IN MEMORIAM VLADIMIR PRELOG (1906-1998) 138

CHIMIA 1999,53, NO.4

Chimia 53 (1999)138-139 © Neue Schweizerische Chemische Gesellschaft ISSN 0009-4293

Vlado as Cheiron

Kurt Mislow*

Over a period of several decades, Vlado ucts. His involvement in stereochemistry bonded interactions. Prelog's pioneering Prelog's laboratory was a mecca for aca- was a direct outgrowth of this passion. It concept, therefore, represented a break- demic guests from abroad, many of them began with his studies of Cinchona alka- through of major proportions. from the United States, and it is my priv- loids during his years in Prague, in the late It seems appropriate here to quote an- ilege to represent them today on the occa- 20s and early 30s, and continued in Zagreb other stanza from Christopher's poem: sion of this commemoration. I intend to with the first of his many scientific tri- share some personal reminiscences of the umphs, the synthesis of adamantane, in Combining his sense of the practic time that I spent with my mentor at the 1941. In 1944, just a few years after his With his vision of scale galactic, ETH, over 40 years ago. In order to place arrival at the ETH, Prelog had already He made Prelog's Rule my remarks in their proper perspective, published papers that specifically ad- An imperative tool however, it will first be necessary to out- dressed questions dealing with stereochem- By concocting a brew atrolactic. line Prelog's vital contributions to the ical aspects of natural products. To give development of modern stereochemistry. just one example, one paper published in So, by the end of the 1950s, stereo- As William Klyne remarked on the occa- that year is titled 'Uber die Konfiguration chemistry had clearly become the domi- sion of Prelog's Nobel Prize in 1975: der asymmetrischen Kohlenstoffatome 3, nant theme inPrelo g' s work. It was around 'van 't HojJis considered as the founder of 4 und 8 der China-Alkaloide'. In hind- that time that I was able to spend the 'chemistry in space'; Prelog has been the sight, we can see in this title the foreshad- academic year 1957-58 as his guest in the High Priest of this cult for the past 20 owing of the CIP rules. The same year also Laboratorium. Pre log had found his first years.' saw the first of the many landmarks in pure inspiration in organic chemistry by work- I would like to begin my tribute to the stereochemistry that are identified with ing with Rudolf LukeS in the 1920s, and master by quoting a stanza from a poem Prelog's name: the famous resolution of this experience had taught him, as he tells that my son Christopher wrote on the Trager's base into its mirror-image com- us in his autobiography 'My 132 Semes- occasion of Prelog's 80th birthday cele- ponents by chromatography on a column ters of Chemistry Studies', that 'the best bration at the ETH-Ziirich in 1986. The of lactose hydrate. way to study science is as an apprentice to full poem was published in Chimia 1986, Justa few years later, in 1947, Prelog's a master who is a model both in his field 40,394 as part of a report on this celebra- acyloin synthesis of medium-sized rings and in his personal characteristics'. So it tion, opened the way to a comprehensive study turned out that, by good fortune, I had of many-membered ring systems. In the come to the right place at the right time, to Of this I have never been surer, first Centenary Lecture of the Chemical apprentice myself to the right master. And hence expect no one's demurrer Society, in 1949, Prelog showed, for the To be under Prelog's spell proved to When I proclaim aloud first time, how the methodology of con- be a memorable experience. Forty years How we're all so damned proud formational analysis can be employed to have passed and memories tend to warp To have known the world's greatest Fach- rationalize the physical and chemical prop- and blur. But I still remember those glory horer. erties of medium-membered ring com- days as though it were yesterday. The air pounds. This groundbreaking work led to at that time was electric with the excite- Throughout his long and illustrious an understanding ofconformation-depend- ment generated by a constant stream of career, Prelog maintained a consuming ent steric effects on structure and reactiv- galvanizing discoveries, by the race to interest in the chemistry of natural prod- ity. During that time, Prelog also succeed- beat the scientific competition, and by the ed in formulating an empirical rule, now hubbub of incessant scientific discussions. known as Prelog's Rule, governing the The wonderfully stimulating atmosphere stereochemical direction ofthe asymmet- was due entirely to Prelog's nurturing ric atrolactic acid synthesis. The under- influence and charisma. As first among lying idea behind this rule was that the equals, or 'Dorfiiltester' as he liked to relative steric bulk of the groups attached characterize himself, Pre log presided over 'Correspondence: Prof. K. Mislow Department of Chemistry to the carbinol carbon was responsible for a stable of brilliant young students and of Princeton University the direction of the asymmetric synthesis. Dozenten, like Albert Eschenmoser and Princeton, NJ 08544. USA It is commonly assumed, nowadays, that DuilioArigoni, who were to achieve world- Tel.: 6092583941 Fax: 609 258 67 46 the course of asymmetric syntheses is, in class reputations. The conviviality in this E-mail: [email protected] general, controlled by differential non- hothouse of ideas, and the affection, deep IN MEMORIAM VLADIMIR PRELOG (1906-1998) 139

CHI MIA 1999, 53, No.4 admiration, and respect that the denizens some occasions where hotly debated argu- occasion. But rarely were they merely of the Laboratorium felt for each other was ments were in the nature of theological entertaining - there was always a message promoted as much by Prelog's intellectu- disputes and tended toward medieval scho- buried in the pleasantry. The intellectual al leadership as by his human kindness, his lasticism. In any event, Prelog's most rigor of his arguments remained uncom- genial manner, his genuine modesty, and significant efforts in this direction consist- promised, but the avuncular manner helped his utter lack of pretentiousness. An arti- ed in the introduction of logically unas- to make the medicine go down more eas- cle in the July 6, 1998, issue of Chemical sailable and internally consistent stereo- ily. And this was his genius as a teacher. & Engineering News carried the headline chemical notations. In 1953, together with The last chapter of Roald Hoffmann's 'Talent thrives at the ETH-Zi.irich' and Barton, Hassel, and Pitzer, he proposed book 'The Same and Not the Same' is described the Swiss Federal Institute as it the axial/equatorial tenninology to describe entitled 'Cheiron'. Cheiron was the wis- is today as a scientific 'paradise'. It surely the spatial arrangement of CYclohexane est, the most righteous, and the most learned was a paradise 40 years ago. And there can bonds. In 1956, together with Cahn and of all the centaurs, famous for his knowl- be no doubt that Pre log was the architect Ingold, he proposed the R1S terminology, edge of medicine and for his skill in hunt- who layed the groundwork for this happy now familiar to everyone as the CIP sys- ing, music, and the art of prophesy. But state of affairs. tem, to specify the configuration of ster- above all, he was a great teacher. Cheiron The highlight of my visit was the stim- eoisomers. And in 1960, together with became the foster father and tutor of many ulation afforded by innumerable lively Klyne, he proposed the syn/anti-clinal/ great heroes of Greek mythology who discussions with the master, who, with peri planar terminology to describe steric learned those arts from him: Peleus,Achil- fatherly benevolence, had taken me under relations across single bonds. les, Asclepius, Castor, Jason, Theseus, his wing. What seemed uppermost in his Beyond all of this, however, Prelog Heracles, Odysseus, and many others. In mind in those days was the need to impose saw the need for a systematic classifica- this chapter, Hoffmann said: 'The teacher a logical structure on stereochemistry so tion of stereoisomers, for a way of cata- in me likes this teacher'. I chose the title as to bring reason and order to a field loguing the innumerable stereoisomers of for my talk with this sentiment in mind, dominated at that time by rank empiri- an organic compound of known constitu- but also, of course, because it happens cism, pragmatism, and intuitive, not to say tion. It was a challenge that he tackled with fortuitously to convey Prelog's intense sloppy, thinking. The time seemed ripe to the characteristic enthusiasm and thor- preoccupation with chirality in chemistry. provide stereochemistry with a conceptu- oughness that was the hallmark of all of his Over the years, this subject had become of ally sound foundation. Prelog's main work. As he expressed it to me in a meta- paramount concern to him; indeed, it is the motivation, as I saw it, was his thirst for phor, the objective was to construct a title of his Nobel lecture. But to return to reason and order, coupled with a sense for comprehensive chest of drawers, each the name of the centaur: Hoffmann did the aesthetic - he even taught me how to drawer labeled with a particular class of point out that 'The Centaur's name comes erase a blackboard properly, that is, in stereoisomer and containing the appropri- from the Greek word for hand' , but he did parallel vertical strokes - and this is what ate stereomodels. This exercise in system- not explain the reason for giving the cen- led him on a quest to frame the principles atic taxonomy was to remain his main taur this name. What does handedness of stereochemistry in the language of ge- passion in the years to come. It resulted in have to dO'with the centaur's activities- ometry, and to the development of what he the construction of theoretical models of which, by the way, included activities called the geometric foundation of stere- stereoisomers from various combinations such as archery and music for which he oisomerism and, at other times, chemical of simplexes, and it inspired the synthesis surely needed both hands? It all seemed topology. It was also around that time that of novel types of stereoisomers - cyclo- quite mysterious to me, so I consulted my the 'cult' of chemistry in space, in Klyne's stereoisomers, vesperenes, and molecules colleague at Princeton, Robert Fagles, who formulation, began to take shape. We called possessing so-called elements of pseu- is in the Comparative Literature depart- it 'chirosophy', and Prelog was the un- doasymmetry . ment. Fagles had recently published a disputed leading light and star attraction Discussions with Prelog proved to be widely acclaimed translation of the Iliad among the coterie of chirosophists (or not only instructive and stimulating, but and the Odyssey, so I thought that he chirosophers) like Andre Dreiding and invariably good fun. He was renowned for might be the right person to ask. Although Jack Dunitz, among others, who shared his inexhaustible supply of jokes, anec- the question was new to him, he came up his objectives. dotes, and aphorisms. Here is another rel- with an answer immediately: he speculat- Among these was the need to give evant stanza from Christopher's poem: ed that the name probably meant to convey precise meaning to the shape of the stere- 'the one whose hands one is in', in other omodel. In part, this entailed cleaning up But Prelog's no mere academic. words, the teacher. Just like our Vlado. stereochemical nomenclature, or to 'puri- His gifts far transcend just the chemic. Upon his death, Cheiron was placed by fy the stereochemical vocabulary', as Gun- His skilled craftsmanship Jupiter among the stars, where he now ter Helmchen recently put it. For example, Of the quick-witted quip appears in the shape of the constellation in his careful and meticulous way, Prelog Makes contagion of mirth epidemic. Sagittarius. The memory of the teacher followed the mathematician Felix Klein in whom we are honoring today will shine drawing a distinction between molecular It would be doing Prelog an injustice, just as brightly in the annals of science, geometry and topography. He was most however, to describe him as merely a and among those of us who had the privi- decidedly not a friend of the semantically brilliant and witty raconteur. His was that, lege of ha ving known the world's greatest challenged, and he tried with some suc- to be sure, as well as a master of the fast Fachhorer. cess to rid the language of stereochemistry repartee, but he was much more than that. of questionable expressions such as 'op- His stories, told with his wry and self- tical isomers' and 'antipodes'. I have to deprecating sense of humor and his well- confess, however, that, in this quest for tuned feeling for the ironic, were always terminological exactitude, there were also captivating and precisely honed to fit the