Photoinduced copper-catalyzed C–N coupling with trifluoromethylated arenes

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 14, 2023

Selective defluorinative functionalization of trifluoromethyl group (-CF3) is an attractive synthetic route to the pharmaceutically privileged fluorine-containing moiety. Herein, we report a strategy based on photoexcited copper catalysis activate C-F bond di- or trifluoromethylated arenes for divergent radical C-N coupling with carbazoles and aromatic amines. The use different ligands can tune reaction products diversity. A range substituted, structurally diverse α,α-difluoromethylamines be obtained from via carbazoles, while interesting double ready difluoromethylated arenes. Based this success, carbazole-centered PNP ligand designed optimal ligand, enabling copper-catalyzed construction imidoyl fluorides amines through functionalization. Interestingly, 1,2-difluoroalkylamination styrenes also developed, delivering γ,γ-difluoroalkylamines, bioisostere β-aminoketones, in synthetically useful yields. DFT studies reveal inner-sphere electron transfer mechanism Cu-catalyzed selective activation C(sp3)-F bonds.

Language: Английский

---

Copper-Catalyzed Enantioconvergent Radical C(sp³)–N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(27), P. 14686 - 14696

Published: July 1, 2023

The enantioconvergent C(sp3)-N cross-coupling of racemic alkyl halides with (hetero)aromatic amines represents an ideal means to afford enantioenriched N-alkyl yet has remained unexplored due the catalyst poisoning specifically for strong-coordinating heteroaromatic amines. Here, we demonstrate a copper-catalyzed radical activated under ambient conditions. key success is judicious selection appropriate multidentate anionic ligands through readily fine-tuning both electronic and steric properties formation stable rigid chelating Cu complex. Thus, this kind ligand could not only enhance reducing capability copper provide pathway but also avoid coordination other coordinating heteroatoms, thereby overcoming and/or chiral displacement. This protocol covers wide range coupling partners (89 examples secondary/tertiary bromides/chlorides amines) high functional group compatibility. When allied follow-up transformations, it provides highly flexible platform access synthetically useful amine building blocks.

Language: Английский

---

Aminodealkenylation: Ozonolysis and copper catalysis convert C(sp ³ )–C(sp ² ) bonds to C(sp ³ )–N bonds

Science, Journal Year: 2023, Volume and Issue: 381(6660), P. 877 - 886

Published: Aug. 24, 2023

Great efforts have been directed toward alkene π bond amination. In contrast, analogous functionalization of the adjacent C(sp

Language: Английский

---

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

---

Recent advances in C(sp³)–N bond formation via metallaphoto-redox catalysis

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(50), P. 6340 - 6361

Published: Jan. 1, 2024

In this review, the state-of-the-art advances in radical-involved C(sp 3 )–N bond formation via metallaphotoredox catalysis have been highlighted, which are organized according to different catalytic modes, reaction types, and substrate classes.

Language: Английский

---

NIR-II emissive anionic copper nanoclusters with intrinsic photoredox activity in single-electron transfer

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 1, 2024

Abstract Ultrasmall copper nanoclusters have recently emerged as promising photocatalysts for organic synthesis, owing to their exceptional light absorption ability and large surface areas efficient interactions with substrates. Despite significant advances in cluster-based visible-light photocatalysis, the types of transformations that can catalyze remain limited date. Herein, we report a structurally well-defined anionic Cu 40 nanocluster emits second near-infrared region (NIR-II, 1000−1700 nm) after photoexcitation conduct single-electron transfer fluoroalkyl iodides without need external ligand activation. This photoredox-active efficiently catalyzes three-component radical couplings alkenes, iodides, trimethylsilyl cyanide under blue-LED irradiation at room temperature. A variety fluorine-containing electrophiles nucleophile be added onto an array including styrenes aliphatic olefins. Our current work demonstrates viability using readily accessible metal establish photocatalytic systems high degree practicality reaction complexity.

Language: Английский

---

Photoexcited Palladium-Catalyzed Deracemization of Allenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(30), P. 21137 - 21146

Published: July 18, 2024

The different enantiomers of specific chiral molecules frequently exhibit disparate biological, physiological, or pharmacological properties. Therefore, the efficient synthesis single is particular importance not only to pharmaceutical sector but also other industrial sectors, such as agrochemical and fine chemical industries. Deracemization, a process during which racemic mixture converted into nonracemic product with 100% atom economy theoretical yield, most straightforward method access enantioenriched challenging task due decrease in entropy microscopic reversibility. Axially allenes bear distinctive structure two orthogonal cumulative π-systems are acknowledged synthetically versatile synthons organic synthesis. selective creation axially high optical purity under mild reaction conditions has always been very popular hot topic remains challenging. Herein, photoexcited palladium-catalyzed deracemization nonprefunctionalized disubstituted disclosed. This provides an economical strategy accommodate broad scope good enantioselectivities yields (53 examples, up 96% yield 95% ee). use suitable palladium complex visible light irradiation essential factor achieving this transformation. A metal-to-ligand charge transfer mechanism was proposed based on control experiments density functional theory calculations. Quantum mechanical studies implicate dual modes asymmetric induction behind our new protocol: (1) sterically controlled stereoselective binding one allene enantiomer ground-state (2) facile, noncovalent interaction-driven excited-state isomerization toward opposite enantiomer. success newly established photochemical should provide inspiration for expansion multisubstituted will open mode enantioselective catalysis.

Language: Английский

---

Copper-Catalyzed Enantioconvergent Radical N-Alkylation of Diverse (Hetero)aromatic Amines

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9444 - 9454

Published: March 21, 2024

The 3d transition metal-catalyzed enantioconvergent radical cross-coupling provides a powerful tool for chiral molecule synthesis. In the classic mechanism, bond formation relies on interaction between nucleophile-sequestered metal complexes and radicals, limiting nucleophile scope to sterically uncongested ones. coupling of congested nucleophiles poses significant challenge due difficulties in transmetalation, restricting reaction generality. Here, we describe probable outer-sphere nucleophilic attack mechanism that circumvents challenging transmetalation associated with nucleophiles. This strategy enables general copper-catalyzed N-alkylation aromatic amines secondary/tertiary alkyl halides exhibits catalyst-controlled stereoselectivity. It accommodates diverse amines, especially bulky secondary primary ones deliver value-added (>110 examples). is expected inspire more nucleophiles, particularly ones, accelerate

Language: Английский

---

Transition-metal-catalyzed enantioselective C–N cross-coupling

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(19), P. 9560 - 9581

Published: Jan. 1, 2024

Chiral amine scaffolds are among the most important building blocks in natural products, drug molecules, and functional materials, which have prompted chemists to focus more on their synthesis. Among accomplishments chiral synthesis, transition-metal-catalyzed enantioselective C-N cross-coupling is considered one of efficient protocols. This approach combines traditional C(sp

Language: Английский

---

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

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

---