Article
Chemistry, Physical
Maria Biosca, Pol de la Cruz-Sanchez, Jorge Faiges, Jessica Margalef, Ernest Salomo, Antoni Riera, Xavier Verdaguer, Joan Ferre, Feliu Maseras, Maria Besora, Oscar Pamies, Montserrat Dieguez
Summary: Ir-MaxPHOX-type catalysts exhibit high catalytic performance in the hydrogenation of a wide range of nonchelating olefins with different geometries, substitution patterns, and degrees of functionalization. These air-stable and readily available catalysts have been successfully used in the asymmetric hydrogenation of di-, tri-, and tetrasubstituted olefins (ee ' s up to 9996). The combination of theoretical calculations and deuterium labeling experiments has revealed the factors responsible for the observed enantioselectivity, allowing for the rationalization of suitable substrates for these Ircatalysts.
Article
Chemistry, Applied
Maria Biosca, Pol de la Cruz-Sanchez, Daniel Tarr, Patricia Llanes, Erik A. Karlsson, Jessica Margalef, Oscar Pamies, Miquel A. Pericas, Montserrat Dieguez
Summary: A chiral phosphine-triazole ligand has been developed for the Ir-catalyzed asymmetric hydrogenation of exocyclic benzofused alkenes, which overcomes previous limitations and exhibits excellent enantioselectivity. The catalyst shows good tolerance towards various substituents and substitution patterns at both aromatic rings, making it an effective tool for hydrogenation of exocyclic olefins.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Tushar Janardan Pawar, Liliette Barcelona-Cazanave, Israel Bonilla-Landa, Magdalena Escobar, J. Oscar C. Jimenez-Halla, Alma Altuzar-Molina, Patricia Romero-Arellano, Andrew J. F. Edmunds, Martin Aluja, Jose Luis Olivares-Romero
Summary: This study presents a highly efficient iridium-catalyzed asymmetric hydrogenation approach for the total synthesis of biologically active (R,L) A. ludens host marking pheromone (HMP). The use of a novel Ir(i)-complex and a chiral P,N-ligand resulted in excellent enantioselectivities of up to 94% ee. The streamlined synthetic route involving seven reaction steps offers improved efficiency and shorter synthesis timelines compared to previous methods.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Wei Zhao, Wenji Wang, Huan Zhou, Qishan Liu, Zhiqing Ma, Haizhou Huang, Mingxin Chang
Summary: A one-pot asymmetric hydrogenation of pyridines with subsequent N-alkylation using a traceless Bronsted acid activation strategy is reported. The reaction exhibits high stereoselectivity and can be used to synthesize indolizidines and quinolizidines. Experimental and theoretical studies reveal that chloride anion and noncovalent interactions play important roles in determining the stereoselectivity of the reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Yin-Feng Ma, Chuan-Jin Hou, De-Quan Wei, Xinwei He, Ting-Ting Chu, Xiu-shuai Chen, Xiang-Ping Hu
Summary: The asymmetric hydrogenation of beta-ketophosphonates with chiral Ir/P,N,N-ligands catalyst leads to high yields of beta-hydroxyphosphonates with good or excellent enantioselectivities under mild conditions.
APPLIED ORGANOMETALLIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Bram B. C. Peters, Norman Birke, Luca Massaro, Pher G. Andersson
Summary: The catalytic asymmetric hydrogenation of olefins is a powerful method for synthesizing chiral compounds. By using an iridium N,P-complex catalyst, various prochiral unsaturated amides can be efficiently reduced with high enantioselectivities. The attractive features of this method include its application in the synthesis of fenpropidin and the potential use of isomeric mixtures as starting materials.
Article
Chemistry, Organic
Pep Rojo, Agusti Lledos, Antoni Riera, Xavier Verdaguer
Summary: A threonine-derived phosphine-oxazoline iridium catalyst with excellent selectivity in the hydrogenation of N-Boc-2,3-diarylallylamines is reported. The reversible cyclometallation process and the influence of substitution at the phenyl group of the oxazoline on this equilibrium are thoroughly investigated. X-Ray analysis reveals the coordination mode of the cyclometallated tridentate ligand. Furthermore, the utilization of Ir(III) pre-catalysts or Ir(I)/Ir(III) mixtures in hydrogenation reactions is proposed based on the observed equilibrium dynamics.
Review
Chemistry, Inorganic & Nuclear
Jessica Margalef, Maria Biosca, Pol de la Cruz Sanchez, Jorge Faiges, Oscar Pamies, Montserrat Dieguez
Summary: The success of phosphine-oxazoline ligands has led to advancements in P-oxazoline ligand families, resulting in diverse structures and more efficient ligands for asymmetric transformations. Through proper design, these heterodonor bidentate ligand families exhibit superior catalytic performance in a variety of asymmetric reactions.
COORDINATION CHEMISTRY REVIEWS
(2021)
Article
Chemistry, Organic
Congcong Yin, Yingmin Pan, Longsheng Zheng, Bijin Lin, Jialin Wen, Xumu Zhang
Summary: Enantioselective hydrogenation of imines via an outer-sphere mechanism was achieved using an iridium tridentate catalyst, resulting in high enantioselectivities and turnover numbers up to 10,000. This method was successfully applied in the synthesis of chiral amines with an alpha-stereocenter, allowing for the preparation of cinacalcet with remarkably high enantioselectivity.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Feng Wan, Nan Wang, Yuxin Zhu, Chuyan Tang, Jerome Claverie, Wenjun Tang
Summary: An efficient asymmetric hydrogenation using a Rh-ArcPhos catalyst has been achieved, resulting in the synthesis of compounds with two chiral centers.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Hanlin Wei, Hao Chen, Jianzhong Chen, Ilya D. D. Gridnev, Wanbin Zhang
Summary: In this study, an efficient earth-abundant transition-metal nickel catalyzed asymmetric hydrogenation of chiral ethylphosphine products was reported. The products were obtained with up to 99% yield, 96% ee (enantiomeric excess) (99% ee, after recrystallization) and 1000 S/C (substrate/catalyst) ratio. This is also the first study on the asymmetric hydrogenation of terminal olefins using a nickel catalyst under a hydrogen atmosphere. Deuterium-labelling experiments and calculations revealed that the two added hydrogen atoms in the products came from hydrogen gas. Additionally, it was suggested that the reaction involves a Ni-II rather than Ni-0 cyclic process based on the weak attractive interactions between the Ni catalyst and terminal olefin substrate.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Amanda L. Kwan, Robert H. Morris
Summary: This article introduces the largest-scale asymmetric catalytic process for the industrial production of (S)-metolachlor, which is achieved through the hydrogenation of N-(2-ethyl-6-methylphenyl)-1-methoxypropan-2-imine. The authors propose a plausible proton-first, outer-sphere mechanism based on density functional theory calculations that explains the reduction of the sterically hindered bond in the imine.
Article
Chemistry, Multidisciplinary
Haibo Wu, Hao Su, Erik J. Schulze, Bram B. C. Peters, Mark D. Nolan, Jianping Yang, Thishana Singh, Marten S. G. Ahlquist, Pher G. Andersson
Summary: The study presents a highly efficient desymmetrization of 1,4-dienes through iridium-catalyzed site- and enantioselective hydrogenation, allowing the installation of two adjacent stereogenic centers. High yields and excellent selectivities were achieved for a range of substrates, and the methodology was demonstrated by synthesizing key intermediates of natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Minjie Zhang, Peng Cui, Kai Zhang, Zhen Shi, Xu Cheng, Xiang Ji, Hao Song, Bowen Ke, Yong Qin
Summary: An efficient method for the asymmetric hydrogenation of tetrasubstituted α-acylpyrazole-β-alkyl cycloalkenes has been developed. The reaction, catalyzed by an Ir-complex, yields 1,2-cis carbo- or heterocycles in up to 99% yield and with enantioselectivities up to 99% ee. The acylpyrazole motif plays a crucial role in directing the Ir-complex to the alkene moiety. This work provides a solution to the longstanding challenge of asymmetric hydrogenation of all-carbon tetrasubstituted β-alkyl cycloalkenes and has implications for the synthesis of bioactive molecules.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Yulong Zhang, Peichao Zhao, Shengnan Sun, Qian Wu, Enxue Shi, Junhua Xiao
Summary: The authors developed a camphor-derived 2,3-diol as a chiral template to synthesize diverse P(III) and P(V) chiral compounds, which are highly desirable for asymmetric catalysis in organic chemistry.
COMMUNICATIONS CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
N. Ian Rinehart, Andrew F. Zahrt, Jeremy J. Henle, Scott E. Denmark
Summary: The design of catalysts in enantioselective catalysis is traditionally based on empirical methods. This study introduces a more quantitative approach by defining a library of catalyst permutations, using 3D representations and statistical learning tools to predict catalyst function and optimize catalyst performance. Through iterative experimental testing and refinement of statistical models, a systematic workflow for catalyst design and optimization is established for various reactions within a given chemical space.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Organic
Andrew F. Zahrt, N. Ian Rinehart, Scott E. Denmark
Summary: This study developed and applied a new steric descriptor for generating models that relate catalyst performance to catalyst structure in enantioselective transformations, demonstrating its generality and interpretability across different reactions. The low dimensionality and ability to capture conformational effects make it well-suited for creating Quantitative Structure-Selectivity Relationships with smaller datasets of asymmetric reactions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
N. Ian Rinehart, Andrew F. Zahrt, Scott E. Denmark
Summary: Traditional catalyst optimization methods are limited and inefficient, so we have developed an informatics-guided workflow utilizing artificial intelligence and machine learning to accelerate catalyst discovery and optimization, as well as to identify high-performing catalysts.
Article
Chemistry, Multidisciplinary
Vincent M. Kassel, Christopher M. Hanneman, Connor P. Delaney, Scott E. Denmark
Summary: Reaction conditions have been developed for refractory heteroaryl-heteroaryl Suzuki-Miyaura cross-couplings using neopentyl heteroarylboronic esters, heteroaryl bromides and chlorides, and potassium trimethylsilanolate (TMSOK) under anhydrous conditions. The addition of trimethyl borate enhances reaction rates by several mechanisms, enabling cross-coupling of diverse reaction partners in good yields and short reaction times.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Emily M. Mumford, Brett N. Hemric, Scott E. Denmark
Summary: This study reports a method for the chemo-, regio-, diastereo-, and enantioselective oxyamination of alkenes using selenium(II/IV) catalysis with a chiral diselenide catalyst. The reaction demonstrates good yields and excellent enantio- and diastereoselectivity for a variety of alkenes and different functional groups. The use of N-tosylamides to generate oxazoline products allows for the assembly of chiral ligands and various protected amino alcohols in an expedited manner.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Chemistry, Organic
Zhong-Lin Tao, Scott E. Denmark
Summary: Enantioselective diamination of alkenes is an important method for accessing enantioenriched, vicinal diamines, with broad applications in asymmetric synthesis. Despite lagging behind dihydroxylation of olefins, successful methods using different reaction mechanisms have been developed for enantioselective olefin diamination. This review highlights recent advances and limitations in the field, aiming to inspire further developments.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Applied
Jie Xu, Cheol K. Chung, Andrew McClory, Kyle A. Mack, Michael E. Dalziel, Alec Fettes, Kyle Clagg, Ngiap-Kie Lim, Georg Wuitschik, Christian Jenny, Laure Finet, Michael Kammerer, Haiming Zhang, Remy Angelaud, Francis Gosselin
Summary: GDC-9545, a selective estrogen receptor degrader, is being developed as a treatment for ER+/HER2- breast cancer. A robust and efficient manufacturing process has been developed to produce GDC-9545.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Applied
Katrina W. Lexa, Kevin M. Belyk, Jeremy Henle, Bangping Xiang, Robert P. Sheridan, Scott E. Denmark, Rebecca T. Ruck, Edward C. Sherer
Summary: Molecular design benefits from the partnership between chemical intuition and machine learning. In this study, different methods for modeling a catalyst system were investigated, and it was found that the 2D random forest approach outperformed other methods. With the passage of time, the model performance improved, and a high-throughput approach was crucial for large-scale optimization.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Multidisciplinary
Connor P. Delaney, Daniel P. Marron, Alexander S. Shved, Richard N. Zare, Robert M. Waymouth, Scott E. Denmark
Summary: Previous studies have shown that the critical transmetalation step in the Suzuki-Miyaura cross-coupling occurs through the oxo-palladium pathway. However, this study demonstrates that the reaction can proceed through the boronate pathway when potassium trimethylsilanolate is used as a promoter. Additionally, a novel binuclear palladium complex was discovered and its role in the catalytic cycle was confirmed.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Anastassia Matviitsuk, Jesse Lee Panger, Scott E. Denmark
Summary: This study reports a chiral selective method for the sulfenofunctionalization of cyclic and (Z)-alkenes, correcting previous findings through experimental results and demonstrating the different behavior of (Z)-alkenes compared to their more established (E)-counterparts.
Article
Chemistry, Multidisciplinary
Jie Xu, Samantha Grosslight, Kyle A. Mack, Sierra C. Nguyen, Kyle Clagg, Ngiap-Kie Lim, Jacob C. Timmerman, Jeff Shen, Nicholas A. White, Lauren E. Sirois, Chong Han, Haiming Zhang, Matthew S. Sigman, Francis Gosselin
Summary: An efficient asymmetric synthesis of a potent KRAS G12C covalent inhibitor, GDC-6036, was reported. The synthesis involved a highly selective Negishi coupling and a series of reaction sequences, leading to the desired compound with a 40% overall yield from the starting materials.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Jordan J. Dotson, Lucy van Dijk, Jacob C. Timmerman, Samantha Grosslight, Richard C. Walroth, Francis Gosselin, Kurt Puentener, Kyle A. Mack, Matthew S. Sigman
Summary: A machine learning workflow is utilized to optimize catalytic reactions with chiral bisphosphine ligands, resulting in the prediction and validation of improved ligands for multiple reaction objectives. This provides a general strategy for reaction optimizations controlled by bisphosphine ligands.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Brennan T. Rose, Jacob C. Timmerman, Seth A. Bawel, Steven Chin, Haiming Zhang, Scott E. Denmark
Summary: The atropselective iodination of 2-amino-6-arylpyridines catalyzed by chiral disulfonimides is achieved using a curated training set of catalysts obtained through a chemoinformatic workflow. Data fusion techniques are employed to predict catalyst performance when linear regression analysis fails. A privileged class of alkynyl-DSI catalysts is identified, demonstrating high stereoselectivity and generality in the iodination of various 2-amino-6-arylpyridines. Preparative-scale demonstrations show the utility of this reaction with high enantioselectivity and good chemical yield.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
N. Ian Rinehart, Rakesh K. Saunthwal, Joel Wellauer, Andrew F. Zahrt, Lukas Schlemper, Alexander S. Shved, Raphael Bigler, Serena Fantasia, Scott E. Denmark
Summary: This study presents a machine-learning tool that accelerates the identification of reaction conditions for palladium-catalyzed carbon-nitrogen couplings. The tool actively learns a large scope of reactions through a systematic experimental design process and demonstrates good performance in predicting new substrate pairings.
