Review
Chemistry, Multidisciplinary
Anna-Carin C. Carlsson, Staffan Karlsson, Rachel H. Munday, Matthew R. . Tatton
Summary: Atropisomerism is a stereochemical phenomenon exhibited by molecules with a rotationally restricted sigma bond. Atropisomers exist as a dynamic mixture and can be interconverted without breaking and reforming bonds. They are frequent targets in medicinal chemistry projects due to their axial chirality and unique 3D structures. However, selecting a single atropisomer presents problems such as interconversion and separation challenges. Chromatography, enzymatic or chiral catalysts can be used for separation, but each method has limitations. This Account discusses the successes, failures, and challenges of developing methods for resolution and synthesis of atropisomeric drug candidates.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Chemistry, Physical
Alexander F. Schmidt, Anna A. Kurokhtina, Elizaveta Larina, Nadezhda A. Lagoda
Summary: Despite extensive studies on the reaction of Pd intermediates in the Suzuki-Miyaura reaction (SMR), direct evidence supporting the widely accepted assumptions regarding the activity of Pd hydroxo complexes is lacking. This study presents results on the reactivity of Pd-OH and/or Pd-OR-containing complexes in the transmetalation step under ligand-free turnover conditions. The catalytic involvement of specific Pd species was determined under real catalytic conditions by measuring the selectivity of competing reactions.
MOLECULAR CATALYSIS
(2023)
Article
Chemistry, Applied
Nadezhda A. Lagoda, Elizaveta Larina, Elena V. Vidyaeva, Anna A. Kurokhtina, Alexander F. Schmidt
Summary: This study distinguishes between the homogeneous and heterogeneous catalytic mechanisms of Pd catalytic systems in the Suzuki-Miyaura reaction, providing convincing evidence for reactions proceeding simultaneously through both mechanisms. The use of ligand-free conditions suggests that the reaction proceeds in the solution phase through a homogeneous mechanism even when heterogeneous precursors are used, based on differential selectivity under competition conditions.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Chemistry, Organic
Giorgio Rizzo, Gianluigi Albano, Teresa Sibillano, Cinzia Giannini, Roberta Musio, Fiorenzo G. Omenetto, Gianluca M. Farinola
Summary: This paper reports the application of a silk fibroin-supported Palladium catalyst (Pd/SF) in Suzuki-Miyaura and Ullmann coupling reactions of aryl chlorides. The existence of catalytic pockets where monoatomic palladium species can form stable complexes with SF is hypothesized and supported by experimental analysis. The size of the catalytic pocket of Pd/SF is estimated to be approximately 15 angstroms using computational modeling.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Sheng-Qi Qiu, Yu Chen, Xiang-Jun Peng, Shi-Jiang He, Jun Kee Cheng, Yong-Bin Wang, Shao-Hua Xiang, Jun Song, Peiyuan Yu, Junmin Zhang, Bin Tan
Summary: In this study, we achieved the arene-alkene Suzuki-Miyaura coupling reaction between hindered aryl halides and vinyl boronates by designing appropriate ligands and reaction parameters. The axially chiral acyclic aryl-alkenes obtained exhibited remarkable efficiency, enantioselectivity, and E/Z selectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Chiara Palladino, Tommaso Fantoni, Lucia Ferrazzano, Alessandra Tolomelli, Walter Cabri
Summary: This study described the development of sustainable and efficient aryl halides with copper-free Heck-Cassar-Sonogashira (HCS) and Suzuki-Miyaura (SM) cross-coupling reactions. The use of N-hydroxyethylpyrrolidone (HEP)/water as solvents and sodium 2'-dicyclohexylphosphino-2,6-dimethoxy-1,1'-biphenyl-3-sulfonate (sSPhos) as a ligand produced the target products with high turnover number (TON), high reaction mass efficiency (RME), and low process mass intensity (PMI). The optimal conditions for HCS and SM coupling reactions were determined, and the achieved PMI and RME were among the best in the field, simplifying purification processes crucial for industrial applications.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Physical
Chau Ming So, On Ying Yuen, Shan Shan Ng, Zicong Chen
Summary: This study presents a general chemoselective Suzuki-Miyaura coupling using a Pd/L33 catalyst, showing efficient coupling of polyhalogenated aryl triflates by controlling reactivity order and key factors, achieving high yields and chemoselectivity with low Pd catalyst loading.
Article
Chemistry, Organic
Ruoqian Fan, Meiying Kuai, Dong Lin, Felix Bauer, Weiwei Fang
Summary: A new palladacyclic N-heterocyclic carbene pre-catalyst was designed and successfully applied for Pd-catalyzed C-N cross-coupling reactions of challenging heteroaryl chlorides. The desired aminated products were achieved in good to excellent yields.
Article
Chemistry, Physical
Sanita B. Tailor, Mattia Manzotti, Gavin J. Smith, Sean A. Davis, Robin B. Bedford
Summary: The cobalt-catalyzed Suzuki biaryl cross-coupling reaction using alkoxide bases, with strict stoichiometric control and selection of the right boron ester, is shown to be achievable. Excessive alkoxide bases or lithium additives can inhibit or poison the catalyst, while a neopentane diol-based boron ester is crucial for optimal performance.Mechanistic and computational studies have been carried out to investigate the reaction mechanism and explain unexpected observations.
Article
Chemistry, Applied
Xiao-Jing Wei, Bingxiang Xue, Jens Handelmann, Zhiyong Hu, Heidar Darmandeh, Viktoria H. Gessner, Lukas J. Goossen
Summary: In this study, a novel catalyst prYPhos was developed to promote Pd-catalyzed Suzuki-Miyaura couplings. Under mild reaction conditions, this catalyst efficiently produced various (hetero)biaryls with good tolerance towards sensitive functional groups and steric hindrance. The results demonstrated that this catalyst exhibited high selectivity in selectively coupling chlorides and leaving triflate groups intact.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Julius Hoepfner, Marius Brehm, Pavel A. Levkin
Summary: The rising costs of pharmaceutical research are currently limiting the productivity of drug discovery and development, but can potentially be reduced through miniaturization of compound synthesis and screening. In this study, the influential palladium-catalyzed Suzuki-Miyaura reaction is successfully implemented at the nanoliter scale on droplet microarrays for the synthesis of an 800-compound library of biphenyls. The synthesis of these compounds requires minimal reagents and solvent volume, and the obtained compounds can be purified and cleaved from excess reactants and catalyst. This novel approach expands the capabilities of droplet microarrays for miniaturized high-throughput chemical synthesis and opens up possibilities for future synthesis and screening of chemical compounds in a single platform.
Article
Chemistry, Multidisciplinary
Max Kadarauch, David M. Whalley, Robert J. Phipps
Summary: The article describes a new chiral ligand, sSPhos, which can achieve highly enantioenriched product synthesis through its electrostatic interactions with the substrate. Compared to traditional methods, sSPhos exhibits broader applicability and higher synthetic efficiency.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Applied
Alexander K. Eltyshev, Timur H. Dzhumaniyazov, Polina O. Suntsova, Artem S. Minin, Varvara A. Pozdina, Wim Dehaen, Enrico Benassi, Nataliya P. Belskaya
Summary: New fluorescent thiazoles were synthesized with specific combinations of substituents, resulting in a wide range of fluorescent colors and intensities. Further research revealed that certain substituent combinations could increase emission rates. These thiazoles displayed multifunctional properties, showing good emission in solid and suspension states, as well as a tunable response in different solvents.
Article
Chemistry, Applied
Kanticha Khomthawee, Nattaporn Nilada, Antika Homchuen, Pranorm Saejueng
Summary: The CS-EDTA-Pd catalyst was prepared by dissolving chitosan and EDTA in acetic acid, forming beads, adsorbing palladium(II), and reducing it to palladium(0) with ethanol reflux. The catalyst was characterized by various techniques. It was then tested in the Suzuki-Miyaura cross-coupling reaction and showed good catalytic activity. The catalyst is inexpensive, easy to prepare, and can be reused multiple times with only a slight loss in product yields.
APPLIED ORGANOMETALLIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Angus Olding, Curtis C. Ho, Allan J. Canty, Nigel T. Lucas, James Horne, Alex C. Bissember
Summary: This study reports the synthesis of a family of unprecedented arylpalladium(II) boronates that are kinetically stable at ambient temperature, and their chemical competence in a Suzuki-Miyaura reaction was demonstrated.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
