Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α‐Arylation of Alcohols through Photoredox,HAT, and Nickel Catalysis |
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| Authors: | Jack Twilton Melodie Christensen Dr. Daniel A. DiRocco Dr. Rebecca T. Ruck Dr. Ian W. Davies Prof. Dr. David W. C. MacMillan |
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| Affiliation: | 1. http://www.princeton.edu/chemistry/macmillan/ 0000-0003-3500-4901 Merck Center for Catalysis at Princeton University, Princeton, NJ, USA;2. Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, USA;3. Merck Center for Catalysis at Princeton University, Princeton, NJ, USA |
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| Abstract: | ![]()
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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| Keywords: | alcohols heterocycles hydrogen atom transfer nickel photoredox catalysis |
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