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Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α‐Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis
Author(s) -
Twilton Jack,
Christensen Melodie,
DiRocco Daniel A.,
Ruck Rebecca T.,
Davies Ian W.,
MacMillan David W. C.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201800749
Subject(s) - chemistry , deprotonation , catalysis , alkoxide , lewis acids and bases , nickel , hydrogen bond , combinatorial chemistry , alcohol , photochemistry , medicinal chemistry , organic chemistry , molecule , ion
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.