Diels-Alder reactions kinetics

In the kinetic runs always a large excess of catalyst was used. Under these conditions IQ does not influence the apparent rate of the Diels-Alder reaction. Kinetic studies by UV-vis spectroscopy require a low concentration of the dienophile( 10" M). The use of only a catalytic amount of Lewis-acid will seriously hamper complexation of the dienophile because of the very low concentrations of both reaction partners under these conditions. The contributions of and to the observed apparent rate constant have been determined by measuring k pp and Ka separately. ... 

Kumar A. Salt Effects on Diels-Alder Reaction Kinetics Chem. Rev. 20011011 19... 

Keywords stereoselectivity, Diels-Alder reaction kinetics... 

Diels-Alder reaction intermediates, 136-142 Diels-Alder reaction kinetics, 126, 134, 137, 142, 143... 

Under the usual conditions their ratio is kinetically controlled. Alder and Stein already discerned that there usually exists a preference for formation of the endo isomer (formulated as a tendency of maximum accumulation of unsaturation, the Alder-Stein rule). Indeed, there are only very few examples of Diels-Alder reactions where the exo isomer is the major product. The interactions underlying this behaviour have been subject of intensive research. Since the reactions leadirig to endo and exo product share the same initial state, the differences between the respective transition-state energies fully account for the observed selectivity. These differences are typically in the range of 10-15 kJ per mole. ... 

Mechanistic investigations have focused on the two pericyclic reactions, probably as a consequence of the close mechanistic relation to the so successful aqueous Diels-Alder reaction. A kinetic inquest into the effect of water on several 1,3-dipolar cycloadditions has been performed by Steiner , van... 

Fortunately, azachalcone derivatives (2.4a-g, Scheme 2.4) turned out to be extremely suitable dienophiles for Lewis-add catalysed Diels-Alder reactions with cyclopentadiene (2.5). This reaction is outlined in Scheme 2.4 and a large part of this thesis will be devoted to the mechanistic details of this process. The presence of a chromophore in 2.4 allows kinetic studies as well as complexation studies by means of UV-vis spectroscopy. Furthermore, the reactivity of 2.4 is such that also the... 

Scheme 2.5. Synthesis of the ionic dienophiles 2.4f and 2.4g. features of the nncatalysed reaction will be discussed The kinetics of the Diels-Alder reaction of 2,4...

The rate of the uncatalysed reaction in all four solvents is rather slow. (The half-life at [2.5] = 1.00 mM is at least 28 hours). However, upon complexation of Cu ion to 2.4a-g the rate of the Diels-Alder reaction between these compounds and 2.5 increases dramatically. Figure 2.2 shows the apparent rate of the Diels-Alder reaction of 2.4a with 2.5 in water as a lunction of the concentration of copper(II)nitrate. At higher catalyst concentrations the rate of the reaction clearly levels off, most likely due to complete binding of the dienophile to the catalyst. Note that in the kinetic experiments... 

In Chapter 2 the Diels-Alder reaction between substituted 3-phenyl-l-(2-pyridyl)-2-propene-l-ones (3.8a-g) and cyclopentadiene (3.9) was described. It was demonstrated that Lewis-acid catalysis of this reaction can lead to impressive accelerations, particularly in aqueous media. In this chapter the effects of ligands attached to the catalyst are described. Ligand effects on the kinetics of the Diels-Alder reaction can be separated into influences on the equilibrium constant for binding of the dienoplule to the catalyst (K ) as well as influences on the rate constant for reaction of the complex with cyclopentadiene (kc-ad (Scheme 3.5). Also the influence of ligands on the endo-exo selectivity are examined. Finally, and perhaps most interestingly, studies aimed at enantioselective catalysis are presented, resulting in the first example of enantioselective Lewis-acid catalysis of an organic transformation in water. 

Careful examination of literature reporting Lewis-acid catalysis of Diels-Alder reactions in combination with kinetic investigations indicate that bidentate (or multidentate) reactants are required in order to ensure efficient catalysis in water. Moreover, studies of a number of model dienophiles revealed that a potentially chelating character is not a guarantee for coordination and subsequent catalysis. Consequently extension of the scope in this direction does not seem feasible. 

This chapter describes the effects of micelles on the Diels-Alder reaction of compounds 5,1 a-g (see Scheme 5.1) with cyclopentadiene (5.2). As far as we know, our study is the first detailed kinetic analysis of micellar catalysis of a Diels-Alder reaction. 

It turned out that the dodecylsulfate surfactants Co(DS)i Ni(DS)2, Cu(DS)2 and Zn(DS)2 containing catalytically active counterions are extremely potent catalysts for the Diels-Alder reaction between 5.1 and 5.2 (see Scheme 5.1). The physical properties of these micelles have been described in the literature and a small number of catalytic studies have been reported. The influence of Cu(DS)2 micelles on the kinetics of quenching of a photoexcited species has been investigated. Interestingly, Kobayashi recently employed surfactants in scandium triflate catalysed aldol reactions". Robinson et al. have demonshuted that the interaction between metal ions and ligand at the surface of dodecylsulfate micelles can be extremely efficient. ... 

Interestingly, at very low concentrations of micellised Qi(DS)2, the rate of the reaction of 5.1a with 5.2 was observed to be zero-order in 5.1 a and only depending on the concentration of Cu(DS)2 and 5.2. This is akin to the turn-over and saturation kinetics exhibited by enzymes. The acceleration relative to the reaction in organic media in the absence of catalyst, also approaches enzyme-like magnitudes compared to the process in acetonitrile (Chapter 2), Cu(DS)2 micelles accelerate the Diels-Alder reaction between 5.1a and 5.2 by a factor of 1.8710 . This extremely high catalytic efficiency shows how a combination of a beneficial aqueous solvent effect, Lewis-acid catalysis and micellar catalysis can lead to tremendous accelerations. 

In contrast to SDS, CTAB and C12E7, CufDSjz micelles catalyse the Diels-Alder reaction between 1 and 2 with enzyme-like efficiency, leading to rate enhancements up to 1.8-10 compared to the reaction in acetonitrile. This results primarily from the essentially complete complexation off to the copper ions at the micellar surface. Comparison of the partition coefficients of 2 over the water phase and the micellar pseudophase, as derived from kinetic analysis using the pseudophase model, reveals a higher affinity of 2 for Cu(DS)2 than for SDS and CTAB. The inhibitory effect resulting from spatial separation of la-g and 2 is likely to be at least less pronoimced for Cu(DS)2 than for the other surfactants. 

Maleic anhydride has been used in many Diels-Alder reactions (29), and the kinetics of its reaction with isoprene have been taken as proof of the essentially transoid stmcture of isoprene monomer (30). The Diels-Alder reaction of isoprene with chloromaleic anhydride has been analy2ed using gas chromatography (31). Reactions with other reactive hydrocarbons have been studied, eg, the reaction with cyclopentadiene yields 2-isopropenylbicyclo[2.2.1]hept-5-ene (32). Isoprene may function both as diene and dienophile in Diels-Alder reactions to form dimers. 

Diels-Alder reactions with butadiene are generally thermally reversible and can proceed in both gas and Hquid phases. The reactions are exothermic and foUow second-order kinetics first-order with respect to each reactant. 

Pyrazolin-5-ones with an exocyclic double bond at the 4-position (369 X = CMe2> react as heterodienes towards alkyl vinyl ethers (77G91). The kinetics of this Diels-Alder reaction giving pyrazolopyrans (370) have been studied. 

Stereochemistry of Diels-Alder Reactions. Thermodynamic vs. Kinetic Control... 

The Diels-Alder reaction of a diene with a substituted olefinic dienophile, e.g. 2, 4, 8, or 12, can go through two geometrically different transition states. With a diene that bears a substituent as a stereochemical marker (any substituent other than hydrogen deuterium will suffice ) at C-1 (e.g. 11a) or substituents at C-1 and C-4 (e.g. 5, 6, 7), the two different transition states lead to diastereomeric products, which differ in the relative configuration at the stereogenic centers connected by the newly formed cr-bonds. The respective transition state as well as the resulting product is termed with the prefix endo or exo. For example, when cyclopentadiene 5 is treated with acrylic acid 15, the cw fo-product 16 and the exo-product 17 can be formed. Formation of the cw fo-product 16 is kinetically favored by secondary orbital interactions (endo rule or Alder rule) Under kinetically controlled conditions it is the major product, and the thermodynamically more stable cxo-product 17 is formed in minor amounts only. 

For most Diels-Alder reactions a concerted mechanism as described above, is generally accepted. In some cases, the kinetic data may suggest the intermediacy of a diradical intermediate 18 ... 

The reactivity of heterocyclic dienes is determined by the nature and number of heteroatoms and, in the case of heteroaromatic compounds, also by the aromatic character. Furans undergo Diels-Alder reactions with strong dienophiles and generally afford cxo-cycloadducts which are thermodynamically more stable than the kinetically favoured c z/o-adducts. 

Another example of an enzymatic one-pot multiple Diels-Alder reaction is illustrated in Table 4.20 [83]. Racemic furfuryl alcohols 130 in the presence of ethoxy vinyl methyl fumarate 131 and enzyme TOYOBO-LIP undergo enzymatic acylation followed by kinetic enzymatic resolution to give the acyl derivatives 132 which then affords the adducts 133 and 134 by intramolecular Diels-Alder reaction 3-methyl-furfuryl alcohol 130 (R = Me) in acetone gives the best results. 

Table 4.20 Asymmetric Diels-Alder reactions via enzymatic kinetic resolution...

The kinetic effects of water and of cyclodextrins on Diels-Alder reactions. Host-guest chemistry, part 18 [65c]... 

Intermolecular befera-Diels-Alder reactions of enamino ketones with highly substituted vinyl ethers. Effect of high pressure on the kinetics and diastereoselectivity [77]... 

Rideout and Breslow first reported [2a] the kinetic data for the accelerating effect of water, for the Diels Alder reactions of cyclopentadiene with methyl vinyl ketone and acrylonitrile and the cycloaddition of anthracene-9-carbinol with N-ethylmaleimide, giving impetus to research in this area (Table 6.1). The reaction in water is 28 to 740 times faster than in the apolar hydrocarbon isooctane. By adding lithium chloride (salting-out agent) the reaction rate increases 2.5 times further, while the presence of guanidinium chloride decreases it. The authors suggested that this exceptional effect of water is the result of a combination of two factors the polarity of the medium and the... 

Engberts [3e, 9] has extensively investigated the Diels Alder reaction in aqueous medium. Recently Engberts and colleagues reported [9c] a kinetic study of a Diels Alder reaction of N-alkyl maleimides with cyclopentadiene, 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene in different solvents. The reaction rates of the cycloadditions with the open-chain diene relative to w-hexane are reported in Table 6.3. The aqueous medium greatly accelerates the Diels Alder reaction and the acceleration increases as the hydrophobic character of the alkyl group of the dienophile increases. These and other kinetic data [3e, 9], along with the observation that the intramolecular Diels-Alder reaction is also accelerated in... 

Lubineau and coworkers [18] have shown that glyoxal 8 (Ri = R2 = H), glyoxylic acid 8 (Ri = H, R2 = OH), pyruvic acid 8 (Ri = Me, R2 = OH) and pyruvaldehyde 8 (Ri = H, R2 = Me) give Diels-Alder reactions in water with poor reactive dienes, although these dienophiles are, for the most part, in the hydrated form. Scheme 6.6 illustrates the reactions with (E)-1,3-dimethyl-butadiene. The reaction yields are generally good and the ratio of adducts 9 and 10 reflects the thermodynamic control of the reaction. In organic solvent, the reaction is kinetically controlled and the diastereoselectivity is reversed. 

A number of Diels Alder reactions have been investigated in supercritical media and some of them will be illustrated. Most of the research has been focused on the influence of the pressure, which greatly influences the density of the fluid, on the kinetic aspects and on the product distribution of the reaction. 

Diels-Alder reactions [165] using thiourea as organocatalyst were recently examined [166]. Kinetic measurements showed that accelerations of the relative reaction rates were more dependent on the thiourea substituents than on the substrates or the solvent (even in highly coordinating polar solvents like wa-... 

We first consider the simple example of an uncatalyzed Diels-Alder reaction shown in Scheme 50.2 in order to demonstrate the use of different excess experiments. The Diels-Alder reaction is known to exhibit second overall order kinetics, as shown in eq. (4). We demonstrate with this known case how reaction progress kinetic analysis may be used to extract the reaction orders in both substrate concentrations, [5] and [6]. ... 

Beno, B. R., Houk, K. N., Singleton, D. A., 1996, Synchronous or Asynchronous An Experimental Transition State from a Direct Comparison of Experimental and Theoretical Kinetic Isotope Effects for a Diels-Alder Reaction , J. Am. Chem. Soc., 118, 9984. 

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