Electrocyclic and Photochemical Reactions

The heterocyclic double bond in simple indoles will take part in cycloaddition reactions with dipolar 4n components,and with electron-deficient dienes (i.e. inverse electron demand), in most reported cases, held close nsing a tetherf° a comparable effect is seen in the intermolecular cycloaddition of 2,3-cycloalkyl-indoles to ortfto-quinone generating a l,4-dioxane. ° The introduction of electron-withdrawing substituents enhances the tendency for cycloaddition to electron-rich dienes 3-acetyl-1-phenylsulfonylin-dole, for example, undergoes aluminium-chloride-catalysed cycloaddition with isoprene, and 3-nitro-l-phenylsulfonylindole reacts with l-acylamino-buta-l,3-dienes without the need for a catalyst. Both 3- and 2-nitro-l-phenylsulfonyl-indoles undergo dipolar cycloadditions with azomethine ylides.  

Both 2- and 3-vinylindoles can take part as 4ti components in Diels-Alder cycloadditions mostly, but not always, these employ A-acyl- or iV-arylsulfony 1-indoles, in which the interaction between nitrogen lone pair and n-system has been reduced. The example shows how this process can be utilised in the rapid construction of a complex pentacycle.  

When tethered 1,2,4-triazines are used, their interaction with the indole 2,3-double bond generates car-bolines. The tether can be incorporated into the product molecule, or be designed to be broken in situ, as in the example below. 1,2,4,5-Tetrazines react with the indole 2,3-bond in an intermolecular sense the initial adduct loses nitrogen and then is oxidised to the aromatic level by a second mole equivalent of the tetrazine  

A 1-vinylamino-indole undergoes a 3,3-sigmatropic rearrangement giving the tricyclic ring system of the eseroline alkaloids  

Claisen ortho-ester rearrangement of indol-3-yl-alkanols introduces the migrating group to the indole 2-position  

Some other apparent cycloadditions probably proceed by non-concerted pathways for example, addition of 1,3-cyclohexadiene in the presence of light and 2,4,6-triphenylpyrylium probably involves radical intermediates, and reactions of 2-phenylsulfonyl-dienes with indolyl Grignard reagents probably proceed in stepwise fashion. 

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The standard observation that thermal and photochemical electrocyclic and cycloaddition reactions always take place by opposite stereochemical pathways [96] is explained directly by the unit of angular momentum carried by a photon. Photochemical activation disturbs the balance between angular-momentum vectors and dictates a different molecular conformation. 

Apply the Woodward-Hoffmann rules to the electrocyclic reaction of hex-atriene to cyclohexadiene considering the appropriate Hiickel MO s. Determine whether the mechanism is conrotatory or disrotatory for both thermal and photochemical reactions. 

Predict the structure, including all aspects of the stereochemistry, based on orbital symmetry principles for the following photochemical electrocyclic and cycloaddition reactions. 

The only pericydic reactions we have used so far have been cycloadditions the Dids-Aider reaction Chapter 17) and photochemical (Chapter 32) or thermal Chapter 33) 2 + 2 cycioadditions. Electrocyclic and sigmatropic reactions are also useful in synthesis and as each is the basis of a method of five-membered ring synthesis, they are conveniently grouped into one chapter here. 

It turns out that all An systems behave like the four-electron case (thermal reactions conrotatory and photochemical reactions disrotatory) and all 4w + 2 systems behave like the six-electron case (thermal reactions disrotatory and photochemical reactions conrotatory). This generalization is shown in the second half of Table 20.1, which gives the rules for all electrocyclic reactions. Now, if you can count the number of electrons correctly you can easily predict the stereochemistry of any electrocyclic reaction without even working out the molecular orbitals. 

Thermal and photochemical electrocyclic reactions are particularly useful in the synthesis of alkaloids (W. Oppolzer, 1973,1978 B K. Wiesner, 1968). A high degree of regio- and stereoselectivity can be reached, if cyclic olefin or enamine components are used in ene reactions or photochemical [2 + 2]cycloadditions. 

A striking illustration of the relationship between orbital symmetry considerations and the outcome of photochemical reactions can be found in the stereochemistry of electrocyclic reactions. In Chapter 11, the distinction between the conrotatory and the disrotatory mode of reaction as a function of the number of electrons in the system was... 

Thermal and photochemical electrocyclic reactions always take place with opposite stereochemistry because the symmetries of the frontier orbitals are always different. Table 30.1 gives some simple rules that make it possible to predict the stereochemistry of electrocyclic reactions. 

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

Trauner and colleagues [39] recently found a striking contrast in the thermal and catalyzed reactions of a triene. Thermal reaction of a trienolate readily underwent disrotatory electrocyclization to afford cyclohexadiene (delocalization band in Scheme 8) in accordance with the Woodward-Hoffmann rule. Surprisingly, treatment of the trienolate with Lewis acid did not result in the formation of the cyclohexadiene but rather gave bicyclo[3.1.0]hexene in a [4n +2nJ manner (pseudoexcitation band in Scheme 8). The catalyzed reaction is similar to the photochemical reaction in the delocalization band. 

There seems to be no great difference in the free energy between acyclic triene and the cyclic diene. This is because of smaller strain in the six-membered ring as compared with the four-membered one. On the other hand in 6n electron system in electrocyclic process there is more efficient absorption in the near regions of u.v. spectrum. This is why under both thermal and photochemical conditions, the (1, 6) electrocyclic reactions are reversible. Side reactions are more frequent in reversible. Side reactions are more frequent in reversible transformations of trienes than in dienes. The dehydrogenation of cyclic dienes to aromatic compounds may also occur in the thermal process. On heating cyclohexadiene yields benzene and hydrogen. 

For so-called electrocyclic processes, which are pericyclic reactions, the photochemical and thermal reactions give different stereoisomers, as shown for the diene and the triene in Figure 7.9. 

Thermal and photochemical electrocyclic reactions are both stereospecific, with the two processes giving rise to stereospecific reactions in the opposite sense. 

It should be noted that products like 443 and 447 are the normal products of photochemical reactions of acyclic 1,3,5-hexatrienes, as well as of divinyl aromatics, but are quite unusual for thermal transformations of such substrates. Presumably, the electrostatic repulsion between CF2 groups prevents the formation of conformation 450 which is necessary for the electrocyclic ring closure (i.e. 438 — 439 and 445 -> 446). Instead, it leads to conformation 451 which is favorable to generate the diradical and then the fused vinyl-cyclopropane intermediates 452 (equation 170). Note that the rearrangement 452 —> 453... 

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