Diels-Alder reactions study

Analogously, the effect of micelles on the rate of the unimolecular retro Diels-Alder reaction has been studied. Also here only a modest retardation" or acceleration" is observed. Likewise, the presence of micelles has been reported to have a modest influence on an intramolecular Diels-Alder reaction . Studies on the endo-exo selectivity of a number of different Diels-Alder reactions in micellar media lead to comparable conclusions. Endo-exo selectivities tend to be somewhat smaller in micellar solutions than in pure water, but still are appreciably larger than those in organic media In contrast, in microemulsions the endo-exo selectivity is reduced significantly" ... 

In 2002, Leadbeater and Torenius reported the base-catalyzed Michael addition of methyl acrylate to imidazole using ionic liquid-doped toluene as a reaction medium (Scheme 6.133 a) [190], A 75% product yield was obtained after 5 min of microwave irradiation at 200 °C employing equimolar amounts of Michael acceptor/donor and triethylamine base. As for the Diels-Alder reaction studied by the same group (see Scheme 6.91), l-(2-propyl)-3-methylimidazolium hexafluorophosphate (pmimPF6) was the ionic liquid utilized (see Table 4.3). Related microwave-promoted Michael additions studied by Jennings and coworkers involving indoles as heterocyclic amines are shown in Schemes 6.133 b [230] and 6.133 c [268], Here, either lithium bis(trimethylsilyl)amide (LiHMDS) or potassium tert-butoxide (KOtBu) was em-... 

The retro-Diels-Alder reactions studied may well involve many transient conhg-urations appropriate to the potential energy surface and vibrational possibihties approaching and traversing transition regions." " ... 

The first Diels-Alder reaction studied under high pressure was the dimerization of cyclopen-tadiene [751]. For recent, more detailed studies of the pressure-dependence of Diels-Alder cycloaddition reactions in solvents of different polarity, as well as discussions of the corresponding mechanistic aspects, see references [857, 874]. 

Kraka, E. Wu, A. Cremer, D. Mechanism of the Diels-Alder reaction studied with the united reaction vaUey approach mechanistic differences between symmetry-allowed and symmetry-forbidden reactions, 7. Phys. Chem. A 2003,107, 9008-9021. 

A chiral phosphonate-substituted azirine was prepared and its Diels-Alder reactions studied <20020L655>. Azirine 105 is prepared by the Swern oxidation of the corresponding aziridine as shown in Scheme 18. The Diels-Alder reaction of azirine 105 with Danishefsky s diene provides aziridine 106 in excellent yield as a single diastereomer. Note that the reaction time for azirines such as used by Gilchrist is only 15 min as compared to 8h with the phosphonate substituted azirines suggesting that the carboxylate-substituted azirines are much more reactive than the phosphonate-substituted azirines <19978271, 2001J(P1)2969, 2005S555>. 

Mechanism of the Diels-Alder Reaction. Studies of the Addition of Maleic Anhydride to Furan and Methylfurans. 

I 7 9 Alkene Pulsed Plasma Functionalized Surfaces An Inte facial Diels-Alder Reaction Study... 

An intense purple crystalline solid m.p. 219-220 C. One of the few monomeric cyclo-pentadienone derivatives, most of which spontaneously undergo self Diels-Alder type dimerization. Used as a diene in many studies of various aspects of the Diels-Alder reaction. ... 

The remainder of this chapter will provide the necessary background, from which the incentive of catalysing Diels-Alder reactions in water and the aims of the study will become apparent. 

In a recent experimental study of the femtosecond dynamics of a Diels-Alder reaction in the gas phase it has been suggested that both concerted and stepwise trajectories are present simultaneously It is interesting to read the heated debates between Houk and Dewar on the... 

Solvents exert their influence on organic reactions through a complicated mixture of all possible types of noncovalent interactions. Chemists have tried to unravel this entanglement and, ideally, want to assess the relative importance of all interactions separately. In a typical approach, a property of a reaction (e.g. its rate or selectivity) is measured in a laige number of different solvents. All these solvents have unique characteristics, quantified by their physical properties (i.e. refractive index, dielectric constant) or empirical parameters (e.g. ET(30)-value, AN). Linear correlations between a reaction property and one or more of these solvent properties (Linear Free Energy Relationships - LFER) reveal which noncovalent interactions are of major importance. The major drawback of this approach lies in the fact that the solvent parameters are often not independent. Alternatively, theoretical models and computer simulations can provide valuable information. Both methods have been applied successfully in studies of the solvent effects on Diels-Alder reactions. 

Studies by the group directed by Mayoral have been limited to Diels-Alder reactions of type A. When water was not included, the rate constants correlate with the solvent hydrogen-bond-donating capacity Upon inclusion of water the solvophobidty parameter, Sp, contributed significantly in... 

In summary, solvents can influence Diels-Alder reactions through a multitude of different interactions, of which the contributions to fire overall rate uniquely depend on the particular solvent-diene-dienophile combination. Scientists usually feel uncomfortable about such a situation and try to extract generalities. When limited to the most extensively studied type A Diels-Alder reactions this approach seems feasible. These Diels-Alder reactions are dominated by hydrogen bonding interactions in combination with solvophobic interactions. This observation predicts a very special role of water as a solvent for type A Diels-Alder reactions, which is described in Section 1.4. 

In 1961 Berson et al. were the first to study systematically the effect of the solvent on the endo-exo selectivity of the Diels-Alder reaction . They interpreted the solvent dependence of the endo-exo ratio by consideririg the different polarities of the individual activated complexes involved. The endo activated complex is of higher polarity than the exo activated complex, because in the former the dipole moments of diene and dienophile are aligned, whereas in the latter they are pointing in... 

Unfortunately, the number of mechanistic studies in this field stands in no proportion to its versatility" . Thermodynamic analysis revealed that the beneficial effect of Lewis-acids on the rate of the Diels-Alder reaction can be primarily ascribed to a reduction of the enthalpy of activation ( AAH = 30-50 kJ/mole) leaving the activation entropy essentially unchanged (TAAS = 0-10 kJ/mol)" . Solvent effects on Lewis-acid catalysed Diels-Alder reactions have received very little attention. A change in solvent affects mainly the coordination step rather than the actual Diels-Alder reaction. Donating solvents severely impede catalysis . This observation justifies the widespread use of inert solvents such as dichloromethane and chloroform for synthetic applications of Lewis-acid catalysed Diels-Alder reactions. 

The extreme influence water can exert on the Diels-Alder reaction was rediscovered by Breslow in 1980, much by coincidence . Whale studying the effect of p-cyclodextrin on the rate of a Diels-Alder reaction in water, accidentally, the addition of the cyclodextrin was omitted, but still rate constants were observed that were one to two orders of magnitude larger than those obtained in organic solvents. The investigations that followed this remarkable observation showed that the acceleration of Diels-Alder reactions by water is a general phenomenon. Table 1.2 contains a selection from the multitude of Diels-Alder reactions in aqueous media that have been studied Note that the rate enhancements induced by water can amount up to a factor 12,800 compared to organic solvents (entry 1 in Table 1.2). 

Tire importance of hydrophobic interactions in the aqueous acceleration is further demonstrated by a qualitative study described by Jenner on the effect of pressure on Diels-Alder reactions in water and a number of organic solvents. Invariably, the reactions in water were less accelerated by pressure than those in organic solvents, which is in line with the notion that pressure diminishes hydrophobic interactions. 

Studies on solvent effects on the endo-exo selectivity of Diels-Alder reactions have revealed the importance of hydrogen bonding interactions besides the already mentioned solvophobic interactions and polarity effects. Further evidence of the significance of the former interactions comes from computer simulations" and the analogy with Lewis-acid catalysis which is known to enhance dramatically the endo-exo selectivity (Section 1.2.4). 

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. 

A few years after the first articles of Breslow had appeared, Grieco elegantly demonstrated that the astonishing rate and selectivity enhancements of Diels-Alder reactions in water can be exploited sirccessfully in organic synthesis. He extensively studied the reactivity of dienes containing... 

Recently the scalirg up of water-based Diels-Alder reactions has been studied. ... 

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

Mechanistic studies have tried to unravel the origin of the special effect of water. Some authors erroneously have held aggregation phenomena responsible for the observed acceleration, whereas others have hinted at effects due to the internal pressure. However, detailed studies have identified two other effects that govern the rate of Diels-Alder reactions in water. 

The relative extents to which enforced hydrophobic interactions and hydrogen bonding influence the rate of the Diels-Alder reaction depends on the particular reaction under study". 

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