Nickel versus Palladium in Cross-Coupling Catalysis: On the Role of Substrate Coordination to Zerovalent Metal Complexes

Abstract

A detailed comparison of the effect of coordinating functional groups on the performance of Suzuki–Miyaura reactions catalysed by nickel and palladium is reported, using competition experiments, robustness screening, and density functional theory calculations. Nickel can interact with a variety of functional groups, which manifests as selectivity in competitive cross-coupling reactions. The presence of these functional groups on exogenous additives has effects on cross-coupling reactions that range from a slight improvement in yield to the complete cessation of the reaction. In contrast, palladium does not interact sufficiently strongly with these functional groups to induce selectivity in cross-coupling reactions; the selectivity of palladium-catalysed cross-coupling reactions is predominantly governed by aryl halide electronic properties.

Aldehydes and ketones influence reactivity and selectivity in nickel-catalysed Suzuki–Miyaura reactions

“…[NiCl(o-tol)(L) n ] (L ¼ dppe (20), Xantphos (21)) 34 were applied in: (i) competition reactions between 5-Br and 3-Br, in which 3-Br reacts exclusively; and (ii) robustness screening reactions using 5-Br as the substrate and benzaldehyde as the additive, showing signicant reaction inhibition (Fig. 6).…”

“…Palladium, specically [PdCl 2 (dppf)], shows a far reduced propensity to undergo selective cross-coupling reactions, but has far better functional group tolerance. 20…”

“…Our initial empirical study showed that various coordinating groups elicit these effects, and that they are considerably more marked for nickel than for palladium. 20 Here, we examine the specic case of aldehydes and ketones in depth using a range of experimental and computational techniques.…”

Palladium‐Catalyzed Cross‐Coupling of Alkenyl Carboxylates

“…Many of these reactions occur at room temperature with no need for inert atmosphere, use water as a co‐solvent, and do not require exogenous base. This process takes advantage of the broad functional‐group tolerance common to many Pd catalyzed reactions to functionalize multiple pharmaceutically relevant heterocycles. The success of this method is in stark contrast to the general perception that Pd catalysts are less reactive or inert toward many C(sp 2 )−O electrophiles …”

C–O Bond Activation as a Strategy in Palladium-Catalyzed Cross-Coupling

“…The synthesis of complex molecules as low-volume high-value products (such as pharmaceuticals, agrochemicals, or advanced materials) requires robust, efficient, and economical chemical processes that work for highly functionalized substrates. Despite the high cost and low natural abundance of Pd, organopalladium catalysis offers many distinct advantages, including excellent functional-group tolerance, 50,51 relatively high catalytic efficiency (i.e., low catalyst loadings), and the ability to act in the presence of water or even air. To us, discovering and exploiting complementary reactivity with both precious-and abundant-metal catalysts is an important goal.…”