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Houk’s group writes final chapter of Winstein’s Norbornyl saga

By Ken Houk

This article was originally published by UCLA Chemistry & Biochemistry

In 1949, in Haines Hall, the Chemistry building before the move to Young Hall in 1952, Professor Saul Winstein and his graduate student Daniel Trifan carried out experiments that led to a new paradigm of bonding in carbocations. These experiments created a controversy about the nature of the norbornyl cation and how it is formed.

75 years later, Professor Ken Houk and his group, led by former graduate student Dr. Woojin Lee, now a postdoc at the University of Southern California (USC), along with graduate student Tyler Benton and Dr. Arka Sengupta, have published a paper in the Journal of Organic Chemistry involving theoretical simulations that settle the remaining points of controversy.

Winstein was right, but that part became clear some time ago.

The simulations from the Houk group establish the timing of bonding changes during the reactions studied by Winstein and Trifan. Houk’s group modeled the reaction theoretically and explored the nature of the norbornyl cation in explicit acetic acid solvent. They made movies of the theoretical simulations that show the three-dimensional structures undergoing reactions and the behavior of the norbornyl cation in solution.

Winstein had proposed a revolutionary bridged structure of the norbornyl cation, shown below.

Professor Jack Roberts at the California Institute of Technology named this and related species “nonclassical ions” to emphasize the break from standard bonding theory of the time. The hypothetical “classical” norbornyl is also shown above.

Professor H.C. Brown of Purdue took exception to this claim and fought against Winstein, with experiments and words. Houk relates, “I saw the two speaking at a symposium in Utah in 1969. They were arguing vigorously and sometimes angrily on stage about the nature of the norbornyl cation. They even got personal at times, so sure were they of their correctness.” Winstein died six months later at the age of 57. He was likely to have won the Nobel Prize, had he lived. Brown did win the Nobel Prize for hydroboration ten years later.

Over the 54 years since Winstein’s death, enormous efforts by chemists have converged on a consensus that Winstein’s structural hypothesis was correct. He had only rate date to conceive the original idea in 1949, but since then, NMR experiments by the late Professor George Olah, and Professor Surya Prakash (now at USC), high accuracy quantum mechanical calculations of structure, and X-ray crystallographic measurements all indicated that Winstein was correct about the “nonclassical” structure of the norbornyl cation. What was missing was detailed time-resolved information about how the bridging reaction occurs and the structure and dynamics of the norbornyl in solution. Brown’s defenders suggested that solvent would favor the classical ion.

Houk’s group has now proven that Winstein’s claims are all valid. Beginning with theoretical developments and computations by Benton and then a full exploration reported in the paper by Lee, the group resolved the final issue that was still of interest to the organic chemistry community – what is the timing of bridging during the generation of norbornyl cation, and does solvation alter its structure.

Houk noted, “I am so excited to have established a connection to some of the great chemistry performed by Saul Winstein. I had the honor to be the Winstein Chair at UCLA from 2009-2021 (after Cram and Stoddart – both Nobelists – and before Abby Doyle, the current Winstein Chair). I have been the beneficiary of tremendous support and friendship from the Winstein family, the late Sylvia Winstein while I was Chair of our department, and now Carolee Winstein, Professor at USC, and her husband, Kip Thorne.”