[Dan]

Here is this week's target, rules can be found here.

[kriggy]

Haha ok lets hit it

Hope I didnt forget something obviously important
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.

[Altered State]

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



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

[kriggy]

Yea it was strange but thats why we are here
Damn those lithium compounds, I always forget that they exist
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)

[Altered State]

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

[kriggy]

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)

[critzz]

Okay, here is my try. Stereochemistry is not one of my strengths though. 

[kriggy]

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

[critzz]

Well, you could be right. I just don't really know what happens to a primary amine under oxidizing conditions.

[Dan]

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.

[critzz]

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.

[kriggy]

Well that makes this rather easy doesnt it?

[phth]

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

[Altered State]

@phth
Great job. Liked it.

[kriggy]

How do you stop the ketene / ethene reacting with itself?