SPEIAL TOPI Electrocyclic and ycloaddition Reactions cis-tetramethylcyclobutene.1 INTRODUTION There are many reactions in which certain symmetry characteristics of molecular orbitals control the overall course of the reaction. These reactions are often called pericyclic reactions because they take place through cyclic transition states. With the background knowledge of molecular orbital theory that we gained from hapters 1 and 13, especially as it applies to conjugated polyenes (dienes, trienes, etc.), we are in a position to examine some of the intriguing aspects of pericyclic reactions. We shall look in detail at two basic types: electrocyclic reactions and cycloaddition reactions..2 ELETROYLI REATIONS A number of reactions, like the one shown here, transform a conjugated polyene into a cyclic compound. 1,3-Butadiene yclobutene In many other reactions, the ring of a cyclic compound opens and a conjugated polyene forms. yclobutene 1,3-Butadiene -1
-2 SPEIAL TOPI ELETROYLI AND YLOADDITION REATIONS Reactions of either type are called electrocyclic reactions. In electrocyclic reactions, s and p bonds are interconverted. In our first example, one p bond of 1,3-butadiene becomes a s bond in cyclobutene. In our second example, the reverse is true: a s bond of cyclobutene becomes a p bond in 1,3-butadiene. Electrocyclic reactions have several characteristic features: 1. They require only or light for initiation. 2. Their mechanisms do not involve radical or ionic intermediates. 3. Bonds are made and broken in a single concerted step involving a cyclic transition state. 4. The reactions are stereospecific. The examples that follow demonstrate this last characteristic of electrocyclic reactions. 3 3 trans,trans-2,4-exadiene h 3 3 cis-3,4-dimethylcyclobutene 3 3 trans,cis,trans-2,4,6-octatriene 3 3 cis-5,6-dimethyl-1,3- cyclohexadiene In each of these examples, a single stereoisomeric form of the reactant yields a single stereoisomeric form of the product. The concerted photochemical cyclization of trans,trans-2,4-hexadiene, for example, yields only cis-3,4-dimethylcyclobutene; it does not yield trans-3,4-dimethylcyclobutene. 3 h 3 trans,trans-2,4-exadiene 3 (not formed) 3 trans-3,4-dimethylcyclobutene OFFMANN AND FUKUI were awarded the Nobel Prize in 1981 for this work. The electrocyclic reactions that we shall study here and the concerted cycloaddition reactions that we shall study in the next section were poorly understood by chemists before 1960. In the years that followed, several scientists, most notably K. Fukui in Japan,.. Longuet-iggins in England, and R. B. Woodward and R. offmann in the United States, provided us with a basis for understanding how these reactions occur and why they take place with such remarkable stereospecificity. All of these scientists worked from molecular orbital theory. In 1965, Woodward and offmann formulated their theoretical insights into a set of rules that not only enabled chemists to understand reactions that were already known but also correctly predicted the outcome of many reactions that had not been attempted. The Woodward offmann rules are formulated for concerted reactions only. oncerted reactions are reactions in which bonds are broken and formed simultaneously and, thus, no intermediates occur. The Woodward offmann rules are based on this hypothesis: in concerted reactions molecular orbitals of the reactant are continuously converted into molecular orbitals of the product. This conversion of molecular orbitals is not a random one, however. Molecular orbitals have symmetry characteristics. Because they do, restrictions exist on which molecular orbitals of the reactant may be transformed into particular molecular orbitals of the product.
.2 ELETROYLI REATIONS -3 According to Woodward and offmann, certain reaction paths are said to be symmetry allowed, whereas others are said to be symmetry forbidden. To say that a particular path is symmetry forbidden does not necessarily mean, however, that the reaction will not occur. It simply means that if the reaction were to occur through a symmetry-forbidden path, the concerted reaction would have a much higher free energy of activation. The reaction may occur, but it will probably do so in a different way: through another path that is symmetry allowed or through a nonconcerted path. A complete analysis of electrocyclic reactions using the Woodward offmann rules requires a correlation of symmetry characteristics of all of the molecular orbitals of the reactants and product. Such analyses are beyond the scope of our discussion here. We shall find, however, that a simplified approach can be undertaken, one that is easy to visualize and, at the same time, is accurate in most instances. In this simplified approach to electrocyclic reactions we focus our attention only on the highest occupied molecular orbital (OMO) of the conjugated polyene. This approach is based on a method developed by Fukui called the frontier orbital method..2a Electrocyclic Reactions of 4n P-Electron Systems Let us begin with an analysis of the thermal interconversion of cis-3,4-dimethylcyclobutene and cis,trans-2,4-hexadiene shown here. 3 3 cis-3,4-dimethylcyclobutene 3 3 cis,trans-2,4-exadiene Electrocyclic reactions are reversible, and so the path for the forward reaction is the same as that for the reverse reaction. In this example it is easier to see what happens to the orbitals if we follow the cyclization reaction, cis,trans-2,4-hexadiene cis-3,4-dimethylcyclobutene. In this cyclization one p bond of the hexadiene is transformed into a s bond of the cyclobutene. But which p bond? And how does the conversion occur? Let us begin by examining the p molecular orbitals of 2,4-hexadiene, and, in particular, let us look at the OMO of the ground state (shown at right and in Fig..1a). The cyclization that we are concerned with now, cis,trans-2,4-hexadiene cis-3,4- dimethylcyclobutene, requires alone. We conclude, therefore, that excited states of the hexadiene are not involved, for these would require the absorption of light. If we focus our attention on c 2 the OMO of the ground state we can see how the p orbitals at 2 and 5 can be transformed into a s bond in the cyclobutene. A bonding s molecular orbital between 2 and 5 is formed when the p orbitals rotate in the same direction (both clockwise, as shown, or both counterclockwise, which leads to an equivalent result). The term conrotatory is used to describe this type of motion of the two p orbitals relative to each other. 3 3 ighest occupied molecular orbital (OMO) of the ground state. 3 3 4 3 3 3 4 2 5 3 onrotatory motion (leads to bonding interaction between 2 and 5) onrotatory motion allows p-orbital lobes of the same phase sign to overlap. It also places the two methyl groups on the same side of the molecule in the product, that is, in the cis configuration. Notice that if conrotatory motion occurs in the opposite
-4 SPEIAL TOPI ELETROYLI AND YLOADDITION REATIONS * 4 * 4 * 3 * 3 (OMO) Antibonding MOs (OMO) Ground state 1 1 Excited state Bonding MOs (a) (b) FIGURE.1 The p molecular orbitals of a 2,4-hexadiene (other parts of the formula omitted for clarity). (a) The electron distribution of the ground state. (b) The electron distribution of the first excited state. (The first excited state is formed when the molecule absorbs a photon of light of the proper wavelength.) Notice that the orbitals of a 2,4-hexadiene are like those of 1,3-butadiene shown in Fig. 13.5. (counterclockwise) direction, lobes of the same phase sign still overlap, and the methyl groups are still cis. 3 3 3 conrotatory motion 3 (leads to bonding interaction) elpful int Use handheld molecular models to explore the stereochemistry that results from conrotatory or disrotatory motion in these and other examples. The pathway with conrotatory motion of the methyl groups is consistent with what we know to be true from experiments: the thermal reaction results in the interconversion of cis-3,4-dimethylcyclobutene and cis,trans-2,4-hexadiene. 3 3 cis,trans-2,4-exadiene onrotatory motion 3 3 cis-3,4-dimethylcyclobutene We can now examine another 2,4-hexadiene 3,4-dimethylcyclobutene interconversion: one that takes place under the influence of light. This reaction is shown here.
.2 ELETROYLI REATIONS -5 3 trans,trans-2,4-exadiene 3 3 hv 3 Disrotatory motion cis-3,4-dimethylcyclobutene In the photochemical reaction, cis-3,4-dimethylcyclobutene and trans,trans-2,4-hexadiene are interconverted. The photochemical interconversion occurs with the methyl groups rotating in opposite directions, that is, with the methyl groups undergoing disrotatory motion. The photochemical reaction can also be understood by considering orbitals of the 2,4-hexadiene. In this reaction, however since the absorption of light is involved we want to look at the first excited state of the hexadiene (Fig..1b). We want to examine c 3 *, because in the first excited state c 3 * is the highest occupied molecular orbital. 3 * 3 ighest occupied molecular orbital of the first excited state 3 We find that disrotatory motion of the orbitals at 2 and 5 of c 3 * allows lobes of the same sign to overlap and form a bonding sigma molecular orbital between them. Disrotatory motion of the orbitals, of course, also requires disrotatory motion of the methyl groups, and, once again, this is consistent with what we find experimentally. The photochemical reaction results in the interconversion of cis-3,4-dimethylcyclobutene and trans,trans-2,4-hexadiene. 3 4 3 3 * 3 3 2 5 3 trans,trans-2,4-exadiene Disrotatory motion (leads to bonding interaction between 2 and 5) cis-3,4-dimethylcyclobutene Since both of the interconversions that we have presented so far involve cis-3,4- dimethylcyclobutene, we can summarize them in the following way: 3 3 3 conrotatory cis, trans-2,4-exadiene 3 cis-3,4-dimethylcyclobutene hv disrotatory 3 3 trans, trans-2,4-exadiene
-6 SPEIAL TOPI ELETROYLI AND YLOADDITION REATIONS We see that these two interconversions occur with precisely opposite stereochemistry. We also see that the stereochemistry of the interconversions depends on whether the reaction is brought about by the application of or light. The first Woodward offmann rule can be stated as follows: 1. A thermal electrocyclic reaction involving 4n P electrons (where n 1, 2, 3,...) proceeds with conrotatory motion; the photochemical reaction proceeds with disrotatory motion. Both of the interconversions that we have studied involve systems of 4 p electrons and both follow this rule. Many other 4n p-electron systems have been studied since Woodward and offmann stated their rule. Virtually all have been found to follow it. PRATIE PROBLEM.1 What product would you expect from a concerted photochemical cyclization of cis,trans- 2,4-hexadiene? 3 3 cis, trans-2,4-exadiene PRATIE PROBLEM.2 (a) Show the orbitals involved in the following thermal electrocyclic reaction. 3 3 3 3 200 3 3 3 3 (b) Do the groups rotate in a conrotatory or disrotatory manner? PRATIE PROBLEM.3 an you suggest a method for carrying out a stereospecific conversion of trans,trans-2,4- hexadiene into cis,trans-2,4-hexadiene? PRATIE PROBLEM.4 The following 2,4,6,8-decatetraenes undergo ring closure to dimethylcyclooctatrienes when ed or irradiated. What product would you expect from each reaction? (a) (b) hv?? 3 3 3 3
.2 ELETROYLI REATIONS -7 For each of the following reactions, (1) state whether conrotatory or disrotatory motion of the groups is involved and (2) state whether you would expect the reaction to occur under the influence of or of light. (a) O 2 3 O 2 3 O 2 3 O 2 3 (b) (c) PRATIE PROBLEM.5 3 3 3 3.2B Electrocyclic Reactions of (4n ) P-Electron Systems The second Woodward offmann rule for electrocyclic reactions is stated as follows: 2. A thermal electrocyclic reaction involving (4n ) P electrons (where n 0, 1, 2,...) proceeds with disrotatory motion; the photochemical reaction proceeds with conrotatory motion. According to this rule, the direction of rotation of the thermal and photochemical reactions of (4n 2) p-electron systems is the opposite of that for corresponding 4n systems. Thus, we can summarize both systems in the way shown in Table.1. TABLE.1 WOODWARD OFFMANN RULES FOR ELETROYLI REATIONS Number of Electrons Motion Rule 4n onrotatory Thermally allowed, photochemically forbidden 4n Disrotatory Photochemically allowed, thermally forbidden 4n 2 Disrotatory Thermally allowed, photochemically forbidden 4n 2 onrotatory Photochemically allowed, thermally forbidden The interconversions of trans-5,6-dimethyl-1,3-cyclohexadiene and the two different 2,4,6-octatrienes that follow illustrate thermal and photochemical interconversions of 6p-electron systems (4n 2, where n 1). 3 3 trans,cis,cis-2,4,6- Octatriene 3 h 3 3 trans-5,6-dimethyl-1,3- cyclohexadiene 3 trans,cis,trans-2,4,6- Octatriene
-8 SPEIAL TOPI ELETROYLI AND YLOADDITION REATIONS In the following thermal reaction, the methyl groups rotate in a disrotatory fashion. 3 trans, cis, cis 3 (disrotatory motion) 3 3 trans In the photochemical reaction, the groups rotate in a conrotatory way. (conrotatory 3 motion) 3 trans, cis, trans h 3 3 trans We can understand how these reactions occur if we examine the p molecular orbitals shown in Fig..2. Once again, we want to pay attention to the highest occupied molecular orbital. For the thermal reaction of a 2,4,6-octatriene, the highest occupied orbital is c 3 because the molecule reacts in its ground state. 6 * 3 3 5 * 3 3 Antibonding orbitals 4 * 3 3 OMO OMO 3 3 3 FIGURE.2 The p molecular orbitals of a 2,4,6-octatriene. The first excited state is formed when the molecule absorbs light of the proper wavelength. (These molecular orbitals are obtained using procedures that are beyond the scope of our discussions.) 1 Ground state 3 3 3 3 First excited state Bonding orbitals
.2 ELETROYLI REATIONS -9 3 3 The OMO (c 3 ) of the ground state of trans,cis,cis-2,4,6-octatriene We see in the following figure that disrotatory motion of orbitals at 2 and 7 of c 3 allows the formation of a bonding sigma molecular orbital between them. Disrotatory motion of the orbitals, of course, also requires disrotatory motion of the groups attached to 2 and 7. Disrotatory motion of the groups is what we observe in the thermal reaction: trans,cis,cis-2,4,6-octatriene trans-5,6-dimethyl-1,3-cyclohexadiene. OMO of ground state 1 3 4 5 3 6 2 7 8 3 3 trans, cis, cis Disrotatory motion leads to bonding interaction. 3 trans When we consider the photochemical reaction, trans,cis,trans-2,4,6-octatriene trans-5,6-dimethyl-1,3-cyclohexadiene, we want to focus our attention on c 4 *. In the photochemical reaction, light causes the promotion of an electron from c 3 to c 4 *, and thus c 4 * becomes the OMO. We also want to look at the symmetry of the orbitals at 2 and 7 of c 4 *, for these are the orbitals that form a s bond. In the interconversion shown here, conrotatory motion of the orbitals allows lobes of the same sign to overlap. Thus, we can understand why conrotatory motion of the groups is what we observe in the photochemical reaction. 3 OMO of first excited state 3 3 4 of trans,cis,trans-2,4,6-octatriene h onrotatory motion leads to bonding interaction. 3 trans 3 Give the stereochemistry of the product that you would expect from each of the following electrocyclic reactions. PRATIE PROBLEM.6 3 (a) (b) 3 hv 3 3 an you suggest a stereospecific method for converting trans-5,6-dimethyl-1,3- cyclohexadiene into cis-5,6-dimethyl-1,3-cyclohexadiene? PRATIE PROBLEM.7
-10 SPEIAL TOPI ELETROYLI AND YLOADDITION REATIONS PRATIE PROBLEM.8 When compound A is ed, compound B can be isolated from the reaction mixture. A sequence of two electrocyclic reactions occurs; the first involves a 4p-electron system, and the second involves a 6p-electron system. Outline both electrocyclic reactions and give the structure of the intermediate that intervenes. A B.3 YLOADDITION REATIONS There are a number of reactions of alkenes and polyenes in which two molecules react to form a cyclic product. These reactions, called cycloaddition reactions, are shown next. A [2 2] cycloaddition Alkene Alkene yclobutane A [4 2] cycloaddition Diene Alkene (dienophile) yclohexene (adduct) hemists classify cycloaddition reactions on the basis of the number of p electrons involved in each component. The reaction of two alkenes to form a cyclobutane is a [2 2] cycloaddition; the reaction of a diene and an alkene to form a cyclohexene is called a [4 2] cycloaddition. We are already familiar with the [4 2] cycloaddition, because it is the Diels Alder reaction that we studied in Section 13.11. ycloaddition reactions resemble electrocyclic reactions in the following important ways: 1. Sigma and pi bonds are interconverted. 2. ycloaddition reactions require only or light for initiation. 3. Radicals and ionic intermediates are not involved in the mechanisms for concerted cycloadditions. 4. Bonds are made and broken in a single concerted step involving a cyclic transition state. 5. ycloaddition reactions are highly stereospecific. As we might expect, concerted cycloaddition reactions resemble electrocyclic reactions in still another important way: the symmetry elements of the interacting molecular orbitals allow us to account for their stereochemistry. The symmetry elements of the interacting molecular orbitals also allow us to account for two other observations that have been made about cycloaddition reactions: 1. Photochemical [2 ] cycloaddition reactions occur readily, whereas thermal [2 ] cycloadditions take place only under extreme conditions. When thermal [2 2] cycloadditions do take place, they occur through radical (or ionic) mechanisms, not through a concerted process. 2. Thermal [4 ] cycloaddition reactions occur readily, and photochemical [4 ] cycloadditions are difficult.
.3 YLOADDITION REATIONS -11.3A [2 ] ycloadditions Let us begin with an analysis of the [2 2] cycloaddition of two ethene molecules to form a molecule of cyclobutane. 2 2 2 2 2 In this reaction we see that two p bonds are converted into two s bonds. But how does this conversion take place? One way of answering this question is by examining the frontier orbitals of the reactants. The frontier orbitals are the OMO of one reactant and the LUMO of the other. We can see how frontier orbital interactions come into play if we examine the possibility of a concerted thermal conversion of two ethene molecules into cyclobutane. Thermal reactions involve molecules reacting in their ground states. The following is the orbital diagram for ethene in its ground state. 2 2 p * LUMO Antibonding orbital Bonding 2 2 p OMO orbital The ground state of ethene The OMO of ethene in its ground state is the p orbital. Since this orbital contains two electrons, it interacts with an unoccupied molecular orbital of another ethene molecule. The LUMO of the ground state of ethene is, of course, p*. Antibonding interaction * 2 2 Symmetry forbidden 2 OMO of one ethene molecule 2 LUMO of another ethene molecule We see from the previous diagram, however, that overlapping the p orbital of one ethene molecule with the p* orbital of another does not lead to bonding between both sets of carbon atoms because orbitals of opposite signs overlap between the top pair of carbon atoms. This reaction is said to be symmetry forbidden. What does this mean? It means that a thermal (or ground state) cycloaddition of ethene would be unlikely to occur in a concerted process. This is exactly what we find experimentally; thermal cycloadditions of ethene, when they occur, take place through nonconcerted, radical mechanisms. What, then, can we decide about the other possibility a photochemical [2 ] cycloaddition? If an ethene molecule absorbs a photon of light of the proper wavelength, an electron is promoted from p to p*. In this excited state the OMO of an ethene
-12 SPEIAL TOPI ELETROYLI AND YLOADDITION REATIONS molecule is p*. The following diagram shows how the OMO of an excited state ethene molecule interacts with the LUMO of a ground state ethene molecule. Bonding interaction 2 2 2 OMO of an excited state ethene molecule Bonding interaction 2 LUMO of a ground state ethene molecule Symmetry allowed ere we find that bonding interactions occur between both 2 groups, that is, lobes of the same sign overlap between both sets of carbon atoms. omplete correlation diagrams also show that the photochemical reaction is symmetry allowed and should occur readily through a concerted process. This, moreover, is what we observe experimentally: Ethene reacts readily in a photochemical cycloaddition. The analysis that we have given for the [2 2] ethene cycloaddition can be made for any alkene [2 2] cycloaddition because the symmetry elements of the p and p* orbitals of all alkenes are the same. PRATIE PROBLEM.9 What products would you expect from the following concerted cycloaddition reactions? (Give stereochemical formulas.) (a) 2 cis-2-butene (b) 2 trans-2-butene PRATIE PROBLEM.10 Show what happens in the following reactions: h.3b [4 ] ycloadditions oncerted [4 ] cycloadditions Diels Alder reactions are thermal reactions. onsiderations of orbital interactions allow us to account for this fact as well. To see how, let us consider the diagram shown in Fig..3. Both modes of orbital overlap shown in Fig..3 lead to bonding interactions and both involve ground states of the reactants. The ground state of a diene has two electrons OMO (diene) LUMO 3 * (diene) + + FIGURE.3 Two symmetry-allowed interactions for a thermal [4 2] cycloaddition. (a) Bonding interaction between the OMO of a diene and the LUMO of a dienophile. (b) Bonding interaction between the LUMO of the diene and the OMO of the dienophile. LUMO * (dienophile) Bonding interaction (symmetry allowed) (a) Bonding interaction (symmetry allowed) (b) OMO (dienophile)
.3 YLOADDITION REATIONS -13 in c 2 (its OMO). The overlap shown in Fig..3a allows these two electrons to flow into the LUMO, p*, of the dienophile. The overlap shown in Fig..3b allows two electrons to flow from the OMO of the dienophile, p, into the LUMO of the diene, c 3 *. This thermal reaction is said to be symmetry allowed. In Section 13.11 we saw that the Diels Alder reaction proceeds with retention of configuration of the dienophile. Because the Diels Alder reaction is usually concerted, it also proceeds with retention of configuration of the diene. R 3 R 4 R 3 R 4 Retention of configuration of the dienophile R 1 R 2 R 2 R 1 Retention of configuration of the diene What products would you expect from the following reactions? PRATIE PROBLEM.11 3 (a) N N N N? 3 3 (b) N N? 3 N N