The reaction between an alkene and acid (H-X) to yield the Markovnikov adduct is a simple, atom-economical way to make compounds of commercial importance. As a result, hydrofunctionalization reactions are widely used in industry for the synthesis of simple molecules and polymeric materials. However, accessing the opposite regioisomer, the anti-Markovnikov adduct, remains difficult and current methods often employ expensive transition metal catalysts.
In order to provide a facile means of achieving the anti-Markovnikov transformation in an economic manner amenable to industrial scale, we have extensively investigated the use of olefin-derived radical cations as intermediates in this transformation. We have found that acridinium photocatalysts can be used to readily access these radical-cations, and that a variety of nucleophiles are able to add to these reactive intermediates with complete anti-Markovnikov selectivity.
In addition, we have been able to extend this work to the synthesis of highly-substituted heterocycles via a polar-radical-crossover-cycloaddition reaction and the difunctionalization of olefins by replacing the hydrogen-atom donor co-catalyst with a halogen-atom source.
Diverse and selective functionalizations of aromatic compounds promise facile construction of biologically active and structurally complex molecules. Our laboratory is focused on developing novel selective bond constructions for aromatic groups, and our strategy centers on generating reactive, open-shell arene radical cations via photoredox catalysis while pairing a suitable nucleophile to access the desired bond construction and functionalized aromatic species.
We are currently interested in developing methods for the direct C−H functionalization of aromatic compounds and have demonstrated mild, site-selective and photoredox-catalyzed C-H amination and C-H cyanation for simple and complex aromatic molecules. Continuing efforts will seek to develop this synthetic space and enable its adoption for real-world applications and translational science.