New paper describes race between groups at UCLA and the Fukui Institute to determine the mechanism of a novel rearrangement discovered in Stoltz lab at Caltech.
Published in the Journal of the American Chemical Society (JACS), the article describes the race to determine the mechanism of a novel rearrangement discovered in the lab of Professor Brian Stoltz at the California Institute of Technology (Caltech).
After working for nearly a year, Professor Ken Houk’s group at UCLA, using traditional methods, and Professor Keiji Morokuma’s group at the Fukui Institute, using automatic methods, were both able to come up with the same exact mechanism, which surprised Houk and other researchers.
How did this come about? Houk explains:
In the course of Stoltz’s group synthesis of natural product curcusone C, an unexpected rearrangement was encountered:
While a sequence of Cope rearrangement and [1r,3s]-sigmatropic shift would effect the transformation, the latter is an unknown, and thermally forbidden according to the Woodward-Hoffmann rules, reaction. Computations by the Houk group established this as a very high energy process. A serious computational study began.
At this time, Houk heard Professor Keiji Morokuma give a talk about his work with Professor Satoshi Maeda, now at Hokkaido, on automatic procedures to identify mechanisms computationally. These methods, AFIR (Automatic Force Induced Reactions) is part of the GRRM (Global Reaction Route Map) developed by Maeda were demonstrated to be useful for a variety of reactions. Morokuma agreed that his group would use this method, while Houk’s group would use the traditional method, exploring the energetics of a variety of plausible pathways to find a mechanistic route.
In the event, both computational groups were able, after about a year, to come up with a mechanism, and it was the same mechanism! The contest was a dead heat! The mechanism involves 5 different thermally allowed sigmatropic shifts: Cope, 1,5-sigmatropic silyl, Claisen, retro-Claisen, and 1,5-sigmatropic shifts, a veritable cornucopia of pericylic reactions! In fact, Huw Davies’s group at Emory had observed previously a related rearrangement involving several of these step.
The sad aspect of this story is that one of the principals, the world-renown computational chemist, Professor Keiji Morokuma, passed away on November 27, 2107, as this work was in progress. Morokuma built an international reputation, first at the University of Rochester, then the Institute for Molecular Science in Okazaki, Japan, then Emory University, and finally at the Fukui Institute in Kyoto.
The experimental discovery of the rearrangement was due to graduate student Chung Whan Lee in Stoltz’s lab. The computational work was performed in Houk’s lab by former postdoctoral researcher Dr. Buck Taylor, now professor at the University of Portland, and Dr. Ashay Patel, now a postdoctoral researcher at UC San Diego, and in Morokuma’s lab by postdoctoral researcher Dr. Galina P. Petrova.
Penny Jennings, Communications Manager, UCLA Department of Chemistry & Biochemistry, penny@chem.ucla.edu.
