Native Amides as Enabling Vehicles for Forging sp³–sp³ Architectures via Interrupted Deaminative Ni-Catalyzed Chain-Walking

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 3869 - 3874

Опубликована: Фев. 8, 2023

Herein, we disclose an interrupted deaminative Ni-catalyzed chain-walking strategy that forges sp3-sp3 architectures at remote, yet previously unfunctionalized, methylene sp3 C-H sites enabled by the presence of native amides. This protocol is characterized its mild conditions and wide scope, including challenging substrate combinations. Site-selectivity can be dictated a judicious choice ligand, thus offering opportunity to enable bond formations are otherwise inaccessible in conventional events.

Язык: Английский

---

Nickel‐Catalyzed Switchable Site‐Selective Alkene Hydroalkylation by Temperature Regulation**

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(31)

Опубликована: Май 25, 2022

Regiodivergent alkene functionalization that produces either regioisomer starting from the same raw materials is desirable. Herein, we report a nickel-catalyzed switchable site-selective hydroalkylation. The selection of reaction temperatures leads to protocols provide regiodivergent hydroalkylated products single substrate. This protocol allows convenient synthesis α- and β-branched protected amines, both which are important fields pharmaceutical chemistry biochemistry. In addition, enantioenriched alkylamines can be accessed in catalytic asymmetric variant. Preliminary mechanistic studies indicate formation more stable nickelacycle provides driving force migration. thermodynamic kinetic properties different reduction elimination intermediates responsible for site-selectivity.

Язык: Английский

---

NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes and the ligand effects on regioselectivity

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Апрель 7, 2022

Abstract Alkene hydrocarbonation reactions have been developed to supplement traditional electrophile-nucleophile cross-coupling reactions. The branch-selective hydroalkylation method applied a broad range of unactivated alkenes remains challenging. Herein, we report NiH-catalysed proximal-selective access β- or γ-branched alkyl carboxylic acids and β-, γ- δ-branched amines. A iodides bromides with different functional groups can be installed excellent regiocontrol availability for site-selective late-stage functionalization biorelevant molecules. Under modified reaction conditions NiCl 2 (PPh 3 ) as the catalyst, migratory takes place provide (rather than γ-) branched products. keys success are use aminoquinoline picolinamide suitable directing combined experimental computational studies ligand effects on regioselectivity detailed mechanisms.

Язык: Английский

---

Ligand‐Controlled NiH‐Catalyzed Regiodivergent Chain‐Walking Hydroalkylation of Alkenes

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(30)

Опубликована: Май 24, 2022

Abstract A NiH‐catalyzed migratory hydroalkylation of alkenyl amines with predictable and switchable regioselectivity is reported. By utilizing a ligand‐controlled, directing group‐assisted strategy, various alkyl units are site‐selectively installed at inert sp 3 C−H sites far away from the original C=C bonds. range structurally diverse α‐ β‐branched protected conveniently synthesized via stabilization 5‐ 6‐membered nickelacycles respectively. This method exhibits broad scope high functional group tolerance, can be applied to late‐stage modification medicinally relevant molecules.

Язык: Английский

---

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

---

Orthogonal Access to α‐/β‐Branched/Linear Aliphatic Amines by Catalyst‐Tuned Regiodivergent Hydroalkylations

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(34)

Опубликована: Июнь 21, 2022

Abstract Linear, α‐branched, and β‐branched aliphatic amines are widespread in pharmaceuticals, agrochemicals, fine chemicals. Thus, the development of direct efficient methods to these structures a tunable manner is highly desirable yet challenging. Herein, catalyst‐controlled synthesis linear from Ni/Co‐catalyzed regio‐ site‐selective hydroalkylations alkenyl with alkyl halides developed. This catalytic protocol features reliable prediction control coupling position alkylation provide orthogonal access identical starting materials. platform unlocks reactivity selectivity nickel hydride cobalt chemistry catalytically repurpose three types under mild conditions.

Язык: Английский

---

Transition Metal-Catalyzed Regioselective Direct C–H Amidation: Interplay between Inner- and Outer-Sphere Pathways for Nitrene Cross-Coupling Reactions

Accounts of Chemical Research, Год журнала: 2022, Номер 55(15), С. 2123 - 2137

Опубликована: Июль 19, 2022

ConspectusCatalytic C–N bond cross-coupling reactions have been a subject of fundamental importance in synthetic organic and medicinal chemistry because amides amines are ubiquitous motifs natural products, functional materials, pharmaceuticals. Since the pioneering works Breslow Mansuy on metalloporphyrin-catalyzed direct hydrocarbon amidation using sulfonyliminoiodinane reagents, substantial development has achieved toward practical selective amination protocols. Notably, Du Bois's group developed dirhodium(II,II) carboxylate catalytic system for C(sp3)–H amidations via Rh-sulfonyl nitrene intermediates. Yet, this protocol suffers from competitive alkene aziridination is limited to electron-rich tertiary ethereal C–H bonds; analogous arenes remained ineffective.This Account discusses our early effort explore cyclopalladated complexes ortho-selective C(aryl)–H amidations. While Buchwald–Hartwig cannot be directly applied arenes, effective 2-arylpyridines occurred when an external oxidant such as K2S2O8 was employed. Preliminary studies suggested that may proceed through reactive Pd-nitrene Aiming develop more diversified protocols, we employed nosyloxycarbamates precursors Pd-catalyzed ortho-amidation N-pivalanilides. Likewise, benzoic acids produce anthranilic acids, which versatile many medicinally valuable heterocycles. In attempt expand C(aryl)–N coupling amines, studied d6 piano-stool Cp*Rh(III) systems [Cp* = pentamethylcyclopentadienyl]. Our work established sound reaction platform based electrophilic aminating reagents including N-chloroamines, hydroxyamides, N-carboxyhydrazides formation aryl–metal complexes.Building upon metal-nitrene platform, moved forward examine γ-lactam synthesis by intramolecular carbonyl insertion. Noted nitrenes prone undergo Curtius-type rearrangement form isocyanate; found π-basic Ru(II) center effectively decomposes dioxazolones afford regioselective γ-C(sp3)–H With chiral diphenylethylenediamines (dpen) ligands bearing electron-withdrawing arylsulfonyl substituents, [(p-cymene)Ru(dpen)] complex catalyzed decomposition γ-lactams formal Enantioselective insertion allylic propargylic bonds also with remarkable tolerance C═C C≡C bonds. selectivity [(p-cymene)Ru] switched give dihydroquinolinones l-proline ligand. Recently, aimed address regiocontrolled unactivated methylene NiH catalyst. benzyl can differentiated their dissociation energies steric properties, groups making up skeleton display similar electronic properties. context, exploited five-membered nickelacycle terminate NiH-mediated chain-walk isomerization, reacted furnish C(sp3)–N at γ-methylene position.This summarizes contribution activation. By exploiting inner-sphere outer-sphere pathways, successfully protocols target The mechanistic underpinning different related affiliated will discussed.

Язык: Английский

---

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

---

Electrochemical NiH‐Catalyzed C(sp³)−C(sp³) Coupling of Alkyl Halides and Alkyl Alkenes

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(44)

Опубликована: Сен. 14, 2023

Herein, an electrochemically driven NiH-catalyzed reductive coupling of alkyl halides and alkenes for the construction Csp3 -Csp3 bonds is firstly reported. Notably, serve dual function as substrates hydrogen sources to generate NiH species under electrochemical conditions. The tunable nature this reaction realized by introducing intramolecular coordinating group substrate, where product can be easily adjusted give desired branched products. method proceeds mild conditions, exhibits a broad substrate scope, affords moderate excellent yields with over 70 examples, including late-stage modification natural products drug derivatives. Mechanistic insights offer evidence process. sp3 -carbon-halogen activated through single electron transfer (SET) nickel catalyst in its low valence state, generated cathodic reduction, generation from pivotal transformation.

Язык: Английский

---

Enantioselective Ni-Catalyzed 1,2-Borylalkynylation of Unactivated Alkenes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(25), С. 17140 - 17149

Опубликована: Июнь 12, 2024

Enantioselective three-component difunctionalization of alkenes with boron reagents represents an attractive strategy for assembling three-dimensional chiral organoboron compounds. However, regio- and enantiocontrol comprise the pivot challenges in these transformations, which predominantly require use activated conjugated alkenes. Herein, by utilizing various carbonyl directing groups, including amides, sulfinamides, ketones, esters, we succeed realizing a nickel-catalyzed 1,2-borylalkynylation unactivated to enable simultaneous incorporation entity sp-fragment across double bond. The products contain boryl, alkynyl, functional groups orthogonal synthetic reactivities, offering three handles further derivatization access valuable intermediates. utility this ligand-enabled asymmetric protocol has been highlighted through late-stage decoration drug-relevant molecules.

Язык: Английский

---