[comp]

Hi,
Anyone have any ideas for an interesting synthesis involving (to demonstrate the use of) directed ortho-lithiation which is possible for use in undergraduate labs? (s- & t-BuLi out of bounds here...)
Thanks in advance!

[Dan]

Define interesting.

Can you use n-BuLi? You will have to be much more specific about your limitations. How long a synthesis, how expensive, purification techniques available etc. etc. etc. Coming up with a feasible undergrad experiment in terms of complexity, time constraints and financial constraints takes quite a lot of research and planning - you will have to do some of the leg work yourself.

Search for o-functionalisation of anisole in the usual databases, you will get hundreds of hits.

There was a cool ortho metalation/alkynylation paper in ACIE last year:

http://onlinelibrary.wiley.com/doi/10.1002/anie.201107821/abstract

No idea if the alkyne coupling partner is commercially available or cheap though.

[comp]

Basically, I have to design a third year undergrad experiment to demonstrate the use of ortho-lithiation in synthesis
I was wondering if anyone knew of a relatively straight forward synthesis of some kind of natural or commonly used product (to make it more relevant to the student)
There are plenty of possibilities out there I'm just trying to narrow them down to what would be more interesting or of more use to an undergraduate for a couple of days work in a lab?
n-BuLi can indeed be used
cost and procedure are of less importance
Sorry if this is too round-about a question!

[orgopete]

Unfortunately, our starting material is not readily available (a pyridylimidazolinone), but it could have been a very good target for an ortho metallation. It has an acidic N-H, so the first deprotonation becomes a simultaneous in situ titration of the butyl lithium. The dianion has a very deep red color so the end-point is easy to determine. Then an additional equivalent can generate the dianion. If a student contaminated the BuLi or simply if the titer has fallen, each student would be aware of it. This is also true if the apparatus is not dry as this also reduces the apparent titer.

I'd consider these characteristics as useful for the experiment. If someone knows a readily available candidate with similar characteristics, perhaps they could make a suggestion.