Organic chemists do a heck of a lot of palladium-catalyzed coupling reactions. And there are lists of catalysts that go all the way down the page for them, for good reason. Some couplings are robust enough to give you product under all sorts of conditions, while others are ridiculously picky, and need just the right sort of liganded Pd to work well. (Then there are solvent effects, additives, and more).
Complicating all this is the way that commercial palladium catalysts themselves vary in quality.(I’ll insert a nonpaid endorsement for both Strem and Frontier Scientific for your palladium-coupling needs in general). Everyone who does these reactions knows that if you’re using good ol’ palladium “tetrakis” that it should be bright, pale yellow, and not orange or (God help you) brown. But some of the other catalysts can be a bit harder to evaluate. Here’s a paper on palladium acetate, and it has some details that may surprise many of its readers.
The authors, from Johnson Matthey, report that the traditional prep for palladium acetate can give material that’s contaminated with both polymeric Pd acetate and with a complex that has a nitro group substituting for one of the acetate ligands. The polymer has been less of a problem in recent years, they say, but many samples have the nitro species in them. So how different are all these species? The authors did the head-to-head comparison, with pure samples of each (and obtaining those is not necessarily straightforward).
In a series of Buchwald-Hartwig couplings (with morpholine and other amines), all three catalysts were effective. But the polymeric acetate was the best of the bunch, performing consistently at low catalyst loadings. This is particularly interesting, given that the stuff appears to be almost completely insoluble. In Suzuki couplings, lower-temperature runs showed the nitro-containing species to be best, probably because of its greater solubility. As the temperature increased, all three Pd catalysts were effective. Meanwhile, some test Heck reactions showed unexplained effects: with 2-bromothiophene, the nitro catalyst was definitely worse, but with 3-bromopyridine, all three worked fine. Finally, they looked at the formation of fancier palladacycle catalysts (such as third-generation BrettPhos). In this case, the pure Pd acetate complex was by far the best. The polymeric material did not give product at all, and the nitro complex gave a number of impurities.
Well, this sounds like the palladium chemistry we all know and love, doesn’t it? Each reaction has its own ideas about what it wants to do, for reasons that are generally unclear, and you can’t necessarily guess what might happen when you change some variable. If it weren’t for the way that these reactions do such useful bond formations, we’d never put up with this crap, but here we are. So add this one to your Puzzling Palladium file, and good luck with your next tricky coupling.