Selective Bromination of sp3 C ∼ H Bonds by Organophotoredox Catalysis

We report that bromination of aliphatic and benzylic sp(3) CH bonds can be achieved with visible light photoredox catalysis by using a low loading of EosinY disodium salt, an inexpensive organic dye, as a photoredox catalyst. The light source is a low-power household lamp and the reaction can be performed without the need of an inert atmosphere and anhydrous solvent. Easy-to-handle CBr4 is the source of bromine and morpholine is necessary for the reaction. Preliminary experimental and computational studies on the mechanism strongly suggest that an N-morpholino radical is responsible for the CH activation step. This led us to propose that this is a radical relay reaction, in which a longer-lived morpholine radical is generated from a CBr3 radical, which is relatively more transient, by a thermodynamically favorable reaction. Additional evidence for the existence of such an N-radical was obtained from radical trapping experiments. The strong preference of this reaction for electron-rich hydrogen atoms, and the high sensitivity to the steric environment around the CH bond enables bromination to occur on the relatively stronger CH bond (as quantified by bond dissociation enthalpy) on the same molecule. The potential for utilizing this reaction to achieve mild and regioselective bromination of sp(3) CH bonds in complex molecules is exemplified by the bromination of (+)-sclareolide and acetate-protected estrone.