Charge-controlled reactions

Self-consistent field molecular orbital calculations by Fenske and coworkers have confirmed that nucleophilic additions to Fischer and related complexes [e.g., (CO)sCr=CXY, (T)5-C5H5)(CO)2Mn=CXY], are frontier orbital-controlled rather than charge-controlled reactions (7-9). Interaction of the HOMO of the nucleophile with the carbene complex LUMO (localized on Ca) destroys the metal-carbon w-interaction and converts the bond to a single one. 

From the above it follows that, in spite of numerous potential possibilities, nitronates would not be good reagents in charge-controlled reactions. However, the structures of these compounds are favorable for concerted reactions, which are schematically shown in Scheme 3.86. 

Baciocchi et al43 have reported the existence of the pH-dependent mechanistic dichotomy for the deprotonation of 4-methoxybenzyl alcohol radical cation in aqueous solution. In neutral and acidic solutions the 4-MeOC6H4CH2OH + radical cation undergoes C-H deprotonation, while in basic solution (pH 10), the reaction is initiated by deprotonation of the OH group. DFT calculations were carried out and reveal that the OH induced O-H deprotonation is consistent with the charge controlled reaction, while the C-H deprotonation, observed when the base is HjO, appears to be effected by frontier orbital interactions43. 

The mechanism of the nitration of benzisoxazoles in sulfuric-nitric acid mixture has been studied with 3-methyl-l,2-benzisoxazole [121], It has been found that at a sulfuric acid concentration of about 80-90% the substrate reacts as a free base, and at a higher concentration the conjugated acid undergoes nitration. It is worth mentioning that in 1,2-benzisoxazole and its 3-methyl derivative the higher electron density is concentrated on the C-7 atom and in the case of charge-controlled reactions the nitration would lead to 7-nitro isomers. Since 5-nitro derivatives are formed, the process of nitration seems to be of orbital-controlled character [121],... 

The total charges on the two reactants are the dominant factors of the reaction (charge-controlled reaction). This type of reaction occurs when the donor is difficult to ionize or polarize (E very low) and the acceptor has a slight tendency to accept electrons (E very high) and when both are strongly solvated, i.e., they are small. The charge-controlled reaction is therefore synonymous with a hard-hard interaction. 

The stereochemical aspect of electrophilic substitution of metallocenes is intriguing. In acylation, the attack comes from the outside (anti to the metal) and the order of reactivities is ferrocene > ruthenocene > osmocene (18). On the other hand, during mercuration the electrophile approaches from the inside (syn to the metal). It is clear that (/) hard electrophiles align themselves farthest from the essentially soft metal in the transition states, and the charge-controlled reactions (acylation) occur more readily with the harder metallocenes, and (ii) soft electrophiles (e.g., Hg ) approach the aromatic ring from the same side as the metal which permits soft-soft interaction. 

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