Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α-Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis.
Jack TwiltonMelodie ChristensenDaniel A DiRoccoRebecca T RuckIan W DaviesDavid W C MacMillanPublished in: Angewandte Chemie (International ed. in English) (2018)
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.
Keyphrases
- visible light
- oxide nanoparticles
- drug discovery
- transition metal
- electron transfer
- reduced graphene oxide
- signaling pathway
- molecular dynamics
- carbon nanotubes
- metal organic framework
- heavy metals
- drug induced
- alcohol consumption
- high glucose
- emergency department
- gold nanoparticles
- risk assessment
- endothelial cells
- adverse drug