Palladium-Catalyzed Enantioselective α-Arylation of α-Fluoroketones

• Main Authors: Jiao, Zhiwei, Beiger, Jason J., Jin, Yushu, Ge, Shaozhong, Zhou, Jianrong Steve, Hartwig, John F.
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2017
• Subjects: Palladium catalysis; Fluoroketone
• Online Access: https://hdl.handle.net/10356/84954; http://hdl.handle.net/10220/43608
• Institution: Nanyang Technological University

The transition-metal-catalyzed α-arylation of carbonyl compounds is a widely practiced method for C–C bond formation. Several enantioselective versions of this process have been reported, but intermolecular, enantioselective coupling reactions of aryl electrophiles with α-fluoro carbonyl compounds have yet to be disclosed. We report enantioselective coupling of aryl and heteroaryl bromides and triflates with α-fluoroindanones catalyzed by palladium complexes of a BINOL-derived monophosphine and Segphos, respectively. The enolates were generated directly from α-fluoroindanones in the presence of potassium phosphate base during the reactions. We also report that reactions of α-fluorotetralones occur in high yields and enantioselectivities when conducted with enolates generated by elimination of trifluoroacetate from trifluoromethyl β-diketone hydrates. These reactions were catalyzed by palladium complexes of the commercially available bisphosphine Difluorphos. Thus, the formation of enantioenriched α-aryl-α-fluoroketones can be readily achieved by C–C bond formation when the appropriate palladium catalyst and α-fluoro enolate precursor were used.