Steve Buchwald @60 (2015)

1 Stephen Lefler Buchwald turns 60 this year, and this milestone is being celebrated widely by past and current co-workers, friends, and colleagues in a variety of ways, including this Special Issue of Advanced Synthesis & Catalysis. The attention is certainly justified: Steve is one of the world’s most famous and admired chemists, not only because of his outsized contributions to chemistry, but also because of his larger-than-life personality. I am lucky to have had a ringside seat to both his career and his personality over the past 30 years. At the risk of irritating Steve, I am happy to share a few thoughts about my good friend on this important occasion. On the personal side, Steve is funny, provocative, and always interesting. If you know Steve, you are likely to have heard some of his strong views on politics, social justice, what makes for a good reaction, which up-and-coming chemists are doing worthwhile work (and which ones are not), and an assortment of other topics. It would be fun, but not appropriate, to go into detail here about Steve’s unique perspective on the world. I’ll simply say that Steve is a brilliant and passionate man, and one of the most principled people I have ever met. And, like the good wine that he is generous to share on occasion, he only gets better with age. On the professional side, Steve’s story also just keeps improving. After obtaining his ScB at Brown and his PhD in bioorganic chemistry with Jeremy Knowles (with a thesis defense that is the stuff of legend), Steve did his postdoctoral studies with Bob Grubbs. It is clear that Steve’s Caltech experience had a transformative effect on his scientific outlook that holds to this day. Steve moved to MIT in 1984 with plans to start an independent program in organometallic chemistry. In the ensuing three decades at MIT, Steve and his group have helped define the forefront of the field. In the early 1990s, Steve invited me to team up with him to create and deliver a short course in organometallic chemistry intended primarily for pharmaceutical chemists. We visited dozens of companies (back when there were dozens of companies to visit), spending 2–3 days teaching the basics of the field and fielding questions from process and medicinal chemists. In those days, cross-coupling reactions were certainly well known and their potential was being grasped by some, but they were still not terribly useful in pharma. Indeed, it always seemed that the question we got most often during the discussion sessions was “I tried a cross-coupling [on substrates of undisclosed structure] and it didn’t work. What should I do?” Whereas my answer was typically “what does your tetrakis look like?” Steve took these questions much more seriously and came to appreciate that many of the limitations of the methodologies had fundamental causes. I think Steve was also influenced deeply by his then-MIT colleague Barry Sharpless’s unwavering fascination with practicality. There may well be other contributing factors that led to his change of focus, but it was during this period that Steve turned his attention from what might be considered exotic reactivity of organometallic complexes, to questions of how fundamental reactivity principles could be applied to chemistry that is genuinely useful. The rest is history, as they say. Over the past 20 years, Steve and his group have sought – and achieved – general solutions to some of the most important metal-catalyzed transformations. Of course, Steve’s most conspicuous achievement in the practical arena is the discovery and development of his eponymous methods for catalytic carbon-heteroatom bond construction. Students and practitioners of organic reaction chemistry broadly defined know that the impact of this chemistry is enormous. Some version of the following statement is often uttered or written about Steve: “Literally every hour of every day, Buchwald’s chemistry is being practiced and applied by a medicinal chemist somewhere in the world.” That may sound hyperbolic, but it is not. Steve certainly has a “name reaction” for the ages that has helped shape what molecules are investigated in industry. But he also has shaken the academic world with a “name family of ligands” that has touched nearly every aspect of research in late-transition metal catalysis. The “Buchwald ligands” are an ever-growing list of bulky, tunable, not-always-innocent monodentate phosphine ligands bearing colorful names honoring his students and cats. They have redefined Cheteroatom and CC coupling and find new applications outside of cross-coupling in labs all over the world. Today, if I get asked “why didn’t my cross-coupling reaction work?” my answer is no longer “what does your tetrakis look like?”. It is “did you try X-Phos?” Steve’s successes in the arena of cross-coupling have been so dramatic that they tend to distract from his remarkable body of work in other areas and especially in the field of asymmetric catalysis. For example, his very recent work in enantioselective hydroamination certainly reinforces the view that he and his chemistry just continue to get better and better. Congratulations, Steve, on a remarkable first 60 years.