Diels-Alder reaction zwitterion intermediate

The Diels-Alder reaction is the best known and most widely used pericyclic reaction. Two limiting mechanisms are possible (see Fig. 10.11) and have been vigorously debated. In the first, the addition takes place in concerted fashion with two equivalent new bonds forming in the transition state (bottom center, Fig. 10.11), while for the second reaction path the addition occurs stepwise (top row, Fig. 10.11). The stepwise path involves the formation of a single bond between the diene (butadiene in our example) and the dienophile (ethylene) and (most likely) a diradical intermediate, although zwitterion structures have also been proposed. In the last step, ring closure results with the formation of a second new carbon carbon bond. Either step may be rate determining. 

More than one mechanism can account for the experimental observation of the Diels-Alder reaction.521,522,528 However, most thermal [4 + 2]-cycloadditions are symmetry-allowed, one-step concerted (but not necessarily synchronous) process with a highly ordered six-membered transition state.529 Two-step mechanisms with the involvement of biradical or zwitterion intermediates can also be operative.522,528... 

The rates of Diels-Alder reactions are little affected by the polarity of the solvent. If a zwitterionic intermediate were involved, the intermediate would be more polar than either of the starting materials, and polar solvents would solvate it more thoroughly. Typically, a large change of solvent dipole moment, from 2.3 to 39, causes an increase in rate by a factor of only 10. In contrast, stepwise ionic cycloadditions take place with increases in rate of several orders of magnitude in polar solvents. This single piece of evidence rules out stepwise ionic pathways for most Diels-Alder reactions, and the only stepwise mechanism left is that involving a diradical. 

In 1989, the irradiation of (E,E)-2,4-hexadiene S3 sensitized by meso-porphyrin IX dimethyl ester led to the formation of cis-3,6-dimethyl-l,2-dioxene (62), which was the major product detected at — 78 °C in Freon 11 [69]. Endoperoxide 62 was purified under vacuum at 0.75 mmHg, and collected in a trap (98% isolated yield). Dienes that can adopt a cisoid conformation, such as 53 or ( , )-l,4-di phenyl butadiene, were photooxidized by the corresponding endoperoxides in high or quantitative yield in a suprafacial Diels-Alder reaction [60, 70], Dienes that cannot readily adopt cisoid conformations, such as (fc, Z)-2,4-hexadienes and (Z, Z)-2,4-hexadienes, lose their stereochemistry in the singlet oxygen [2 + 4]-cyclo-addition [60], (E,Z)- and (Z,Z)-dienes give a complex mixture of hydroperoxides and aldehydes, which suggests the intervention of intermediate zwitterions or 1,4-diradicals [71]. 

Benzyne produced from the zwitterion can also be captured by dienes in a Diels—Alder reaction (see Chapter 35). But this merely shows that benzyne can exist for a short time. It does not at all prove that benzyne is an intermediate in aromatic substitution reactions. Fortunately, there is very convincing evidence for this as well. 

Some Diels-Alder reactions have only modest rate responses to changes in solvent,and when contrasted with a [2 + 2] addition exhibiting a strong dependence on solvent polarity, a neat mechanistic demarcation may be drawn distinctions between concerted versus nonconcerted reactions, and between early and late transition states, may be advanced. The large solvent effect in the [2 + 2] addition may be ascribed to solvent stabilization of a zwitterionic intermediate. However, when similar reactants, one set giving Diels-Alder product, the other [2 + 2] product, are examined for solvent effects on reaction rates, the dependencies may be virtually identical. A case in point is provided by the reactions of TCNE with 9,10-dimethylanthracene (Diels-Alder reaction) and with 2,5-dimethylhexa-2,4-diene ([2 + 2] cycloaddition). 

The complementary substitution of the heterodiene with one or more strongly electron-donating substituents raises the heterodiene homo and in selected instances has proven sufficient to promote its 4or participation in HOMOdtene-controlled Diels-Alder reactions. The combined use of a nucleophilic heterodiene and reactive, electrophilic alkenes, e.g. ketenes, permits the observation of Diels-Alder products often formed in competition with [2 + 2] cycloaddition products and represents examples of stepwise [4 + 2] cycloaddition reactions proceeding with zwitterionic intermediate generation. 

Alder reaction the major Diels-Alder product is the trans adduct rather than the cis adduct (Scheme 11). Such a stereochemistry indicates that the Diels-Alder reactions proceed by a stepwise mechanism rather than a concerted mechanism. The photo-induced electron transfer from Danishefsky s diene to Ceo gives the triplet radical ion pair. The triplet radical ion pair is then converted to the singlet radical ion pair to give a zwitterionic intermediate (or a diradical intermediate) in competition with the back electron transfer to the reactant pair. The bond formation occurs stepwise with no symmetry restriction for the bond formation. Thus, both trans and cis adducts were obtained as the final products [305]. 

This process, formally related to the Diels Alder reaction, may also proceed by various mechanisms (Scheme 6.257)1421 1443 similar to those of [2 + 2] cycloaddition (Scheme 6.251), such as a concerted process or formation of charge-transfer (exciplex, 532), biradical (533), zwitterion (534) or perepoxide (535) intermediates. A concerted pathway1444 and exciplex1445 intermediacy was proposed to be involved in most cases. The [4 + 2] photooxygenation may be accompanied by other related processes (e.g. [2 + 2]). 

A beautiful illustration of a delicate balance between a stepwise and a concerted reaction has been found in the reactions of 1,1-dimethylbutadiene 6.133.716 This diene rarely adopts the s-cis conformation necessary for the Diels-Alder reaction with tetracyanoethylene giving the cyclohexene 6.136. However, it can react in the more abundant s-trans conformation in a stepwise manner, leading to a moderately well stabilised zwitterion 6.134. The intermediate allyl cation is configurationally stable, and a ring cannot form to C-l, because that would give a trans double bond between C-2 and C-3 in the cyclohexene 6.137. Instead a cyclobutane 6.135 is formed. All this is revealed by the solvent effect. In the polar solvent acetonitrile the stepwise ionic pathway is favoured, and the major product (9 1) is the cyclobutane 6.135. In the nonpolar solvent hexane, the major product (4 1) is the cyclohexene 6.136 with the Diels-Alder reaction favoured. 

Attempts to detect biradical intermediates in the Diels-Alder reaction have been unsuccessful and compounds that catalyse singlet-triplet transitions have no influence on the reaction. Similarly, the kinetic effects of para substituents in 1-phenylbutadiene, although large in absolute terms, are considered too small for a rate-determining transition state corresponding to a zwitterion intermediate. 

The almost universal application of the cis principle provides strong evidence for a mechanism for the Diels-Alder reaction in which both new bonds between the diene and the dienophile are formed at the same time. This includes a mechanism in which the two new a-bonds are formed simultaneously but at different rates and it does not completely exclude a two-step mechanism, if the rate of formation of the second bond in the (diradical or zwitterionic) intermediate were faster than the rate of rotation about a carbon-carbon bond. 

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