I’m going to be working up an Arbuzov reaction this morning, which is an odd thing for me to say. That’s because to the best of my recollection, which is pretty good, I’ve only run any of those during one period in my lab career. That was back in grad school, along about 1985, I’d say. I hope this one proves more useful than that one did – I was trying to make some dimethyl diazomethylphosphonate, and the prep was a relentless barrage of No Fun. (The first part of the sequence was identical to this).
I keep a list in my head of songs that I’ve only heard one time (no, I don’t appear to be normal, thanks for asking), and perhaps it’s time for me to assemble a list of reactions that I’ve only run once. That’s a tougher one, because if a reaction fails, you may well run the thing again. Still, I’ve only done one hydrogenation at 2000 psi with rhodium on alumina (July 3, 1984, and it looked like used lawnmower oil afterwards, I should add), and I’ve only used samarium iodide one time (and it didn’t work). But for a longer list I might have to settle for some things that I ran for a brief period and never have since.
The Claisen rearrangement would fall into that class, for sure. A feature of my early grad school work, I’ve never had the need to run one since. I can't think of the reaction without smelling ethyl vinyl ether in my memory, which is not a feature, in case you're wondering. I did a lot of carbohydrate reactions back then that I haven’t had the need to return to, either – Ferrier rearrangements being just one of them. And, like many other chemists, I had a brief photochemistry period, in my case during my post-doc, and have never run one of those again, either. Others that enjoyed their day in the sun and have never been seen again in my hood are the Prins reaction, nitrone cycloaddition (not since I was an undergrad in 1983), Lindlar hydrogenation, and the Henry reaction.
The thing is, any of these could make a comeback at any time. They’re still all perfectly reasonable reactions, and depending on what comes out of the next high-throughput screen or literature search, I might be setting one up next week. You never know. But there are some reactions that I think I’ve said goodbye to forever. In some cases, that’s because better alternatives are now available - I mentioned here that I haven’t used PCC for oxidations in years, and I think that one’s been pretty much superseded.
Others are history because I either very much doubt I’ll have the need for them, or because I just flat out Don’ Wanna. For example, I made Dess-Martin periodinane three times on a hundred-gram scale, during a period in the early 1990s when it wasn’t commercially available, and I plan, with any luck, never to do that again. The prep has been improved since those days, but that explosive intermediate was never something I enjoyed seeing. I don’t think I’ll be synthesizing fluorosulfonic acid starting from hydrofluoric acid any time soon, either. I did that one as an undergrad, too, if you can believe that – this guy must have had confidence in me, which I’m not at all sure was warranted by the evidence at hand. Nor do I foresee any need to make Fremy’s Salt from scratch again. (You can see someone else do it here, though - the internet amazes me sometimes). And if I never do another reaction that requires half a mole of phosgene, that’ll be fine with me, too.