The wonders of arsenic

Some years ago (circa 1995), I learned about the magic of arsenic trichloride. I think it was Karl Christe (when he was still at the Edwards Air Force Base in California), who told me about this wonderfully “benign” material. At that time, I was desperately trying to dissolve a polycyclic aromatic molecule. Apparently, when nothing else works, arsenic trichloride is supposed to solve all your problems, particularly when it comes to dissolving polyaromatics. For many years I have been trying to find the original source describing this wisdom and, as luck would have it, accidentally came across the paper I have been looking for. Here it is, so put it to test if you are brave enough. According to the authors of this old work, arsenic chloride is cheaper than deuterated chloroform. I am not sure about that, but I know several people who swear by the unique properties of this liquid. You might ask: “So did you give it a shot?”. Nope, I did not. I am not that brave after all!

Greasy affairs

For as long as I can remember, I have been told that silicone grease on glass joints is a bad idea. I remember taking this advice to heart because the alternative was to see an IR-like mess in the aliphatic region of my proton NMRs. The benefits of cleaner spectra outweighed an occasional frozen glass joint, although now that I think about it, Teflon tape on the inside had similar lubricating effect (and turned into my preferred way of avoiding frozen joints during grad school). Later on, I would tell this same story about grease to several generations of my doctoral students. The silicone nightmare is part of our synthetic folklore and efforts to avoid it represent a broadly accepted laboratory practice. However, we have a bit of a dilemma here, especially if we look at the review article quoted below. The title has “grease” and “serendipity” in it, so you can see where the paper is headed. We are conditioned not to use grease in reaction setup because we do not want to see garbage in NMR spectra. But it is possible to make things a bit too sterile, isn’t it? Otherwise certain serendipitous findings, such as the nickel example on display, will never be made. I am not saying that this particular carbene complex is noteworthy as a catalyst precursor, but who knows? There may very well be a niche for “OSiOSiO” bridges out there. They are interesting and largely underexplored. Unless generated unintentionally, that is… The “OSiOSiO”-based ligand was observed during an attempt to run what many would consider a fairly standard inorganic prep to make nickel-carbene complexes. I do think that the wording “greased Schlenk” might be a bit much, but I am here to faithfully reproduce what I see, ladies and gentlemen. I note that this review by Saito is not his first paper on the subject (this is more of a “Grease 2.0”). I salute you, Professor Saito, and I am glad that grease is developing a faithful following.2.jpg

A water mop

There are nuances in terminology, culture, and default assumptions among different branches of science. What appears natural in one area often goes against the grain and intuition in another, particularly when it is difficult to put forth well justified arguments at a molecular level.

In the past, I commented on the peculiar properties of PEG (polyethylene glycol). In my discussions with colleagues in protein crystallography, I have always found it odd to hear references to PEG as the “dehydrating agent”. It is especially uncomfortable when PEG is administered in an aqueous buffer to a vessel containing protein crystals. But our biological colleagues have no trouble with this concept at all. Below is a reference to the propensity of PEG to exert “extreme dehydration” on protein crystals. I used this paper in my talk (IRTG conference here in Toronto) earlier this week. While no one has issues with heterogeneous molecular sieves as water mops, many a chemist cringe at the thought of dehydration in water, given the homogeneous nature of one of the parties to the interaction. While this sounds like an oxymoron, dehydration of this sort is something protein crystallographers are rather comfortable with. In the paper below, PEG-driven dehydration is called upon to drastically alter the quality of protein crystals.



A bold way to make guanidines

During a recent trip to the ISACS Conference in Irvine, CA (organized by my friend Vy Dong), I came across what I think is the craziest synthetic sequence I have had a pleasure of seeing in some time. This work is now more than a year old, yet it was still very invigorating to hear Seth Herzon describe it in detail. The reaction sequence depicted below is the pivotal cascade in Herzon’s synthesis of (+)-batzelladine B. In this process, deprotonation of the acetylene intermediate with n-butyllithium followed by the addition of lithium benzyl octanoate triggers 1,2-addition to the β-ketoester, retro-aldol ring-opening, and proton transfer to afford the enolyne intermediate. Subsequent to that, isomerization to the acylallene takes place, which is followed by Michael addition and neutralization of the resulting enolate. The role of DMPU is notable: this additive was found to be necessary to promote the retro-aldol ring- opening. This sequence takes the top prize in how chemoselectivity is achieved in an environment with multiple basic sites.