Article
Chemistry, Multidisciplinary
Hyung-Joon Kang, Changseok Lee, Sungwoo Hong
Summary: Kinetic resolution is a powerful strategy for isolating enantioenriched compounds from mixtures, and the development of selective catalytic processes is an active research area. In this study, a nickel-catalyzed kinetic resolution of racemic alpha-substituted unconjugated carbonyl alkenes was achieved through enantio-, diastereo-, and regioselective hydroamination, resulting in chiral alpha-substituted butenamides and syn-beta(2,3)-amino acid derivatives with high enantiomeric purity (up to 99% ee) and selectivity factor up to >684. The unique structure of the chiral nickel complex plays a key role in the efficient kinetic resolution and enantioselective bond construction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Yunliang Yu, Nazarii Sabat, Meriem Daghmoum, Zhenhao Zhang, Pascal Retailleau, Gilles Frison, Angela Marinetti, Xavier Guinchard
Summary: Enantioselective tandem cycloisomerization/addition reactions of 2-alkynyl enones with 1- and 2-naphthols were investigated using gold(I) catalysts featuring hybrid phosphine-phosphoric acid chiral ligands, based on the tethered counterion-directed catalysis strategy. The reactions proceeded at low catalyst loading (0.2-1 mol%) without the need for silver additives, and the naphthols acted as both O- and C-nucleophiles, resulting in the formation of addition products with high enantioselectivity. The mechanism of these reactions was elucidated by DFT calculations.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Physical
Hannah M. Baumann, Eric Dybeck, Christopher L. McClendon, Frank C. Pickard, Vytautas Gapsys, Laura Perez-Benito, David F. Hahn, Gary Tresadern, Alan M. Mathiowetz, David L. Mobley
Summary: Binding free energy calculations are used to predict the potency of compounds binding to protein sites in a physically rigorous manner. Relative binding free energy (RBFE) calculations are commonly used but limited by the requirement of ligands sharing a common scaffold and binding mode. Absolute binding free energy (ABFE) calculations are an alternate method for non-congeneric ligands but suffer from long convergence times. The SepTop method overcomes the limitations of both RBFE and ABFE methods by allowing large scaffold changes between ligands with comparable convergence time. It provides a more efficient and flexible approach for ranking ligands in drug design.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Review
Chemistry, Physical
Wenqian Li, Muhammad Bilal, Anil Kumar Singh, Farooq Sher, S. Salman Ashraf, Marcelo Franco, Juliana Heloisa Pine Americo-Pinheiro, Hafiz M. N. Iqbal
Summary: This article reviews protein engineering approaches that focus on regulating the catalytic microenvironment of enzymes. By adjusting pH, creating water-like microenvironments, and activating enzyme catalysis in organic solvents and gas phase, the effectiveness of catalysts can be optimized, making them important for industrial bioprocesses.
Article
Chemistry, Inorganic & Nuclear
Laura Rodriguez-Cid, Wenjie Qian, Joseline Iribarra-Araya, Alvaro Etcheverry-Berrios, Eulalia Martinez-Olmos, Duane Choquesillo-Lazarte, Eva Carolina Sanudo, Olivier Roubeau, Ana Maria Lopez-Periago, Arantzazu Gonzalez-Campo, Jose G. Planas, Monica Soler, Concepcion Domingo, Nuria Aliaga-Alcalde
Summary: A new heteroditopic ligand, 3pyCCMoid, was presented and used to create novel coordination polymers with Zn-II centers exhibiting different structures and dimensionalities. The study focused on analyzing the impact of synthetic methods and reaction conditions on the formation of final materials, with a special emphasis on the characterization of 2D materials and their stability in water.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Applied
Jianning Liao, Qihuan Han, Min Liu, Wangyu Shi, Jiaqing Xu, Wei Wang, Yongjun Wu, Hongchao Guo
Summary: Phosphine-catalyzed annulation of acidic hydrogen-tethered allylic carbonates with electron-deficient alkenes was achieved, providing various polysubstituted spirocyclohexenes, spirocyclohexanones or cyclohexanones in moderate to high yields under mild reaction conditions. The reactions were successfully scaled up and the products were further transformed. The acidic hydrogen-tethered allylic carbonates exhibited good reactivity and potential for broader applications.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Bingcheng Wang, Yufeng Sun, Zhan Lu
Summary: A cobalt-catalyzed sequential dehydrogenative Heck silylation/hydroamination reaction was reported to access 1-amino-2-silyl compounds with high regioselectivity. The reaction exhibited good functional group tolerance under mild conditions.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Cancan Feng, Luqing Tang, Fan Yang, Yangjie Wu
Summary: In this study, we reported a copper-catalyzed carbonyl-assisted hydroboration of terminal aliphatic alkenes with Markovnikov regioselectivity, using readily available and stable B(2)Pin(2) as the boron source. The reaction showed smooth progress with exclusive Markovnikov regioselectivity, providing easy access to a range of branched secondary alkyl boronic esters in moderate to excellent yields. The solvent was demonstrated to be the source of hydrogen, as confirmed by the deuterium experiments.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Applied
Yuyan Zhang, Mariya Shamzhy, Martin Kubu, Jiri Cejka
Summary: Zeolites can efficiently and selectively catalyze the hydroamination of alkenes, alkynes, and dienes due to their pore system and tunable acidity. This study investigated the activity of hierarchical micro-mesoporous zeolites in the hydroamination reaction and found that nanosponge MFI zeolite displayed the highest activity and yield.
MICROPOROUS AND MESOPOROUS MATERIALS
(2022)
Article
Chemistry, Organic
Jaehan Bang, Seyun Gi, Yoonjung Lee, Kian L. Tan, Sunggi Lee
Summary: This study describes the meta-selective C-H functionalization of arylsilanes using a Si-tethered directing group. The method allows for selective alkenylation of arenes with various functional groups, including electron-deficient olefins. Further functional group transformations of the silicon-tethered directing group efficiently produce multi-substituted arenes.
Article
Chemistry, Multidisciplinary
Peng-Wei Sun, Ze Zhang, Xinyao Wang, Linshan Li, Yuxin Li, Zhengming Li
Summary: Metal-catalyzed hydroamination of alkenes is an effective method for synthesizing amines. This study developed a cobalt-catalyzed intermolecular hydroamination reaction using NFSI as the nitrogen source, which exhibited excellent selectivity and yield.
CHINESE JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Organic
Jun-Sheng Wei, Song Yang, Yin Wei, Sima Shamsaddinimotlagh, Hossein Tavakol, Min Shi
Summary: A gold(i)-catalyzed intramolecular cyclization reaction was developed to synthesize functionalized morpholines, piperazines, and oxazepanes. The reaction proceeds via a carbene or non-carbene process and exhibits a broad substrate scope, good functional group tolerance, and mild reaction conditions. The reaction pathway can be modulated by the steric bulkiness or chain length of the substrate.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Daven Foster, Pengchao Gao, Ziyun Zhang, Gellert Sipos, Alexandre N. Sobolev, Gareth Nealon, Laura Falivene, Luigi Cavallo, Reto Dorta
Summary: Chiral, cationic NHC-iridium complexes have been introduced as catalysts for the intramolecular hydroamination reaction of unactivated aminoalkenes, showing high activity and selectivity. By eliminating a major deactivation pathway, the efficiency of the reaction is improved. Through experimental and computational studies, valuable insights into the reaction mechanism have been gained.
Article
Chemistry, Multidisciplinary
Yaqi Zhang, Qiang Ni, Bendu Pan, Long Jiang, Liqin Qiu
Summary: A successful development of Ni-Al bimetallic catalysis for intramolecular enantioselective and regioselective C-H cyclization of 4-oxoquinazolines with tethered alkenes is reported. New secondary phosphine oxides (SPOs) with large steric hindrance (SPO6-11) were designed and synthesized, showing higher efficiency in asymmetric catalytic reactions than traditional ligands. A new class of chiral tricyclic pyrroloquinazolinones were obtained with high yield and enantiomeric excess.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Physical
Tobias Taeufer, Richy Hauptmann, Firas El-Hage, Thea S. Mayer, Haijun Jiao, Jabor Rabeah, Jola Pospech
Summary: The study demonstrates the applicability of a heteroaromatic photoredox catalyst in an additive-free photo-mediated hydroamination of stilbenes. Initiated by an organic pyrimidopteridine catalyst, the synthesis of various alpha-phenyl phenethylamine derivatives was achieved, with the stereogenic center of alpha-chiral amines fully preserved. Both starting materials serve as competent quenching partners in the reaction mechanism, as indicated by fluorescence-quenching experiments and spectroscopic analysis.
Article
Chemistry, Multidisciplinary
Ana Koperniku, Laurel L. Schafer
Summary: The zirconium catalyzed hydroaminoalkylation of alkenes with N-aryl- and sterically demanding N-alkyl-alpha-arylated secondary amines using commercially available Zr(NMe2)(4) is reported. The catalyst is compatible with challenging alpha-heteroarylated amines and functionalized alkene substrates, providing a new disconnection strategy for selectively substituted saturated alpha-arylated heterocycles.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Han Hao, Thibault Bagnol, Mathieu Pucheault, Laurel L. Schafer
Summary: By utilizing a specific titanium precatalyst, the hydroamination of alkynylphosphines to prepare 2-amino-phosphines in high yield and on gram scale has been achieved. The broad substrate scope allows for the rapid assembly of a variety of ligands in one pot, making preparation of metal P,N-complexes for catalysis or small molecule activation easy and efficient.
Article
Chemistry, Physical
Manfred Manssen, Danfeng Deng, Cameron H. M. Zheng, Rebecca C. DiPucchio, Dafa Chen, Laurel L. Schafer
Summary: Hydroaminoalkylation involves the catalytic synthesis of amines from easily accessible amine and alkene feedstocks, utilizing a cost-efficient titanium catalyst with high catalytic activity and regioselectivity. The synthesized amine-containing monomers are suitable for generating amine-containing materials and building blocks for medicinal chemistry.
Article
Chemistry, Physical
Jingjun Huang, Matthew Isaac, Ryan Watt, Joseph Becica, Emma Dennis, Makhsud Saidaminov, William A. Sabbers, David C. Leitch
Summary: The study introduces an easily prepared and stable mononuclear Pd(0) source that is effective for catalytic reactions and has good solubility properties.
Article
Chemistry, Multidisciplinary
Rebecca C. DiPucchio, Karst E. Lenzen, Pargol Daneshmand, Maria B. Ezhova, Laurel L. Schafer
Summary: This study presents a method for the direct alkylation of unprotected amine heterocycles using an early transition-metal system, allowing for short reaction times and selective formation of branched reaction products in most cases. By avoiding the use of high loadings of precious metal catalysts, this method offers a more efficient approach to alkylate saturated N-heterocycles.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Kushal Dhake, Kyla J. Woelk, Joseph Becica, Andy Un, Sarah E. Jenny, David C. Leitch
Summary: The development of two divergent and complementary Lewis acid catalyzed additions of bicyclobutanes to imines is described. Microscale high-throughput experimentation was integral to the discovery and optimization of both reactions. N-arylimines undergo formal (3+2) cycloaddition with bicyclobutanes to yield azabicyclo[2.1.1]hexanes in a single step; in contrast, N-alkylimines undergo an addition/elimination sequence to generate cyclobutenyl methanamine products with high diastereoselectivity. These new products contain a variety of synthetic handles for further elaboration, including many functional groups relevant to pharmaceutical synthesis. The divergent reactivity observed is attributed to differences in basicity and nucleophilicity of the nitrogen atom in a common carbocation intermediate, leading to either nucleophilic attack (N-aryl) or E1 elimination (N-alkyl).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Nahiane Pipaon Fernandez, Gregory Gaube, Kyla J. Woelk, Mathias Burns, Damian P. Hruszkewycz, David C. Leitch
Summary: We present a new method for direct C-C bond formation using tandem C-O/C-H activation mediated by palladium catalyst. This approach allows for base-free direct C-H alkenylation by combining C-O oxidative addition at enol pivalates and concerted metalation-deprotonation of functionalized heterocycles. Mechanistic studies show that C-O oxidative addition is reversible and C-H activation occurs directly from the Pd(II) C-O oxidative addition product. In situ P-31 NMR spectroscopy reveals that (Cy3P)(2)Pd-(alkenyl)(OPiv) species is the predominant catalyst resting state during the reactions.
Article
Chemistry, Multidisciplinary
Jingru Lu, Irina Paci, David C. Leitch
Summary: In this study, a multivariate linear regression model is presented that accurately predicts the relative rate and regioselectivity of nucleophilic aromatic substitution reactions based on the electrophile structure. The model utilizes experimentally determined relative SNAr rates as a diverse training/test set and demonstrates excellent correlation with previously measured results, as well as accurate prediction of site selectivity for multihalogenated substrates. This easily implementable reactivity model has the potential to be a powerful tool in synthetic planning.
Article
Chemistry, Multidisciplinary
Jingru Lu, Sofia Donnecke, Irina Paci, David C. Leitch
Summary: Making accurate predictions of chemical reactivity based on molecular structure is still a challenging task. This article presents an approach to reactivity prediction for catalytic reactions using quantitative structure-reactivity models. The authors demonstrate this approach with a mechanistically based model for a key step in catalytic processes.
Article
Chemistry, Multidisciplinary
Gregory Gaube, Nahiane Pipaon Fernandez, David C. Leitch
Summary: The synthesis of organoboron derivatives through Pd-catalyzed Miyaura borylation is a key application of catalytic cross-coupling, with the choice of optimal system heavily reliant on the substrate structure.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Materials Science, Multidisciplinary
Damon J. Gilmour, Tanja Tomkovic, Nirmalendu Kuanr, Mitchell R. Perry, Hans Gildenast, Savvas G. Hatzikiriakos, Laurel L. Schafer
Summary: The successful catalytic synthesis of amine-functionalized polyolefins transforms simple starting materials into polar-functionalized polymers with complete atom economy. These materials exhibit tunable rheological properties, autonomous self-healing, and unexpected adhesion to PTFE through dynamic associative interactions like hydrogen bonding.
ACS APPLIED POLYMER MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Joseph Becica, Owen D. Glaze, Damian P. Hruszkewycz, Graham E. Dobereiner, David C. Leitch
Summary: A specific combination of catalyst, solvent, base, and additives was crucial for both activity and selectivity in the Mizoroki-Heck arylation of electron-rich alkenes. This was especially important when translating screening hits into preparative-scale synthesis.
REACTION CHEMISTRY & ENGINEERING
(2021)
Article
Chemistry, Multidisciplinary
Emma Dennis, Soumya Kundu, Deepak Thrithamarassery Gangadharan, Jingjun Huang, Victor M. Burlakov, Devon Richtsmeier, Magdalena Bazalova-Carter, David C. Leitch, Makhsud Saidaminov
Summary: By growing lead bromide microwires with the aid of a gradient, long and thin wires have been successfully achieved, surpassing the limitations of pure PbBr2 solution and overcoming the issues of wire breakage, contamination, and poor reproducibility associated with conventional methods.
Article
Chemistry, Organic
Joseph Becica, David C. Leitch
Summary: Palladium catalysis can provide new oxygenate-based feedstocks and building blocks by activating strong C-O bonds, demonstrating not only difficult C-O oxidative additions but also Suzuki-type cross-couplings of alkenyl carboxylates under mild conditions. Depending on the reaction conditions, either a typical Pd(0)/(II) mechanism or a redox-neutral Pd(II)-only mechanism can operate, with C-C bond formation occurring through carbopalladation of the alkene, and C-O cleavage by beta-carboxyl elimination in the latter pathway.
Article
Chemistry, Inorganic & Nuclear
Joseph Becica, Gregory Gaube, William A. Sabbers, David C. Leitch
DALTON TRANSACTIONS
(2020)
