![]() I think the observed selectivity of Boc to hydrolytic removal in the case of Boc aziridine ester is due to unique functional group arrangement – the two carbonyls are very close to the Boc group and the oxygen electrostatic repulsion is trying to force the Boc group carbonyl out of plane of the aziridine ring. They see preferential Boc removal in the presence of ester only in case of highly activated Boc groups, such as 1-Boc indole, with a lazier aromatic acid ester, otherwise the ester is generally more reactive and is hydrolyzed first (BocTrpOMe provides BocTrpOH).ģ. in TBAF.3H2O solution)Ģ) They describe fairly facile aminoacid ester hydrolysis with their refluxing TBAF system, and mention that ester hydrolysis buffers TBAF to a point it becomes ineffective – this again looks like OH(-) attack, not F(-). What they forgot was that phenolate is an excellent leaving group and active carbamates like RNH-CO-OAr are commonly used as more stable surrogates of isocyanates (they turn to RNCO under basic conditions, i.e. But they have not observed symmetric ureas with any other carbamates they tried, e.g. Sure enough Coudet et al saw them – but only in the specific case when they were deprotecting RNH-CO-OPh and they took it as a proof. I am ready to bet 500 USD that the actual reagent is F(-).xH2O which acts as a milder version of HO(-)ġ) If there were carbamoyl fluoride intermediate, we would see symmetric urea formation as byproducts. I was just reading the Coudet papers, and I think the carbamoyl fluoride is totally fanciful – they were using commercial 1M TBAF in THF and they forgot that commercial TBAF solutions are made from TBAF.3H2O. The trick is nice but I do not buy the mechanism with carbamoyl fluoride as intermediate. This simple TBAF trick might be consequential to a lot of people interested in the chemistry of aziridines. Unless you are familiar with the pain of dealing with these three-membered rings, you might not think that a new way to remove Boc is worthy of note. That 2004 study centered on the use of common amines and there was nothing as exotic as aziridines. Really strange, I know, but there is some very clever evidence in the Coudert paper. In it, the authors considered a number of substrates and even carried out mechanistic studies that seem to suggest that the reaction proceeds through the formation of carbamoyl fluoride. I dug a bit deeper and found that the TBAF condition goes back to the 2004 Tetrahedron report by Coudert and colleagues. In the interest of full disclosure, I learned about this deprotection from a paper I recently refereed. When I saw the yield of 98%, I was literally floored. I am not sure how many of you are experienced with aziridines, but they do not easily withstand typical Boc removal with TFA. ![]() When I read the one by Lattanzi and colleagues, I thought that their nice asymmetric chemistry had been somewhat overshadowed by a single carbamate cleavage condition using TBAF. I typically do not comment on deprotection conditions, but there is something special in the two papers below.
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