Explaining Woodward-Hoffmann rules

Woodward and Hoffmann provided an understanding of pericyclic reaction mechanisms based on conservation of orbital symmetry. A few years later, Ross et al. [118] coined the term pseudopericyclic for a set of reactions they discovered, which were not explained by the Woodward-Hoffmann rules (like the oxidation of tricyclic... 

Woodward-Hoffmann rule org chem A concept which can predict or explain the stereochemistry of certain types of reactions in organic chemistry it is also described as the conservation of orbital symmetry. wCid-ward haf-mon, rul ... 

We have emphasized that the Diels-Alder reaction generally takes place rapidly and conveniently. In sharp contrast, the apparently similar dimerization of olefins to cyclobutanes (5-49) gives very poor results in most cases, except when photochemically induced. Fukui, Woodward, and Hoffmann have shown that these contrasting results can be explained by the principle of conservation of orbital symmetry,895 which predicts that certain reactions are allowed and others forbidden. The orbital-symmetry rules (also called the Woodward-Hoffmann rules) apply only to concerted reactions, e.g., mechanism a, and are based on the principle that reactions take place in such a way as to maintain maximum bonding throughout the course of the reaction. There are several ways of applying the orbital-symmetry principle to cycloaddition reactions, three of which are used more frequently than others.896 Of these three we will discuss two the frontier-orbital method and the Mobius-Huckel method. The third, called the correlation diagram method,897 is less convenient to apply than the other two. 

Such cycloadditions involve the addition of a 2tt- electron system (alkene) to a 4ir- electron system (ylide) and have been predicted to occur in a concerted manner according to the Woodward-Hoffmann rules. The two most important factors involved in the cycloaddition reactions are (i) the energy and symmetry of the reacting orbitals and (ii) the thermodynamic stability of the cycloadduct. The reactivity of 1,3-dipolar systems has been successfully accounted for in terms of HOMO-LUMO interactions using frontier MO theory (71TL2717). This approach has been extended to explain the 1,3 reactivities of the nonclassical A,B-diheteropentalenes <77HC(30)317). 

Much of what we have said about the electronic factors controlling whether a cycloaddition reaction can be concerted or not originally was formulated by the American chemists R. B. Woodward and R. Hoffmann several years ago, in terms of what came to be called the orbital symmetry principles, or the Woodward-Hoffmann rules. Orbital symmetry arguments are too complicated for this book, and we shall, instead, use the 4n + 2 electron rule for-normal Hiickel arrangements of tt systems and the An electron rule for Mobius arrangements. This is a particularly simple approach among several available to account for the phenomena to which Woodward and Hoffmann drew special attention and explained by what they call conservation of orbital symmetry.- ... 

In this primer, Ian Fleming leads you in a more or 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 heart 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. 

Whether for these reasons or not, the reactivity indices excited little interest among organic chemists, and it was only after Woodward and Hoffmann s early papers that perturbational methods were widely invoked again. Fukui and Fujimoto17-90 adopted Fukui s frontier orbital theory to explain the Woodward-Hoffmann rules, and both they91 and Hoffmann and Woodward92 were able to explain stereoselective effects [such as the preference in the Cope rearrangement (1) (2) for the chair-like intermediate (16) rather than the boat-like one (17), and the tendency for Diels-... 

In 1965, the American chemists R. B. Woodward and R. Hoffmann ( conservation of orbital symmetry or Woodward-Hoffmann rules) and Japanese chemist K. Fukui ( frontier orbital theory ) proposed theories to explain these results as well as those for other reactions. (Woodward won the Nobel Prize in Chemistry in 1965 for his synthetic work. In 1981, after the death of Woodward, Hoffmann and Fukui shared the same prize for the theories discussed here.)... 

Whether the reaction is supra- or antarafacial ought to be reflected in the relative stereochemistry of the cyclized products—and indeed it is. This reaction gives solely the diastereoisomer on the left, with the methyl groups syn—clear proof that the reaction is suprafacial. This is a difficult result to explain without the enlightenment provided by the Woodward-Hoffmann rules ... 

All these photocyclizations are well explained in terms of an electrocyclic mechanism of nitrogen-containing, six 7r-electron conjugated system, according to the Woodward - Hoffmann rule, by postulating the intermediacy of a common trans cyclic structure from which respective types of products are formed depending on the reaction conditions either a nonoxidative, oxidative, or reductive condition. 

The reaction of ketenes with alkenes is assumed to occur via a concerted nonsynchronous mechanism, where the approach of the reacting partners is orthogonal. " As a consequence, the bulkier substituent of the ketene will end up on the sterically more crowded face of the cyclobutanone product. There are two descriptions that explain the experimental results 1) according to the Woodward-Hoffmann rules, the LUMO of the ketene reacts antarafacially with the HOMO of the alkene that reacts suprafacially " 2) the HOMO of the alkene forms a bond with the pz orbital of... 

If the Stevens rearrangement is a concerted reaction, it is a symmetry-forbidden process based on the Woodward-Hoffmann rules. Indeed, it was shown to occur via an intramolecular hemolytic cleavage-radical pair recombination process, which explains the lack of crossover products and the observed retention of configuration at the migrating... 

You may think that there s not much to say about the no-mechanism pericyclic reactions, but there is. First, how they proceed stereochemically and even whether they proceed at all depends on whether the reaction is conducted thermally or pho-tochemically. For example, many [2 + 2] cycloadditions proceed only photochem-ically, whereas all [4 + 2] cycloadditions proceed thermally. Second, all pericyclic reactions proceed stereospecifically, but the stereochemistry of the products sometimes depends on the reaction conditions. For example, 2,4,6-octatriene gives cis-5,6-dimethylcyclohexadiene upon heating and /ran,v-5,6-dimethylcyclohexadienc upon photolysis. These phenomena can be explained by examining the MOs of the reactants. The rules governing whether pericyclic reactions proceed and the stereochemical courses when they do proceed are known as the Woodward-Hoffmann rules. 

The Woodward-Hoffmann rules1 for pericyclic reactions can be explained by frontier orbital theory, as Fukui3 has demonstrated. If you already know anything about frontier orbital theory, it is quite likely that you know it as one of the ways in which the Woodward-Hoffmann rules are accounted for. If this is the case, you should leave out the next 23 pages, and turn to page 109. 

This rule is almost always obeyed, and we shall find that the signs of the coefficients of the frontier orbitals regularly account for it. Frontier orbital theory is not the only way to explain the patterns of reactivity covered by the Woodward-Hoffmann rules, but it is one of the easiest. 

The treatment of the Woodward-Hoffmann rules in this book is relatively short, partly because they can be explained in other ways, and partly because they have been well treated in a number of other places. The treatment of the finer points is relatively long, but we should not lose sight of the fact that the Woodward-Hoffmann rules, and the chemistry associated with them, are much more important than what follows. 

Another question posed in Chapter 1 was Why does the Diels-Alder reaction give endo adducts Whereas the Woodward-Hoffmann rules have been explained in several (related154) ways, the frontier orbital method is virtually the only one to have been used to account for secondary effects like this.155... 

In discussing the Woodward-Hoffmann rules, we were indifferent as to which of the two components of a cycloaddition would provide the HOMO and which the LUMO. The two pairs of frontier orbitals bear a complementary relationship to each other they both invariably give the same answer, and we could safely make an arbitrary choice. To explain the effects of substituents on the rates of Diels-Alder reactions, however, we need to know which is the more... 

With these three reagents, and their singular properties, we are straying into an unusual borderline region between pericyclic and stepwise reactions. Elsewhere, this is less of a problem, and the existence of a large class of reactions safely called pericyclic is well established. We must now turn to the ideas, based on molecular orbital theory, which have been advanced to explain why the Woodward-Hoffmann rules work so well. 

Nevertheless, frontier orbital theory, for all that it works, does not explain why the barrier to forbidden reactions is so high. Perturbation theory uses the sum of all filled-with-filled and filled-with-unfilled interactions (Chapter 3), with the frontier orbitals making only one contribution to this sum. Frontier orbital interactions cannot explain why, whenever it has been measured, the transition structure for the forbidden pathway is as much as 40 kJ mol 1 or more above that for the allowed pathway. Frontier orbital theory is much better at dealing with small differences in reactivity. We shall return later in this chapter to frontier orbital theory to explain the much weaker elements of selectivity, like the effect of substituents on the rates and regioselectivity, and the endo rule, but we must look for something better to explain why pericyclic reactions conform to the Woodward-Hoffmann rules with such dedication. 

It is more difficult to explain the effect of substituents on the rates, and on the regio- and stereoselectivities of the unimolecular pericyclic reactions. We cannot strictly look at the HOMO and LUMO of each component, as we could with bimolecular reactions, and therefore cannot properly use frontier orbitals to explain the effects of electron-donating and electron-withdrawing substituents on the rates.905 The effects are profound, sometimes even strong enough to override the Woodward-Hoffmann rules.906... 

The Woodward - Hoffmann rules explain which products will be obtained in the course of certain concerted organic reactions. In particular, they are applicable for pericyclic reactions, in which the reaction consists of a reorganization of pairs of electrons. The rules were set up around 1965 by Woodward and Hoffmann Originally, the rules were used as guideline in the total synthesis of the vitamin B 2. 

Japanese chemist Kenlchi Fukui (1919-98) in the 1950s and is an alternative approach to the Woodward-Hoffmann rules. It has been very successful in explaining such reactions as the Diels-Alder reaction. 

In the course of one particular synthesis, Woodward noticed that a thermally induced reaction produced only one of two possible products. He discussed the problem with Roald Hoffmann, a Jewish refugee from Poland currently at Harvard completing some work in theoretical chemistry (he gave up experimental chemistry after one experiment sprayed purple dye on the walls of a new laboratory). Together they came up with the Woodward-Hoffmann rules, which use the symmetry of frontier molecular orbitals to predict the outcome of certain photochemical and thermal reactions. Not only did the Woodward-Hoffmann rules explain a backlog of previously unexplained results, they suggested new reaction routes. This work con-... 

Another explanation has been proposed by K. Fukuii on the basis of frontier molecular orbitals (HOMO—LUMO) of the substrates this method is known as the frontier molecular orbitals (FMO) method. Alternatively, the PMO theory based on the Woodward—Hoffmann rule and Hiickel-Mobius method is also used to explain the results of pericyclic reactions. 

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