Scholarly Work - Chemistry & Biochemistry

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    Nickel-Based Catalysts for the Selective Monoarylation of Dichloropyridines: Ligand Effects and Mechanistic Insights
    (American Chemical Society, 2024-04) Duran-Camacho, Geraldo; Bland, Douglas C.; Li, Fangzheng; Neufeldt, Sharon R.; Sanford, Melanie S.
    This report describes a detailed study of Ni phosphine catalysts for the Suzuki–Miyaura coupling of dichloropyridines with halogen-containing (hetero)aryl boronic acids. With most phosphine ligands, these transformations afford mixtures of mono- and diarylated cross-coupling products as well as competing oligomerization of the boronic acid. However, a ligand screen revealed that PPh2Me and PPh3 afford high yield and selectivity for monoarylation over diarylation as well as minimal competing oligomerization of the boronic acid. Several key observations were made regarding the selectivity of these reactions, including: (1) phosphine ligands that afford high selectivity for monoarylation fall within a narrow range of Tolman cone angles (between 136 and 157°); (2) more electron-rich trialkylphosphines afford predominantly diarylated products, while less electron-rich di- and triarylphosphines favor monoarylation; (3) diarylation proceeds via intramolecular oxidative addition; and (4) the solvent (MeCN) plays a crucial role in achieving high monoarylation selectivity. Experimental and density functional theory studies suggest that all of these data can be explained based on the reactivity of a key intermediate: a Ni0–π complex of the monoarylated product. With larger, more electron-rich trialkylphosphine ligands, this π complex undergoes intramolecular oxidative addition faster than ligand substitution by the MeCN solvent, leading to selective diarylation. In contrast, with relatively small di- and triarylphosphine ligands, associative ligand substitution by MeCN is competitive with oxidative addition, resulting in the selective formation of monoarylated products. The generality of this method is demonstrated with a variety of dichloropyridines and chloro-substituted aryl boronic acids. Furthermore, the optimal ligand (PPh2Me) and solvent (MeCN) are leveraged to achieve Ni-catalyzed monoarylation of a broader set of dichloroarene substrates.
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    Combined Experimental and Computational Mechanistic Investigation of the Palladium-Catalyzed Decarboxylative Cross-Coupling of Sodium Benzoates with Chloroarenes
    (American Chemical Society, 2021-08) Humke, Jenna N.; Daley, Ryan A.; Morrenzin, Aaron S.; Neufeldt, Sharon R.; Topczewski, Joseph J.
    Reported herein is a mechanistic investigation into the palladium catalyzed decarboxylative cross-coupling of sodium benzoates and chloroarenes. The reaction was found to be first order in Pd. A minimal substituent effect was observed with respect to the chloroarene and the reaction was zero order with respect to chloroarene. Palladium mediated decarboxylation was assigned as the turn-over limiting step based on an Eyring plot and DFT computations. Catalyst performance was found to vary based on the electrophile, which is best explained by catalyst decomposition at Pd(0). The COD ligand contained in the precatalyst CODPd(CH2TMS)2 (Pd1) was shown to be a beneficial additive. The bench stable Buchwald complex XPhos-PdG2 could be used with exogenous COD and XPhos instead of complex Pd1. Adding exogenous XPhos significantly increased the catalyst TON and enhanced reproducibility.
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    Mechanistic Investigation into the Gold-Catalyzed Decarboxylative Cross-Coupling of Iodoarenes
    (American Chemical Society, 2021-07) Daley, Ryan A.; Morrenzin, Aaron S.; Neufeldt, Sharon R.; Topczewski, Joseph J.
    While many gold catalyzed reactions have been thoroughly developed, most are not thought to involve redox events at gold. In contrast, recent advances have demonstrated the feasibility of redox gold catalysis. This report describes a detailed mechanistic investigation of the gold catalyzed decarboxylative cross-coupling, which likely proceeds via a high valent Au(I/III) pathway. This investigation includes a kinetic analysis, stoichiometric experiments with Au(III) complexes, and DFT calculations. These data support a turnover limiting oxidative addition to form an Au(III) aryl complex, with an off cycle resting state. The dominant pathway appears to proceed through a silver mediated decarboxylation with a subsequent Ag(I) to Au(III) transmetalation. These data provide some rationale for the significant counterion effects between SbF6– and NTf2– and may explain why MeDalphos is not a superior ligand for the catalytic reaction.
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    C–O-Selective Cross-Coupling of Chlorinated Phenol Derivatives
    (Georg Thieme Verlag KG, 2021-05) Neufeldt, Sharon R.; Russell, John E. A.
    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 Introduction2 Density Functional Theory Studies on Oxidative Addition at Nickel(0)3 Stoichiometric Oxidative Addition Studies4 Development of a Tosylate-Selective Suzuki Coupling5 Conclusion and Outlook
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