Can we predict ambident regioselectivity using the chemical hardness?

Area of Science:

• Chemistry
• Chemical Reactivity
• Theoretical Chemistry

Background:

• The hard/soft acid/base (HSAB) principle is fundamental to understanding chemical reactivity.
• A "local" version of the HSAB principle was developed to predict regioselectivity in reactions.
• Experimental data frequently contradicts predictions made by the local HSAB principle.

Purpose of the Study:

• To re-examine the assumptions underlying the standard proof of the local HSAB rule.
• To identify the flaws in the existing theoretical framework.
• To propose revised models for predicting regioselectivity.

Main Methods:

• Analysis of the assumptions in the standard proof of the local HSAB rule.
• Theoretical examination of charge transfer and reorganization in reacting molecules.
• Development of new regioselectivity models based on revised principles.

Main Results:

• The standard proof of the local HSAB rule is based on a flawed premise.
• Accurate regioselectivity prediction requires considering charge reorganization within non-reacting molecular parts, not just charge transfer.
• New models accounting for charge reorganization have been derived.

Conclusions:

• The local HSAB principle, as currently formulated, is unreliable for predicting regioselectivity.
• Incorporating molecular charge reorganization is crucial for advancing the HSAB principle.
• The proposed reorganization models offer a more accurate framework for chemical reactivity predictions.