Robert Burns Woodward

Robert Burns Woodward
Institutions	Harvard University
Nationality	American
Awards	Nobel Prize in Chemistry (1965)
Known for	Total synthesis of complex natural products
Occupation	Chemist
Field	Organic chemistry; organic synthesis
Wikidata	Q232316

Robert Burns Woodward (1917–1979) was an American chemist who set new standards in organic chemistry—the branch of science that studies carbon-containing molecules. A long-time professor at Harvard University, Woodward became famous for the total synthesis of complex natural molecules. Total synthesis is the art of building a molecule found in nature from simpler chemical pieces. In Merrill’s era, Woodward and his students achieved the first laboratory construction of many bioactive compounds, including the malaria drug quinine, the steroid cortisone (and related cholesterol), the alkaloids strychnine and reserpine, the plant pigment chlorophyll, and the vitamin B12 molecule. He also formulated widely used predictive rules in chemistry (such as the Woodward–Fieser UV absorption rules and the Woodward–Hoffmann rules for certain reactions). For these groundbreaking contributions—summarized as “outstanding achievements in the art of organic synthesis”—he received the Nobel Prize in Chemistry in 1965. In his lifetime Woodward was known for his brilliant insight, eloquent lectures, and insistence that chemistry could be as much art as science.

Early life and education

Robert Woodward was born on April 10, 1917, in Boston, Massachusetts. He was an only child; his father died when Woodward was less than two years old, so he was raised by his mother in Quincy, just south of Boston. From a young age Woodward showed exceptional curiosity and intellect. He reportedly skipped three years in school, completing both grammar and high school in nine years instead of twelve. As a youth he built a home laboratory in his basement and eagerly worked through experiments from a classic German chemistry manual. He even wrote to the German consul in Boston to request recent issues of chemistry journals. Through these efforts he taught himself many modern chemical reactions, such as the Diels–Alder reaction (a way to join two carbon rings) before he had even started college.

In 1933, at age 16, Woodward entered the Massachusetts Institute of Technology (MIT) to study chemistry; this was unusually young. At MIT he frustrated some professors by wanting to design his own course of study, but they accommodated his talent. He earned his Bachelor of Science degree in 1936 and, remarkably, completed his Ph.D. in 1937, all by age 20. His MIT doctoral work was done under Professor Warren R. Wagner, and it established Woodward as a rising star in chemistry.

Immediately after finishing at MIT, Woodward worked briefly as an instructor. In the fall of 1937 he joined Harvard University in Cambridge, Massachusetts, as an assistant to Professor Elmer Kohler. He remained at Harvard for the rest of his career. Over the next decades he moved up through the ranks: postdoctoral fellow (1937–1940), member of the Harvard Society of Fellows (1938–1940), and then instructor and assistant professor in the Chemistry department. He became a full professor in 1950. In 1953 he was named Morris Loeb Professor of Chemistry, and in 1960 he was appointed Donner Professor of Science. During World War II and afterward he also taught short courses, mentored students, and traveled to give lectures around the world. In 1963 the Swiss pharmaceutical firm Ciba (now part of Novartis) established a Woodward Research Institute in Basel and made Woodward its director; this cutting-edge laboratory brought together international scientists to pursue ambitious chemical projects.

Woodward married twice and had four children. He was known for heavy smoking and a personal flair (the story goes he collected blue neckties), but even friends remarked that he was happiest lecturing or working through problems on the blackboard. He did not enjoy formal teaching, preferring to teach in his lab or through public lectures. By his death in 1979 he had earned more than 20 honorary degrees and numerous medals from scientific societies around the world.

Major works and ideas

Woodward’s career is most famous for the total synthesis of complex molecules found in nature. These accomplishments demonstrated that very large and complicated structures could actually be built from simpler chemicals, proving the power of modern chemistry. One of his early breakthroughs was Correlating chemical structure with spectroscopic properties. In 1941–42, Woodward published papers showing how the ultraviolet (UV) light absorbed by an organic molecule depended on certain structural features, such as conjugated double bonds. From this work emerged the Woodward–Fieser rules (so named because later Harvard chemists Louis and Mary Fieser expanded them). These rules are empirical guidelines chemists use to predict the max wavelength of UV light absorbed by a compound, which in turn helps identify how many double bonds or rings the molecule has. In short, Woodward introduced the routine use of UV spectroscopy into organic chemistry and showed how it could be interpreted.

In 1944 Woodward gained worldwide fame with the formal total synthesis of quinine, the antimalarial drug. Quinine had been isolated from the bark of cinchona trees in the 19th century, but producing it in the lab had long been a challenge. Woodward and his co-author William von Eggers Doering published a 23-step synthetic route to quinine (they actually made an intermediate called quinotoxine, which could be converted to quinine by another published method). The synthesis was exquisitely planned, and Life magazine ran a story calling it a "century’s search" completed. However, it produced only about 30 milligrams of quinotoxine, making it impractical as a commercial process. Nevertheless, the achievement was a watershed: it proved that a chemist could design a multistep “blueprint” of reactions to assemble a natural drug, even if on minuscule scale.

Following quinine, Woodward tackled many other natural targets. He solved the structure of ferrocene (an iron-containing organic molecule) by collaborating with chemist Geoffrey Wilkinson in 1952; they proposed that ferrocene had a “sandwich” structure of iron between two flat carbon rings. The ferrocene discovery helped launch modern organometallic chemistry (Wilkinson eventually won a Nobel Prize for it). Woodward also synthetized important pharmaceuticals and biological compounds. In 1956 he published the first synthesis of reserpine, a complex alkaloid used to treat high blood pressure; this route used 32 steps and involved a remarkable trick of forcing a molecule into a strained conformation to fix its stereochemistry (arrangement in 3D space). In the late 1950s he and colleagues built steroids and related compounds: they made cholesterol and cortisone, among others, which are important in biology.

Perhaps Woodward’s grandest megaproject was chlorophyll, the green pigment in plants. Over four years (published in 1960), Woodward’s group assembled chlorophyll a through a multi-stage pathway. This was one of the largest syntheses of its time, combining multiple ring systems. It was partly a gamble based on Woodward’s insight that an advanced porphyrin (a four-ring structure) could be converted into chlorophyll under the right conditions. Finally in the 1970s he undertook vitamin B₁₂, a molecule much larger (about 100 atoms), with partner Albert Eschenmoser of Switzerland. After Woodward’s death, Eschenmoser and others completed the B₁₂ synthesis, which was heralded as one of chemistry’s greatest feats. Woodward’s lab was working on the antibiotic erythromycin when he suddenly died of a heart attack in 1979; his coworkers finished that synthesis later.

In the mid-1960s Woodward turned to a theoretical challenge and joined with Roald Hoffmann (a young scientist at Harvard) to study pericyclic reactions. Pericyclic reactions are a class of organic transformations that occur in a single concerted step, such as electrocyclic reactions and cycloadditions. Woodward and Hoffmann developed the Woodward–Hoffmann rules, based on quantum mechanistic arguments, to predict which such reactions would be allowed or forbidden. These rules explained why certain cyclic rearrangements occur only under heat or light. The collaboration between Woodward’s chemical intuition and Hoffmann’s expertise in molecular orbital theory provided a unifying principle for many reactions. (The Woodward–Hoffmann rules became so important that Hoffmann shared the Nobel Prize in 1981 for this work, although Woodward had passed away by then.)

Throughout his research Woodward made systematic use of modern laboratory instruments. He was one of the first organic chemists to apply infrared (IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy routinely to structure problems. These techniques allow chemists to deduce what functional groups are present and how atoms connect. He also used high-performance liquid chromatography (HPLC) for purification — an advanced method at the time. By embracing every new tool, Woodward could quickly verify the products of each reaction step in a long synthesis. In that sense he helped define how organic chemists analyze compounds today.

Method

Woodward’s approach to chemistry was famously strategic and, in his own words, artistic. He often declared that “there could be art in organic synthesis.” Each target molecule was treated like a complex puzzle. He would draw its structure and work backwards, mentally breaking it into simpler pieces, often through what chemists now call retrosynthetic analysis. In other words, he asked in reverse which smaller 'precursor' molecules could be joined to build the target. This reasoning led to hypothetical routes that sometimes seemed far-fetched, but which guided actual experiments.

A key feature of Woodward’s methodology was originality and daring. He rarely used a single generic method over and over; instead, every new synthesis was a creative design. As one colleague put it, his targets were “blank canvases,” and he chose reagents not by novelty but by their power in context. Typically Woodward’s “palette” included relatively simple reagents — acids, bases, mild oxidants and reductants — but used in novel sequences. He fixated on reaction mechanisms and molecular shape. If an intermediate needed a particular three-dimensional arrangement, he devised reactions (often clever acid-base or heating steps) to reconfigure the molecule’s conformation or stereochemistry.

Woodward’s notebooks reveal that he thought in terms of how electrons flow and rings open or close. This is where the Woodward–Hoffmann work on orbital symmetry came in: it formalized the idea that some rearrangements were allowed if their electron structures lined up properly. Even before that theory, Woodward would draw arrow-pushing diagrams to see how electrons might shift during a deformation of the molecule. His ability to predict the outcome of novel ring formations or rearrangements was legendary.

While relying on mental models, Woodward also embraced experimentation to test ideas. He would synthesize a smaller “model” compound or set up a trial reaction before committing to a long synthetic path. At each step he used spectroscopy (UV, IR, NMR) and chromatography to confirm that the structure of an intermediate was correct. This combination of theoretical planning and rigorous analysis defined his style: he was not a loose, trial-and-error chemist but rather a master planner who checked every step carefully.

Woodward’s lectures themselves reflected his method. He often started at the top-left corner of a chalkboard and, writing with clear handwriting and diagrams, systematically derived intricate ideas across the board, finishing at the lower-right with a complete solution. His teaching and lab approach both showed that to him, chemistry was an exacting craft with room for beauty.

Influence

Robert Woodward’s influence on chemistry is immense and long-lasting. A barometer of his impact is the “academic family tree” – he trained hundreds of chemists who then led their own labs. By one count, around 400 postdoctoral researchers worked in Woodward’s groups in Canterbury (Harvard) or Basel. Many of these students became professors or industry leaders worldwide. As a result, dozens of modern laboratories can trace their academic lineage back to him.

In the classroom, Woodward’s contributions are still invoked today. Almost every undergraduate chemistry textbook mentions the Woodward–Hoffmann rules, and many mention the Woodward–Fieser rules. His name is one of the few that stick in the minds of students who take organic chemistry (along with names like Fischer, Curie, or E.J. Corey). In fact, one modern professor commented that in his classes the only chemist names remembered by nonmajors a year later are Woodward and Corey's.

Woodward was also celebrated for his communication skills. His lectures — often lasting three hours — were described as “riveting.” News accounts from the time speak of audiences of students hanging on every word as he covered the board. He won several awards for teaching and exposition. His written papers and Nobel lecture are noted for their clarity and precision. Years after his death, a scholar in chemical education published a paper on "Woodward’s Words," highlighting how careful and eloquent his writing could be. Students sometimes joke that his style was almost literary – or claiming, as Woodward once did in jest, that “I teach all the time so I don’t have to teach formal courses.” In labs around the world, organic chemists say they try to plan synthetics “the way Woodward would,” giving him legendary status.

Science journalists and professional societies have honored Woodward as an icon. On April 10, 2017 (the 100th anniversary of his birth), the American Chemical Society’s journal Chemical & Engineering News celebrated his legacy in a special issue. Colleagues continue to cite his milestones when introducing new research in natural product synthesis. Outside chemistry, Woodward remains less known, but within scientific circles he is remembered on par with the great innovators of the century.

Critiques

While Woodward is almost universally revered in chemistry, some criticisms of aspects of his work have been noted (mostly in hindsight, as the field evolved). A common observation is that his focus on the intellectual puzzle sometimes came at the expense of practicality. For instance, his famous quinine synthesis produced only a tiny amount of material, far too little for any real drug use. Many of Woodward’s syntheses were long (dozens of steps) and often had low overall yields, meaning only a small fraction of starting materials ended up as the final molecule. In later decades, as the pharmaceutical industry emphasized efficiency, other chemists developed “shorter” routes or engineered enzymes to make natural products more cheaply. By comparison, some of Woodward’s methods look like costly demonstrations rather than production processes. However, supporters point out that Woodward was charting territory that had never been explored, and later work often built on or shortened his routes.

Another note is that Woodward was not primarily a cooperator on industrial-scale projects. The example of asking chemists at Ciba to set up an institute around him shows he was seen as a visionary, but after his death in 1979 the Ciba-Woodward Institute was closed. In personal style, he could be blunt and intensely demanding, which some younger chemists found intimidating. He also mostly trained men (reflecting the era), and members of his lab later commented on the intense workload he set.

In terms of science, some have remarked that Woodward’s lab notebooks sometimes omitted “obvious” details (like solvent amounts or times) in published papers, meaning that other researchers had to experiment to reproduce steps. Modern chemistry now often emphasizes thorough documentation of conditions to ensure reproducibility. Also, while Woodward devised many clever routes, he did not invent many new types of reactions himself (unlike some chemists who specialize in creating new reactions). He leaned on existing reactions in novel ways. This is not so much a critique as an observation: one might say he was not a “reaction inventor” but a “master architect of reaction sequences.”

Overall, these critiques are minor compared to his influence. Many chemists agree that even Woodward’s impractical steps were educational: they taught new strategies and eventually inspired better methods. In any case, by the mid-20th century Woodward’s role was as a trailblazer, and challenges that later chemists face often build on the foundations he set.

Legacy

Robert B. Woodward’s legacy endures in chemistry every day. His syntheses are still taught in graduate courses as classic examples of strategy: a student learning how to make complex drugs will likely hear about Woodward’s quinine or chlorophyll routes. Laboratories across the world carry his influence in their “way of thinking.” The idea that any molecule can be reached in principle by the right sequence of reactions (if it is chemically feasible) is partly traced to Woodward and his successors.

Textbooks and popular accounts often mention him when discussing the “art of synthesis.” He has been quoted in books and articles as calling organic chemistry an art, and his name appears in history sections of chemistry books. Several awards and prizes have been given in his name or in his honor. For instance, the American Chemical Society gave him the first-ever Arthur C. Cope Scholar Award in 1973, and its annual Arthur C. Cope Award is one of the top prizes in organic chemistry.

On a more physical level, some of his early lab notebooks and facilities have become historical artifacts. During centennial celebrations of his birth, photos of Woodward in lab surfaced to remind chemists of the era he came from. In academia, being part of Woodward’s “family tree” is still a point of pride for many professors.

The Woodward Research Institute in Basel, which he directed, was closed after his death, but the vision it embodied lived on in later R&D labs. His death at only 62, right as a major project (erythromycin) was underway, added a note of tragedy: however, the institute continued for a time as a symbol of what industry could achieve by inviting top academics. Today, some of the challenges Woodward tackled (like efficient production of vitamins and natural compounds) are addressed by modern biotech and green chemistry, but they all owe a debt to his pioneering spirit.

In summary, Woodward’s name and methods remain woven into the fabric of organic chemistry. The 2017 Chemical & Engineering News series on his 100th birthday noted how chemists still debate “What would Woodward do?” when faced with a hard synthesis problem. Few individuals in that field have been as consistently cited by future generations. His contributions helped move chemistry from being mainly a helping hand for medicine and industry to being a highly creative science in its own right.

Selected achievements

1944 – Woodward & Doering, formal total synthesis of quinine (Journal of American Chemical Society). This was the first time a complex alkaloid like quinine was made in the lab, albeit in very low yield.
1952 – Woodward and G. Wilkinson propose the sandwich structure of ferrocene (Journal of the American Chemical Society), founding modern organometallic chemistry.
1956 – Woodward publishes the total synthesis of reserpine (Journal of the American Chemical Society), linking early ideas of molecular conformation to achieve the correct stereochemistry.
1960 – Woodward and coworkers complete the total synthesis of chlorophyll a (Journal of the American Chemical Society), a four-year effort assembling the green plant pigment.
1965 – Awarded the Nobel Prize in Chemistry “for outstanding achievements in the art of organic synthesis.”
1965–1966 – With Roald Hoffmann, Woodward formulates the Woodward–Hoffmann rules (Accounts of Chemical Research; Journal of the American Chemical Society), explaining the outcomes of pericyclic (concerted cyclic) reactions. These rules later became a standard part of organic chemistry.

Timeline

1917 – Born April 10 in Boston, Massachusetts.
1933 – Enters MIT at age 16.
1936 – Receives B.S. in chemistry from MIT.
1937 – Earns Ph.D. from MIT; at age 20 begins position at Harvard University.
1944 – Completes formal total synthesis of quinine (with W.F. Doering).
1950 – Promoted to full Professor at Harvard.
1953 – Named Morris Loeb Professor of Chemistry (Harvard).
1956 – Publishes total synthesis of reserpine.
1960 – Publishes total synthesis of chlorophyll.
1963 – Begins directorship of Woodsworth Research Institute (Basel, Switzerland).
1964 – Awarded U.S. National Medal of Science.
1965 – Awarded the Nobel Prize in Chemistry.
1966 – Publishes (with R. Hoffmann) the principles of pericyclic reaction (Woodward–Hoffmann rules).
1979 – Dies July 8 in Cambridge, Massachusetts, at age 62.