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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: nkenton on February 08, 2012, 08:46:20 PM

Title: Problem of the Week II
Post by: nkenton on February 08, 2012, 08:46:20 PM

Justify the transformation (from Overman's strychnine synthesis):

Have fun!

Hint: Think "named reactions"

Title: Re: Problem of the Week II
Post by: nkenton on February 08, 2012, 08:46:46 PM

This was formed in 98% yield apparently

Title: Re: Problem of the Week II
Post by: Alberto_Kravina on February 09, 2012, 02:57:07 AM

that's really a good one, it was even on our natural product synthesis exam and is a perfect way to make 3-acyl-pyrrolidines. cheers  8)

Title: Re: Problem of the Week II
Post by: Dan on February 09, 2012, 03:57:23 AM

Can I ask if there are any other oxidising agents present, because I'm struggling to get up to the ketone level. I don't want to check the paper myself because it would spoil the fun.

So far I've formed an iminium between the amine and the formaldehyde and done an aza-Cope. Problem is my product doesn't seem to have the required electronics to form the architecture of the final compound, because my alkene is polarised the wrong way. I feel like there needs to be some oxygen in the starting material. If there was a lone pair donor substituent (OH, NH, SH etc.) at the allylic position then I can see what's happening, but for now I'm stumped.

Title: Re: Problem of the Week II
Post by: Alberto_Kravina on February 09, 2012, 04:13:23 PM

Quote from: Dan on February 09, 2012, 03:57:23 AM

Can I ask if there are any other oxidising agents present, because I'm struggling to get up to the ketone level. I don't want to check the paper myself because it would spoil the fun.

So far I've formed an iminium between the amine and the formaldehyde and done an aza-Cope. Problem is my product doesn't seem to have the required electronics to form the architecture of the final compound, because my alkene is polarised the wrong way. I feel like there needs to be some oxygen in the starting material. If there was a lone pair donor substituent (OH, NH, SH etc.) at the allylic position then I can see what's happening, but for now I'm stumped.

good point, didn't even notice it since I already knew the reaction and did not look carefully at the given starting material. an OH group is missing in the allylic position, Tandem Aza-Cope-M_ _ _ _ _ _ (didn't want to spoil it for other people)

Title: Re: Problem of the Week II
Post by: stewie griffin on February 09, 2012, 09:44:29 PM

Any time I see a Nitrogen, paraformaldehyde, and Overman's name I automatically think Aza-Cope-Mannich  :)

Title: Re: Problem of the Week II
Post by: Honclbrif on February 11, 2012, 01:21:39 PM

Ok, I'm not getting to the end on this one. Here's what I've got so far:

(https://www.chemicalforums.com/proxy.php?request=http%3A%2F%2Fwww.majhost.com%2Fgallery%2Fpoorjon%2Fmisc%2Fptwii.gif&hash=fc589cfe1a5bb4076ef9394f998f326f28ed8e51)

Imine formation followed by Aze-Cope Mannich. After that, elimination to restore aromaticity? Then I've got nothing. I have no idea where the oxygen comes from. Have I been on the right track so far?

Title: Re: Problem of the Week II
Post by: Dan on February 12, 2012, 06:59:00 AM

Yeah, that is exactly what I was doing. The architecture of the final product is incorrect though. If the double bond was polarised in the opposite direction - by the presence of an oxygen atom, if it was an enol - then the product architecture would be correct and it would form a ketone. I think there's a hydroxyl substituent missing in the starting material, I think there should be an allylic alcohol in it - hopefully the OP can clear this up?

Title: Re: Problem of the Week II
Post by: Honclbrif on February 14, 2012, 03:12:27 PM

There is a missing hydroxyl!

http://pubs.acs.org/doi/abs/10.1021/ja00073a057

Compound 13.