Highly Enantioselective Synthesis of N‐Unprotected Unnatural α‐Amino Acid Derivatives by Ruthenium‐Catalyzed Direct Asymmetric Reductive Amination

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(25)

Published: March 25, 2022

Abstract An unprecedented highly enantioselective Ru‐catalyzed direct asymmetric reductive amination of α‐keto amides with ammonium salts has been disclosed, efficiently offering valuable enantioenriched N‐unprotected unnatural α‐amino acid derivatives bearing a broad range aryl or alkyl α‐substituents. This protocol features easily accessible substrates, good functional‐group tolerance and excellent enantiocontrol, making it complementary approach to the known methods. Moreover, this method is also applicable preparation containing an additional stereogenic center at β‐position through dynamic kinetic resolution (DKR) process. Convenient transformations obtained products into chiral acids, drug intermediates, peptides, organocatalysts/ligands further showcase utility method.

Language: Английский

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Light-driven redox deracemization of indolines and tetrahydroquinolines using a photocatalyst coupled with chiral phosphoric acid

Chemical Science, Journal Year: 2023, Volume and Issue: 14(7), P. 1715 - 1723

Published: Jan. 1, 2023

A light-driven redox deracemization to prepare optically pure cyclamines from their racemates is developed. This reaction provides a wide range of chiral indolines and tetrahydroquinolines with high yields enantioselectivities.

Language: Английский

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Desymmetric Reductive Amination of 1,3-Cyclopentadiones to Single Stereoisomer of β-Amino Ketones with an All-Carbon Quaternary Stereocenter by Engineered Amine Dehydrogenases

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(7), P. 5053 - 5061

Published: March 29, 2023

Regio- and stereoselective reductive amination of diketones offers an attractive method to access chiral β-amino ketones with multiple stereocenters which are unique scaffolds building blocks for bioactive molecules, but it is still a great challenge in organic chemistry. In this study, mutant amine dehydrogenases (LsAmDHs) were created by directed evolution l-phenylalanine dehydrogenase from Lysinibacillus sphaericus catalyze the desymmetric 2,2-disubstituted-1,3-cyclopentadiones. Using these beneficial LsAmDHs, corresponding (2R, 3R)-β-amino all-carbon quaternary stereocenter prepared up 99% de ee 84% isolated yields. A cyclopenta[b]hydroquinoline derivative was obtained 2-methyl-2-(2′-bromobenzyl)-1,3-cyclopentadione or 2-methyl-2-(2′-chlorobenzyl)-1,3-cyclopentadione via sequential enzymatic intramolecular Buchwald–Hartwig cross coupling reaction. Molecular docking dynamics simulations provided some insights into roles key mutations on improved activity excellent stereoselectivity toward un-native substrates. This study not only developed biocatalysts realize unprecedented 2,2-disubstituted-1,3-cyclopentadiones single stereoisomer also suggested that engineering provides useful tool address challenges asymmetric diketones.

Language: Английский

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Design and Application of New Pyridine-Derived Chiral Ligands in Asymmetric Catalysis

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(6), P. 957 - 970

Published: March 6, 2024

ConspectusThe innovation of chiral ligands has been crucial for the asymmetric synthesis functional molecules, as demonstrated by several types widely applied "privileged" ligands. In this context, pyridine-derived ligands, far some oldest and most utilized in catalysis, have attracted considerable research interest past half-century. However, development broadly applicable pyridine units (CPUs) plagued intertwining challenges, thus delaying advancements many reactions.This Account aims to summarize recent progress new CPU-containing focusing on a rationally designed, modular, tunable CPU developed our laboratory. A significant problem thwarting conventional designs is paradox between broad reactivity stereoselectivity; that is, while enhanced stereoselectivity may be achieved introducing elements close N atom, concomitant increase local steric hindrance often limits catalytic activity scope. Our newly features rigid [6-5-3] fused-ring framework spirocyclic ketal side wall. The well-defined three-dimensional structure minimizes (inner layer) tunes peripheral environment (outer remote substituents, securing stereoselectivity. Different chelating were readily assembled using structural module, with applications mechanistically diverse transition-metal-catalyzed reactions. Thus, series 2,2′-bipyridine successfully employed general, efficient, highly enantioselective nickel-catalyzed intermolecular reductive addition, Ullmann coupling ortho-chlorinated aryl aldehydes, carboxylation benzylic (pseudo)halides CO2. Notably, these exhibited superior reactions compared common N-based iridium-catalyzed C–H borylation was N,B-bidentate ligand. Furthermore, challenging, additive-free, broad-scope transfer hydrogenative direct amination half-sandwich iridium catalyst supported N,C-bidentate excellent performance high stereoselectivity, which, when combined experimental computational mechanistic investigations, "double-layer control" design concept.Considering described herein should inspire creation novel catalysts drive

Language: Английский

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Titanium in photocatalytic organic transformations: current applications and future developments

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(33), P. 6650 - 6664

Published: Jan. 1, 2024

Titanium, as an important transition metal, has garnered extensive attention in both industry and academia due to its excellent mechanical properties, corrosion resistance, unique reactivity organic synthesis. In the field of photocatalysis, titanium-based compounds such titanium dioxide (TiO

Language: Английский

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Asymmetric Catalytic Approaches Employing α,β‐Unsaturated Imines

European Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 26(15)

Published: Feb. 8, 2023

Abstract Nitrogen‐containing heterocyclic compounds have consistently been a noticeable center of attention due to their significant utilization in the domain synthetic organic chemistry, agrochemicals, and pharmaceuticals. α,β‐Unsaturated imines or conjugated provide lot cyclic as well acyclic products through reacting with versatile family compounds. This review summarizes recent advances enantioselective reactions α,β‐unsaturated by using methodologies for synthesizing various nitrogen‐containing heterocycles that contain four six‐membered rings. The synthesis rarely found seven‐, eight‐ nine‐membered also reported.

Language: Английский

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Bimetallic Synergy in Single-Atom Alloy Nanocatalysts for CO₂ Reduction to Ethylene

ACS Applied Nano Materials, Journal Year: 2023, Volume and Issue: 6(4), P. 2394 - 2402

Published: Feb. 10, 2023

Carbon dioxide reduction has been regarded as a promising strategy for the generation of value-added multi-carbon compounds. Taking advantage synergy distinct chemical characters adsorption sites, single-atom Sc-doped Cu(111) surface exhibits excellent performance C2H4 selectivity. O is more strongly bound to Sc than C Cu, leading facilitation CO2 activation and desorption. The dopant promotes C–C dimerization through CO dimer into COCO, which difficult occur on pristine Cu(111), COCO─involved reaction pathway favorable both in thermodynamics kinetics. This study sheds light nanocatalyst design products with different from reactants. Typically, control electron-deficient electron-sufficient sites catalyst surfaces beneficial reactions oxygenated reactants hydrocarbon products.

Language: Английский

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Paving the Way for Reductive Amination: Boosting Catalytic Ammonolysis of Schiff Base

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(19), P. 13034 - 13042

Published: Sept. 22, 2023

The synthesis of primary amines through reductive/hydrogen-borrowing amination has garnered significant attention due to their wide application in the chemical industry. key challenge reaction arises from two competing balances: hydrogenations imine versus Schiff base and ammonolysis hydrogenation base. former received extensive attention, latter, which directly determines selectivity amine, recently emerged as a fresh view for enhancing catalytic performance. Thus, gaining insights into promoting latter is becoming increasingly urgent catalyst design. This Perspective starts by presenting overall design principles mainly discusses influence balances on effective approaches tackle them. A profound emphasis placed advancing bases an in-depth understanding structure–activity relationships mechanisms. Finally, three directions deserving future investigations are provided. distinctive not only enhances importance comprehension amine but also unveils efficient avenues

Language: Английский

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Identifying a superior Ptδ+ species for the hydrogen-borrowing amination of alcohol at low temperature

Journal of Catalysis, Journal Year: 2024, Volume and Issue: 432, P. 115407 - 115407

Published: March 2, 2024

Language: Английский

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Utilizing biocatalysis and a sulfolane-mediated reductive acetal opening to access nemtabrutinib from cyrene

Green Chemistry, Journal Year: 2022, Volume and Issue: 25(2), P. 606 - 613

Published: Dec. 23, 2022

The development of a protecting group-free, 2-step synthesis 5-amino-2-hydroxymethyltetrahydropyran 1a from biorenewable Cyrene™ is described which renders access to BTK-inhibitor nemtabrutinib (2) more efficient and sustainable.

Language: Английский

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