Vitamin B₁₂‐Photocatalyzed Cyclopropanation of Electron‐Deficient Alkenes Using Dichloromethane as the Methylene Source**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(2)

Published: Nov. 28, 2023

Abstract The cyclopropyl group is of great importance in medicinal chemistry, as it can be leveraged to influence a range pharmaceutical properties drug molecules. This report describes Vitamin B 12 ‐photocatalyzed approach for the cyclopropanation electron‐deficient alkenes using dichloromethane (CH 2 Cl ) methylene source. reaction proceeds good excellent yields under mild conditions, has functional compatibility, and highly chemoselective. scope could also extended preparation D ‐cyclopropyl methyl‐substituted adducts starting from CD 1,1‐dichloroethane, respectively.

Language: Английский

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Effect of 6,6′-Substituents on Bipyridine-Ligated Ni Catalysts for Cross-Electrophile Coupling

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(9), P. 6897 - 6914

Published: April 19, 2024

A family of 4,4′-tBu2-2,2′-bipyridine (tBubpy) ligands with substituents in either the 6-position, 4,4′-tBu2-6-Me-bpy (tBubpyMe), or 6 and 6′-positions, 4,4′-tBu2-6,6′-R2-bpy (tBubpyR2; R = Me, iPr, sBu, Ph, Mes), was synthesized. These were used to prepare Ni complexes 0, I, II oxidation states. We observed that 6′-positions tBubpy ligand impact properties complexes. For example, bulkier 6,6′-positions better stabilized (tBubpyR2)NiICl species resulted a cleaner reduction from (tBubpyR2)NiIICl2. However, hindered prevented coordination tBubpyR2 Ni0(cod)2. In addition, by using type (tBubpyMe)NiCl2 (tBubpyR2)NiCl2 as precatalysts for different XEC reactions, we demonstrated 6,6′-substituents lead major differences catalytic performance. Specifically, while (tBubpyMe)NiIICl2 is one most active catalysts reported date can facilitate reactions at room temperature, lower turnover frequencies containing ligands. detailed study on intermediates (tBubpy)Ni(Ar)I (tBubpyMe2)Ni(Ar)I revealed several factors likely contributed activity. whereas are low spin relatively stable, high-spin less stable. Furthermore, captures primary benzylic alkyl radicals more slowly than (tBubpy)Ni(Ar)I, consistent activity former catalysis. Our findings will assist design tailor-made Ni-catalyzed transformations.

Language: Английский

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Tunable and Practical Homogeneous Organic Reductants for Cross-Electrophile Coupling

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(49), P. 21024 - 21036

Published: Nov. 30, 2021

The syntheses of four new tunable homogeneous organic reductants based on a tetraaminoethylene scaffold are reported. have enhanced air stability compared to current for metal-mediated reductive transformations, such as cross-electrophile coupling (XEC), and solids at room temperature. In particular, the weakest reductant is indefinitely stable in has reduction potential −0.85 V versus ferrocene, which significantly milder than conventional used XEC. All can facilitate C(sp2)–C(sp3) Ni-catalyzed XEC reactions compatible with complex substrates that relevant medicinal chemistry. span range nearly 0.5 potential, allows control over rate electron transfer events Specifically, we report strategy controlled alkyl radical generation key our approach tune from Katritzky salts, liberate radicals upon single reduction, by varying redox potentials salt utilized catalysis. Using method, perform between benzylic salts aryl halides. method tolerates variety functional groups, some particularly challenging most transformations. Overall, expect will both replace transformations due their relatively facile synthesis lead development novel synthetic methods tunability.

Language: Английский

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Nickel-Catalyzed Reductive Cross-Coupling of Heteroaryl Chlorides and Aryl Chlorides

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(20), P. 12785 - 12793

Published: Oct. 6, 2021

We report a nickel-catalyzed cross-electrophile coupling reaction of aryl chlorides and heteroaryl enabled by synergistic combination consisting halide effects the addition magnesium salt. The relies on electronic difference between aromatic heteroaromatic partners to afford cross-coupled biaryl products using single catalyst. A variety heterocycles were amenable reaction, as well wide range chlorides, with electron-deficient performing best in reaction. Preliminary mechanistic evidence demonstrates MgCl2 is essential accelerating reduction Ni(II), that small quantities iodide lead improved yields.

Language: Английский

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ChemBead Enabled High‐Throughput Cross‐Electrophile Coupling Reveals a New Complementary Ligand

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(51), P. 12981 - 12986

Published: July 7, 2021

High-throughput experimentation (HTE) methods are central to modern medicinal chemistry. While many HTE approaches C-N and Csp

Language: Английский

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Machine Learning-Guided Development of Trialkylphosphine Ni^(I) Dimers and Applications in Site-Selective Catalysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(28), P. 15414 - 15424

Published: July 6, 2023

Owing to the unknown correlation of a metal’s ligand and its resulting preferred speciation in terms oxidation state, geometry, nuclearity, rational design multinuclear catalysts remains challenging. With goal accelerate identification suitable ligands that form trialkylphosphine-derived dihalogen-bridged Ni(I) dimers, we herein employed an assumption-based machine learning approach. The workflow offers guidance space for desired without (or only minimal) prior experimental data points. We experimentally verified predictions synthesized numerous novel dimers as well explored their potential catalysis. demonstrate C–I selective arylations polyhalogenated arenes bearing competing C–Br C–Cl sites under 5 min at room temperature using 0.2 mol % newly developed dimer, [Ni(I)(μ-Br)PAd2(n-Bu)]2, which is so far unmet with alternative dinuclear or mononuclear Ni Pd catalysts.

Language: Английский

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A Ball-Milling-Enabled Cross-Electrophile Coupling

Organic Letters, Journal Year: 2021, Volume and Issue: 23(16), P. 6337 - 6341

Published: Aug. 3, 2021

The nickel-catalyzed cross-electrophile coupling of aryl halides and alkyl enabled by ball-milling is herein described. Under a mechanochemical manifold, the reductive C–C bond formation was achieved in absence bulk solvent air/moisture sensitive setups, reaction times 2 h. mechanical action provided ball milling permits use range zinc sources to turnover nickel catalytic cycle, enabling synthesis 28 coupled products.

Language: Английский

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Mechanistic views and computational studies on transition-metal-catalyzed reductive coupling reactions

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(24), P. 9986 - 10015

Published: Jan. 1, 2022

Theoretical studies on transition-metal-catalyzed reductive coupling reactions have been summarized and discussed.

Language: Английский

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Nickel‐Catalyzed C−I‐Selective C(sp²)−C(sp³) Cross‐Electrophile Coupling of Bromo(iodo)arenes with Alkyl Bromides

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(26)

Published: May 4, 2023

Despite several methodologies established for C(sp2 )-I selective )-C(sp3 ) bond formations, achieving arene-flanked quaternary carbons by cross-coupling of tertiary alkyl precursors with bromo(iodo)arenes in a manner is rare. Here we report general Ni-catalyzed cross-electrophile coupling (XEC) reaction, which, beyond 3° bromides (for constructing carbons), 2° and 1° are also demonstrated to be viable partners. Moreover, this mild XEC displays excellent selectivity functional group compatibility. The practicality simplifying the routes medicinally relevant synthetically challenging compounds. Extensive experiments show that terpyridine-ligated NiI halide can exclusively activate bromides, forming -alkyl complex through Zn reduction. Attendant density theory (DFT) calculations reveal two different pathways oxidative addition bromo(iodo)arenes, explaining both high generality our XEC.

Language: Английский

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Computationally Guided Ligand Discovery from Compound Libraries and Discovery of a New Class of Ligands for Ni-Catalyzed Cross-Electrophile Coupling of Challenging Quinoline Halides

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(10), P. 6947 - 6954

Published: March 1, 2024

Although screening technology has heavily impacted the fields of metal catalysis and drug discovery, its application to discovery new catalyst classes been limited. The diversity on- off-cycle pathways, combined with incomplete mechanistic understanding, means that screens potential ligands have thus far guided by intuitive analysis binding potential. This resulted in ligands, but low hit rates limited use this strategy because large require considerable cost effort. Here, we demonstrate a method identify promising directions via simple scalable computational linear regression tools leads substantial improvement rate, enabling smaller find ligands. approach particular example Ni-catalyzed cross-electrophile coupling aryl halides alkyl revealed previously overlooked trend: reactions more electron-poor amidine result higher yield. Focused utilizing trend were successful than serendipity-based led two types pyridyl oxadiazoles oximes. These are especially effective for couplings bromo- chloroquinolines isoquinolines, where they now state art. simplicity these models parameters derived from metal-free ligand structures should make widely accessible.

Language: Английский

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