Mechanistic Insights into Copper-Mediated Benzylic C(sp3)−H Bond Trifluoromethylation DOI

Xiahe Chen,

Hang Liu,

Debo Ding

et al.

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

The trifluoromethylation of primary and secondary benzylic C(sp 3 )−H bonds by Cu II species proceeds via a radical recombination/reductive elimination pathway, while tertiary prefer the single-electron transfer (SET) pathway.

Language: Английский

Catalytically Relevant Organocopper(III) Complexes Formed through Aryl-Radical-Enabled Oxidative Addition DOI
Wenhao Yan, Andrew T. Poore, Lingfeng Yin

et al.

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

Citations

13
Site‐Specific Deaminative Trifluoromethylation of Aliphatic Primary Amines** DOI

Jiang‐Hao Xue,

Yin Li,

Yuan Liu

et al.

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

Citations

12
Oxidative Substitution of Organocopper(II) by a Carbon-Centered Radical DOI

Yuecheng Weng,

Yuxuan Jin,

Jian Wu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(33), P. 23555 - 23565

Published: Aug. 8, 2024

Copper-catalyzed coupling reactions of alkyl halides are believed to prominently involve copper(II) species and radicals as pivotal intermediates, with their exact interaction mechanism being the subject considerable debate. In this study, a visible light-responsive fluoroalkylcopper(III) complex, [(terpy)Cu(CF3)2(CH2CO2tBu)] Trans-1, was designed explore mechanism. Upon exposure blue LED irradiation, Trans-1 undergoes copper–carbon bond homolysis, generating Cu(II) carbon-centered radicals, where radical then recombines intermediate, resulting in formation Cis-1, Cis isomer Trans-1. Beyond this, well-defined fluoroalkylcopper(II) intermediate ligated sterically hindered ligand isolated underwent full characterization electronic structure studies. The collective experimental, computational, spectroscopic findings work strongly suggest that organocopper(II) engages via an "oxidative substitution" mechanism, which is likely operational pathway for copper-catalyzed C–H trifluoromethylation reactions.

Language: Английский

Citations

9
Access to Versatile Functionalized Cu(III) Complexes Enabled by Direct Transmetalation to Well‐Defined Copper(III) Fluoride Complex Me4N+[Cu(CF3)3F]‐ DOI
Guangyu Wang,

Huaiyuan Li,

Xuebing Leng

et al.

Chinese Journal of Chemistry, Journal Year: 2024, Volume and Issue: 42(10), P. 1107 - 1113

Published: Jan. 30, 2024

Comprehensive Summary The invention of a well‐defined Cu(III) fluoride complex Me 4 N + [Cu(CF 3 ) (F)] ‐ 1 enabled to access versatile functionalized complexes [Me N] [Cu(X)(CF ] (X = C 6 F 5 , C≡C, CN, Cl, t BuOO, SCN, OAc, SAr), many them for the first time. availability these allowed us evaluate trans ‐influence order ligand in complexes: Bn > CF – py ~ CH C≡C NO 2 PhO BuOO COO .

Language: Английский

Citations

6
High‐Valent Copper Catalysis Enables Regioselective Fluoroarylation of Gem‐Difluorinated Cyclopropanes DOI Creative Commons
Xiuli Wu,

Xiangyu Song,

Ying Xia

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(18)

Published: March 9, 2024

Abstract Transition‐metal (TM) catalyzed reaction of gem ‐difluorinated cyclopropanes ( ‐DFCPs) has drawn much attention recently. The generally occurs via the activation distal C─C bond in ‐DFCPs by a low‐valent TM through oxidative addition, eventually producing mono‐fluoro olefins as coupling products. However, achieving regioselective proximal that overcomes intrinsic reactivity catalysis remains elusive. Here, new mode enabled high‐valent copper catalysis, which allows exclusive congested is presented. achieves fluoroarylation uses NFSI (N‐fluorobenzenesulfonimide) electrophilic fluoro reagent and arenes C─H nucleophiles, enabling synthesis diverse CF 3 ‐containing scaffolds. It proposed species plays an important role possibly σ‐bond metathesis.

Language: Английский

Citations

6
Catalytic Asymmetric Oxidative Coupling between C(sp3)–H Bonds and Carboxylic Acids DOI
Xianming Liu, Fu Li,

Tongkun Wang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

The direct enantioselective functionalization of C(sp3)–H bonds in organic molecules could fundamentally transform the synthesis chiral molecules. In particular, oxidation these would dramatically change production methods alcohols and esters, which are prevalent natural products, pharmaceuticals, fine chemicals. Remarkable advances have been made construction carbon–carbon carbon–nitrogen through bond functionalization. However, formation carbon–oxygen from remains a considerable challenge. We herein report highly oxidative coupling with carboxylic acids. method applies to allylic propargylic C–H employs various acids as oxygenating agents. successfully synthesized range esters directly readily available alkenes alkynes, greatly simplifying related alcohols.

Language: Английский

Citations

4
An Organocopper(III) Fluoride Triggering C−CF3 Bond Formation DOI Creative Commons
Daniel Joven‐Sancho, Andrea Echeverri, Nathalie Saffon‐Merceron

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(11)

Published: Dec. 26, 2023

Abstract Copper(III) fluorides are catalytically competent, yet elusive, intermediates in cross‐coupling. The synthesis of [PPh 4 ][Cu III (CF 3 ) F] ( 2 ), the first stable (isolable) Cu −F, was accomplished via chloride addition to [Cu (py)] 1 yielding Cl(py)] ⋅Cl), followed by treatment with AgF. halides ⋅Cl and were fully characterized using nuclear magnetic resonance (NMR) spectroscopy, single crystal X‐ray diffraction (Sc‐XRD) elemental analysis (EA). Complex proved capable forging C−CF bonds from silyl‐capped alkynes. In‐depth mechanistic studies combining probes, theoretical calculations, trapping intermediate a ([PPh (C≡CPh)]) radical tests unveil key role acetylides that undergo facile e − reductive elimination furnishing trifluoromethylated alkynes (RC≡CCF which industrially relevant synthons drug discovery, pharma agrochemistry.

Language: Английский

Citations

9
New reactivity of late 3d transition metal complexes in catalytic reactions of alkynes DOI
Shenghan Teng,

Peiyao Liang,

Jianrong Steve Zhou

et al.

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review summarizes seven types of new reactivities found in late 3d metal complexes and catalytic examples recent years.

Language: Английский

Citations

0
Key intermediates in CuI to CuIII catalytic cycle for ethoxycarbonyl difluoro-methylation DOI

Yixiao Zhao,

Gavin C. Tsui,

Qilong Shen

et al.

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111051 - 111051

Published: March 1, 2025

Language: Английский

Citations

0
Copper-Mediated Direct Trifluoromethylation of Trichloromethyl Alkanes DOI
Ziming Wu, Zehai Lu, Yongrui Luo

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

CF3CCl2-containing compounds are of significant synthetic value but typically synthesized from environmentally harmful hydrochlorofluorocarbons (CFCs). Herein, we report the use a well-defined Cu(I) complex, [(bpy)Cu(CF3)], as an efficient trifluoromethylating reagent for direct trifluoromethylation trichloroalkanes under mild conditions, affording products with excellent chemoselectivity. This protocol also enabled gram-scale synthesis cyhalothric acid ester, which is key intermediate in production pyrethroid pesticides.

Language: Английский

Citations

0