Phil Baran and co-workers Ming Yan and Yu Kawamata at Scripps have published an overview of what they feel is needed in synthetic organic electrochemistry, and I have to applaud them for it. The whole area has a lot of potential, but the current state of the field is messy. (Sorry for that sentence; I couldn’t resist. OK, sorry for that one, too. In my defense, the Yan/Kawamata/Baran article avails itself of plenty of easy targets in the same way!). In 2015, electrochemistry was one of the techniques nominated in the comments to this post as containing the largest amount of sheer voodoo, and I’ve also mentioned it in the “surely there must be something else” category. In 2012, I had this to say:
I definitely don’t think that the technique is useless, but it surely doesn’t get used much. One problem is that there are so many different conditions – solvents, electrolytes, electrode materials, voltage/current regimens. If you’ve never done the stuff before, it’s hard to know where to start. And that leads to the next problem, which is that so much of the equipment in the field has been home-made. That makes the activation barrier to trying it yourself that much higher: do you want to do this reaction enough to want to build your own apparatus and troubleshoot it? Or do you have something else to do? If someone sold a standard electrochemistry kit (controller box to run different conditions, set of different electrode materials, etc.), that would free some people up to find out what it could do for them, rather than wondering if they’ve built a decent setup.
It took the Baran group a while to get going on that request, but these are exactly the problems addressed in this paper (mainly because they’re exactly the problems that anyone who’s ever done any electrochemistry has quickly come to realize!) It’s a call for reproducible conditions, which are best arrived at by standardized, modular devices that can run at different scales, including analytical mode, and have interfaces that makes sense to synthetic organic chemists. No such electrochemistry instrument has ever existed, to the best of my knowledge. As long as you have to build your own homebrew rig to do anything useful, very few people will try these reactions at all, and as long as the field is full of homebrew rigs, very few people will be able to reproduce what you do manage to accomplish. The paper mentions just this sort of problem:
In our own experience with electrochemical C–H oxidation reactions, this process is prohibitively challenging with added factors such as electrode, electrolyte, current, potential, and resistance all playing crucial roles in the reaction. We have exercised extra caution to ensure the uniformity of all conceivable variables including the size of electrodes while crafting our “home–made” cells; detailed experimental protocols were furnished in the supporting information. However, we were baffled by feedback from industrial collaborators that, despite having adhered closely to our instructions, they were unable to obtain products in similar yields. After several rigorous troubleshooting sessions, we realized that it was the distance between electrodes that triggered the vexing problems
There are, of course, a number of people working on electrochemical methods, and they may or may not be pleased by this call to action. The idea is not to minimize the contributions that people have made over the years – the article itself has a variety of references to very interesting-looking reactions that have been developed by a whole list of other groups. But looking at these transformations, you have to wonder why such a versatile technology hasn’t been picked up more – surely people are interested in C-C bond formation, amination, C-H bond oxidations, and so on? It’s because of just those problems detailed above. The barriers to entry are too high, and the chances of wasted time and effort are too worrisome. And even if you find something, no one else will run the reaction, because they don’t have the equipment, either. So make sure everyone can get the same equipment, and things might just start to change.
And that brings us to this device, introduced at the recent ACS meeting in DC (OK, OK). It’s a collaboration between the Baran group and IKA. It’s scheduled to be available by the end of the year, and it seems that units have already been sent out for evaluation to some of the groups who are working in the electrochemical area. IKA also has an electrochemical flow apparatus for scaleup, and I’ll be most interested to see how all these work together. It’ll presumably be a year or two before we all start seeing results from the “ElectraSyn 2.0”, but here’s hoping that it opens up some new techniques for those of us who’d rather not rummage around looking for the soldering iron.
Update: see the Supporting Information for this paper for an example of what it’s like to build your own electrochemical apparatus. The paper itself, on CH oxidation, is an excellent illustration of why we should care. This new paper on amination, also very interesting, has a look at the ElectraSyn 2.0 in action in its Supporting Information.
Update 2: see this paper for another proposal for a standardized electrochemical cell.