Outcome-changing effect of polarity reversal in hydrogen-atom-abstraction reactions

We have examined hydrogen-atom-abstraction reactions for combinations of electrophilic/nucleophilic radicals with electrophilic/nucleophilic substrates. We find that reaction between an electrophilic radical and a nucleophilic substrate is relatively favorable, and vice versa, but the reactions between a radical and a substrate that are both electrophilic or both nucleophilic are relatively unfavorable, consistent with the literature reports of Roberts. As a result, the regioselectivity for the abstraction from a polar substrate can be reversed by reversing the polarity of the attacking radical. Our calculations support Roberts' polarity-reversal-catalysis concept and suggest that addition of a catalyst of appropriate electrophilicity/nucleophilicity can lead to an enhancement of the reaction rate of approximately 5 orders of magnitude. By exploiting the control over regioselectivity associated with the polar nature of the radical and the substrate, we demonstrate the possibility of directing the regioselectivity of hydrogen abstraction from amino acid derivatives and simultaneously providing a significant rate acceleration.