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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: tmartin on December 10, 2009, 10:12:34 AM

Title: Knock off of Problem of the Week 12/10
Post by: tmartin on December 10, 2009, 10:12:34 AM

Ok, so to steal azmanam's gig for a day... (with his permission  ;D).  Here is a problem for some thought.
I'll try to make it a few parts to drag it out a little... What is the product of this reaction (you can ignore stereochemistry)?

For clarity: the Pd catalyst is a pi-allyl Pd species with Cl and PPh3 as ligands.

Title: Re: Knock off of Problem of the Week 12/10
Post by: stewie griffin on December 10, 2009, 02:56:28 PM

I'm confused  :'(
Is everything thrown in the flask at the same time???

Title: Re: Knock off of Problem of the Week 12/10
Post by: tmartin on December 10, 2009, 03:59:20 PM

Well, at one point everything will be in the flask at the same time  :P

I haven't looked at the supporting info, but I believe the order of addition is: Mix the palladium catalyst with the boronic acid, allene, and then aldehyde.

In terms of stoichiometry, 1 eq aldehyde, 2-5 eq of allene, 1-2 eq of boronic acid.

Title: Re: Knock off of Problem of the Week 12/10
Post by: stewie griffin on December 10, 2009, 04:17:44 PM

Here's an attempt. I'm not really up to speed on my palladium chemistry outside of standard ox add, transmetallation, red.elim.
Note how I cheated and put the metal in the infamous [] since I don't know what the original ligands would end up doing.

Title: Re: Knock off of Problem of the Week 12/10
Post by: Heory on December 11, 2009, 12:11:41 AM

 ???
I'm not sure about this:

Title: Re: Knock off of Problem of the Week 12/10
Post by: tmartin on December 11, 2009, 07:33:34 AM

You both have arrived at the correct answer for A.  I also think both of your mechanisms are reasonable.  I believe that the carbopalladation step will proceed to give the Pd inserting away from the R1 group (as Heory denotes).  Interesting stereochemical model.  The authors do not specifically say their rationale, however they also only obtain slight selectivities, ranging from 1:1 up to 4.4:1 for the syn diastereomers.  After the carbopalladation reaction, R1 can be either cis or trans to the aromatic group, and I'm inferring there is a mixture.

Ok, so for the next part of the question:

When R1 is some group, say C6H13, the reaction goes as indicated above.  However, when R1 is an ester, the reaction proceeds to give another product...so...what is that product and how do we arrive there?

Title: Re: Knock off of Problem of the Week 12/10
Post by: Heory on December 11, 2009, 08:20:01 AM

Regioselectivity was changed?

Title: Re: Knock off of Problem of the Week 12/10
Post by: tmartin on December 11, 2009, 08:38:57 AM

Would there be any consequences of that?

Title: Re: Knock off of Problem of the Week 12/10
Post by: Heory on December 11, 2009, 08:52:58 AM

The product is a six-membered alpha,beta-unsaturated lactone?

Title: Re: Knock off of Problem of the Week 12/10
Post by: tmartin on December 11, 2009, 10:40:42 AM

Ok, so what is the rationale to arrive at that product (why the reversed regiochem)?

Title: Re: Knock off of Problem of the Week 12/10
Post by: Heory on December 11, 2009, 10:48:34 AM

Well, I am not quite sure how the regioselectivity reversion occured. I think the strong electron-withdrawing character of the ester group made the region between the two carbon atoms more electron-rich (as I drew), which overwhelmed the steric hindrance.

Title: Re: Knock off of Problem of the Week 12/10
Post by: tmartin on December 11, 2009, 11:35:37 AM

That will do, I believe.  Nice work.  ;D

Here is the reference:

Hopkins, C.D.; Guan, L.; Malinakova, H. C. J. Org. Chem. 2005, 70, 6848-6862.

Interesting multicomponent reaction with allenes in my opinion.  Would be really interesting if they could obtain better selectivities somehow.  Grigg and co-workers did some work on this front with imines, I believe, and I think Jamison has used allenes to make silyl protected allylic alcohols with high selectivites.