Regional matching of atomic softnesses in chemical reactions: A two-reactant charge sensitivity study

A semiempirical charge sensitivity analysis in atomic resolution is used to examine the regional softness parameters within two pairs of coordinating atoms in cyclization reactions, in a search for possible softness matching rules to be used as diagnostic tools for predicting regiochemistry trends. The cycloaddition reactions of a few typical 1,3-dipoles with the phosphoru s-containing dipolarophiles and substituted ethylenes are examined. Two typ es of the two-reactant charge response properties of strongly interacting s ubsystems are tested: the valence state (polarizational, P) softnesses of a toms in the polarized reactants, before the globally isoelectronic charge t ransfer (CT), and the in situ CT softnesses. The present analysis identifie s a simple regional softness matching rule in terms of two-reactant propert ies, called the maximum complementarity rule, which is shown to provide a v ery successful predictor of regioselectivity, particularly at the P + CT le vel of description. It correctly indexes a relative accessibility of altern ative transition states in a series of illustrative 1,3-dipolar cycloadditi ons. The rule is compared with the earlier regional HSAB principle, formula ted in terms of quantities of the separated reactants. The physical implica tions of various regional softness matching principles are discussed, and t he two-reactant influences on atomic FF indices are examined in some detail .