Diels-Alder cycloaddition reaction mechanism

Figure 14.7 Mechanism of the Diels-Alder cycloaddition reaction. The reaction occurs in a single step through a cyclic transition state in which the two new carbon-carbon bonds form simultaneously.

We ve seen that the Diels-Alder cycloaddition reaction is a one-step, peri-cyclic process that occurs through a cyclic transition state. Propose a mechanism for the following reaction ... 

Using the Pericyclic module, the Diels-Alder cycloaddition reaction of 1,3-cyclohexadiene (8) with maleic anhydride (9) (a known synthesis of endo-bicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic anhydride, 10 (70))y was properly predicted by CAMEO, but only as a minor product (Scheme 3). CAMEO pr cted the 3-(l,4-cyclohexadiene) succinic anhydride (11) adduct as the major product via a "forward ene" mechanism. 

Like the Diels-Alder cycloaddition reaction discussed in Section 8.14, the Claisen rearrangement reaction takes place in a single step through a pericyclic mechanism in which a reorganization of bonding electrons occurs through a six-memhered, cyclic transition state. The 6-allylcyclohexa-2,4-dienone intermediate then isomerizes to o-allylphenol (Figure 13.8). 

The mechanism of the Diels-Alder cycloaddition is different from that of other reactions we ve studied because it is neither polar nor radical. Rather, the Diels-Alder reaction is a pericyclic process. Pericyclic reactions, which we ll discuss in more detail in Chapter 30, take place in a single step by a cyclic redistribution of bonding electrons. The two reactants simply join together through a cyclic transition state in which the two new carbon-carbon bonds form at the same time. 

Anionic Diels-Alder reactions have been studied less extensively with the interest having been focused mainly on the cycloaddition of enolates of a,/l-unsaturated ketones with electron-poor olefins [24] (Equations 1.8 and 1.9). These reactions are fast and stereoselective and can be regarded as a sequential double Michael condensation, but a mechanism involving a Diels-Alder cycloaddition seems to be preferred [24b,f, 25]. 

In an attempt to further elucidate the mechanism of this process, these workers monitored the reaction between propiophenone enolsilane and fumaroylimide by in situ infrared (IR) spectroscopy, Scheme 25 (240). In the absence of alcoholic additives, the accumulation of an intermediate is observed prior to appearance of product. When i-PrOH is introduced, immediate decomposition of the intermediate occurs with concomitant formation of product. Evans suggests that the intermediate observed in this reaction is dihydropyran (374). Indeed, this reaction may be viewed as a hetero-Diels-Alder cycloaddition followed by alcohol induced decomposition to the desired Michael adduct. That 374 may be acting as a competent inhibitor was suggested by an observed rate reduction when this reaction was conducted in the presence of IV-methyloxazolidinone. 

Scheme 41 Mechanism of the aza-Diels-Alder-type reaction of cyclohexenone 2.3.12 1,3-Dipolar Cycloaddition...

The mechanistically quite similar double Michael reaction of 2-silyloxy dienes and enones has been shown recently to go via a similar two-step mechanism rather than a Diels-Alder cycloaddition S. Kobayashi, Y. Sagawa, H. Akamatsu and T. Mukaiyama, Chem. Lett., 1988, 1777. 

The aromaticities of symmetry-allowed and -forbidden transition states for electrocyclic reactions and sigmatropic rearrangements involving two, four, and six r-electrons, and Diels-Alder cycloadditions, have been investigated by ab initio CASSCF calculations and analysis based on an index of deviation from aromaticity. The order of the aromaticity levels was found to correspond to the energy barriers for some of the reactions studied, and also to the allowed or forbidden nature of the transition states.2 The uses of catalytic metal vinylidene complexes in electrocycliza-tion, [l,5]-hydrogen shift reactions, and 2 + 2-cycloadditions, and the mechanisms of these transformations, have been reviewed.3... 

Solvent effect on rate constants. In this section, the rate constant will be predicted qualitatively in CO2 for the Diels-Alder cycloaddition of isoprene and maleic anhydride, a reaction which has been well-characterized in the liquid state (23,24). In a previous paper, we used E data for phenol blue in ethylene to predict the rate constant of the Menschutkin reaction of tripropylamine and methyliodide (19). The reaction mechanisms are quite different, yet the solvent effect on the rate constant of both reactions can be correlated with E of phenol blue in liquid solvents. The dipole moment increases in the Menschutkin reaction going from the reactant state to the transition state and in phenol blue during electronic excitation, so that the two phenomena are correlated. In the above Diels-Alder reaction, the reaction coordinate is isopolar with a negative activation volume (8,23),... 

Annulated pyridines are reported to be synthesized via a [4+2] cycloaddition involving oxazoles (Scheme 121 Table 10) <20010L877>. The reaction mechanism is classified as a domino process with an intramolecular Diels-Alder cycloaddition followed by a retro-Michael reaction. 

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