Field of Science

Gilbert Stork on steaks, synthesis and more

Few chemists in the twentieth century have contributed as many important ideas to the science and art of organic synthesis as Gilbert Stork. Stork has made any number of groundbreaking and elegant contributions to the discipline, from the enamine reaction to radical chemistry to pathbreaking total syntheses like his synthesis of quinine. And from his perch at Columbia University where he has been for almost fifty years, he has emerged as one of his generation's most productive trainers of leading chemists in academia and industry. Here's a nice presentation listing his achievements.

Stork is now being celebrated on occasion of his 90th birthday by chemist and historian Jeff Seeman in Angewandte Chemie. Jeff brings us a wonderful collection of anecdotes, quotes and stories, both by Stork himself and by his friends and colleagues which include some of the twentieth century's leading organic chemists. There are also dozens of memorable photos. Unlike some of his contemporaries, Story is a rather unassuming man who has shunned the limelight, so it's a treat to hear these stories. There's lots of amusing stuff in there, from Stork's literally explosive relationship with cars to his being thrust into the unenviable situation of having to give a talk right after a stellar lecture by R. B. Woodward. For me two stories stood out.

First, a tale of steak disposal that momentarily triggered a panic attack and illustrated a nice lesson about kinetics (notwithstanding the fact that aqua regia contains hydrochloric, not sulfuric acid):

“There was this one really idiotic time. I remember I was really scared that I was going to blow up the entire Chemistry Department at the University of Wisconsin. I had a steak on the window ledge of my office. It was the winter, and I used the window ledge as a refrigerator. You obviously were not supposed to be cooking steaks in the lab, but I had a small lab where I was usually alone in there, and so I had a steak. But I also was not aware that biodegradable material is biodegradable, and this steak was clearly degraded on the window ledge. And the question was, what to do with it? And I decided to toss the steak in a hot acid bath which we used to clean up glassware. So, it's fuming nitric and sulfuric acid. It's really aqua regia in that bath, in that heavy lead dish, and the steak.

“And then, as I just had thrown it in there, and it fumed furiously and red fumes of who knows what, nitrous oxide of various kinds were being produced there. I became frantically concerned because fat is glycerides. So, I am hydrolyzing the fat to glycerin. You make nitroglycerine by taking glycerin and nitric acid and sulfuric acid, and obviously, I am going to produce a pile of nitroglycerine and blow up the entire building with my steak.

“Now, what is an interesting point there, why didn't it? And of course, the reason is kinetics. That is, the kinetics of oxidation of the glycerol at that temperature is much, much, much, I mean, infinitely faster than the cold temperature nitration of glycerin. And so the place was safe.”

And second, some reflections on the real value and utility of chemical synthesis:

“The toughest question to ask in synthetic organic chemistry after the work is done is: what have you learned? And you can have extraordinarily complex things. They look complex as hell. Maybe they have 80 asymmetric centers and maybe the answer is, [you've learned] nothing. I mean, you could have learned that humans are capable of enormous focused efforts and are capable of sticking with a problem which is extraordinarily complicated.

On the other hand, if somebody makes polyethylene, as somebody obvi- ously did, then you learn a lot, even though it will not thrill most synthetic chemists because this would be comparable to building a highway for an architect. I mean, it's important, but it's fairly dull compared to [building] the Guggenheim Museum, for instance... ”

“So something could be not terribly glamorous but extremely important, or vice versa. I think that B12 was vice versa. It's enormously complicated.”

That's a really important point he makes, and one that should define the choice of a research problem especially for a young investigator. There's not much point in attempting that 80 step synthesis using "hammer-and-tong" chemistry if it's not going to teach you much; that's also one of the reasons that people like Woodward get so much credit for synthesizing something first, since they really demonstrated that such complex synthesis was possible. On the other hand, throwing in two simple chemicals and watching them form an astonishingly intricate infinite lattice can really teach you something new. So can synthesizing a boringly repetitive polymer with novel properties.

The real deal in chemistry as in any other science is understanding, and the nature of experiments that impart real understanding changes with the evolution of chemical science. Stork's message for new researchers is clear; pick a problem that may not be glamorous, but whose solution would teach you something new. Stamina is not quite as important as creativity and discovery, and although perseverance is admirable, you don't make an important contribution just by proving that you can stick with a problem for ten years. Even though it may appear that way, science is not a marathon; it's scuba diving.

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  1. It doesn't seem to me that one can say that the synthesis of B12 was useless and be taken seriously. Eschenmoser described some its effects on his research into the origins of life. Didn't the Eschenmoser coupling and orbital symmetry rules also come out of it? These don't seem useless to me - they're more than come out of most total syntheses, including Stork's quinine synthesis.

    On the other hand, when I think of maitotoxin, it's not hard for me to see Stork's point.

    1. Yes, Woodward did get the idea for orbital symmetry from a B12 reaction that didn't quite go the way it should have, so I too am not completely sure about Stork's statement. On the other hand, the orbital symmetry observation was serendipitous, and the original objective seemed simply to prove that something as staggeringly complicated as B12 could be made. Maybe Stork is contrasting it with other syntheses like reserpine, where the objective clearly was to demonstrate stereoselective construction, a goal which is much more important than just a complex synthesis.

  2. I am very glad that Seeman takes the time to record this history and present it in a compelling manner. He is providing a great service to the field.

    1. Indeed, he is doing something wholly valuable and unique especially since there are not many chemistry historians around. I am sure you are aware of his edited memoirs of leading chemists published by the ACS.

  3. Stork's comment on B12 is more of a swipe at Woodward then anything else. There was always bad blood. (See 10.1002/anie.200601551 for a great story on the quinine synthesis with 10.1002/anie.200705421 for a great conclusion to the story.)

    1. I don't know if I would call it "bad blood". I did read Seeman's fascinating history of the quinine synthesis. I think in the absence of definitive evidence that Rabe and Kindler had indeed synthesized quinine from quinotoxine, Stork was probably right to be skeptical about Woodward's "total" synthesis of quinine.

  4. My favorite Stork story was one I heard from my PhD advisor. It started with a discussion about how relatively absent-minded Stork could be and that one of those spells struck him as he was driving to the Gordon conference in New Hampshire. He was lost in thought or just plain not paying attention and missed the exit, but didn't notice for a while. So when he finally realized this, he put the car in reverse and backed up for few a miles so that he could get off the highway on the right exit.

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