Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α‐Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis. Issue 19 (6th April 2018)

• Record Type: Journal Article
• Authors: Twilton, Jack; Christensen, Melodie; DiRocco, Daniel A.; Ruck, Rebecca T.; Davies, Ian W.; MacMillan, David W. C.
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 19(2018)
• Page Start: 5369
• Page End: 5373
• Publication Date: 2018-04-06
• Subjects: alcohols -- heterocycles -- hydrogen atom transfer -- nickel -- photoredox catalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201800749
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : The power of three : A triple catalysis method was developed for C−C bond formation at the α‐carbon of alcohols using aryl halide electrophiles. This method provides generic access to a broad range of benzylic and heteroaryl benzylic motifs. A new strategy for the selective functionalization of alcohols by leveraging a Lewis acid additive was utilized to enable selective hydrogen atom transfer at the α‐carbon and suppress competing C−O coupling.