I really like reading Adam Nelson’s papers. The one I saw in Synlett today is noteworthy because of the kind of vignette that does not typically make it into a TOC (Table of Contents) graphic. I call it the “roadkill”, which is one of the most frustrating things in today’s world of science publishing. The published content seems to be ballooning out of hand. Not only do we have way too many journals, but the sheer volume of stuff is so enormous that it is impossible to do what was feasible even 15 years ago: flip through the contents of an issue and find roadside nuggets.
Speaking of nuggets, the one I found in Adam’s paper is a mere afterthought to the main point of the manuscript, which happens to be construction of heterocycles by multicomponent reactions. As I was going through the paper, I noted how a TFA amide was converted into a cyclic urea. As someone who knows (or used to know) a thing or two about trifluromethylation (my Chemical Reviews paper with Prakash was influenced by the challenge of trifluoromethyl group transfer using organosilicon reagents: http://pubs.acs.org/doi/pdf/10.1021/cr9408991), I think there is something unique here. Can you name another case that involves a TFA amide losing its trifluoromethyl group in a reaction? I can’t. The authors did not make a big deal out of this, but they should have (in my opinion). While there have been cases in which metal catalysts had triggered fluoroalkyl group transfer from fluoroalkylated acid derivatives, the seemingly trivial afterthought in Adam’s paper is worthy of note. Trapping the resulting trifluoromethyl anion with electrophiles might be interesting in a different context. Again, I am assuming that TFA amides have not found any use in this capacity, which may not be the case. After all, I have not followed this area of inquiry for a number of years.
The ejection of a trifluoromethyl anion from related hemiaminaloates is known. This is the reason why many reactions that generate CF3 anion are done in DMF or NMP ( amide traps CF3 anion to stabilize it). This chemistry works with trifluoroacetyl esters too, one can mix KOtBu with ethyl trifluoroacetate to generate CF3 anion, which presumably is formed after the addition of KOtBu to ethyltrifluoroacetate.
I believe Colby (Purdue?) has done work in this area.
Thanks a lot, this is great (here is that Colby reference: http://pubs.acs.org/doi/abs/10.1021/ol303291x). This is true – but what about TFA amides as starting materials? I can’t find such cases (which is why this example from Nelson is intriguing to me).
PS And here is an excellent paper from Langlois: http://www.sciencedirect.com/science/article/pii/S0040403902027181…
this sequence reminds me of a paper by the great Ugi-master S. Marcaccini, where he obtanied the loss of Chloroform by using Trichloroacetic acid in an Ugi reaction: SYNLETT 2008, No. 1, pp 0033–0036 (Berni)
Thanks for bringing this up! Very relevant indeed.