Diels salt effect

Furthermore, the number of diene - dienoplrile combinations that can be expected to undergo a Lewis-acid catalysed Diels-Alder reaction is limited. Studies by Wijnen leave little doubt that the rate of typical Diels-Alder reactions, where the dienophile is activated by one or more carbonyl functionalities, does not respond to the presence of Lewis acids in aqueous solution , at least not beyond the extent that is expected for non-specific interactions (salt effects). No coordination of the Lewis acid to the dienophile was observed in these cases, which is perhaps not surprising. Water is... 

Turning the argument around reactions that do not involve proton transfer steps will only experience a significant effect of the Lewis acids if a direct interaction exists between catalyst and reactant. The conventional Diels-Alder reaction is a representative of this class of reactions. As long as monodentate reactants are used, the effects of Lewis acids on this reaction do not exceed the magnitude expected for simple salt effects, i.e. there are no indications for a direct interaction between Lewis-acid and substrate. 

Table 6.2 Sodium and guanidinium salt effects (relative reaction rates) of Diels-Alder reaction of anthracene-9-carbinol and N-ethylmaleimide...

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

Diets-Alder catalysis.2 This cation radical enhances the reactivity of a neutral or electron-rich eis-1,3-diene in Diels-Alder reactions. Thus 1,3-cyclohexadiene undergoes Diels-Alder dimerization only at temperatures around 200°. The presence of 5-10 mole % of this salt effects dimerization even at —78°, with the usual endo/ exo selectivity (5 1). It also permits facile condensation of 1,3-cyclohexadiene with a hindered dienophile such as 2,5-dimethyl-2,4-hexadiene (equation 1) the dimer of the former diene is a minor product (20% yield). 

Much more impressive rate accelerations for several Diels-Alder (and other) reactions have been observed by employing solutions of lithium perchlorate (up to 5 m) in diethyl ether (LPDE solutions) [802-806]. The dramatic rate accelerations found for Diels-Alder reactions in LPDE solutions appear to stem from Lewis acid catalysis by the coordinative unsaturated Li+ ion (see the end of Section 3.1). The Lewis acid catalysis by LPDE is applicable to those Diels-Alder reactions in which the lithium cation can coordinate with suitable functional groups in the reactants e.g. Li+---0=C). Addition of lithium-specific crown ethers e.g. [12]crown-4) leads to a loss of the catalytic activity of the Li+. For a recent extensive review of salt effects on Diels-Alder reactions, see reference [802]. 

The salt effect is normal for the aqueous Diels-Alder reactions shown in Table... 

Tab. 10.18. Salt effect in Diels-Alder reactions in water and glycol at ambient pressure .

Tab. 10.22. Salt effect on endo selectivity in the aqueous Diels-Alder reaction of furan with methyl vinyl ketone (300 MPa, 32 °C).

Breslow, R. and Rizzo, C.J., Chaotropic salt effects in a hydrophobically accelerated Diels-Alder reaction, /. Am. Chem. Soc., 1991,113,4340-4341. 

Theoretical studies have been carried out on the conrotatory and disrotatory reaction pathways of hexa-l,3,5-triene to cyclohexadiene, and the effect of solvent and salt effects on the rates of the electrocyclic ring closure of (IZ, 3Z, 5 )-l,2,6-triphenylhexa-l,3,5-triene has been determined. An ab initio study of the electro-cyclization of (Z)-hexa-l,3,5-triene and its hetero-substituted analogues has been undertaken.The involvement of a lone pair on the nitrogen or oxygen atom appears to facilitate the interaction between the terminal atoms that bond to each other to close the ring. It has been reported that the intramoiecular aza-Diels-Alder reaction of an a./S-unsaturated hydrazones to a quinone, as in (197), is followed by an unprecedented rearrangement in which the aminoaryi moiety formally undergoes a 1,2-shift to yield benzo- or pyrido-[fc]acridine-6,11-dienes (198). 

Casetta, M. Colona, S. Manfredi, A., Hydrophobic control of organic stereochemistry. Changes of regioselectivity in Diels-Alder reactions by salt effects, Gazz. Chim. Ital, 1989, 119,533-5. 

R. Breslow and Carmelo J. Rizzo, "Chaotropic Salt Effects in a Hydrophobically Accelerated Diels-Alder Reaction", T. Am. Chem. Soc. 113,4340-4341 (1991). 

Breslow supported this suggestion by demonstrating that the cycloaddition can be further accelerated by adding anti cliaotropic salts such as lithium chloride, whereas chaotropic salts such as guanidium chloride led to a retardation " "" ". On the basis of these experiments Breslow excluded all other possible explanations for the special effect of water on the Diels-Alder reaction " . 

Three years after the Breslow report on the large effects of water on the rate of the Diels-Alder reaction, he also demonstrated tliat the endo-exo selectivity of this reaction benefits markedly from employing aqueous media . Based on the influence of salting-in and saltirg-out agents, Breslow pinpoints hydrophobic effects as the most important contributor to the enhanced endo-exo... 

Breslow studied the dimerisation of cyclopentadiene and the reaction between substituted maleimides and 9-(hydroxymethyl)anthracene in alcohol-water mixtures. He successfully correlated the rate constant with the solubility of the starting materials for each Diels-Alder reaction. From these relations he estimated the change in solvent accessible surface between initial state and activated complex " . Again, Breslow completely neglects hydrogen bonding interactions, but since he only studied alcohol-water mixtures, the enforced hydrophobic interactions will dominate the behaviour. Recently, also Diels-Alder reactions in dilute salt solutions in aqueous ethanol have been studied and minor rate increases have been observed Lubineau has demonstrated that addition of sugars can induce an extra acceleration of the aqueous Diels-Alder reaction . Also the effect of surfactants on Diels-Alder reactions has been studied. This topic will be extensively reviewed in Chapter 4. 

Table 1.21 Effect of metal salt on enantioselectivity in the Diels-Alder reaction of cyclopentadiene and acryloyloxazolidinone [22 ...

Kobayashi et al. have reported the use of a chiral lanthanide(III) catalyst for the Diels-Alder reaction [51] (Scheme 1.63, Table 1.26). Catalyst 33 was prepared from bi-naphthol, lanthanide triflate, and ds-l,2,6-trimethylpiperidine (Scheme 1.62). When the chiral catalyst prepared from ytterbium triflate (Yb(OTf)3) and the lithium or sodium salt of binaphthol was used, less than 10% ee was obtained, so the amine exerts a great effect on the enantioselectivity. After extensive screening of amines, ds-1,2,6-... 

The first studies on cation-radical Diels-Alder reactions were undertaken by Bauld in 1981 who showed [33a] the powerful catalytic effect of aminium cation radical salts on certain Diels-Alder cycloadditions. For example, the reaction of 1,3-cyclohexadiene with trans, iraw5-2,4-hexadiene in the presence of Ar3N is complete in 1 h and gives only the endo adduct (Equation 1.14) [33]. 

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... 

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