Substituent effects Diels-Alder reaction rates

So far the four metal ions have been compared with respect to their effect on (1) the equilibrium constant for complexation to 2.4c, (2) the rate constant of the Diels-Alder reaction of the complexes with 2.5 and (3) the substituent effect on processes (1) and (2). We have tried to correlate these data with some physical parameters of the respective metal-ions. The second ionisation potential of the metal should, in principle, reflect its Lewis acidity. Furthermore the values for Iq i might be strongly influenced by the Lewis-acidity of the metal. A quantitative correlation between these two parameters... 

For the ordinary Diels-Alder reaction the dienophile preferentially is of the electron-poor type electron-withdrawing substituents have a rate enhancing effect. Ethylene and simple alkenes are less reactive. Substituent Z in 2 can be e.g. CHO, COR, COOH, COOR, CN, Ar, NO2, halogen, C=C. Good dienophiles are for example maleic anhydride, acrolein, acrylonitrile, dehydrobenzene, tetracya-noethylene (TCNE), acetylene dicarboxylic esters. The diene preferentially is of the electron-rich type thus it should not bear an electron-withdrawing substituent. 

Similar results were obtained for analogous complexes of the de-( er -butyl)ated macrocycle (L24)2-. The ter7-butyl substituents do not affect the regiochemistry of this particular Diels-Alder reaction, but they clearly increase its rate. The observed trend is indicative of a small stabilization of the transition-state by hydrophobic effects (AAG 3 kJ/mol k coinpiex/k l) lckgr(nin(i = expiAAG /RT)). This would be consistent with our earlier observation that complexes bearing less polar carboxylate anions have the higher stability constants (see Section III.E). 

Diels-Alder reactions of oxazoles afford useful syntheses of pyridines (Scheme 53) (74AHC( 17)99). A study of the effect of substituents on the Diels-Alder reactivity of oxazoles has indicated that rates decrease with the following substituents alkoxy > alkyl > acyl >> phenyl. The failure of 2- and 5-phenyl-substituted oxazoles to react with heterodienophiles is probably due to steric crowding. In certain cases, bicyclic adducts of type (359) have been isolated and even studied by an X-ray method (87BCJ432) they can also decompose to yield furans (Scheme 54). With benzyne, generated at 0°C from 1-aminobenzotriazole and lead tetraacetate under dilute conditions, oxazoles form cycloadducts (e.g. 360) in essentially quantitative yield (90JOC929). They can be handled at room temperature and are decomposed at elevated temperatures to isobenzofuran. 

DFT calculations on the intramolecular Diels-Alder reaction of penta-l,3-dienyl acrylates predict stereoselectivities that are in good agreement with the experimen- (g) tal results.85 Another DFT study at the B3LYP/6-31G(d) level of the intramolecular Diels-Alder cycloaddition of 5-vinylcyclohexa-1,3-dienes has been reported. Reaction rates are influenced by dienophile twisting and substituent effects.86 The intramolecular dehydro-Diels-Alder reactions of ynamides (79) provides a new synthesis of benzo[fc]-, tetrahydrobenzo[fc]-, naphtho[l,2-/j -, and dibenzo[a,c]carbazoles... 

Substituent Effects on Reaction Rates of Diels-Alder Reactions... 

As in the case of Diels-Alder reactions or of [2+2]-cycloadditions of ketenes, the rate of 1,3-dipolar cycloadditions is affected by donor and acceptor substituents in the substrates. Again, Equation 15.2 can be used to obtain a good approximation of their effects, since this equation applies to any one-step cycloaddition. We restated this equation once before as the approximation expressed in Equation 15.3. In that case, it was our aim to understand the rate of Diels-Alder reactions, and we are now faced with the task of making a statement concerning the rate of 1,3-dipolar cycloadditions. To this end it is advantageous to employ a different approximation to Equation 15.2, and that approximation is expressed in Equation 15.8. 

Diels-Alder reactions also may occur when the electronic situation of the substrates is completely reversed, that is, when electron-rich dienophiles react with electron-poor dienes. [4+2]-Cycloadditions of this type are called Diels-Alder reactions with inverse electron demand. 1,3-Dienes that contain heteroatoms such as O and N in the diene backbone are the dienes of choice for this kind of cycloaddition. The data in Figure 12.22 show the rate-enhancing effect of the presence of donor substituents in the dienophile. 

Only a few examples of a Diels-Alder type reaction of the valence tautomeric ketene of mesoionic 1,3-dithiolones are known. Thus the reactions of differently substituted mesoionic compounds (2) with o-chloranil give the unusual adducts (142), derived via [4 + 2] cycloaddition to the non-detectable valence tautomeric ketene (141) which is in equilibrium with (2). The reaction rate depends upon the nature of the substituents, for example substituents with —I and/or —M effects lower the reaction rates (81ZN(B)609). 

The addition of a C-2 (equation 1 R = H > alkyl, aryl > OMe NR2), C-3, or C-4 electron-donating substituent to a 1 -oxa-1,3-butadiene electronically decreases its rate of 4ir participation in a LUMOdiene-controlled Diels-Alder reaction (c/. Table 5). Nonetheless, a useful set of C-3 substituted l-oxa-l,3-buta-dienes have proven to be effective dienes ° and have been employed in the preparation of carbohydrates (Table 6). The productive use of such dienes may be attributed to the relative increased stability of the cisoid versus transoid diene conformation that in turn may be responsible for the Diels-Alder reactivity of the dienes. Clear demonstrations of the anticipated [4 + 2] cycloaddition rate deceleration of 1-oxa-1,3-butadienes bearing a C-4 electron-donating substituent have been detailed (Table 6 entry 4). >> "3 In selected instances, the addition of a strong electron-donating substituent (OR, NR2) to the C-4 position provides sufficient nucleophilic character to the 1-oxa-1,3-butadiene to permit the observation of [4 + 2] cycloaddition reactions with reactive, electrophilic alkenes including ketenes and sul-fenes, often in competition with [2 + 2] cycloaddition reactions. ... 

Craig and coworkers have reported rate constants for the reaction of 2-substituted 1,3-butadienes with maleic anhydride in benzene at 25 °C their values are X, k Cl, 0,019 H, 0.19 Me, 0,57 Et, l.l5 /-Pr, 2.2 t-Bu, 5.6 OMe, 1.9. As the Diels-Alder reaction proceeds through the s-cis conformation of the diene, and substituents in the 2-and 3-positions can affect the fraction of the diene in this conformation, steric effects must be considered. The data set was correlated therefore with the CRS equation ... 

In discussing the Woodward-Hoffmann rules, we were indifferent as to which of the two components of a cycloaddition would provide the HOMO and which the LUMO. The two pairs of frontier orbitals bear a complementary relationship to each other they both invariably give the same answer, and we could safely make an arbitrary choice. To explain the effects of substituents on the rates of Diels-Alder reactions, however, we need to know which is the more... 

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