Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α-Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis
Jack Twilton
Merck Center for Catalysis at Princeton University, Washington Road, Princeton, NJ, 08544 USA
Search for more papers by this authorMelodie Christensen
Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065 USA
Search for more papers by this authorDr. Daniel A. DiRocco
Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065 USA
Search for more papers by this authorDr. Rebecca T. Ruck
Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065 USA
Search for more papers by this authorDr. Ian W. Davies
Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. David W. C. MacMillan
Merck Center for Catalysis at Princeton University, Washington Road, Princeton, NJ, 08544 USA
Search for more papers by this authorJack Twilton
Merck Center for Catalysis at Princeton University, Washington Road, Princeton, NJ, 08544 USA
Search for more papers by this authorMelodie Christensen
Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065 USA
Search for more papers by this authorDr. Daniel A. DiRocco
Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065 USA
Search for more papers by this authorDr. Rebecca T. Ruck
Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065 USA
Search for more papers by this authorDr. Ian W. Davies
Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. David W. C. MacMillan
Merck Center for Catalysis at Princeton University, Washington Road, Princeton, NJ, 08544 USA
Search for more papers by this authorAbstract
The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer catalysis, and a Lewis acid activation mode, has led to the development of an arylation method for the selective functionalization of alcohol α-hydroxy C−H bonds. This approach employs zinc-mediated alcohol deprotonation to activate α-hydroxy C−H bonds while simultaneously suppressing C−O bond formation by inhibiting the formation of nickel alkoxide species. The use of Zn-based Lewis acids also deactivates other hydridic bonds such as α-amino and α-oxy C−H bonds. This approach facilitates rapid access to benzylic alcohols, an important motif in drug discovery. A 3-step synthesis of the drug Prozac exemplifies the utility of this new method.
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