The use of a Pd(II)/Pd(0) redox couple to effect catalytic fluorination of aryl halides remains a challenging but potentially powerful route to the selective installation of fluorine into substrates relevant to pharmaceutical, agrochemical, and materials science applications using simple fluoride salts as the fluorine source. While ostensibly operating by a catalyst cycle analogous to other C−X cross-coupling reactions, such as Buchwald-Hartwig amination, there is little systematic understanding about how the key palladium-fluoride catalytic intermediates form and subsequently undergo carbon-fluorine reductive elimination. Due to its sterically hindered, stable, and strongly coordinating character, we hypothesized that tri(1-adamantyl) phosphine (Ad3P) could be effective at promoting C–F reductive elimination from LPdIIAr(F) complexes by simultaneously lowering the activation energy of this desired reaction through steric effects, disfavoring unwanted dimerization to a stabilized four-coordinate μ2-fluoro ground state, and/or inhibiting unproductive decomposition side reactions. This work aimed to (1) theoretically study the effect of ligand perturbations on C–F reductive elimination thermodynamics using density functional theory (DFT), (2) synthesize LPdIIAr(F) complexes ligated by Ad3P, and (3) thermally promote C–F reductive elimination from those complexes. Preliminary DFT calculations suggest that sterically hindered ligands like Ad3P and electron deficient aryl ligands in the LPdIIAr(F) structure both enhance C–F reductive elimination rates, but under the wide range of experimentally tested conditions and routes (i.e., Pd–Br, Pd–I, cationic Pd(II) precursors), synthesis of suitable Pd–F species to validate the computational predictions was hindered by synthetic challenges in the seemingly straightforward halide exchange step. Our results may indicate that, in addition to the challenge of C–F reductive elimination from Pd(II), preceding steps that generate low-coordinate Pd(II) fluoro complexes may also be problematic steps during catalysis that should be considered in future catalysis studies.

Synthesis of a sterically hindered three-coordinate Pd(II) complex for C–F reductive elimination

2019 Spring National Meeting

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