Nickel‐Catalyzed Asymmetric Hydrogenation of α‐Substituted Vinylphosphonates and Diarylvinylphosphine Oxides

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(6)

Published: Dec. 12, 2022

Chiral α-substituted ethylphosphonate and ethylphosphine oxide compounds are widely used in drugs, pesticides, ligands. However, their catalytic asymmetric synthesis is still rare. Of the only hydrogenation methods available at present, all cases use rare metal catalysts. Herein, we report an efficient earth-abundant transition-metal nickel catalyzed affording corresponding chiral products with up to 99 % yield, 96 ee (enantiomeric excess) (99 ee, after recrystallization) 1000 S/C (substrate/catalyst); this also first study on of terminal olefins using a catalyst under hydrogen atmosphere. The mechanism was investigated via deuterium-labelling experiments calculations which indicate that two added atoms come from gas. Additionally, it believed reaction involves NiII rather than Ni0 cyclic process based weak attractive interactions between Ni olefin substrate.

Language: Английский

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Cobalt‐Catalyzed Efficient Convergent Asymmetric Hydrogenation of E/Z‐Enamides

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(26)

Published: April 12, 2023

Using the diphosphine-cobalt-zinc catalytic system, an efficient asymmetric hydrogenation of internal simple enamides has been realized. In particular, Ph-BPE ligand can achieve convergent E/Z-substrates. High yields and excellent enantioselectivities were obtained for both acyclic cyclic bearing α-alkyl-β-aryl, α-aryl-β-aryl, α-aryl-β-alkyl substituents. Hydrogenated products be applied synthesis useful chiral drugs such as Arfromoterol, Rotigotine, Norsertraline. addition, reasonable mechanism stereocontrol mode are proposed based on DFT calculations.

Language: Английский

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Precise Synthesis of ChiralZ‐Allylamides by Cobalt‐Catalyzed Asymmetric Sequential Hydrogenations

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(15)

Published: Feb. 8, 2023

Asymmetric sequential hydrogenations of conjugated enynes have been developed using a Ph-BPE-CoI catalyst for the precise synthesis chiral Z-allylamides in high activity (up to 1000 substrate/catalyst (S/C)) and with excellent enantioselectivity >99 % enantiomeric excess (ee)). Mechanism experiments theoretical calculations support cationic CoI /CoIII redox catalytic cycle. The difference between cobalt complexes Ph-BPE QuinoxP* was explained by process decomposition rate-determining step second hydrogenation.

Language: Английский

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Copper‐Catalyzed Chemoselective Asymmetric Hydrogenation of C=O Bonds of Exocyclic α,β‐Unsaturated Pentanones

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(35)

Published: June 12, 2023

A highly chemoselective earth-abundant transition metal copper catalyzed asymmetric hydrogenation of C=O bonds exocyclic α,β-unsaturated pentanones was realized using H2 . The desired products were obtained with up to 99 % yield and 96 ee (enantiomeric excess) (99 ee, after recrystallization). corresponding chiral allylic pentanol can be converted into several bioactive molecules. mechanism investigated via deuterium-labelling experiments control experiments, which indicate that the keto-enol isomerization rate substrate is faster than also show Cu-H complex only catalyze chemoselectively reduction carbonyl group. Computational results multiple attractive dispersion interactions (MADI effect) between catalyst bulky substituents play important roles stabilize states reduce generation by-products.

Language: Английский

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Fe/Thiol Cooperative Hydrogen Atom Transfer Olefin Hydrogenation: Mechanistic Insights That Inform Enantioselective Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(25), P. 17296 - 17310

Published: June 14, 2024

Asymmetric hydrogenation of activated olefins using transition metal catalysis is a powerful tool for the synthesis complex molecules, but traditional catalysts have difficulty with enantioselective reduction electron-neutral, electron-rich, and minimally functionalized olefins. Hydrogenation based on radical, metal-catalyzed hydrogen atom transfer (mHAT) mechanisms offers an outstanding opportunity to overcome these difficulties, enabling mild challenging selectivity that complementary hydrogenations H2. Further, mHAT presents asymmetric induction through cooperative (cHAT) chiral thiols. Here, we report insights from mechanistic study iron-catalyzed achiral cHAT reaction leverage deliver stereocontrol Kinetic analysis variation silane structure point hydride iron as likely rate-limiting step. The data indicate selectivity-determining step quenching alkyl radical by thiol, which becomes more potent H donor when coordinated iron(II). resulting iron(III)–thiolate in equilibrium other species, including FeII(acac)2, shown be predominant off-cycle species. enantiodetermining nature thiol trapping enables net commercially available glucose-derived catalyst up 80:20 enantiomeric ratio. To best our knowledge, this first demonstration via mHAT. These findings advance understanding act proof principle development reactions.

Language: Английский

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Nickel-catalyzed asymmetric hydrogenation for the preparation of α-substituted propionic acids

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 28, 2024

Abstract Transition metal-catalyzed asymmetric hydrogenation is one of the most efficient methods for preparation chiral α-substituted propionic acids. However, research on this method, employing cleaner earth-abundant metal catalysts, still insufficient in both academic and industrial contexts. Herein, we report an nickel-catalyzed acrylic acids affording corresponding with up to 99.4% ee (enantiomeric excess) 10,000 S/C (substrate/catalyst). In particular, method can be used obtain ( R )-dihydroartemisinic acid 99.8:0.2 dr (diastereomeric ratio) 5000 S/C, which essential intermediate antimalarial drug Artemisinin. The reaction mechanism has been investigated via experiments DFT (Density Functional Theory) calculations, indicate that protonolysis C-Ni bond key intramolecular proton transfer from carboxylic group substrate, rate-determining step.

Language: Английский

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Cobalt catalyzed practical hydroboration of terminal alkynes with time-dependent stereoselectivity

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 12, 2024

Abstract Stereodefined vinylboron compounds are important organic synthons. The synthesis of E −1-vinylboron typically involves the addition a B-H bond to terminal alkynes. selective generation thermodynamically unfavorable Z -isomers remains challenging, necessitating improved methods. Here, such proficient and cost-effective catalytic system is introduced, comprising cobalt salt readily accessible air-stable CNC pincer ligand. This enables transformation alkynes, even in presence bulky substituents, with excellent -selectivity. High turnover numbers (>1,600) frequencies (>132,000 h −1 ) achieved at room temperature, reaction can be scaled up 30 mmol smoothly. Kinetic studies reveal formal second-order dependence on concentration. Mechanistic investigations indicate that alkynes exhibit higher affinity for catalyst than alkene products, resulting exceptional -selective performance. Furthermore, rare time-dependent stereoselectivity observed, allowing quantitative conversion -vinylboronate esters -isomers.

Language: Английский

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Enantioconvergent Hydroboration of E/Z-Mixed Trisubstituted Alkenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(30), P. 21089 - 21098

Published: July 12, 2024

The lack of mode for chirality recognition makes it particularly challenging to carry out asymmetric transformations on

Language: Английский

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Stereoconvergent and Enantioselective Synthesis of Z-Homoallylic Alcohols via Nickel-Catalyzed Reductive Coupling of Z/E-1,3-Dienes with Aldehydes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(32), P. 22157 - 22165

Published: Aug. 5, 2024

Stereoconvergent reactions enable the transformation of mixed stereoisomers into well-defined, chiral products─a crucial strategy for handling

Language: Английский

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Cobalt‐Catalyzed Asymmetric Hydrogenation: Substrate Specificity and Mechanistic Variability

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(10)

Published: Nov. 28, 2023

Asymmetric hydrogenation finds widespread application in academia and industry. And indeed, a number of processes have been implemented for the production pharma agro intermediates as well flavors & fragrances. Although these are all based on use late transition metals catalysts, there is an increasing interest base metal catalysis view their lower cost expected different substrate scope. Catalysts cobalt already shown potential enantioselective chemistry. This review outlines impressive progress made recent years cobalt-catalyzed asymmetric unsaturated substrates. We also illustrate ligand dependent specificity mechanistic variability detail. may guide further catalyst development this research area.

Language: Английский

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