UBC Theses and Dissertations
Pt-catalyzed cross-coupling of arylfluorides : reaction development and mechanistic analysis Wang, Tongen
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.
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