Rationalization of Experimental Results

The recognition of the species which is undergoing reaction, of the quantitative effects of heteroatoms, of interactions between heteroatoms and substituents, and of the importance of hydrogen bonding have made possible, for the first time, a rational, quantitative, overall treatment of heteroaromatic reactivity patterns. 

The heterocyclic literature is enormous, and a significant fraction deals with electrophilic substitution reactions of heteroaromatics. A great many authors have provided quantitative data, but the data are scattered through the literature, rarely reviewed comprehensively, and still less interpreted. Indeed, a proper interpretation is possible only by taking the wider view. This is what this book is intended to provide. It has been found possible not only to give interpretations of all of these quantitative data—in many cases for the first time—but to consider, additionally, much of the semiquantitative and qualitative work on the electrophilic substitution of heterocycles. 

In our rationalization, we have relied heavily on the classical concept of aromaticity with particular emphasis on bond order and bond fixation. These concepts, together with acid-base and tautomeric equilibria and hydrogen bonding, are capable of explaining nearly all of the quantitative 

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Although the correlation between ket and the driving force determined by Eq. (14) has been confirmed by various experimental approaches, the effect of the Galvani potential difference remains to be fully understood. The elegant theoretical description by Schmickler seems to be in conflict with a great deal of experimental results. Even clearer evidence of the k t dependence on A 0 has been presented by Fermin et al. for photo-induced electron-transfer processes involving water-soluble porphyrins [50,83]. As discussed in the next section, the rationalization of the potential dependence of ket iti these systems is complicated by perturbations of the interfacial potential associated with the specific adsorption of the ionic dye. 

The dienes and polyenes are compounds which intervene in a large number of organic reactions, as will be seen in different chapters of this book. Several excellent reviews have been devoted to theoretical studies about their reactivity, with special emphasis on the mechanism of pericyclic reactions3-5. As was mentioned in the introduction, this section will only treat, as an example, the Diels-Alder reaction, since it has been the most studied one by theoreticians. Our goal is not to cover all aspects, but instead to show the high potential and usefulness of theoretical methods in order to interpret and rationalize the experimental results. In the rest of the chapter we will concentrate on the last ab initio calculations. 

The first chapter in this volume is a particularly timely one given the recent surge of activity in natural product synthesis based upon stereocontrolled Aldol Condensations. D. A. Evans, one of the principal protagonists in this effort, and his associates, J. V. Nelson and T. R. Taber, have surveyed the several modem variants of the Aldol Condensation and discuss models to rationalize the experimental results, particularly with respect to stereochemistry, in a chapter entitled Stereoselective Aldol Condensations. The authors examine Aldol diastereoselection under thermodynamic and kinetic control as well as enantioselection in Aldol Condensations involving chiral reactants. 

For both the hydrogen and chlorine compounds, until now only the C2 species are reported in the literature (33) whereas with fluorine substituents both isomers, difluorodisulfane as well as thiothionyl difluoride have been isolated and their structures determined by microwave spectroscopy (34). Surprisingly, the F2S=S molecule, which exhibits one of the shortest S=S bonds of onyl 189pm length, is thermodynamically more stable (34), and -even more - for both isomers, FSSF and F2S=S, almost identical ionization patterns are observed (35). In order to rationalize these experimental results, and especially to find out,whether there are chances for the spectroscopist to also detect the Cg isomers, 828=8 and Cl2S=S, hypersurface calculations were performed. 

Sn2 reactions provide an interesting example of the utility of electrostatic potential maps in rationalizing an experimental result, while challenging conventional wisdom . It is well established that a nucleophile such as bromide reacts much faster with methyl bromide than it does with ter/ -butyl bromide. The reason normally cited is that while the transition state for the Sn2 reaction with methyl bromide is uncrowded , that for the corresponding reaction with tert-hutyl bromide is sterically crowded . However, this interpretation does... 

A great deal of experimental results have been rationalized on that basis for instance, compound 284 gives only the olefin 286 via an anti process while the isomer 285 gave a mixture of olefin 286 (syn mode) and 287 (anti mode). 

In this review the synthetic aspects of asymmetric hydroformylation will be discussed first the experimental data relevant to attempt a rationalization of the results will then be considered. The closely related synthesis of optically active aldehydes by hydroformylation of optically active olefinic substrates in the presence of achiral catalysts7,8 and the different asymmetric hydrocarbonylation reactions, such as the synthesis of esters from olefins, carbon monoxide and alcohols in the presence of optically active catalysts9 , are beyond the scope of this review and will not be discussed here. 

The Rondan-Houk theory rationalizes many experimental results and leads to several predictions which have since been confirmed. Exceptions have been explained by Houk and co-workers, using numerical calculations. In a sense, the problem of electrocyclic reaction torquoselectivity may be considered solved. 

Stereochemistry is a concept of paramount importance in chemistry. Stereoselective reactions, be they diastereoselective or enantioselective, are therefore a valuable tool in producing compounds of the desired stereochemistry. Every stereoselective reaction has an energetically preferred transition state that can explain the formation of the major stereoisomer. A reasonable transition state is very important not only in rationalizing the experimental results, but also in further advancing the chemical system that one is studying. 

To rationalize these experimental results, the authors [91] proposed that the common intermediate is a 7r-allyl complex of nickel 272 that can give rise either to the SN2-type coupled product 273, or the SN2 -type compound 274, depending on the steric demands [Eq. (93)]. 

The reaction course of the allylic substitution, which can nicely rationalize the experimental results shown in the foregoing, was proposed by Goering et al., based on their extensive studies on regio- and stereochemical outcome of this reaction [11,90,117, 127,128]. Scheme 1 summarizes their argument. The copper species 1 generated from CuY... 

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