Diels-Alder pericyclic reaction has been one of the versatile tools in the armory of synthetic organic to access novel polycyclic frameworks and finds applications in the diversified areas. when both of reagents in the reaction are asymmetrically substituted, the orientation effect (regioselectivity) is observed. For a 1-substituted diene, a head-to-head (ortho) or a head-to-tail (meta) cycloaddition is possible. In this case the ortho isomer is preferred (ortho rule) and the head-to-head (meta) cycloadducts, in which the para isomer is favoured (para rule). In this research, the regioselectivity for more than sixty Diels-Alder reactins has been studied using hardness, polarizability and electrophilicity of the corresponding products as global reactivity indexes, it is shown that in many cases, the Maximum Hardness and Minimum Polarizability Principles (MHP and MPP) cannot predict the major regioisomer of a Diels-Alder reaction; whereas the analysis of global electrophilicities of the products shows that at least in those cases which diffuse basis sets are used , the major product of the reaction has always the less electrophilicity values. it seems that there is a tendency in atoms to arrange themselves so that the obtained molecule reaches the minimum electrophilicity. This rule may be called the Minimum Electrophilicity Principle; MEP.
