Mechanism and enantioselectivity in α-alkylation of carbonyl compounds via photoredox organocatalysis: A DFT study

The alpha-alkylation of carbonyl compounds (aldehyde and beta-ketocarbonyl) via photoredox organocatalysis has been theoretically studied with density functional theory (DFT). The key step in the alpha-allcylation is the couple of the electron-rich enamine intermediate and the electrophilic radical. The former is formed of a chiral amine catalyst and carbonyl compound; and the latter results from the photocatalytic reduction of alkyl halide. Three probable pathways have been proposed to account for this key step, including oxidation-electrophilic addition, oxidation-radical coupling and radical addition-oxidation. The difficulty in distinguishing these pathways lies in how to compare the electron transfer and the radical addition. In the present work, besides the prediction of the standard redox potential, a new method has been developed and the calculations show that the radical addition-oxidation pathway is the most favorable. The new method contains three key points: (i) two similar reactions with different ee values were chosen to compare; (ii) due to different orientation (Re- vs. Si-), the ee value relates to the free energy difference for a pair of enantiomer intermediates or to the activation free energy difference for the radical additions; (iii) the more the (activation) free energy difference, the better the ee value. (C) 2016 Elsevier B.V. All rights reserved.