[phth]

I think its because it has to be a LUMO-LUMO orbital interaction so photons activate it.  The first step is interesting if instead of a hexyl group it is a functionality that can be modified later like a protected alcohol.  So the first reactions enantiomers are separated, and the cyclization is carried out until the amide is formed.  Now we install either methyl or hexyl to the amide and modify the alcohol functional group to resemble the same enantiomer as the final product. That is how I think the all of the pdt from the first reaciton can be used to generate a single enantiomer

[SinkingTako]

phth, great job! I really like your synthesis

Also, can anyone recommend a good book on learning strerochemical control?

[phth]

This is the best book IMHO:
http://www.amazon.com/exec/obidos/ASIN/0199270295/organischeche-20#customerReviews
http://www.organic-chemistry.org/books/reviews/0198503466.shtm
But here is a great resource with editorial reviews including books of all difficulties:
http://www.organic-chemistry.org/books/navi/organicchemistry.shtm

[Dan]

Nice creative route phth. Two comments:

1. You seem to have gained a C in the rearrangement. I think you need an extra methylene in the starting material - so you go via a [4.2.0] bicyclic aminal.

2. Can you propose a synthesis of the starting material (so that the route starts from commercially available material)?

[phth]

Also, I like because it G_{st. material}-G_{end product} is a good ratio to work with when its as high as possible to begin with.  The Schmidt, Curtius reaction are nitrenes, and synonymous with carbene reactions.  Carbenoid Rh₂(OAc)₄ may work with this also, but im not sure about cross metathesis.  Stepwise react with acyl chloride -78C to 0C, and heating more than this generates the ketene or another reaction like CH insertion.

[SinkingTako]

This week there is a tie. Both critzz and phth have 8 steps (kriggy comes very close!).

Who's winner? let's get OP to decide!

[critzz]

I always like to see those electrocyclic reactions in total syntheses, but I lack the ability to come up with those reaction paths myself.
What does a typical electrocyclic reaction procedure with hν look like (reaction conditions etc.)?

[kriggy]

This week there is a tie. Both critzz and phth have 8 steps (kriggy comes very close!).

Who's winner? let's get OP to decide!

Its not ONLY about number of steps. Having more steps that are reliable is better than fewer but unreliable IMO.
I realy like phth´s pathway. Its very creative

[Altered State]

Ketenes can also be prepared from the corresponding acyl chloride, treating it with a base. An amine is enough, I believe.
I liked phth pathway too.
Looking forward to see what is the next challenge. I hope I have time to go for a route this time, I'm really busy these days, and Christmas celebrations don't help

[Dan]

Apologies for not looking into this thread to often, I've been on holiday.

I am inclined to go with phth's proposal as the winning entry. I like the creativity of the approach. I would like to see a synthesis of the proposed starting chiral acid chloride though...

I will share with you my own suggestion. I spent some time trying to come up with a chiral pool synthesis from pyrogluctamic acid, but failed to find something good. Eventually I settled on this as the shortest route. It is an enantioselective synthesis using Noyori asymmetric hydrogenation for stereocontrol. Not very inventive, but it is short.

1. Double addition of of lithiated hexyne to succinic anhydride at low temp (diketone obtained on aqueous workup)
2. Lindlar reduction  [Edit: Alkenes formed in this step should be Z, not E]
3. Double Noyori reduction (the chirality sense at both asymmetric centres is the same)
4. Double tosylation
5. Double S_N2 displacement by the chiral allylic amine (itself prepared in 3 steps from 3-octen-2-one via Noyori chemistry).
6. Grubbs metathesis
7. Alkene hydrogenation

Longest linear sequence is 7 steps.

[orgopete]

1. Double addition of of lithiated hexyne to succinic anhydride at low temp (diketone obtained on aqueous workup)
2. Lindlar reduction

I thought the step 1) intermediate would be a keto-carboxylate. If so second equiv to add to ketone, no?

Step 2), trans?

[Dan]

1. Double addition of of lithiated hexyne to succinic anhydride at low temp (diketone obtained on aqueous workup)
2. Lindlar reduction

I thought the step 1) intermediate would be a keto-carboxylate. If so second equiv to add to ketone, no?

I was hoping that at low T the tetrahedral intermediate would be stable enough to do this:

i.e.

Stable at low T?
   
[but with OLi instead of OH - smiles won't let me have Li...]

I don't have journal access at the moment so I can't check precedent until next week...

Step 2), trans?

Oops. Of course Lindlar will give Z-alkenes - though this should not be a problem given their ultimate fate.

Alternative reduction methods (e.g. Cr(II) salts Link) could be used to get the E-enones shown.

[Altered State]

Shouldn't we propose a new problem? It's been a few days from Saturday.
What do you think about this? http://pubs.acs.org/JACSbeta/jvi/images/issue29/ol403350e.jpg

[kriggy]

Shouldn't we propose a new problem? It's been a few days from Saturday.
What do you think about this? http://pubs.acs.org/JACSbeta/jvi/images/issue29/ol403350e.jpg

Seems to me that someone has too much free time 
(or are you looking for ideas how to start total synthesis  )

[Altered State]

Shouldn't we propose a new problem? It's been a few days from Saturday.
What do you think about this? http://pubs.acs.org/JACSbeta/jvi/images/issue29/ol403350e.jpg

Seems to me that someone has too much free time 
(or are you looking for ideas how to start total synthesis  )

A bit of free time after Christmas
I don't really care about the molecule, but the hung is that this is supposed to be a weekly thing, if we don't stock to that, it will probably die again... I've experienced it similar (though unrelated) threads in other forums.