The Direction of Nucleophilic Attack and Orbital Steering

The reaction path for addition of the simplest nucleophilic reactant, the hydride ion, calculated by an ab initio and the MINDO/3 method is depicted in Fig. 5.7. At large distances between the hydride ion and the electrophilic center, predominant are the electrostatic forces of interaction between the reactants, and the nucleophile occupies a position collinear with the C=0 bond, as in XXXIa. At the distances less than 3 A, the role of the orbital interaction, i.e., the exchange repulsion and charge transfer effects, becomes decisive. The attacking nucleophile leaves the plane of the carbonyl group and approaches the carbonyl fragment, in the zone of formation of the new bond, at an angle of 109.5°. 

This picture closely agrees with predictions of the structural correlation method (Sect. 1.3.5.3, Fig. 1.18) and conforms well to the predictions founded on a study of the regions of charge concentration and charge depletion, as defined by the Laplacian of electron density, to identify the sites of nucleophilic attack of formaldehyde and acetaldehyde [112]. It may easily be interpreted by considering the interactions between the frontier orbitals of reactants. The main 

Having compared these data with the geometry of the molecules calculated by the molecular mechanics method, the same authors concluded that in XXXVIIIc optimal orientation is achieved of the nucleo philic group OH with respect to carbonyl, namely, the angle of approach of 98°, while even insignificant deviations ( 10°) from it appreciably inhibit the reaction. The requirement for such refined adjustment of the reaction site became known as the orbital steering concept provoking lively discussion [118,119]. 

Theoretical checking of this concept led to a more precise definition of its scope. Using as an example the ion-molecular reaction of addition of the methoxide anion to formaldehyde (see Table 5.4), which served as a model for the reaction in complexes of the enzyme trypsin with its substrates, Scheiner and Lipscomb [98] have shown that the region of the attractive potential on the reaction PES, 

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