Pericyclic cycloadditions

The Diels-Alder reaction is a pericyclic cycloaddition when bond-forming and bond-breaking processes are concerted in the six-membered transition state... 

Another rare kind of 6-electron ionic cycloaddition is that between a pentadienyl cation and an alkene. A telling example is the key step 2.66 — 2.67 in a synthesis of gymnomitrol 2.68, where the nature of the pericyclic step is heavily disguised, but all the more remarkable for that. Ionization of the acetal gives the cationic quinone system 2.66. That this is a pentadienyl cation can be seen in the drawing of a canonical structure on the left, with the components of the pericyclic cycloaddition emphasized in bold. Intramolecular [4+2] cycloaddition takes place, with the pentadienyl cation as the 4-electron component and the cyclopentene as the 2-electron component. Th is reaction is an excellent example of how a reaction can become embedded in so much framework that its pericyclic nature is obscured. 

Crudely, but adequately for now, we may state rule governing which cycloadditions can take place and which not. A thermal pericyclic cycloaddition is allowed if the total number of electrons involved can be expressed in the form (4n+2), where n is an integer. If the total number of electrons can be expressed in the form 4n it is forbidden. Another way of saying the same thing is that reactions with an odd number of curly arrows are allowed and those with an even number are forbidden. This rule needs to be qualified, as we shall see shortly, and in due course in Chapter 3 made more precise, along with the rules for all the other kinds of pericyclic reaction, in one all-encompassing rule. For now, we need to introduce the rule for photochemical pericyclic cycloadditions. 

The preliminary rules, thermal and photochemical, given on p.16, need now to be qualified—they apply only to cycloadditions that are suprafacial on both components. Nevertheless, almost all pericyclic cycloadditions are suprafacial on both components. It is physically difficult for one conjugated system to suffer antarafacial attack from another, since it implies that one or another of the components can reach round from one surface to the other 2,85. Only if at least one of the components has a long conjugated system can it twist enough to make this even remotely reasonable. Straightforward antarafacial attack in cycloadditions is therefore very rare indeed. Keep in mind, however, that these rules only apply to pericyclic cycloadditions— there are other kinds of cycloaddition, in which the two bonds are formed one at a time, and to which none of these rules applies. 

All the other kinds of pericyclic cycloaddition discussed so for, not just Diels-Alder reactions, are also suprafacial on both components. Thus, 1,3-dipolar cycloadditions involve suprafacial attack on the dipolarophile, as in... 

All the other cycloadditions, such as the [4+2] cycloadditions of allyl cations and anions, and the [8+2] and [6+4] cycloadditions of longer conjugated systems, have also been found to be suprafacial on both components, wherever it has been possible to test them. Thus the trans phenyl groups on the cyclopentene 2.65 show that the two new bonds were formed suprafacially on the rrans-stilbene. The tricyclic adducts 2.61, 2.77, 2.79, and 2.83, and the tetracyclic adduct 2.82, show that both components in each case have reacted suprafacially, although only suprafacial reactions are possible in cases like these, since the products from antarafacial attack on either component would have been prohibitively strained. Nevertheless, the fact that they have undergone cycloaddition is important, for it is the failure of thermal [2+2], [4+4] and [6+6], and photochemical [4+2], [8+2] and [6+4] pericyclic cycloadditions to take place, even when all-suprafacial options are open to them, that is significant. 

A stepwise ionic reaction looking like a forbidden [2+2] pericyclic cycloaddition ... 

One group of anomalous reactions is that of ketenes with alkenes. These reactions appear to have some of the characteristics of pericyclic cycloadditions, such as being stereospecifically syn with respect to the double... 

Arene oxide-oxepin systems have also been reported to undergo [2 + 4] or [4 + 6] pericyclic cycloaddition reactions with heterocyclic dienes like the tetrazine 279 and the triazine 280. 65 Thus 86 96 reacts with 279 and 280 to yield the dihydrooxepino [4,5-d] pyridazine 281 and the oxepino [4,5-c] pyridine 282, respectively, via a [2 + 4] cycloaddition as well as the phthalazine 283 and isoquinoline 284, respectively, probably via a [6 + 4] cycloaddition reaction. However, 157 gives only 285 and 286 arising from a [2 + 4] cycloaddition reaction. 

Adequately for most purposes, we can state a rule for which cycloadditions can take place and which not thermal pericyclic cycloadditions are allowed if the total number of electrons involved can be expressed in the form An + 2), where n is an integer. 

Reactions of Ketenes, AUenes and Carbenes which Appear to be Forbidden. Some [2 + 2] cycloadditions only appear to be forbidden. One of these is the cycloaddition of ketenes to alkenes. These reactions have some of the characteristics of pericyclic cycloadditions, such as being stereospecifi-cally syn with respect to the double bond geometry, and hence suprafacial at least on the one component, as in the reactions of the stereoisomeric cyclo-octenes 6.110 and 6.112 giving the diastereoisomeric cyclobutanones 6.111 and 6.113. However, stereospecificity is not always complete, and many ketene cycloadditions take place only when there is a strong donor substituent on the alkene. An ionic stepwise pathway by way of an intermediate zwitterion is therefore entirely reasonable in accounting for many ketene cycloadditions. 

In the course of a pericyclic cycloaddition, the interacting terminal lobes of each component may overlap either in a suprafacial mode or in an antarafacial mode. If both the new bonds form from the same face of the molecule it is known as a suprafacial mode (also known as supra-supra). It is antarafacial if one bond forms from one surface and the other bond forms from the other surface (also known as supra-antara) (Fig. 8.13). 

In the [2-i4] pericyclic cycloaddition reaction known as the Diels-Alder reaction, fluonne-containing compounds have been widely used as dienes, dieno-philes, or both Much of the fundamental work, including many comprehensive and systematic studies, was done before 1972, and Hudlicky provides an excellent summary of this work [9] Additional sources for early work in this area are reviews in Organic Reactiom [61] and Fluorine Chemistry Reviews [62]... 

More readily identifiable geometrical factors probably outweigh the contribution of the frontier orbitals in the remarkable reaction 6.47 between tetracyanoethylene and heptafulvalene giving the adduct 6.49 (see p. 261). The HOMO coefficients for heptafulvalene 6.420 (see p. 347) are highest at the central double bond, but a Diels-Alder reaction, with one bond forming at this site is impossible. The best reasonable possibility for a pericyclic cycloaddition, from the frontier orbital point of view, would be a Diels-Alder reaction across the 1,4-positions (HOMO coefficients of -0.199 and 0.253), but this evidently does not occur, probably because the carbon atoms are held too far apart. This is well-known to influence the rates of Diels-Alder reactions cyclopentadiene reacts much faster than cyclohexadiene, which reacts much faster than cycloheptatriene (see p. 302). The only remaining reaction is at the site which actually has the lowest frontier-orbital electron population, the antarafacial reaction across the 1, f-positions, which have HOMO coefficients of —0.199. 

One question that needs to be addressed is why are the activation volumes of pericyclic cycloadditions smaller (more negative) than those of the corresponding stepwise reactions involving diradical intermediates In the past it was assumed that the simultaneous formation of two new n bonds in a pericyclic [4 - - 2] cycloaddition leads to a larger contraction of volume than the formation of one bond in the stepwise process. The interpretation presented [28] is limited by the scope of Eyring transition state theory where the activation volume is related to the transition state volume, as mentioned above, and does not incorporate dynamic effects related to pressure-induced changes in viscosity [41]. An extensive discussion of reaction rates in highly viscous solvents can be found in Chapter 3. 

One of the main reasons is probably related to the small rate constant increase in the low pressure range (0-300 MPa) even for fairly pressure-dependent reactions such as pericyclic cycloadditions. The kinetic effect is derived from the relationship of Evans and Polanyi in the transition state theory as ... 

The Diels-Alder " is one of the most important reactions in synthesis because it makes two C-C bonds in one step and because it is regio- and stereoselective. It is a pericyclic cycloaddition between a conjugated diene (1) and a conjugated alkene (2) (the dienophile), forming a cydohexene. 

Cycloaddition reactions involve the combination of two molecules to form a new ring. Concerted pericyclic cycloadditions involve reorganization of the Tr-electron systems of the reactants to form two new a bonds. Examples might include cyclodimerization of alkenes, cycloaddition of allyl cation to an alkene, and the addition reaction between alkenes and dienes (Diels-Alder reaction). 

Pericyclic cycloaddition reactions have attracted a considerable interest of chemists due to some distinct advantages. First of all, a new ring is formed from two reacting molecules without elimination of any group or atom. Secondly, the reactions are accompanied by overall decrease in bond multiplicity. The most significant pericyclic cycloaddition reactions are [4+2]-cycloaddition (Diels-Alder reaction) and [3+2]-cycloaddition (1,3-dipolar cycloaddition) [105-107]. 

Pericyclic reactions in which p-orbitals at the ends of the rt-component of each system overlap and form the new a-bonds on the same surface are called suprafacial cycloaddition. Almost aU pericyclic cycloaddition reactions are suprafacial on both systems and thus the stereochemistry is maintained due to their concerted nature. This specification is usually made by placing a suitable subscript (s or a) after the number referring to the Tr-component. For example,... 

Conversely, cases are known where % cycloadditions take place by the ERj mechanism in preference to an alternative allowed Diels-Alder process. A good example is the reaction of butadiene with trifluoroethylene to give the adducts (236)-(239). The fact that (236) and (239) are formed in equal amounts shows that the reaction is not a pericyclic cycloaddition but must take place via the biradical (240). In this the F2C—CFH bond is single, so rotation is possible, the configuration of the original reactants being lost. Even the 13% of normal Diels-Alder product may be, and probably is, formed by cyclization of the same intermediate biradical, either (240) or the precursor (241) of (238). 

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