Interview Professor Kendall N. Houk

Professor Ken Honk is a Distinguished Professor in the Department of Chemistry at the University of California at Los Angeles. Honk began his academic career at the Louisiana State University, rising to become professor before moving to the University of Pittsburgh. After spending 6 years there, he relocated to the UCLA in 1986. 

The focus of Houk s early academic career was on pericyclic reactions. He began as an experimental chemist, but the relatively strong computational staff and facilities at LSU allowed Houk to first begin testing the ability of semiem-pirical methods in predicting regiochemistry. Studies of pericyclic reactions, especially from a computational perspective, span his entire academic career. 

Houk s involvement in proline-catalyzed asymmetric induction began in a similar way. Occasionally something very interesting appears in the literature, especially so if it is amendable to elucidation by computational methods, Houk recalls. We are especially interested in synthetic methods where the experimentalist is unclear of just how things work. This was Ihe case with the proline work. We saw the work of Barbas and List on the aldol reaction, and we were aware of the Hajos-Parrish reaction. So we started computations on simple models, and then looked at the Hajos-Parrish reaction, and we came upon an explanation for its stereoselectivity. This was all done without communicating with any of the experimentalists.  

After these studies were published. Professors Barbas and List independently contacted Houk, and the List collaboration developed. Houk remembers that List suggested Why don t you try the reaction of cyclohexanone plus ben-zaldehyde. We ll do the experiments but I won t tell you the results—so you can make a real prediction. And that s the way it developed. That took quite some time—3 to 4 months to do all the computations—since we had to predict something. That s a more arduous task than explaining something. We were concerned about missing a TS, so we went about a systematic search. And then we told List our results and there was really spectacular agreement.  

The story, however, is not yet complete. A new student re-examined the problem and located additional TSs. It turns out that there are two conformations of proline, Honk explains. We had tested this out in model systems, and one conformation is preferred over the other. But it turns out that in some of the transition states, the second conformer is better. So now when we take into account all of the results, our predictions don t fit experiments so well. List then redid the experiments—and he got different results, too These reactions turn out to be extremely sensitive to the amount of water present. List is trying to get an experiment as close to anhydrous conditions as possible. The final picture is not yet clear.  

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