00:00:00 This is August 26, 1981. A meeting of the American Chemical Society in New York is

00:00:13 sponsoring a special symposium to honor the memory of R.B. Woodward. Among the

00:00:22 participants at this symposium are four of Woodward's former collaborators,

00:00:28 Ernest Wenkert from the University of California at San Diego, Jerome Burson,

00:00:34 professor at Yale University, Dan Kemp, professor at MIT, and James Hendrickson,

00:00:43 who is a professor at Brandeis University. I'm Harry Wasserman from Yale

00:00:51 University, and our association with Woodward spans a period of about 25

00:01:01 years of his career. I'd like to relate our association with him by

00:01:10 describing a little bit of the period in which each of us was working with Woodward.

00:01:18 I began graduate work at Harvard in 1941 at a time when Woodward was just made an

00:01:30 instructor on the staff of the chemistry department. During the weeks, the early

00:01:37 weeks of September, he took two graduate students, Gilbert Small and myself, and I

00:01:44 worked with him for one year, 1941 to 42, then left Harvard during World War II to

00:01:53 go in the service and came back at the end of 45 and finished in 48. During the

00:01:59 period of 1940, the end of 1945 to 48, I completed my graduate work. Ernest, would

00:02:11 you say a little bit about the time that you were associated with Woodward? Sure. I was an

00:02:20 undergraduate at the University of Washington in Seattle, that's far away

00:02:25 from the East Coast, and I was advised to go to Harvard University by a recent

00:02:32 young assistant professor who had arrived on the scene who was a Harvard man by the

00:02:36 name of Hip Dobbin, and as a consequence, when I came to Harvard, I chose what at

00:02:43 that time was still a young but highly attractive professor named the R.B.

00:02:50 Woodward. I spent my period of studentship spanned an interesting

00:02:57 period because, as you yourself have just mentioned, there was a large group of

00:03:03 veterans who had just come back from the war, and Woodward knew very personally and

00:03:09 directly as a young man, and then the group that included myself of totally

00:03:15 new young people with wet behind the ears.

00:03:21 I had finished my graduate work in 1949 at Columbia, where I worked with

00:03:30 Bill Dering, and I think it's interesting to note how the special

00:03:35 quality that Woodward had was already manifest in certain circles at that time.

00:03:41 Woodward was only 32 years old, and yet Dering was absolutely adamant about his

00:03:49 instructions to me to do post-opera work with Woodward. He worked very hard at

00:03:53 arranging this, and as matters turned out, it was possible to do that, but in

00:03:59 order to accept a postdoctoral position with Woodward, I had to turn down an

00:04:04 offer of an academic job, which sounds crazy in retrospect and perhaps isn't

00:04:12 done very often these days, particularly not by someone going to

00:04:17 work with a 32-year-old associate professor, which is what Woodward was at that time.

00:04:22 Nevertheless, I've never regretted it, and I think Dering's advice was absolutely correct.

00:04:28 I just will add to my own experience that when I first came to Harvard, having

00:04:33 graduated MIT, I had planned to work with one of the senior members of the staff,

00:04:39 Paul Bartlett or Louis Fieser. Fieser was doing war work, and Bartlett had just

00:04:45 taken on a rather large group of students. Bartlett advised me at that

00:04:50 time to seriously consider working with a young new faculty member down the hall

00:04:57 before I made my final decision. So I walked down the hall to the old Chem 5

00:05:03 laboratory, and there I found a skinny young man wearing granny glasses, rolling

00:05:10 his own cigarettes, and he outlined in the space of a few hours the synthesis

00:05:18 of cantharidine, quinine, and cortisone, and estrone, and I then decided that he

00:05:31 was the person I wanted to work for, despite the protestations of my friends

00:05:35 at MIT, who advised me that I'd never get a job working with an

00:05:40 unknown new person. Jim? That's interesting. I'd gone out to Caltech as

00:05:46 an undergraduate, and had Linus Pauling for a freshman chemistry teacher, and I

00:05:52 thought he was quite a fine teacher, but after that I didn't like many of my

00:05:55 teachers. I'd gone to Caltech, I guess, because I'd seen something about Caltech

00:06:00 in Life magazine. When I grew up in Toledo, Ohio, that's about all I knew

00:06:03 about the outer world, and I'd also seen R.B. Woodward in Life magazine because

00:06:08 he'd synthesized quinine. I was interested in organic chemistry in high

00:06:11 school, and I went four years to Caltech, and there wasn't any real organic

00:06:16 chemistry at all. I kept thinking, well, where is this quinine? I don't understand

00:06:20 this, and so then I went to, I applied to Harvard for graduate school, and went the

00:06:28 first fall to Woodward's lectures, and there it was, and I suddenly remembered,

00:06:33 yes, I remember his picture in Life magazine some years ago. So I was there

00:06:38 as a graduate student from 1950 to 54. I went away for a year to do a postdoctoral

00:06:48 fellowship with Derek Barton in London, and came back and did two postdoctoral

00:06:55 years with Woodward. So I was actually on three different projects with him in

00:07:01 over a span of 51 to 57 before going to UCLA to teach.

00:07:07 I arrived in 58 and left in 64. My arrival, a major project, I guess, was still

00:07:16 chlorophyll synthesis, which was in the process of completion. Woodward's group

00:07:20 at that time was very large. It was spread over many floors and in several

00:07:24 buildings. It wasn't easy, I remember, to get in to see him, and he really

00:07:29 discouraged, initially at least, graduate students even approaching his group, but

00:07:34 a number of us persisted, and after some months of trying to make an appointment

00:07:40 with him, he arranged that we spend not one, but two six-hour evenings in his

00:07:46 office, in the course of which he outlined 15 or so research problems that

00:07:54 ranged in scope from classical natural product problems to orienting peptide

00:08:00 and protein molecules on electrode surfaces, and I well remember how, after

00:08:05 the first of those evenings, I emerged unimaginably weary with a feeling that

00:08:13 the entire world of chemistry that I knew, and a great deal that I did not, had

00:08:18 passed in one continuous session. All of us were dogged tired, but he, of course,

00:08:23 was perfectly refreshed at 12 midnight or whenever, and quite prepared to go on

00:08:29 talking. Well, the sessions that are taking place this week have had as their

00:08:39 emphasis Woodward's contribution to organic chemistry. The many aspects of

00:08:49 organic chemistry which he was able to influence. What we would like to discuss

00:08:55 this afternoon is another aspect of Woodward's impact on science, and that is

00:09:02 his impact as a teacher, and I'd like Dan Kemp to start this discussion with some

00:09:11 observations on this subject. I think one starts with a paradox. To many of

00:09:19 Woodward's colleagues, it was irritating that he did almost no formal coursework

00:09:25 or instruction. He was not interested in classroom teaching, and yet, I think for

00:09:31 any of his associates, he had to rank as the greatest teacher that they knew. The

00:09:38 paradox, I think, is resolved if one thinks a little about teaching. It moves

00:09:44 in two levels. I think one level is concerned with formal transmittal of

00:09:50 information, facts, techniques, but there's another deeper level where one

00:09:56 communicates what's valuable, and that, I think, is of much greater permanence and

00:10:03 really greater importance, and that's where his great contribution as a

00:10:08 teacher lay. In fact, the paradox is resolved when one reflects that one of

00:10:13 the things that he taught is that if anything is worth doing at all, it should

00:10:18 be done as passionately and as intensely, as intelligently as one possibly could,

00:10:23 and what he abhorred, I think, about classroom teaching is that because it

00:10:27 occurred daily or frequently, one didn't have the time to hone and to reflect, to

00:10:32 create the epitome of the subject, to distill it forward, because certainly all

00:10:37 who were fortunate enough to hear him lecture in a classroom situation on

00:10:41 those rare occasions saw a masterpiece every time that he spoke. I think one

00:10:47 other example, for the time being, will suffice of what he did as a teacher in

00:10:51 terms of instilling value. Organic chemistry is an architectural subject. It

00:10:59 hinges on structure, but I think not all its practitioners have seen structure as

00:11:06 intensely as he did, and in fact that's surely one of his lasting contributions.

00:11:10 Many who first observed him drawing molecules on the blackboard felt there

00:11:15 was affectation in the time and patience that he took to construct pictures of

00:11:19 things, but as you sat there watching these structures unfold, watching the

00:11:25 care with which he presented them, you began to realize how important they

00:11:30 were, how they were really something to be taken as seriously as anything in the

00:11:34 subject, and I think similarly, if one ever got into an argument that depended

00:11:40 upon examining a number of factors, one of the messages he taught very quickly

00:11:45 was that you wrote them down patiently, carefully, you examined each one, weighted

00:11:51 its due concern, and if it took two or three hours to do so, fine, that's the way

00:11:57 to do it. Nothing casual, and I think that intensity was part of the key to it.

00:12:04 You could feel that intensity when he drew those structures. I mean, this idea

00:12:08 of being affectation just wasn't, that wasn't it. When he put that chalk on the

00:12:14 blackboard, the electricity would come out from it, and you could feel every

00:12:17 carbon out of them, and see and feel the relations between them, and that just drew

00:12:22 you right in. If you were excited about the subject to begin with, this, it made

00:12:26 it more important. You found, I'm sure in all our times, I mean, I certainly

00:12:31 remembered how graduate students and postdocs both would spend hours

00:12:34 practicing. Yes. So that they could reach the point where they could, in honesty,

00:12:38 present a structure themselves on the board in front of Harvey Woodward. Well, I'm

00:12:41 sure that the beauty of his presentations at the blackboard was due

00:12:50 to great care and a tremendous amount of practice on his own part. He took great

00:12:59 pains before he gave a lecture to come very well prepared, even to the point of

00:13:03 carrying with him his own kit. He would have his own colored chalk, cloth, white

00:13:10 cloth to use as an eraser. Everything would be planned with great care. It was

00:13:17 very deceptive, because when he gave a lecture at the blackboard, it seemed as

00:13:22 though the form that just appeared there and covered the blackboard as though by

00:13:27 chance, and yet it was clear that he had given very careful thought to this, and

00:13:33 planned this out to the last detail. And this, of course, was representative of the

00:13:41 way that he approached any problem. He absolutely left no stone unturned in

00:13:48 analyzing a structural problem. I would make an observation that perhaps hasn't

00:13:57 been stressed, that concerns the the ability of Woodward to teach in the

00:14:05 course of writing a scientific paper. I think if you read that the Woodward

00:14:11 papers, particularly if you read the footnotes, there's a whole course in

00:14:15 organic chemistry in those footnotes. There's one example that that I still

00:14:22 use in teaching my courses. It concerns the synthesis of quinine, in which one

00:14:31 of the last steps, in fact the crucial step, is the introduction of a vinyl

00:14:36 group. You recall that? After the nitrite cleavage of that bicyclic compound,

00:14:46 which leads to a precursor of the homo meriquinine, the introduction of the

00:14:52 vinyl group is accomplished by an elimination reaction. Woodward goes to

00:14:56 great pains to tell you why the whole synthesis was constructed in such a way

00:15:01 that the group to be eliminated was on the end carbon, rather than on the center

00:15:07 carbon. Because if it had been in the center carbon, the chances are very great

00:15:10 that the double bond would have gone in the wrong position. And that was all in one

00:15:15 jewel-like footnote. You just read that and your eyes opened up for the first

00:15:20 time. It was a marvelous quality. He did that repeatedly. The teramycin structure

00:15:25 proof strikes me as a perfect example of that. The paper was not so much to

00:15:30 establish the structure per se as to show you, make you live the logic as it

00:15:36 evolved. And I can't help but think of a case in which he proposed an incorrect

00:15:42 structure at a group seminar. He had been working on a molecule called streptanigrid.

00:15:46 He had had an industrial group in his office presenting factual material. He

00:15:51 had come up with a bold hypothesis that the material was bilaterally symmetrical.

00:15:55 And there were not enough facts at the time to produce a structure. But he said

00:16:00 biogenetically this made sense. And so he called a special group seminar. It was in

00:16:06 the dead of summer when the seminars tended not to meet. So he was

00:16:10 communicating his enthusiasm and the logic, even though, in fact, it turned out

00:16:16 this was not a correct analysis. I think many thought him a person who carefully

00:16:22 wove his presentations so they put always the best foot forward. Well,

00:16:26 here's a case where he really was putting the deductive content for the

00:16:30 people in the class first, together with that chance to get the enthusiasm of the

00:16:34 moment. Here is the result right from the office. In fact, I well

00:16:39 remember he had gone into Kirby Scherer's laboratory and said the night

00:16:43 before, you know, this proposed structure has a strange urea in it. What's this

00:16:46 carbonyl absorption going to be? Now, if you were to go into the laboratory and

00:16:50 make this by fennel tonight, I'd be very pleased. And in the middle of a dramatic

00:16:56 moment, he said, and we we have this anomalous carbonyl. It's not like a urea,

00:17:00 but of course structurally it's not a urea. And last night at 3 in the morning

00:17:06 I found Mr. Scherer in the laboratory and lying in my desk at 9 was this

00:17:13 result. And you see it's precisely in accord with expectations. That was in a

00:17:17 sense. Right, I think one of the things that might be pointed out on this

00:17:24 occasion at a symposium where there is such an emphasis on synthetic organic

00:17:30 chemistry is Woodward's contributions in the early days to the structural

00:17:37 elucidation of organic compounds at a time when he was able to bring this

00:17:45 intellectual exercise to full fruition of the art. And I think that many of the

00:17:53 students who studied with him learned chemistry in this process. The fact

00:18:01 that he neglected no data, whether it was data from chemical degradation, from

00:18:09 what spectroscopic data was available, everything had to fit. And he was

00:18:19 willing to throw out conventional thinking and to start over if some of

00:18:26 the facts... Yeah, you know, it's a curious thing that there seems to have been a

00:18:30 fairly short period in his career in which he actually taught classroom

00:18:34 teaching. Happens to have been, I mean, the time I was there he mostly was doing

00:18:38 that and giving this course in natural products. But of course the course in the

00:18:43 chemistry of natural products as he gave it was always, it was called selected

00:18:48 topics, and it was always one subject from which you start with one subject

00:18:54 and then all of chemistry grows and flows from that subject. You really learn

00:18:58 all of chemistry. You're not really just learning the chemistry of quinine or

00:19:02 patchwine or something. But they were always, there were always exercises in

00:19:08 the deduction of structure. And most of the chemists nowadays know that

00:19:13 structure is not deduced anymore. It's simply produced for you by an x-ray

00:19:18 machine. And this whole exercise in the logic of organic chemistry is largely

00:19:23 faded from view. It's one of the most exciting parts of organic chemistry in

00:19:28 those days and is no longer available. And yet the building of the logic, the

00:19:37 clarity and the brilliance and the excitement of creating the logic of

00:19:43 deducing structure just by, in effect, mental application to some experimental

00:19:49 facts, he practically invented that exercise. Robinson used to be

00:19:54 very good at it, but he guessed, you know, and Robinson would guess two or three

00:19:58 times, and then when he was right he'd forget the other two or three, and he'd

00:20:01 pick on the time when he was right. Woodward did it once and for all because

00:20:05 he went through the entire logic very carefully and made his presentation, and

00:20:09 that was in fact the right answer. And of course the evening seminar was the format for this, in which problems were posed, and in a sense that the

00:20:17 solutions, which were deemed inadequate or incorrect, were as effective a teaching

00:20:22 tool. Well he encouraged that. The format of his seminars was such

00:20:27 that he encouraged individuals to go to the board and present wrong structures.

00:20:32 There was no penalty for doing it because he was able to show, to use

00:20:37 this as a teaching aid. Except in the mind of the presenters. Woodward made it as comfortable for the presenter to make a mistake. He didn't humiliate the students. He was always extremely fair and courteous, but at the same

00:20:53 time always used, carried the deductive content forward as far as possible. If

00:20:57 there, I can well remember several points I learned at that point. Two

00:21:01 successive, unstable, or unlikely steps in a mechanism multiply together the

00:21:06 probabilities. And that was a point he made when he said this is otherwise

00:21:10 acceptable, a plausible path, but you have to start with this high-energy

00:21:13 species and make something that is yet more unstable from it. And there was a

00:21:19 little point, in a sense it was the Renaissance workshop style, rather than

00:21:22 lecture style. In fact, one of the fascinating things about the

00:21:27 seminars was not only the marvelous direct pedagogic appeal, because there

00:21:33 you did your deductive thinking, and you saw it delineated, even when you made a

00:21:39 fool of yourself, but also the human touch. And in fact, the human touch, which

00:21:44 at a later time certainly did me well in appreciating the scientific world. And

00:21:48 that is that he made very, very clear that when he was attacking, and when he

00:21:54 was in fact tearing something apart, it was a something, not the someone.

00:21:59 And one of the fascinating things was that this was a period of time when I

00:22:04 think the scientific world had not yet realized there's a difference, and they

00:22:07 were rather vicious, almost sort of reminiscent to the rhetorics of the last

00:22:13 part of last century in the German literature. He made it very clear indeed

00:22:18 that he was focusing on the chemistry and not on the chemist, and it really

00:22:23 didn't make any difference. And as soon as you appreciated this, which

00:22:26 invariably took at least a year or two years of graduate study, and you felt

00:22:30 more comfortable, then you realized that even when you made a fool of yourself, no,

00:22:34 you learned, and the rest of the group learned. I still remember a comment he

00:22:38 made in a totally different connection, in which a graduate student at my

00:22:42 institution had discovered a rather brilliant point, but had made a gaffe in

00:22:49 its presentation at a rather low level. And R.B.'s comment was, but anyone can

00:22:54 make that kind of mistake. Don't you really recognize that? Absolutely. I

00:23:00 think the other aspect of this work on the structure of organic compounds was

00:23:09 the way that he infused aesthetics into the exercise. When a structure was

00:23:16 completed, and he wrote it on the blackboard, there was this breathtaking

00:23:21 quality of creativity. It was just as though he had created some beautiful work of art.

00:23:28 And he, as Dan pointed out, he would take such great pains to draw the structure

00:23:36 out carefully, and to delineate the three-dimensional quality of it, just as

00:23:41 though he were a sculptor creating something. I think all his students

00:23:49 picked up this feeling of appreciation, a feeling of aesthetics for organic chemistry.

00:23:55 I think that the business that Jim raised about structure determination

00:24:01 being a lost art, it's certainly true at the professional level. I mean, one

00:24:08 doesn't find most serious organic chemists spending a lot of time now

00:24:12 determining structure. But the didactic value of this lives on, and the students

00:24:19 recognize this. They instinctively turn to that. And my own group seminars, for

00:24:25 example, we still have problems of that kind, and we handle them very much in the

00:24:30 workman's spirit. Well, in fact, you know, it's rather amusing that in the field of

00:24:36 synthetic organic chemistry, so the real strength of Woodward, very much the same

00:24:41 type of thinking went by, and still goes on. And that is that when, let's say, you

00:24:47 have a highly polyfunctionalized molecule, and you're carrying out a unique

00:24:50 reaction at one spot, obviously the predictability of success is fairly low,

00:24:56 and the consequence of which is, you may get surprises. Well, the identification of

00:25:01 the product, while now not a natural product, being truly a synthetic product,

00:25:06 is identical in its analysis to what you would have in the other,

00:25:11 and in fact, which we have in the structural... But of course, synthetic acid, which was mentioned in one of the lectures,

00:25:15 there is such a thing as not a natural product, but it's a compound that needs figuring out.

00:25:20 But still, there was a unique moment in chemical history when this wonderful

00:25:26 goldmine, or storehouse, of classically derived structural information, really

00:25:32 hard natural products, remained unresolved because the mechanistic

00:25:36 thinking that R.B. provided, and Robinson, of course, had started, all came together

00:25:41 with spectroscopic tools. It lasted about, probably from the late 1890s, I

00:25:48 would say, from the time of Wagner and the terpene chemists, until about 1959, or

00:25:57 the end of the 1950s. And from there on, the subject just became fossilized. And he

00:26:05 was a perfect match for that age. I guess that's what continually amazes me.

00:26:10 You see, I think, Dan, that one of the things that contributed to

00:26:14 the interest in that subject was the intrinsic interest of the

00:26:19 molecules themselves, because people recognized that they were significant

00:26:25 beyond their chemical structure. They were physiologically active, many of them, or

00:26:29 they played a role, as Ernie has been a leader, in allowing one to

00:26:38 postulate mechanisms, and Jim has also participated in this work,

00:26:45 mechanisms about how natural molecules are formed. So there was a glamour

00:26:50 associated with them that was beyond their mere chemistry. But that now has,

00:26:56 you know, what is really the residue of that field now is what is

00:27:01 called biosynthetic chemistry, or biosynthesis of natural products, where a

00:27:06 lot of the work is now really at the enzymatic level, the really important

00:27:11 scientific contribution. You know, there was another glamour, as you well know, in

00:27:15 that same period that Roald Hoffman talked about this morning, that this was

00:27:18 also a time when one really had some possibilities in application of theory

00:27:25 to raising the chance that whole new classes of structures might turn out to

00:27:31 be stable and interesting and unsuspected. I mean, ferrocene is, in a sense, a pristine

00:27:37 case of this. And I think part of the excitement, at least in my period, was, on

00:27:43 the one hand, the natural product work you're talking about, these immensely

00:27:46 important, time-honored subjects, strychnine, which have been around for the

00:27:51 history of the discipline, morphine similarly, steroids more recent, but still

00:27:55 immensely valuable objects. But at the same time, cyclopentadienyl anion and

00:28:01 tropylamine and the possibility of homohermeticity, perhaps there is a whole

00:28:06 new area of organic which can open up, which theory leads to. And I think at

00:28:12 that moment, there was a romanticism. I can still recall R.B., Chris Foote, of

00:28:18 course, worked on a kind of a non-classical ion problem, and I can

00:28:23 still remember R.B. calling a number of us together who were interested in that. He said,

00:28:26 I've finally figured what the cyclopentadienyl cation is going to

00:28:31 turn out to be. He drew a benzene ring with a methione, a positively charged

00:28:36 methione complex to it. Sitting on the top? Sitting on the top. He said, if you

00:28:40 average all the Lewis structures, this is what you come up with. He said, that's what it's

00:28:44 going to be. And that lent immense excitement, I think. Doors might open. And

00:28:50 I think we don't have that right now. It's interesting, what we're all probing in a

00:28:54 way about his teaching is somehow how he conveyed to all of us, or at least

00:28:59 turned on what was latent in all of us, a sense of this enormous excitement and

00:29:06 artistic satisfaction that chemistry could provide, if it was only done in the

00:29:11 right way. And somebody said the other day in one of the lectures, maybe it was Barton,

00:29:15 in the old days, nobody used to think. The point was, they'd just go to the bench

00:29:19 and work and get results. And here was what we're telling you, that chemistry, it

00:29:25 was, one thing was what you did in the laboratory, but something else was how

00:29:30 you thought about all these details, and how the logic held them all together, and

00:29:34 how when you saw all that, it was such a beautiful structure, that it took on even

00:29:38 aesthetic pleasure, which then was reflected in these beautiful drawings on

00:29:42 the blackboard. And we'd go from the upper left-hand corner, as somebody said

00:29:47 the other day in the introduction, put all those structures on the board and

00:29:50 finish at the lower right-hand corner, just at the end of the hour. Which, of

00:29:54 course, means that he had thought about the communication of all this very, very

00:29:59 carefully. Right. Along with this, of course, came his intense preoccupation

00:30:05 with precision, with mastering all the details. More than anyone else that I

00:30:13 know, he was able to concentrate on a problem and spend enormous amount of

00:30:20 time analyzing the background of any problem. When I say enormous amounts of

00:30:27 time, everybody who has been associated with him knows what his working habits

00:30:32 were. But he constantly impressed his students with his knowledge of the

00:30:43 literature. He was certainly the most widely read person that I know in

00:30:49 organic chemistry, and he had a memory for all of these facts, which he was able

00:30:55 to use very effectively. And one of the most extraordinary things, incidentally,

00:31:00 again, as a pedagogic tool, certainly left a deep impression on me, I think left a

00:31:04 deep impression on science as a whole, is that through his reading and through his

00:31:10 only innate curiosity about things, he was drawing upon, especially theory,

00:31:16 certainly practices of very, very different disciplines. I mean, the thing

00:31:22 that actually cleanly delineated a differential and a breaking of the era

00:31:28 from before him to since him is the fact that mechanistic reasoning, which, as a

00:31:36 matter of fact, if you go to European universities, you even find in terms of a

00:31:40 separate department, not just part of the same department, or you will

00:31:44 find, let's say, in many international journals, as a separate part of a journal,

00:31:49 that mechanistic reasoning somehow or other was alien to a scene of where you

00:31:54 wanted to construct something artfully. And what he really, what he appreciated

00:31:59 right from the very beginning, and what he certainly taught to all of us, was

00:32:03 that how horrifying it might have been to a young organic chemist, thermodynamics

00:32:08 was a living thing, and kinetics was equally a living thing, and we might

00:32:12 not have used a true K, might never have actually run a full-blown experiment to

00:32:19 get a rate or anything of this sort. We knew very well it was hidden in the type

00:32:23 of statements that you made, and if you were, in fact, not partaking of that type

00:32:27 of thought, you would make all types of faux pas. So that this notion of it being

00:32:33 all of chemistry as focused upon a unique field, namely of how do you

00:32:39 construct these horrendous molecules with all their beauty, etc., was something

00:32:43 he brought across with immense pressure. And it's interesting that in some ways

00:32:49 it's a shame that it took so many, many years until people really appreciated

00:32:53 that this was the power of the field. The fact really was that for a young

00:32:58 organic chemist to have become a, I mean, no one could become a Woodward, but to

00:33:05 become, in fact, a truly outstanding organic chemist meant that he had

00:33:09 to be knowledgeable in all these other areas, plus his own area of synthesis.

00:33:16 Yet with a hierarchy of standards, I think that's something that impressed me

00:33:21 very much, that the experimental art was really foremost, kind of a ground base, if

00:33:27 you wish. Maybe there's a flute obbligato in the mechanistic thing that's all

00:33:32 important, but still I still remember asking him in my first graduate year,

00:33:36 should I get elemental analyses on all of these new substances? And he looked at

00:33:41 me and he said, if you make something that is a new substance, do it to the

00:33:46 courtesy of complete characterization. And I think that's a point that's well worth

00:33:52 emphasizing, that he made so many aspects of organic chemistry look easy. When he

00:33:59 discussed a reaction, he moved arrows. He certainly was the father of the

00:34:05 arrow-pushing aspect of organic chemistry. I would love to say that the people in England

00:34:10 probably think that Sir Robert Robinson did. At least in this country. But

00:34:18 underneath that, of course, was a very strong understanding of the theoretical

00:34:29 aspects of organic chemistry. He had a very good understanding of physical

00:34:33 organic chemistry, and many of the people who imitated him did so without really

00:34:39 understanding. Well, in fact, let me just tell you one experience I had which

00:34:45 really drew upon that with a vengeance. He, once during a seminar, presented a

00:34:51 six-electron transfer reaction, cyclic transition state, and somebody had

00:34:57 in fact written the arrows in, quote, the wrong direction, unquote. And we have

00:35:02 spent about half an hour with him in the leadership of asking, well, does it

00:35:06 matter? And it was a fascinating experience, because there was no

00:35:11 question whatever, the audience absolutely was biased that it didn't

00:35:14 matter. And only through that type of discussion did we suddenly understand

00:35:19 the formalism of it all, and the much more serious significance of what are

00:35:25 electrons all about, what are bonds all about, etc. And it was, I mean, it clearly

00:35:31 showed that he was a teacher in order to use pedagogic tools, and crutches, and

00:35:37 techniques, and gimmicks, and what have you, as everybody needs to, in order to

00:35:41 pull the young student into it. But what was that young student if he was left at

00:35:45 the door where the deep significance of what he was doing was unlearned? And he

00:35:52 certainly managed to get them past that stage. But along with that facility

00:35:58 that he had, mechanistic and theoretical aspects of organic chemistry, as Dan

00:36:05 pointed out, he never underestimated the importance of the experiment. Over and

00:36:10 over again, he pointed out that organic chemistry is an experimental science. He

00:36:15 would even go so far as... A point you made this morning, Jerry, about the quote, there are rarely sufficient excuses for not doing the experiment.

00:36:24 Everybody must have heard that at some time or another. He would point out, perhaps

00:36:29 sometime, perhaps a little facetiously, but I think he was convinced of it, that

00:36:33 there are no general reactions. Every reaction has to be... has to try it on its own.

00:36:40 In that connection, I can't help but recall a conversation that Claude Wittner

00:36:44 quoted to me once. Claude said to him, you know, I think I now understand why you

00:36:50 prefer synthesis and find it the highest art. Because, you know, we sometimes

00:36:55 talked about that as among graduate students. His research seminars focus so

00:37:00 much on the mechanistic aspects. Rarely did one discuss synthetic strategy, for

00:37:04 example, and yet his own bias was clearly that mechanism is extremely

00:37:10 important, but the first love is synthesis. And Claude said, well, I think I now see

00:37:14 that when you take a mixture melting point at two crystalline materials, one

00:37:18 natural and one synthetic, all of the theories can blow away, but you're left

00:37:22 with the fact that you didn't make it. And he said exactly. He said one basically

00:37:27 has to be aware of what are the levels of proof, and that this is the absolute

00:37:33 one. The theories, however much they're valuable, may or may not hold up. And I

00:37:38 think the mechanistic studies he did, there was always that element of honest

00:37:42 reservation. But there is in every mechanistic study. That's it. The characteristic of

00:37:47 mechanistic study, I take it from a veteran in this area, that there is no

00:37:51 matter how carefully you think you've proven something, there's always somebody

00:37:55 with another opinion. Absolutely. Whereas the mixed melting point, there's no argument.

00:37:59 That's right. If you've got it, you've got it. And I can understand that absolutely,

00:38:04 that sense of satisfaction that he must have had about closing the circle. No

00:38:08 argument. Yes, that's true. But I think, you know, we can we can make lists about

00:38:14 the qualities that he had and try to identify what the special features were

00:38:21 about the way that he thought. But there was something else that made him what he

00:38:26 was and made him unique. And I remember a particular case. It's a little bit

00:38:32 awkward because I don't want to mention names here. It's a little bit embarrassing

00:38:36 for some of the people involved in the story. So I'll make it anonymous as much

00:38:40 as I can. Let us guess. This was during my, I went back to Harvard on sabbatical

00:38:51 in 1959. So I had been away about ten years, but the seminar was still going on

00:38:55 as usual. And one night, one of the postdocs, who was in Woodward's group at

00:39:02 that time, presented a seminar on some work he had done. He was a very good man, who

00:39:08 a very well-known organic chemist today. And he had one, he had done this work in

00:39:12 collaboration with an even better known organic chemist. In fact, a very famous

00:39:18 organic chemist. Perhaps Dan was at this seminar. I certainly was. I remember it vividly. Well, the seminar was a model of clarity and

00:39:28 precision, and the work was presented in a very compelling style. And I think that

00:39:35 at the end of the talk, which lasted an hour or so, the audience was quite

00:39:39 convinced that this group had correctly solved the structure of this

00:39:44 rather complex natural product. Everything looked exactly right. The only

00:39:48 thing missing was, as I recall, total synthesis. But all of the information

00:39:53 that needed to be obtained was obtained. There was careful spectroscopic

00:39:58 examination of... One biochemical quirk. It was biochemically, biosynthetically anomalous.

00:40:05 Ah, but that emerged only later, you said. And at the end of the hour,

00:40:11 there was applause for the speaker, a few desultory questions from

00:40:18 the audience, and things seemed to be winding down. And it seemed to be time

00:40:23 for Woodward to stand up and present what he usually did after the formal

00:40:28 seminar, some special problem to engage the attention of the audience as a kind

00:40:34 of dessert. But that didn't happen. And while everyone sat there in silence, one

00:40:43 could see Woodward seated in the front row, smoking a cigarette and drawing

00:40:49 structures on the paper, and it looked as though he was lost in thought. But what

00:40:55 we didn't know was that he was still thinking about the seminar. And time

00:40:59 passed, and I would say about 20 minutes went by. He often did that. People were

00:41:04 talking about the Red Sox, or where they were going to dinner the following

00:41:10 night, all sorts of things. It was clear that there was no one in that room who

00:41:15 had any question about the conclusions that had been presented to us except

00:41:20 Woodward. And that didn't emerge until about, I think, a full half hour later,

00:41:25 when he cleared his throat and said, I have a few questions to ask. And at that

00:41:35 point, he stood up and drew on the blackboard an alternative structure for

00:41:41 what had just been presented. One that he pointed out was biogenetically

00:41:49 acceptable in contrast to the one that had been presented, which was not, at

00:41:54 least in terms of the biogenetic schemes that were being thought about at

00:41:58 that time. And he said, I wonder if anything in all the evidence you have

00:42:02 presented to us rules out the possibility that this structure, rather

00:42:06 than the one that you have told us, is correct. And it was clear that the person

00:42:12 who had presented the seminar had not thought about that structure. That had

00:42:15 not been a subject of discussion. He made some honorable attempt to defend his own

00:42:23 point of view, but in fact there was no distinction to be made based on the

00:42:26 evidence at hand. Well, one other thing, as I recall, there had been an acidic

00:42:31 degradation in the original structure. Yes. And he even went to the point of

00:42:36 saying that now the place where these differ has to do with the position of an

00:42:41 alkyl group. Exactly. And you have used rather strong acid in this step. And a

00:42:49 rearrangement has taken place. And a rearrangement could easily have taken place, which would...

00:42:52 That's right. Well, as it turned out, of course, I tell you this story not for

00:42:57 any trivial purpose. Woodward's structure was, in fact, correct, as was shown by

00:43:02 subsequent experimentation. But the point I'm trying to make here is, you see, that

00:43:06 that intensity of application, that feeling that what was going on at that

00:43:14 seminar was truly important and merited one's deepest emotional concern... Rather

00:43:20 than just listening, saying yes. Rather than just listening, saying yes. It sounds all very

00:43:23 plausible. Yes. That is something that was unique to Woodward. And something

00:43:28 that's even less definable, and that is the feeling that he must have had inside.

00:43:33 And I assume that this was not just a staged operation, that he did not, in fact,

00:43:37 have worked it all out beforehand. I'm assuming it was all on the up-and-up.

00:43:42 And therefore, what must have... And it doesn't really matter whether he did or

00:43:47 not, because even if he worked it out in advance, perhaps we didn't deserve the

00:43:53 drama. But nevertheless, at some point, he must have said, there was

00:43:57 something not quite right. Consistent. Something that doesn't fit. Right. And

00:44:04 he pursued that. And it's important to get it right. That was a lesson. It's the importance of doing the work. I don't do it well. I don't do it at all.

00:44:14 Let me even comment on that, because I can vividly remember that. I was in my

00:44:18 first graduate year. And in terms of educational content per second, that

00:44:25 moment surely had reached some sort of maximum. Because what this said to us was,

00:44:30 here is this easy route. You follow what the speaker is telling you. And that

00:44:35 isn't all that easy for a first-year graduate student to follow the logic of

00:44:38 a talk. But here is a much rockier path, where you have to be thinking at each

00:44:42 point of alternatives. And that's what the real game is. And here's the evidence. I

00:44:47 think that aspect of his communication with other scientists is one which may

00:44:56 not be evident in his published papers. And it is supposedly. Because Woodward

00:45:01 traveled a lot. He was constantly being consulted. He was so interested in

00:45:06 organic chemistry that it was easy to discuss one's research with him. And

00:45:12 every one of us probably knows of examples of contributions that Woodward

00:45:18 has made to structure, to synthesis, to aspects of theory, which were simply

00:45:25 based on exchange of information. He loved to talk about chemistry, and he was

00:45:31 able to concentrate on the problem. Actually, there was even a particular

00:45:41 behavior pattern which he had, which, if misunderstood, could be unbelievably

00:45:47 ego-squelching to you. And which, in fact, I think some weak personalities in the

00:45:54 world probably have considered to be ego-squelching. And that had to do with

00:45:58 the fact that he has, all his career, had such huge research groups that the

00:46:04 probability was always exceedingly high that no matter what topic you might

00:46:09 bring up, that he hadn't already done some bit of work somewhere in that area.

00:46:15 So I remember coming to him on many an occasion when I came through

00:46:20 Cambridge. And, of course, he wanted to know what I was doing at the time. And

00:46:23 invariably what would happen would be after half an hour of chatting back and

00:46:27 forth, he would say, Ernie, wait a moment. And he would go to his outer office, where

00:46:33 he would have huge filing cabinets, and he would go through them a bit, and after

00:46:38 a while come up with a little file. And before long I discovered that ten years

00:46:43 earlier he had obviously already done what I thought was fabulous work. And, but

00:46:49 what was very interesting about this was that you could turn this game around in

00:46:53 in the other way. That is, you could in fact appreciate that this was one of the

00:46:57 things, one of his strengths, in fact. And rather than being squelched, actually

00:47:02 learn something about chemistry, and thereby enrich your own chemistry. I

00:47:07 think this was something that was really very fascinating, because in

00:47:12 fact the afternoon discussions, oftentimes slightly inebriating, because

00:47:18 he was a great one of offering you drinks in his office, nevertheless

00:47:23 were a tremendous give-and-take, and in the presence of yet other data that you

00:47:28 knew nothing about, made it a bit more exciting.

00:47:30 I think one can't leave the subject of his seminar without mentioning the other

00:47:35 seminar, namely Saul Winstein's, that was happening at about the same time. It was

00:47:40 also the tremendous didactic experience of a quite different sort.

00:47:44 Winstein had the reputation for being able to memorize the speaker's numbers

00:47:49 as they were being presented, to think about them as they were being offered,

00:47:54 and then to feed them back to the speaker at the end of the talk in the

00:47:57 form of questions, and woe to the person who was not sufficiently acquainted with

00:48:01 his or her own data to be able to defend themselves. I well remember being told by

00:48:07 several people, the one Stein saying to a rather distinguished chemist when he

00:48:11 asked him a question, and the man said, I don't know, and he said, well why don't you

00:48:15 know? And those two things together had similar flavors in the sense of

00:48:20 intensity of thought and absolute integrity in terms of pushing the limits

00:48:26 of thought and perspective right to the hilt, and they were certainly, I think,

00:48:33 very close in terms of their own regard for each other. I think true, and I think

00:48:40 the other thing, now that you mention Winstein, and it might well be said

00:48:46 that Woodward was very fond of sport. He loved to tease his colleagues and tease

00:48:51 his students. You mean non-athletic sport? He made a game. He really did make a game

00:49:01 out of a chemical problem. His style in writing papers carried us even one

00:49:10 step further. They were battles to be won. But always fun? Well, they

00:49:17 were challenges. They were a gallant band of Swiss that were hurled at the

00:49:23 barricades at the last minute in strychnine sentences, so that he infused

00:49:30 his research and his research group with a spirit of drama. He had a

00:49:37 wonderful feeling for the dramatic quality of a presentation. Not only was

00:49:44 there a high order of aesthetics, but there was a timing and a drama to his

00:49:50 presentations such that one was always excited at hearing one of his lectures,

00:49:58 and I think we're probably going to have to wind things up now. I don't know

00:50:05 whether... I think there was another group waiting in the wings to talk about other

00:50:10 aspects of Woodward's career, and so maybe we can summarize Woodward's

00:50:17 contribution as a teacher by pointing out that the rigor of his thinking was

00:50:27 something that every one of us carry away from an experience with him. Jerry, do you

00:50:35 want to add any comments to summarize? I would just summarize by saying he taught

00:50:40 by example. By example. And his example was unparalleled. There was no second. That

00:50:46 was how things should be done, and we all tried the best we can to reach that level.