Reflex Carbocation Release from Covalent Molecules by Endogenous Free Radicals

Abstract

Carbocations are pervasive in contemporary organic synthesis, so new and innocuous methods of making them are always desirable. A theoretical approach revealed that compounds in which radical generation takes place may release carbocations advantageously. The radical types and molecular substructures that promote this effect were identified. The best substructures were found to be 1,3-dicarbonyl compounds, particularly those based on the Meldrum’s acid theme. Sulfate esters and dithiane rings could also be employed. Radicals generated on oxygen atoms or ethyne units were particularly effective. For these species, carbocation release could be reflex, that is, concurrent with radical generation. Only small radical enhancements were observed for release of lithium cations because of the ionic character of most of the precursors. Ethyne units could be incorporated as spacers between the radical center and the site of carbocation generation. Moreover, the enhancement was transmitted down polyethyne chains of at least six units.

Dissociations of free radicals to generate protons, electrophiles or nucleophiles: role in DNA strand breaks

“…We used a similar computational approach to test this scenario, starting with R m Z units that had shown the largest enhancements for proton release. 45 We found that carbocation release was indeed significantly enhanced for species having certain radical centres adjacent to potential cations. For spontaneous carbocation release, heterolysis needed to be exothermic, or more specifically exergonic, as well as enhanced.…”

Radical-Stimulated Nucleophile Release

“…A computational study established that carbocation release would also be strongly radical enhanced from functionalized Meldrum’s acids, from dithianes, from carbonate, and from other esters . For exergonic heterolytic dissociations, carbocations containing electron-releasing substituents were necessary.…”

“…a a Energies in kcal/mol A computational study established that carbocation release would also be strongly radical enhanced from functionalized Meldrum's acids, from dithianes, from carbonate and other esters. 6 For exergonic heterolytic dissociations, carbocations containing electron-releasing substituents were necessary. For example, the free energy for release of the 2-methoxypropylium cation from the carbonate radical (2 • ) derived from 2-methoxypropan-2-yl hydrogen carbonate was enhanced by about 13 kcal/mol in comparison with the non-radical model (see Scheme 1 (b)).…”