I may talk a good game, but don't let me fool you: I really don't understand some of the things that happen in my lab. I was talking with some colleagues the other day, and told them about a reaction I had in my PhD work. I was using a so-called "higher-order cuprate" reagent, which you make from copper cyanide and lithium reagents, and it worked just fine for me the first time out.

And then it worked just fine again, on a larger scale, and then it worked just fine one more time. And at that point, it stopped working, forever. I never got the tiniest bit of product out of the reaction again, only starting material and varioius forms of junk. It was as if someone had turned a switch.

We're supposed to be able to work these problems out, and I tried. I checked my solvents, my starting materials, and my technique. I analyzed my lithium reagents, and I tried every bottle of copper cyanide we had. Then I made my own, the most beautiful copper cyanide you'd ever want, assuming that you'd ever want some. Result, zilch. I reversed field, thinking that I'd used an old bottle which might have some oxidation products in it that made things work. But aging the stuff by heating it in an open flask didn't help, either. Nothing did. I kept looking at my flask of product from before, a key intermediate in my synthesis, and wondering how on Earth I'd ever made it.

Well, as I finally wrote in my dissertations, "cuprate reagents of all sorts were abandoned after this experience." I never did find out what happened, and eventually worked out another way to get the product (which reminds me, if anyone out there needs to use dimethylmagnesium, talk to me - have I got a recipe for you!) Organometallic reagents are famous for being tricky, but you'd think that a science as old as organic chemistry - we are a science, right? - would be able to deal with such problems. Maybe not.

(Note: the structure and reactivity of all kinds of cuprate reagents have been the subject of food fights for many years. Here's a sample, but if you're not seriously into organometallic chemistry you're going to feel as if you'd stepped into a room full of people discussing Zoroastrian theology. A later and less contentious look at the field can be found here as a PDF.)