The biggest challenge was to somehow inhibit a competing side reaction called β-hydride elimination. Rather than forming the carbon-nitrogen bond you wanted, this would form a carbon-hydrogen bond. This was one factor limiting the yield. We needed to develop catalysts that would get around this process.

  And how did you succeed?

Through a combination of mechanistic studies and empirical studies. And, as is usually the case, a little luck played a part as well.

  What was the luck factor?

Well, the key discovery we made back in 1998 was that a ligand called BINAP turned out to be a very good ligand. This is a chiral bis-phosphene. It was developed by Ryoji Noyori, who used this ligand for hydrogenation chemistry and won the Nobel Prize for the work. BINAP was a ligand people usually used in asymmetric transformations. The serendipity came about by way of another graduate student in the laboratory, Seble Wagaw, who was trying to do something else entirely and realized that BINAP provided a reaction much more rapid and cleaner than anything we had seen previously.

  How would you describe the overall significance of the work you did with the Buchwald lab, and your highly cited 1998 Journal of the American Chemical Society paper?

There are really two sets of significant points. For starters, these techniques we’ve come up with basically provide a very powerful method to form aromatic carbon-nitrogen bonds. This chemistry is being used both in academia as well as in industry to make a lot of compounds that were simply very difficult to make without it. For instance, Dick Schrock, who is also at MIT, used this chemistry to make a ligand for some of his metal complexes that he uses in reductions of molecular nitrogen to ammonia, and this chemistry has been used to make a number of natural products. So it is arguably the mildest method available for the formation of aromatic carbon nitrogen bonds.

The other area of impact of this work, the other focus, was on developing very active palladium catalysts to transform aromatic chlorides. It turns out aromatic chlorides are a lot cheaper than aromatic bromides or aromatic iodides. From the industrial standpoint, this is very useful. The problem was that, for a long time, people believed these aromatic chlorides were usually un-reactive in these kinds of palladium-catalyzed cross-coupling reactions. Maybe at temperatures over 130°C they’d work, but that was it. We were working on developing new palladium catalysts, and that led us to catalysts that can transform these very un-reactive aromatic chlorides under very mild conditions and even at room temperature in some cases.

  How do you decide which journals you’ll submit your articles to?

Basically we want to submit our work to the highest-impact journals, to get the work out there and have it accessible to the maximum number of people who want to use it. Most of our important work we try to publish in the Journal of the American Chemical Society. If not there, we will go to Angewandte Chemie or the other American Chemical Society journals, such as the Journal of Organic Chemistry. We want to put our work in journals that reach the highest readership and the most people interested in using this chemistry.

  How has your understanding of this chemistry evolved since you entered the field in the past decade?

First I would say we have a much greater mechanistic understanding of some of the steps in these reactions. All these metal-catalyzed reactions are not really one, but series of two, three, or four reactions in a catalytic cycle. The final step in that cycle, for either carbon-carbon bond formation or carbon-nitrogen bond formation is called reductive elimination. Over the course of the last nine or ten years, we learned a lot about how to facilitate the reductive elimination step in these catalytic cycles without slowing down the other steps. These catalytic reactions are a kind of complex balancing act. Sometimes it’s easy to figure out how to speed up one reaction out of three or four. The tricky part is to speed up one without messing up the others. In a lot of cases, the electronic parameters required for each reaction are different and can in fact be opposite, so when you speed up one you may slow down the others. I think we’ve made good strides forward in understanding these reactions, although people are still very active in this area.

Another issue has been controlling this β-hydride elimination reaction. Probably the most interesting development in the last few years in this area has been work out of Greg Fu’s lab at MIT showing that you can use alkyl halides in carbon-carbon bond-forming reactions catalyzed by palladium, providing you make the appropriate choice of catalyst.

  Are you satisfied with what you’ve achieved?