Robert Burns Woodward

Organic Chemist

  • Born: April 10, 1917
  • Birthplace: Boston, Massachusetts
  • Died: July 8, 1979
  • Place of death: Cambridge, Massachusetts

American chemist

Woodward was the preeminent organic chemist in the postwar United States. Renowned for the total synthesis of complex natural products, for more than thirty years he achieved syntheses of unparalleled creativeness and elegance.

Area of achievement Chemistry

Early Life

Robert Burns Woodward was the only child born to Margaret Burns and Arthur Chester Woodward. His father died in October of 1918 at the age of thirty-three. His mother was a native of Glasgow, Scotland, and claimed descent from the poet Robert Burns. Young Woodward grew up in Quincy, near Boston, and attended its public schools. Chemistry attracted him from an early age, although he was vague on what started the interest. He indulged in this hobby in a home laboratory, fascinated from the start by the beauty of molecular structures. A gifted child, Woodward skipped grades three times, which enabled him to enroll at the Massachusetts Institute of Technology in 1933 at the age of sixteen. Possessing a staggering amount of chemical knowledge, he earned a Ph.D. from MIT within four years.

Woodward’s experiences at MIT were not positive at first. The slow pace of the curriculum led to boredom and inattention to his studies, to such an extent that he was requested not to return for his sophomore year. Some of the faculty, however, recognized his unusual capabilities and arranged a reinstatement which allowed him to forgo all requirements and class attendance as long as he took the course examinations. This unusual arrangement enabled him to devise his own program and take as many as fifteen courses in a semester. Furthermore, he requested laboratory space, then permitted only for graduate students; the faculty agreed to consider this if he would supply a list of experiments. His list was so original that he was given his own laboratory for the remainder of his stay at MIT. His doctoral dissertation was inspired by the lecture of a professor on the difficulties in synthesizing a sex hormone.

After a brief period in 1937 as instructor at the University of Illinois, Woodward returned to Boston, rising from Harvard University instructor to full professor in 1950, Morris Loeb Professor of Chemistry in 1953, and Donner Professor of Science in 1960, the latter position freeing him from lecturing.

Woodward was married twice, to Irja Pullman, whom he had known for many years, in 1938, and to Eudoxia Muller, a Polaroid consultant, in 1946; there were two children from each marriage. His passion for chemistry and his habit of pursuing it during all hours of the day and night made him difficult to live with, and both marriages ended in divorce.

Woodward was a tall, powerfully built man, very neat and well-groomed, his daily attire including a dark blue suit and a plain, light-blue necktie. He was addicted to puzzles and games and enjoyed being the life of a party, taking great pleasure as a storyteller. He developed a deep interest in literature of all types, especially biography. Woodward was an inveterate smoker and a heavy drinker of whiskey. From his youth onward, he normally slept only three hours a day. This ability to do without sleep, coupled with his incessant smoking and heavy consumption of alcohol, led him to believe that he was different from other people and would not be subject to the frailties of others. A lone wolf throughout his life, he made few intimate friends and, despite appearances, he was a very lonely human being.

Life’s Work

When Woodward began his research at Harvard, synthetic organic chemistry had major limitations. Chemists were still using the same techniques of separation and purification of natural products as had chemists of 1890. To obtain a total synthesis of a natural product was an enormous challenge, especially with the lack of control over the essential three-dimensional arrangement of atoms in space (stereochemistry). Yet Woodward chose to specialize in this realm of naturally occurring animal and plant substances because it was one of endless fascination and unlimited opportunities.

Woodward’s success lay in combining two contemporary developments in chemistry. An instrumental revolution was taking place during his research career, with ultraviolet, infrared, and nuclear magnetic resonance spectroscopy coming into general use by chemists as well as novel methods of chromatography for the separation and purification of substances. He combined these and other tools of the instrumental revolution with a master plan based on theoretical developments involving electronic reaction mechanisms. He could determine theoretically how chemical bonds form, break, and rearrange, and the stereochemical configurations that would result, and envisage the entire synthetic route before any laboratory work was done. In this way, Woodward made organic synthesis into both an art of creative planning and design and an experimental science involving hard, tedious laboratory work. A typical Woodward synthesis was noted for its planning. In the execution of the plan, he rarely took a physical part. His reputation assured him of coworkers of high quality; his role was to direct and inspire them.

The revolution in organic synthesis was first announced in 1944 when Woodward, along with another brilliant young chemist, William Doering, synthesized the antimalarial drug quinine. It was important enough to make page one of The New York Times, since it was part of the World War II effort to find quinine substitutes. (Natural quinine came from cinchona tree bark, and the plantations were in Japanese control.) Woodward and Doering achieved the synthesis in fourteen months, starting with a common coal-tar derivative, and showed what could be done with an original plan, the mapping of every step, and resourceful experimental work.

Following the quinine synthesis, Woodward turned to another important wartime project: penicillin, then a strategic material desperately needed to combat infections. In 1945, he was the first to propose, defend, and show the consequences of the fused ring structure basic to all penicillins. He continued to make important contributions to antibiotic research over the years. He investigated the broad spectrum antibiotics terramycin and aureomycin following their discovery, establishing the complete structures of these tetracyclic molecules by 1952.

After the war, Woodward continued to pursue problems of structure determination and synthesis. In 1947, he solved the structure of the complex natural poison strychnine in a brilliant interpretation of an array of experimental data and transformations. He also synthesized strychnine in 1954; it was one of several important syntheses of alkaloid drugs.

Woodward made headlines again in 1951 with the first total synthesis of a natural steroid. After sixteen months of hard work, involving twenty steps from a coal-tar derivative, he obtained the steroid nucleus, which, since many steroids had already been interconverted, represented a synthesis of many of them, such as cortisone and cholesterol. Time and Newsweek featured stories and interviews with him. Cortisone, made with difficulty from oxbile, was scarce and expensive. His synthesis was from relatively cheap coal tar and promised an abundance of the antiarthritis drug. Woodward tried to dampen the enthusiasm; his was only a laboratory synthesis. In fact, his feat was practical, and cortisone came to be provided to arthritis sufferers in synthetic form.

While most of his synthetic work concerned natural products, Woodward made important contributions to other areas. In 1952, in one of his most inspired insights, he revealed the structure of dicyclopentadienyl iron or “ferrocene,” as he named it. Discovered in 1951, its nature was intensely debated, and Woodward daringly proposed the famed sandwich structure of an atom of iron sandwiched between two cyclopentadienyl rings. This was a new type of organometallic substance and the basis of a new class of molecules having unique pi electron binding. (Pi bonding refers to modern molecular orbital theory in organic chemistry.)

One brilliant synthesis after another marked the 1950’s. Woodward followed the 1954 synthesis of lysergic acid, the basis for the hallucinogenic drug LSD, with a masterful synthesis in 1956 of reserpine the first of the tranquilizing drugs. The reserpine synthesis stood out for its complete stereospecificity and high yield; it was the most elegant synthesis ever achieved and, as with cortisone, so well done that his plan could be adapted to commercial production.

Woodward kept reaching for higher levels of complexity and took on the challenge of chlorophyll, the green pigment in plants responsible for the conversion of solar energy into the basic materials of life. The synthesis took four years (1956-1960) of work by his dedicated research group of Harvard graduate students and postdoctoral fellows.

The year 1965 was noteworthy for two developments. The first was Woodward winning the Nobel Prize “for his outstanding achievement in the art of organic synthesis.” The wording is significant; the honor was not only for the synthesis of natural products but also for the distinctive way that the synthesis was achieved. Interestingly, in his address on receiving the prize, Woodward did not reflect on his past accomplishments but used the occasion to illuminate the “art” of synthesis by reporting on his latest work, the synthesis of the antibiotic cephalosporin C.

The cephalosporin work was not done at Harvard, for in 1963, Woodward acquired a second research group with the creation of the Woodward Research Institute in Basel, Switzerland, by Ciba Limited, with Woodward as director; like Harvard, it became a center of impressive achievements.

Also in 1965 came what may have been Woodward’s most significant contribution to organic chemistry. He was deeply interested in theoretical chemistry and had published in this area from time to time. With a distinguished collaborator, Roald Hoffmann (a Cornell professor and Nobel Prize winner in 1981), Woodward disclosed a new principle, the conservation of orbital symmetry. This discovery has been quoted more frequently than anything else he published. The conception came out of his synthetic work in which some puzzling stereochemical phenomena appeared. Baffled, he and Hoffmann eventually realized that something fundamental was behind the unexpected results. The explanation was the conservation of orbital symmetry, a quantum mechanical description of chemical bonding and reactivity, extending it to the course and stereochemistry of organic reactions and allowing for the prediction of both the way a reaction would proceed and the stereochemistry of the products. This principle stands as one of the most basic theoretical advances in the history of organic chemistry and almost immediately changed profoundly the thinking of chemists.

The most formidable problem undertaken by Woodward was the total synthesis of vitamin B12; its complexity was greater than anything he had ever encountered. With another collaborator, Albert Eschenmoser of Zurich, and about one hundred coworkers, Woodward devised a strategy involving a pyrotechnic display of appearing and disappearing rings with the vitamin appearing at the end of an eleven-year hunt in 1972.

Woodward never stopped working; there were always more challenges. From his Basel group came the synthesis of a prostaglandin in 1973, a member of the relatively new and fascinating class of biologically active substances. He even joined with Hoffman after a ten-year interval in an attempt to design some molecular systems with novel conducting properties, a new field to both men and testimony to his versatility. At the time of his death following a heart attack at his Cambridge home, he was planning the synthesis of another antibiotic.

In addition to the achievements that appeared in his publications, Woodward’s lectures and seminars were a major source of influence. He held lectureships worldwide, and few scientists could match the elegance, precision, and great artistic quality of his talks at the blackboard, with formulas and reaction sequences outlined in a unique graphic style that produced both clarity and aesthetic satisfaction. Every presentation was dramatic, creative, and lucid. Woodward enjoyed the attention that he commanded, relishing holding an audience enthralled for hours.

By the end of his life, Woodward had become the most honored of American scientists. In addition to the Nobel Prize, there was the National Medal of Science presented by President Johnson in 1964 and some thirty international awards, including the Pius XI Gold Medal of the Pontifical Academy of Sciences (1961) and the Order of the Rising Sun from Japan (1970). Some twenty-five universities in North America, Europe, Asia, and Australia awarded him honorary degrees, and almost all major scientific societies made him an honorary member. In 1979, in the announcement of his death released by Harvard, Woodward was described as “the greatest organic chemist of modern times.”

Significance

Woodward’s mastery of all available physical, instrumental, and theoretical methods guided him through the pathways of organic reactions and his astonishing array of achievements. He combined the three major strands in modern organic chemistry, the structural and synthetic, the physical and theoretical, and the instrumental, and set new standards of quality with his syntheses and structural elucidations of complex natural products. He taught others how to think and plan in detail; he taught theoreticians how to interact with experimentalists in the quest for solutions. Woodward represented a new generation of organic chemists who combined the best of modern theoretical and experimental methods in highly original and creative ways to solve incredibly complex and difficult problems.

Bibliography

Benfey, Otto Theodore, and Peter J. T. Morris, eds. Robert Burns Woodward: Architect and Artist in the World of Molecules. Philadelphia: Chemical Heritage Foundation, 2001. Collection of some of Woodward’s most important papers and lectures, with commentaries and photographs.

Berson, Jerome A. Chemical Creativity: Ideas from the World of Woodward, Hückel, Meerwein, and Others. New York: Wiley-VCH, 1999. A history of chemistry that charts how Woodward and others conceived new ideas that resulted in significant contributions to the field.

Dolphin, David. “Robert Burns Woodward: Three Score Years and Then?” Heterocycles 7 (December, 1977): 29-35. This issue of a Japanese journal was dedicated to Woodward on the occasion of his sixtieth birthday. Dolphin, a former student, gives a more detailed picture of the man, his character and habits, than does any other essay.

Nobel Foundation. Chemistry. New York: Elsevier, 1972. This volume includes the brief speech that accompanied the presentation of the Nobel Prize to Woodward; a biographical sketch; and the full text of Woodward’s lecture at the Nobel Prize ceremony.

Ollis, W. D. “Robert Burns Woodward An Appreciation.” Chemistry in Britain 16 (April, 1980): 210-216. Ollis, another former associate, gives the most lucid scientific account of Woodward’s researches in all major areas of endeavor.

Tarbell, D. Stanley. “Organic Chemistry: The Past 100 Years.” Chemical and Engineering News 54 (April 6, 1976): 110-123. This is an excellent account of the development of organic chemistry in the United States, considering Woodward’s predecessors and contemporaries, the development of methods and instruments, and how Woodward used these as well as what was novel and important about his work.

Todd, Lord Alexander R., and Sir John Cornforth. “Robert Burns Woodward.” Biographical Memoirs of Fellows of the Royal Society of London 27 (1981); 629-695. The only extensive study of Woodward. It contains listings of appointments, medals and awards, honorary degrees, and society memberships, and a seven-page bibliography of his 196 publications. Todd wrote the biographical section, and Cornforth wrote an analysis of the scientific work. While the biographical section is suitable reading for the layperson, the scientific analysis is probably too difficult for most readers.

Wassermann, Harry H. “Profile and Scientific Contributions of Professor R. B. Woodward.” Heterocycles 7 (December, 1977): 1-28. This article first appeared in a Japanese journal, in an issue dedicated to Woodward. Includes a bibliography and lists of awards and achievements comparable to those provided in the Royal Society article, as well as a coherent description of Woodward’s accomplishments.

1901-1940: 1906-1913: Willstätter Discovers the Composition of Chlorophyll.