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1. Solvent Effects on the Selectivity of Palladium‐Catalyzed Suzuki‐Miyaura Couplings

   https://doi.org/10.1002/ijch.201900082  

   Reeves, Emily K.; Bauman, Olivia R.; Mitchem, Gunner B.; Neufeldt, Sharon R. (August 2019, Israel Journal of Chemistry)

   Abstract The use of polar solvents MeCN or dimethylformamide (DMF) was previously shown to induce a selectivity switch in the Pd/P^tBu₃‐catalyzed Suzuki‐Miyaura coupling of chloroaryl triflates. This phenomenon was attributed to the ability of polar solvents to stabilize anionic transition states for oxidative addition. However, we demonstrate that selectivity in this reaction does not trend with solvent dielectic constant. Unlike MeCN and DMF, water, alcohols, and several polar aprotic solvents such as MeNO₂, acetone, and propylene carbonate provide the same selectivity as nonpolar solvents. These results indicate that the role of solvent on the selectivity of Suzuki‐Miyaura couplings may be more complex than previously envisioned. Furthermore, this observation has the potential for synthetic value as it greatly broadens the scope of solvents that can be used for chloride‐selective cross coupling of chloroaryl triflates. 

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2. Chemical Modification of Silk Proteins via Palladium‐Mediated Suzuki−Miyaura Reactions

   https://doi.org/10.1002/macp.202300307  

   Santen, Racine M.; Owens, Kayla M.; Echague, Keith C.; Murphy, Amanda R. (October 2023, Macromolecular Chemistry and Physics)

   Abstract Suzuki−Miyaura cross‐coupling reactions are used to modify the tyrosine residues onBombyx morisilkworm silk proteins using a water‐soluble palladium catalyst. First, model reactions using tyrosine derivatives are screened to determine optimal reaction conditions. For these reactions, a variety of aryl boronic acids, solvents, buffers, and temperature ranges are explored. Qualitative information on the reaction progress is collected via high‐performance liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR). Optimized reactions are then applied to silk proteins. It is demonstrated the ability to modify silk fibroin in solution by first iodinating the tyrosine residues on the protein, and then carrying out Suzuki‐Miyaura reactions with a variety of boronic acid derivatives. Modification of silk is confirmed with NMR, ion‐exchange chromatography (IEC), UV‐vis, and infrared spectroscopy (IR). 

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3. General Base‐Free Suzuki‐Miyaura Cross‐Coupling Reaction via Electrophilic Substitution Transmetalation

   https://doi.org/10.1002/anie.202512496  

   Zhang, Meng; Shan, Jing‐Ran; Xie, Yuke; Wei, Lanen; Xiong, Haigen; Xie, Ge‐Ning; Qi, Ting; Shi, Qinqin; Houk, K N; Huang, Hui (July 2025, Angewandte Chemie International Edition)

   Abstract The transition‐metal‐catalyzed Suzuki‐Miyaura cross‐coupling (SMC) reaction of organoboron nucleophiles with aryl (pseudo)halide electrophiles is a reliable method for carbon‐carbon bond formation. This reaction generally requires the use of an exogenous base to promote transmetalation process, which limits the substrate scope of the reaction due to undesired protodeboronation and functional group incompatibilities. Here, we established a base‐free SMC reaction via a conceptually different electrophilic substitution transmetalation (EST). This transformation is applicable to a wide range of base‐sensitive and sterically hindered organoborons. Key to this advance is the formation of a stable cationic palladium(II) or nickel(II) intermediate via experimental and theoretical investigations. In a broader context, this research further expands the synthetic boundary of cross‐coupling chemistry. 

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4. Multi‐Threshold Analysis for Chemical Space Mapping of Ni‐Catalyzed Suzuki‐Miyaura Couplings

   https://doi.org/10.1002/ejoc.202400428  

   LeSueur, Austin; Tao, Nari; Doyle, Abigail; Sigman, Matthew (September 2024, European Journal of Organic Chemistry)

   Abstract A key challenge in synthetic chemistry is the selection of high‐performing ligands for cross‐coupling reactions. To address this challenge, this work presents a classification workflow to identify physicochemical descriptors that bin monophosphine ligands as active or inactive in Ni‐catalyzed Suzuki‐Miyaura coupling reactions. Using five previously published high‐throughput experimentation datasets for training, we found that a binary classifier using a phosphine's minimum buried volume and Boltzmann‐averaged minimum electrostatic potential is most effective at distinguishing high and low‐yielding ligands. Experimental validations are also presented. Using the two physicochemical descriptors from the binary classifier to represent the chemical space of monophosphine ligands leads to a more predictive guide for structure‐reactivity relationships compared with classic chemical space representations. 

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5. Suzuki–Miyaura catalyst-transfer polymerization: new mechanistic insights

   https://doi.org/10.1039/D3PY00580A  

   Howell, Mitchell T; Kei, Peter; Anokhin, Maksim V; Losovyj, Yaroslav; Fronczek, Frank R; Nesterov, Evgueni E (September 2023, Polymer Chemistry)

   Controlled preparation of structurally precise complex conjugated polymer systems remains to be a major synthetic challenge still to be addressed, and this push is stimulated by the improved device performance as well as unique fundamental characteristics that the well-defined conjugated polymer materials possess. Catalyst-transfer polymerization (CTP) based on Pd-catalyzed Suzuki-Miyaura cross-coupling reaction is currently one of the most promising methods towards achieving such a goal, especially with the recent implementation of N-methyliminodiacetic acid (MIDA) boronates as monomers in CTP. Further expansion and development of practical applications of CTP methods will hinge on a clear mechanistic understanding of both the entire process and the particular steps involved in the catalytic cycle. In this work, we introduced Ag⁺-mediated Suzuki-Miyaura CTP and demonstrated that presence of Ag⁺ shifted a key transmetalation step toward the oxo-Pd pathway, leading to direct participation of MIDA-boronates in the transmetalation step and hence in the polymerization process, and resulting in the overall more efficient polymerization. In addition, we found that, under Ag⁺-mediated conditions, MIDA-boronates can also directly participate in small-molecule cross-coupling reactions. The direct participation of MIDA-boronates in Suzuki-Miyaura cross-coupling has not been envisaged previously and could enable new interesting possibilities to control this reaction both for small-molecule and macromolecular syntheses. In contrast to MIDA-boronates, boronic acid monomers likely undergo transmetalation through an alternative boronate pathway, although they may also be directed to react via the oxo-Pd transmetalation pathway in Ag⁺-mediated conditions. The interplay between the two transmetalation pathways which are both involved in the catalyst-transfer polymerization, and the opportunity to selectively enhance one of them not only improves mechanistic understanding of Suzuki-Miyaura CTP process but also provides a previously unexplored possibility to gain more effective control over the polymerization to obtain structurally better-defined conjugated polymers. 

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