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Abstract

Palladium(0) complexes are widely used as homogeneous catalysts for formation of carbon-carbon, carbon-oxygen, and carbon-nitrogen bonds. In general, the active catalysts are too unstable to store, and so precursors [often in the Pd(II) oxidation state] are prepared with stabilizing ligands that dissociate under the reaction conditions. However, the mechanisms and efficiency whereby these precursors transform into active catalysts have largely gone unaddressed, as has the potentially inhibitory effect of the stabilizing ligands left behind in the reaction solution. Biscoe et al. undertook a more careful approach by synthesizing a stable Pd(II) precursor complex resembling a reaction intermediate along the catalytic cycle. In three efficient steps, they appended a cyclometalated phenyl ring with a tethered chelating amine group to the Pd center. Exposure of this precatalyst to basic reaction conditions in the presence of aryl chlorides and amines led to rapid liberation of the protective ligand as an inert dihydroindole, leaving the resultant Pd(0) complex free to proceed with a similar C-N coupling cycle of the bulk reagents. In comparison with traditional precatalysts, these complexes dramatically accelerated coupling reactions (in one case from 4 days to 4 hours), allowing loadings below 1 mol % and reaction temperatures at or below 25°C for sensitive substrates. The absence of interfering precatalyst ligands also facilitated clear mechanistic studies. — JSY