Selective Bromination of sp³ CH Bonds by Organophotoredox Catalysis

Abstract

Abstract We report that bromination of aliphatic and benzylic sp 3 CH bonds can be achieved with visible light photoredox catalysis by using a low loading of Eosin Y 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 CBr 4 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 CH 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 CBr 3 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 CH bond enables bromination to occur on the relatively stronger CH 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 CH bonds in complex molecules is exemplified by the bromination of (+)‐sclareolide and acetate‐protected estrone.