This article was originally published in Caltech’s weekly newspaper, The California Tech.
A team of Caltech scientists and students has discovered a groundbreaking new method of synthesizing carbon-silicon bonds—a method that is easier, cleaner, and a thousand times cheaper than the current state-of-the-art. The Tech sat down with graduate student Anton Toutov and undergrad Kerry Betz, members of the Grubbs lab; and postdoc Wen-Bo “Boger” Liu, a member of the Stoltz lab; to hear the story of how they pursued a seemingly improbable reaction to make a cutting-edge achievement in chemistry.
Lori Dajose: First of all, let’s talk about why your new method is so revolutionary to chemistry.
Kerry Betz: Well, carbon-hydrogen (C–H) bond silylation—replacing a hydrogen atom with a silicon group in a molecule—is normally pretty challenging. You have to use these expensive, rare, and sometimes dangerous metals like platinum, palladium, and iridium, as catalysts. But our reaction uses potassium tert-butoxide as the catalyst. Potassium is naturally abundant, making our compound safe and inexpensive—no more need for those precious metals.
Boger Liu: Additionally, replacing a carbon-hydrogen bond with a carbon-silicon bond is really crucial in making important molecules called organosilanes, chemical building blocks valuable in manufacturing basically everything from new medicines to new functional materials, like next-generation liquid crystals for LCD screens. The idea of making organosilanes catalytically without precious metals seemed so naive and lofty—it was unprecedented. This “precious metal paradigm” was like an axiom in chemistry that few scientists had attempted to challenge.
From left: Kerry Betz (’15), Anton Toutov, and Wen-Bo “Boger” Liu have recently published a paper detailing the use of potassium tert-butoxide as a catalyst in silylation reactions. Photo courtesy of Allison Maker.
LD: What inspired you to challenge it?
Anton Toutov: Two and a half years ago, I noticed organosilanes occurring as unexpected byproducts from my unrelated experiments with biofuels. It was kind of random, but this really provided the crucial proof-of-principle that we didn’t need to use crazy expensive precious metal catalysts for the carbon-silicon reaction to occur. I just decided to run with it.
LD: And you started looking for people to run with you.
KB: Yes. Around the same time that Anton’s project was gaining momentum, I was looking for summer research. I met with several potential mentors, him included. He was just so incredibly excited and animated talking about it, and I thought, “Wow, he seems like a really fun guy to work with!” I was relatively new to this type of chemistry, so I didn’t have the same bias that more experienced researchers had with regards to this precious metals paradigm.
LD: Boger, you teamed up with Kerry and Anton a few months later. What inspired you to join?
BL: Well, one of the key components of the reaction involves breaking a carbon-hydrogen bond in a heteroarene and replacing it with a carbon-silicon bond. I had done some research on the first half of that process—methods for breaking C-H bonds. Anton and I would have coffee every Saturday, and one day he showed me how he had been using a potassium catalyst for this reaction. I couldn’t believe it. I knew this would change the entire field of C-H silylation chemistry. It was natural for me to get on board with him.
AT: I had worked on the problem alone for some time and solved it to an appreciable degree, and then I knew I could use some really talented and passionate people to help improve the reaction further, and broaden its scope. When Kerry and Boger joined the project, it just took off.
BL: Originally, we began by applying the method to a class of molecules called heterocycles, biologically important scaffolds present everywhere in nature. When it became unbelievably clear that it was really working, we each branched out to apply the method to different classes of molecules.
AT: We were each working in our own direction, simultaneously pushing the project forward on several different fronts. Kerry was making molecules that have never been made before, discovering interesting subtleties about the reaction, and developing some sophisticated hypotheses. She’s now a completely independent research chemist, and a leading world authority on Earth-abundant metal catalysis, working on extending this method to other molecules. I’m so proud of her. And Boger, he is such an amazing talent. He helped me to optimize the reaction to an excellent level, synthesized a large amount of new molecules using our method, and helped me to develop several new methods based on our general concept. He has also been working on elucidating the mechanism of the reaction, which is currently a big mystery that nobody in the world seems to understand! All in all, I had just the best team imaginable with which I could bring my C–H silylation reaction to life.
Kerry Betz is the third author on the recent silylation paper. She is an undergraduate in the lab of Professor Robert Grubbs, who won the Nobel Prize in Chemistry in 2005. Photo courtesy of Allison Maker.
LD: Your method isn’t just a new way of synthesizing organosilanes—it’s also a better way than the existing state-of-the-art. Tell me about that.
BL: First of all, we found that the reaction could actually occur under pretty mild conditions. We’re talking room-temperature here—the lowest temperatures this reaction has ever occurred at. In addition, there were no harmful or dangerous byproducts, just hydrogen gas—which is valuable itself!
KB: The method is really environmentally friendly. Using precious metals produces toxic metal waste that has to be filtered out from your desired products—our method has no such drawbacks. On top of being green, it is thousands of times cheaper than using precious metal catalysts. And if being clean and cheap wasn’t enough, it is also pretty easy. This is the kind of thing that could probably be taught in an introductory freshman lab, like Ch3a. It’s shocking how it just blows away this precious-metal paradigm that has been around for almost a century.
LD: Your paper was recently accepted and published in Nature. What was it like for you, to be published in such a prestigious journal?
BL: Well, we got the acceptance email on my birthday. It was a fantastic present.
KB: My birthday was a few days before we got our paper accepted, so it was like a birthday present for me too. I was actually having a really bad day. Then I got a card from Anton saying, “Happy birthday… oh and by the way, congratulations on your publication acceptance into Nature.” It has been so amazing; I’ve been able to help this project come from an uncertain, possibly controversial beginning, to an unprecedented and publishable conclusion.
AT: Yes, and it’s really just the beginning. There’s so much to come, and we are the pioneering lab for this research. Our hope is that this discovery will change the way that people think about chemistry, and about the logic of chemical synthesis in particular.
The full paper was published in Nature on February 5, 2015, titled “Silylation of C-H bonds in aromatic heterocycles by an Earth-abundant catalyst.”