Diels-Alder reactions concerted/stepwise mechanisms

The spiro dimer of a-tocopherol (9, see also Fig. 6.4) is formed as mixture of two diastereomers by dimerization of the o-QM 3 in a hetero-Diels-Alder reaction with inverse electron demand. Both isomers are linked by a fluxion process (Fig. 6.22), which was proven by NMR spectroscopy.53 The detailed mechanism of the interconversion, which is catalyzed by acids, was proposed to be either stepwise or concerted.53-55... 

Chen, J., Houk, K. N., Foote, C. S., 1998, Theoretical Study of the Concerted and Stepwise Mechanisms of Triazolinedione Diels-Alder Reactions , J. Am. Chem. Soc., 120, 12303. 

The observation that the transition state volumes in many Diels-Alder reactions are product-like, has been regarded as an indication of a concerted mechanism. In order to test this hypothesis and to gain further insight into the often more complex mechanism of Diels-Alder reactions, the effect of pressure on competing [4 + 2] and [2 + 2] or [4 + 4] cycloadditions has been investigated. In competitive reactions the difference between the activation volumes, and hence the transition state volumes, is derived directly from the pressure dependence of the product ratio, [4 + 2]/[2 + 2]p = [4 + 2]/[2 + 2]p=i exp —< AF (p — 1)/RT. All [2 + 2] or [4 + 4] cycloadditions listed in Tables 3 and 4 doubtlessly occur in two steps via diradical intermediates and can therefore be used as internal standards of activation volumes expected for stepwise processes. Thus, a relatively simple measurement of the pressure dependence of the product ratio can give important information about the mechanism of Diels-Alder reactions. 

These experimental secondary deuterium KIEs observed in Diels-Alder reactions have been compared with the respective theoretical KIEs for the stepwise mechanism involving a diradical intermediate (equation 88a) and for concerted synchronous and asynchronous mechanisms (equation 88b) for the Diels-Alder reaction of butadiene with ethylene207. 

Mechanistic and theoretical studies of the Diels-Alder reaction have resulted in the characterization of this reaction as a concerted, although not necessarily synchronous, single-step process28-31 45. The parent reaction, the addition of 1,3-butadiene to ethylene yielding cyclohexene, has been the subject of an ongoing mechanistic debate. Experimental results supported a concerted mechanism, whereas results from calculations seemed to be dependent on the method used. Semi-empirical calculations predicted a stepwise mechanism, whereas ab initio calculations were in favor of a concerted pathway. At the end of the 80s experimental and theoretical evidence converged on the synchronous mechanism29-31. 

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. 

Fig. 10.11 The stepwise and concerted mechanisms for the Diels-Alder reaction between butadiene and ethylene. The reactants (lower left) proceed to the product, cyclohexene (lower right) either through a two step, two transition state mechanism involving the formation of a diradical intermediate (top center), or more directly through the symmetric synchronous transition state (bottom center) (Storer, J. W., Raimondi, L., and Houk, K. N., J. Am. Chem. Soc. 116, 9675 (1994))...

Intramolecular ionic Diels-Alder reactions were carried out in highly polar media to afford carbocyclic ring systems. The strategy, which obviates the need for high temperatures and pressures, features in situ generation of heteroatom-stabUized allyl cations that undergo subsequent (4 + 2) cycloaddition at ambient temperature. Typically, reactions were complete within 1 hour after addition of substrate. Some cycloadducts were the result of a concerted process, whereas others were formed via a stepwise reaction mechanism (Grieco, 1996). 

Olefins can add to double bonds in a reaction different from those discussed in 5-15, which, however, is still formally the addition of RH to a double bond. This reaction is called the ene synthesis44,1 and bears a certain similarity to the Diels-Alder reaction (5-47). For the reaction to proceed without a catalyst, one of the components must be a reactive dienophile (see 5-47 for a definition of this word) such as maleic anhydride, but the other (which supplies the hydrogen) may be a simple alkene such as propene. There has been much discussion of the mechanism of this reaction, and both concerted pericyclic (as shown above) and stepwise mechanisms have been suggested. The reaction between maleic anhydride and optically active PhCHMeCH=CH2 gave an optically active product,441 which is strong evi-... 

A review of direct observation of the transition state has traced the development of the femtosecond reaction dynamic technique, which has been used to demonstrate that the retro-Diels-Alder reaction can proceed by a stepwise mechanism as well as the usual concerted process.28 The oxide anion accelerated retro-Diels-Alder reaction has also been reviewed29 and the promise of this mild reaction for synthetic application has been emphasized. 

Silyloxy-2-aldehydes can undergo hetero-Diels-Alder reaction with aldehydes to give useful heterocycles.350 A model reaction, H2C=C(OSiH3)-N=CH2 with formaldehyde, has been explored theoretically. Lewis acids such as boron trifluoride catalyse the reaction by coordinating to the aldehyde oxygen, making the aldehyde more electrophilic. Concerted and stepwise mechanisms for this process are considered. 

Theoretical KIEs were predicted in (U)Becke3LYP/6-31G calculations for a concerted and stepwise Diels-Alder reaction as shown in Figure 3. Any of predicted KIEs is not in good agreement with experimental data. The 13C KIEs calculated for concerted mechanism match with experiment, but the 2H KIEs are lower by few percent. The great difference between the theoretical and... 

For hetero Diels-Alder reactions it has been shown by calculations that the transition structures are usually less symmetric than for the all-carbon Diels-Alder reactions also a change from a concerted non-synchronous to a stepwise mechanism depending on the substituents at the reacting species and the reaction conditions can occur. 

S. Sakai, Theoretical Analysis of Concerted and Stepwise Mechanisms of Diels-Alder Reaction Between Butadiene and Ethylene. J. Phys. Chem. A, 2000, 104, 922-927. 

Diels-Alder reactions of heterodienophiles have been known for decades, but only recently has this methodology become widely accepted by the synthetic community. There is enormous diversity in the structural types of compounds which can act as heterodienophiles, and a wide array of heterocyclic adducts can be prepared via these [4 + 2] cycloadditions. It seems clear that hetero Diels-Alder reactions span a range of mechanism from concerted to stepwise ionic processes. In many instances, mechanistic information is totally lacking. The discussion below therefore classifies heterodienophiles by structural rather than mechanistic class. Only the major types of synthetically useful heterodienophiles have been included. Moreover, the significant regio- and stereo-chemical features of the reactions have been exemplified as much as possible using recently reported cases. Other more comprehensive and more specialized reviews should be consulted for older material and more obscure hetero Diels-Alder cycloadditions. 

Two studies on the mechanism of this type of [4 + 2] cycloaddition which have led to very di erent interpretations have appeared. Mock and Nugent suggested that the Diels-Alder reactions of N-sulfi-nyl-p-toluenesulfonamide are stepwise, ionic processes. On the other hand, Hanson and Stockbum prefer a concerted, pericyclic mechanism in accord with frontier molecular orbital theory. Both proposals satisfactorily rationalize the observed regioselectivity of these reactions. 

Diels-Alder reactions of Ceo are generally believed to proceed via a thermally allowed concerted (suprafacial) process or a photochemical concerted (antarafacial) process [283-286]. However, an alternative stepwise (open-shell) mechanism for the Diels-Alder reaction has recently merited increasing attention [287-294], Along this line several reports describe an electron transfer with the formation of radical ion pairs as primary step of the Diels-Alder reactions, followed by a stepwise bond formation [295-301], The photochemical Diels Alder reaction of Ceo with an-... 

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]. 

Orlova, G., Goddard, J. D. Competition between Diradical Stepwise and Concerted Mechanisms in Chalcogeno-Diels-Alder Reactions A Density Functional Study. J. Org. Chem. 2001, 66, 4026-4035. 

Sakai, S. Theoretical analysis of concerted and stepwise mechanisms of the hetero-Diels-Alder reaction of butadiene with formaldehyde and thioformaldehyde. THEOCHEM 200Z, 630, 177-185. 

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