Article
Chemistry, Multidisciplinary
Jingyi Wang, Xuzhong Shen, Xu Chen, Yinwei Bao, Jian He, Zhan Lu
Summary: In this study, cobalt-catalyzed enantioconvergent cross-coupling of alpha-bromoketones with aryl zinc reagents was achieved, leading to the synthesis of chiral ketones with alpha-tertiary stereogenic centers. Ligand modification was found to be critical for improving the reactivity and selectivity of this transformation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Celine Dorval, Oleh Stetsiuk, Sylvaine Gaillard, Elodie Dubois, Corinne Gosmini, Gregory Danoun
Summary: A novel Negishi-type cross-coupling reaction using only cobalt bromide salt as the catalyst is described in this study. This original reaction demonstrates high tolerance to various glutarimide amides and organozinc coupling partners. Additionally, the reaction can be performed on a large scale using an eco-compatible solvent such as ethyl acetate.
Letter
Chemistry, Organic
Panchi Guo, Hao Jin, Jinhui Han, Liang Xu, Pengfei Li, Miao Zhan
Summary: This study demonstrates a nickel-catalyzed Negishi cross-coupling reaction for the synthesis of versatile organoboron products with high functional-group tolerance. The reaction allows for the coupling of unactivated tertiary alkyl electrophiles with boron-stabilized organozinc reagents. The importance of the Bpin group in accessing the quaternary carbon center is highlighted, and the practicality of the prepared quaternary organoboronates is showcased through their conversion to other useful compounds.
Article
Chemistry, Multidisciplinary
Liangliang Zhang, Martin Oestreich
Summary: A new nickel/zinc-catalyzed cross-electrophile coupling reaction has been reported, utilizing alkyl electrophiles activated by an alpha-cyano group and chlorosilanes. Elemental zinc serves as the stoichiometric reductant in this reductive coupling process, allowing for the formation of a C(sp(3))-Si bond starting from two electrophilic reactants. This method differs from previous approaches that rely on the combination of carbon nucleophiles and silicon electrophiles.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Xu Luo, Dali Yang, Xiaoqian He, Shengchun Wang, Dongchao Zhang, Jiaxin Xu, Chih-Wen Pao, Jeng-Lung Chen, Jyh-Fu Lee, Hengjiang Cong, Yu Lan, Hesham Alhumade, Janine Cossy, Ruopeng Bai, Yi-Hung Chen, Hong Yi, Aiwen Lei
Summary: The authors report an on-cycle mechanism for CoCl2bpy2 catalyzed Negishi-type cross-coupling, elucidating the full catalytic cycle through multiple spectroscopic studies. Solvent and ligand were found to be crucial for generating catalytically active Co(I) species, with acetonitrile and bipyridine ligand resisting Co(I) disproportionation events. Combined investigations using Q-XAFS, EPR, IR, and DFT calculations provide comprehensive mechanistic insights into the structural information of the catalytic cobalt species and the entire Co(I)/Co(III) cycle. Additionally, the acetonitrile and bipyridine system can be extended to acylation, allylation, and benzylation reactions of aryl zinc reagents, demonstrating a broad substrate scope with a catalytic amount of Co salt. Overall, this work offers a fundamental mechanistic perspective for designing cobalt-catalyzed cross-coupling reactions.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Xufeng Ma, Han Wang, Yao Liu, Xing Zhao, Jun Zhang
Summary: Mixed alkyl/aryl diphos ligands have shown enhanced activity and selectivity in iron-catalyzed cross coupling reactions, with the electronic effect of the ligands playing a crucial role in catalytic performance. Fe catalyst supported by L8 exhibited the best catalytic performance and good functional group tolerance.
Article
Chemistry, Multidisciplinary
Wen-Tao Zhao, Huan Meng, Jia-Ni Lin, Wei Shu
Summary: In this study, a ligand-controlled regiodivergent alkylation of alkyl bromides at different positions has been developed via Ni-catalyzed alkyl-alkyl cross-electrophile coupling with a second alkyl bromide. The reaction selectively isomerizes one alkyl bromide in a controlled manner, providing diverse alkylated structures at different sites. The reaction exhibits excellent chemo- and regioselectivity at three similar positions, showcasing the remarkable ligand-tuned reactivity between alkyl-alkyl cross-coupling and nickel migration. This reaction offers a catalytic platform for the synthesis of diverse saturated architectures from identical starting materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Steffen Dachwitz, Bjarne Scharkowski, Norbert Sewald
Summary: Mild transition-metal catalysed cross-couplings allow for direct functionalization of biocatalytically halogenated tryptophans and provide a simple way to synthesize (homo)tryptophan regioisomers. This method offers non-canonical constitutional surrogates of tryptophan for use in peptide synthesis.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Sisi Wu, Weijia Shi, Gang Zou
Summary: Liquid-assisted grinding has been successfully used to eliminate the need for chemical activators and anhydrous solvents in nickel-catalyzed, manganese-mediated cross-electrophile coupling between aryl and alkyl bromides. The optimal condition obtained through a combined evaluation of reaction and mechanical parameters allowed for the synthesis of various n-alkyl aromatics with different functional groups in good yields with a 1 mol% catalyst loading. The practical application of liquid-assisted grinding-enabled aryl/alkyl cross-electrophile coupling has been demonstrated in the gram-scale synthesis of 6-methoxytetralone.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Xiaoyuan Ying, Yuxi Li, Luyang Li, Chao Li
Summary: A general Ni-catalyzed C(sp(2))-I selective cross-electrophile coupling (XEC) reaction has been developed for the construction of arene-flanked quaternary carbons. This reaction exhibits excellent C(sp(2))-I selectivity and functional group compatibility, and enables the synthesis of medicinally relevant and synthetically challenging compounds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Xiaoyu Tong, Ze-Peng Yang, Carlos E. Del Angel E. Aguilar, Gregory C. Fu
Summary: This study reports an iron catalyst for cross-coupling reactions of alkyl electrophiles using olefins and hydrosilanes instead of alkylmetal reagents. Carbon-carbon bond formation occurs at room temperature, and the method utilizes commercially available components. Mechanistic studies suggest the generation of an alkyl radical from the alkyl electrophile and reversible elementary steps.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Regina M. Oechsner, J. Philipp Wagner, Ivana Fleischer
Summary: We present a catalytic system that allows for mild and fast coupling of aryl chlorides with primary, secondary, and previously challenging tertiary alkyl thiols using an air-stable nickel(II) precatayst in combination with cost-effective potassium acetate as a base at room temperature. This system exhibits excellent tolerance towards various functional groups and yields thioethers in high yields, including pharmaceutical compounds. The chemoselective functionalization of disubstituted substrates is successfully demonstrated.
Article
Chemistry, Physical
Yan Xu, Muliang Zhang, Martin Oestreich
Summary: A new reaction method, using nickel catalysis, has been reported for the cross-coupling of different functional groups. This method utilizes a Hantzsch ester as the reductant without the need for an exogenous photocatalyst, and it exhibits excellent functional group tolerance.
Article
Chemistry, Multidisciplinary
Sandeep Kumar Thakur, Mandeep Kaur, Krishna Kumar Manar, Manu Adhikari, Angshuman Roy Choudhury, Sanjay Singh
Summary: This study describes a method for Negishi cross-coupling reaction using nickel complexes as catalysts. The Ni(I)-Ni(III) cycle is identified as the key intermediate in the reaction, while the Ni(0)/Ni(II) species may be involved in the catalytic cycle.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Longlong Xi, Liting Du, Zhuangzhi Shi
Summary: A nickel-catalyzed reductive cross-coupling reaction has been reported for the synthesis of substituted fluoroarenes through chelation-assisted C-F activation of polyfluoroarenes and alkyl electrophiles. The method shows excellent regioselectivity and can be applied to various primary and secondary alkyl (pseudo)halides.
CHINESE CHEMICAL LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Stavros K. Kariofillis, Shutian Jiang, Andrzej M. Zuranski, Shivaani S. Gandhi, Jesus I. Martinez Alvarado, Abigail G. Doyle
Summary: In this study, a Ni/photoredox-catalyzed (deutero)methylation and alkylation of aryl halides was developed using benzaldehyde di(alkyl) acetals as alcohol-derived radical sources. Data science techniques were applied to categorize a diverse collection of aryl bromides and compare them with previous methods, leading to quantitative analysis of reactivity trends and potential functional group incompatibility.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Chemistry, Multidisciplinary
Agustin Millet, Paul T. Cesana, Kassandra Sedillo, Matthew J. Bird, Gabriela S. Schlau-Cohen, Abigail G. Doyle, David W. C. MacMillan, Gregory D. Scholes
Summary: Photoredox catalysis allows for milder, cheaper, and more environmentally friendly chemical reactions. The BioLEC Energy Frontier Research Center aims to utilize bioinspired schemes to promote the application of photoredox catalysis in chemical manufacturing, reducing energy consumption and emissions. This review highlights the major advances made by the Center, emphasizing the impact of interdisciplinary collaboration on the field's progress.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Stephen Ting, Wendy L. Williams, Abigail G. Doyle
Summary: This study reports the synthesis of a well-defined nickel complex that undergoes oxidative addition with aryl halides, characterized by solution-phase speciation and a redox equilibrium. This has significant implications for organometallic studies of nickel catalysis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Chemistry, Multidisciplinary
Chung-Yang (Dennis) Huang, Stefan Hecht
Summary: This review explores the significance of indigo as a historical dye and its recent potential as a functional motif due to its intriguing photochemical properties. The synthesis of indigo core and available methods for derivatizing indigo are described, serving as synthetic strategies for building desired molecular structures. The photochemical behavior of indigos, particularly E-Z photoisomerization and photoinduced electron transfer, is discussed, emphasizing the connections between molecular structures and photochemical properties as guiding principles for designing indigos as photoresponsive tools.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Andrzej M. Zuranski, Shivaani S. Gandhi, Abigail G. Doyle
Summary: The application of machine learning techniques to high-throughput experimentation datasets has been increasingly popular. However, modeling the interaction effects between reaction components using machine learning algorithms is still a challenge. To address this, we propose a two-part statistical modeling approach that combines classical analysis of variance and regression analysis using chemistry-informed features. By applying this approach to a previously published dataset, we achieve a significant improvement in performance compared to a random forest model. Additionally, this approach can facilitate the generation of new mechanistic hypotheses and deepen the understanding of chemical reactivity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Isabelle Nathalie-Marie Leibler, Shivaani S. Gandhi, Makeda A. Tekle-Smith, Abigail G. Doyle
Summary: This Perspective article provides an overview of the progress and current limitations of nucleophilic fluorination methodologies. Despite the challenges, researchers have been actively studying and developing this transformation to gain a better understanding of its mechanism, create user-friendly fluorination reagents, and contribute to the invention of synthetic methods for radiofluorination. The article discusses studies from the Doyle group and others in the field, highlighting developments in fluoride reagent development and the mechanistic implications of reagent identity. It also outlines the inaccessible chemical space and future directions for filling the existing gaps in synthetic technologies.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Tianhua Tang, Avijit Hazra, Daniel S. Min, Wendy L. Williams, Eli Jones, Abigail G. Doyle, Matthew S. Sigman
Summary: In this study, the oxidative addition process of Ni(I) with aryl iodides was investigated using electroanalytical and statistical modeling techniques. Essential electronic and steric factors influencing the addition rate were identified through multivariate linear regression models based on over 200 experimental rate measurements. The mechanisms of oxidative addition were classified into three-center concerted or halogen-atom abstraction pathways based on the ligand type. A global heat map of predicted oxidative addition rates was created, which was shown to be applicable in understanding the reaction outcome in a Ni-catalyzed coupling reaction through a case study.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Kai Sun, Chung-Yang Dennis Huang, Masaya Sawamura, Yohei Shimizu
Summary: A boron-catalyzed direct a-trifluoromethylthiolation of carboxylic acids was developed without the need of substrate pre-activation. The method allows for direct modification of bioactive carboxylic acids. Data science analyses provided suitable models for substrate classification and yield prediction.
Article
Chemistry, Physical
Julia E. Borowski, Samuel H. Newman-Stonebraker, Abigail G. Doyle
Summary: A comparison study of mono- and bisphosphine ligands in Ni-catalyzed Suzuki-Miyaura cross-coupling reactions revealed that monophosphines exhibit higher reactivity, particularly with electronically deactivated and sterically hindered substrates. Mechanistic experiments showed that monoligated (P1Ni) species accelerate the organometallic steps of the catalytic cycle, while bisligated (P2Ni) species prevent off-cycle reactions and catalyst poisoning by heterocyclic motifs. These findings provide guidelines for ligand selection against challenging substrates and future ligand design tailored to the mechanistic demands of Ni-catalyzed cross-coupling reactions.
Article
Chemistry, Multidisciplinary
Wendy L. Williams, Neyci E. Gutierrez-Valencia, Abigail G. Doyle
Summary: This paper reports the first branched-selective cross-coupling of 2-alkyl aziridines with aryl iodides using a Ti/Ni dual-catalytic system. The study demonstrates the tolerance towards functional groups and the effect of the steric and electronic profile on reactivity, resulting in predictive reactivity models and insights into the mechanism.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Madeline E. Ruos, R. Garrison Kinney, Oliver T. Ring, Abigail G. Doyle
Summary: We report a visible-light photoredox-catalyzed method that enables nucleophilic amination of primary and secondary benzylic C(sp(3))-H bonds. A novel amidyl radical precursor and organic photocatalyst operate in tandem to transform primary and secondary benzylic C(sp(3))-H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover. Furthermore, the resulting carbocations can be intercepted by various N-centered nucleophiles, leading to the formation of pharmaceutically relevant C(sp(3))-N bonds under unified reaction conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
John H. H. Dunlap, Jeffrey G. G. Ethier, Amelia A. A. Putnam-Neeb, Sanjay Iyer, Shao-Xiong Lennon Luo, Haosheng Feng, Jose Antonio Garrido Torres, Abigail G. G. Doyle, Timothy M. M. Swager, Richard A. A. Vaia, Peter Mirau, Christopher A. A. Crouse, Luke A. A. Baldwin
Summary: We implemented a human-in-the-loop approach for multi-objective experimental design using a Bayesian optimization platform (EDBO+) to optimize the synthesis of butylpyridinium bromide under continuous flow conditions. The EDBO+ algorithm simultaneously optimized reaction yield and production rate, generating a well-defined Pareto front. We demonstrated the versatility of EDBO+ by expanding the reaction space mid-campaign. Continuous flow techniques improved control over reaction parameters, offering potential for automated synthesis and scalability. Additionally, we used the open-source module nmrglue for semi-automated NMR spectroscopy analysis and compared results obtained from manual processing methods, providing insight into the effect of data analysis on model predictions. Quaternization of poly(4-vinylpyridine) with bromobutane showcased the application of continuous flow chemistry for synthesizing functional materials.
Article
Chemistry, Multidisciplinary
Mandana Saebi, Bozhao Nan, John E. E. Herr, Jessica Wahlers, Zhichun Guo, Andrzej M. M. Zuranski, Thierry Kogej, Per-Ola Norrby, Abigail G. G. Doyle, Nitesh V. V. Chawla, Olaf Wiest
Summary: The lack of publicly available, large, and unbiased datasets poses a challenge for applying machine learning in synthetic chemistry. While data from electronic lab notebooks (ELNs) can potentially provide less biased large datasets, there is currently a lack of publicly available ELN datasets. This study presents the first real-world dataset from the ELNs of a pharmaceutical company, and explores its relationship with high-throughput experimentation datasets. The study shows that an attributed graph neural network performs well on high-throughput experimentation datasets for yield predictions, but fails to be predictive when trained on the ELN dataset. The implications of using ELN data for training ML-based models for yield predictions are discussed.
Article
Chemistry, Multidisciplinary
Kim Kuntze, Jani Viljakka, Matti Virkki, Chung-Yang (Dennis) Huang, Stefan Hecht, Arri Priimagi
Summary: By simple synthetic derivatisation, indigo dye can be converted into a red-light E-Z photoswitch, which exhibits negative photochromism and tuneable thermal isomerisation kinetics. This makes indigo derivatives highly attractive for materials and living systems applications. However, the translation of indigo photoswitching dynamics from solution to solid state, which is crucial for most applications, is not well understood. In this study, the photoswitching performance of six structurally distinct indigo derivatives in five polymers of varying rigidity is investigated. Three key strategies are identified to enable efficient photoswitching under red light: choosing a soft polymer matrix, creating free volume around the indigo molecules, and applying low dye loading to inhibit aggregation. Implementation of these strategies leads to isomerisation performance nearly identical to that in solution, paving the way for designing new red-light photochromic materials based on indigos.
Article
Chemistry, Multidisciplinary
Andrzej M. Zuranski, Jason Y. Wang, Benjamin J. Shields, Abigail G. Doyle
Summary: Auto-QChem is an automatic, high-throughput, and end-to-end DFT calculation workflow that computes chemical descriptors for organic molecules. It is tailored towards users without extensive programming experience and has various functionalities and applications.
REACTION CHEMISTRY & ENGINEERING
(2022)
