Robert Woodward

**Robert Burns Woodward** (April 10, 1917 – July 8, 1979) was an American organic chemist. He made many important discoveries in modern organic chemistry. He worked on the synthesis and structure of complex natural products. He worked closely with Roald Hoffmann on the theory of chemical reactions. Woodward won the Nobel Prize in Chemistry for 1965.

## Early life and education

Woodward was born in Boston, Massachusetts. When he was one year old, his father died in the influenza pandemic of 1918.

He was interested in chemistry at an early age. By the time he entered high school, he had already done most of the experiments in Ludwig Gattermann's textbook of experimental organic chemistry. In 1928, Woodward asked the Consul-General of the German consulate in Boston, to send him copies of a few original papers published in German journals. He was fascinated to read Otto Diels and Kurt Alder's original communication about the Diels–Alder reaction.

In 1933, he entered the Massachusetts Institute of Technology (MIT), but did not do well enough to continue. MIT readmitted him in 1935, and by 1936 he had received the Bachelor of Science degree. Only one year later, MIT awarded him the doctorate. This was very unusual at the time, because most MIT students earned only a Bachelor of Science degree after four years. Woodward's studies were about the synthesis of the female sex hormone estrone, a natural type of estrogen. He held a Junior Fellowship at Harvard University from 1937 to 1938, and stayed at Harvard for the rest of his life. In the 1960s, Woodward was named Donner Professor of Science, a post which allowed him to spend all his time on research.

## Early work

In the early 1940s Wooward was using ultraviolet spectroscopy to discover the structure of natural products. Woodward collected a large amount of information, and then worked out a series of rules, later called the Woodward's rules. These rules could be used to find out the structures of new natural products, as well as non-natural synthesized molecules. Woodward was always quick to use newly developed techniques. Woodward's discovery saved chemists from spending a lot of time using chemical methods to work out the structures of compounds.

In 1944 Woodward and William von Eggers Doering reported the synthesis of the alkaloid quinine, used to treat malaria. The synthesis was a breakthrough, as quinine was hard to get from Japanese occupied southeast Asia. In fact, Woodward's method could not be used on a practical scale, but it was a landmark for chemical synthesis. Organic synthesis was still largely a matter of trial and error, and nobody thought such complex structures could actually be constructed. Woodward showed that organic synthesis could be made into a science. Woodward's synthesis of quinine was the first of many of his very complicated and elegant syntheses.

## Later work and its impact

By the 1930s, the British chemists Christopher Ingold and Robert Robinson among others had studied the mechanisms of organic reactions. They had come up with rules which could predict reactivity of organic molecules. Woodward was probably the first synthetic organic chemist who used these rules to predict what steps would work in a synthesis.

### Organic syntheses and Nobel Prize

During the late 1940s, Woodward synthesized many complex natural products including quinine, cholesterol, cortisone, strychnine, lysergic acid, reserpine, chlorophyll, cephalosporin, and colchicine. With these, Woodward opened up a new era of synthesis, sometimes called the 'Woodwardian era'. He showed that natural products could be synthesized by careful applications of the principles of physical organic chemistry, and by very careful planning.

Many of Woodward's syntheses were described as spectacular by his colleagues. Before he did them, some people thought it would be impossible to create these substances in the lab. Woodward's syntheses were also described as having an element of art in them, and since then, synthetic chemists have always looked for elegance as well as utility in synthesis. His work also involved the exhaustive use of the then newly developed techniques of infrared spectroscopy and later, nuclear magnetic resonance spectroscopy. Another important feature of Woodward's syntheses was their attention to stereochemistry or the particular configuration of molecules in three dimensional space. Most natural products of medicinal importance are effective, for example as drugs, only when they possess a specific stereochemistry. This creates the demand for 'stereospecific synthesis', producing a compound with a defined stereochemistry. Woodward was a pioneer in showing how one could conduct reactions that were stereospecific. Many of his syntheses involved forcing a molecule into a certain configuration by installing rigid structural elements in it, another tactic that has become standard today. In this regard, especially his syntheses of reserpine and strychnine were landmarks.

During World War II, Woodward was an advisor to the War Production Board on the penicillin project.
Woodward also applied the technique of infrared spectroscopy and chemical degradation to determine the structures of complicated molecules. Notable among these structure determinations were santonic acid, strychnine, magnamycin and terramycin.  About terramycin, Woodward's colleague and Nobel Laureate Derek Barton said:
> "The most brilliant analysis ever done on a structural puzzle was surely the solution (1953) of the terramycin problem. It was a problem of great industrial importance, and hence many able chemists had performed an enormous amount of work trying to determine the structure. There seemed to be too much data to resolve the problem, because a significant number of observations, although experimentally correct, were very misleading. Woodward took a large piece of cardboard, wrote on it all the facts and, by thought alone, deduced the correct structure for terramycin. Nobody else could have done that at the time."

In each one of these cases, Woodward again showed how rational facts and chemical principles, combined with chemical intuition, could be used to achieve the task.

In the early 1950s, Woodward, and British chemist Geoffrey Wilkinson, proposed a structure for ferrocene, a compound consisting of a combination of an organic molecule with iron. This marked the beginning of the field of transition metal organometallic chemistry. The field later grew which grew to be important to the chemical industry. Wilkinson won the Nobel Prize for this work in 1973, with Ernst Otto Fischer. Some historians think that Woodward should have shared this prize along with Wilkinson. Woodward himself thought so, and voiced his thoughts in a letter sent to the Nobel Committee.

Woodward won the Nobel Prize in 1965 for his synthesis of complex organic molecules. In his Nobel lecture, he described the total synthesis of the antibiotic cephalosporin, and claimed that he had pushed the synthesis schedule so that it would be completed around the time of the Nobel ceremony.

### B<sub>12</sub> synthesis and Woodward-Hoffmann rules

In the early 1960s, Woodward began work on what was the most complex natural product synthesized to date- vitamin B<sub>12</sub>. In a remarkable collaboration with his colleague Albert Eschenmoser in Zurich, a team of almost one hundred students and postdoctoral workers worked for many years on the synthesis of this molecule. The work was finally published in 1973, and it marked a landmark in the history of organic chemistry. The synthesis included almost a hundred steps, and involved the rigorous planning and analyses that had always characterised Woodward's work. This work, more than any other, convinced organic chemists that the synthesis of any complex substance was possible, given enough time and planning. However, as of 2006, no other total synthesis of Vitamin B<sub>12</sub> has been published.

That same year, based on observations that Woodward had made during the B<sub>12</sub> synthesis, he and Roald Hoffmann devised rules (now called the Woodward–Hoffmann rules) for elucidating the stereochemistry of the products of organic reactions. Woodward based his ideas on his experiences as a synthetic organic chemist; he asked Hoffman to perform theoretical calculations to verify the ideas. This was done using Hoffmann's Extended Hückel method. The predictions of these rules were verified by many experiments. Hoffmann shared the 1981 Nobel Prize for this work along with Kenichi Fukui, a Japanese chemist who had done similar work using a different approach. Woodward had died two years before and so was not eligible to share this Prize.

A recent paper in the journal _Nature_ describes how mechanical stress can be used to reshape chemical reaction pathways to lead to products that apparently violate Woodward–Hoffman rules.

## Woodward Institute and later life

While at Harvard, Woodward took on the directorship of the
**Woodward Research Institute**, based at Basel, Switzerland in 1963. He also became a trustee of his alma mater, MIT, from 1966 to 1971, and of the Weizmann Institute of Science in Israel.

Woodward died in Cambridge, Massachusetts from a heart attack in his sleep. At the time, he was working on the synthesis of an antibiotic, erythromycin. A student of his said:

> "I owe a lot to Woodward. He showed me that one could attack difficult problems without a clear idea of their outcome, but with confidence that intelligence and effort would solve them. He showed me the beauty of modern organic chemistry, and the relevance to the field of detailed careful reasoning. He showed me that one does not need to specialize. Woodward made great contributions to the strategy of synthesis, to the deduction of difficult structures, to the invention of new chemistry, and to theoretical aspects as well. He taught his students by example the satisfaction that comes from total immersion in our science. I treasure the memory of my association with this remarkable chemist."

## Publications

During his lifetime, Woodward authored or coauthored almost 200 publications, of which 85 are full papers. The remainder comprising preliminary communications, the text of lectures, and reviews. The pace of his scientific activity soon outstripped his capacity to publish all experimental details, and much of the work in which he participated was not published until a few years after his death. Woodward trained more than two hundred Ph.D. students and postdoctoral workers, many of whom later went on to distinguished careers.

## Idiosyncrasies

His lectures were legendary and frequently used to last for three or four hours. [His longest known lecture defined the unit of time known as the "Woodward", and thereafter his other lectures were deemed to be so many "milli-Woodwards" long!] In many of these, he eschewed the use of slides and used to draw beautiful structures by using multicolored chalk. As a result, it was always easy to take good notes at a Woodward lecture. Typically, to begin a lecture, Woodward would arrive and lay out two large white handkerchiefs on the countertop.  Upon one would be four or five colors of chalk (new pieces), neatly sorted by color, in a long row.  Upon the other handkerchief would be placed an equally impressive row of cigarettes. The previous cigarette would be used to light the next one.  His famous Thursday seminars at Harvard often lasted well into the night. He had a fixation with blue, and all his suits, his car, and even his parking space were coloured in blue. In one of his laboratories, his students hung a large black and white photograph of the master from the ceiling, complete with a large blue "tie" appended. There it hung for some years (early 1970s), until scorched in a minor laboratory fire.  He detested exercise, could get along with only a few hours of sleep every night, was a heavy smoker, and enjoyed Scotch whisky and a martini or two. Hoffmann would correspond with Woodward using blue paper.

## Sources

1. Robert Burns Woodward: Architect and Artist in the World of Molecules; Otto Theodor Benfey, Peter J. T. Morris, Chemical Heritage Foundation, April 2001.
1. Robert Burns Woodward and the Art of Organic Synthesis: To Accompany an Exhibit by the Beckman Center for the History of Chemistry (Publication / Beckman Center for the History of Chemistry); Mary E. Bowden; Chemical Heritage Foundation, March 1992

## Other websites

- Robert Burns Woodward
- Video podcast of Robert Burns Woodward talking about cephalosporin

## Infobox (scientist)

- **name**: Robert Woodward
- **image**: Robert Burns Woodward in 1965.jpg
- **birth place**: Boston, Massachusetts
- **death place**: Cambridge, Massachusetts
- **citizenship**: United States
- **field**: Organic chemistry
- **work institution**: Harvard University
- **alma mater**: Massachusetts Institute of Technology, MIT
- **doctoral students**: Harry Wasserman, Ronald Breslow, Stuart Schreiber, Ken Houk, William R. Roush
- **known for**: Organic syntheses, solution of several important structural puzzles, Woodward-Hoffmann rules
- **prizes**: National Medal of Science (1964)
  Nobel Prize in Chemistry (1965)
  Copley Medal (1978)