Diels reaction volumes

In Table 2 Diels-Alder reactions are complied showing ratios of activation volume to reaction volume that are smaller than or close to unity (0 = AV /AV < 1) and in Table 3 those that are close to or even larger than unity (0 > 1). Within the scope of transition state theory, the activation volume can be considered to be a measure of the partial molar volume of the transition state [AV = F — F (reactants)]. Accordingly, the transition state volumes of these reactions are close to or even smaller than the... 

Intermolecular [4 + 2] cycloadditions exhibit strongly negative activation volumes and reaction volumes. High pressure, therefore, can be applied to accelerate Diels-Alder reactions and to shift the reaction equilibrium towards the cycloadducts. These effects are of particular advantage to (1) promote odierwise slow [4 + 2] cycloadditions involving heat or Lewis acid sensitive educts or products (2) suppress cycloreversion processes which are eidier thermodynamically favored or would interfere with a kinetically controlled stereochemistry. In view of a recent review (1985) only a few examples are presented here. 

The pressure dependence of the orbital symmetry-allowed [6 - - 4] cycloaddition of tropone with 1,3-dienes was first studied by le Noble and Ojosipe , who reported extremely small absolute values of and AV. A reinvestigation by Takeshita and his coworkers showed, however, that the activation and reaction volumes of these cycloadditions are of the same order of magnitude as those of Diels-Alder reactions (Scheme l7 entry 1). Dogan confirmed this finding with a study of the reaction between 1,3-butadiene and tropone in which a [6 + 4] cycloaddition competes with a [4 + 2] Diels-Alder reaction. The activation volume of the overall reaction was again found to be highly negative. However, the ratio between the [6+4] and [4+2] cycloadduct turned out to be almost pressure-independent, which means that the ifference between the activation volumes (SAT ) is almost zero and hence the activation volumes of both reactions are of the same value. 

Scheme 2.6. Activation and reaction volumes determined experimentially and calculated van der Waals volumes and packing coefficients of retro-Diels-Alder reactions [48]. All volumes (in cm mol" ) related to the temperature of reaction.

Microwave irradiation has been widely used in organic synthesis on a laboratory scale during the last few years. Several categories of reactions, for example, Diels-Alder reactions, ortAo-Claisen condensations, ene-reactions, oxidations, esterification of carboxylic acids with alcohols, and hydrolysis of esters and amides to carboxylic acids, have been successfully carried out in conventional microwave ovens. Table 26.4, adapted from Majetich and Hicks (1994), provides representative examples of some of these reactions. It can be seen that the conditions under which the conventional and microwave reactions are carried out differ significantly for most reactions. Hence, in comparing reactions with micro-waves with conventional syntheses with reflux, it is necassary to make the comparisons based on the total amount of energy input to the reaction volume. 

In summary, it seems that for most Diels-Alder reactions secondary orbital interactions afford a satisfactory rationalisation of the endo-exo selectivity. However, since the endo-exo ratio is determined by small differences in transition state energies, the influence of other interactions, most often steric in origin and different for each particular reaction, is likely to be felt. The compact character of the Diels-Alder activated complex (the activation volume of the retro Diels-Alder reaction is negative) will attenuate these eflfects. The ideas of Sustmann" and Mattay ° provide an attractive alternative explanation, but, at the moment, lack the proper experimental foundation. 

Alternatively, authors have repeatedly invoked the internal pressure of water as an explanation of the rate enhancements of Diels-Alder reactions in this solvent ". They were probably inspired by the well known large effects of the external pressure " on rates of cycloadditions. However, the internal pressure of water is very low and offers no valid explanation for its effect on the Diels-Alder reaction. The internal pressure is defined as the energy required to bring about an infinitesimal change in the volume of the solvents at constant temperature pi = (r)E / Due to the open and... 

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. 

The observation that in the activated complex the reaction centre has lost its hydrophobic character, can have important consequences. The retro Diels-Alder reaction, for instance, will also benefit from the breakdown of the hydrophobic hydration shell during the activation process. The initial state of this reaction has a nonpolar character. Due to the principle of microscopic reversibility, the activated complex of the retro Diels-Alder reaction is identical to that of the bimoleciilar Diels-Alder reaction which means this complex has a negligible nonpolar character near the reaction centre. O nsequently, also in the activation process of the retro Diels-Alder reaction a significant breakdown of hydrophobic hydration takes placed Note that for this process the volume of activation is small, which implies that the number of water molecules involved in hydration of the reacting system does not change significantly in the activation process. 

We conclude that the beneficial effects of water are not necessarily limited to reactions that are characterised by a negative volume of activation. We infer that, apart from the retro Diels-Alder reaction also other reactions, in which no significant reduction or perhaps even an increase of solvent accessible surface area takes place, can be accelerated by water. A reduction of the nonpolar nature during the activation process is a prerequisite in these cases. 

Most Diels-Alder reactions, particularly the thermal ones and those involving apolar dienes and dienophiles, are described by a concerted mechanism [17]. The reaction between 1,3-butadiene and ethene is a prototype of concerted synchronous reactions that have been investigated both experimentally and theoretically [18]. A concerted unsymmetrical transition state has been invoked to justify the stereochemistry of AICI3-catalyzed cycloadditions of alkylcyclohexenones with methyl-butadienes [12]. The high syn stereospecificity of the reaction, the low solvent effect on the reaction rate, and the large negative values of both activation entropy and activation volume comprise the chemical evidence usually given in favor of a pericyclic Diels-Alder reaction. 

According to the frontier orbital theory, a bond preferentially forms between the atoms with the largest frontier orbital amplitudes (Sect. 3.4 in the Chapter Elements of a Chemical Orbital Theory by Inagaki in this volume). This is applicable for the regioselectivities of Diels-Alder reactions [15]. The orbital mixing rules are shown here to be useful to understand and design the regioselectivities. 

The orbital mixing theory was developed by Inagaki and Fukui [1] to predict the direction of nonequivalent orbital extension of plane-asymmetric olefins and to understand the n facial selectivity. The orbital mixing rules were successfully apphed to understand diverse chemical phenomena [2] and to design n facial selective Diels-Alder reactions [28-34], The applications to the n facial selectivities of Diels-Alder reactions are reviewed by Ishida and Inagaki elesewhere in this volume. Ohwada [26, 27, 35, 36] proposed that the orbital phase relation between the reaction sites and the groups in their environment could control the n facial selectivities and review the orbital phase environments and the selectivities elsewhere in this volume. Here, we review applications of the orbital mixing rules to the n facial selectivities of reactions other than the Diels-Alder reactions. 

During the past decade, many papers have dealt with the facial selectivities of Diels-Alder reactions, particularly in relation to dienes [153-159], and various attempts have been made to rationalize the origins of the selectivities [160]. The facial selectivities of Diels-Alder reactions are discussed in detail in Chapter jt-Fadal Selectivity of Diels-Alder Reactions by Ishida and hiagaki in this volume. In this and the following section, we will consider the facial selectivities of Diels-Alder reactions in terms of orbital phase enviromnent. 

Inagaki, Fujimoto and Fukui demonstrated that ir-facial selectivity in the Diels-Alder reaction of 5-acetoxy- and 5-chloro-l,3-cyclopentadienes, 1 and 2, can be explained in terms of deformation of a frontier molecular orbital FMO [2], The orbital mixing rule was proposed to predict the nonequivalent orbital deformation due to asymmetric perturbation of the substituent orbital (Chapter Orbital Mixing Rules by Inagaki in this volume). 

In the case of the reverse-electron-demand Diels-Alder reactions, the secondary orbital interaction between the Jt-HOMO of dienophile and the LUMO of 114 or the effect of the orbital phase enviromnents (Chapter Orbital Phase Enviromnents and Stereoselectivities by Ohwada in this volume) cannot be ruled out as the factor controlling the selectivity (Scheme 55). 

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