Cycloaddition reactions orbital symmetry rules

As discussed in Section 10.4 of Part A, concerted suprafacial [2tt + 2tt] cycloadditions are forbidden by orbital symmetry rules. Two types of [2 + 2] cycloadditions are of synthetic value addition reactions of ketenes and photochemical additions. The latter group includes reactions of alkenes, dienes, enones, and carbonyl compounds, and these additions are discussed in the sections that follow. 

The interpretation of chemical reactivity in terms of molecular orbital symmetry. The central principle is that orbital symmetry is conserved in concerted reactions. An orbital must retain a certain symmetry element (for example, a reflection plane) during the course of a molecular reorganization in concerted reactions. It should be emphasized that orbital-symmetry rules (also referred to as Woodward-Hoffmann rules) apply only to concerted reactions. The rules are very useful in characterizing which types of reactions are likely to occur under thermal or photochemical conditions. Examples of reactions governed by orbital symmetry restrictions include cycloaddition reactions and pericyclic reactions. 

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. 

There is evidence that the reactions can take place by all three mechanisms, depending on the structure of the reactants. A thermal [,2S +, 2,] mechanism is ruled out for most of these substrates by the orbital symmetry rules, but a [ 2S + 2a) mechanism is allowed (p. 851), and there is much evidence that ketenes and certain other linear molecules939 in which the steric hindrance to such an approach is minimal can and often do react by this mechanism. In a [ 2S + a2a] cycloaddition the molecules must approach each other in such a way (Figure 15.12a) that the + lobe of the HOMO of one molecule (I) overlaps with both + lobes of the LUMO of the other (II), even though these lobes are on opposite sides of the nodal plane of II. The geometry of this approach requires that the groups S and U of molecule II project into the plane of molecule I. This has not been found to happen for ordinary... 

Photoinduced [2 + 2] cycloaddition (Section 4.9) of alkenes (alkynes) to form cyclobutane (cyclobutene) derivatives is one of the best studied reactions in photochemistry.680 682 According to the Woodward Hoffmann orbital symmetry rules,336 the cycloaddition of one singlet excited (Si) and one ground-state alkene is allowed by a suprafacial suprafacial concerted stereospecific pathway (Scheme 6.45) 695 699 700 Rare concerted [4 + 2] and [4 + 4] photocycloadditions of conjugated singlet excited dienes must occur in a suprafacial antarafacial and suprafacial suprafacial manner, respectively.690 Since the suprafacial antarafacial reactant approach is geometrically difficult to achieve, [4 + 2] reactions usually proceed stepwise (involving biradical intermediates). [2 + 2] or [4 + 4] photocycloadditions can occur in either a concerted or stepwise fashion. 

MOs, while tlie two 7t c orbitals lead to the tt and tt MOs. In the initial stage of (he dimerization, the interaction between two ethylencs is weak so that 7t+ and tt. lie far below the n+ and tt levels, so that only 7t+ and rr are occupied. Of the a orbitals of cyclobutane described earlier, only those related to the tt., 7t1 and nl levels by symmetry are shown in Figure 11.1. Not all the occupied MOs of the reactant lead to occupied orbitals in the product. In particular, tt. correlates with one component of the empty set in cyclobutane. The tt+ combination ultimately becomes one component of the filled set in cyclobutane. So the reaction is symmetry forbidden. The reader should carefully compare the correlation diagram for ethylene dimerization here with the Ho + O2 reaction in ITgure 5.8. flie two correlation diagrams are very similar, as they should be, since in this instance the spatial dfstributions of tt and n " are similar to those of and respectively, in H2. These two reactions are probably the premier examples of symmetry-forbidden reactions. A related symmetry-allowed example is the concerted cycloaddition of ethylene and butadiene, the Diels-Alder reaction. We shall not cover the orbital symmetry rules for organic, pericyclic reactions. There are several excellent reviews that the reader should consult.But it should be pointed out that the orbital symmetry rules have stereochemical implications in terms of the reaction path and products formed. The development of these rules by Woodward and Hoffmann... 

In this reaction, formation of exo adduct predominates. This is in contrast to the Diels—Alder reaction, which gives endo adduct as the major product. Moreover, the [6 + 4] cycloaddition takes place in preference to a Diels—Alder [4 + 2] cycloaddition (both are thermally allowed). Such a situation is known as periselectivity and is explained by the fact that the coefficients of the frontier molecular orbitals of the LUMO of the tropone are highest at atoms C-2 and C-7. It has been found that the ends of conjugated systems have the largest coefficients in the frontier orbitals, and in accordance with the orbital symmetry rules, pericyclic reactions make use of the longest part of such systems. However, such reactions have to be permissible by the geometry of the molecule. 

The mechanism of the Diels-Alder reaction was first fully described by Woodward and Hoffmann using their orbital symmetry rules for cycloadditions. The Woodward-Hoffmann rules state that the Diels-Alder reaction is a thermal [4jts + 2 Tis] cycloaddition involving overlap of the diene s highest occupied molecular orbital (HOMO) t / with the dienophile s lowest unoccupied molecular orbital (LUMO) /. In the case of an inverse electron demand Diels-Alder reaction, the dienophile s HOMO / combines with the diene s LUMO... 

With these descriptors in hand, we can look at the generalized orbital symmetry rule. There is a definite binary nature to the theory of pericyclic reactions. For cycloadditions, [2-f2] is forbidden (all suprafacial), whereas [4-F2] is allowed (all suprafacial). Continuing with the series, [6+2] is forbidden, and [8+2] is allowed. We will also encounter patterns in the other kinds of pericyclic reactions presented electrocyclic reactions, sigmatropic shifts, etc. Based on patterns such as these. Woodward and Hoffmann proposed the following rule for all pericyclic reactions ... 

Occasionally, though, you will run across a more exotic pericyclic process, and will want to decide if it is allowed. In a complex case, a reaction that is not a simple electrocyclic ringopening or cycloaddition, often the basic orbital symmetry rules or FMO analyses are not easily applied. In contrast, aromatic transition state theory and the generalized orbital symmetry rule are easy to apply to any reaction. With aromatic transition state theory, we simply draw the cyclic array of orbitals, establish whether we have a Mobius or Hiickel topology, and then count electrons. Also, the generalized orbital symmetry rule is easy to apply. We simply break the reaction into two or more components and analyze the number of electrons and the ability of the components to react in a suprafacial or antarafacial manner. 

The present state of knowledge concerning homogeneous catalysis of ethylene polymerization by vanadium and by chromium compounds has been reviewed. The relevance of orbital symmetry rules to transition-metal catalysis of [2 + 2] cycloaddition reactions has been discussed. Examples of oligomerization reactions, catalysed by transition-metal complexes, are given in Table 3,105-m... 

Although in principle the thermal [2-I-2-I-2] cycloaddition process is allowed by orbital symmetry rules, there are problems with the entropy component, which may be overcome by using transition metal catalysis. This approach (Scheme 2.35) is one of the most convenient for the synthesis of pyridines 2.100. Metal-induced cycloaddition of two alkyne and one nitrile molecules has been described in general reviews of cycloaddition reactions [3,4]. However in some reviews on heterocycles the nitriles are considered as equivalent to alkyne in the [2+2+2] cyclotrimerization reaction [76], in particular, for the synthesis of pyridines and pyridinones in the reactions catalyzed by cobalt, ruthenium, titanium, and zirconium. 

An explanation for the finding that concerted [4 -I- 2] cycloadditions take place thermally, while concerted [2 + 2] cycloadditions occur under photochemical conditions, is given through the principle of conservation of orbital symmetry. According to the Woodw ard-Hofmann rules derived thereof, a concerted, pericyclic [4 -I- 2] cycloaddition reaction from the ground state is symmetry-allowed. 

It must be emphasized once again that the rules apply only to cycloaddition reactions that take place by cyclic mechanisms, that is, where two s bonds are formed (or broken) at about the same time. The rule does not apply to cases where one bond is clearly formed (or broken) before the other. It must further be emphasized that the fact that the thermal Diels-Alder reaction (mechanism a) is allowed by the principle of conservation of orbital symmetry does not constitute proof that any given Diels-Alder reaction proceeds by this mechanism. The principle merely says the mechanism is allowed, not that it must go by this pathway. However, the principle does say that thermal 2 + 2 cycloadditions in which the molecules assume a face-to-face geometry cannot take place by a cyclic mechanism because their activation energies would be too high (however, see below). As we shall see (15-49), such reactions largely occur by two-step mechanisms. Similarly. 2 + 4 photochemical cycloadditions are also known, but the fact that they are not stereospecific indicates that they also take place by the two-step diradical mechanism (mechanism... 

Unlike thermal [2 + 2] cycloadditions which normally do not proceed readily unless certain structural features are present (see Section 1.3.1.1.), metal-catalyzed [2 + 2] cycloadditions should be allowed according to orbital symmetry conservation rules. There is now evidence that most metal-catalyzed [2 + 2] cycloadditions proceed stepwise via metallacycloalkanes as intermediates and both their formation and transformation are believed to occur by concerted processes. In many instances such reactions occur with high regioselectivity. Another mode for [2 + 2] cyclodimerization and cycloadditions involves radical cation intermediates (hole-catalyzed) obtained from oxidation of alkcnes by strong electron acceptors such as triarylammini-um radical cation salts.1 These reactions are similar to photochemical electron transfer (PET) initiated [2 + 2] cyclodimerization and cycloadditions in which an electron acceptor is used in the irradiation process.2 Because of the reversibility of these processes there is very little stereoselectivity observed in the cyclobutanes formed. 

Although thermal [2 + 2] cycloadditions are forbidden as concerted reactions by the orbital symmetry conservation rules the same structural features which promote intermolecular cy-cioadditions will also promote intramolecular reactions. In addition, the proximity between two alkene moieties dictated by the tether length and rigidity would make these processes entropically favorable. A few reports have documented thermal intramolecular cycloadditions to cyclopropenes and activated alkenes. The thermal Cope rearrangement of allylcyclopropenes apparently proceeds by a two-step mechanism in which intramolecular [2 + 2] adducts have been observed.72-73... 

If the motion had been disrotatory, this would still have been evidence for a cyclic mechanism. If the mechanism were a diradical or some other kind of noncyclic process, it is likely that no stereospecificity of either kind would have been observed. The reverse reaction is also conrotatory. In contrast, the photochemical cyclobutene—1,3-diene interconversion is disrotatory in either direction.368 On the other hand, the cyclohexadiene—1,3,5-triene interconversion shows precisely the opposite behavior. The thermal process is disrotatory, while the photochemical process is conrotatory (in either direction). These startling results are a consequence of the symmetry rules mentioned in Chapter 15 (p. 846).Vl,As in the case of cycloaddition reactions, we will use the frontier-orbital and Mdbius-HQckel approaches.37"... 

The photochemical dimerization of unsaturated hydrocarbons such as olefins and aromatics, cycloaddition reactions including the addition of 02 ( A ) to form endoperoxides and photochemical Diels-Alders reaction can be rationalized by the Woodward-Hoffman Rule. The rule is based on the principle that the symmetry of the reactants must be conserved in the products. From the analysis of the orbital and state symmetries of the initial and final state, a state correlation diagram can be set up which immediately helps to make predictions regarding the feasibility of the reaction. If a reaction is not allowed by the rule for the conservation of symmetry, it may not occur even if thermodynamically allowed. 

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.- ... 

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