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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 international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201800749
Subject(s) - chemistry , catalysis , deprotonation , alkoxide , lewis acids and bases , nickel , hydrogen bond , alcohol , combinatorial chemistry , hydrogen atom abstraction , photochemistry , stereochemistry , medicinal chemistry , organic chemistry , hydrogen , molecule , ion
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.