Electrocydic reactions

The combination of pericyclic transformations as cycloadditions, sigmatropic rearrangements, electrocydic reactions and ene reactions with each other, and also with non-pericyclic transformations, allows a very rapid increase in the complexity of products. As most of the pericyclic reactions run quite well under neutral or mild Lewis acid acidic conditions, many different set-ups are possible. The majority of the published pericyclic domino reactions deals with two successive cycloadditions, mostly as [4+2]/[4+2] combinations, but there are also [2+2], [2+5], [4+3] (Nazarov), [5+2], and [6+2] cycloadditions. Although there are many examples of the combination of hetero-Diels-Alder reactions with 1,3-dipolar cycloadditions (see Section 4.1), no examples could be found of a domino all-carbon-[4+2]/[3+2] cycloaddition. Co-catalyzed [2+2+2] cycloadditions will be discussed in Chapter 6. 

To date, only a few examples are known where a domino reaction starts with an electrocydic reaction, although the value of this approach is clearly demonstrated by the beautiful synthesis of estradiol methyl ether 4-319 through a domino elec-trocyclic/cycloaddition process. There is also an impressive example of a double thermal electrocyclization being used however, the starting material for this domino reaction was prepared in situ by a transition metal-catalyzed transformation, and is therefore discussed in Chapter 6. 

An interesting possibility for the construction of a tetracyclic system 174 with two cyclobutane rings arises by addition of lithiated alkoxyallenes 120 to 173 followed by two consecutive electrocydic reactions. Products such as 174 are useful precursors for benz[a]anthracene-7,12-diones (Scheme 8.43) [110]. 

Figure 12.3 uses a four-center electrocydic reaction [29] to illustrate the sensitivity to initial conditions. There are two simple yes/no questions. One is Did or did not... 

A second process that occurs concurrendy with the dissociation— redistribution process is an intermolecular rearrangement by which cyclohexadienone groups move along a polymer chain. The reaction maybe represented as two electrocydic reactions analogous to a double Fries rearrangement. When the cyclohexadienone reaches a terminal position, the intermediate is the same as in equation 8, and enolization converts it to the phenol (eq. 9). 

These rules do not apply strictly, but provide useful guidelines for synthesis design. The rules are generally not applicable to electrocydic reactions or to substrates containing non-second-period elements (e.g. P or S), because their longer bond lengths imply different geometric constraints. 

Click Coached Tutorial Problems for more practice using MOs to predict the stereochemistry of Electrocydic Reactions,... 

The observed stereochemistry of electrocydic reactions is codified in the following table, where the total number of electrons (/V) involved in the major bonding changes is expressed as a multiple (4n), or not a multiple (4n -I- 2), ol" four. 

It is the stereochemistry of electrocydic reactions that is of chief interest to us. To observe this, we must have suitably substituted molecules. Let us consider first the interconversion of 3,4-dimethylcydobutene and 2,4 hexadiene (Fig. 29.12). The cyclobutene exists as as and trans isomers. The hexadiene exists in three forms cis,ds asjrans and trans,trans. As we can see, the cis cyclobutene yields only... 

Electrocydic reactions, then, are completely stereospecific. The exact stereochemistry depends upon two things (a) the number of double bonds in the polyene, and (b) whether reaction is thermal or photochemical. It is one of the triumphs of the orbital symmetry approach that it can account for all these facts indeed, most of the examples known today were predicted by Woodward and Hoffmann before the facts were known. 

A cycloaddition reaction is one in which two unsaturated molecules add to one another, ieJding a C3 clic product. As with electrocydic reactions, cycloadditions are controlled by the orbital symmetry of the reactants. Symmetry-allowed processes often take place readily, but symmetry-disallowed processes take place with great difficulty, if at all, and then only by non-concerted pathways. Let s look at two examples to see how they differ. 

Electrocydic reaction A ring closure that involves cyclic movement of electrons. 

Another reaction that can be described in terms of orbital symmetry is the ring closing reaction of cis—1,3—butadiene to produce cyclobutene. The reaction is an example of a class of reactions known as electrocydic reactions. There are two different pathways that can be imagined for this reaction, which can be illustrated as shown in Figure 9.5. Both mechanisms involve rotation of the terminal CH2 groups but in different ways. 

The simplest class of reaction that is conveniently treated by the Woodward-Hoffmann rules is that termed electrocydic. An electrocydic reaction is defined as the formation of a single bond between thejends of a line system of tt-electrons and the reverse process. It is examplified by the thermal ring-opening of cyclobutenes to butadienes ... 

Scheme 14 Synthesis of furaquinocins assembly of furanonaphthoquinone by 47T-6tt electrocydic reactions [91]...

Scheme 18 Tandem 8 7r-6 7r electrocydic reactions of 2-(vinylphenyl)-3-isobutenylcyclo-butenone [99-101]...

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