[azmanam]

Different format today: I give you the conditions, you come up with the mechanism AND the product.  Steppin' it up a level.

QUESTION: Provide a complete, arrow-pushing mechanism for the following one-pot, biomimetic transformation.  As a result of your mechanism, please predict the product.

I came up with a very plausible mechanism... but it was completely wrong.  Mainly because the site said TFAA instead of Ac₂O, and I read it as TFA, not TFAA... Kinda different reagents that react, uh, somewhat differently.

As always, bonus if you can name the reaction.

[da692]

Try number one

[azmanam]

Good first try.  The Bayer Villiger was my first guess, too.  Two things - 1, Bayer Villiger reactions usually insert into the more substituted side of the carbonyl.  2, While I was able to get the Bayer Villiger to go to the observed product (when I used the wrong 2nd reagent), Bayer Villiger is not the initial step of this reaction.

What else can be oxidized in this system?

[blind]

N-oxide formation?

[azmanam]

yup!

[wintermute]

As for the first step: polonovski reaction imho

[wintermute]

with hydroxy groups acetylated of course

[wintermute]

oops, enamine reacts with acetanhydride instead of acetate, sorry.

[azmanam]

Getting closer, now.  The result of the first part of the reaction is N-oxide formation.  It is probably a concerted step with the peracid, and the product of the first step is the N-oxide drawn as the last structure on the first line of wintermute's scheme.

The first part of the second step is correct, too.  The anhydride reacts with the N-oxide to acylate that O-.  After that, you have acetate participating in an elimination.  That is not proposed to happen.  After the N-oxide is acylated, the mechanism goes in another direction.

ps, we can assume there is only 1 equivalent of acetic anhydride.

[wintermute]

OK, then. Acetylated N-oxide could undergo deoxygenation promoted by lactonization. resulting iminium salt is reduced by cyanoborohydride in next step. i am not 100% sure about the selectivity, but think hydride is delivered from sterically less hindered face and perhaps even hydroxy group can help by complexation.

[azmanam]

soooo close.  You've got the right idea.  Check the conformation of the molecule re: the lactonization.

[wintermute]

next try

[azmanam]

Quite right, good work.  And I didn't notice earlier when you correctly identified the Polonovski Reaction, a reaction I hadn't heard of, and one for which I can't find a competent web page.  Here's the preview page from Li's Named Reactions book:

http://www.springerlink.com/content/k1k121223x453n2h/

If you have Kurti's Strategic Applications, there's a write up of the reaction in that book as well.

Based on the conformation of the spirocycle after lactonization, the less sterically hindered face is actually the bottom face of the iminium, so H is down in the final product (see image).

This step was the subject of a 2002 paper by Kobayashi on the biomimetic transformation of Serratinine into Serratezomine A.  Link below (subscription required)  Thanks for playing everyone, see you next week.

http://dx.doi.org/10.1021/jo025821w