As long as I can remember, I have always had a problem with the concept of isolated yield. I mentioned this in the past, and I will say it again: this fuzzy metric is driving me insane. Isolated? By whom? By a first year undergraduate student or by a postdoc? We work at educational institutions and there is a lot to be said about how students grow in confidence and experience. This always has a direct effect on their technique.

The point is, there are subjective and objective metrics in science. While isolated yields are clearly subjective in nature (there is a real person behind the number), conversion and selectivity (I primarily refer to chemoselectivity here) are parameters that exist irrespective of our meddling with reactions. Personally, I am in favour of not considering anything subjective when it comes to process control and optimization. This means that our students need to have a good grasp of monitoring reaction selectivity. If you multiply selectivity by conversion, you get assay yield, which is just perfect as it decouples us from our inadequacies and focuses on what’s of interest to anyone who wants to read our papers – I refer to what actually happens in our reactions. There are many analytical tools available to our students and I want to focus on one of them tonight: GC and its use in catalysis. Choosing the right internal standard is the first step: one needs to ensure that the corresponding molecule is not being chewed up while the reaction of interest is taking place. Once you have the right internal standard figured out, there is a tendency to assume that things should be fairly straightforward. Not so fast. Here is a great paper we discussed at our group meeting earlier today. When I visited the UK a number of years ago, I became aware of this short, yet highly educational piece by Professor Fairlamb. The central message is simple: the fact that you have a nice GC vial containing a mini-worked-up aliquot does not mean that the reaction has stopped. This paper emphatically demonstrates that colloidal palladium cannot be seen by a naked eye, and that no matter how clear your vial is, your analysis might be in jeopardy. I love Figure 1: you can clearly see that the Sonogashira reaction still goes on in the GC vial as you wait for your sample to be processed. I wonder how many other reactions display this behavior during analysis…

http://www.sciencedirect.com/science/article/pii/S0040403904005763

Professor Shawn Collins of the University of Montreal visited us today as the external examiner at Ramsey Beveridge’s PhD defense (Ramsey is one of Rob Batey’s PhD students). The defense went really smoothly and it was great to hear about Ramsey’s accomplishments in the area of total synthesis of macrocyclic natural products. Shawn gave a really nice talk earlier in the day. Some of his lab’s methods tackle the challenge of ring-chain equilibrium in macrocycle synthesis. They bias reactions away from oligomers and polymers without relying on high-dilution. In order to do that, Shawn resorts to biphasic systems that sequester catalysts in a highly polar and/or hydrophilic phase through the use of hydrophilic ligands (http://pubs.acs.org/doi/abs/10.1021/ja208902t). Time and again, it was clear that polyethylene glycol (PEG) has been playing a major role in this research. Shawn’s talk reminded me of a discussion I had with Professor Frey at the University of Mainz last week where we were contemplating some of the mysteries of PEG. Seriously, what is the deal with all these linear PEG-like polyethers? PEG is widely used in areas that range from drug formulation to materials chemistry. The bizarre solvent properties of this and related polether polymers are perhaps best illustrated using a comparison shown below. It is intuitively clear that addition of a methyl group to PEG would increase hydrophobicity, which is the experimentally observed result with PPG (it becomes less water-soluble). However, removal of a methylene group from PEG leads to POM, which is not soluble in water at all (remember those clamps for holding flasks in fume hoods? They are made of POM…). There are models that aim to rationalize this difference in properties and one of them suggests that solvation of water accounts for the observed difference in properties.

Professor Sigi Waldvogel picked me up from the Frankfurt airport yesterday and we went straight to his lab’s barbeque, which was an awesome way to meet the students and sample some local delicacies, including the delicious federweisser, the likes of which I have never tasted before. This is the so-called “young wine” that can be bought locally and can certainly not be transported very far because it is still brewing. There is no tight cover on the bottle, as you can see – just a bit of foil (otherwise there would be an explosion due to CO2). This stuff, along with beer and sausages, made for a memorable evening.

Earlier today, I had a great time visiting the University of Mainz. I already blogged about one of Sigi’s great Angewandte papers in the past. He continues to trail blaze in the area of electroorganic synthesis and I hope we will find ways to collaborate, particularly given Sigi’s experience with boron-doped diamond as electrode material. I will post something on that in the future.

I also had a pleasure of meeting Professor Till Opatz, who is running a very innovative program in natural products chemistry. Amongst many interesting vignettes he shared with me was a paper that I completely missed several years ago. I am now glad that I have discovered this work as it serves an important lesson in compound characterization. Below is what I am talking about. The nucleophilic attack at the I(+)-activated alkyne was reported some years ago by Larock and colleagues. These authors postulated the regiochemistry shown in the top box. As it turns out, the reaction outcome is different, which was Till’s discovery. I know for sure that there are people in my lab who will be interested in reading this work. The clarification made by Till’s group goes to show that it is prudent to exercise utmost care in structural assignment and to consider all possible outcomes that fit the data. And how many gold-catalyzed reactions might be revisited, ladies and gentlemen? I don’t know. Just saying.

http://pubs.acs.org/doi/abs/10.1021/jo3017378

Everyone thinks that they know what “Catch-22” means. This term is used in various contexts and it is good to remember its origins. “Catch-22” comes from a novel by Joseph Heller that bears the same name:

http://www.amazon.com/Catch-22-50th-Anniversary-Joseph-Heller/dp/1451626657/ref=sr_1_1?s=books&ie=UTF8&qid=1409696559&sr=1-1&keywords=catch+22

The story is set in Italy in World War II and describes a military bombardier, Yossarian, who keeps getting more and more dangerous bombing raids assigned to him. Catch-22 is a sinister air force rule that stipulates that one is suspected to be insane if he willingly continues to take part in perilous combat missions, however, if he makes a request to be removed from his bombing duties, he is proven to be sane, which means that he is ineligible to be relieved and must be able to cope with more assignments. This book is a masterpiece and I encourage you to read it, if you have not done so already. And no, I do not think there is any analogy whatsoever to how we treat graduate students with our never-ending lists of projects and requests…