A novel route to fluoroarenes from trifluoroethanol

• Main Author: Wilson, Peter
• Published: University of Strathclyde 2014
• Subjects: 540
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.635537

This Thesis describes the preparation of fluoroarenes using a palladium-catalysed coupling/electrocyclisation methodology. Difluoroenolzinc coupling partners, 1-(N,N-diethylcarbamoyloxy)-2,2-difluoro-1-zinc chloride and 2,2-difluoro-1-(2'-methoxy-ethoxymethoxy)-1-zinc chloride were prepared from trifluoroethanol at near ambient temperature and underwent Negishi coupling with a range of aryl-halides. A co-solvent (N,N-dimethylpropylene urea) was necessary to generate 2,2-difluoro-1-(2'-methoxy-ethoxymethoxy)-1-zinc chloride in good yield. The zinc coupling partners were also converted to (iodo)difluoroenols which participated in Suzuki-Miyaura coupling with a range of aryl-boronic acids and potassium aryl-trifluoroborates. Side reactions of the Suzuki-Miyaura couplings were circumvented by using tertiary butanol as the reaction solvent. Low temperature preparation of trifluoroborate coupling partners, potassium 2,2-difluoro-1-(N,N-diethylcarbamoyloxy)ethenyl trifluoroborate and potassium 2,2-difluoro-1-(2'-methoxy-ethoxymethoxy)ethenyl trifluoroborate, from trifluoroethanol was also accomplished. The trifluoroborates underwent Suzuki-Miyaura coupling with a range of aryl-halides. This Suzuki-Miyaura coupling protocol was used to prepare a range of fluorinated electrocyclisation precursors in modest to good yield. Subsequent electrocyclisation afforded fluorobenzene, fluoronaphthalene and fluorophenanthrene species. The electrocyclisations were investigated computationally in an attempt to rationalise the ease/difficulty of cyclisation.