Palladium-Catalysed C–F Alumination of Fluorobenzenes: Mechanistic Diversity and Origin of Selectivity

A palladium pre-catalyst, [Pd(PCy3)2] is reported for the efficient and selective C–F alumination of fluorobenzenes with the aluminium(I) reagent [{(ArNCMe)2CH}Al] (1, Ar = 2,6-di-iso-propylphenyl). The catalytic protocol results in the transformation of sp2 C–F bonds to sp2 C–Al bonds and provides a route into reactive organoaluminium complexes (2a-h) from fluorocarbons. The catalyst is highly active. Reactions proceed within 5 minutes at 25 oC (and at appreciable rates at even –50 oC) and the scope includes low-fluorine-content substrates such as fluorobenzene, difluorobenzenes and trifluorobenzenes. The reaction proceeds with complete chemoselectivity (C–F vs C–H) and high regioselectivities ( >90% for C–F bonds adjacent to the most acidic C–H sites). The heterometallic complex [Pd(PCy3)(1)2] was shown to be catalytically competent. Catalytic C–F alumination proceeds with a KIE of 1.1–1.3. DFT calculations have been used to model potential mechanisms for C–F bond activation. These calculations suggest that two competing mechanisms may be in operation. Pathway 1 involves a ligand-assisted oxidative addition to [Pd(1)2] and leads directly to the product. Pathway 2 involves a stepwise C–H to C–F functionalisation mechanism in which the C–H bond is broken and reformed along the reaction coordinate, allowing it to act as a directing group for the adjacent C–F site. This second mechanism explains the experimentally observed regioselectivity. Experimental support for this C–H activation playing a key role in C–F alumination was obtained by employing [{(MesNCMe)2CH}AlH2] (3, Mes = 2,4,6-tri-methylphenyl) as a reagent in place of 1. In this instance, the kinetic C–H alumination intermediate could be isolated. Under catalytic conditions this intermediate converts to the thermodynamic C–F alumination product.