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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Enantioselective Access to Spirolactams via Nitrenoid Transfer Enabled by Enhanced Noncovalent Interactions

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(17), С. 6363 - 6369

Опубликована: Апрель 22, 2021

Described herein is the Ir-catalyzed enantioselective access to chiral spirolactam products via nitrenoid transfer aromatic ipso-carbons. The key strategy for precise stereocontrol enhance secondary attractive and repulsive interactions between catalyst substrates by introduction of a traceless O-silyl achiral auxiliary, thus effectively differentiating two prochiral faces arenol-derived 1,4,2-dioxazol-5-one substrates.

Язык: Английский

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Endo-Selective Intramolecular Alkyne Hydroamidation Enabled by NiH Catalysis Incorporating Alkenylnickel Isomerization

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(22), С. 10064 - 10074

Опубликована: Май 27, 2022

Intramolecular alkyne hydroamidation represents a straightforward approach for the access to synthetically valuable cyclic enamides. Despite some advances made in this realm, ability attain precise regiocontrol still remains challenging, especially endo cyclization that leads six-membered and larger azacyclic rings. Herein, we report NiH-catalyzed intramolecular of alkynyl dioxazolones allows an excellent selectivity, thus affording range six- eight-membered endocyclic enamides with broad scope. Mechanistic investigations revealed Ni(I) catalysis is operative current system, proceeding via regioselective syn-hydronickelation, alkenylnickel E/Z isomerization, Ni-centered inner-sphere nitrenoid transfer. In particular, key isomerization step, which previously lacked mechanistic understandings, was found take place through η2-vinyl transition state. The synthetic value protocol demonstrated by diastereoselective modifications obtained highly functionalized δ-lactam scaffolds.

Язык: Английский

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Regiodivergent Electrophotocatalytic Aminooxygenation of Aryl Olefins

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(41), С. 18803 - 18809

Опубликована: Окт. 4, 2022

A method for the regiodivergent aminooxygenation of aryl olefins under electrophotocatalytic conditions is described. The procedure employs a trisaminocyclopropenium (TAC) ion catalyst with visible light irradiation controlled electrochemical potential to convert corresponding oxazolines high chemo- and diastereoselectivity. With judicious choice between two inexpensive abundant reagents, namely water urethane, either 2-amino-1-ol or 1-amino-2-ol derivatives could be prepared from same substrate. This amenable multigram synthesis oxazoline products low loadings.

Язык: Английский

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O-Allylhydroxyamine: A Bifunctional Olefin for Construction of Axially and Centrally Chiral Amino Alcohols via Asymmetric Carboamidation

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(14), С. 8150 - 8162

Опубликована: Апрель 4, 2023

Difunctionalization of olefins offers an attractive approach to access complex chiral structures. Reported herein is the design N-protected O-allylhydroxyamines as bifunctional that undergo catalytic asymmetric 1,2-carboamidation with three classes (hetero)arenes afford amino alcohols via C-H activation. The C═C bond in O-allylhydroxyamine activated by intramolecular electrophilic amidating moiety well a migrating directing group. carboamidation reaction pattern depends on nature (hetero)arene reagent. Simple achiral reacted give centrally β-amino excellent enantioselectivity. employment axially prochiral or racemic heteroarenes afforded both axial and central chirality enantio- diastereoselectivity. In case heteroarenes, coupling follows kinetic resolution s-factor up >600. A nitrene-based mechanism has been suggested based experimental studies, unique mode induction diastereoselectivity proposed. Applications alcohol products have demonstrated.

Язык: Английский

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Silylarylation of Alkenes via meta-Selective C–H Activation of Arenes under Ruthenium/Iron Cooperative Catalysis: Mechanistic Insights from Combined Experimental and Computational Studies

ACS Catalysis, Год журнала: 2024, Номер 14(7), С. 4510 - 4522

Опубликована: Март 12, 2024

Organosilicons are privileged skeletons in the domains of pharmaceutical chemistry, organic synthesis, and materials science. Hence, investigating catalytic techniques for synthesis organosilicon compounds has received a great deal emphasis. Carbosilylation alkenes is an efficient technique to introduce diverse molecular architectures containing silicon into chemical space. However, organohalides pseudohalides prerequisites most existing carbosilylation protocols. On other hand, utilization C–H activation been sowing seeds successful development intricate scaffolds. In this regard, synthetic accessibility complexed derivatives by through meta-C–H approach remained intangible. Herein, we present three-component strategy arylsilylation olefins with (het)arenes silanes integrating iron-catalyzed silyl radical generation, coupled intrinsic reactivity alkene, ruthenium-catalyzed functionalization (het)arene, leading targeted cross-coupled carbosilylated product. addition, theoretical investigations state-of-the-art dispersion corrected density functional theory at B3PW91-D3/Def2TZVP/CPCM(PhCF3) shed intriguing insights on selectivity probable mechanistic pathway underexplored cooperative 3d/4d transition metal catalysis, such as formation its addition alkene catalyzed iron, followed meta-selective ruthenium bound arene, furnishing C4 substituted (het)arene functionalized compounds.

Язык: Английский

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Catalytic, Enantioselective Syn-Oxyamination of Alkenes

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(33), С. 13408 - 13417

Опубликована: Авг. 10, 2021

The chemo-, regio-, diastereo-, and enantioselective 1,2-oxyamination of alkenes using selenium(II/IV) catalysis with a chiral diselenide catalyst is reported. This method uses N-tosylamides to generate oxazoline products that are useful both as protected 1,2-amino alcohol motifs ligands. reaction proceeds in good yields excellent enantio- diastereoselectivity for variety pendant functional groups such sulfonamides, alkyl halides, glycol-protected ketones. Furthermore, the rapid generation demonstrated expeditious assembly PHOX ligands well diversely amino alcohols.

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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