a ae a ed eee DOVOYLVOOOCOLOOOOUFT [aaa tank eo sped nad ds ao nd OXFORD SCIENCE PUBLICATIONS — OO Jf E 2 LL. ¢ sSeries Editor’s Foreword Ionic, radical and perieyclic reactions are the three main groups of organic reactions. Bvery organic chemist has to be able to recognize each of these types of reaction, and know something of their mechanisms and the factors that affect how well they work in organic synthesis. In this primer, Ian Fleming leads you in a more of less continuous narrative from the simple characteristics of pericyclic reactions to a reasonably full appreciation of their stereochemical idiosyncrasies. He introduces pericyclic reactions and divides them into their four classes in Chapter 1. In Chapter 2 he covers the main features of the most important class, cycloadditions—their scope, reactivity, and stereochemistry. In the heatt of the book, in Chapter 3, he explains these features, using molecular orbital theory, but without the mathematics. He also introduces there the two Woodward—Hoffmann rules that will enable you to predict the stereochemical outcome for any pericyclic reaction, one rule for thermal reactions and its opposite for photochemical reactions. The remaining chapters use this theoretical framework to show how the rules work with the other three classes—electrocyclic reactions, sigmatropic, rearrangements and group transfer reactions. By the end of the book, you will be able to recognize any pericyclic reaction, and predict with confidence whether it is allowed and with what stereochemistry. This primer by Ian Fleming on Pericyclic Reactions complements the Primer (No. 36) by Tony Kirby on Stereoelectronic Effects and will be of interest to apprentice and master chemist alike. Professor Stephen G. Davies The Dyson Perrins Laboratory, University of Oxford Preface Pericyclic chemistry is more than thirty years old, and its history is no longer part of the subject. I have barely commented in the text on how the subject developed, so perhaps I can say something here to place it ina historical context. By the end of the 1950s the main features of ionic and radical reactions were reasonably well understood, but pericyclic reactions were not even recognized as, a separate class. Diels-Alder reactions, and a good many others, were known individually. Curly arrows were used to show where the bonds went to in these reactions, but the absence of a sense of direction to the arrows was unsettling. Doering provocatively called them ‘no-mechanism reactions’ in the early 1960s.There were a number of such reactions, often with disconcerting aspects, that were simply not understood, because they seemed to fly in the face of all sense. Why, if dienes added to alkenes, didn’t alkenes easily dimerize to make cyclobutanes—the reaction was known to be exothermic but rarely happened? On the other hand, acetylenes and allenes did give 4-membered rings when treated with electrophiles—why were they different? Why did cés-3,4- dimethylcyclobutene open to give the thermodynamically less stable cis,trans- butadiene? Why did calciferol transfer a hydrogen atom easily from C-9 to C-18, (steroid numbering; itis a shift of 7 atoms along a triene), whereas most trienes, like cycloheptatriene, where it ought to have been even easier, didn’t? Why did pentadienyl cations cyclize, with bond formation from C-1 to C-5, when both atoms, since they both carried partial positive charge, ought to repel each other? Most organic chemists at the time didn’t notice these problems, and those who did were not aware of how many there were or how much they resembled each other. This began to change in the autumn of 1963, when R. B. Woodward, in the course of his synthesis of vitamin By2, came across another seemingly inexplicable example of counter-thermodynamic stereochemistry—it would now be recognized as the disrotatory electrocyclic ring closing of a hexatriene. The reactions I listed as questions above were in his mind, and now, with his very ‘own reaction to think about as well, he recognized a pattern, and sought an explanation for all these bewildering observations in molecular orbital theory. He and R. Hoffmann, starting in 1965, introduced a series of rules governing the stereochemistry of the various classes of pericyclic reactions. They showed, with a significant contribution from Abrahamson and Longuet-Higgins, how to explain them all using correlation diagrams based on the symmetry of the molecular orbitals. Then in 1969 they introduced the word pericyclic, and showed that all the rules could be subsumed in the pair of rules used in this, book, They were exciting times, as order was revealed, as explanation followed, and as predictions were made and fulfilled. I was there when Ranganathan first brought the Bj2 result to light, and heard Woodward at group meetings discussing the reactions I listed as questions above. I will finish with a very personal memory of his drawing for me, at my bench late one evening in the spring of 1964, the four atoms of butadiene and the six atoms of hexatriene, with, the lobes of the p-orbitals filled in for what we would now call the HOMO, relating the pattern that emerged to Ranganathan’s results, and saying, “It must have something to do with the molecular orbitals.” From this tentative perception, the subject grew to maturity in six intense years. I hope this book, densely packed as it is, will bring you to an appreciation of the beautiful pattern that emerged, to become one of the fundamental branches of organic chemistry, June 1998, Cambridge Ian Fleming