Today, Vinogradova, Muller, and Buchwald have an excellent piece of investigative science in Angew. Chem. Int. Ed. that I think is great, just great. And honestly, I'm a bit jaded and easily unimpressed (especially when the work isn't directly applicable to me finishing my Ph.D.). In fact, I liked this paper enough to write about it, and not just tweet it on the sidebar <---over there.
Lets start with a summary of why I think its great.
1. They decided to take a closer look at a "known" system - and they learned something new.
2. They crystallized a liquid using the work by Fujita et al.
...And onward with a more in depth look...
So it seems that Buchwald et al. were interested in aryl isocyanates, specifically group transfer of isocyanates and isothiocyanates utilizing hypervalent iodine reagents. Upon preparing compound 3 and treating with silver isocyanate or silver isothiocyanate they observed ring-closed I-bound cyanates (4) and ring-opened O-bound isothiocyanates (5) [see Figure 2 below, taken without permission from the paper].
Which brings us to the thiotrifluoromethylating reagent (1) reported by Shen et al. back in 2013. Following all literature precedent, they assigned compound 1 as the ring-closed benziodoxole, and since the characterization data matched their desired compound there was no reason to worry. There is a decent body of literature to support this conclusion.
However, when the Buchwald group compared the NMR spectra of compounds 1-6, something seemed strangely amiss. Notably, proton Hb fell into one of two categories: ring-open benzyl alcohols (1, 2, 5, 6) around 7 ppm, or ring-closed benziodoxoles around 7.5 ppm (3, 4). Now here is reason #1 I like this paper - they decided to take a closer look at what was going on. I personally think these details would have been easy to overlook... after all it didn't affect the reactivity.
First, they utilized some 13C NMR work by the late Alan Katritzky, which corroborated their thoughts. They also prepared a crystalline variant of compound 1 (not shown), which confirmed an O-bound thiotrifluoromethyl group.
But it was time to go deeper.
And this is the second reason I like this paper, and actually the reason I read it in the first place... remember this Nature paper on crystallizing non-crystalline compounds that everyone was stoked on? And then how everyone was less than stoked on? Well, the Buchwald lab stuck with it, and even showed me this Nature Protocols paper by Fujita (that I missed) which details a better protocol for their "crystalline sponge" method. And, it worked. Cool! I suppose the full value of this method will be realized in time, but this a great (first, to the best of my knowledge) use of Fujita's method outside their own lab. Thus, Buchwald confidently revised the structure of compound 1 to the benzyl alcohol shown (which they refer to as a "thioperoxide," this is probably IUPAC, but I don't like it... peroxide to me is O-O... thioperoxide sounds like S-S, but that's disulfide. Now that I think about it, I kind of like dioxide to talk about O-O. I digress. Sorry.).
As Buchwald et al. point out, these new observations don't affect the reactivity, although they may open for discussion new mechanistic pathways. And most interestingly (to me), is that this is the first use of the still promising "crystal sponge" method by the Fujita group.