Catalyst Activation, Deactivation, and Degradation in Palladium‐Mediated Negishi Cross‐Coupling Reactions

Abstract

Pd-mediated Negishi cross-coupling reactions were studied by a combination of kinetic measurements, electrospray-ionization (ESI) mass spectrometry, (31)P NMR and UV/Vis spectroscopy. The kinetic measurements point to a rate-determining oxidative addition. Surprisingly, this step seems to involve not only the Pd catalyst and the aryl halide substrate, but also the organozinc reagent. In this context, the ESI-mass spectrometric observation of heterobimetallic Pd-Zn complexes [L2 PdZnR](+) (L=S-PHOS, R=Bu, Ph, Bn) is particularly revealing. The inferred presence of these and related neutral complexes with a direct Pd-Zn interaction in solution explains how the organozinc reagent can modulate the reactivity of the Pd catalyst. Previous theoretical calculations by González-Pérez et al. (Organometallics- 2012, 31, 2053) suggest that the complexation by the organozinc reagent lowers the activity of the Pd catalyst. Presumably, a similar effect also causes the rate decrease observed upon addition of ZnBr2 . In contrast, added LiBr apparently counteracts the formation of Pd-Zn complexes and restores the high activity of the Pd catalyst. At longer reaction times, deactivation processes due to degradation of the S-PHOS ligand and aggregation of the Pd catalyst come into play, thus further contributing to the appreciable complexity of the title reaction.

Reaction Intermediates Kinetics in Solution Investigated by Electrospray Ionization Mass Spectrometry: Diaurated Complexes

“…[1][2][3][4][5] The introduction of electrospray ionization (ESI) allowed direct probing of reaction mixtures and ESI-MS was established as a method for "fishing out" reaction intermediates. 6,7 A big advantage of using ESI-MS is its sensitivity. Reactive intermediates that are often present at very low concentrations can be detected, isolated in the gas phase and can have their reactivity probed.…”

Stability and Unimolecular Reactivity of Palladate(II) Complexes [LnPdR3]− (L=Phosphine, R=Organyl, n=0 and 1)

“…In general, organozinc reagents are less reactive than the corresponding Grignard reagents. [7] Even more surprising is the observation of the stable Pd IV species[ PdBn 5 ] À under the present conditions. [9] However,t hese reactions occurred under conditions differentf rom the present ones.…”

Photoinduced Palladium‐Catalyzed Negishi Cross‐Couplings Enabled by the Visible‐Light Absorption of Palladium–Zinc Complexes

“…Thep resence of Pd 0 -Zn complexes in Negishi reactions was recently reported in the literature, [15] but their photochemical behavior remained unknown. Thep resence of Pd 0 -Zn complexes in Negishi reactions was recently reported in the literature, [15] but their photochemical behavior remained unknown.…”