00:00:01 We're in New York at the ACS meeting at a memorial symposium for R.B. Woodward organized by the Organic Division.

00:00:11 I'm Christopher Foote from UCLA. I have with me Jerry Berson from Yale University, Dave Lemal from Dartmouth College.

00:00:20 We have been asked to trade a few reminiscences about Woodward, with whom all of us were associated at one time or another.

00:00:30 As in the area of mechanistic chemistry, Woodward, of course, is best known for his contributions to synthetic chemistry,

00:00:39 but quite a number of his former workers have gone into the area of mechanistic chemistry,

00:00:47 and all of us feel that Woodward had some part in that. So perhaps we should get into trading a few reminiscences.

00:00:58 Jerry, you had an anecdote or two?

00:01:00 One thing that I'll say, at the risk of repeating something I said earlier in another session,

00:01:10 is its specific instance of Woodward's application of mechanistic reasoning to synthesis.

00:01:16 Now this is not quite on the main subject, but I think it illustrates his quickness off the mark in using mechanistic concepts,

00:01:27 in working these into his synthetic design. In the total synthesis of quinine,

00:01:37 which must have been in the planning stages in about 1940, I would guess, perhaps earlier.

00:01:44 But we know that work on it began about then or maybe a year later.

00:01:51 If you recall the design of that synthesis, it comes near the end with that marvelous ring-opening reaction that uses a nitrite cleavage with a ketone.

00:02:04 And then there is a reduction of an amine and elimination, which is designed to put the terminal double bond in the vinyl group of the homo-meroquinene,

00:02:20 which is a precursor for making quinotoxin.

00:02:24 Now that reaction, that whole synthesis was designed around one reaction, which was the elimination of trimethylamine from the quaternary salt of the amine that was produced

00:02:38 after reduction of the oxime obtained from the nitrite cleavage.

00:02:44 And that was a very daring thing to be doing in 1940, because most people in those days, I dare say, were not too concerned about which direction you could expect elimination to take place.

00:02:59 And a lot of chemists would have thought, well, this is going to give a mixture because there are two possible hydrogens that can be eliminated.

00:03:07 But what Woodward pointed out in an absolutely telling footnote in that paper was that this was all perfectly intentional and rationally designed,

00:03:16 because he had been reading the papers of Ingold, which had been published in about 1938,

00:03:20 in which an extensive study of the direction of elimination of quaternary ammonium salts had been made,

00:03:27 and had left no doubt that the thing would go in the right way, and of course it did.

00:03:32 So within a very short time, he was using mechanistic investigation at the forefront of the field,

00:03:38 and it takes a little leap of the imagination to realize that that was a hot problem in 1938,

00:03:43 but he was incorporating it into the design of complex natural products.

00:03:46 Yes, I think it was Frank Westheimer on Monday who told us that one of the things that Woodward had done was teach us how to think carefully about organic chemistry.

00:03:55 No, perhaps it was Derek Barton that said that, yes.

00:03:58 I think that's right.

00:04:01 In that connection, and I have some thoughts here triggered by the leap of imagination you alluded to,

00:04:08 it seems to me that one of the things that he taught us was that even great edifices of logic were built out of small bricks,

00:04:17 and that when one took apart some of his inspired intellectual constructions,

00:04:24 when you took them apart in a methodical, logical way, the way he did, each individual step made a great deal of sense.

00:04:32 And I think that kind of thinking, though he applied it most to synthetic problems,

00:04:40 created a habit of mind in his students that was then applicable to the scientific investigations in areas far afield from natural product synthesis, certainly.

00:04:48 And many of the students did go very far afield.

00:04:51 Yes, I think one of the nicest examples of this, actually, is provided by Gerhard Kloth,

00:04:56 who, when working with Woodward, worked on the structure of the macrolide antibiotic magnamycin,

00:05:02 certainly natural products chemistry,

00:05:05 and who not so very long after beat all the theoreticians and the NMR experts in conceiving of the radical pair theory of Sidniff,

00:05:14 which was about as far from natural products chemistry as one might stray from organic chemistry.

00:05:19 Exactly. But I can remember in particular a Woodward seminar in which Woodward reported on an early result of Gerhard's.

00:05:28 He was forever bringing in very nice tidbits from either synthetic or mechanistic chemistry, things that impressed him.

00:05:36 This was the elimination of lithium chloride, I think, from dichloromethane.

00:05:44 No, it was to get a cyclization reaction.

00:05:47 It was in the reaction to get cyclopropene from allyl chloride.

00:05:50 Yes, which was a particularly neat example of, well, what isn't really physical organic chemistry,

00:05:58 but it's preparative chemistry, preparation of a small and interesting molecule, particularly a novel bit of chemistry.

00:06:06 And it was bringing up things of this sort and constantly bringing up things of this sort in that seminar

00:06:13 that fired the imaginations of many of us.

00:06:16 Yeah, I think that's right.

00:06:18 I think that probably the crowning contribution to mechanistic chemistry was the Woodward-Hoffman rules, of course.

00:06:27 This, as Roald Hoffman told us this morning, and I wished he could have been here this afternoon,

00:06:35 was really the culmination of some 30, 25 years of thought about the Diels-Alder reaction, cycloadditions,

00:06:48 which finally crystallized in the vitamin B12 area in a particular cycloaddition,

00:06:56 which had to go a certain way and which surprisingly went the wrong way.

00:07:01 And not simply brushing that aside as an unexplained anomaly, but thinking hard about it,

00:07:08 which also reminds me that at the time I was there some seven years earlier

00:07:14 that the ring opening of cyclobutene had been discussed in a Thursday evening seminar.

00:07:19 I was trying to find my notes on that seminar the other day, and unfortunately I couldn't.

00:07:23 But I remember that this was the subject of at least an hour's discussion at that seminar.

00:07:29 The fact that it opened in a certain way and very elaborate steric rationales were constructed for the way it opened,

00:07:36 and all of these were more or less discarded.

00:07:39 So it was clear that this sort of thing was constantly coming to the forefront of his mind,

00:07:44 dipping back down again when no satisfactory explanation presented itself,

00:07:49 but it was constantly being thought of.

00:07:53 Well, I think he took the orbital symmetry thing very seriously indeed.

00:07:58 I think he really did not consider himself a physical organic chemist in the conventional sense,

00:08:05 although he would probably not have been insulted if someone called him a mechanistic chemist

00:08:11 or a mechanistically oriented chemist.

00:08:13 And I think what I think would distinguish him from many people that we think of as physical organic chemists

00:08:24 would be his emphasis on molecular structure rather than on the accumulation of a body of quantitative data

00:08:37 in the form of rates or equilibrium constants, which is the more conventional way of doing physical organic chemistry.

00:08:44 I think there's validity in both approaches, but I think that his personal style was to work with the molecules themselves.

00:08:51 In fact, if you heard Woodward give a discussion of a mechanistic problem,

00:08:56 he would start in his characteristic way drawing the structure on the blackboard very carefully.

00:09:05 And the longer he talked about this and the greater the depth with which he penetrated,

00:09:11 the more you felt that if you only were smart enough to see it,

00:09:16 the structure itself was telling you how the molecule should behave.

00:09:20 And of course it is, really. It is.

00:09:22 It's just we're not quite smart enough to see it yet.

00:09:25 That's a very good emphasis on the structural, yes.

00:09:29 And of course many of the problems that he worked out,

00:09:34 many of the things that are really landmark studies in the field of mechanistic investigation,

00:09:42 were done with a strong structural bias.

00:09:46 In fact, they were almost always designed to have an elegant yes or no kind of resolution to them.

00:09:57 I'm thinking, for example, of the work with Tom Katz on the cope rearrangement of the cyclopentadienes.

00:10:07 There is one study which has never really been published, as far as I know.

00:10:13 Absolutely classic piece of work, which incidentally leaves a certain unresolved problem in the literature.

00:10:23 And that concerns the mechanism of the dienone-phenol rearrangement.

00:10:31 I don't know if you know about this, but the only place it's been published is in the Festschrift of Robert Robinson in 1955.

00:10:39 Perspectives in Organic Chemistry.

00:10:40 Perspectives in Organic Chemistry.

00:10:42 And that was a system designed to yield an absolutely beautiful distinction

00:10:47 between the doer type of pi-complex intermediate and the true spiro-diene intermediate

00:10:54 that one would write in a conventional rearrangement.

00:10:57 And it led to an absolutely unequivocal answer that the spiro-diene was correct

00:11:02 and it was not going through the pi-complex.

00:11:03 Now the reason, and it doesn't seem to have been pointed out by reviewers of the subject as far as I know,

00:11:11 is that there is an absolutely contrary result in the literature by a man named Futaki in Japan

00:11:18 who did some extremely elegant C14 labeling experiments in a somewhat different system

00:11:26 which leads to the exact opposite answer, just as cleanly.

00:11:29 So here's a case where Woodward got an answer and it undoubtedly is correct for that case,

00:11:38 but it's not the whole answer.

00:11:42 Well, I call to mind the classic study, the collaboration with Winstein on the anti-7-norborn-enil case

00:11:50 which was a structural problem if ever there was one,

00:11:53 where one found 14 powers of 10, as I recall, rate acceleration from introduction of the double bond.

00:12:00 Now my memory is a little hazy about that, but there was a bet between Winstein and Woodward

00:12:06 over the outcome of that experiment.

00:12:08 I don't remember who was on which side, but I think that Woodward bet that the product would be inversion

00:12:17 and that Winstein bet the other way.

00:12:19 Do you know the answer to that?

00:12:22 No, I don't know. I didn't know about this bet.

00:12:25 I think I know the answer to the question, which is more complicated than they put it at that time,

00:12:30 but I don't know who was on which side.

00:12:33 That's an interesting question.

00:12:35 That particular problem was one that fascinated Woodward,

00:12:39 and of course is related directly to the fascination with structure.

00:12:47 One of the features of that particular system, which is so bizarre,

00:12:52 is not the fact that the anti-7-norborn-enil is so fast,

00:12:55 because it's not really much faster than many other secondary tosylates,

00:12:58 it's that the saturated one is so enormously slow.

00:13:03 When I came to Harvard, one of the things he set as possible problems for me

00:13:08 was to make some homologs where the ring angle was slightly expanded

00:13:12 in order to see if that would speed things up, as it turned out it did.

00:13:18 So it was not a purely steric, that is, there was not a pure steric hindrance argument,

00:13:22 it was an internal angle strain argument.

00:13:28 To prove this, I gathered a lot of numbers, which he was sublimely uninterested in,

00:13:32 but he was interested in the result.

00:13:34 There were darn hard numbers to get, too.

00:13:41 One physical, organic, or mechanistic problem that I recall getting involved in

00:13:47 that really never resulted in a publication,

00:13:49 but which represented an important insight on his part,

00:13:53 was the notion that a highly strained system

00:13:58 undergoing an orbital symmetry forbidden process might end up being chemiluminescent.

00:14:04 And he first suggested this to me.

00:14:08 I happened to be at Harvard the day this inspiration struck,

00:14:12 so I was privy to it very early on.

00:14:16 He had the idea of taking hexamethyldurbenzene and heating it up

00:14:20 with the thought that one might generate benzene in an excited state

00:14:24 and get emission out of it.

00:14:26 And he knew that I was in possession of some of this precious substance

00:14:30 and urged me to try the experiment.

00:14:32 And after some pressing, I did it and reported success to him,

00:14:38 which he found very exhilarating,

00:14:41 until on further study I discovered that the quantum yield for emission was 10 to the minus 9.

00:14:47 Yeah, well, I was at a meeting where he reported your success without your knowledge.

00:14:52 I know, I know.

00:14:53 The people at that meeting got the impression that it was highly successful indeed.

00:14:57 Well, that was my fault, not his.

00:15:00 It was only later that I discovered, later but before publishing,

00:15:04 that I discovered that the quantum yield was 10 to the minus 9.

00:15:07 And clearly there were impurities playing a part in this particular example,

00:15:12 so nothing was ever published on hexamethyldurbenzene.

00:15:15 But the conception was a beautiful one,

00:15:17 and of course in the hands of Turow and Breslow later on led to fruition.

00:15:23 And it's been an idea that's had a good deal of currency since.

00:15:27 Yeah, yeah.

00:15:28 Well, I also think of Woodward's fascination with the newest physical methods

00:15:34 which were available, of course,

00:15:36 as pioneering the use of ultraviolet spectroscopy as an organic chemical tool,

00:15:42 very early on getting into the use of infrared,

00:15:46 NMR as soon as an instrument was available

00:15:48 which would produce anything but a meaningless blob,

00:15:54 ORD, he has a paper with Moffat, Jurassic, and Moskowitz, as I recall,

00:16:02 use of x-ray crystallography at a time when no one would have dreamed

00:16:06 of using x-ray crystallography to establish the structure

00:16:08 of an intermediate in an organic synthesis.

00:16:12 You know, that business about the infrared spectroscopy

00:16:17 reminds me of something that Roald said this morning

00:16:19 about his interaction with some of his colleagues

00:16:22 on the physical chemistry side.

00:16:25 And I recall when I went to Harvard as a postdoc in 1949,

00:16:33 in fact, my Ph.D. thesis was the first application

00:16:38 of infrared spectroscopy to structure determination

00:16:41 that had ever been done in organic chemistry at Columbia.

00:16:44 And it was done on a Perkin-Elmer Model 12.

00:16:48 No, in fact, it was done on a homemade instrument

00:16:52 up on the eighth floor in Chandler Chemistry Lab.

00:16:56 But by that time, Harvard already was equipped with the commercial Baird instrument

00:17:01 and Woodward was far ahead of anything we were doing in the application of this.

00:17:06 And when I came to Harvard, I asked how he had stolen a march on everyone else.

00:17:12 How did he know in advance that this was going to be so important?

00:17:16 And, of course, a lot of it came from his experiences

00:17:19 in the penicillin work during the war.

00:17:21 But one of the things that he mentioned in a rather disparaging way

00:17:27 was that he was, of course, in consultation

00:17:30 with a number of his physical chemistry colleagues

00:17:33 about the use of infrared spectroscopy in proper ways of interpreting experiments.

00:17:38 And the physical chemists would...

00:17:42 He said, had it been left to the physical chemists,

00:17:45 this tool would never have been introduced

00:17:47 because, as far as they were concerned,

00:17:49 all carbonyl groups had the same frequency of absorption.

00:17:53 And, in fact, there was a very considerable question

00:17:56 as to whether there was any such absorption as a carbonyl absorption

00:17:59 since naturally everything is coupled in the real world.

00:18:03 But what his, if I may use the term,

00:18:06 and I think it's not too strong a term,

00:18:08 his genius was to be able to go beyond that

00:18:10 and say, well, here are some organic structures.

00:18:14 I will take the spectra and, by gosh,

00:18:16 these carbonyl groups or whatever is causing this,

00:18:20 they're causing shifts.

00:18:21 And those shifts are explicable in terms of structure.

00:18:24 Therefore, even if I don't understand the fundamental origin,

00:18:28 that's useful, that's empirical.

00:18:30 And so he just barreled ahead and did it.

00:18:33 Yes, I remember a particularly brilliant tour de force that he gave,

00:18:37 another Thursday evening seminar.

00:18:39 He'd had some people from Lilly down to see him the day before.

00:18:44 They presented him with some information they had on a new antibiotic,

00:18:47 I believe it was streptonegrin, as a matter of fact,

00:18:49 which turned out to be quite important in an antibiotic.

00:18:52 The structure was unknown, but they had a lot of physical data

00:18:55 and elemental analysis and probably some part structures.

00:18:59 I don't remember anymore.

00:19:01 But he went through an analysis of this data

00:19:04 and laid out in absolutely logical and beautiful fashion

00:19:08 what must be the correct structure.

00:19:12 It required a postulate that there was a urea in it

00:19:15 in a biphenylene system which must be twisted

00:19:19 so that the normal infrared absorption was shifted from the normal position.

00:19:24 There were no models of that available,

00:19:27 and he suggested that someone in the audience might wish to make it.

00:19:31 Biphenylene urea, is that the correct name for it?

00:19:34 It's the urea bridging the ortho position of biphenyl group.

00:19:38 I can see it, but I can't name it.

00:19:41 Kirby Scherer proceeded to take the challenge

00:19:44 and found some ortho amino biphenyl,

00:19:49 made the urea overnight and left it on his desk the next morning.

00:19:54 It had, in fact, the correct infrared spectrum.

00:19:57 Unfortunately, the structure of streptonegrin turned out to be something totally different,

00:20:01 but it's still a nice example of this sort of analysis.

00:20:06 What we're reminiscing about Thursday evening seminars,

00:20:09 I can't resist commenting on the one that I found most inspiring

00:20:12 during my graduate career.

00:20:14 This was one that was given by a graduate student

00:20:17 who subsequently became a very well-known and respected chemist,

00:20:21 rose very high in a notable company.

00:20:25 He had been a graduate student of Woodward's for five years

00:20:28 and was really nowhere in his graduate work.

00:20:32 But he gave a seminar on some ancient work of Otto Diehl's.

00:20:36 It dated from the teens, I believe.

00:20:39 It took him an hour and a half to lay it all out on the blackboard.

00:20:42 It was just a wonderful collection of structures and transformations.

00:20:47 With the sophistication that 1950s graduate students had,

00:20:51 they could recognize that most of this had to be wrong somehow.

00:20:55 But the problem that we were set was to figure out what it all meant.

00:21:00 Of course, we all scribbled meaninglessly for hours.

00:21:04 At least my own efforts were quite unavailing.

00:21:06 At more than 30, Woodward got up, walked to the blackboard,

00:21:10 and during the next couple of hours laid out in great detail, great clarity,

00:21:16 the entire work of Otto Diehl's totally reinterpreted.

00:21:19 There wasn't one structure in common with one of the ones

00:21:22 that had originally appeared in the literature.

00:21:26 Reinterpreted the entire array of chemistry.

00:21:30 The graduate student who had given the seminar

00:21:32 proceeded to go into the laboratory,

00:21:35 take key parts of the work, get the compounds,

00:21:37 get spectroscopic data on them,

00:21:39 which supported in detail all of Woodward's proposals.

00:21:43 He quickly wrote a Ph.D. thesis and was gone within a few months.

00:21:47 Was that work ever published?

00:21:49 I don't believe so.

00:21:50 I think it was one of the many Woodward theses

00:21:52 that reside quietly in the Harvard Library.

00:21:55 But it was just a magnificent intellectual feat,

00:21:58 as far as I was concerned, that I found tremendously inspiring.

00:22:02 And speaking of mechanistic chemistry,

00:22:04 clearly it required a very good feel for mechanism

00:22:08 to trace one's way from one structure to the next

00:22:11 in this enormous morass of data.

00:22:15 I think he probably used mechanism more as an aid to thinking

00:22:19 and remembering things than as an end in itself,

00:22:22 and yet saw beauty in mechanism as in structure, I think.

00:22:30 The use of IR again recalls Andy Kendi's thesis,

00:22:33 which also never saw the light of day,

00:22:35 in which Kendi added diazomethane to ketene, as I recall,

00:22:43 getting something with an infrared spectrum of 1815 reciprocal centimeters,

00:22:48 which of course is cyclopropanone, as we all know now,

00:22:52 but which at that time couldn't be trapped.

00:22:58 Turow did very much the same thing many years later,

00:23:01 maybe ten years later.

00:23:07 That business of when one can claim to have made a compound,

00:23:14 that's undergone an interesting metamorphosis really.

00:23:17 This is a little bit off the subject,

00:23:19 but I think since you raised the question of cyclopropanone,

00:23:22 nowadays the instrumental techniques allow us really to identify a compound

00:23:26 even though we can't claim to have it in hand.

00:23:29 All kinds of species have been identified to everyone's satisfaction,

00:23:32 or at least seemingly so,

00:23:35 and yet they haven't been subjected to carbon-hydrogen analysis,

00:23:39 and they haven't been put in a bottle and stored on a shelf.

00:23:43 I think that some of the old-time chemists,

00:23:45 and by that I mean chemists who were active even as recently as 50 years ago,

00:23:49 would really find this difficult to accept.

00:23:54 Criteria for identity, for existence, have really changed.

00:23:59 That's right, although I recall that even in my thesis

00:24:03 I made two derivatives of everything and got them analyzed.

00:24:06 Oh, you bet. You bet.

00:24:08 And if one can do it, it's still the right thing to do.

00:24:12 But it seems that there is a tacit agreement on the part of people active in the field

00:24:18 that in order to move forward we have to take the risk

00:24:23 that there may be occasional mistakes made by this method of identification.

00:24:28 So in that way I think we're coming a little closer to the biochemists

00:24:31 who've never been able to put their intermediates in bottles

00:24:35 and have always taken much more indirect evidence.

00:24:38 We have learned that structure determination at 8 degrees Kelvin in argon matrices is not easy.

00:24:43 It ain't easy. That's right.

00:24:48 Well, going back to very general things, your earlier comment about vitamin B12

00:24:54 brought to mind I think a very general idea which Woodward taught all of us,

00:24:59 and that was the idea of snatching victory from defeat.

00:25:03 I can recall in Chemistry 203, I think it was called,

00:25:08 Chemistry of Natural Products, which he occasionally taught at the end of a term.

00:25:15 He gave, of course, very memorable lectures,

00:25:18 and I recall one series on meserpine, which was really a pedagogical masterpiece.

00:25:22 One of the lessons that emerged strongly from that was that

00:25:26 when the reaction went the wrong way and gave you something totally unwanted and unexpected,

00:25:31 maybe with a little thought you could recognize that this was the best possible development,

00:25:36 and there was a really neater way to get where you were going in the long run

00:25:39 if you simply used your head and took maximum advantage of what nature had given you.

00:25:46 And, of course, the things that went awry in the B12 synthesis that led to the orbital symmetry concept

00:25:53 represent perhaps the example Pareg belongs to,

00:25:56 of taking a victory and turning it into, or defeat and turning it into a rather spectacular victory.

00:26:02 Yeah.

00:26:05 Yes, the same synthesis further on led to, I think,

00:26:11 the first use of preparative high-pressure liquid chromatography in organic synthesis.

00:26:16 Now, that was not exactly a success,

00:26:18 but it was snatching something from the jaws of defeat at that stage,

00:26:22 since at that point they had a lot of isomers or something like that.

00:26:25 Was that or nothing.

00:26:27 It was certainly a success for W.A. Waters.

00:26:29 That's right.

00:26:34 Well, one could ask the question whether mechanism did more for synthesis

00:26:41 or synthesis did more for mechanism in the vitamin B12 story.

00:26:45 I mean, in the history of science, it's not clear to me

00:26:50 which of those two accomplishments will prove to be the greater.

00:26:54 But I think one could make some kind of case

00:26:57 that the stimulus that was given to mechanistic thinking

00:27:02 by the attempt and ultimate success in synthesis of vitamin B12 was really unparalleled.

00:27:12 And that the orbital symmetry thing very probably would have come along somehow or other,

00:27:18 but I don't think it would have had quite the impact if it hadn't happened in just the way that it did.

00:27:25 And that was a serendipitous outcome of a project

00:27:31 that was designed for a completely different purpose.

00:27:34 Also, having two very highly prepared minds there to grab these things.

00:27:41 We were discussing earlier the fact that orbital symmetry correlations

00:27:46 had suggested themselves to a number of people before as early as 1961, I think,

00:27:53 when having put in a footnote in a paper in the vitamin D series,

00:27:58 Osterhoff's comment that the stereochemistry probably had something to do

00:28:04 with the occupancy of the highest real molecular orbital.

00:28:09 But that simply was never generalized.

00:28:15 Well, you know, that's an interesting point that you raise.

00:28:18 And one can trace, I think, with some accuracy,

00:28:23 and I hope this does no violence to the memory of Osterhoff,

00:28:27 who was an admirable physical chemist and certainly a fine gentleman,

00:28:33 and made many contributions in different areas of chemistry.

00:28:38 Now, the reason why the Dutch group did not come up with orbital symmetry at the time,

00:28:46 even though they had the facts available to them,

00:28:49 I'm sure has to do with Osterhoff's recognition that, in fact,

00:28:57 the ground state orbital symmetry rules are not invariably turned around for photochemistry.

00:29:05 And he recognized very early in the game that the fact that the stereochemistry

00:29:11 in the butadiene ring closure was, photochemically, was opposite to that

00:29:16 in the cyclobutene ring opening, thermally.

00:29:20 He had, at a very early stage, tested the idea that it was to do with the phase properties

00:29:26 of the highest occupied MO, and found that that idea was not correct at a rigorous level.

00:29:32 Because, in fact, it's not the first excited state that counts.

00:29:36 It's the second excited state, and there's a level crossing,

00:29:39 and the thing is extremely complicated in a photochemical reaction.

00:29:42 Well, there was a case of too much rigor.

00:29:45 They blew it because they knew what the right answer was,

00:29:48 but they got this small point and sacrificed all the rest of it.

00:29:53 Hoffman, in his charming discussion of this this morning,

00:29:56 brought up the fact that it was the very sloppy extended Huckel calculations

00:30:02 which allowed him the insight which was necessary.

00:30:07 Well, I've heard Osterhoff discuss this particular point of why it was

00:30:10 that he didn't expand upon his original insight.

00:30:14 He ascribes it largely to the fact that his own upbringing

00:30:17 was within the framework of Ehlen's bond theory,

00:30:20 and that trying to pursue the original notion within that framework,

00:30:24 he simply hit a wall.

00:30:27 And had he been a molecular orbital jock, the outcome might have been very different.

00:30:33 Yeah.

00:30:34 I don't know.

00:30:35 The other thing, of course, that one can say is that the Woodward-Hoffman combination was unique.

00:30:42 I mean, having a very fine organic chemist, Osterhoff a very fine physical chemist,

00:30:47 but there was not, as you put it, the two prepared minds did not coexist at the right time.

00:30:53 They were very good, but they were not really ready for what they had in their hands.

00:30:58 That's right.

00:30:59 Woodward had in his head practically all of the vitamin D stuff.

00:31:03 That's right.

00:31:04 All of the cyclopropane ring openings,

00:31:07 an enormous number of other cycloadditions and ring openings.

00:31:14 He saw all the relatedness of these things.

00:31:16 Because he'd been looking at them for five or six years trying to understand them.

00:31:20 That's exactly right.

00:31:22 Hoffman, as he told us this morning, had picked up on Woodward's suggestion

00:31:27 that the occupancy of the highest filled orbital was important

00:31:31 because he didn't believe it at first.

00:31:33 He checked it out by calculation and found that it in fact worked.

00:31:38 And I'm trying to remember exactly his anecdote about the fact that he was asked at the end of the seminar

00:31:44 to comment on this idea when he'd just finished doing the calculations,

00:31:48 which Woodward didn't know.

00:31:50 And so he was quite well prepared to comment on it.

00:31:54 Well, speaking of the contributions of others to the whole orbital symmetry idea,

00:31:58 of course, Kenichi Fukui was in a sense prepared

00:32:01 and had indeed prior to Woodward and Hoffman come up with some insights awfully close to the key ones.

00:32:08 And I think did not come away with more of the credit in part

00:32:13 because he wasn't prepared to run with the ball quite as fast as the Woodward-Hoffman combination.

00:32:18 He didn't have the command of organic chemistry.

00:32:20 Well, he didn't have the command of examples which he could show that he explained.

00:32:23 That's exactly right. That's exactly right.

00:32:26 That's the unique thing about the Woodward-Hoffman combination

00:32:29 is that they had all that information and they had the theoretical tools as well.

00:32:34 And I would say the following, that they did a superb job with it,

00:32:41 but in retrospect there were half a dozen people who should have recognized what they did

00:32:49 and who had all the information available to them.

00:32:52 They just hadn't been working as hard to have a problem.

00:32:54 That's right. All of them feel slightly cheated.

00:32:57 I mean, it just went right past a lot of people.

00:33:00 I think that has to be true of an awful lot of the great discoveries in science.

00:33:03 That's right.

00:33:04 I'm sure that's true.

00:33:05 We were fortunate enough to witness one of these really epic-making events

00:33:09 when a great simplifying truth suddenly bursts on the world and everybody says,

00:33:15 yes, that's the way it is.

00:33:16 Of course. Of course.

00:33:18 Well, I think perhaps we've come to a point where we could leave

00:33:29 unless anyone has any further anecdotes to share.

00:33:32 I certainly enjoyed the chance to chat with you.

00:33:37 Thanks very much for the invitation to be with you.

00:33:40 Thank you.

00:33:48 Thank you.

00:34:18 Thank you.

00:34:48 Thank you.