Time for some lab talk. There are usually a number of different ways to attack a given problem in organic chemistry. You go with what you know, or what looks most likely to work, or what you actually have the equipment (or funds) to realize. This range of choices goes all the way down to what you’d think would be pretty trivial questions, such as: how do I heat up my reaction?
The standard way to do this is to take the usual flask you’d run the thing in at room temperature and dunk it into something hot. That can be an oil bath with a heating coil in it (good temperature control, but messy), a solid heating mantle of ceramic or metal (clean, but doesn’t change temperature so readily), a woven glass heating mantle, a sand bath on a hot plate, what have you.
Then you can go a bit higher-tech, and heat up your reaction with microwaves. I talked about this here a few years ago (and I note that somehow that stretch of blog time has never been archived on this site; I'll have to work that in some time). The early days of the technology featured (first) kitchen models hauled directly into the lab, then carousel devices built to go inside their cooking spaces. But over the years things have settled down to custom-built chemistry microwave setups, walk-up instruments that let you drop a sample tube in, set the temperature and time that you want, and walk away to pick things up later. Microwave heating has become a preferred way to run a lot of palladium-catalyzed reactions.
Does the microwave do anything special other than heat things up, though? That’s been an arguing point for several years. Various “microwave effects” have been proposed, with mechanisms ranging from the unlikely to the pretty believable. In that last category is the thought that when you’re using powdered metal catalysts, that since these absorb microwaves strongly they give some sort of local micro-heating effect that drives the reactions forward.
Could be – but apparently isn’t. A recent paper from Oliver Kappe's lab in Graz, Austria looks at Heck reactions done that way. Kappe is a recognized pioneer and expert in microwave synthesis (see his latest book, linked below), and if you're interested in the field he's well worth reading. In this case, careful experimentation established that the microwave reactions work well because of their heating profile: they get up to temperature very quickly, which seems to be beneficial. But they found no evidence of a specific microwave effect when they ran the reactions under similar heat gradients but with different energy sources.
They also tried this reaction via yet another heating technique, flow chemistry, which I last spoke about here. That turned out to be pretty interesting, too. They were pumping their two starting materials hot over a cartridge of supported palladium-on-carbon catalyst, but found a couple of odd effects. For one thing, the first flow runs tended to give a lot of side reactions, which was surprising considering how clean the conventional runs were. Looking over the system carefully, the team found that the two reactants were separating from each other as they went down the catalyst tube. They couldn’t couple as efficiently because they were pulling away from each other – the alkene coupling partner came out first, while the aryl halide dragged behind, presumably slowed down by interactions with the powdered carbon support.
The other unexpected effect was that even after partially fixing that problem, after a dozen runs or so the reactions weren't working so well. Then the earlier fractions collected and left to sit turned out to be depositing shiny mirrors of palladium metal on the insides of the glass tubes, and all became clear. The Heck reaction was leaching the palladium metal off the solid support! This had been a mechanistic proposal before, but the flow apparatus provides some real evidence to back it up. When you do this in batch mode, via microwave or whatever, the palladium species get a chance to re-absorb onto the carbon as the reaction cools down, and you're none the wiser, but the flow system just washes 'em on through.
What finally did the trick was to add very small amount of the palladium to the starting system, pump that through a hot tube reactor, and use another scavenger column to clean out the metal. You can get away with that in a Heck reaction, since they can run using ridiculously low catalyst loads. I have to say, I hadn't thought so much about this possibility; that's somewhere in between my Type I and Type II flow reactions in my own scheme.
I mentioned that Kappe has a new book, titled Practical Microwave Synthesis for Organic Chemists: Strategies, Instruments, and Protocols. I haven't seen it personally, but if you're interested in microwave work, it looks worthwhile.