Ligand‐Controlled Palladium‐Catalyzed Regiodivergent Defluorinative Allylation of gem‐Difluorocyclopropanes via σ‐Bond Activation

Chinese Journal of Chemistry, Год журнала: 2022, Номер 40(19), С. 2345 - 2355

Опубликована: Июнь 28, 2022

Comprehensive Summary Monofluoroalkenes are important and versatile privileged components in pharmacologically relevant molecules. Here, we report a method for the selective construction of these compounds diversity‐oriented fashion through regiodivergent cross‐coupling gem ‐difluorocyclopropanes with allylboronates by employing palladium catalyst two different ligands, which were used as allyl electrophiles C—C C—F bond activation. In presence 2‐biphenylyl(diphenyl)phosphine ligand, linear‐selective allyl–allyl formation is highly obtained, while utilizing sterically hindered BrettPhos (dicyclohexyl[3,6‐dimethoxy‐2',4',6'‐tris(1‐methylethyl)[1,1'‐biphenyl]‐2‐yl]phosphine) ligand favors generation branched‐selective product. Experimental computational studies investigated key steps reactions, revealing origin ligand‐controlled regiodivergence.

Язык: Английский

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Structurally Diverse Bench‐Stable Nickel(0) Pre‐Catalysts: A Practical Toolkit for In Situ Ligation Protocols**

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(9)

Опубликована: Дек. 16, 2022

A flurry of recent research has centered on harnessing the power nickel catalysis in organic synthesis. These efforts have been bolstered by contemporaneous development well-defined (pre)catalysts with diverse structure and reactivity. In this report, we present ten different bench-stable, 18-electron, formally zero-valent nickel-olefin complexes that are competent pre-catalysts various reactions. Our investigation includes preparations novel, bench-stable Ni(COD)(L) (COD=1,5-cyclooctadiene), which L=quinone, cyclopentadienone, thiophene-S-oxide, fulvene. Characterization NMR, IR, single-crystal X-ray diffraction, cyclic voltammetry, thermogravimetric analysis, natural bond orbital analysis sheds light structure, bonding, properties these complexes. Applications an assortment nickel-catalyzed reactions underscore complementary nature within toolkit.

Язык: Английский

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Ligand-Controlled Regiodivergent Nickel-Catalyzed Hydroaminoalkylation of Unactivated Alkenes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(5), С. 3458 - 3470

Опубликована: Янв. 25, 2024

Ligand modulation of transition-metal catalysts to achieve optimal reactivity and selectivity in alkene hydrofunctionalization is a fundamental challenge synthetic organic chemistry. Hydroaminoalkylation, an atom-economical approach for alkylating amines using alkenes, particularly significant amine synthesis the pharmaceutical, agrochemical, fine chemical industries. However, existing methods usually require specific substrate combinations precise regio- stereoselectivity, which limits their practical utility. Protocols allowing regiodivergent hydroaminoalkylation from same starting materials, controlling both regiochemical stereochemical outcomes, are currently absent. Herein, we report ligand-controlled, nickel-catalyzed unactivated alkenes with

Язык: Английский

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Benchtop Nickel Catalysis Invigorated by Electron-Deficient Diene Ligands

Accounts of Chemical Research, Год журнала: 2024, Номер 57(3), С. 312 - 326

Опубликована: Янв. 18, 2024

ConspectusDue to the rarity of precious metals like palladium, nickel catalysis is becoming an increasingly important player in organic synthesis, especially for formation bonds with sp3-hybridized carbon centers. Traditionally, catalytic processes involving active Ni(0) species have relied on Ni(COD)2 or situ reduction Ni(II) salts. However, air- and temperature-sensitive material that requires use inert-atmosphere glovebox, protocols salts using metallic organometallic reductants add additional complications reaction development.This Account chronicles development air-stable precursors as replacements reduction. Based Schrauzer's seminal discovery Ni(COD)(DQ) zerovalent organonickel complex, our research laboratories at Scripps Research Bristol Myers Squibb developed a class precatalysts based Ni(COD)(EDD) (EDD = electron-deficient diene) framework, relying steric electronic properties supporting diene render metal center stable air, moisture, even silica gel but reactive ligand substitution redox changes.The complexes can be accessed through exchange Ni(COD)2, Ni(acac)2 DIBAL-H, electrochemically via cathodic followed by addition EDD one pot. As toolkit, demonstrate reactivity equivalent enhanced compared catalyzing C–C C–N cross-couplings, Miyaura borylations, C–H activations, other transformations. Since initial report Ni(COD)(DQ), its C(sp2)–CN activation, metallophotoredox, electric field-induced cross-coupling also been demonstrated.By incorporating precatalyst toolkit into campaigns, able perform C(sp3)–S(alkyl) couplings metallonitrenoid carboamination, both which represent challenging transformations were inaccessible traditional phosphine, nitrogen, olefin ligands. Computational experimental studies how quinone ligands are hemilabile, adopting η1(O)-bound geometries relieve strain stabilize transition states intermediates; redox-active, transiently oxidize center; electron-withdrawing -donating, depending oxidation state coordination geometry. These show enable key steps beyond imparting air-stability.Since documenting activity many observed unique this precatalyst. was found offer superior cross coupling form N,N-diaryl sulfonamides preparation biaryls from aryl halides benzene Ni-mediated, base-assisted homolytic aromatic substitution.

Язык: Английский

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Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β‐Difluorinated Carbocycles

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(22)

Опубликована: Март 14, 2024

Abstract Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute arena of fluorinated medium rings where installing difluoromethylene unit subtly alters ring conformation by expanding internal angle (∠C−CF 2 −C>∠C−CH −C): this provides handle modulate physicochemistry (e.g. p K ). To reconcile disparity, highly modular expansion has been devised that leverages simple α,β‐unsaturated esters and amides, processes them one‐carbon homologated with concomitant geminal difluorination (6 10 membered rings, up 95 % yield). process rare example formal an alkene enabled sequential I(III)‐enabled O ‐activation. Validation enantioselective catalysis generation unprecedented scaffolds reported (up 93 : 7 e.r .) together X‐ray structural analyses product derivatization.

Язык: Английский

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Development and Mechanistic Studies of (E)-Selective Isomerization/Tandem Hydroarylation Reactions of Alkenes with a Nickel(0)/Phosphine Catalyst

ACS Catalysis, Год журнала: 2021, Номер 11(11), С. 6741 - 6749

Опубликована: Май 26, 2021

A stereoselective alkene isomerization and sequential hydroarylation with arylboronic acid using a nickel(0) catalyst has been developed. The bulky monophosphine PAd2(n-Bu) is an effective ligand in these reactions to furnish both various stereo-defined internal alkenes products (isomerization: up 98%, E/Z = 98:2; tandem hydroarylation: 82%). Mechanistic studies based on experiments computational calculations suggested that the proceeds via intra- or intermolecular hydrogen shift. Furthermore, concerted multibond recombination boronic acid-assisted oxidative protometallation of was found be reasonable mechanism for formation alkylnickel(II) species from alkene, nickel(0), alcohol, hydroarylation.

Язык: Английский

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Nickel-catalyzed hydroarylation reaction: a useful tool in organic synthesis

Organic Chemistry Frontiers, Год журнала: 2022, Номер 9(18), С. 5074 - 5103

Опубликована: Янв. 1, 2022

The nickel-catalyzed hydroarylation reaction opens up new routes to access complex organic compounds in a highly regio and stereoselective fashion from easily available precursors, such as olefin, alkyne, arene, aryl halide, boronic acid.

Язык: Английский

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Ligand-enabled Ni-catalyzed hydroarylation and hydroalkenylation of internal alkenes with organoborons

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

Опубликована: Ноя. 12, 2022

The transition metal-catalyzed hydrofunctionalization of alkenes offers an efficient solution for the rapid construction complex functional molecules, and significant progress has been made during last decades. However, internal remains a challenge due to low reactivity difficulties controlling regioselectivity. Here, we report hydroarylation hydroalkenylation lacking directing group with aryl alkenyl boronic acids in presence nickel catalyst, featuring broad substrate scope wide tolerance under redox-neutral conditions. key achieving this reaction is identification bulky 1-adamantyl β-diketone ligand, which capable overcoming 1,2-disubstituted alkenes. Preliminary mechanistic studies unveiled that undergoes Ar-Ni(II)-H initiated process, generated by oxidative addition alcoholic solvent Ni(0) species sequential transmetalation. In addition, proves be turnover-limiting step.

Язык: Английский

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Ligand‐Dictated Regiodivergent Allylic Functionalizations via Palladium‐Catalyzed Remote Substitution

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(28)

Опубликована: Март 15, 2023

Different from classical allylic substitutions that require a vicinal leaving group, an olefin bearing remote group is scarcely viewed as potential allylation substrate. Herein, we describe feasible protocols to achieve regiodivergent C-H functionalizations via palladium-catalyzed substitution, which provides novel strategy for the seldomly studied migratory Tsuji-Trost reaction. Dictated by suitable ligand, process involved 4,3-hydrofunctionalization of generated conjugated diene intermediate metal walking observed in generally >20 : 1 regioselectivity. Unexpectedly, related 1,4-hydrofunctionalization pathway found be major route with newly synthesized electron-rich bisphosphine challenges conventional viewpoint on regioselectivity hydrofunctionalizations linear internal dienes η3 -substitution. A series deuterium experiments and kinetic studies provide preliminary insight into catalytic cycle.

Язык: Английский

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Catalytic Regioselective Olefin Hydroarylation(alkenylation) by Sequential Carbonickelation-Hydride Transfer

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(25), С. 9498 - 9506

Опубликована: Июнь 21, 2021

Alkene hydrocarbofunctionalization represents one of the most important classes chemical transformations, but related branched-selective examples with unactivated olefins are scarce. Here, we report that catalytic amounts a dimeric Ni(I) complex and an exogenous alkoxide base promote Markovnikov-selective hydroarylation(alkenylation) activated using organo bromides or triflates derived from widely available phenols ketones. Products bearing aryl- alkenyl-substituted tertiary quaternary centers could be isolated in up to 95% yield >99:1 regioisomeric ratios. Contrary previous dual-catalytic methods rely on metal-hydride atom transfer (MHAT) olefin prior carbofunctionalization cocatalyst, our mechanistic evidence points toward nonradical reaction pathway begins site-selective carbonickelation across C═C bond followed by hydride as source. Utility single-catalyst protocol is highlighted through synthesis medicinally relevant scaffolds.

Язык: Английский

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