Rational Design of Bioinspired Catalysts for Selective Oxidations

ACS Catalysis, Год журнала: 2020, Номер 10(15), С. 8611 - 8631

Опубликована: Июль 2, 2020

Recognizing Nature's unique ability to perform challenging oxygenation reactions with exquisite selectivity parameters at iron-dependent oxygenases, chemists have long sought understand and mimic these enzymatic processes artificial systems. In the last two decades, replication of reactivity non-heme iron oxygenases has become feasible even simple coordination complexes manganese. A bona fide minimalistic functional model was tetradentate-N4 ligand based complex [Fe(tpa)(CH3CN)2]2+(Fe(tpa), tpa = tris(2-methylpyridyl)amine), which activates H2O2 via a mechanism that mirrors key steps O2 activation mononuclear centers: controlled O–O bond cleavage, generation high-valent Fe═O oxidant, promotion almost full spectrum its oxidative (C–H hydroxylation, olefin epoxidation, syn-dihydroxylation, desaturation). These landmark discoveries set mechanistic framework use nitrogen-rich ligands as catalysts for oxidizing organic substrates under synthetically relevant conditions. Due proof-of-concept demonstrations potential in synthesis, this chemistry flourished over past decade. parallel realization class diverse transformations, effort been spent manipulate catalyst structure aim tuning both oxidation reactions. This perspective provides an overview progress research. Some features archetypical Fe(tpa) stayed surprisingly true throughout evolution, but series alterations modulate electronic, steric, or binding properties allowed rational elicitation specific selectivity. some cases, replacement by manganese also proven beneficial. Overall, optimization enabled development highly asymmetric site-selective enantioselective C–H

Язык: Английский

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Nickel-Catalyzed 1,2-Carboamination of Alkenyl Alcohols

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(34), С. 13962 - 13970

Опубликована: Авг. 20, 2021

An alcohol-directed, nickel-catalyzed three-component umpolung carboamination of unactivated alkenes with aryl/alkenylboronic esters and electrophilic aminating reagents is reported. This transformation enabled by specifically tailored O-(2,6-dimethoxybenzoyl)hydroxylamine electrophiles that suppress competitive processes, including undesired β-hydride elimination transesterification between the alcohol substrate electrophile. The reaction delivers desired 1,2-carboaminated products generally high regio- syn-diastereoselectivity exhibits a broad scope coupling partners alkenes, complex natural products. Various mechanistic experiments analysis stereochemical outcome cyclic alkene substrate, as confirmed X-ray crystallographic analysis, support alcohol-directed syn-insertion an organonickel(I) species.

Язык: Английский

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Urea as a Redox-Active Directing Group under Asymmetric Photocatalysis of Iridium-Chiral Borate Ion Pairs

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(46), С. 19462 - 19467

Опубликована: Ноя. 5, 2020

The development of a photoinduced, highly diastereo- and enantioselective [3 + 2]-cycloaddition N-cyclopropylurea with α-alkylstyrenes is reported. This asymmetric radical cycloaddition relies on the strategic placement urea cyclopropylamine as redox-active directing group (DG) anion-binding ability use an ion pair, comprising iridium polypyridyl complex weakly coordinating chiral borate ion, photocatalyst. structure anion component catalyst governs reactivity, pertinent structural modification enables high levels catalytic activity stereocontrol. system tolerates range hence offers rapid access to various aminocyclopentanes contiguous tertiary quaternary stereocenters, DG readily removable.

Язык: Английский

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Chiral Separations in Preparative Scale: A Medicinal Chemistry Point of View

Molecules, Год журнала: 2020, Номер 25(8), С. 1931 - 1931

Опубликована: Апрель 21, 2020

Enantiomeric separation is a key step in the development of new chiral drug. Preparative liquid chromatography (LC) continues to be technique choice either during drug discovery process, achieve few milligrams, or scale-up clinical trial, needing kilograms material. However, last years, instrumental and technical developments allowed an exponential increase preparative enantioseparation using other techniques. Besides LC, supercritical fluid (SFC) counter-current (CCC) have aroused interest for separation. This overview will highlight importance separations Medicinal Chemistry, especially early stages pipeline drugs development. Few examples within different methodologies selected, emphasizing trends The advantages drawbacks critically discussed.

Язык: Английский

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Substrate-Directed Enantioselective Aziridination of Alkenyl Alcohols Controlled by a Chiral Cation

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(13), С. 7516 - 7527

Опубликована: Март 24, 2023

Alkene aziridination is a highly versatile transformation for the construction of chiral nitrogen-containing compounds. Inspired by success analogous substrate-directed epoxidations, we report an enantioselective alkenyl alcohols, which enables asymmetric nitrene transfer to alkenes with varied substitution patterns, including those not covered current protocols. We believe that our method effective because it substrate-directed, exploiting network attractive non-covalent interactions between substrate, achiral dianionic rhodium(II,II) tetracarboxylate dimer, and its two associated cinchona alkaloid-derived cations. It these cations provide defined pocket in can occur. In addition thorough evaluation compatible alkene classes, advance practical mnemonic predict reaction outcome disclose range post-functionalization protocols highlight unique synthetic potential enantioenriched aziridine-alcohol products.

Язык: Английский

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Coordination Assistance: A Powerful Strategy for Metal-Catalyzed Regio- and Enantioselective Hydroalkynylation of Internal Alkenes

Accounts of Chemical Research, Год журнала: 2023, Номер 56(3), С. 308 - 321

Опубликована: Янв. 11, 2023

ConspectusAlkenes are versatile compounds that readily available on a large scale from industry or through organic synthesis. The widespread occurrence of alkenes provides the continuous impetus for development catalytic asymmetric alkene hydrofunctionalizations, which enables expeditious construction complex chiral molecules starting materials. Catalytic hydrofunctionalization internal presents notable challenge, due to their low reactivity, many potential side reactions, and simultaneous control regio-, diastereo-, enantioselectivities.Dehydroamino acids enamides among first substrates provide enantioselectivities in hydrogenation. crucial importance an amide coordinating group is established by series classical mechanistic studies. This initial success greatly stimulated further hydrogenation hydrofunctionalization. Building these pioneering works as well related we have adopted coordination assistance powerful tool address challenges associated with alkenes. Using functional substrate native group, two-point binding mode metal center effectively enhances reactivity facilitates diastereo- enantioselectivities. Through this strategy, developed number methods excellent enantiocontrols.In Account, summarize recent advance our lab using key element achieve regio- enantioselective hydroalkynylation First, describe early work aimed at controlling enantioselectivity disubstituted enamide substrate. Both α- β-alkynylation were achieved channeling reaction pathway into Chalk-Harrod modified mechanism. Next, discuss catalysts regiodivergent trisubstituted access vicinal stereocenters quaternary carbon stereocenters. We also α,β-unsaturated amides unconventional site-selectivity combination isomerization regioselective hydroalkynylation. basis remote stereocenter β,γ-unsaturated amides. show principle applicable terminal well. A ligand-controlled mechanism shift discussed alkynylation position 1,1,-disubstituted Finally, briefly mention application other hydrofunctionalizations such hydroboration hydrosilylation, where previously inaccessible selectivity achieved. Collectively, demonstrate power hydrofunctionalizations. anticipate strategy will create platform enable diverse transformations.

Язык: Английский

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Substrate-Directed Lewis-Acid Catalysis for Peptide Synthesis

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(31), С. 12288 - 12295

Опубликована: Июль 16, 2019

A Lewis-acid-catalyzed method for the substrate-directed formation of peptide bonds has been developed, and this powerful approach is utilized new "remote" activation carboxyl groups under solvent-free conditions. The presented following advantages: (1) high-yielding synthesis uses a tantalum catalyst any amino acids; (2) reaction proceeds without racemization; (3) chemical ligation using titanium applicable to convergent synthesis. These advantages overcome some unresolved problems in classical

Язык: Английский

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Diboronic Acid Anhydrides as Effective Catalysts for the Hydroxy-Directed Dehydrative Amidation of Carboxylic Acids

Organic Letters, Год журнала: 2019, Номер 21(11), С. 4303 - 4308

Опубликована: Май 23, 2019

The direct catalytic dehydrative amidation of β-hydroxycarboxylic acids with amines is described. A biphenyl-based diboronic acid anhydride a B-O-B skeleton shown to be an exceptionally effective catalyst for the reaction, providing amides in high excellent yields low loading (minimum 0.01 mol %, TON up 7,500). This hydroxy-directed shows chemoselectivity and applicable gram-scale drug synthesis.

Язык: Английский

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Enantio‐ and Diastereoselective, Complete Hydrogenation of Benzofurans by Cascade Catalysis

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(24), С. 13677 - 13681

Опубликована: Апрель 12, 2021

We report an enantio- and diastereoselective, complete hydrogenation of multiply substituted benzofurans in a one-pot cascade catalysis. The developed protocol facilitates the controlled installation up to six new defined stereocenters produces architecturally complex octahydrobenzofurans, prevalent many bioactive molecules. A unique match chiral homogeneous ruthenium-N-heterocyclic carbene situ activated rhodium catalyst from precursor act sequence enable presented process.

Язык: Английский

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Peptide Bond-Forming Reaction via Amino Acid Silyl Esters: New Catalytic Reactivity of an Aminosilane

ACS Catalysis, Год журнала: 2020, Номер 10(16), С. 9594 - 9603

Опубликована: Июль 31, 2020

The epimerization-free formation of peptide bonds is crucial for the development therapeutics and pharmaceuticals. Herein, we report a hydrosilane-mediated approach construction between most amino acids under ambient conditions. This concise protocol with an original silylating reagent HSi(OCH(CF3)2)3 facilitates use bearing broad variety functional groups without any epimerization. Moreover, catalytic system using aminosilane catalyst enables not only acceleration in silylation carboxylic but also amide synthesis minimal substrate (electrophile/nucleophile/silylating = 1:1:1) waste production (hydrogen gas siloxane). These simple powerful approaches are established as potentially general paradigm desired peptides high yields.

Язык: Английский

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