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Topic: POTW 27-12-14  (Read 9798 times)

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Offline Dan

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POTW 27-12-14
« on: December 27, 2014, 08:24:38 AM »
Here is this week's target, rules can be found here.
« Last Edit: January 13, 2015, 12:09:38 PM by Mitch »
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Offline kriggy

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Re: POTW 27-12-14
« Reply #1 on: December 27, 2014, 03:43:19 PM »
Haha ok lets hit it :)

Hope I didnt forget something obviously important :D
Im not realy sure about the acetal I saw it somewhere that it protects the keton I want and not the conjugated one. The 2nd thing is that Im not sure if NaOH is strong enough to deprotonate the nitrohexane. But another base could be used. The pyrrolidine formation should proceed easily as the nitro group is reduced to amino since its intermolecular reaction. Shiff base is reduced by the hydrogen present in the reaction  mixture.

Offline Altered State

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Re: POTW 27-12-14
« Reply #2 on: December 29, 2014, 06:29:33 AM »
Haha ok lets hit it :)
http://i.imgur.com/4poywAV.png

May I suggest another initial route?
It seems kind of strange to me using those starting materials :P



In this case you don't have to worry about the selectivity of the protection anymore, a few less steps (I think?) and less redox reactions (I like routes with less redox steps possible)


I cannot be sure about stereochemistry tho

Offline kriggy

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Re: POTW 27-12-14
« Reply #3 on: December 29, 2014, 07:00:49 AM »
Yea it was strange but thats why we are here :)
Damn those lithium compounds, I always forget that they exist :D
THe thing is that I saw synthesis of very similar compound in "Disconection approach" few days ago so I didnt want to just copy their synthesis since that would be useless for me to learn something (but I still used the nitro->amino-> reductive amination pathway which I realy like)

Offline Altered State

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Re: POTW 27-12-14
« Reply #4 on: December 29, 2014, 08:14:23 AM »
Yea it was strange but thats why we are here :)

True that. Even though there are better or worse methods, what is amazing of organic synthesis is the many approaches one can take!

(but I still used the nitro->amino-> reductive amination pathway which I realy like)

I like it very much too. I would like to know about the yields of those cyclations

Offline kriggy

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Re: POTW 27-12-14
« Reply #5 on: December 29, 2014, 10:38:58 AM »

I like it very much too. I would like to know about the yields of those cyclations
You can find more on page 58 of "disconection approach" or in articles they quote:
R.V.Stevens, A.W.M. Lee, J.Chem.Soc., Chem. Commun., 1982,102
R.V.Stevens, Acc. CHem.Res., 1984, 17, 289

I didnt read those articles but disconection approach says 68 for the second cyclizaton but the compound is bit different (one ring is 6 membered and the alkyl chain is shorter)
« Last Edit: December 29, 2014, 11:26:44 AM by kriggy »

Offline critzz

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Re: POTW 27-12-14
« Reply #6 on: December 29, 2014, 10:49:37 AM »
Okay, here is my try. Stereochemistry is not one of my strengths though.  :(


Offline kriggy

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Re: POTW 27-12-14
« Reply #7 on: December 29, 2014, 11:33:43 AM »
Very nice, is there any particular reason to oxidize the OH before you remove the benzyl protecting goup? YOu could remove it 1st and the do the oxidation and you wouldnt have to protect the ketone

Offline critzz

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Re: POTW 27-12-14
« Reply #8 on: December 29, 2014, 12:18:12 PM »
Well, you could be right. I just don't really know what happens to a primary amine under oxidizing conditions.

Offline Dan

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Re: POTW 27-12-14
« Reply #9 on: December 29, 2014, 12:53:27 PM »
Nice route critzz, I like the Paal-Knorr approach and have been thinking about that too, but I can't get the right diastereoisomer.

Can you comment on the diastereoselectivity (facial selectivity) of the hydrogenation? I would expect addition of hydrogen predominantly from the least hindered face, which would give the wrong diastereoisomer (see blow). I might be totally wrong though.
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Offline critzz

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Re: POTW 27-12-14
« Reply #10 on: December 29, 2014, 03:51:08 PM »
Haha, I mixed up the kinetic and thermodynamically favored product.
I guess both diastereomers are formed, rendering this synthesis useless (at least I tried).

However, I might have found something interesting about these pyrrole reductions?

http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-4-3

Especially scheme 7, 9 and the end conclusion.

Offline kriggy

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Re: POTW 27-12-14
« Reply #11 on: December 29, 2014, 04:21:57 PM »
Well that makes this rather easy doesnt it?

Offline phth

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Re: POTW 27-12-14
« Reply #12 on: December 30, 2014, 08:58:38 PM »
I think that this is another good way to install the stereochemistry of the bridgehead CH, but gotta sepereate enantiomers in the first step which could be more stereoselective by doing the addition using a mono substutited alkene instead of ethylene

Offline Altered State

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Re: POTW 27-12-14
« Reply #13 on: December 31, 2014, 05:00:06 AM »
@phth
Great job. Liked it.

Offline kriggy

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Re: POTW 27-12-14
« Reply #14 on: December 31, 2014, 06:06:09 AM »
How do you stop the ketene / ethene reacting with itself?

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