Electrosynthesis is one of my long-time passions, although my lab has not done it recently (but we shall…). I nonetheless pay attention to novel materials that people start to use these days. Here is one: boron-doped diamond. This material has been known to inorganic chemists, but recently the group of Nishiyama in Japan showed that anodic oxidation on the surface of boron-doped diamond leads to very effective formation of methoxy radicals. Learning from this fairly simple case, the authors expanded the method to the synthesis of a natural product, licarin.

http://onlinelibrary.wiley.com/doi/10.1002/anie.201200878/abstract

I am curious if this and other unusual electrode materials will find new applications in selective oxidation.

Keep in mind that there is, of course, reduction accompanying any electrochemical oxidation. Protons typically get reduced to hydrogen gas on platinum. People rarely draw this reaction, though (it is assumed). Another thing to remember is that ANODE is where oxidation takes place, whereas CATHODE is for reduction. That’s a simple rule to keep in mind.

Since we are on the subject of oxidation, let’s increase complexity a bit… Here is Siegfrid Waldvogel’s excellent recent contribution to organic electrosynthesis. A good cumulative exam question, I must say! The increase in 3D complexity achieved in this synthesis is staggering:

http://onlinelibrary.wiley.com/doi/10.1002/anie.201006637/abstract

Many of the molecules studied in our lab at the University of Toronto belong to the amphoteric class (hence, the title of this blog). Amphoteric molecules contain counterintuitive combinations of functional groups that are expected to react with each other, yet don’t do it prematurely due to a good kinetic reason (this is case-dependent). Not long ago I caught myself thinking that we do not put things into proper perspective and rarely trace the origins of the idea to its humble beginnings. To do that, we have to go back to the Greek philosophers and, in particular, Heraclitus, the father of dialectics. Here is his paraphrased quote:

I think we can all name a couple of examples from the literature that use this concept metaphorically. One of my favourite books, Bulgakov’s “Master and Margarita”, hinges on the idea that good and evil can’t live without each other (i.e. they need each other because neither can exist without a contrast). In our case things are much more benign – a nucleophile and electrophile that co-exist… But still…

When asked: “What is the pKa of benzylamine?”, one of my postdoc friends from the old days with Barry Sharpless at Scripps would strike back: “In which solvent?”. This is a great way to buy time, I suppose, while being a bit of a smart ass. I have found this answer to be somewhat irritating but, if you think about it, it is also true that context is everything…

Below you see arginine. No one (in a million years) would suspect arginine to be a hydrophobic amino acid. This label would go against intuition that comes naturally to a chemist. Yet, hydrophobicity is also context-dependent. As a matter of fact, arginine is a residue par excellence in terms of stacking with aromatic groups, thereby plugging all sorts of hydrophobic pockets. Here is a view from a crystal structure Elena and I solved recently. You see how arginine’s guanidine group is perfectly positioned inside one of the aromatic cages that makes this particular protein special. We want to interrogate the pocket, yet it is filled. Arginine – please go away, darn it! We need our fragments there, not you…

Those of us who care about cyclic peptides eventually come to grips with the idea that, despite their relative strength, amide bonds can be fragile when placed within constrained environments. This is the reason why cyclic tripeptides are inherently unstable. The proximity of amide bonds accounts for the transannular reactivity shown below (left). While this sort of reactivity is certainly undesired if one wants to have access to a 9-membered ring composed of amide bonds, it also provides enabling opportunities in synthesis. I can name a couple of examples right here. The first one comes courtesy of Phil Baran (http://pubs.acs.org/doi/abs/10.1021/ja2047232), and showcases how a 9-membered ring collapses in the course of palau’amine synthesis. The second one is a nice example from Dirk Trauner’s lab (http://www.nature.com/nchem/journal/v3/n7/abs/nchem.1072.html). In this case, loline synthesis was shown to proceed through nitrogen attack at the intermediate bromonium ion. These examples prove that powerful reactions can be designed with  transannular reactivity in mind. Unfortunately, these cases further underscore the notion that the majority of medium ring amides are not to be associated with stability…