Robert Burns Woodward

Robert Burns Woodward
Born	(1917-04-10)April 10, 1917 Boston, Massachusetts, U.S.
Died	July 8, 1979(1979-07-08) (aged 62) Cambridge, Massachusetts, U.S.
Citizenship	United States
Fields	Organic chemistry
Institutions	Harvard University
Alma mater	MIT
Doctoral students	Harry Wasserman Christopher Foote Ken Houk Ronald Breslow Stuart Schreiber William R. Roush
Known for	Landmark organic syntheses Woodward cis-hydroxylation Molecular structure determination Woodward–Hoffmann rules
Notable awards	ForMemRS (1956)[1] Davy Medal (1959) National Medal of Science (1964) Nobel Prize in Chemistry (1965) Willard Gibbs Award (1967) Copley Medal (1978)

Robert Burns Woodward (April 10, 1917 – July 8, 1979) was an American organic chemist. He is considered by many to be the preeminent organic chemist of the twentieth century,^[2] having made many key contributions to the subject, especially in the synthesis of complex natural products and the determination of their molecular structure. He also worked closely with Roald Hoffmann on theoretical studies of chemical reactions. He was awarded the Nobel Prize in Chemistry in 1965.

Early life and education

Woodward was born in Boston, Massachusetts, to Margaret (née Burns, an immigrant from Scotland) and Arthur Chester Woodward, son of Roxbury, Massachusetts apothecary, Harlow Elliot Woodward. When Robert was one year old, his father died in the flu pandemic of 1918.

From a very early age, Woodward was attracted to and engaged in private study of chemistry while he attended a public primary school, and then Quincy High School,^[3] in Quincy, Massachusetts. By the time he entered high school, he had already managed to perform most of the experiments in Ludwig Gattermann's then widely used textbook of experimental organic chemistry. In 1928, Woodward contacted the Consul-General of the German consulate in Boston (Baron von Tippelskirch ^[4]), and through him, managed to obtain copies of a few original papers published in German journals. Later, in his Cope lecture, he recalled how he had been fascinated when, among these papers, he chanced upon Diels and Alder's original communication about the Diels–Alder reaction. Throughout his career, Woodward was to repeatedly and powerfully use and investigate this reaction, both in theoretical and experimental ways. In 1933, he entered the Massachusetts Institute of Technology (MIT), but neglected his formal studies badly enough to be excluded at the end of the 1934 fall term. MIT readmitted him in the 1935 fall term, and by 1936 he had received the Bachelor of Science degree. Only one year later, MIT awarded him the doctorate, when his classmates were still graduating with their bachelor's degrees.^[5] Woodward's doctoral work involved investigations related to the synthesis of the female sex hormone estrone.^[6] MIT required that graduate students have research advisors. Woodward's advisors were James Flack Norris and Avery Adrian Morton,^[7] although it is not clear whether he actually took any of their advice. After a short postdoctoral stint at the University of Illinois, he took a Junior Fellowship at Harvard University from 1937 to 1938, and remained at Harvard in various capacities for the rest of his life. In the 1960s, Woodward was named Donner Professor of Science, a title that freed him from teaching formal courses so that he could devote his entire time to research.

Research and career

Early work

The first major contribution of Woodward's career in the early 1940s was a series of papers describing the application of ultraviolet spectroscopy in the elucidation of the structure of natural products. Woodward collected together a large amount of empirical data, and then devised a series of rules later called the Woodward's rules, which could be applied to finding out the structures of new natural substances, as well as non-natural synthesized molecules. The expedient use of newly developed instrumental techniques was a characteristic Woodward exemplified throughout his career, and it marked a radical change from the extremely tedious and long chemical methods of structural elucidation that had been used until then.

In 1944, with his post doctoral researcher, William von Eggers Doering, Woodward reported the synthesis of the alkaloid quinine, used to treat malaria. Although the synthesis was publicized as a breakthrough in procuring the hard to get medicinal compound from Japanese occupied southeast Asia, in reality it was too long and tedious to adopt on a practical scale. Nevertheless, it was a landmark for chemical synthesis. Woodward's particular insight in this synthesis was to realise that the German chemist Paul Rabe had converted a precursor of quinine called quinotoxine to quinine in 1905. Hence, a synthesis of quinotoxine (which Woodward actually synthesized) would establish a route to synthesizing quinine. When Woodward accomplished this feat, organic synthesis was still largely a matter of trial and error, and nobody thought that such complex structures could actually be constructed. Woodward showed that organic synthesis could be made into a rational science, and that synthesis could be aided by well-established principles of reactivity and structure. This synthesis was the first one in a series of exceedingly complicated and elegant syntheses that he would undertake.

Later work and its impact

Woodward talked about Chlorophyll in 1965

Culminating in the 1930s, the British chemists Christopher Ingold and Robert Robinson among others had investigated the mechanisms of organic reactions, and had come up with empirical rules which could predict reactivity of organic molecules. Woodward was perhaps the first synthetic organic chemist who used these ideas as a predictive framework in synthesis. Woodward's style was the inspiration for the work of hundreds of successive synthetic chemists who synthesized medicinally important and structurally complex natural products.

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.^[8] With these, Woodward opened up a new era of synthesis, sometimes called the 'Woodwardian era' in which he showed that natural products could be synthesized by careful applications of the principles of physical organic chemistry, and by meticulous planning.

Many of Woodward's syntheses were described as spectacular by his colleagues and before he did them, it was thought by some that 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 'stereoselective synthesis', producing a compound with a defined stereochemistry. While today a typical synthetic route routinely involves such a procedure, Woodward was a pioneer in showing how, with exhaustive and rational planning, one could conduct reactions that were stereoselective. 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. Although often given credit for proposing the beta-lactam structure of penicillin, it was actually first proposed by chemists at Merck and Edward Abraham at Oxford and then investigated by other groups, as well (e.g., Shell). Woodward at first endorsed an incorrect tricyclic (thiazolidine fused, amino bridged oxazinone) structure put forth by the penicillin group at Peoria. Subsequently, he put his imprimatur on the beta-lactam structure, all of this in opposition to the thiazolidine–oxazolone structure proposed by Robert Robinson, the then leading organic chemist of his generation. Ultimately, the beta-lactam structure was shown to be correct by Dorothy Hodgkin using X-ray crystallography in 1945.

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, along with the British chemist Geoffrey Wilkinson, then at Harvard, postulated a novel structure for ferrocene, a compound consisting of a combination of an organic molecule with iron.^[9] This marked the beginning of the field of transition metal organometallic chemistry which grew into an industrially very significant field.^[10] Wilkinson won the Nobel Prize for this work in 1973, along with Ernst Otto Fischer.^[11] Some historians think that Woodward should have shared this prize along with Wilkinson. Remarkably, Woodward himself thought so, and voiced his thoughts in a letter sent to the Nobel Committee.^[12]

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.

B₁₂ synthesis and Woodward–Hoffmann rules

In the early 1960s, Woodward began work on what was the most complex natural product synthesized to date—vitamin B₁₂. 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 characteristic 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 (see also palytoxin, synthesized by the research group of Yoshito Kishi, one of Woodward's postdoctoral students). As of 2016, no other total synthesis of Vitamin B₁₂ has been published.

That same year, based on observations that Woodward had made during the B₁₂ synthesis, he and Roald Hoffmann devised rules (now called the Woodward–Hoffmann rules) for elucidating the stereochemistry of the products of organic reactions.^[13] Woodward formulated his ideas (which were based on the symmetry properties of molecular orbitals) based on his experiences as a synthetic organic chemist; he asked Hoffman to perform theoretical calculations to verify these ideas, which were done using Hoffmann's Extended Hückel method. The predictions of these rules, called the "Woodward–Hoffmann 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 in 1979 and Nobel Prizes are not awarded posthumously.

Woodward Institute

While at Harvard, Woodward took on the directorship of the Woodward Research Institute, based at Basel, Switzerland, in 1963.^[14] 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 about him:

I owe a lot to R. B. 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.

Some of his best-known students include Robert M. Williams (Colorado State), Harry Wasserman (Yale), Yoshito Kishi (Harvard), Stuart Schreiber (Harvard), William R. Roush (Scripps-Florida), Steven A. Benner (UF), Christopher S. Foote (UCLA), Kendall Houk (UCLA), porphyrin chemist Kevin M. Smith, Ronald Breslow (Columbia University) and David Dolphin (UBC).

Woodward had an encyclopaedic knowledge of chemistry, and an extraordinary memory for detail.^[15] Probably the quality that most set him apart from his peers was his remarkable ability to tie together disparate threads of knowledge from the chemical literature and bring them to bear on a chemical problem.^[15]

Honors and awards

For his work, Woodward received many awards, honors and honorary doctorates, including election to the National Academy of Sciences in 1953, and membership in academies around the world. He was also a consultant to many companies such as Polaroid, Pfizer, and Merck. Other awards include:

Honorary degrees

Woodward also received over twenty honorary degrees,^[17] including honorary doctorates from the following universities:

Personal life

Family

In 1938 he married Irja Pullman; they had two daughters: Siiri Anna (b. 1939) and Jean Kirsten (b. 1944). In 1946, he married Eudoxia Muller, an artist and technician whom he met at the Polaroid Corp. This marriage, which lasted until 1972, produced a daughter, and a son: Crystal Elisabeth (b. 1947), and Eric Richard Arthur (b. 1953).^[5]

Idiosyncrasies

His lectures frequently lasted for three or four hours. ^[4] His longest known lecture defined the unit of time known as the "Woodward", after which his other lectures were deemed to be so many "milli-Woodwards" long.^[18] In many of these, he eschewed the use of slides and drew structures by using multicolored chalk. 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 Thursday seminars at Harvard often lasted well into the night. He had a fixation with blue, and many of his suits, his car, and even his parking space were coloured in blue.^[4] 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 martinis.^[1][19]

References

Bibliography

Laureates of the Nobel Prize in Chemistry
1901–1925	1901 Jacobus van 't Hoff 1902 Emil Fischer 1903 Svante Arrhenius 1904 William Ramsay 1905 Adolf von Baeyer 1906 Henri Moissan 1907 Eduard Buchner 1908 Ernest Rutherford 1909 Wilhelm Ostwald 1910 Otto Wallach 1911 Marie Curie 1912 Victor Grignard / Paul Sabatier 1913 Alfred Werner 1914 Theodore Richards 1915 Richard Willstätter 1916 1917 1918 Fritz Haber 1919 1920 Walther Nernst 1921 Frederick Soddy 1922 Francis Aston 1923 Fritz Pregl 1924 1925 Richard Zsigmondy
1926–1950	1926 Theodor Svedberg 1927 Heinrich Wieland 1928 Adolf Windaus 1929 Arthur Harden / Hans von Euler-Chelpin 1930 Hans Fischer 1931 Carl Bosch / Friedrich Bergius 1932 Irving Langmuir 1933 1934 Harold Urey 1935 Frédéric Joliot-Curie / Irène Joliot-Curie 1936 Peter Debye 1937 Norman Haworth / Paul Karrer 1938 Richard Kuhn 1939 Adolf Butenandt / Leopold Ružička 1940 1941 1942 1943 George de Hevesy 1944 Otto Hahn 1945 Artturi Virtanen 1946 James B. Sumner / John Northrop / Wendell Meredith Stanley 1947 Robert Robinson 1948 Arne Tiselius 1949 William Giauque 1950 Otto Diels / Kurt Alder
1951–1975	1951 Edwin McMillan / Glenn T. Seaborg 1952 Archer Martin / Richard Synge 1953 Hermann Staudinger 1954 Linus Pauling 1955 Vincent du Vigneaud 1956 Cyril Hinshelwood / Nikolay Semyonov 1957 Alexander Todd 1958 Frederick Sanger 1959 Jaroslav Heyrovský 1960 Willard Libby 1961 Melvin Calvin 1962 Max Perutz / John Kendrew 1963 Karl Ziegler / Giulio Natta 1964 Dorothy Hodgkin 1965 Robert Woodward 1966 Robert S. Mulliken 1967 Manfred Eigen / Ronald Norrish / George Porter 1968 Lars Onsager 1969 Derek Barton / Odd Hassel 1970 Luis Federico Leloir 1971 Gerhard Herzberg 1972 Christian B. Anfinsen / Stanford Moore / William Stein 1973 Ernst Otto Fischer / Geoffrey Wilkinson 1974 Paul Flory 1975 John Cornforth / Vladimir Prelog
1976–2000	1976 William Lipscomb 1977 Ilya Prigogine 1978 Peter D. Mitchell 1979 Herbert C. Brown / Georg Wittig 1980 Paul Berg / Walter Gilbert / Frederick Sanger 1981 Kenichi Fukui / Roald Hoffmann 1982 Aaron Klug 1983 Henry Taube 1984 Robert Merrifield 1985 Herbert A. Hauptman / Jerome Karle 1986 Dudley R. Herschbach / Yuan T. Lee / John Polanyi 1987 Donald J. Cram / Jean-Marie Lehn / Charles J. Pedersen 1988 Johann Deisenhofer / Robert Huber / Hartmut Michel 1989 Sidney Altman / Thomas Cech 1990 Elias Corey 1991 Richard R. Ernst 1992 Rudolph A. Marcus 1993 Kary Mullis / Michael Smith 1994 George Olah 1995 Paul J. Crutzen / Mario J. Molina / Frank Rowland 1996 Robert Curl / Harold Kroto / Richard Smalley 1997 Paul D. Boyer / John E. Walker / Jens Christian Skou 1998 Walter Kohn / John Pople 1999 Ahmed Zewail 2000 Alan J. Heeger / Alan MacDiarmid / Hideki Shirakawa
2001–present	2001 William Knowles / Ryoji Noyori / K. Barry Sharpless 2002 John B. Fenn / Koichi Tanaka / Kurt Wüthrich 2003 Peter Agre / Roderick MacKinnon 2004 Aaron Ciechanover / Avram Hershko / Irwin Rose 2005 Robert H. Grubbs / Richard R. Schrock / Yves Chauvin 2006 Roger D. Kornberg 2007 Gerhard Ertl 2008 Osamu Shimomura / Martin Chalfie / Roger Y. Tsien 2009 Venkatraman Ramakrishnan / Thomas A. Steitz / Ada E. Yonath 2010 Richard F. Heck / Akira Suzuki / Ei-ichi Negishi 2011 Dan Shechtman 2012 Robert Lefkowitz / Brian Kobilka 2013 Martin Karplus / Michael Levitt / Arieh Warshel 2014 Eric Betzig / Stefan Hell / William E. Moerner 2015 Tomas Lindahl / Paul L. Modrich / Aziz Sancar 2016 Jean-Pierre Sauvage / Fraser Stoddart / Ben Feringa