[AlphaScent]

This is a scheme I came up with that would make a synthesis much more streamline and more convergent in nature.
Does anyone see any fundamental flaws with the reaction sequence?  Can I couple that trans bromide using a grignard form of the undecyn-1-ol?

Thank you for your input!

Cheers!

[magician4]

one thing that jumped to the eye:

your bromination (following +/- the Appel protocol, I think) in my opinion has a problem: here, the elementary bromine might add to your double bond as a competing reaction, and I would try to avoid that

alternatively, Φ₃P / CBr₄ or simply Φ₃PBr₂ might be the better choice

regards

Ingo

[AlphaScent]

Magician,

I feel kind of foolish.  What a trivial mistake.  The elemental bromine would no doubt add across the double bond.  Your approach is a good idea.  What do you think about making the tosylate and then reacting with sodium iodide in acetone or acetonitrile.  This could work as well and be most reactive.

[AlphaScent]

Sorry about the PDF guys.  Will do graphics next time.

[magician4]

What do you think about making the tosylate and then reacting with sodium iodide in acetone or acetonitrile.  This could work as well and be most reactive.

many ways will lead to Rome...

and yes, you could prepare an alkyliodide this way from your initial alcohol.
just so, I don't see the advantage over PΦ₃ / CBr₄ and thatlike in this case.

btw., with respect to your acetylene-alkylation: If you were planing to work with Na/NH₃ anyway, why not use NaNH₂ to deprotonate your acetylene and have a simple SN-reaction for alkylation?

as a side benefit, you won't need the HMPT ( a solvent I always tried to avoid, even in paper chemistry)

regards

Ingo

[KrCo]

Just a question (I have never used DHP, as a protecting group, so it is really only a question  )

When you want to protect the OH group, you are planning to use DCM/PTSA protocol and when you are going to deprotect it, you use the same. Does it really work? Maybe the ratio is different and this is the key?

Here, the authors suggest protic (e.g. methanol) solvent for deprotection:
http://www.organic-chemistry.org/protectivegroups/hydroxyl/thp-ethers.htm 

[Archer]

Just a question (I have never used DHP, as a protecting group, so it is really only a question  )

When you want to protect the OH group, you are planning to use DCM/PTSA protocol and when you are going to deprotect it, you use the same. Does it really work? Maybe the ratio is different and this is the key?

Here, the authors suggest protic (e.g. methanol) solvent for deprotection:
http://www.organic-chemistry.org/protectivegroups/hydroxyl/thp-ethers.htm

It's a wonderful protecting group unless you have a chiral centre in your molecule (even then I still use it but characterisation is challenging). You can use very mild conditions for protection and removal if your alcohol is acid sebsitive.

[AlphaScent]

Magician,

You are indeed right.  I have never used Φ₃P/CBr₄ befo,re.  This will brominate my alkene without disturbing it?  Also, I thought of initially using n-butyl lithium as my base, but I think it is too strong in this case.  I have done a similar reaction to this in the past and that is why I went with it.  85% yield.  I understand you aversion to HMPA, but I really don't mind it.  Isn't that difficult to remove like DMF.  That is what I try to stay away from.  We have sodium amide in my lab already.  We make our own 4-pentyn-1-ol from furfuryl chloride with it.  I will think about it and discuss it with my peers.  Thanks for your thoughts.

KrCo,

I have done the deprotection in both.  Depends on your compund usually.  I like to work with DCM due to the volatility compared to methanol.  Protections can be difficult and problematic with halohydrins.  That is my only beef with it.  It is really cheap compared to TBDMS and such.

[Archer]

You are indeed right.  I have never used Φ₃P/CBr₄

Please forgive my ignorance but what is Φ₃P/CBr₄ ?

[discodermolide]

You are indeed right.  I have never used Φ₃P/CBr₄

Please forgive my ignorance but what is Φ₃P/CBr₄ ?

Triphenylphosphine and carbon tetrabromide. A nice way of alcohol bromination, provided you can get rid of the triphenylphosphine oxide.

[AlphaScent]

Disco it is sooo funny you say that.  I actually despise triphenylphosphine oxide on a cellular level.  Biggest pain in the butt to remove.  I have never done the Φ3P/CBr4 method.  Only Φ3P/Br2 method.  Triphenylphosphine oxide is still a pain there as well. 

Does anyone think in my alkylation step just a tosylate would work effectively?

[Archer]

I wasn't familiar with Φ representing a phenyl group.

If the tosylate doesn't work then Finklestein on the tosylate  iodide may be an option.

[AlphaScent]

Archer,

The Phi sign, Φ, is all my professor in undergrad used to use when writing phenyl.  Never Ph or anything.  Thats where i learned it.

I would love to do finkelstein, only the sodium iodide is a bit expensive and my lab already has a bunch of tosyl chloride. 

I am hoping that 3-pentyn-1-ol > tosylate> E bond> coupling with grignard works.  But im sure that pathway just with an iodide instead of a tosylate would def work.

[Corribus]

The Phi sign, Φ, is all my professor in undergrad used to use when writing phenyl.  Never Ph or anything.  Thats where i learned it.

It's because all organic chemists are secretly unhappy that they never get to use equations, so they sneak in Greek letters wherever they can so as not to feel inferior to their physical counterparts.

[Archer]

It's because all organic chemists are secretly unhappy that they never get to use equations, so they sneak in Greek letters wherever they can so as not to feel inferior to their physical counterparts.

Very early on in my PhD I got criticised for using the Greek letter Ψ to refer to "pseudo" as in Ψ- axial since then I have steered clear of them.