Abstract
Fagnou et al. reported direct arylation reactions that use palladium catalysts to couple Ar1–X to Ar2–H with the aid of a coordinated base. These reactions are particularly favourable for polyfluorinated arenes Ar2–H (see S. I. Gorelsky, D. Lapointe and K. Fagnou, J. Am. Chem. Soc. 2008, 130, 10848). In this paper, we show by means of a DFT analysis how the energetics and activation energies vary with fluorine substitution and examine the structures of intermediates and transition states. The reactant is modelled by Pd(OAc)(Ph)(PMe3)(DMA) (DMA = dimethylacetamide). The sequence consists of (a) replacement of DMA by arene, (b) Concerted Deprotonation Metallation (CMD), (c) decoordination of AcOH, (d) reductive elimination of biaryl. Many of the variations are dominated by the number of fluorine substituents ortho to the C–H bond and fall into three groups labelled accordingly: Set0Fo, Set1Fo, and Set2Fo. In the first step a coordinated solvent is replaced by the arene. The arenes of Set0Fo and Set1Fo coordinate in a conventional η2-CHdouble bond, length as m-dashCH mode, whereas the arenes of Set2Fo coordinate in an η1-CH mode assisted by an Ocdots, three dots, centeredH–C hydrogen bond from the coordinated acetate. Both the energy barriers to CMD and the product energies fall into the three typical sets with the highest barrier and highest product energy being for Set0Fo. They correlate more satisfactorily with the variations in Pd–C bond energies than with the C–H acidities. The barriers to reductive elimination from Pd(Ph)(ArF)(PMe3)(AcOH) increase systematically from Set0Fo to Set2Fo as the Pd–C bond becomes stronger in a regular fashion from Set0Fo to Set2Fo. Again there is a strong correlation between the energy barriers to reductive elimination and the Pd–C bond energies. It is found overall that the key aspects of the reactions are: (a) the lowering of the energy of the CMD step by the ortho fluorine substituents, (b) the regioselective activation of C–H bonds ortho to fluorine which is also determined at the CMD step, (c) the decoordination of AcOH, which maintains the transition state for reductive elimination at low Gibbs free energy. The presence of fluorine increases the effectiveness of the reaction in the sense of points a and b via the increasing strength of the palladium-carbon bond.