robert burns woodward, 1917-1979ffffffff-e65b-5674-ffff... · 1960: octant rule for optical...

Robert Burns Woodward, 1917-1979

Instrumentation, Mechanism and Stereocontrol in Total Synthesis

Thursday, October 14, 2010

R. B. Woodward, 1917-1979

• From Quincy, MA• 1925: Chemistry set• Ludwig Gatterman’s The Practical

Methods of Organic Chemistry• Copies of German literature from

1928• 1933: Enters MIT• 1937: Bachelor’s and PhD • Semester at University of Illinois• 1937: Harvard University


Why Chemistry?Arthur C. Cope Lecture, 1973

First, mathematics lacks the sensuous elements which play so large a role in my attraction to chemistry. I love crystals, the beauty of their form--and their formation; liquids, dormant, distilling, sloshing!; the fumes, the odors--good and bad; the rainbow of colors; the gleaming vessels, of every size, shape and purpose. Much as I might think about chemistry, it would not exist for me without these physical, visual, tangible, sensuous things.


Why Chemistry?Arthur C. Cope Lecture, 1973

Second, while in mathematics, presumably one’s imagination may run riot without limit, in chemistry, one’s ideas, however beautiful, logical, elegant, imaginative they may be in their own right, are simply without value unless they are actually applicable to the one physical environment we have--in short, they are only good if they work! I personally enjoy very much the very special challenge which this physical restraint presents.


Exhibiting Control over Nature

1944: Synthesis of quinine, structure of penicillin1947: Structure of strychnine1952: Structure of FerroceneTotal syntheses:

1951: Cholesterol1953: Strychnine1956: Lysergic acid1958: Reserpine1960: Chlorophyll1963: Colchicine1972: Vitamin B12


Quinine, 1944

N

H3CO

HON

HH

Cholesterol, 1951HO

H

H H

Lysergic Acid, 1956

N

HN

H

OHO


Reserpine, 1958NNH

H3CO

H

H H

H3COOC OOCH3

OCH3

OCH3

O

OCH3

Colchicine, 1963

O

H3CO

HN

O

H3CO

OCH3

OCH3

N

OO

N

H

HStrychnine, 1953

H

N

NOO


Vitamin B12, 1972(With Albert Eschenmoser)


Contributions to Theory and Practice

1941: Woodward Rules for ultraviolet spectroscopy1950s: Advocate for IR and NMR spectroscopy1960: Octant Rule for Optical Rotatory Dispersion1965: Nobel Prize1965: Woodward-Hoffman Rules for orbital symmetry1979: Death at age 62.1983: Hoffman awarded Nobel Prize


Reputation

Work HabitsCigarettes and Scotch whiskeyLegendary lecturesStudent devotionWoodward Blue


Loyal Students and Woodward’s Sedan ChairThursday, October 14, 2010

Influences and Trademarks

• Autodidactic• Encyclopedic knowledge of the

chemical literature• Application of mechanism for

control in making and breaking bonds

• Physical Instrumentation as a replacement for degradative methods for structure elucidation.

• Total synthesis as a means for developing new chemistry

• Post World War II “Big Science”• Use of imagination and creativity

With Robert Robinson, 1951


Journal of the American Chemical Society, 1941Thursday, October 14, 2010

Journal of the American Chemical Society, 1961Thursday, October 14, 2010

Penicillin


To have placed primary emphasis on the importance of theory . . . is not to derogate a second factor of a very [great] moment — the development and application of physical methods. No new general principle is involved here. Chemists should always have been willing, nay eager, to utilize to the full any experimental method or tool which would give them greater and more precise insight into the operations which they were conducting. But for a long time organic chemists, for some reason — perhaps a too great compartmentalization of chemistry, perhaps a too insular pride — were loath to make use of even the relatively simple physical tools which were available. Happily, this recalcitrance has now largely disappeared.

Woodward, “Synthesis,” 1956

The Instrumental Revolution, 1940-1970


I wonder whether chemistry would have been richer or poorer if [Adolf von] Baeyer had been able to put indigo into a machine and get the structure right away; we should probably know nothing about the isatins and numerous important synthetic reactions, and so on. It would have been a serious loss, and that is what will happen in the future if the disciples of the physical methods of end-all and be-all organic chemistry get their way.

Robert Robinson, 1973



While it is undeniable that organic chemistry will be deprived of one special and highly satisfying kind of opportunity for the exercise of intellectual élan and experimental skill when the tradition of purely chemical structure elucidation declines, it is true too that the not infrequent dross of such investigation will also be shed; nor is there any reason to suppose that the challenge for the hand and the intellect must be less, or the fruits less tantalizing, when chemistry begins atthe advanced vantage point of an established structure.

Woodward, “Total Synthesis of Strychnine,” 1963




• Woodward enthusiastic about instruments (UV, IR 1940s)• 1958: NMR elucidation of oleandomycin• Two principle changes advocated by Woodward:

- Pure samples were no longer necessary- Direct access to instruments by organic chemists

• Practical application of physical techniques (“black boxing” of the theory itself).

• Empirical generalizations between structure and absorptions.• Instrumentation makes structures more “real.”


Redefining Analysis and Synthesis

• Lavoisier’s analysis and synthesis of water.• Classical degradation products (“analysis” products) are “simpler” than the

unknown.• Substances can be put back together (“synthesized”) via these simpler

products.

• Analysis is different with instruments.• Synthesis for Woodward is de novo, not a “reassembly” from the simpler

analysis products.


Why End with Woodward?

• Woodward’s accomplishment in “Synthesis” echoes the goals of chemists• Combination of science (predictive correlations) with practical craft

(syntheses)• Chemist’s power to imitate nature.• Ability to manipulate the “building blocks” of nature to our advantage (cf.

Hodgkin symposium).• Proposing total syntheses requires tremendous visual imagination of the

microworld that must then be tested in the laboratory.• Total control of bond formation and cleavage requires knowledge of

mechanistic chemistry.• An “end point”?


Further Reading

• O. Theodor Benfey and Peter John Turnbull Morris, Robert Burns Woodward: Architect and Artist in the World of Molecules, Philadelphia: Chemical Heritage Foundation, 2001.

• Jeffrey I. Seeman, “The Woodward-Doering/Rabe-Kindler Total Synthesis of Quinine: Setting the Record Straight,” Angewandte Chemie, International Edition in English, 46 (2007): 1378-413

• Leo Slater, “Woodward, Robinson, and Strychnine: Chemical Structure and Chemists’ Challenge,” Ambix, 48 (2001): 161-89

• Leo Slater, “Instruments and Rules: R. B. Woodward and the Tools of Twentieth-Century Organic Chemistry,” Studies in History and Philosophy of Science, 33 (2002): 1-33

• Leo B. Slater, “Industry and Academy: The Synthesis of Steroids,” Historical Studies in the Physical and Biological Sciences, 30 (2000): 443-89


robert burns woodward, 1917-1979ffffffff-e65b-5674-ffff... · 1960: octant rule for optical...

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