Calculation of electronic properties of aromatic dienophiles for reactivity prediction in diels-alder reactions

Introduction Diels-Alder reaction (D-A) is one of the most widely used synthetic strategies for the synthesis of natural products due to its character of generating cyclic systems. By this reaction cyclic compounds characteristic of some families of alkaloids may be directly developed, thus being of high value in synthesis (Biolatto et al., 1999; Della Rosa et al., 2004a). The use of aromatic compounds as dienes has been widely studied in D-A reactions, however, the use of them as dienophiles is a new and interesting branch that allows to state large and versatile synthetic sequences. The global electrophilicity index (ω), introduced by Maynard et al. (1998), and then formalized by Parr et al. (1999), allows to predict the trend of electron-acceptors (electrophiles) to acquire additional electronic charges from the environment. This index involves the electronegativity of the electron acceptor (χ =-μ) and its chemical hardness (η), that is to say, resistance to electron charge exchange with the environment. Recently, some studies on Density Functional Theory applied to D-A reactions have shown that the diene/dienophile classification in a single electrophilicity scale is a powerful tool to predict the feasibility of a cycloaddition approach and the type of mechanism involved (Domingo, 2002; Domingo and Aurell, 2002; Domingo et al., 2002 a,b). In this work, and as a contribution to the understanding of the reactivity of heteroaromatic dienophiles in D-A reactions with normal electron demand, previously developed experimentally (Della Rosa et al., 2004 a,b, 2005), the electronic properties of these dienophiles and some dienes were studied from a theoretical point of view. The dienophiles investigated are of the type of five-membered aromatic heterocycles mono-and disubstituted by electron-acceptor groups (A) (Fig. 1), while the dienes were isoprene and trans-1-methoxy-3trimethylsilyloxy-1,3-butadiene (Danishefsky’s diene) (Fig. 2).