I have been silent for a bit, but that is because of travelling… I am literally 150 miles from Sochi (the host of Winter Olympics), if I can get over the Caucausus mountains that is. I am at a small town called Pyatigorsk in southern Russia, which is where my father is from. That is a rare coincidence. In fact, he decided to join me on this trip. A conference is dedicated to the chemistry of heterocycles and is taking place here in Pyatigorsk. I am enjoying every moment of it, having already learnt a ton of new stuff. Vladimir Gevorgyan gave his usual fireworks type of a lecture, which was awesome. I must admit that I was really intrigued by the talk given by Prof. Makosza from Poland. He is an elderly gentleman speaking in a rather unassuming way. The next thing you realize is that you have the father of phase-transfer catalysis in front of you! The latter is well familiar to many people by now, but I was particularly intrigued by his foray into vicarious nucleophilic aromatic substitution. I do think (and many people would agree, I am sure) that this area has been unjustly overlooked by many of us. Take a look at the following example, by the way. Could you have anticipated this outcome? I can’t say that I could.

While it is easy to control cis- vs trans- double bonds in Wittig reactions (think about stabilized vs non-stabilized ylides), it is certainly not the case with amide bonds. In fact, one of the fascinating questions I like to think about together with my students is why we are always tempted to draw trans-amides as products of amide bond forming reactions. Granted, trans isomers are more stable. But who’s to say that they always form under kinetic control? This is a mystery… One might say that this is not one of those “relevant” mysteries as in linear peptides cis amides will certainly (and rapidly) isomerize… But hold on a second: this does not need to happen in cyclic variants. I give you a very informative example from the late Prof. Goodman. This aminal-containing macrocycle contains one amide bond that is largely cis in solution. The reason this is cool is that this case is not based on proline, which tends to give a large proportion of cis-amides for different reasons. We need to think more about deliberate control of cis/trans isomers in these systems.

http://pubs.acs.org/doi/abs/10.1021/ja00199a058

Please indulge me for one more fluorine-related post (I don’t know what’s happening to me) but I promise that I will leave the subject for a while. This is not about some late-breaking news or anything like that. It isn’t even about a paper that is particularly useful in the eyes of a modern function- and goal-oriented chemist. This work is not even new, but it is what we should all care about: it is thought-provoking. This paper was submitted to JACS by Prof. Sakurai almost 20 years ago. It details a molecule that was dubbed by the authors as a “merry-go-round” kind. You can see it in the graphic below. At first glance, its silicon NMR spectrum should contain a doublet. But it ain’t. There is a triplet and the reason for that is that the fluxional behavior around C-Si bonds leads to a unique situation in which each silicon is hexavalent, yet neutral! And then the most interesting thing happens: at higher temperatures Si NMR is actually a septet. The reason: degenerate fluorine migration (hence the name “merry-go-round”) such that each Si “sees” six fluorines at a time.

Hey – no one blogged in the days of Prof. Sakurai’s paper, so I will do it. Incidentally, this was one of the works I fell in love with while doing my PhD with Prakash and Olah. I think we can all name a few papers we remember from a while back. Some of them do leave a lasting impression.

http://pubs.acs.org/doi/abs/10.1021/ja00087a054

I did not know there are so many black bears here in BC… I can’t say that I saw one, but the stories I heard from Rob Britton earlier today were fabulous. Rob was the host during my visit to SFU, which is located in Burnaby, about a 30-minute ride from Vancouver. Rob’s work in the area of chloroaldehydes has been of particular interest to me. The chemoselectivity of this process is notable, given what’s brewing in the reaction mixture (I refer to NCS and proline co-existance). His lab has put this process to some great use in natural product synthesis.

http://pubs.acs.org/doi/full/10.1021/ol401370b

While there were no bears in sight, our dinner with Rob Britton and Bob Young (a former VP of Chemistry at Merck-Frosst, now a Professor at SFU) in Deep Cove, North Vancouver, was a great conclusion to the scientific part of the trip…

I had a great time at UBC yesterday. Amongst other science stories in my talk I described how we make crystals of peptides at SGC. Somehow this really got the graduate students interested. They peppered me with questions, which was fun.

This visit was a chance for me to see some old friends and meet new people. I would like to say my special thanks to Jen Love, who invited me and organized my visit. Throughout the day, there was a certain “fluorine” theme I could not help but notice. Dave Perrin, who is always passionate about science told me about some of his lab’s work that has convinced the world about how specific activity of radiolabelled trifluoroborates is to be understood. I encouraged you to read this scholarly work:

http://onlinelibrary.wiley.com/doi/10.1002/anie.201208551/abstract

Steve Withers described a great story related to his neuraminidase inhibitors. Although I saw his paper in Science not too long ago, I was thrilled to hear the story from the man himself. Each of the fluorines is critical to the behaviour of this intriguing inhibitor (below) and the work is a testament to the fine balance of relative rates that is possible through the careful selection of substituents.

http://www.sciencemag.org/content/340/6128/71.abstract

Glenn Sammis concluded the triumvirate of fluorine-related vignettes for me and showcased how his lab (in collaboration with J. –F. Paquin) managed to get radical fluorination to go:

http://onlinelibrary.wiley.com/doi/10.1002/anie.201206352/suppinfo

I also had a great time with Marco Ciufolini, Jen Love, and Laurel Schafer. I have followed their work for a number of years and will dedicate a special section some time in the near future. My former student Taka is in Marco’s lab. It was great to see him (good luck with the total synthesis, Taka!).

I started my three-day West Coast trip today. The first stop was at the University of Victoria. I have to say that Victoria is probably the most beautiful place I have been to and I have been to many… The town is right on the Pacific Ocean coast and is a short 15 minute flight from Vancouver. The harbor somehow reminded me of Copenhagen, but it is better.

I gave a talk at the Chemistry Department here, spreading my lab’s gospel of amphoteric reactivity. Most importantly, I got to meet some of the folks whose work I have known for a number of years, and also made some new acquaintances. Fraser Hof’s work in interrogating methyllysine binding domains is really exciting, I can’t wait to read about the latest findings his lab made in recent moths. My graduate student Rebecca Courtemanche hails from Fraser’s lab and I gave Rebecca a big shout out in my talk. Robin Hicks told me about his lab’s research on redox-active ligands based on indigo. Indigo! This is the stuff the jeans are coloured with! Really creative stuff. Who would have thought that this old dye holds so many surprises. I also met Jeremy Wulff, one of UVic’s youngest faculty members. His lab does so many interesting things. I think that his cyclic peptide work geared towards interrogating a protein/protein interface mediated by two beta sheets is very thought-provoking. I am looking forward to seeing some time soon in the literature.

A recent paper in Angewandte by Neil Burford really caught me by surprise, I must say. Neil told me about this piece in detail. We all know that palladium does reductive elimination really well, which is the basis of the vast majority of cross-couplings. But what about reductive elimination from a main group element? I was not aware that this is possible. Yet, Burford’s lab showed that reductive elimination happens in a very curious fashion from antimony compounds. I wonder if main group elements will one day be shown to display this kind of behavior in catalytic reactions…

http://onlinelibrary.wiley.com/doi/10.1002/anie.201210012/abstract

I think all students in sciences rightfully ask questions about their future employment. We live in uncertain times and job prospects are of great concern to our students. I still remember 1997 when I was a PDF at Scripps. My friends all thought I was a complete fool to go into academia. They kept saying: “rather than doing something so crazy, you need to think about what’s more or less guaranteed for life, Andrei”… They referred to jobs at Pfizer, Merck, etc. Of course you know what happened then. The ground rule that governs capitalism is the bottom line. Accordingly, it became profitable for big corporations to outsource production and, later, discovery, to places like China and India. People started losing their jobs in North America and it has been tough here for several years. But guess what? The pendulum eventually swings back. The same laws that governed leakage of jobs to Asia must eventually move to equalize the costs here and there. You might still say that the difference in costs remains large and will continue to stay that way for a while. Well then… I give you widespread corruption in places like China. We are all aware of some serious issues that keep popping up these days, all pointing to fraudulent practices in the pharmaceutical R and D in China. Several big companies are now implicated in scandals and we can foresee a situation when it becomes too risky to do business there. It is always that good old risk/benefit analysis. The jobs may then very well come back to North America. Check out the following high profile report published in Science:

http://www.sciencemag.org/content/341/6145/445.summary