Charge control reactivity

Aminothia2ole-3-oxides in neutral medium react differently on alky) isocyanates (355) and arylisocyanates (356) (Scheme 204) (684). The interpretation of this difference rests on the Concepts of charge control versus frontier control reactivity (1594 see also p. 63). Esters of... 

These concepts play an important role in the Hard and Soft Acid and Base (HSAB) principle, which states that hard acids prefer to react with hard bases, and vice versa. By means of Koopmann s theorem (Section 3.4) the hardness is related to the HOMO-LUMO energy difference, i.e. a small gap indicates a soft molecule. From second-order perturbation theory it also follows that a small gap between occupied and unoccupied orbitals will give a large contribution to the polarizability (Section 10.6), i.e. softness is a measure of how easily the electron density can be distorted by external fields, for example those generated by another molecule. In terms of the perturbation equation (15.1), a hard-hard interaction is primarily charge controlled, while a soft-soft interaction is orbital controlled. Both FMO and HSAB theories may be considered as being limiting cases of chemical reactivity described by the Fukui ftinction. 

The importance of both frontier orbital-controlled and electronic charge-controlled factors in determining chemical reactivity has been recognized (16). These concepts are the key to interpreting two types of reactivity expected for carbene complexes, i.e., reactions with nucleophilic... 

As conjugated systems with alternating 7T-charges, the polymethine dyes are comparatively highly reactive compounds (3). Substitution rather than addition occurs to the equalized 7T-bond. If the nucleophilic and electrophilic reactions are charge-controlled, reactants can attack regiospecifically. 

Reactions of carbocations with free CN- occur preferentially at carbon, and not nitrogen as predicted by the principle of hard and soft acids and bases.69 Isocyano compounds (N-attack) are only formed with highly reactive carbocations where the reaction with cyanide occurs without an activation barrier because the diffusion limit has been reached. A study with the nitrite nucleophile led to a similar observation.70 This led to a conclusion that the ambident reactivity of nitrite in terms of charge control versus orbital control needs revision. In particular, it is proposed that SNl-type reactions of carbocations with nitrite only give kinetically controlled products when these reactions proceed without activation energy (i.e. are diffusion controlled). Activation controlled combinations are reversible and result in the thermodynamically more stable product. The kinetics of the reactions of benzhydrylium ions with alkoxides dissolved in the corresponding alcohols were determined.71 The order of nucleophilicities (OH- MeO- < EtO- < n-PrCT < / -PrO ) shows that alkoxides differ in reactivity only moderately, but are considerably more nucleophilic than hydroxide. 

Experimentally, MeBr gives O-methylation in the gas-phase reactions25 but RBr favors C-alkylation in solution. In general, charge control dominates gas-phase reactions because strong Coulombic effects26 are not attenuated by counterions or solvents. Since solution reactions are usually under frontier orbital control, the reactivity... 

As with carbene complexes, metal carbynes display a range of reactivity with electrophiles and nucleophiles. Molecular orbital calculations show that even cationic Fischer carbyne complexes are polarized as M, +=C A neutral Fischer- and Schrock carbyne complexes have an even greater negative charge on Ccarbyne.93 If all reactions between carbyne complexes and other species were charge-controlled, we would predict that nucleophiles would always attack at the metal and electrophiles at Ccarbyne. As we should expect by now, the picture is more complicated in practice. 

For a review of orbital control and charge control, see G. Klopman, Chemical Reactivity and Reaction Paths, John Wiley, New York, 1974, Chapter 4. 

The existence of a charge density presupposes a concomitant set of MOs and Sect 2.3 describes how chemical reactivity can be based on the notion of Frontier Molecular Orbital (FMO) control i.e. the most important orbital interactions are between the HOMO on one species and the LUMO on the other or vice versa. FMO control, together with electrostatic charge control, provides a powerful qualitative basis for interpreting reactivity. The relative energies and compositions of MOs are vital and many computer programs now provide 3-dimensional representations of MOs to facilitate analysis. 

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