Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α-Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis.

Autor: Twilton J; Merck Center for Catalysis at Princeton University, Washington Road, Princeton, NJ, 08544, USA., Christensen M; Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065, USA., DiRocco DA; Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065, USA., Ruck RT; Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065, USA., Davies IW; Process Research and Development, MRL, Merck Sharp & Dohme Corp., Rahway, NJ, 07065, USA., MacMillan DWC; Merck Center for Catalysis at Princeton University, Washington Road, Princeton, NJ, 08544, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2018 May 04; Vol. 57 (19), pp. 5369-5373. Date of Electronic Publication: 2018 Apr 06.
DOI: 10.1002/anie.201800749
Abstrakt: 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.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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