Search for: All records

Two limiting mechanisms are possible for oxidative addition of (hetero)aryl (pseudo)halides at Pd(0): a 3-centered concerted and a nucleophilic displacement mechanism. Until now, there has been little understanding about when each mechanism is relevant. Prior investigations to distinguish between these pathways were limited to a few specific combinations of substrate and ligand. Here, we computationally evaluated over 180 transition structures for oxidative addition in order to determine mechanistic trends based on substrate, ligand(s), and coordination number. Natural abundance 13C kinetic isotope effects pro-vide experimental results consistent with computational predictions. Key findings include that (1) differences in HOMO symmetries dictate that, although 12e– PdL is strongly biased toward a 3-centered concerted mechanism, 14e– PdL2 often prefers a nucleophilic displacement mechanism; (2) ligand electronics and sterics, including ligand bite angle, influence the preferred mechanism of reaction at PdL2; (3) phenyl triflate always reacts through a displacement mechanism regardless of catalyst structure due to the stability of a triflate anion and the inability of oxygen to effectively donate electron density to Pd; and (4) the high reactivity of C—X bonds adjacent to nitrogen in pyridine substrates relates to stereoelectronic stabilization of a nucleophilic displacement transition state. This work has implications for controlling rate and selectivity in catalytic couplings, and we demonstrate application of the mechanistic insight toward chemodivergent cross-couplings of bromochloroheteroarenes. 

Reaction solvent was previously shown to influence the selectivity of Pd/PtBu3-catalyzed Suzuki-Miyaura cross-couplings of chloroaryl triflates. The role of solvents has been hypothesized to relate to their polarity, whereby polar solvents stabilize anionic transition states involving [Pd(PtBu3)(X)]– (X = anionic ligand) and nonpolar solvents do not. However, here we report detailed studies that reveal a more complicated mechanistic picture. In particular, these results suggest that the selectivity change observed in certain solvents is primarily due to solvent coordination to palladium. Polar coordinating and polar noncoordinating solvents lead to dramatically different selectivity. In coordinating solvents, preferential reaction at triflate is likely catalyzed by Pd(PtBu3)(solv), whereas noncoordinating solvents lead to reaction at chloride through monoligated Pd(PtBu3). The role of solvent coordination is supported by stoichiometric oxidative addition experiments, density functional theory (DFT) calculations, and catalytic cross-coupling studies. Additional results suggest that anionic [Pd(PtBu3)(X)]– is also relevant to triflate selectivity in certain scenarios, particularly when halide anions are available in high concentrations. 

Abstract Chemoselective cross-coupling of phenol derivatives is valuable for generating products that retain halides. Here we discuss recent developments in selective cross-couplings of chloroaryl phenol derivatives, with a particular focus on reactions of chloroaryl tosylates. The first example of a C–O-selective Ni-catalyzed Suzuki–Miyaura coupling of chloroaryl tosylates is discussed in detail. 1 Introduction 2 Density Functional Theory Studies on Oxidative Addition at Nickel(0) 3 Stoichiometric Oxidative Addition Studies 4 Development of a Tosylate-Selective Suzuki Coupling 5 Conclusion and Outlook