88 Letters in Organic Chemistry, 2011, 8, 88-94 1570-1786/11 $58.00+.00 © 2011 Bentham Science Publishers Ltd. Theoretical Analysis of Substituted Diels - Alder Reagents to Determine the Polar or Non Polar Character of the Reaction Patricia Pérez* and Eduardo Chamorro Universidad Andres Bello, Departamento de Ciencias Químicas, Facultad de Ecología y Recursos Naturales, Laboratorio de Química Teórica, Av. República 275, 8370146 Santiago, Chile Received April 26, 2010: Revised October 27, 2010: Accepted November 19, 2010 Abstract: The non-polar character of Diels–Alder (DA) reactions using 1- and 2-substituted butadienes and ethylene is discussed. Linear correlations between variations in the energy barrier and the electrophilicity index have been obtained. The charge transfer (CT) process in the cycloaddition reactions depends on the substitution pattern on almost all ethylene reagents. The current work stresses that a polar DA reaction will occur when only the ethylene is substituted by electron- withdrawing (EW) groups increasing its electrophilicity or when both DA reagents are being activated by EW and electron-releasing (ER) groups, enhancing their electrophilic and nucleophilic nature. Keywords: Polar Diels-Alder reactions, non polar Diels-Alder reactions, substituted butadienes and ethylenes, electrophilicity, nucleophilicity. 1. INTRODUCTION One of the most important and powerful reactions of the synthetic organic chemistry is the Diels–Alder (DA) reaction [1, 2]. By varying the electronic nature of the diene and dienophile, many different types of carbocyclic structures can be built up. However, not all possibilities occur easily. For instance, the DA reaction between butadiene and ethylene must be forced to take place: after 17 hours at 165C and 900 atmospheres, it gives a 78% yield [3]. Nevertheless, the presence of electron-withdrawing (EW) groups in the dienophile and electron-releasing (ER) groups in the diene or vice versa can significantly accelerate the process [4]. Few years ago, Domingo et al. [5] have introduced a simple model to define the electrophilicity for DA reagents, based on the global electrophilicity index,  , proposed by Parr [6]. It was the first time having diene and dienophile species involved in DA reactions classified within a unique electrophilicity scale [5]. When electronic activation of the  system is reached by adding EW and (or) ER substituents on one or both reagents the reaction rate of the cycloaddition notably increases. Thus a change in reactivity has been proved by the difference in electrophilicity of the diene/dienophile reaction pairs,  , which was proposed as a measure of the polar character [5, 7]. However, in some cycloaddition reactions the polar character cannot completely be visualized by the  values. For this reason, recently we have introduced a relative global nucleophilicity index ( N ) [8] based on the HOMO energies of the organic nucleophiles, which help us to find the global nucleophilic/electrophilic interaction to yield a polar mechanisms. Under this approximation, global nucleophilicity and electrophilicity indices have been applied *Address correspondence to this author at the Universidad Andres Bello, Departamento de Ciencias Químicas, Facultad de Ecología y Recursos Naturales, Laboratorio de Química Teórica, Av. República 275, 8370146 Santiago, Chile; Tel: 56-2-6615756; Fax: 56-2-6618269; E-mail: p.perez@unab.cl to a great variety of reagents for cycloaddition reactions [9- 13] including DA and 1,3-dipolar cycloaddition reactions. In the polar model, the DA reactions are characterized by the dominant electrophile–nucleophile interactions [5, 14]. In these reactions, the progress of the charge transfer (CT) throughout the cycloaddition and, therefore, their feasibility, is well established once both, the nucleophilic and electrophilic behaviors of the reagents involved in the reaction have been identified by their position within the electrophilicity scale [5]. Within this reactivity model, the regioselectivity is rationalized by the most favorable polar interaction between the most electrophilic center of the electrophile and the most nucleophilic center of the nucleophile during a two-center interaction. The local descriptors, namely, the condensed-to-site electrophilicity [15-17] (  k ) and nucleophilicity [18-21] ( N k ) indices, are probed to be relevant tools for a wide characterization of these reactive sites in chemical species [22, 23]. Indeed, Peeters et al. [24] have showed the influence of the diene substitution on the transition state (TSs) stabilization in DA reactions. The authors concluded that the electronic nature of the substituent effects can (de)stabilize DA TSs [24] emphasizing that the reactivity of substituted dienes in [4+2] cycloadditions on ethylene can be predicted by the R and F electronic parameters [25]. The aim of this Letter is to get the reliability of the electrophilicity and nucleophilicity indices to predict the electronic character of the DA reactions using the Peeters’ systems [24] as benchmark (see Scheme 1). We want to emphasize that the increase of the electron-rich character of the diene (i.e. the nucleophilicity) and the increase of the electron-deficient character of the dienophile (i.e. the electrophilicity) or vice versa, results in an enhancement of the CT by lowering the activation barrier, providing in fact the conceptual basis to classify the cycloaddition reactions as polar or non polar process [14].