[cisdiols]

Hi,

I am at the last stage of my total synthesis (~12 step nat. prd.). I have a macrolactone ring with a propargyl ketone in it. I am hoping to prepare the cis-enone via Lindlar reduction. A scifinder search reveals around 200-300 hits (narrowed down 96) with moieties similar to mine. No, comes the fun part, I have 2 mgs remaining. A common theme of these literature precedence (None of which were macrolactone rings) employ Lindlar's catalyst (which don't describe whether its impregnated on BaSO4 or CaCO3), whether it is poisoned with lead and whether they added quinoline.

My first attempt was in toluene with 5% Pd/CaCO3 (amount: half of my starting material); presented a new spot along with starting material. Additional catalyst was added after 2 hrs (I added 9mgs of cat. along with 50uL quinoline); this pushed my reaction to completion. I tried to isolate the product my prep. plate tlc; however, the quinoline masked my product. Therefore, I tried to strip my product of the tlc. The NMR of the reaction before prep. plate and after showed that there was possib. prod. degradation...most likely due to my cis-enone.

Now my questions are:
- Is quinoline essential/required?
- If quinoline is required, is there a way to get rid of it quickly without using base/acid. I've tried CuSO4 aq. soln. This does not work.

Thanks

[movies]

I don't have a ton of experience with the Lindlar protocol, but I have used it a few times.  I always added quinoline and even then I saw a fair amount of over reduction to the alkane.  I don't think the quinoline is absolutely required, but definitely slows down the reaction a lot.  I would definitely try a lead-poisoned catalyst with and without quinoline to see what you get.  I seem to recall that the BaSO₄-supported catalyst is less active than the CaCO₃ version, but I can't find anything to verify that right now.  I know you don't have much material, so I definitely recommend a model system!!!

What I remember from labmates who were using the Lindlar frequently was that they had a particular bottle of the reagent that they did some optimization with and then used that bottle for their scale-up runs.  Whenever they needed a new bottle, they went back and re-optimized a little bit.  The point being, every bottle of Lindlar catalyst is a little different so you need to figure out how active your bottle really is.

[cisdiols]

Thanks for the reply. I attempted the reaction again without quinoline. It went to completion; however, I think the reaction wrecked havoc.

Time to sit down and analyse spectra. Bit disheartened, as it is the last step of my total synth.

[movies]

Hmmm - sorry to hear that.  My guess is that you are seeing over-reduction.  I am sure it is something that you can overcome, but I certainly understand your frustration with being so close to the end!  As I said before, I would definitely try to work out some conditions on a model system before using up more of your advanced material.

You may want to consider diimide reduction as an alternative to the Lindlar method.  It is a very mild reduction that tolerates a lot of reduction-sensitive functional groups.

[orgopete]

I have used commercial samples of catalyst successfully. I can understand over reductions quite easily with the catalysts though. I did my reduction at atmospheric pressure and plotted the reduction. After one equivalent, the reduction did not stop, it simply continued at a slower rate. If you are using a Parr apparatus and reducing to completion, that may not work as you expected.

I don't know if this is useful to you or not, but that was my experience.

[cisdiols]

Howdy guys, thanks for the replies. It seems like it didn't over reduce (stopped it when starting material disappeared). I found that I was still getting selectivity (Cis- or Z- alkene) without quinoline.