Cycloaddition rules

Using the nomenclature of Dewar and Zimmerman, the transition state for the 2, + 2S cycloaddition is a 4n Hiickel system (zero nodes) and is antiaromatic in the ground state and aromatic in the excited state. The transition state for the 2S + 20 cycloaddition is a 4n Mobius system (one node) and is aromatic in the ground state and antiaromatic in the excited state (see Chapter 8). The general cycloaddition rules are given in Table 9.5. 

Scheme 99) (416). The 4-acetyloxy-5-ary]thiazo]e or 4-methoxy-5-arylthiazole, which are models of the protomer (174b) do not give cycloaddition products under the same experimental conditions. This rules out the possibility of a Diels-Alder reaction involving the protomer (174b) (416). 

Refer to the molecular orbital diagrams of allyl cation (Figure 10 13) and those presented earlier in this chapter for ethylene and 1 3 butadiene (Figures 10 9 and 10 10) to decide which of the following cycloaddition reactions are allowed and which are forbidden according to the Woodward-Floffmann rules... 

In general, stereochemical predictions based on the Alder rule can be made by aligning the diene and dienophile in such a way that the unsaturated substituent on the dienophile overlaps the diene n system. The stereoselectivity predicted by the Alder rule is independent of the requirement for suprafacial-suprafacial cycloaddition, since both the endo and exo transition states meet this requirement. 

The selection rules for cycloaddition reactions can also be derived from consideration of the aromaticity of the transition state. The transition states for [2tc -f 2tc] and [4tc -1- 2tc] cycloadditions are depicted in Fig. 11.11. For the [4tc-1-2tc] suprafacial-suprafacial cycloaddition, the transition state is aromatic. For [2tc -F 2tc] cycloaddition, the suprafacial-suprafacial mode is antiaromatic, but the suprafacial-antarafacial mode is aromatic. In order to specify the topology of cycloaddition reactions, subscripts are added to the numerical classification. Thus, a Diels-Alder reaction is a [4tc -f 2 ] cycloaddition. The... 

The prediction of the Woodward-Hofrmann rules that thermal concerted cycloadditions are allowed for combinations in which 4 -1- 2 7c electrons are involved has stimulated the search for combinations with 10 and larger numbers of participating electrons. An example of a [6 -1- 4] cycloaddition is the reaction of tropone with 2,5-dimethyl-3,4-diphenylcyclopentadienone ... 

UV irradiation. Indeed, thermal reaction of 1-phenyl-3,4-dimethylphosphole with (C5HloNH)Mo(CO)4 leads to 155 (M = Mo) and not to 154 (M = Mo, R = Ph). Complex 155 (M = Mo) converts into 154 (M = Mo, R = Ph) under UV irradiation. This route was confirmed by a photochemical reaction between 3,4-dimethyl-l-phenylphosphole and Mo(CO)6 when both 146 (M = Mo, R = Ph, R = R = H, R = R" = Me) and 155 (M = Mo) resulted (89IC4536). In excess phosphole, the product was 156. A similar chromium complex is known [82JCS(CC)667]. Complex 146 (M = Mo, R = Ph, r2 = R = H, R = R = Me) enters [4 -H 2] Diels-Alder cycloaddition with diphenylvinylphosphine to give 157. However, from the viewpoint of Woodward-Hoffmann rules and on the basis of the study of UV irradiation of 1,2,5-trimethylphosphole, it is highly probable that [2 - - 2] dimers are the initial products of dimerization, and [4 - - 2] dimers are the final results of thermally allowed intramolecular rearrangement of [2 - - 2] dimers. This hypothesis was confirmed by the data obtained from the reaction of 1-phenylphosphole with molybdenum hexacarbonyl under UV irradiation the head-to-tail structure of the complex 158. 

According to the Woodw ard-Hofmann rules the concerted thermal [2n + 2n] cycloaddition reaction of alkenes 1 in a suprafacial manner is symmetry-forbidden, and is observed in special cases only. In contrast the photochemical [2n + 2n cycloaddition is symmetry-allowed, and is a useful method for the synthesis of cyclobutane derivatives 2. 

An explanation for the finding that concerted [4 -I- 2] cycloadditions take place thermally, while concerted [2 + 2] cycloadditions occur under photochemical conditions, is given through the principle of conservation of orbital symmetry. According to the Woodw ard-Hofmann rules derived thereof, a concerted, pericyclic [4 -I- 2] cycloaddition reaction from the ground state is symmetry-allowed. 

The photochemical cycloaddition of a carbonyl compound 1 to an alkene 2 to yield an oxetane 3, is called the Patemo-Buchi reaction - This reaction belongs to the more general class of photochemical [2 + 2]-cycloadditions, and is just as these, according to the Woodward-Hofmann rules, photochemically a symmetry-allowed process, and thermally a symmetry-forbidden process. 

How can we predict whether a given cycloaddition reaction will occur with suprafacial or with antarafacial geometry According to frontier orbital theory, a cycloaddition reaction takes place when a bonding interaction occurs between the HOMO of one reactant and the LUMO of the other. An intuitive explanation of this rule is to imagine that one reactant donates electrons to the other. As with elec-trocyclic reactions, it s the electrons in the HOMO of the first reactant that are least tightly held and most likely to be donated. But when the second reactant accepts those electrons, they must go into a vacant, unoccupied orbital—the LUMO. 

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. 

The ortho-para rule is explained by FMO theory on the basis of the orbital coefficients of the atoms forming the cr-bonds. The regiochemistry is determined by the overlap of the orbitals that have larger coefficients (larger lobes in Scheme 1.15). The greater the difference between the orbital coefficients of the two end atoms of diene and two atoms of dienophile, which form the two cr-bonds, the more regioselective the cycloaddition. 

In a photochemical cycloaddition, one component is electronically excited as a consequence of the promotion of one electron from the HOMO to the LUMO. The HOMO -LUMO of the component in the excited state interact with the HOMO-LUMO orbitals of the other component in the ground state. These interactions are bonding in [2+2] cycloadditions, giving an intermediate called exciplex, but are antibonding at one end in the [,i4j + 2j] Diels-Alder reaction (Scheme 1.17) therefore this type of cycloaddition cannot be concerted and any stereospecificity can be lost. According to the Woodward-Hoffmann rules [65], a concerted Diels-Alder reaction is thermally allowed but photochemically forbidden. 

The presence of two substituents at C-4 also strongly influences the regios-electivity as shown in the cycloaddition of dienone 13 with isoprene (2) (Equation 3.1). In violation of the para-rule for Diels-Alder reaction, only metfl-adduct was obtained [19,20]. 

As applied to cycloaddition reactions the rule is that reactions are allowed only when all overlaps between the HOMO of one reactant and the LUMO of the other are such that a positive lobe overlaps only with another positive lobe and a negative lobe only with another negative lobe. We may recall that monoalkenes have two n molecular orbitals (p. 9) and that conjugated dienes have four (p. 36), as shown in Figure 15.1. A concerted cyclization of two monoalkenes (a 2 -f- 2 reaction) is not allowed because it would require that a positive lobe overlap with a negative lobe (Fig. 15.2). On the other hand, the Diels-Alder reaction (a 2 -f 4 reaction) is allowed, whether considered from either direction (Fig. 15.3). 

FIGURE 15.6 Transition states illustrating Huckel-Mobius rules for cycloaddition reactions. 

The rule may then be stated A thermal pericyclic reaction involving a Hiickel system is allowed only if the total number of electrons is 4n + 2. A thermal pericyclic reaction involving a Mobius system is allowed only if the total number of electrons is 4n. For photochemical reactions these rules are reversed. Since both the 2 + 4 and 2 + 2 cycloadditions are Hiickel systems, the Mdbius-Hiickel method predicts that the 2 + 4 reaction, with 6 electrons, is thermally allowed, but the 2 + 2 reaction is not. One the other hand, the 2 + 2 reaction is allowed photochemically, while the 2 + 4 reaction is forbidden. 

It must be emphasized once again that the rules apply only to cycloaddition reactions that take place by cyclic mechanisms, that is, where two s bonds are formed (or broken) at about the same time. The rule does not apply to cases where one bond is clearly formed (or broken) before the other. It must further be emphasized that the fact that the thermal Diels-Alder reaction (mechanism a) is allowed by the principle of conservation of orbital symmetry does not constitute proof that any given Diels-Alder reaction proceeds by this mechanism. The principle merely says the mechanism is allowed, not that it must go by this pathway. However, the principle does say that thermal 2 + 2 cycloadditions in which the molecules assume a face-to-face geometry cannot take place by a cyclic mechanism because their activation energies would be too high (however, see below). As we shall see (15-49), such reactions largely occur by two-step mechanisms. Similarly. 2 + 4 photochemical cycloadditions are also known, but the fact that they are not stereospecific indicates that they also take place by the two-step diradical mechanism (mechanism... 

As we saw in 15-58, the Woodward-Hoffmann rules allow suprafacial concerted cycloadditions to take place thermally if the total number of electrons is 4n 4- 2 and... 

The suprafacial thermal addition of an allylic cation to a diene (a [3 -f- 4] cycloaddition) is allowed by the Woodward-Hoflfmann rales (this reaction would be expected to follow the same rules as the Diels-Alder reaction ). Such cyclo-... 

Photochemical [2h-2] cycloadditions of olefins occur with retention of configuration according to the Woodward-Hoffmarm rule [6,7], These are excited-state reactions in the delocalization band of the mechanistic spectrum. A striking example of the symmetry-allowed reaction was observed when the neat cis- and tran -butenes were irradiated (delocahzation band in Scheme 3) [8],... 

According to the calculations at high levels of theory, the [4+2] cycloaddition reactions of dienes with the singlet ( A oxygen follow stepwise pathways [37, 38], These results, which were unexpected from the Woodward-Hoffmann rule and the frontier orbital theory, suggest that the [4+2] cycloadditions of the singlet ( A oxygen could be the reactions in the pseudoexcitation band. 

As discussed in Section 10.4 of Part A, concerted suprafacial [2tt + 2tt] cycloadditions are forbidden by orbital symmetry rules. Two types of [2 + 2] cycloadditions are of synthetic value addition reactions of ketenes and photochemical additions. The latter group includes reactions of alkenes, dienes, enones, and carbonyl compounds, and these additions are discussed in the sections that follow. 

Cycloadditions of ketenes and alkenes have synthetic utility for the preparation of cyclobutanones.163 The stereoselectivity of ketene-alkene cycloaddition can be analyzed in terms of the Woodward-Hoffmann rules.164 To be an allowed process, the [2ir + 2-tt] cycloaddition must be suprafacial in one component and antarafacial in the other. An alternative description of the TS is a 2irs + (2tts + 2tts) addition.165 Figure 6.13 illustrates these combinations. Note that both representations predict formation of the d.v-substituted cyclobutanone. 

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