Copper‐Catalyzed Hydrodefluorination of Fluoroarenes by Copper Hydride Intermediates

Abstract

C F bond activation attracts much attention because of the rapid growth of fluorocarbons in pharmaceuticals, agrochemicals, and new materials. Such transformations not only provide new routes to the fluorinated organics, but also offer a fundamental understanding for C F bond cleavage and functionalization. Previous experimental and theoretical studies demonstrated the effectiveness of late transition metals (group 8–10) such as Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, and Pt for their electron-rich nature and the relatively weak M F bonds, which are important for catalytic functionality. Recently, we explored the reactivity of group 11 metal complexes and found that gold(I) complexes have good catalytic reactivity toward hydrodefluorination (HDF) of fluoroarenes. Despite the tremendous progress made, most catalytic systems suffered from either low catalyst turnovers, limited substrate scope, or harsh reaction conditions. For example, gold(I) complexes are reactive only for the substrates with strong electron-withdrawing substituents, and their efficiency was greatly dependent on the electronicdonating additives. To address these issues, we continued to explore the more-active group 11 metals such as copper, as we were inspired by the success of gold. In this context, we report herein the first example of a copper(I)-catalyzed HDF of fluoroarenes, and it features high reactivity, good regioselectivity, and a broad substrate scope. Since Subramanian and Manzer reported the CuF2mediated fluorination of aromatics, copper-catalyzed C F bond formation has been developed by the groups of Hartwig, Lectka, and others. In contrast, for catalytic C F bond activation, copper has been rarely studied. Ribas and coworkers recently showed that a Cu/Cu redox cycle activated C X bonds (X=halogens) using triazamacrocyclic ligand, thus indicating an oxidative addition mechanism. Herein, we found that for HDF reactions, copper hydrides exhibited an unprecedented reactivity toward C F bonds. Moreover, density functional theory (DFT) calculations suggest that C F bond activation by copper hydrides proceeds through a mechanism involving nucleophilic attack, and represents an alternative strategy for copper activating C F bonds. At the outset of our study, we searched for optimal HDF reaction conditions for perfluoronitrobenzene (PFNB). We first applied the our previous catalytic gold system but replaced gold(I) with [Cu(MeCN)4PF6]. Screening silanes (see Table S1 in the Supporting Information) such as HSi(OMe)3, HSiEt3, PMHS, H2SiPh2, and HSiMe2Ph, showed that HSiMe2Ph was the best hydrogen source (conv. 40%). Solvent screening resulted THF providing the highest yield (60%; see Table S2 in the Supporting Information). We then examined ligand effects and the results are listed in Table 1. In