[Heory]

Go on, azmanam. Certainly you can finish the problem.
 
 
 

[Heory]

Actually neither product of philmont702a' path 2 is the framework of opiod-type molecules. Check it carefully.

[azmanam]

Actually, it looks a lot like the molecular skeleton of part of morphine.  It's not morphine and it's not likely going to be taken on to morphine, but it is the same carbon skeleton.

To do a FC, you need a carbocation, I don't like this pathway much, but here's my guess.

[Heory]

azmanam, your product is so strained that I think its formation is impossible. Sorry I made a mistake, the first product of philmont702a's path 2 is is the framework of opiod-type molecules, and maybe that way proposed by him was right, which was different from my own idea. I don't have the standard anwswer for the problem, we can have a disscussion. But both the products are certain. My only reference is my text book Medicinal Chemistry, so I had to take a photo. I copied it from the synthesis  of pentazocine, which is of the opiod-type.Maybe we are too boring with this problem now, so I post it.

[Heory]

The following is my own idea, I'm not quite sure whether it's right. For F-C rxn, 6-membered ring is most easily to be formed.

[Ulfsaar]

 
That is so strange^ I can't understand why does not the amino group make addition to the carbonly group instead of  the Prins reaction?In a special words  that is 囧

[azmanam]

Your product in red, and my molecule in blue (showing philmont's pdt's similarity to morphine) are the same except for the loss of the methyl group from the aryl ring.

OMe (or OH in your case) is a srong o,p director.  6 membered ring from straightaway FC rxn at the meta position is unlikely.  I like the p-directed FC followed by alkyl shift better.

I'm at home w/o chemdraw, but we can talk about stereochem when I get to work.  I don't think you've drawn the newman projection of the aldehyde piece correctly.  You have the aryl group directly attached to the aldehyde carbon, but there is a methylene in between.  The methylene makes the aryl chain much smaller than it looks and I suspect will not impart much selectivity on the prins step.  I suspect the stereodivergent step will be at the FC stage.

[Heory]

Yes, in my newman projection, the right group is Bn not Ar, but still Bn is the largest group that binds the aldehyde's carbonyl carbon.
Of course I agree that OH is a srong o,p director, but if the cabocation attacked p-position, strain of TS of the 5-membered ring would be quite large, or even the TS couldn't be organised, I think. OH is a srong o,p director, doesn't mean that activity of m-position is decreased by OH. Actually OH activated all position of the benzene ring, but o,p is more reactive than m.
Selectivity on the Prins step (maybe not very favorable) decides that on the F-C step.

[philmont702a]

ortho/para directing:  The OH is definitely an ortho/para director.  Thus, it will react preferentially at those positions FIRST, then if put under enough duress may react further. 

5-membered ring: The rates for 5 membered rings are faster than 6, which are faster than 7, etc.  This goes for a multitude of reactions from RCM to Dieckmann condensations. 

Stereochem: Though I can see from your newman projection why you might think that stereochemistry might be imparted on this reaction, that same newman projection can be rotated and the strain would not be significantly different.  If any selectivity is observed, it is minimal, and definitely diastereoselective, not enantioselective.  The stereochemistry you are predicting for the product is more probable to come from the cyclization step of the friedel-crafts reaction.  However, there appears to be no significant director for the stereochemistry of that step.

[Heory]

 ;)bad network.

[azmanam]

Here are the relevant references.  One is in German, and we don't have access to it anyway (though I think it is the key reference we need!) and the other doesn't discuss the mechanism in any detail, only to say the product is one with the new alkyl group meta to the OH.

http://dx.doi.org/10.1002/ange.19470590703
http://dx.doi.org/10.1002/jhet.5570060108

I disagree that the 5-membered spirocycle is disfavored.  I made a model of it and it fits together quite nicely.  Chem3D shows the piperidine in a nice chair, the 5-membered ring in a nice envelope and - in the lowest energy conformer - the correct C-C bond (the one from aryl to tertiary carbon) to be situated nicely to migrate. 

[Heory]

 

[azmanam]

I'm going to stir up the mud again.  Going back to the aldehyde and amine (the product of the Darzen's reaction), you can get to the product through imine formation.  If I would have drawn the immediate product of the Eshweiler-Clark cyclization correctly, we would have[1].  I really believe the lone pair on nitrogen is more nucleophilic than the pi bond of the alkene in this first step.  I believe imine formation happens followed by 6-endo-trig cyclization (favored under Baldwin's rules.  This transition state is much more ordered.  That gets us to the same carbocation which can be trapped by water to get us to the same piperidine/alcohol for the HBr step.

And, no, I really truly don't believe the meta position will attack anything.  The ortho and para positions are much, much more nucleophilic.  All it takes is a chair flip and rotation of the methylene linker to put the aryl group in close proximity to the carbocation without much steric interference.  Build a model, it fits quite nicely.  At that point, analogous to Bayer-Villiger type mechanisms, the more electron rich carbon atom (the tertiary one) will migrate.  It also happens to be nicely oriented to provide maximum overlap of the C-C sigma bond and the pi* orbital for migration.

[1] http://www.chemicalforums.com/index.php?topic=37220.msg142811#msg142811

[movies]

That is so strange^ I can't understand why does not the amino group make addition to the carbonly group instead of  the Prins reaction?In a special words  that is 囧

I agree.  Why not like this?  Iminium ion cyclizations are certainly well precedented!


EDIT: Looks like azmanam beat me to it!

[sjb]

I agree.  Why not like this?  Iminium ion cyclizations are certainly well precedented!

Whilst iminium ion cyclisations are precedented, is there not a danger that the pH is so low that there is not really any significant RNH₂ around, rather RNH₃⁺, and so not nucleophilic enough?