Deoxygenative radical cross-coupling of C(sp3)−O/C(sp3)−H bonds promoted by hydrogen-bond interaction DOI Creative Commons
Yue Wang, Suping Zhang,

Ke Zeng

et al.

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

Published: Aug. 8, 2024

Building C(sp3)-rich architectures using simple and readily available starting materials will greatly advance modern drug discovery. C(sp3)−H C(sp3)−O bonds are commonly used to strategically disassemble construct bioactive compounds, respectively. However, the direct cross coupling of these two chemical form C(sp3)−C(sp3) is rarely explored in existing literature. Conventional methods for forming via radical-radical pathways often suffer from poor selectivity, severely limiting their practicality synthetic applications. In this study, we present a single electron transfer (SET) strategy that enables cleavage amine α-C − H heterobenzylic C O bonds. Preliminary mechanistic studies reveal hydrogen bond interaction between substrates phosphoric acid facilitates cross-coupling radicals with high chemoselectivity. This methodology provides an effective approach variety aza-heterocyclic unnatural amino acids molecules. Herein, authors report

Language: Английский

Metallaphotoredox catalysis for sp3C–H functionalizations through hydrogen atom transfer (HAT) DOI
Jingchang Zhang, Magnus Rueping

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(12), P. 4099 - 4120

Published: Jan. 1, 2023

sp 3 C–H functionalizations under the combination of photocatalytic HAT and transition metal catalysis.

Language: Английский

Citations

98
Recent advances in the accessibility, synthetic utility, and biological applications of aziridines DOI Creative Commons
Christian Dank, Laura Ielo

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(22), P. 4553 - 4573

Published: Jan. 1, 2023

Compounds featuring aziridine moieties are widely known and extensively reported in the literature. Due to their great potential from both synthetic pharmacological points of view, many researchers have focused efforts on development new methodologies for preparation transformation these interesting compounds. Over years, more ways obtain molecules bearing three-membered functional groups, which challenging due inherent reactivity, been described. Among them, several sustainable. In this review, we report recent advances biological chemical evolution derivatives, particular, variety described synthesis aziridines transformations leading formation such as 4-7 membered heterocycles pharmaceutical interest promising activities.

Language: Английский

Citations

39
Branched-Selective Cross-Electrophile Coupling of 2-Alkyl Aziridines and (Hetero)aryl Iodides Using Ti/Ni Catalysis DOI
Wendy L. Williams,

Neyci E. Gutiérrez-Valencia,

Abigail G. Doyle

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(44), P. 24175 - 24183

Published: Oct. 27, 2023

The arylation of 2-alkyl aziridines by nucleophilic ring-opening or transition-metal-catalyzed cross-coupling enables facile access to biologically relevant β-phenethylamine derivatives. However, both approaches largely favor C–C bond formation at the less-substituted carbon aziridine, thus enabling only linear products. Consequently, despite attractive disconnection that it poses, synthesis branched arylated products from has remained inaccessible. Herein, we address this long-standing challenge and report first branched-selective with aryl iodides. This unique selectivity is enabled a Ti/Ni dual-catalytic system. We demonstrate robustness method twofold approach: an additive screening campaign probe functional group tolerance feature-driven substrate scope study effect local steric electronic profile each coupling partner on reactivity. Furthermore, diversity generation predictive reactivity models guided mechanistic understanding. Mechanistic studies demonstrated arises TiIII-induced radical aziridine.

Language: Английский

Citations

27
Low-energy photoredox catalysis DOI
David C. Cabanero, Tomislav Rovis

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Language: Английский

Citations

16
Photoredox/Nickel Dual Catalysis-Enabled Aryl Formylation with 2,2-Dimethoxy-N,N-dimethylethan-1-amine as CO Source DOI
Jie Gao,

Xian‐Chen He,

Yanling Liu

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(7), P. 1478 - 1482

Published: Feb. 9, 2024

Herein, a dual photoredox/nickel catalyzed formylation of aryl bromide with commercially available 2,2-dimethoxy-N,N-dimethylethan-1-amine as an effective CO source has been successfully achieved, delivering series aromatic aldehydes in moderate to good yields. Compared the traditional reductive carbonylation process, this newly designed synthetic protocol provides straightforward toolbox access aldehydes, obviating use carbon monoxide and stoichiometric reductants. Finally, utility direct reaction was demonstrated pharmaceutical analogue synthesis.

Language: Английский

Citations

10
Photogenerated Ni(I)–Bipyridine Halide Complexes: Structure–Function Relationships for Competitive C(sp2)–Cl Oxidative Addition and Dimerization Reactivity Pathways DOI
David A. Cagan, Daniel Bím, Brendon J. McNicholas

et al.

Inorganic Chemistry, Journal Year: 2023, Volume and Issue: 62(24), P. 9538 - 9551

Published: June 6, 2023

We report the facile photochemical generation of a library Ni(I)-bpy halide complexes (Ni(I)(Rbpy)X (R = t-Bu, H, MeOOC; X Cl, Br, I) and benchmark their relative reactivity toward competitive oxidative addition off-cycle dimerization pathways. Structure-function relationships between ligand set are developed, with particular emphasis on rationalizing previously uncharacterized ligand-controlled high energy challenging C(sp2)-Cl bonds. Through dual Hammett computational analysis, mechanism formal is found to proceed through an SNAr-type pathway, consisting nucleophilic two-electron transfer Ni(I) 3d(z2) orbital Caryl-Cl σ* orbital, which contrasts observed for activation weaker C(sp2)-Br/I The bpy substituent provides strong influence reactivity, ultimately determining whether or even occurs. Here, we elucidate origin this as arising from perturbations effective nuclear charge (Zeff) center. Electron donation metal decreases Zeff, leads significant destabilization entire 3d manifold. Decreasing electron binding energies powerful donor activate These changes also prove have analogous effect dimerization, in Zeff leading more rapid dimerization. Ligand-induced modulation thus tunable target by can be altered, providing direct route stimulate stronger C-X bonds potentially unveiling new ways accomplish Ni-mediated photocatalytic cycles.

Language: Английский

Citations

21
Nickel-Catalyzed Enantioselective C(sp3)–C(sp3) Cross-Electrophile Coupling of N-Sulfonyl Styrenyl Aziridines with Alkyl Bromides DOI
Yun Lan,

Qiaoying Han,

Pingyong Liao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(37), P. 25426 - 25432

Published: Sept. 4, 2024

Herein, we report the first example of a highly enantioselective alkylative aziridine ring opening. Under catalysis chiral nickel/pyridine-imidazoline complex, asymmetric C(sp

Language: Английский

Citations

7
Dynamic Kinetic Activation of Aziridines Enables Radical-Polar Crossover (4 + 3) Cycloaddition with 1,3-Dienes DOI
Lei Wang, Panpan Zhou, Dong Xie

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

The cycloaddition of aziridines with unsaturated compounds is a valuable method for synthesizing nitrogen heterocycles. However, this process predominantly substrate-controlled, posing significant challenges in regulating the regioselectivity C–N bond cleavage. In study, we report nickel-catalyzed dynamic kinetic activation strategy that enables catalyst-controlled aziridines. Various types aziridines, including 2-phenyl, 2-carbonyl, 2-alkyl, and disubstituted consistently cleave their more sterically hindered bonds to generate 1,3-radical anion intermediates. These intermediates participate highly regioselective 1,4-Heck/allylic substitution cascade aromatic branched 1,3-dienes, resulting radical-polar crossover (4 + 3) produces seven-membered azepine products. This approach not only complements traditional dipolar cycloaddition, which typically act as zwitterionic 1,3-dipoles, but also introduces an unusual mode 1,3-dienes. Experimental investigations density functional theory (DFT) calculations provide insight into reaction mechanism.

Language: Английский

Citations

1
Electrochemical Ring Opening and [3 + 2] Cycloaddition of Aziridines: Access to 1,2-Bifunctionalized Products and Imidazolines DOI
Shiv Dutt,

Neelam Duhan,

Vikas Kale

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: 27(4), P. 989 - 994

Published: Jan. 21, 2025

Herein, we report an electricity-driven activation of aziridine via direct anodic oxidation to give N-heterocycles and 1,2-bifunctionalized products by excluding any oxidant/reductant or metal catalyst. Many structurally modified aziridines were employed in the presence different nitriles. A large variety nucleophiles screened furnish chemoselectively O-alkylated C-alkylated products. Late-stage derivatization with natural medicinally active compounds has also been done. Remarkably, our strategy was found be a greener, sustainable, atom-economical approach (E-factor = ca. 0.8). Azetidine compatible protocol generated six-membered N-heterocycles. The detailed mechanistic study highlighted that reaction is driven generation radical cation followed SN2 nucleophilic attack.

Language: Английский

Citations

1
Nickel-Catalyzed Rearranged Alkenylation of 2-Arylaziridines with Aryl Alkenes to Access Allylamines DOI
Xiangkai Kong,

Ming-Bai Gou,

Bo Li

et al.

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

Published: March 10, 2025

The transition-metal-catalyzed ring-opening functionalization of aziridines presents a promising approach for synthesizing structurally complex amines. However, the rearranged poses significant challenges. Herein, we report first alkenylation with aryl alkenes via Ni-Brønsted acid co-catalysis, leading to rapid synthesis diverse array allylamines yields reaching up 91%. Mechanistic studies suggest that reaction occurs through rearrangement aziridine generate an imine intermediate. This intermediate is subsequently captured by alkene under nickel catalysis, ultimately formation allylamines.

Language: Английский

Citations

1