Examples of Pericyclic Reactions

In this section, we will briefly review the various kinds of pericyclic reactions so far discovered in order to show how Evans principle can be used to interpret them. Many additional examples will be found in the reviews listed at the end of this chapter. 

The majority of cycloaddition reactions involve interactions between two (occasionally three) n systems as in the Diels-Alder reaction [equation (5.284)] or the analogous additions of allyl cations to dienes (148)-(150). Such n cycloadditions usually take place by cis addition to each conjugated system because the corresponding transition states are less strained. The reactions are then of Hiickel type (see, e.g.. Figs. 5.35a and 5.36a) and follow the same rules for aromaticity as do ordinary conjugated hydrocarbons. Some examples follow  

This is one of the rare cases of a triple addition. The interactions between the 2p AOs in the transition state are indicated by dotted lines. It is easily seen that addition to each double bond is cis, so the six-membered ring in the transition state is isoconjugate with benzene. 

This example illustrates another point. Cyclodecapentaene (154) is in fact rather unstable because it cannot exist in a planar form, for steric reasons. These steric problems arise, however, entirely from the framework of a bonds. It has nothing to do with aromaticity, this being a function of the n electrons. In applying the rules for aromaticity to diagrams such as (153) or (154), we should therefore ignore all steric effects since these are clearly irrelevant to a consideration of the delocalized MOs in the corresponding transition state. 

The bonds marked with asterisks are easily seen to be essential single bonds in the two transition states (cf. azulene p. 100). Deleting them, the transition states are seen to be isoconjugate with (155), which contains six-and ten-membered rings, both aromatic. The second steps are the reverse of n cycloadditions, taking place via transition states analogous to those in the initial additions. This can be seen very easily if the intermediate adducts are written as (156) or (157). 

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Biological examples of pericyclic reactions are relatively rare, although one much-studied example occurs during biosynthesis in bacteria of the essential amino acid phenylalanine. Phenylalanine arises from the precursor chorismate,... 

There are a number of examples of pericyclic reactions for which the interaction diagram is not simply connected. We define a non-simply connected pericyclic system as one in which in the interaction diagram at least one basis orbital is connected to more than two others. An example is shown with its interaction diagram in Equations 11.37-11.38. 

In this chapter we shall illustrate the application of the selection rules to particular examples of pericyclic reactions. The chemical literature provides a wealth of illustrative examples, many collected in review articles.1... 

Many pericyclic reactions are stereospecific and, because they have to be run at temperatures higher than ambient, are very robust. It is somewhat surprising that there are very few examples of pericyclic reactions being run at scale, especially in light of our understanding of the factors that control the stereochemical course of the reaction either through the use of a chiral auxiliary or catalyst (Chapter 26). 

The graph D is called the dynamic graph of the reaction. The character of a chemical reaction is given by the structure Ep of D, as shown in the example of pericyclic reactions, which are distinguished by the fact that all the D graphs are cycles (see Figure 3.1). 

So far, cycloadditions have been our only examples of pericyclic reactions. There are several other classes of pericyclic reactions, of which the most notable are cheletropic reactions, sigmatropic rearrangements and electrocyclic reactions. In essence, frontier orbital theory treats each of them as a cycloaddition reaction. 

In the remainder of this chapter we will consider further cycloaddition reactions and other examples of pericyclic reactions. We will use the aromatic transition state approach for simplicity, although in all cases an approach based on HOMO-LUMO interactions would give the same result. 

An interesting example of pericyclic reaction is cyclization of precalciferol to steroisomeric I and II under thermal condition both of which are cis-products. Similar reaction under photochemical conditions, i.e., upon irradiation gives ergsterol(III), which is irans-product. Thus pericyclic reaction may result is different products under thermal and photochemical conditions. 

There are several general classes of pericyclic reactions for which orbital symmetry factors determine both the stereochemistry and relative reactivity. The first class that we will consider are electrocyclic reactions. An electrocyclic reaction is defined as the formation of a single bond between the ends of a linear conjugated system of n electrons and the reverse process. An example is the thermal ring opening of cyclobutenes to butadienes ... 

The first pair of examples we would like to discuss occurs in a field which lends itself naturally to be conquered by theory. Indeed, the past three decades have seen the exploration of mechanistic details of pericyclic reactions as one of the major success stories of computational chemistry. Rooted in qualitative molecular orbital theory, the key concept of... 

As pericyclic reactions are largely unaffected by polar reagents, solvent changes, radical initiators, etc., the only means of influencing them is thermally or photochemically. It is a significant feature of pericyclic reactions that these two influences often effect markedly different results, either in terms of whether a reaction can be induced to proceed readily (or at all), or in terms of the stereochemical course that it then follows. Thus the Diels-Alder reaction (cf. above), an example of a cycloaddition process, can normally be induced thermally but not photochemically, while the cycloaddition of two molecules of alkene, e.g. (4) to form a cyclobutane (5),... 

The third major category of pericyclic reactions can be looked upon as involving the migration of a a bond—hence the name—within a 7t-electron framework. The simplest examples involve the migration of a a bond that carries a hydrogen atom. 

Pericyclic reactions are concerted reactions that take place in a single step without any intermediates, and involve a cyclic redistribution of bonding electrons. The concerted nature of these reactions gives fine stereochemical control over the generation of the product. The best-known examples of this reaction are the Diels-Alder reaction (cyclo-addition) and sigmatropic rearrangement. 

Figure 12.2. Three classifications of pericyclic reactions, with examples of thermally allowed reactions. Cheletropic is a special case of electrocyclic.

Pericyclic reactions are unimolecular, concerted, uncatalyzed transformations. They take place in a highly stereoselective manner governed by symmetry proper-ties of interacting orbitals. - Characteristic of all these rearrangements is that they are reversible and may be effected thermally or photochemically. The compounds in equilibrium are usually interconverted through a cyclic transition state,224 although biradical mechanisms may also be operative. A few characteristic examples of pericyclic rearrangements relevant to hydrocarbon isomerizations are presented here. 

The Woodward-Hoffmann rules also allow the prediction of the stereochemistry of pericyclic reactions. The Diels-Alder reaction is an example of (re4s + re2s) cycloaddition. The subscript s, meaning suprafacial, indicates that both elements of the addition take place on the same side of the re-system. Addition to opposite sides is termed antarafacial. The Woodward-Hoffmann rules apply only to concerted reactions and are derived from the symmetry properties of the orbitals involved in the transition state. These rules may be summarised as shown in Table 7.1. 

The first chapter, High Pressure Synthesis of Heterocycles Related to Bioactive Molecules by Kiyoshi Matsumoto, presents a unique high-pressure synthetic methodology in heterocyclic chemistry. Basic principles and fruitful examples for pericyclic reactions, such as Diels-Alder reactions, 1,3-dipolar reactions, and also for ionic reactions, such as Sn and addition reactions, are discussed. The review will be of considerable interest to heterocyclic chemists and synthetic chemists. 

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