[Dan]

A quick and interesting one this time...

Rationalise the following transformation (R=Boc):

[Wastrel]

We have a protected amine that deprotects in strong acid and a beta keto lactone which wants to hydrolyse and decarboxylate.  I can't see any other changes.  But this is a problem of the week and the BOC group is shown lurking near the carboxyl.  Is it something mad like the t-but cation attacking the carboxyl oxygen?

[Dan]

We have a protected amine that deprotects in strong acid and a beta keto lactone which wants to hydrolyse and decarboxylate.  I can't see any other changes. 

There are no other changes, but the mechanism is quite interesting. What do you think it is?

But this is a problem of the week and the BOC group is shown lurking near the carboxyl.  Is it something mad like the t-but cation attacking the carboxyl oxygen?

No, nothing mad going on.

[Wastrel]

I had something braindead involving the proton on the (quaternary) nitrogen transfering to the carboxyl oxygen so that water could attack but after several hours of thinking about the problem I just wasn't getting anywhere.  I was looking for something Cope like.

Then I googled 2 very general terms in the hope of seeing something inspirational and instead google spat out the exact solution as the second result.  It is clean and it is neat and I probably wouldn't have got if I spent a month staring at the problem.

I respectfully withdraw.

[Dan]

Fair enough. Good of you to leave it open for others to ponder, and glad you like the reaction.

Do we have any other takers?

[qw098]

I'm a third year chemistry major in my second term of third year. I am working on this problem but with no gains

[stewie griffin]

I can't say I've seen many decarboxylations where the alpha carbon is part of an olefin (unless the olefin is part of an aromatic ring...I've seen those).
I'm going to guess that the lactone hydrolyzes, the liberated alcohol then reacts with the olefin to form an oxirane. Then decarboxylation occurs followed by E1 elimination to open the oxirane and regenerate the olefin.

[Dan]

I'm going to guess that the lactone hydrolyzes, the liberated alcohol then reacts with the olefin to form an oxirane. Then decarboxylation occurs followed by E1 elimination to open the oxirane and regenerate the olefin.

Good to see you back Stewie.

Close. The general idea is right, but there are lower energy intermediates than oxiranes available - assess your potential nucleophiles.

[stewie griffin]

Yes I've been away for awhile. The world of industrial salt chemistry is fun but I started to miss some good old organic problems.
Well now that you mention it, the deprotected nitrogen should be more nucleophilic than the hydroxyl and it would also form a 5 membered ring instead of a three membered ring.

[Dan]

Correct.

Carbamate and Lactone hydrolysis, then a 1,4-aza-Michael addition to the unsaturated beta-ketoacid. This allows decarboxylation, and a retro-Michael produces the observed product - the naturally occurring Galbulimima alkaloid GB13.

The authors showed that the retro Michael can be reversed in the presence of a lewis acid, and used this to access a more complicated related natural alkaloid Himgaline.

Paper: http://pubs.acs.org/doi/abs/10.1021/ja065198n 

[Wastrel]

Just as a footnote my search term was "microwave decarboxylation" without quotes, I hit images, the first picture was and still is that of a dinner plate, and the second image was and still is the decarboxylation step from the synthesis of Himgaline.  In other circumstances that would be lucky.  *facepalms*.