Article
Chemistry, Physical
Xiaowu Fang, Songwei Wen, Peishen Jin, Wenjing Bao, Shanshan Liu, Hengjiang Cong, Xiao Shen
Summary: Fluorinated enol silanes are widely used in synthetic transformations, but previous methods only allowed for the synthesis of racemic products. In this study, an enantioselective reductive coupling reaction was developed to access enantioenriched fluorinated enol silanes. The practicality of this methodology was demonstrated through multistep-one-isolation processes, and the synthetic potential of enantioenriched fluorinated enol silanes in the synthesis of valuable chiral organofluorine compounds was also shown.
Article
Chemistry, Multidisciplinary
Yangdong Hou, Zhang Zhang, Xinyu Sun, Zheng Yang, Yu-Xin Luan, Pingping Tang
Summary: Due to the strong electron-withdrawing nature and high lipophilicity of trifluoromethoxy group (OCF3), there is a high demand for methods to introduce OCF3 into organic molecules. However, direct enantioselective trifluoromethoxylation is still in its early stages, with limited enantioselectivity and/or reaction types. In this study, we describe the first copper-catalyzed enantioselective trifluoromethoxylation of propargyl sulfonates using trifluoromethyl arylsulfonate (TFMS) as the trifluoromethoxy source, achieving up to 96% enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Zi-Qi Li, Omar Apolinar, Ruohan Deng, Keary M. Engle
Summary: Research on nickel-catalyzed Markovnikov-selective hydroarylation and hydroalkenylation of non-conjugated alkenes has developed a toolkit of methods that can react with various substrates under mild conditions, with regioselectivity controlled through catalyst coordination with functional groups within the substrates. Reaction conditions were adjusted for each substrate class to maximize product yield, and detailed studies shed light on the mechanism of these transformations, highlighting transmetalation as the turnover-limiting step.
Article
Chemistry, Physical
Peng-Fei Yang, Lei Zhu, Jian-Xing Liang, Han-Tong Zhao, Jian-Xin Zhang, Xian-Wang Zeng, Qin Ouyang, Wei Shu
Summary: A highly challenging and desirable method for directly constructing fully alkyl-substituted tertiary chiral centers remote to activating groups is reported. This method involves regio-and stereoselective hydrometalation of unactivated alkenes with nontrivial Markovnikov selectivity, followed by cross-coupling with unactivated alkyl electrophiles to generate trialkyl tertiary saturated stereogenic centers. The mild and robust conditions allow for the use of different types of unactivated alkenes and alkyl electrophiles, resulting in diverse trialkyl tertiary stereogenic carbon centers with broad functional group tolerance.
Article
Chemistry, Multidisciplinary
Amit Kumar Simlandy, Turki M. Alturaifi, Johny M. Nguyen, Lucas J. Oxtoby, Quynh Nguyen Wong, Jason S. Chen, Peng Liu, Keary M. Engle
Summary: We report a transient directing group (TDG) strategy for site-selective palladium-catalyzed reductive Heck-type hydroalkenylation and hydroalkynylation of alkenylaldehydes using alkenyl and alkynyl bromides. This strategy allows for the construction of a stereocenter at the delta-position with respect to the aldehyde. Computational studies reveal the beneficial roles of rigid TDGs, such as L-tert-leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Sumon Sarkar, Soumen Ghosh, Daria Kurandina, Yusuf Noffel, Vladimir Gevorgyan
Summary: Photoinduced enhancement of hydricity of palladium hydride species enables unprecedented hydride addition-like (hydridic) hydropalladation of electron-deficient alkenes, which allows for chemoselective head-to-tail cross-hydroalkenylation of electron-deficient and electron-rich alkenes. This mild and general protocol works with a wide range of densely functionalized and complex alkenes. Notably, this approach also allows for highly challenging cross-dimerization of electronically diverse vinyl arenes and heteroarenes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Ziyan Zhang, Vladimir Gevorgyan
Summary: A mild palladium hydride-catalyzed difunctionalization of conjugated dienes and enynes is reported. This method enables the chemoselectivity switch of the initial hydropalladation step by enhancing the hydricity of PdH species with visible light, allowing for cascade annulation of various easily available and abundant substrates, such as acrylic acids, acrylic amides, and Baylis-Hillman adducts, towards a wide range of alkenyl or alkynyl lactones, lactams, and tetrahydrofurans.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Andrew Whyte, Jonathan Bajohr, Ramon Arora, Alexa Torelli, Mark Lautens
Summary: An enantioselective consecutive cyclization/coupling process catalyzed by palladium was reported in this study. The stereoinduction was achieved through an enantioselective carbopalladation, leading to the generation of an intermediate that promotes a nucleopalladation step. This dual cyclization sequence was compatible with various nucleophiles and aryl iodides, producing numerous bisheterocycles in good yields and high regio- and enantioselectivities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Sheng Feng, Yuyang Dong, Stephen L. Buchwald
Summary: In this study, an alternative method for the asymmetric hydroaminocarbonylation of olefins using dual copper hydride and palladium catalysis was described. This method enables the synthesis of enantioenriched amides using readily available carbamoyl chlorides as the carbamoylating reagent, and is applicable to various types of olefins with good yields and excellent enantioselectivities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Zhenghui Kang, Wenju Chang, Xue Tian, Xiang Fu, Wenxuan Zhao, Xinfang Xu, Yong Liang, Wenhao Hu
Summary: The study presents a novel asymmetric allylation reaction through ternary cooperative catalysis, enabling the expedient access to chiral alpha,alpha-disubstituted ketones with high enantioselectivity. Experimental and computational studies have elucidated the mechanism and origin of enantioselectivity in this three-component reaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Geng-Geng Luo, Zhong-Hua Pan, Bao-Liang Han, Guang-Lei Dong, Cheng-Long Deng, Mohammad Azam, Yun-Wen Tao, Jiao He, Cun-Fa Sun, Di Sun
Summary: Accurate identification and understanding of defect sites in nanomaterials are crucial for establishing defect-activity relationships. However, the synthesis and isolation of atomically precise coinage-metal nanoclusters with surface vacancy defects are challenging. In this study, a mixed-ligand strategy was employed to synthesize a chiral and metal-deficient copper nanocluster with high hydrogen content. Its crystal structure reveals specific defect sites and experimental results prove its catalytic activity in the hydrogenation reaction. This work paves the way for further research on well-defined chiral metal-deficient nanoclusters and their applications in asymmetrical catalysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Rhone Brocha P. Silalahi, Yongsung Jo, Jian-Hong Liao, Tzu-Hao Chiu, Eunsaem Park, Woojun Choi, Hao Liang, Samia Kahlal, Jean-Yves Saillard, Dongil Lee, C. W. Liu
Summary: The first hydride-containing 2-electron palladium/copper alloys, PdHCu11 and PdHCu12, were synthesized. X-ray diffraction reveals that the PdHCu11 and PdHCu12 kernels consist of a central PdH unit encapsulated within a vertex-missing Cu-11 cuboctahedron and complete Cu-12 cuboctahedron, respectively. PdHCu11 shows excellent HER activity, with an onset potential of -0.05 V (at 10 mA cm(-2)) and consistent HER activity during 1000 cycles in 0.5 M H2SO4.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Florian Papp, Daniel Sowa Prendes, Sourav Manna, Ann-Katrin Seitz, Sofiya Kostiukovska, Julian Loeffler, Viktoria H. Gessner, Lukas J. Goossen
Summary: Palladium complexes with ylide-functionalized phosphine ligands catalyze the arylation of N-protected hydantoins with aryl chlorides, enabling the synthesis of a wide variety of hydantoins, including derivatives of the anticonvulsant drugs phenytoin and mephenytoin. Selective monoarylations, sequential diarylations, and arylation-alkylation sequences have been achieved, along with stepwise deprotection strategies.
Article
Chemistry, Multidisciplinary
Michael G. J. Doyle, Alexis L. Gabbey, Wesley McNutt, Rylan J. Lundgren
Summary: In this study, electron-deficient arylacetates were utilized as benzyl nucleophile surrogates to successfully generate enantioenriched acyclic molecules containing quaternary carbon centers via a two-step substitution-decarboxylation process. Products were often obtained with >90% ee using a commercially available catalyst.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Ji Liu, Edward M. Laguna, Arun Raj Kizhakkayil Mangadan, Kyoungmin Kang, Aaron Aponick
Summary: A simple procedure for intermolecular enantioselective palladium-catalyzed decarboxylative allylation of beta-ketoacids is described. The method uses allyl carbonates as coupling substrates and allows direct access to alpha-allylated ketones with newly formed quaternary stereocenters. Experimental results suggest the transformation proceeds via an inner-sphere mechanism rather than the traditional outer-sphere process, and the reaction demonstrates potential usefulness in the enantioselective synthesis of (+)-adalinine.
Article
Chemistry, Multidisciplinary
Aaron J. Mallek, Bradley L. Pentelute, Stephen L. Buchwald
Summary: This study discusses the selective N-arylation of p-aminophenylalanine in polypeptides using pre-formed palladium oxidative addition complexes, enabling chemoselective C-N bond formation on peptides containing multiple other amino groups. By utilizing palladium complexes derived from electron-poor aryl halides, p-aminophenylalanine can be fully arylated at micromolar concentrations in aqueous buffer in a short amount of time. A complementary protocol using the non-nucleophilic, organic base 1,5-diazabicyclo(4.3.0)non-5-ene (DBN) expands the substrate scope and provides high conversion rates of up to 97%.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Muhammad Jbara, Sebastian Pomplun, Carly K. Schissel, Susana Wilson Hawken, Ann Boija, Isaac Klein, Jacob Rodriguez, Stephen L. Buchwald, Bradley L. Pentelute
Summary: Novel synthetic TF mimetics have been developed to inhibit oncogenic Myc-driven transcription by antagonistic DNA-binding, leading to reduced cancer cell proliferation. The use of flow chemistry and palladium(II) OACs offers a practical strategy to generate bioactive compounds for inhibiting tumor cell proliferation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Chuan-Jin Hou, Alexander W. Schuppe, James Levi Knippel, Anton Z. Ni, Stephen L. Buchwald
Summary: A method for stereoselective hydroalkenylation of alkynes using enol triflates was reported in this study. The formation of Z,Z- or Z,E-1,3-dienes with excellent stereoselectivity and yield was achieved by leveraging an in situ-generated and geometrically pure vinyl-Cu(I) species. This approach allowed for the synthesis of highly substituted Z-dienes, including pentasubstituted 1,3-dienes, which are challenging to prepare using existing methods.
Article
Chemistry, Multidisciplinary
Sheng Feng, Yuyang Dong, Stephen L. Buchwald
Summary: In this study, an alternative method for the asymmetric hydroaminocarbonylation of olefins using dual copper hydride and palladium catalysis was described. This method enables the synthesis of enantioenriched amides using readily available carbamoyl chlorides as the carbamoylating reagent, and is applicable to various types of olefins with good yields and excellent enantioselectivities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Correction
Chemistry, Multidisciplinary
Martin Gazvoda, Heemal H. Dhanjee, Jacob Rodriguez, Joseph S. Brown, Charlotte E. Farquhar, Nicholas L. Truex, Andrei Loas, Stephen L. Buchwald, Bradley L. Pentelute
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Yuyang Dong, Alexander W. Schuppe, Binh Khanh Mai, Peng Liu, Stephen L. Buchwald
Summary: This article introduces a CuH-catalyzed selective reductive coupling reaction of vinyl heteroarenes with aldehydes and ketones. The selectivity of the reaction is controlled by the choice of the ancillary ligand. This method shows excellent selectivity, tolerates various functional groups and heterocycles, and provides a direct route to functionalized saturated heterocyclic structures.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Martin Gazvoda, Heemal H. Dhanjee, Jacob Rodriguez, Joseph S. Brown, Charlotte E. Farquhar, Nicholas L. Truex, Andrei Loas, Stephen L. Buchwald, Bradley L. Pentelute
Summary: This article describes a method for embedding carborane moieties into small molecules, peptides, and proteins. The strategy involves palladium-mediated C-X bond formation and enables selective conjugation of carborane-containing groups with other molecules in aqueous buffer. The method has been successfully applied to nanobodies, fully synthetic affibodies, and antibody therapeutics such as Herceptin and Cetuximab.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
James Levi Knippel, Anton Z. Ni, Alexander W. Schuppe, Stephen L. Buchwald
Summary: In this study, a general method for the enantioselective preparation of alpha-stereogenic allyl metalloids using dual CuH- and Pd-catalysis is reported. This approach allows access to enantioenriched allyl silanes, germanes, and boronate esters with broad functional group compatibility through a stereoretentive Cu-to-Pd transmetalation of an in situ generated alkyl copper species.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Yuyang Dong, Kwangmin Shin, Binh Khanh Mai, Peng Liu, Stephen L. Buchwald
Summary: This paper reports an asymmetric olefin hydromethylation protocol enabled by CuH catalysis, in which methyl tosylate is used as a methyl source and iodide ion converts it into the active reactant methyl iodide. The method demonstrates broad applicability and tolerance.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Elaine C. Reichert, Kaibo Feng, Aaron C. Sather, Stephen L. Buchwald
Summary: We report a versatile method for the Pd-catalyzed C-N cross-coupling of heteroaryl halides with primary and secondary amines, achieving good-to-excellent yields. The use of a specific base and a supported Pd catalyst enables the coupling of challenging heteroarenes and sterically demanding amines. This method has broad applicability and allows the synthesis of densely functionalized medicinal chemistry building blocks.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Yuxuan Ye, Seoung-Tae Kim, Ryan P. King, Mu-Hyun Baik, Stephen L. Buchwald
Summary: Pd-catalyzed nucleophilic fluorination reactions are important for the synthesis of fluoroarenes and fluoroalkenes. However, the regioselectivity of these reactions is often poor, generating a mixture of difficult-to-separate regioisomeric products. In this study, the addition of a substoichiometric quantity of TESCF3 significantly improved the regioselectivity by diminishing the formation of LPd-cyclohexyne complexes through an unexpected dearomatization pathway involving nucleophilic attack from a trifluoromethyl anion (CF3-).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Seoung-Tae Kim, Michael J. Strauss, Albert Cabre, Stephen L. Buchwald
Summary: A new class of anionic ligands for Cu-catalyzed C-N couplings has been developed, which enables efficient amination of aryl bromides under mild conditions. This ligand design increases the electron density on Cu and stabilizes the active anionic CuI complex, leading to enhanced reactivity and a broad substrate scope.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Simon L. Rossler, Nathalie M. Grob, Stephen L. Buchwald, Bradley L. Pentelute
Summary: This study establishes abiotic peptides as carriers of information for the encoding of small-molecule synthesis. These peptides are used to encode diverse small-molecule synthesis and successfully discover protein ligands. This work demonstrates the potential for abiotic peptides in accelerating the discovery of therapeutic targets.
Article
Chemistry, Multidisciplinary
Dennis A. Kutateladze, Binh Khanh Mai, Yuyang Dong, Yu Zhang, Peng Liu, Stephen L. Buchwald
Summary: A copper hydride-catalyzed approach has been developed for the synthesis of Z-configured trisubstituted alkenes with high stereo- and regioselectivity. This method provides a valuable strategy for accessing challenging classes of alkenes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Anthony J. Rojas, Justin M. Wolfe, Heemal H. Dhanjee, Ivan Buslov, Nicholas L. Truex, Richard Y. Liu, Walter Massefski, Bradley L. Pentelute, Stephen L. Buchwald
Summary: The synthesis of palladium oxidative addition complexes derived from unprotected peptides is described. These complexes can react with thiols in aqueous buffer, providing an efficient method for bioconjugation. Using this strategy, peptides can be functionalized with small molecules to prepare modified aryl thioether side-chains at low micromolar concentrations. Additionally, peptide-peptide and peptide-protein ligations are demonstrated under dilute aqueous conditions.
