oa Editorial [Hot Topic: Applications of Reactivity Indices based on Density Functional Theory to the Study of Organic Reactions. The Case of the Diels-Alder Reaction (Guest Editor: Luis R. Domingo)]

The Diels-Alder (DA) reaction is arguably one of the most powerful reactions in the arsenal of the synthetic organic chemist. From the establishment of the DA reaction in the 1920s by Otto Diels and Kurt Alder, a tremendous amount of experimental and theoretical work has been devoted to the study of the mechanism and the selectivity of these cycloaddition reactions. Several theories and rules have been proposed in the literature for the study of the reactivity and selectivity of DA reactions, namely the transition state theory (TST) and the frontier molecular orbital (FMO) theory. For many years, I have studied the molecular mechanism of DA reactions. An exhaustive study of DA reactions involving different substitutions at the diene and dienophile has allowed for a rationalization of the main factor responsible for the activation energy of DA reactions. A good correlation between the activation energy and the polar character of the DA reaction measured as the charge transfer (CT) at the transition state structure (TS) has been found (Org. Biomol. Chem. 2009, 7, 3576). This finding allowed for the establishment of the polar mechanism, which is characterized by electrophilic/nucleophilic interactions in the TS, instead of frontier molecular orbital interactions as proposed by the FMO theory. Several years ago, a series of studies devoted to the application of the reactivity indices defined within the conceptual density functional theory (DFT) for the study of polar cycloadditions were performed in collaboration with Contreras and Perez. The initial goal was to correlate the global electrophilicity index proposed by Parr, ω, with the activation barriers of the DA reactions previously studied in our laboratory. Thus, the common dienes and dienophiles involved in DA reactions were classified in a unique electrophilicity scale for the first time. The Δω of the diene/dienophile pairs was proposed as a measure of the polar character of the reactions. Since it does not apply to complex molecules having electrophilic/nucleophilic behaviors, we have recently introduced a simple empirical nucleophilicity index, N. On the other hand, the use of the local electrophilicity, ωk, and nucleophilicity, Nk, which also were proposed by us, allow for the understanding of the regio- and chemoselectivity in polar DA reactions. Although, the actual correlation between the experimental and the polar theoretical model is found between the reaction rate constants and the CT at the TSs, it is difficult for the experimental organic chemists to characterize the TSs for a series of DA reactions using the TST. Our studies have stated that the use of the global reactivity indices is a semiquantitative approach to estimate the polar character of DA reactions. However, it has to be noted that for complex molecules a local reactivity can not be accounted for adequately by global indices. Finally, I would like to emphasize that although some experimental/theoretical papers have appeared in the literature, in which the electrophilicity of the reagents is discussed within the electrophilicity scale, they do not make any sense if these analyses are not presented within the polar DA reaction model, since they are merely an approximation of the CT analysis that will take place at the TSs of the polar DA reactions. In this Special Issue, several studies based on the analysis of the DFT reactivity indices of different reagents involved in DA reactions are presented, thus reflecting the broad range of application of DFT indices in the study of reactivity and regioselectivity of polar DA reactions.