Recognition in the Domain of Molecular Chirality: From Noncovalent Interactions to Separation of Enantiomers

Chemical Reviews, Год журнала: 2022, Номер 122(16), С. 13235 - 13400

Опубликована: Авг. 2, 2022

It is not a coincidence that both chirality and noncovalent interactions are ubiquitous in nature synthetic molecular systems. Noncovalent interactivity between chiral molecules underlies enantioselective recognition as fundamental phenomenon regulating life human activities. Thus, represent the narrative thread of fascinating story which goes across several disciplines medical, chemical, physical, biological, other natural sciences. This review has been conceived with awareness modern attitude toward its consequences needs to be founded on multidisciplinary approaches disclose basis essential phenomena domain With primary aim discussing this topic an integrated way, comprehensive pool rational systematic information provided, concerns fundamentals chirality, description interactions, their implications processes occurring different contexts. A specific focus devoted enantioselection chromatography electromigration techniques because unique feature "multistep" processes. second motivation for writing make clear statement about state art, tools we have at our disposal, what still missing fully understand mechanisms underlying recognition.

Язык: Английский

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Mechanism-Guided Development of Transition-Metal-Catalyzed C–N Bond-Forming Reactions Using Dioxazolones as the Versatile Amidating Source

Accounts of Chemical Research, Год журнала: 2021, Номер 54(11), С. 2683 - 2700

Опубликована: Май 12, 2021

ConspectusCatalytic reactions that construct carbon–nitrogen bonds are one of central themes in both synthetic and medicinal chemistry since the obtainable nitrogen-containing motifs commonly encountered natural products have also seen a growing prominence as key structural features marketed drugs preclinical candidates. Pd-catalyzed cross-couplings, such Buchwald–Hartwig amination, at forefront methods practical settings. However, they require prefunctionalized substrates (hetero)aryl halides must be prepared independently, often by multiple operations. One emerging way to circumvent these preparatory steps directly convert ubiquitous C–H into valuable C–N is catalytic which allows chemists devise shorter more efficient retrosynthetic schemes. The past two decades witnessed considerable progress expanding repertoire this strategy, especially identifying effective amino group precursors. In context, dioxazolones experienced dramatic resurgence recent years versatile nitrogen source combination with transition-metal catalyst systems facilitate decarboxylation access metal-acylnitrenoid intermediates. addition their high robustness easy accessibility from abundant carboxylic acids, unique reactivity transient intermediates amido transfer has led fruitful journey for mild amidation reactions.This Account summarizes our contributions development bond-forming using nitrenoid precursors, categorized subsets according mechanistic differences: inner- versus outer-sphere pathways. first section describes how we could unveil potential realm inner-sphere amidation, where demonstrated serve not only manageable alternatives acyl azides but highly reagents significantly reduce loading temperature. Taking advantage conditions 9 Cp*M complexes (M = Rh, Ir, Co) or isoelectronic Ru species, dramatically expanded accessible scope. Mechanistic investigations revealed putative metal-nitrenoid species involved intermediate during catalysis, leads facile bond formation. On basis underpinning, succeeded developing novel platforms harness intermediacy metal-nitrenoids explore insertion via an pathway. Indeed, tailored catalysts were capable suppressing competitive Curtius-type decomposition, thus granting lactam products. We further repurposed upon modification chelating ligands identity transition metal achieve three goals: (i) addressing selectivity issues control regio-, chemo-, enantioselectivities, (ii) sustainable catalysis first-low metals, (iii) navigating chemical space (di)functionalization alkenes/alkynes. Together own research efforts, highlighted herein some important relevant advances other groups. finally conclude brief overview eye toward developments.

Язык: Английский

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Metal Stereogenicity in Asymmetric Transition Metal Catalysis

Chemical Reviews, Год журнала: 2023, Номер 123(8), С. 4764 - 4794

Опубликована: Март 29, 2023

Chiral transition metal catalysts represent a powerful and economic tool for implementing stereocenters in organic synthesis, with the center providing strong chemical activation upon its interaction substrates or reagents, while overall chirality of complex achieves desired stereoselectivity. Often, chiral topology implements stereogenic center, which is then involved origin asymmetric induction. This review provides comprehensive survey reported formally constitutes stereocenter. A goes along an complex, regardless whether ligands are achiral. Implications catalyst design mechanism induction discussed half-sandwich, tetracoordinated, pentacoordinated, hexacoordinated complexes containing center. The distinguishes between originating from coordination to those solely composed optically inactive (achiral rapidly interconverting enantiomers) prior complexation (dubbed “chiral-at-metal” catalysts).

Язык: Английский

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Synthesis of Chiral Spirolactams via Sequential C−H Olefination/Asymmetric [4+1] Spirocyclization under a Simple Co^II/Chiral Spiro Phosphoric Acid Binary System

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(43), С. 23187 - 23192

Опубликована: Авг. 26, 2021

Abstract An unprecedented enantioselective synthesis of spiro‐γ‐lactams via a sequential C−H olefination/asymmetric [4+1] spirocyclization under simple Co II /chiral spiro phosphoric acid (SPA) binary system is reported. A range biologically important are obtained with high levels enantioselectivity (up to 98 % ee ). The concise, asymmetric an aldose reductase inhibitor was successfully achieved. Notably, contrast previous reports that relied on the use cyclopentadienyl or its derivatives (achiral Cp*, Cp tBu , chiral x ) ligated III complexes requiring tedious steps prepare, cheap and commercially available cobalt(II) acetate tetrahydrate used as efficient precatalyst.

Язык: Английский

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Noncovalent interaction with a spirobipyridine ligand enables efficient iridium-catalyzed C–H activation

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 17, 2024

Abstract Exploitation of noncovalent interactions for recognition an organic substrate has received much attention the design metal catalysts in synthesis. The CH–π interaction is especially interest molecular because both C–H bonds and π electrons are fundamental properties molecules. However, their weak nature, these have been less utilized control reactions. We show here that can be used to kinetically accelerate catalytic activation arenes by directly recognizing π-electrons arene substrates with a spirobipyridine ligand. Computation ligand kinetic isotope effect study provide evidence between backbone substrate. rational exploitation will open new avenues catalysis.

Язык: Английский

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Biocatalytic, Intermolecular C−H Bond Functionalization for the Synthesis of Enantioenriched Amides

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(47), С. 24864 - 24869

Опубликована: Сен. 17, 2021

Abstract Directed evolution of heme proteins has opened access to new‐to‐nature enzymatic activity that can be harnessed tackle synthetic challenges. Among these, reactions resulting from active site iron‐nitrenoid intermediates present a powerful strategy forge C−N bonds with high site‐ and stereoselectivity. Here we report biocatalytic, intermolecular benzylic C−H amidation reaction operating at mild scalable conditions. With hydroxamate esters as nitrene precursors, feedstock aromatic compounds converted chiral amides excellent enantioselectivity (up >99 % ee ) yields 87 %). Kinetic computational analysis the reveals rate‐determining nitrenoid formation followed by stepwise hydrogen atom transfer‐mediated functionalization.

Язык: Английский

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Chain Walking as a Strategy for Iridium-Catalyzed Migratory Amidation of Alkenyl Alcohols to Access α-Amino Ketones

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(9), С. 4277 - 4285

Опубликована: Фев. 24, 2022

Catalytic carbon–nitrogen bond formation in hydrocarbons is an appealing synthetic tool to access valuable nitrogen-containing compounds. Although a number of approaches have been developed construct bifunctional α-amino carbonyl scaffold this realm, installation amino functionality at the remote and unfunctionalized aliphatic sites remains underdeveloped. Here we present tandem iridium catalysis that enables redox-relay amidation alkenyl alcohols via chain walking metal-nitrenoid transfer, which eventually offers new route various ketones with excellent regioselectivity. The virtue transformation unrefined isomeric mixture can be utilized as readily available starting materials lead regioconvergent amidation. Mechanistic investigations revealed reaction proceeds process involving two key components intermolecular nitrenoid transfer assistance hydrogen bonding, thus representing competence Ir for olefin migratory C–N coupling high efficiency exquisite selectivity.

Язык: Английский

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Catalytic, asymmetric carbon–nitrogen bond formation using metal nitrenoids: from metal–ligand complexes via metalloporphyrins to enzymes

Chemical Science, Год журнала: 2023, Номер 14(44), С. 12447 - 12476

Опубликована: Янв. 1, 2023

The introduction of nitrogen atoms into small molecules is fundamental importance and it vital that ever more efficient selective methods for achieving this are developed. With aim, the potential nitrene chemistry has long been appreciated but its application constrained by extreme reactivity these labile species. This liability however can be attenuated complexation with a transition metal resulting nitrenoids have unique highly versatile which includes amination certain types aliphatic C-H bonds as well reactions alkenes to afford aziridines. At least one new chiral centre typically formed in processes development catalysts exert control over enantioselectivity nitrenoid-mediated become growing area research, particularly past two decades. Compared some synthetic methods, nitrenoid notable chemists draw from diverse array metals , ranging metal-ligand complexes, bearing variety ligand types, via bio-inspired metalloporphyrins, all way through to, very recently, engineered enzymes themselves. In latter category particular, rapid progress being made, rate suggests approach may instrumental addressing outstanding challenges field. review covers key developments strategies shaped field, addition latest advances, up until September 2023.

Язык: Английский

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Asymmetric Aminative Dearomatization of 2-Naphthols via Non-covalent N-Heterocyclic Carbene Catalysis

Organic Letters, Год журнала: 2023, Номер 25(13), С. 2323 - 2327

Опубликована: Март 30, 2023

Herein, successful utilization of non-covalent N-heterocyclic carbene (NHC) catalysis toward asymmetric aminative dearomatization naphthols is presented. The NHC-catalyzed process offers enantioselective synthesis cyclic enones possessing a nitrogen-containing α-quaternary stereocenter. reaction applies to various functionalized substrates including acid-labile groups and shown be scalable. Substrate activation via an O-H···NHC hydrogen-bonding interaction suggested based on the results obtained in mechanistic studies.

Язык: Английский

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Regioselective Dearomative Amidoximation of Nonactivated Arenes Enabled by Photohomolytic Cleavage of N‐nitrosamides

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(8)

Опубликована: Янв. 5, 2024

Abstract Dearomative spirocyclization reactions represent a promising means to convert arenes into three‐dimensional architectures; however, controlling the regioselectivity of radical dearomatization with nonactivated afford spirocyclizative 1,2‐difunctionalization other than its kinetically preferred 1,4‐difunctionalization is exceptionally challenging. Here we disclose novel strategy for dearomative 1,2‐ or 1,4‐amidoximation (hetero)arenes enabled by direct visible‐light‐induced homolysis N−NO bonds nitrosamides, giving rise various highly regioselective amidoximated spirocycles that previously have been inaccessible required elaborate synthetic efforts. The mechanism and origins observed regioselectivities were investigated control experiments density functional theory calculations.

Язык: Английский

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