P-Stereogenic Phosphorus Ligands in Asymmetric Catalysis

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(14), P. 8657 - 8739

Published: July 2, 2024

Chiral phosphorus ligands play a crucial role in asymmetric catalysis for the efficient synthesis of useful optically active compounds. They are largely categorized into two classes: backbone chirality and P-stereogenic ligands. Most reported belong to former class. Privileged ones such as BINAP DuPhos frequently employed wide range catalytic transformations. In contrast, latter class has remained small family many years mainly because their synthetic difficulty. The late 1990s saw emergence novel with superior enantioinduction ability Rh-catalyzed hydrogenation reactions. Since then, numerous have been synthesized used This Review summarizes thus far, including stereochemical electronic properties that afford high excellent enantioselectivities. Examples reactions use this described together applications construction key intermediates natural products therapeutic agents. literature covered dates back 1968 up until December 2023, centering on studies published later years.

Language: Английский

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Nanoarchitectonics of Non-Noble-Metal-Based Heterogeneous Catalysts for Transfer Hydrogenation Reactions: Detailed Insights on Different Hydrogen Sources

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(6), P. 4211 - 4248

Published: March 5, 2024

Catalytic transfer hydrogenation (CTH) methodology has drawn profound attention of researchers as an economical and environmentally benign alternate to conventional method. Unlike method, CTH exhibits better reaction efficiency atom economy, it makes use simple, easily accessible, low-cost hydrogen sources. Current research on reactions is oriented toward the development non-noble-metal-based catalysts due their high abundance potential large-scale applicability. In this Review, different organic transformation reactions, such nitroarenes, nitriles, alkenes, alkynes, carbonyl compounds, hydrogenolysis, reductive amination, formylation using sources have been summarized comprehensively. addition, synthesis strategies heterogeneous structure–activity relationship involving metal–support interaction, single-atom catalysis, synergistic effect are highlighted. Furthermore, optimization parameters─such temperature, time, solvents, additives─for enhancing catalytic activity selectivity product discussed in detail. This Review provides detailed insights into recent progress made with a specific focus catalyst development, sources, mechanistic exploration.

Language: Английский

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MAdPHOS, a P-Stereogenic Aminodiphosphane Ligand with Adamantyl Groups: Synthesis, NH/PH Tautomerism, and Rhodium and Nickel Complexes

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

A novel chiral ligand, named MAdPHOS, bearing a P-stereogenic phosphane and diadamantyl linked by NH bridge has been synthesized. This bulky, C1-symmetric, PNP ligand prepared from enantiopure tert-butylmethyl aminophosphane was obtained as crystalline solid. The NH/PH tautomerism, air-stability, σ-donor capacity of MAdPHOS have assessed herein. free prepared, showing much higher stability, in the solid form, than its tert-butyl analogue MaxPHOS. Both rhodium nickel COD complexes prepared. Rh-MAdPHOS complex shown outstanding enantioselectivities asymmetric hydrogenation enamides.

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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Recent advances in the metal-catalyzed asymmetric alkene hydrogenation of cyclic conjugated carbonyl compounds

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(10), P. 2934 - 2953

Published: Jan. 1, 2024

This review summarizes the recent advances (2016–2023) in stereoselective metal-catalyzed hydrogenation of cyclic α,β-unsaturated ketones, lactams and lactones since considerable developments were made. Where possible application these methodologies synthesis is outlined.

Language: Английский

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Alkane Dehydrogenation and H/D Exchange by a Cationic Pincer-Ir(III) Hydride: Cooperative C–H Addition and β-H Elimination Modes Induce Anomalous Selectivity

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

We report that the cationic iridium complex (iPrPCP)IrH+ catalyzes transfer-dehydrogenation of alkanes to give alkenes and hydrogen isotope exchange (HIE) arenes. Contrary established selectivity trends found for C-H activation by transition metal complexes, strained cycloalkanes, including cyclopentane, cycloheptane, cyclooctane, undergo addition much more readily than n-alkanes, which in turn are reactive cyclohexane. Aromatic bonds also H/D less rapidly those but favorably The order reactivity toward dehydrogenation correlates qualitatively with reaction thermodynamics, magnitude is greater can be explained thermodynamics. Accordingly, cycloalkenes corresponding cycloalkanes hydrogenation cyclohexene, despite favorable thermodynamics such hydrogenations. Computational (DFT) studies allow rationalization origin unusual selectivity. Specifically, initial strongly assisted β-agostic interactions, particularly cycloalkanes. Subsequent α-C-H addition, H atom bond transferred directly hydride ligand a dihydrogen ligand. overall processes, β-H-transfer hydride, calculated generally have minima on IRC surface although not necessarily enthalpy or free energy surfaces; these extremely shallow 1,2-dehydrogenations effectively concerted asynchronous.

Language: Английский

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A meta-learning approach for selectivity prediction in asymmetric catalysis

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 15, 2025

Abstract Transition metal-catalyzed asymmetric reactions are of high contemporary importance in organic synthesis. Recently, machine learning (ML) has shown promise accelerating the development newer catalytic protocols. However, need for large amount experimental data can present a bottleneck implementing ML models. Here, we propose meta-learning workflow that harness literature-derived to extract shared reaction features and requires only few examples predict outcome new reactions. Prototypical networks used as method enantioselectivity hydrogenation olefins. This model consistently provides significant performance improvement over other popular methods such random forests graph neural networks. The our meta-model is analyzed with varying sizes training demonstrate its utility even limited data. A good on an out-of-sample test set further indicates general applicability approach. We believe this work will provide leap forward identifying promising early phases when minimal available.

Language: Английский

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Peroxo-Diiron(III/III) as the Reactive Intermediate for N-Hydroxylation Reactions in the Multidomain Metalloenzyme SznF: Evidence from Molecular Dynamics and Quantum Mechanical/Molecular Mechanical Calculations

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(9), P. 5808 - 5818

Published: April 13, 2023

Upon oxygen activation, the non-heme diiron enzymes can generate various active species for oxidative transformations. In this work, catalytic mechanism of site (heme-oxygenase-like oxidase (HDO) domain) in SznF has been comprehensively studied by molecular docking, classical dynamics (MD) and quantum mechanical/molecular mechanical (QM/MM) MD simulations, hybrid QM/MM calculations. The HDO domain catalyzes selective hydroxylation Nω-methyl-l-arginine (l-NMA) to Nδ-hydroxy-Nω-methyl-l-Arg (l-HMA) Nδ,Nω-dihydroxy-Nω,-methyl-l-Arg (l-DHMA), which is a key step synthesis nitrosourea pharmacophore pancreatic cancer drug streptozotocin (SZN). Our study shows that peroxo-diiron(III/III) intermediate Sznf maintains butterfly-like conformation, while further protonation diiron(III/III) found be inaccessible unfavorable thermodynamically. Among mechanisms, we most favorable involves nucleophilic attack guanidium group onto peroxo P1, drives heterolytic cleavage O–O bond. Moreover, selectivity N-hydroxylation fully supported suggesting reactive SznF. present expands our understanding on O2 activation enzymes.

Language: Английский

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Enantioselective synthesis of chiral 2,2,2-trifluoroethyl lactams via asymmetric hydrogenation

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(10), P. 2498 - 2504

Published: Jan. 1, 2023

Enantioselective hydrogenation of α-trifluoromethylidene lactams catalyzed by the Rh/f-spiroPhos complex is first developed, providing an efficient approach for synthesis various chiral trifluoroethyl lactams, with up to 99.9% ee and high turnover numbers (up 10500).

Language: Английский

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Unlocking the Asymmetric Hydrogenation of Tetrasubstituted Acyclic Enones

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(9)

Published: Dec. 14, 2023

Asymmetric hydrogenation (AH) of tetrasubstituted olefins generating two stereocenters is still an open topic. There are only a few reports on the AH with conjugated functional groups, while this process can create useful intermediates for subsequent elaboration relevant end products. Most successfully submitted to belong small number classes; remarkably, acyclic enones represents unsolved challenge. Herein, we disclose class air-stable Ir-P,N catalysts, prepared in three steps from commercially available amino alcohols, that hydrogenate, minutes, wide range electronically and sterically diverse (including exocyclic ones) high yields enantioselectivities. The factors responsible excellent selectivities were elucidated by combining deuterogenation experiments theoretical calculations. calculations indicated reduction follows Ir

Language: Английский

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