Is it just me, or do others thing that we’ve been on a run of really interesting new synthetic methods the last few years? I ask partly because of this paper that’s just come out on Angewandte Chemie, from the Baran group. They are, of course, well-known purveyors of new synthetic methods, and this looks like a good one. It’s a decarboxylative coupling between alkyl carboxylic acids (as activated esters, which can be prepared in situ) and aryl boronic acids.
The organic chemists in the crowd will immediately appreciate a big feature of this system, in that a huge number of of both carboxylic acids and aryl boronic acids are commercially available. These are very common intermediates indeed, so this chemistry opens up a lot of new coupling products. The catalyst is merely nickel chloride, bright green and cheap as dirt, with a phenanthroline ligand added. The paper shows this reaction occurring in the presence of a number of common functional groups, and I’m willing to bet that a lot of synthetic organic and medicinal chemists will look over the paper and see immediate applications for some of their own work.
I also commend the Baran lab for furnishing a 180-page Supplementary Information file, free to download to all comers, that provides extensive details on how to run the reaction. That’s the way to get people to try it! This is especially important here, because it turns out that the reaction, though robust when you get it right, is picky about solvent, base, and concentration (although it can deal with water in the system, and can be run on multigram scale). The only objection I can see someone making is on the grounds of atom economy: the activated ester is a rather large beast, and it looks like it comes back out of the reaction as the pthalimide, so it’s not recyclable as such. For the sorts of chemical diversity that this reaction can provide, though, I think it’s well worth it – and in terms of atom economy, you also have to consider the multistep routes that would have to be used otherwise in many of these cases. This looks to become a standard method, and very soon.