Other Pericyclic Reactions

Although photochemical cycloadditions can prove difficult to scale up, they do offer access to cycloadducts not directly accessible by other methods [465,466], The initial studies into asymmetric synthesis by photochemical means were in the solid phase or organized assemblies, and few examples were known in solution [467,468], Circular polarized light, a chiral agent, has the potential to induce asymmetric synthesis, although useful ee s have not yet been obtained [466], 

The condensation of an imine with a Reformatsky-type reagent and tandem reactions can result in asymmetric induction [3,195,469-472], The reaction of a ketene with an electron-rich alkene results in a [2 + 2] cycloaddition, although other systems can also be used [473-475], The stereochemistry of the adduct is 

Many types of pericyclic and cycloaddition reactions have been documented. Although there are no general guidelines for the asymmetric preparation, reagents such as chiral catalysts are providing more general routes. Many of the reactions discussed rely on the use of low temperature. Although it is expensive to conduct low-temperature reactions on an industrial scale, reactions that need temperatures as low as -105 °C can be conducted. It should be noted that at such temperatures, only stainless steel vessels that require neutral or basic conditions can be used at these extreme temperatures. In addition, reactions that involve the use of a metal can cause contamination problems in waste water or the product. 

Other sections of this chapter should be accessed as many chiral auxiliaries and catalysts appear to cross over from one type of pericyclic reaction to another. It should also be noted that although a large number of pericyclic reactions are known, large differences in asymmetric induction can occur with only subtle changes in reagents. This is especially true of the Diels-Alder reaction. 

The Claisen rearrangement, Cope rearrangement, and associated variants are powerful tools that can be used to create a number of new chiral centers in an expeditious manner, but the use of heavy metals such as mercury should be avoided. Of these reactions, the Ireland Claisen ester enolate reaction provides the most versatile synthetic pathway with minimal scale up problems. 

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 

To provide a baseline from which to compare the substituted system, we first compute the n energy of the unsubstituted starting material on the left in Fig. 6.53 a and the fully aromatic version of the corresponding transition structure on the right. The starting material will have the n energy of two independent % bonds, 

An empty orbital is a crude model for the usual Z-substituents, although it was appropriate for the cation 6.435, so we ought to do the comparison again with a vinyl group as a model for a C-substituent, and we can then guess that the usual Z-substituents will have an effect somewhere in between the two. The starting material in Fig. 6.53c has three independent n bonds, 6/3 below the a level, and the transition structure is modelled by styrene, 10.43/3 below the a level. The difference therefore is 0.43/3 relative to the unsubstituted case, not quite as effective as an isolated p orbital, whether filled or empty. 

Claisen rearrangements introduce the complication of oxygen lone pairs within the rearranging system, rather than as substituents on the perimeter. They may be ignored and the transition structure treated as benzene-like, or they may interrupt the conjugation, and the transition structure is then like a heptatrienyl anion.915 Predictions based on the simple theory above, whichever of these models is taken, match most of the substituent effects, and more elaborate treatments with calculations account for the anomalous accelerating effect of a donor substituent at C-6.916 

This simple way of explaining substituent effects is effective, and even gives quite good quantitative correlations for electrocyclic reactions and sigmatropic rearrangements.917 It can also be applied to cycloadditions, although the latter are usually explained by the frontier orbitals discussed in Section 6.5.3. 

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A simple example is the chlorination of methane (CH4), in which CH4 and elemental chlorine are mixed and irradiated to yield a mixture of chlorohydrocarbons, such as CH3C1 and CCI4. The energy for reaction comes from the UV photons. Diels-Alder and other pericyclic reactions also require photons of light. 

Reviews describe several organic reactions that are successfully carried out in aqueous media (Li, 1993 Li, 2000). In some cases, notably in the Diels-Alder reaction and in other pericyclic reactions, the hydrophobic effect accelerates the reaction and... 

This chapter does not cover Diels-Alder and other pericyclic reactions, in any detail, since these have been the subject of several recent reviews3-8. Nor is the chemistry of double-bonded functional groups involving allenes or carbenes covered in any great detail. 

In a similar way, it would be possible to analyse the mechanisms of any other pericyclic reaction, provided the structure of the intermediate is known with sufficient certainty. This requirement can probably be satisfied for the reactions... 

The best solvent from an ecological point of view is without doubt no solvent. There are many great reactions that can already be carried out in the absence of a solvent, for example numerous industrially important gas-phase reactions and many polymerizations. Diels-Alder and other pericyclic reactions are also often carried out without solvents. Reports on solvent-free reactions have, however, become increasingly frequent and specialized over the past few years. Areas of growth include reactions between solids [5], between gases and solids [6], and on supported inorganic materials [7], which in many cases are accelerated or even made possible through microwave irradiation [8]. 

In addition to participating in [2 + l]-cycloaddition reactions, divalent reactive intermediates can form ylides in the presence of carbonyl or other Lewis basic functionalities.108 These ylides participate in cycloaddition or other pericyclic reactions to furnish products with dramatically increased complexity. While carbenes (or metal carbenoids) are well known to participate in these pericyclic reactions, silylenes, in contrast, were reported to react with aldehydes or ketones to form cyclic siloxanes109,110 or enoxysilanes.111,112 Reaction of silylene with an a,p-unsaturated ester was known to produce an oxasilacyclopentene.109,113,114 By forming a silver silylenoid reactive intermediate, Woerpel and coworkers enabled involvement of divalent silylenes in pericyclic reactions involving silacarbonyl ylides115 to afford synthetically useful products.82,116,117... 

You may well feel that there is very little to be gained from the Woodward-Hoffrnann treatment of die Diels-Alder reaction. It does not explain the endo selectivity nor the regioselectivity. However, the Woodward-Hoffrnann treatment of other pericyclic reactions (particularly electrocyclic reactions, in the next chapter) is helpful. You need to know about this treatment because the Diels-Alder reaction is often described an an all-suprafacial [4 + 2] cycloaddition. Now you know what that means. 

Whether they go in the direction of ring opening or ring closure, electrocyclic reactions are subject to the same rules as all other pericyclic reactions—you saw the same principle at work in Chapter 35 where we applied the Woodward-Hoffmann rules both to cycloadditions and to reverse cycloadditions. With most of the pericyclic reactions you have seen so far, we have given you the choice of using either HOMO-LUMO reasoning or the Woodward-Hoffmann rules. With electrocyclic reactions, you really have to use the Woodward-Hoffmann rules because (at least for the ring closures) there is only one molecular orbital involved. 

This rotation is the reason why you must carefully distinguish electrocyclic reactions from all other pericyclic reactions. In cycloadditions and sigmatropic rearrangements there are small rotations as bond angles adjust from 109° to 120° and vice versa, but in electrocyclic reactions, rotations of nearly 90° are required as a planar polyene becomes a ring, or vice versa. These rules follow directly from application of the Woodward-Hoffmann rules—you can check this for yourself. 

The elucidation of reaction mechanisms is a central topic in organic chemistry that led to many elegant studies emphasizing the interplay of theory and experiment as demonstrated, for example, by the seminal contributions of the Houk group to the understanding of the Diels-Alder and other pericyclic reactions.38 This reaction class is rather typical for the elucidation of reaction mechanisms. On the experimental side, the toolbox of solvent, substituent and isotope effect studies as well as stereochemical probes have been used extensively, while the reactants, products, intermediates and transition structures involved have been calculated at all feasible levels of theory. As a result, these reactions often serve as a success story in physical organic chemistry. 

Instead of proceeding with a historical presentation, we discuss the computational results by methodology. Using HF/6-31G, the only feature located on the 2h sUce through the PES is a transition state with /ijg = 2.046 This geometry looks quite reasonable however, as is found with many other pericyclic reactions, the activation barrier is dramatically overestimated AH, = 55.0 kcal moE versus... 

In a related study, Borden and coworkers have examined whether other pericyclic reactions might express chameleonic behavior. Using B3LYP/6-31G calculations, they located transition states for the 1,5-hydrogen shift in phenyl-substituted 1,3-pentadienes (21-23). The activation enthalpy for the... 

Like other pericyclic reactions, electrocyclic reactions may be initiated either thermally or photochemically. The selection rules enable us to correlate the stereochemical relationship of the starting materials and products with the method of activation required for the reaction and the number of tt electrons in the reacting system. 

Pericyclic reactions can be combined easily with other pericyclic reactions to give sequences. Whether inter- or intra-molecular, the all-carbon atom or the hetero-atom, normal, neutral or with inverse electron demand this reaction is one of the most efficient methods in the repertoire of the organic chemist. 

The comparison of results obtained with different methods could be extended to other classes of reactions. There is a considerable wealth of results for several classes of reactions with simple mechanisms, like Sjv2, S l, ET reactions, which are the favourite examples selected by theoreticians to test new models. There is a rapid increase in the number of reactions for which a comparison among different methods is possible, and there is also an increase in the complexity of the studied mechanisms. We quote, as examples, Menshutkin and Friedel-Craft s reactions, Claisen s rearrangement, Diels-Alder s and other pericyclic reactions. 

Cycloaddition reactions of the C(3)=N bond of azirines are common (Scheme 45) <71AHC(13)45, B-83MI 101-03,84CHEC-I(7)47>. Azirines can participate in [4 + 2] cycloadditions with dienes including cyclopentadienones, isobenzofurans, triazines, and tetrazines. They also participate in 1,3-dipolar cycloadditions with azomethine ylides, nitrile oxides, mesoionic compounds, and diazomethane. Cycloadditions with heterocumulenes, benzyne, and carbenes are known. Azirines also participate in other pericyclic reactions, such as ene reactions. 

The last exception has an unusual twist, literally. The transition state is a strange loop with a half-twist, a Mobius loop. In contrast to a normal loop, Mobius loops are predicted to be stable with An electrons in them. Given enough heat, the cyclobutene sigma bond twists open to form a diene. This and other pericyclic reactions are discussed in more detail in Chapter 12. 

The principle presented here on two pericyclic reactions (Diels-Alder cycloaddition and cyclobutene ring opening) can be successfully applied to studies of the reaction outcome for many other pericyclic reactions. 

Other pericyclic reactions of alkynes that have been studied computationally include the addition of singlet methylene to acetylene [109], the addition of carbon monosulfide to acetylene [110], the [2 + 2] dimerization [100, 111], and the dihydrogen transfer reaction between acetylene and ethylene [112, 113]. 

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