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Pt-catalyzed cross-coupling of arylfluorides : reaction development and mechanistic analysis

University of British Columbia

Fluoroaromatics have been widely utilized in practical applications such as plastics, refrigerants, pharmaceuticals and pesticides. In fact, it has been reported that 30% of new agrochemicals and 20% of new drugs contain fluorine. However, as no aryl fluorides have been isolated from natural products, fluoroaromatic building blocks are only available through synthesis. Partial functionalization of polyfluoroaromatics is a promising methodology to generate functionalized fluoroarenes. The work reported in this thesis firstly focuses on the development of Pt(II)-catalyzed cross-coupling of polyfluoroaryl imines. This methodology has been applied to a wide range of polyfluoroaryl imines with a variety of functional groups, producing methylated fluoroaryl imines in high yields and with high selectivity for the imine-directed ortho position, even in the presence of much weaker Br-aryl and CN-aryl bonds. These methylated fluoroaryl imine products are potential synthetic building blocks for the construction of pharmaceutically active molecules and agrochemicals. Next, insight into the mechanism of this Pt(II)-catalyzed cross-coupling of polyfluoroaryl imines is provided. We propose that the catalytic reaction involves the following steps: C-F activation, transmetalation and reductive elimination. Specifically, the Me₂Pt(IV)-F complex formed in the C-F activation step with Me₂Pt(II) undergoes transmetalation with Me₂Zn to generate a Me₃Pt(IV) species. Reductive elimination from Me₃Pt(IV) leads to the formation of the methylated imine product and re-generates Me₂Pt(II), which can then promote C-F activation of remaining substrates, thus completing the catalytic cycle. Both transmetalation and reductive elimination occur from 5-coordinate species. Finally, examples of unusual preference for Csp²-Csp³ coupling over Csp²-Csp² or Csp³-Csp³ coupling are illustrated. We anticipated that a biphenyl product would be formed in the reductive elimination of a tetrafluorinated aryl-Me₂Pt(IV)Ph complex, based on the premise that Csp²-Csp² coupling is much faster than Csp²-Csp³ or Csp³-Csp³ coupling. However, the dominant organic products in the reductive elimination from a tetrafluorinated aryl-Me₂Pt(IV)Ph complex are methylated imine and toluene, both of which result from Csp²-Csp³ coupling. In contrast, the biphenyl product is only formed in trace amounts. These unexpected results can be explained by Hartwig’s “push-pull” theory that the largest difference of electronic properties between two ligands leads to the fastest rate of reductive elimination.

Text

2010-11-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/24153

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/