Cu-Mediated Thianthrenation and Phenoxathiination of Arylborons

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 10431 - 10440

Published: April 26, 2023

Great success in synthetic chemistry is motivated by the development of novel and reactive linchpins for carbon-carbon carbon-heteroatom bond formation reactions, which has dramatically altered chemists' approach to building molecules. Herein, we report ready synthesis aryl sulfonium salts, a versatile electrophilic linchpin, via Cu-mediated thianthrenation phenoxathiination commercially available arylborons with thianthrene phenoxathiine, providing series salts high efficiency. More importantly, leveraging sequential Ir-catalyzed C-H borylation arylborons, formal arenes also achieved. The undirected normally occurred at less steric hindrance position, thus complementary method comparison thianthrenation. This process capable late-stage functionalization pharmaceuticals, might find wide applications both industry academic sectors.

Language: Английский

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Oxidative addition of an alkyl halide to form a stable Cu(III) product

Science, Journal Year: 2023, Volume and Issue: 381(6662), P. 1072 - 1079

Published: Sept. 7, 2023

The step that cleaves the carbon-halogen bond in copper-catalyzed cross-coupling reactions remains ill defined because of multiple redox manifolds available to copper and instability high-valent product formed. We report oxidative addition α-haloacetonitrile ionic neutral copper(I) complexes form previously elusive but here fully characterized copper(III) complexes. stability these stems from strong Cu−CF 3 high barrier for C( CF )−C( CH 2 CN ) bond-forming reductive elimination. mechanistic studies we performed suggest proceeds by means two different pathways: an S N 2-type substitution complex a halogen-atom transfer complex. observed pronounced ligand acceleration addition, which correlates with couplings azoles, amines, or alkynes alkyl electrophiles.

Language: Английский

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General (hetero)polyaryl amine synthesis via multicomponent cycloaromatization of amines

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Language: Английский

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Combining Valence-to-Core X-ray Emission and Cu K-edge X-ray Absorption Spectroscopies to Experimentally Assess Oxidation State in Organometallic Cu(I)/(II)/(III) Complexes

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(6), P. 2520 - 2534

Published: Jan. 20, 2022

A series of organometallic copper complexes in formal oxidation states ranging from +1 to +3 have been characterized by a combination Cu K-edge X-ray absorption (XAS) and Kβ valence-to-core emission spectroscopies (VtC XES). Each state exhibits distinctly different XAS VtC XES transition energies due the differences Zeff, concomitant with changes physical +2 +3. Herein, we demonstrate sensitivity N-heterocyclic carbene (NHC) ligated organocopper complexes. We then extend these methods study [Cu(CF3)4]- ion. Complemented computational methods, observed spectral transitions are correlated electronic structure Zeff. These calculations that contraction 1s orbitals deeper binding energy upon center manifests spectroscopically as stepped increase both Kβ2,5 features increasing within [Cun+(NHC2)]n+ series. The newly synthesized Cu(III) cation [CuIII(NHC4)]3+ spectroscopic an remarkably similar [Cu(CF3)4]-, supporting assignment low-spin d8 for [Cu(CF3)4]-. Combining further demonstrates necessity combining multiple when investigating structures highly covalent complexes, providing template future investigations into synthetic biological metal centers.

Language: Английский

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Aryl Radical Enabled, Copper-Catalyzed Sonogashira-Type Cross-Coupling of Alkynes with Alkyl Iodides

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(4), P. 2761 - 2770

Published: Feb. 8, 2023

Despite the success of Sonogashira coupling for synthesis arylalkynes and conjugated enynes, engagement unactivated alkyl halides in such reactions remains historically challenging. We report herein a strategy that merges Cu-catalyzed alkyne transfer with aryl radical activation carbon-halide bonds to enable general approach iodides terminal alkynes. This unprecedented Sonogashira-type cross-coupling reaction tolerates broad range functional groups has been applied late-stage densely functionalized pharmaceutical agents as well positron emission tomography tracers.

Language: Английский

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Catalytically Relevant Organocopper(III) Complexes Formed through Aryl-Radical-Enabled Oxidative Addition

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(22), P. 15176 - 15185

Published: May 21, 2024

Stepwise oxidative addition of copper(I) complexes to form copper(III) species via single electron transfer (SET) events has been widely proposed in copper catalysis. However, direct observation and detailed investigation these fundamental steps remain elusive owing largely the typically slow rate instability species. We report herein a novel aryl-radical-enabled stepwise pathway that allows for formation well-defined alkyl–CuIII from CuI complexes. The process is enabled by SET an aryl diazonium salt CuII radical. Subsequent iodine abstraction alkyl iodide radical affords radical, which then reacts with complex. structure resultant [(bpy)CuIII(CF3)2(alkyl)] characterized NMR spectroscopy X-ray crystallography. Competition experiments have revealed at different iodides undergo consistent carbon-centered radicals. intermediate formed during identified as four-coordinate complex, [CuII(CH3CN)2(CF3)2], through electronic paramagnetic resonance (EPR) studies. catalytic relevance high-valent organo-CuIII demonstrated C–C bond-forming reductive elimination reactivity. Finally, localized orbital bonding analysis formal CuIII indicates inverted ligand fields σ(Cu–CH2) bonds. These results demonstrate catalysis provide general strategy investigate

Language: Английский

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Site‐Specific Deaminative Trifluoromethylation of Aliphatic Primary Amines**

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(8)

Published: Jan. 5, 2024

Abstract The introduction of trifluoromethyl groups into organic molecules is paramount importance in modern synthetic chemistry and medicinal chemistry. While methods for constructing C(sp 2 )−CF 3 bonds have been well established, the advancement practical comprehensive approaches forming remains considerably restricted. In this work, we describe an efficient site‐specific deaminative trifluoromethylation reaction aliphatic primary amines to afford corresponding alkyl compounds. proceeds at room temperature with readily accessible N ‐anomeric amide (Levin's reagent) bench‐stable bpyCu(CF ) (Grushin's reagent, bpy=2,2′‐bipyridine) under blue light. protocol features mild conditions, good functional group tolerance, moderate yields. Remarkably, method can be applied direct, late‐stage natural products bioactive molecules. Experimental mechanistic studies were conducted, a radical mechanism proposed, wherein dual roles Grushin's reagent elucidated.

Language: Английский

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Copper–Carbon Homolysis Competes with Reductive Elimination in Well-Defined Copper(III) Complexes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(48), P. 26152 - 26159

Published: Nov. 22, 2023

Despite the recent advancements of Cu catalysis for cross-coupling alkyl electrophiles and frequently proposed involvement alkyl-Cu(III) complexes in such reactions, little is known about reactivity these high-valent complexes. Specifically, although reversible interconversion between an alkyl-CuIII complex radical/CuII pair has been catalysis, direct observation steps well-defined CuIII remains elusive. In this study, we report synthesis investigation complexes, which exclusively undergo a Cu-C homolysis pathway to generate radicals CuII species. Kinetic studies suggest bond dissociation energy 28.6 kcal/mol CuIII-C bonds. Moreover, four-coordinate could be converted solvated alkyl-CuIII-(CF3)2, undergoes highly efficient C-CF3 bond-forming reductive elimination even at low temperatures (-4 °C). These results provide strong support recombination with form species, elusive step that Cu-catalyzed mechanisms. Furthermore, our work demonstrated significantly influenced by subtle changes coordination environment. Lastly, reactive neutral alkyl-CuIII-(CF3)2 species (or weakly bound solvent molecules) suggests they might true intermediates many trifluoromethylation reactions.

Language: Английский

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Radiocopper in Radiopharmacy and Medical Use: Current Status and Perspective

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Of the 32 known copper isotopes, some have interesting properties for nuclear medicine, example short-lived 60Cu, 61Cu, 62Cu, moderate long-lived 64Cu and 67Cu. Due to their emission properties, isotopes are suitable both imaging diagnostics (60Cu, 64Cu) targeted radiotherapy (64Cu 67Cu). As chemical virtually identical, a single radiopharmaceutical structure can be labeled with different depending on clinical application. This, combined ability combine radioisotopes same ligand, makes them extremely versatile. The purpose of this review is introduce world radiopharmaceuticals summarize recent advances in methods producing preclinical research radioisotopes.

Language: Английский

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Sulfonium Ylide Enabled, Copper-Catalyzed Difluoromethylation, Monofluoromethylation, and Monofluoroalkylation of Lithium Aryl ⁿButyl Borates

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4644 - 4653

Published: March 4, 2025

A copper-catalyzed fluoroalkylation of lithium aryl nbutyl borates with electrophilic fluoroalkylating reagent YlideFluor for the preparation di-, trifluoromethyl-, and monofluoroalkyl-substituted (hetero)arenes under mild conditions was described. Control experiments indicated that a fluoroalkyl radical, rather than difluorocarbene intermediate, is involved in catalytic process. In addition, stoichiometric reactions demonstrated transmetalation copper catalyst borate takes place before single-electron-transfer (SET) oxidation an ate-type Cu(I) intermediate [CuI(Ar)(SCN)]− by YlideFluor. Based on these mechanistic results, reasonable cycle proposed.

Language: Английский

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