Philip Eaton, renowned chemist and ‘founder of cubane,’ 1936-2023

Prof. Emeritus Philip Eaton, a pioneering University of Chicago chemist widely recognized as the “founder of cubane”—a molecule previously thought impossible to create because of its geometry—died on July 21 at the age of 87.

Eaton was a renowned leader in the synthesis and study of highly strained compounds, which provide insight into the effect of strain on chemical bonding and reactivity. Known for his insatiable intellectual curiosity, Eaton pursued problems that pushed the boundaries of our understanding of chemistry and paved the way for many advances in the field of organic chemistry.

Eaton made his name in 1964 by successfully synthesizing the molecule cubane. As a result, cubane and its derivatives have become highly sought-after molecules for energy storage and have found numerous applications in materials science, pharmaceuticals, and explosives.

“To this day, it’s a landmark. If you look up a textbook on organic synthesis, Eaton’s cubane synthesis will be showcased,” said Prof. Viresh Rawal, Eaton’s colleague and chair of the UChicago Department of Chemistry. “It is often used to demonstrate the power of chemical synthesis and the ingenuity that such molecules inspire.”

‘Pushing the limit’

Philip Eugene Eaton was born on June 2, 1936, in New York City. He received his A.B. from Princeton in 1957 and completed his doctoral work at Harvard under the mentorship of Peter Yates. While at Harvard, Eaton made the landmark discovery of Lewis acid catalysis of the Diels-Alder reaction, the results of which paved the way for innumerable advances in organic chemistry, actively expanding the impact and possibilities of the field.

“He was always interested in pushing the limit of what’s understood in terms of reactivity,” said Rawal. “So he would work on things that were considered to be improbable.”

After a brief assistant professorship at the University of California, Berkeley, Eaton joined the University of Chicago faculty in 1962. In just two short years, he would synthesize the cubane molecule that made him famous.

The cubane name derives from the cube-shaped geometry of the molecule. Since carbon normally bonds at angles of 109.5 degrees, the forced 90-degree angles of the cube framework introduce a high degree of strain into the molecule—so much so that prior to Eaton’s seminal synthesis, most chemists and theoreticians deemed the very existence of the molecule impossible.

“Not only did Phil synthesize cubane, but he did so by a very creative strategy that used photochemistry to excite the molecule into a cage structure and a ring contracting reaction to attain the desired carbon framework,” said Rawal.

Eaton’s synthesis proved that cubane—although thermodynamically unstable—was kinetically extremely stable. In fact, the molecule previously thought to be too highly strained to exist was stable enough to be stored indefinitely in a vial in the lab.

He went on to synthesize a host of other highly strained, structurally exceptional organic molecules, such as cubane, pentaprismane, propellanes, paddlanes and octanitrocubane—all of which he used to probe the effects and limits of molecular bonding.

Profound changes

While Eaton’s contributions to organic chemistry are profound, his work continues to shape current thinking about synthesis and reactivity. His examination of new ring systems specifically designed to probe the effects of molecular geometry on bonding, reactivity, and strain brought him many other successes in synthesizing what are known in chemistry as “unnatural compounds.”

“Phil said one thing to me that I remember to this day,” said Chuan He, Eaton’s colleague and the John T. Wilson Distinguished Service Professor of Chemistry. “He said: ‘So many people work on natural products; I decided to work on unnatural products.’ I think that captures the essence of the University of Chicago. We strive to work on things that are different, unique or sometimes unpopular.”

Eaton continued to explore cubane throughout the rest of his career and, in 1999, successfully synthesized octanitrocubane—a derivative of cubane that, according to Gregory Zayia, one of Eaton’s last PhD students, represented the ultimate achievement in the development of explosives tracing back to the discovery of trinitrotoluene (better known as TNT) and Nobel’s work with nitroglycerine.

The successful synthesis of this great white whale of the unnatural products world represented the culmination of an intensive two-decade quest by the Eaton group and necessitated the development of a considerable amount of new and important chemistry along the way, Zayia said. “The colossal synthetic achievement was even reported in The New York Times—a testament to its significance.”

Eaton was a devoted husband. His beloved wife, Phyllis, preceded him in death by less than two months.

In addition to his chemical innovations, Eaton is remembered as a caring and generous educator. One former student recalled that Eaton provided symphony, theater and opera tickets for his students to encourage their cultural growth beyond the laboratory. Eaton also enjoyed travel, art and architecture.

Speaking of Eaton’s time at the University of Chicago, Rawal said: “Phil was an inspiring teacher to thousands of students and a research mentor to scores of graduate students and postdoctoral associates. He will be greatly missed.”