Selective bromination of sp3 C-H bonds by organophotoredox catalysis

• Main Authors: Kee, Choon Wee, Chan, Ke Min, Wong, Ming Wah, Tan, Choon-Hong
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2014
• Subjects: DRNTU::Science::Chemistry::Organic chemistry
• Online Access: https://hdl.handle.net/10356/101201; http://hdl.handle.net/10220/19712
• Institution: Nanyang Technological University

We report that bromination of aliphatic and benzylic sp3 C[BOND]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 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 C[BOND]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 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 C[BOND]H bond enables bromination to occur on the relatively stronger C[BOND]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 sp3 C[BOND]H bonds in complex molecules is exemplified by the bromination of (+)-sclareolide and acetate-protected estrone.