Sir Derek Barton (1983) - Creativity in Organic Chemistry

The title of my talk certainly included the key word of this meeting. The minister, I noticed, used the word creativity at least 10 times in his talk. When a minister uses a word, it’s always a good thing to pay attention to. In fact Kappa Cornforth, who is not only a brilliant chemist but also a very able poet, was so inspired by my title that he wrote a poem. And he has given me permission to read this poem to you. Now, I don’t think that you should try to translate it, a poem is too sophisticated and subtle a thing for easy translation. But here you are, here is Kappa Cornforth’s poem about creativity. You see that it is a limerick and you can see how it is supposed to rhyme. And here is the poem: Three kings who were at the nativity Praised Joseph for his creativity And credit is rarely allotted more fairly For all forms of ghosted activity. I think that's charming. Bravo for Kappa Cornforth. Now, I was going to give you a nice talk about creativity with lots of chemical reactions but Count Bernadotte got at me and told me that I had to tell you how to win a Nobel prize when you are not yet 31. So I am giving my talk for those people present who have less than 31 years. Organic chemistry is about organic molecules and there are a number of simple definitions that all students of organic chemistry know. I just remind them... we must take away these lights, where is the light expert... So, now we have to have a number of definitions and in molecules we recognise molecular structure. First of all, we have to determine the molecular formula, which is the number of atoms and the kinds of atoms. Then we have to determine the constitution, a concept originally due to Kekule, that is to say which atoms are bonded to which. We then have to define the configuration, which goes back to the time of van’t Hoff and Le Bel in the last century, and the configurations are the ways of arranging the molecule about the asymmetric centres. And I take the most simple definition at this point, say the asymmetric centres involving carbon atoms where you have four different bonds to one carbon. And as van’t Hoff pointed out, you have 2 to the N isomers, where N is the number of asymmetric centres, and that is a very fine formula which has stood the test of time. And Emil Fischer, for example, spent a long time showing how true it was in sugar chemistry. Now we come to conformation. And conformation, the definition of conformation always leads to argument. I give you my definition, which is a very simple definition, my definition is that the conformation of a molecule of defined constitution and configuration is the various arrangements of that molecule in space, which are not super-poseable. That is to say you allow for bond rotation, angle flexing, bond stretching, that gives you an infinity of conformations for every molecule. You would think that that idea, that concept would be of no value but it so happens that organic molecules usually like to have a preferred conformation. Usually one conformation or several preferred conformations. And the study of these conformations is conformation analysis, that is how the molecule really is in three dimensions, and the correlation of that 3-dimensional preference with chemical and physical properties. Well, to most people today all that sounds very obvious and simple. That is because conformational analysis, which was not known really or not appreciated in 1950, in the 1940’s, has since become something which is taught in all universities, which is taught even to high school students. Let us just take one or two little examples of a simple nature. Here we have our old friend cyclohexane. And cyclohexane has always been used by people who study conformation, because of its symmetry. And you remember that we have two kinds of cyclohexane, if we start putting substituents on, here we’re putting them in the one and four positions, and if they are on the same side of the molecule, imagining the cyclohexane to be flat, which is what we thought it was at one time, then this is cis, and if they are on the opposite sides, they are trans. And we all know nowadays that it is the chair conformation of cyclohexane which is preferred to the boat, or what is in reality the preferred form of the boat when we really do have a boat, that is the twist boat. And I have here some molecular models that I will talk about later and there you can see very clearly, there is a perfectly respectable chair and I just have to flip it and it becomes a boat and then I twist it a little more and it become a twist boat. And we recognise two kinds of hydrogen bonds in the cyclohexane chair conformation, and they are of course just a geometrical analysis of the molecule, those bonds parallel to the threefold axis or axial, and those which are not axial, are equatorial. And to arrive at that took us some time but eventually everybody agreed about that. I know you know all this and I’m going to go through it rather quickly. But there may be some people who don’t. Now, here is another little piece of conformation analysis where we’re looking at what are the conformations of these two compounds, the cis-disubstituted compound and the trans-disubstituted compound. And you see here is one chair and if we pull up this end and push down the other end, we would turn it into another form of chair. And you notice that we have one equatorial bond there and one axial bond there, which will become one equatorial bond and one axial bond. So in fact we have performed no operation whatsoever in chemical terms. All we have done is to contribute to the entropy of the molecule. It’s not true for the trans isomer because there we have two equatorial bonds, and when we flip the ring up and down, we end up with two axial bonds for X. So that’s a real difference that you can - the structures are not superposeable and you can start to discuss why. Now, I am going to say something about Professor Hassel, because I shared the 1969 Nobel prize with Professor Hassel, and the citation was for the concept of conformation. Now, Professor Hassel was born in 1897 and he died two years ago. He spent nearly all his life at Oslo University, though he did his graduate studies in Germany. He was at the university from 1925 to 1964, and then later on, as Professor emeritus, he was Professor from 1934 to 1964. And he went to Germany to learn about x-ray crystallography, but when he got back to Oslo, he found of course that he couldn’t afford any x-ray crystallography apparatus, so he had to make do with measuring dipole moments, which in those days was something you could do relatively inexpensively. And then he moved on to electron diffraction. But these two techniques had a rather bad reputation in the 1930s with organic chemists. Organic chemists at that time didn’t believe very much in the results because there were plenty of symmetrical molecules which were supposed to have dipole moments and which of course really didn’t. And for electron diffraction, you had to compare the density on a photographic plate and that was done with the eye, without an instrument, and so there was always room for interpretation, it’s a subjective measurement. And I draw your attention to one little paper, which I thought was rather nice, from Professor Hassel in 1939, in the JACS, this is a preliminary communication. And in this preliminary communication he describes the tetrabromide of cyclohexane 1,4 diene. It’s a well known compound, nicely crystalline substance, and he said, well, it has two bromines equatorial and two bromines axial. And he determined that by dipole moments, by electron diffraction and then he did some x-ray diffraction. And he writes in his paper something which I think is typical about preliminary communications, he writes: as we would have wished in the case of the x-ray crystallographic part, we should not like to delay publication much longer and are therefore publishing our results now in preliminary form.” And it will not surprise you to learn that there was no subsequent publication in any other form. But of course the war came along and that completely changed the nature of science. In 1943 Professor Hassel published a very important paper in a very obscure journal, and in Norwegian, too. And so nobody knew about this paper. Why he did this, well, of course the country at that time was occupied and probably he didn’t want to send it for publication in Germany and he couldn’t send it for publication in America or in the UK, so he published it in Norwegian. And it was later translated and republished in this reference. So if you want to read it, there it is. And what he does is to summarise his results, dipole moments and electron diffraction results principly, on halogenated cyclohexanes. And he shows that this is the preferred conformation of cyclohexal chloride, this is the preferred conformation for the 1,2 trans dihalides, this is the preferred conformation for the 1,4 trans dihalides and this for the 1,3 cis dihalide. And he suggests that this one can’t exist, but, as you will see later, natural product chemists are perfectly familiar with molecules of that kind. So what he does then is to say that, well, the conformation is preferred when the substituents, the majority of substituents are equatorial. And this is the less preferred conformation when the substituents are axial. That of course is a very simplistic way of presenting things as we now know, but nevertheless at that time it was a very stimulating and important observation. The only problem was, as I said, that we didn’t know about it, because we couldn’t read this journal and nobody really knew about it until it was republished. Now, to continue with this 1943 contribution of Professor Hassel. He didn’t get all of it quite right, he was worried about cyclohexane 1,4 diol, because he said it aught to be in the chair, but it had a dipole moment. So he didn’t want to say there was any of the boat there to explain the dipole moment, which is the real explanation, he wanted to say everything was absolutely clear, it was chair or boat, couldn’t have both, and that therefore cyclohexanedione had to exist partly enolised under the conditions of his experiment. That of course is not true but it’s just a little thing in passing. In 1943 to 1944 he was arrested and he spent two years in prison, so he didn’t make any contributions to the literature during that time. After the war, in 1944 I think, he came back to the University of Oslo and took up his work again with Professor Bastianson. Bastianson, a very able assistant at that time, later became professor of physical chemistry in Oslo, like Hassel, and is now rector. And what they published in Nature in 1946 was this, and this is what first attracted me to the subject of conformational analysis, Hassel and Bastianson found that trans-decalin existed in a 2-chair form, as everybody thought it should, and that cis-decalin existed in another 2-chair form. And that was completely contrary to what was written in all the text books at that time. If you look at the text books of the 1920s and 1930s, you will find that cis-decalin is supposed to exist in a 2-boat conformation. Now, where did that strange idea come from? It came from a writings by Moore in 1918, who had said that cis- and trans-decalin must be different compounds. Must exist and must be different compounds. Now, today of course it’s quite obvious to us that they’re two compounds. But at the time many people believed that cyclohexane was flat, and if you put two flat cyclohexanes together, they said you will only get one decahydronaphthaline, and in fact, of course, the real correct theory teaches that you will get two. So there we are, that changed the text books. Then there was one more publication from Professor Hassel on sugars, where he correctly interpreted the conformations and where he recognised for the first time the existence of the anomeric effect. Now, in 1953 I had to review a field of conformation analysis, and I wrote about Professor Hassel as follows, I think I’ll read it to you: on the electron diffraction of cyclohexane compounds in the vapour phase have contributed greatly to our knowledge of these more subtle aspects of stereochemistry.” I have never been able to find any reference where Professor Hassel wrote anything about me. Now, conformational analysis is nowadays one of the subjects which has a history book about it. And this book deals with the work of Hassel and myself, and it deals also with the work of Professor Prelog and Professor Cornforth. And it’s written by Ramsey and it was published in 1981. And he gives the principle events in conformation analysis, apart from Hassel and myself. And he says, well, in 1890 Sachse wrote a paper about cyclohexane existing in chair and boat forms. That is quite true, that paper had absolutely no affect upon organic chemists, because they could never isolate their isomers which would have been predicted by this postulate. And therefore they said it was wrong and, any case, von Baeyer told us that cyclohexane was probably flat. Then, 1918 the work of Moore, the publication that they’re both theoretical papers, to which I’ve already referred. In the 1920s Hermans and Böeseken in Holland did some very elegant work on the reaction of alpha dials with boric acid and they showed that complexes were formed when the hydroxyls had the right conformational relationship in space. And really that was early conformational analysis. Nobody paid much attention to it though. And then, in 1929, Haworth, the great organic sugar chemist who later got the Nobel prize for vitamin C, he wrote a book on the sugars and he defines the word ‘conformation’ in the way that I have defined it, more or less. And that’s the first reference in the literature I think to the word. Then in 1937/1938 Isbell in another obscure publication studied the bromine oxidation of sugars and corrected and interpreted the results correctly. And finally I must make reference to Professor Prelog, who in 1950 published a paper in the British journal on the conformations of medium sized rings. And I well remember Professor Prelog’s lecture in London in 1949 when he told us about this very interesting work. Now, I said that we could choose the preferred conformation of molecules, we’ve already said the chair is the preferred conformation. This all comes about because of the existence of the ethane barrier. And the ethane barrier was something discovered by Kemp and Pitzer in 1936, who were studying entropy and were then calculating entropy, they were determining entropy calorimetrically and then, calculating it by statistical mechanics, what it should be, and they didn’t get the same result, unless they postulated a barrier to rotation of about 3 kilocals in ethane. And you see that there are two forms, two extreme forms of ethane, the eclipsed and the staggered. And these models, there we are, it’s completely eclipsed there, you can only see that one hydrogen sits on top of the other. And then the alternative is the staggered, where they are at a maximum distance away from each other. And if the forces are attractive, then it is the eclipsed form which would be favoured, and if the forces are repulsive, then it would be the staggered form which would be favoured. These are non bonded interactions between hydrogens, of course. And if you transfer that down to cyclohexane, where all the bonds are completely staggered in the chair conformation, that would favour the chair conformation. Now at this point Professor Eyring came in and made a contribution which everybody thought was very important. Eyring at that time was the leading theoretical chemist in the world, certainly in the States, and everybody followed what he calculated with great attention. And he calculated in a paper in the JACS in 1939 that the eclipsed was more stable than staggered. And so that was exactly the opposite to the reality, but naturally in the 1930s people didn’t know. And then Langseth and Bak in 1940 in the Journal of Chemical Physics published a paper on Raman spectra. And they said that they had showed that cyclohexane was plainer, which of course it’s not. And they said they also showed that this tetrachloroethene was eclipsed for the preferred conformation. So it wasn’t really quite so clear as we now know it to be, it wasn’t clear in the early 1940s. And Professor Hassel in 1943, when he wrote his famous paper, he went to great lengths to show that Langseth and Bak were completely wrong. He didn’t say anything about Eyring. Now I am going to say a little about myself. And you will notice that my list of accomplishments is much longer than Professor Hassel’s. And that is because I know much more about myself than I do about him. And you see I was born in 1918 and that I’m going to die in the next century. And that’s because I wish to attend the Nobel celebrations in 2001, which will be the centenary year and there’s bound to be some splendid celebrations in Stockholm, and I’m sure that the king’s famous Bordeaux will be flowing as it did before. Now, as I said before, the Nobel prize, I shared it, because of my publication and experience in 1950, this very short paper on the conformation of the steroid nucleus. It was a very short paper because I had to type it myself, not having any secretarial facilities. I was 31 at this time when it was published. How did I get to that point, that is what I am trying to teach the younger chemists here. Well, first of all I went to school, everybody has to do that, then my father died suddenly and I left school, so I spent two years in industry doing routine work. And I convinced myself very quickly that this was such a horrible way to spend your life, there must be something better and that better had to be at the university. So although I passed no formal examinations, I got to work and in one year I did three years exams and I got to Imperial College. Imperial College is an excellent place to go to because it’s a very serious university where students still work. The war came along, so we did war time related work and a PhD was quickly obtained in 1942. And if you wish me to write you a letter on a piece of paper that you will never read I can still do it. Then a year in industry, that was a formative period, because in organophosphorus chemistry, where I didn’t discover the Wittig reaction or anything important like that, but I did discover that I didn’t like industry very much because I wanted to do – I knew what I wanted to do and it wasn’t what other people were going to tell me to do. So I took half the salary that I was being paid and I went back to Imperial college as a demonstrator, a demonstrator in practical inorganic chemistry to mechanical engineers. And there is no lower position that you can have in a university than that, that’s really the bottom. But after one year I was promoted and I was allowed to teach physical chemistry so I had three years teaching physical chemistry, chemical kinetics, and then I had one year at Harvard where I wrote this paper, where I replaced R.B.Woodward for a year teaching, and then five years in Birkbeck where I could finally do organic chemistry, that was the night school so it was a very good place to be, because you could work 14 or 15 hours a day, and the only thing was that it wasn’t very good for your wife, had a bad effect on wives. Then the University of Glasgow for two years and then back to Imperial college for 21 years. And now I am in Gif, since 1977 in fact, and I find that my life in the CNRS has completely rejuvenated me, it’s a very stimulating organisation. All Nobel prize winners who get near to 59 should come and join us in the CNRS. Now, I will tell you a little bit about my work at that time, because it’s relevant. What have we established so far, we’ve established that – I tried several things before I found out what I really liked and that I was prepared to pay the price. Now, here you see the first piece of work that I did and your first published work is always interesting and on the first published work it was my own work that I did myself. P.Alexander, he is Professor Alexander now, professor of cancerology in London, but at that time he was just a student like me. And he was studying inert dust insecticides. And he noticed that when the insect died, some of them, particularly this one, tribolium, it gave off something which changed the colour of the inert dust and so there must be an excretion. So I grew the insects, isolated the compound and showed it was ethylquinone and that’s in the biochemical journal in 1943 and it’s the first identification of a volatile substance produced by an insect I believe. But we never went any further in that field. But that was good because that was done in my spare time, that was done after 6 o’clock in the evening or on Sundays, because the rest of the time I was with the secret inks. And here, in 1942 to 1948, I did purely theoretical work on molecular rotation differences, that is looking at the literature of steroids and triterpenoids and trying to correlate the structures proposed with their optical rotations. And this way we could correct quite a number of structures, it’s a principle which goes right back to van’t Hoff, so there’s nothing original in it, it was just the application that was interesting. And then in 1948 force field calculations. I was so impressed by Hassel’s cis-decalin work that I set out to calculate what should be the relative energies of these molecules. And this is the first force field calculations applied to cyclohexane and ethane and things like that. The other work was done by Westheimer on hindered rotation and Hughes and Ingold on the SN2 process. And to do this I designed these molecules, these models that you see here, these were, I did the calculations and gave the plans to a watch maker who then made the models, and these were the models which you converted into steroids, get to be quite big, which enabled me to really get a feeling for conformational analysis. So these force field calculations of course were very trivial things, they just required lots and lots of time and with these models I could measure instead of having to calculate all the distances. But I got things in the right order, more or less in the right numbers, too. And then there was the 1950 paper on the conformational analysis of the steroid nucleus into which I will not go in detail at this time. But I will say that to write this one had to have a prepared mind and what I had was a background in physical chemistry, some knowledge of inorganic chemistry, because I taught that too. But a love for organic chemistry and a complete knowledge, more or less complete knowledge of all steroid and triterpenoid publications at the time, because there weren’t so many. And this part I had all done in my spare time when I wasn’t doing the work for which I was paid to do. And so I would say to you that if you want to do something when you’re young, you have to be really motivated, you have to like it, you have to work very hard, you have to read a lot of literature, you have to do a lot of thinking. And if you are multidisciplinary, you have much better chance of finding something interesting than if you stick to just one discipline. Now, in 1951 Arthur Birch was able to write in the annual reports, and I read this to because it was only one year after the publication: promises to have the same degree of importance as the use of resonance in aromatic systems.” I think he was right. Now, what did I do after 1950 in the world of conformational analysis? We turned first of all to the pentacyclic triterpenoids, these are rather complicated molecules, as you see, they have 8 or 9 centres of asymmetry, depending on whether you look at the unsaturated or the saturated molecule. So there are 128 resomates there and 256 there. We were able to get the problem down to 1 out of 2 resomates by just conformational analysis, by looking at the molecule in this way. And then the x-ray crystallographers came along and I’ve always worked in close collaboration with x-ray crystallographers, I’ve always believed in x-ray crystallography, very rarely do they get anything wrong, just occasionally get something wrong, usually because their assistant has copied it down the wrong way round, their technician, that seems to be the problem. Anyway, this was given to Carlisle, former collaborator of Dorothy Crowfoot, Dorothy Hodgkin, and he got the right result, very nicely. And then in 1953 was lanosterol. And lanosterol was a molecule, which as soon as you had the structure, the constitution, you could write down stereochemistry. And then a little bit later we come to cycloartenol, and this is 1954 and again, as soon as you could write the constitution you could write the stereochemistry. And it’s interesting that we were working, with others of course, in parallel on the lanosterol problem and the cycloartenol problem at the same time and that they are both the key molecules in steroid biosynthesis now. The cycloartenol is a key molecule for plant steroid synthesis and the lanosterol, of course, is the key molecule for the biosynthesis of steroids in mammals and animals. Now, the first exception is always interesting. At this point you see in the early 1950s, everybody was saying everything is always a chair, so there were chairs everywhere and there were never any boats. And then, in collaboration with Professor Magee, Chelsea college, we came across a boat. Now there were some boats where the boat did not have the choice of being a chair, but we all said, everybody said at that time if a 6 member ring has the choice, it will be a chair and never a boat. We came across the first example where a 6 member ring decided to be a boat, even though it could have been a chair, but it is an exceptional case. We were brominating this molecule, these are two meso groups which are actually related to each other, and therefore Hassel wouldn’t have liked that, but that’s the way it is in nature. And we expected of course to obtain two bromo compounds. A bromo compound with a bromine equatorial and a bromo compound with a bromine axial. And instead of that we got indeed two bromo compounds, a major isomer with a bromine equatorial and a minor isomer which should have had the bromine axial but had the bromine equatorial. Now, you could determine which was equatorial and which was axial by infrared and UB spectroscopy at that time, it was a reliable technique. So we knew we were correct in our conclusions and we had to explain it. And the simplest explanation was to say that you had brominated it axially and then the molecule had flipped because it was a ketone, so it was easier to flip it. And secondly, if you did this flipping, the bromine which, if it had been axial, would interact with the two meso groups, would have turned itself over and become equatorial instead. Well, everything that happened afterwards, this is a phenomenon which was studied very extensively in fact, everything that happened afterwards has confirmed this interpretation. And you’ll notice that when you reduce this ketone with borohydride and you go back to a cyclohexane without a trigonal atom, then the conformation changes back again to the preferred chair and you have this very hindered situation where a bromine is axial and pushing against two meso groups which are also axial. So it’s a very hindered exceptional situation. And finally, in 1957 and later in 1960, we investigated what we called conformational transmission, which is our way of saying how a double bond or a feature in a molecule can be transmitted from one end to the other. In triterpenes we made these kinetic studies, we prepared benzyladenine derivatives and measured the kinetics of their formation and showed that the rates really varied quite remarkably with the kind of double bond that you had or didn’t have in the distant ring. So if we take this as 100 with a double bond shifted just one place, it’s 17, that is a factor of more than 5 in rate, which is a very large rate difference. And over here when we saturate it we get 44 and in the steroids it’s even more impressive, all the condensation goes into the 2 position, as we established, but the rates are quite different, the saturated case is 182 on this scale, the scale of this lanostenone. This is 47, the double bond in 7 8, and when you shift the double bond just one position in the ring, in the second ring, the rate increases to 645. So the difference, delta 6 over delta 7 is a factor of 14, and we said this is a clear example of conformational transmission from one ring to another ring. Now, Allinger, first of all Hendrickson and then later Allinger, brought in this method of force field calculations using much improved equations and using of course the computer, and that changes everything. What took me three months laboriously to do by hand in 1947, they can do in a fraction of a second and do it much better. So that completely changes the conformational analysis in fact, you can now do your calculation quicker, much quicker than doing the experiment. And Clark Still is demonstrating exactly how you can do chemical synthesis in that way. Well, what Allinger did then was to recalculate all these effects and see if they existed according to force fields. And happily the answer is that they do and there’s a perfect correlation between our results and those calculated by Allinger using his kind of force field. So I’ve told you then how you can win this Nobel prize, you have to work hard, you have to have a slightly eccentric background, you have to be very catholic in your taste, you have to look in all directions, you have to read a lot and you have to think and it’s thinking which is I think the most important thing. And thinking is something which we don’t do enough of in organic chemistry and happily I have five minutes in which to tell you about thinking. If you look at the great advances that have been made in organic chemistry since the war, I would certainly like to put conformation analysis amongst those, there is also the correlation of orbitals that we will be hearing about in the next talk. That’s certainly very important. And then there are the various reactions which have completely changed synthetic chemistry. Herb Brown, I know, will tell us about hydroboration and borohydrides, that is certainly correct. We could cite the Wittig reaction, that is correct, too. But have we finished, we could talk about Ziegler Natta polymerisation that also completely changed organic chemistry. But nowadays there are some pessimists around and I met one yesterday, a journalist who said there’s nothing going on in chemistry anymore. And I think this, well, I can’t talk about other branches of chemistry, but I know a bit about organometallic chemistry, and I know something about organic chemistry and I am completely opposed to this kind of talk. And the reason, the problem with organic chemistry is that we don’t think enough and that our professors don’t have enough imagination. So when you go back you should tell your professor he should have more imagination. Then things will be better. Now, let me prove to you that we have not come to the end of all the interesting and wonderful things we can find in organic chemistry. Sharpless has announced a couple of years ago how you can attain efficiencies of optical synthesis, asymmetric synthesis, which nearly equal those of enzymes, in some cases do equal those of enzymes. And he does this in a very simple way with titanium, four-valent titanium, as the key to the synthesis, using diethyl tartrate, it’s as simple as that, as the asymmetric inducing reagent and tert-Butyl hydroperoxide, and then he mixes this together and you get these wonderful yields in asymmetric synthesis. In my opinion this, unless someone does something better, this is going to be as important in synthesis as the Wittig reaction. And if I had not been instructed to talk about conformational analysis today, I would have been talking I think about our work on the oxidation of saturated hydrocarbons. Because we have developed a system now which in a very simple way will oxidise saturated hydrocarbons, very selectively and faster than it will oxidise olefins or aromatics and faster than it will oxidise compounds of sulphur as well. So it’s a very selective system, the yields are, if you allow, for recovered hydrocarbon, I think more or less quantitative. And I would like to think that by the time we have the next meeting, when I will talk about it, some very interesting things will have happened. And the system is based on an imaginary P450 enzyme as it was before we had any porphyrins around. What was the world like before we had porphyrins, when we didn’t have any oxygen, or not much, and there was acid of course, lots of acid around. And we said, well, if we’re going to imitate P450, what we need is a hydrocarbon, oxygen, triplet oxygen, and two electrons and two protons. And this is going to give us the alcohol and water. That’s what nature does in P450 enzymes, let us imitate it but let us imitate it in an anaerobic way, prebiotic anaerobic way. So we just took iron powder, it was as simple as that, and acetic acid and pyridine, with a little water and triplet oxygen and hydrocarbon. And with that system you get excellent yields of oxidised saturated hydrocarbon with a preference for attack on CH2, so you get preferentially CH2 going to keta. Mechanism, we’ve shown that this is due to a complex acetative of iron which is reduced by the iron powder and which has this extraordinary properties of selectively oxidised saturated hydrocarbons, you can replace the reducing, iron is not necessary, you can replace it by zinc or you can do it electrochemically which is more important. And using the complex acetate of iron, you can have catalytic turnover numbers of 2,000 or 3,000, which is certainly the kind of numbers that our friends in industry like to see, they don’t like to see 1 or 2, they like to see 2,000 or 3,000. So I think this is going to be important, anyway I’ve told you about it, as that’s my contribution in five minutes to creativity, and thank you for your attention.

Sir Derek Barton (1983)

Creativity in Organic Chemistry

Sir Derek Barton (1983)

Creativity in Organic Chemistry

Comment

In the long history of the Lindau meetings, 1983 must have been a good year. One reason is the special set of a little more than 10 Nobel Laureates that accepted the invitation and participated in the meeting. But in the lectures one can also find references to Count Lennart Bernadotte, the main driving spirit behind the meetings. In this lecture, e.g., Derek Barton discloses that he had planned to give a straight chemistry lecture with many chemical formulas, but that Count Lennart had asked him instead to tell the audience how to win a Nobel Prize when you are not yet 31. From my own memories of Count Lennart, this would have been a typical request to speakers that the Count thought could improvise. And at 64, Sir Derek certainly shows that he knows how to do just that. Not only does he give the young part of the audience good advice, but he also starts out by reading a limerick on creativity composed for him by another speaker, John Cornforth. So what is particular with the age 31? It turns out that Derek Barton published his first important paper on the conformation of organic molecules in 1950, at the age of 31. This may have been the most important paper for the Nobel Chemistry Committee and, if so, the 20 years that elapsed between the actual research work and the Nobel Prize have become quite typical during the second half of the 20th Century. So the question put by Count Lennart might have been phrased “how to make an important research work when you are not yet 31”. Sir Derek’s advice is to be motivated, work hard, read a lot, be multidisciplinary and most importantly, think. Since his opinion is that Professors of Organic Chemistry think too little, his advice to the young audience is to go back to their universities and tell their professors to think more. It would be interesting to know what fraction of the audience actually followed this particular advice!

Anders Bárány

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