I’m a PhD chemist and I am working on an asymmetric alkylation. After many test, i found the better base for this reaction is KHMDS (LiHMDS works too but the yield is only about 25%). But, to lock the chiral inductor group in a good conformation, I need to form a lithium alkoxide, the potassium alkoxide is too weak (I work at -78°C).
So i want to know if you think it is possible to form the lithium alkoxide and then the potassium enolate. Does the litium alkoxide will be strong enought to don’t form a mix lithium/potassium alkoxide?
I hope that you will understand my problem,
Thank you, are you talking about the books?
Yes, I agree with you but actually she is pregnant and it’s really hard to see her. I’m working with biologist, there are few chemists here and they couldn’t answer me.
If i post my question here it’s not because i’m lazy. I just didn’t found anything on this topic.
While I am not a chemist, it doesn’t look like it to me. I would think that some references turned up by a bibilographic search would be much more relevant than others.
Chimera, knowing that the general process is possible does not require a bibliographical search. Knowing the specifics does, and note that he hasn’t said he already searched.
Knowing whether it has previously been performed for those particular substances requires searching in two or three sources, three sources which any chemist worth his sodium chloride should be familiar with, and requires the knowledge of which specific substances is he talking about: CAS contains both information on the physical and chemical properties of substances and on articles (so it’s where you would find information on when and how have other people used that synthetic pathway); the CDC Handbook of Chemistry and Physics and the Merck Catalog contain information on the physical and chemical properties of substances but not on articles.
Why would one be interested in searching for the properties, minus the articles? Because if you find the properties, at least you know the substance is stable enough to be synthesized, isolated and, if it’s in the Catalog, sold. The reason we use the Merck Catalog and not one from another company is that theirs happens to be the biggest: the Dow Catalog would work as well, in principle.
One could also run calculations to determine whether those molecules are stable or not - in fact, depending on what specific molecules one is talking about, calculations are not even needed (there are things that you just look at them and it’s like “oh no way that can fit, err excuse me: in all likelihood the steric constraints will be too great”). But again that requires knowing the specific molecules, you don’t need it to know that the general pathway is likely… but at the same time, going from the general to the particular needs information not provided.
We learned to run those searches in our first lab, and several of the exercises in the undergrad labs I taught in the US required searching in CAS. For a researcher (in fact, for any chemist who wants to know what he’s doing), it’s as basic as knowing your anions from your cations.
Ok in that case no, I don’t think you’re going to be able “to form the lithium alkoxide and then the potassium enolate.” I was hoping you could make them separately and hope your reaction was faster than the metal exchange. I think your nBuLi (or whatever) is going to react to form both an enolate and an alkoxide. But if you want to be sure, you can always deprotonate, quench with a D+ source, and check the 1H-NMR.
That said, if your material isn’t too precious and you can run this on small enough scale, it might be a situation where you just try and justify it later. Even though the enol is more acidic than the alcohol (is it? the right functionality can flip it), lithium salts in THF can give you some strong kinetic preference that might work in your favor, but I’m not really sure in this case.
Thank you for your answer. =)
I think the enol is less acidic, because it is an enol of amide (pKa 30). But i will try your idea to check by 1H-NMR after quench with a D+ source.
Thanks a lot!
