sure how to go from my second intermediate to the final product...
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on August 31, 2009, 12:27:53 PM
sounds good so far.  make sure you can account for all the stereochem at the end
Title: Re: Problem of the Week - 08/31/09
Post by: blind on August 31, 2009, 12:30:32 PM
Yeah, aside from the R2/R3 groups, stereochem fit product..

The drawing above was missing some stuff, here's the revised one, although it sounds like it wouldn't make much of a difference...
Title: Re: Problem of the Week - 08/31/09
Post by: Ida Isotope on August 31, 2009, 11:16:24 PM
I've never heard of either of those synthesis reactions. I am taking advanced organic chem this fall though so I guess I should get familiar with them.
Title: Re: Problem of the Week - 08/31/09
Post by: nj_bartel on September 01, 2009, 12:46:02 AM
I can never predict these darned rearrangements with any success :/
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on September 01, 2009, 06:02:09 AM
Quote
I am taking advanced organic chem this fall though so I guess I should get familiar with them.

There are all sorts of interesting pericyclic reactions you'll learn as apart of your course.  the ones in this mechanism are some of the common ones, so I'm sure you'll be introduced to them - prolly in this adv organic class you're taking.

Quote
I can never predict these darned rearrangements

pericyclic reactions are my favorite mechanism type.  Is that weird that I have a favorite mechanism?  imho the hardest part is seeing it in 3d and predicting the stereochem.  the stereochem of the oxy cope is still not predicted by the drawn conformation, wanna give that a try?

Quote
here's the revised one

still no acid in sol'n.  the third step's not quite right yet.
Title: Re: Problem of the Week - 08/31/09
Post by: nj_bartel on September 01, 2009, 09:35:11 AM
No it's not weird :P.  I think the problem is we skipped pericyclics at my school.  Gonna have to give that chapter a read when I get some free time.
Title: Re: Problem of the Week - 08/31/09
Post by: Dan on September 01, 2009, 11:16:07 AM
I reckon it ends with an Ene reaction, see scheme

Edit: Ahh, but my stereochem turned out wrong...
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on September 01, 2009, 11:51:44 AM
yup, last step is hetero-ene

yup, stereochem is wrong in final product.

what to do, what to do... :)
Title: Re: Problem of the Week - 08/31/09
Post by: Dan on September 01, 2009, 12:25:18 PM
Hmmm, by the power of ring flipping...
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on September 01, 2009, 01:27:36 PM
Yes, the ring flip is the key.  Good work.

As fun as pericyclic reactions are, this was a conformational analysis problem at heart.  The oxy cope needed the six-membered chairlike transition state to get the desired stereochem, and the ring flip was important for the ene.

I'm not sure why the shown diastereomer is the product of this exercise.  Perhaps just to get people to think conformational-ly.  In the event, the diastereomer that Dan drew (and I drew when I first attempted the mechanism) is the favored mechanism in the reaction.  In the paper, dr's range from 2.2:1 (alcohol up) to > 25:1 (alcohol up). 

http://dx.doi.org/10.1021/ja066830f

In any event, since we have time left this week, here's a follow up question

Follow Up QUESTION:  In a non-tandem process, the oxy-cope is known for similar compounds with just the free alcohol (that is, without the allyl group - see figure).  If the rate for the free-alcohol version of the oxy-cope is set at K1 = 1, the anionic oxy-cope benefits from a significant rate enhancement, K2 = 1010-1017

Why?
Title: Re: Problem of the Week - 08/31/09
Post by: Dan on September 01, 2009, 01:29:18 PM
Hang on, I've been scribbling away and I'm still not convinced. What is wrong with the following scheme, in which all the pericyclic reactions proceed by chair transition states?
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on September 01, 2009, 01:34:19 PM
nothing.  see the paper.  it's substrate dependent, but the 'wrong product' is the major diastereomer in the systems tested.  I'm guessing the diastereomer given as the 'right product' is intended to make the student take a second look.  Just a guess though.
Title: Re: Problem of the Week - 08/31/09
Post by: blind on September 01, 2009, 03:46:03 PM
Follow Up QUESTION:  In a non-tandem process, the oxy-cope is known for similar compounds with just the free alcohol (that is, without the allyl group - see figure).  If the rate for the free-alcohol version of the oxy-cope is set at K1 = 1, the anionic oxy-cope benefits from a significant rate enhancement, K2 = 1010-1017

Why?


Does it have something to do with the metal?
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on September 01, 2009, 03:49:49 PM
potassium is better than sodium, but any counter cation will increase the rate.
Title: Re: Problem of the Week - 08/31/09
Post by: sjb on September 02, 2009, 03:33:13 AM
In any event, since we have time left this week, here's a follow up question

Follow Up QUESTION:  In a non-tandem process, the oxy-cope is known for similar compounds with just the free alcohol (that is, without the allyl group - see figure).  If the rate for the free-alcohol version of the oxy-cope is set at K1 = 1, the anionic oxy-cope benefits from a significant rate enhancement, K2 = 1010-1017

Why?


If I recall correctly, it's to do with the enol  ::equil:: ketone / enolate equilibrium, and so indirectly pKas etc.

S
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on September 02, 2009, 10:49:32 AM
Yes, the enolate is much more stable than the alkoxide, and that will keep K-2 small relative to K-1.  It wasn't the answer I was thinking of, but it is correct.

There's another phenomenon at play that makes K2 larger than K1.  Anyone see what else might be going on?
Title: Re: Problem of the Week - 08/31/09
Post by: azmanam on September 07, 2009, 10:13:12 AM
The answer lies in the bond dissociation energy.  The alkoxide results in ground state destabilization compared to the neutral alcohol.  Below are a couple of ways of depicting it.

http://dx.doi.org/10.1016/S0040-4020(97)00679-0