Mechanistic Investigation of Ni-Catalyzed Reductive Cross-Coupling of Alkenyl and Benzyl Electrophiles

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(27), P. 14705 - 14715

Published: June 26, 2023

Mechanistic investigations of the Ni-catalyzed asymmetric reductive alkenylation

Language: Английский

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Alcohol-alcohol cross-coupling enabled by S _H 2 radical sorting

Science, Journal Year: 2024, Volume and Issue: 383(6689), P. 1350 - 1357

Published: March 21, 2024

Alcohols represent a functional group class with unparalleled abundance and structural diversity. In an era of chemical synthesis that prioritizes reducing time to target maximizing exploration space, harnessing these building blocks for carbon-carbon bond-forming reactions is key goal in organic chemistry. particular, leveraging single activation mode form new C(sp

Language: Английский

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Mechanisms of Photoredox Catalysis Featuring Nickel–Bipyridine Complexes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(11), P. 9055 - 9076

Published: May 29, 2024

Metallaphotoredox catalysis can unlock useful pathways for transforming organic reactants into desirable products, largely due to the conversion of photon energy chemical potential drive redox and bond transformation processes. Despite importance these processes cross-coupling reactions other transformations, their mechanistic details are only superficially understood. In this review, we have provided a detailed summary various photoredox mechanisms that been proposed date Ni-bipyridine (bpy) complexes, focusing separately on photosensitized direct excitation reaction By highlighting multiple key findings, depict how mechanisms, which ultimately define substrate scope, themselves defined by ground- excited-state geometric electronic structures Ni-based intermediates. We further identify knowledge gaps motivate future studies development synergistic research approaches spanning physical, organic, inorganic chemistry communities.

Language: Английский

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Computational Methods Enable the Prediction of Improved Catalysts for Nickel-Catalyzed Cross-Electrophile Coupling

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 3043 - 3051

Published: Jan. 26, 2024

Cross-electrophile coupling has emerged as an attractive and efficient method for the synthesis of C(sp2)–C(sp3) bonds. These reactions are most often catalyzed by nickel complexes nitrogenous ligands, especially 2,2′-bipyridines. Precise prediction, selection, design optimal ligands remains challenging, despite significant increases in reaction scope mechanistic understanding. Molecular parameterization statistical modeling provide a path to development improved bipyridine that will enhance selectivity existing broaden electrophiles can be coupled. Herein, we describe generation computational ligand library, correlation observed outcomes with features silico Ni-catalyzed cross-electrophile coupling. The new nitrogen-substituted display 5-fold increase product formation versus homodimerization when compared current state art. This yield was general several couplings, including challenging aryl chloride N-alkylpyridinium salt.

Language: Английский

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Insights into Recent Nickel-Catalyzed Reductive and Redox C–C Coupling of Electrophiles, C(sp³)–H Bonds and Alkenes

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(8), P. 1149 - 1162

Published: March 28, 2024

ConspectusTransition metal-catalyzed reductive cross-coupling of two carbon electrophiles, also known as cross-electrophile coupling (XEC), has transformed the landscape C–C chemistry. Nickel catalysts, in particular, have demonstrated exceptional performance facilitating XEC reactions, allowing for diverse elegant transformations by employing various electrophiles to forge bonds. Nevertheless, several crucial challenges remain be addressed. First, intrinsic chemoselectivity between structurally similar Ni-catalyzed C(sp3)–C(sp3) and C(sp2)–C(sp2) not been well understood; this necessitates an excess one partners achieve synthetically useful outcomes. Second, substitution economically environmentally benign nonmetal reductants Zn/Mn can help scale up reactions avoid trace metals pharmaceutical products, but research direction progressed slowly. Finally, it is highly warranted leverage mechanistic insights from develop innovative thermoredox protocols, specifically designed tackle associated with difficult substrates such C(sp3)–H bonds unactivated alkenes.In Account, we address aforementioned issues reviewing our recent work on C–X C–O strategy alkenes, use diboron esters coupling. We focus perspectives transformations, particularly how key C–NiIII–C intermediates are generated, order explain chemoselective regioselective results. The Account consists four sections. discuss Zn/Mn-mediated bond formations based selected alkyl/aryl, allyl/benzyl, other electrophiles. describe versatile C(sp3)–C(sp2) couplings, emphasis consideration construction Third, leveraging C(sp3)–O effective C(sp3)–C formation via situ halogenation alcohols preparation α-vinylated -arylated unusual amino esters. In final section, illustrate functionalization challenging aryl alkyl halides afford taking advantage compatibility Zn oxidant di-tert-butylperoxide (DTBP). Furthermore, a SiH/DTBP-mediated hydrodimerization terminal alkenes selectively head-to-head methyl branched This process, conducted presence or absence catalytic CuBr2, provides solution long-standing challenge: site-selective hydrocoupling produce

Language: Английский

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Kinetically-Controlled Ni-Catalyzed Direct Carboxylation of Unactivated Secondary Alkyl Bromides without Chain Walking

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(3), P. 1753 - 1759

Published: Jan. 9, 2024

Herein, we report the direct carboxylation of unactivated secondary alkyl bromides enabled by merger photoredox and nickel catalysis, a previously inaccessible endeavor in arena. Site-selectivity is dictated kinetically controlled insertion CO2 at initial C(sp3)–Br site rapid formation Ni(I)–alkyl species, thus avoiding undesired β-hydride elimination chain-walking processes. Preliminary mechanistic experiments reveal subtleties stereoelectronic effects for guiding reactivity site-selectivity.

Language: Английский

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Ligand-Enabled “Two-in-One” Metallaphotocatalytic Cross Couplings

ACS Catalysis, Journal Year: 2025, Volume and Issue: 15(3), P. 1635 - 1654

Published: Jan. 15, 2025

Metallaphotoredox cross coupling (MCC) is ranking among the most advanced synthetic methodology as it can access chemical space that difficult to attain under conventional conditions. Earlier developed MCC mandates an independent transition metal catalyst and respective photocatalyst, thus constituting a dual catalytic manifold. Complementarily, paradigm-shifting metallaphotoredox strategy capitalizes on single photoreactive complex emerging, which brings not only operational simplification but also unexpected mechanistic insights. This perspective compiled recent advances in monocatalytic couplings categorized them based ligands confer distinct photoreactivities various mechanisms. To this end, ligand-enabled oxidative addition, transmetalation, reductive elimination other radical-involving pathways were summarized with notable examples. In way, we wish provide handy guideline for readers who are interested emerging field inspire more future endeavors MCCs beyond.

Language: Английский

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A Paradigm Shift in Catalysis: Electro- and Photomediated Nickel-Catalyzed Cross-Coupling Reactions

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(20), P. 2851 - 2865

Published: Sept. 29, 2023

ConspectusTransition-metal catalyzed cross-coupling reactions are fundamental in organic chemistry, facilitating strategic bond formations for accessing natural products, materials, agrochemicals, and pharmaceuticals. Redox chemistry enables access to elusive mechanisms through single-electron processes as an alternative classical two-electron strategies predominated by palladium catalysis. The seminal reports of Baran, MacMillan, Doyle, Molander, Weix, Lin, Fu, Reisman, others merging redox perturbation (photochemical, electrochemical, purely chemical) with catalysis pivotal the current resurgence mechanistic understanding first-row transition metal-based hallmark this platform is systematic modulation transition-metal oxidation states a photoredox catalyst or at heterogeneous electrode surface. Electrocatalysis photocatalysis enhance metal catalysis' capacity formation electron- energy-transfer that promote otherwise challenging elementary steps mechanisms. Cross-coupling conditions promoted electrocatalysis mild, proceeds exceptionally high chemoselectivity wide functional group tolerance. interfacing abundant has brought about paradigm shift technology practitioners quickly applying these tools synthesizing fine chemicals pharmaceutically relevant motifs. In particular, merger Ni electro- photochemistry ushered new era carbon-carbon carbon-heteroatom cross-couplings expanded generality compared their thermally driven counterparts. Over past decade, we have developed enabling photo- electrochemical methods throughout our combined research experience industry (BMS, AstraZeneca) academia (Professor Scripps Research) cross-disciplinary collaborative environments. Account, will outline recent progress from present laboratories electrochemically mediated Ni-catalyzed cross-couplings. By highlighting methodologies, also compare features both photochemical forging C(sp2)-C(sp3), C(sp3)-C(sp3), C-O, C-N, C-S bonds. Through side-by-side comparisons, hope demystify subtle differences between two complementary enact control over Finally, building off collective ourselves rest community, propose tactical user guide aid practitioner rapidly such synthetic designs.

Language: Английский

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Comproportionation and disproportionation in nickel and copper complexes

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(19), P. 6601 - 6616

Published: Jan. 1, 2023

This review covers factors that contribute to comproportionation and disproportionation reactions in transition metal complexes provide insight into the importance of these electron transfer events Ni- Cu-catalyzed transformations.

Language: Английский

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Nickel-Catalyzed Radical Mechanisms: Informing Cross-Coupling for Synthesizing Non-Canonical Biomolecules

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(24), P. 3640 - 3653

Published: Nov. 30, 2023

ConspectusNickel excels at facilitating selective radical chemistry, playing a pivotal role in metalloenzyme catalysis and modern cross-coupling reactions. Radicals, being nonpolar neutral, exhibit orthogonal reactivity to nucleophilic basic functional groups commonly present biomolecules. Harnessing this compatibility, we delve into the application of nickel-catalyzed pathways synthesis noncanonical peptides carbohydrates, critical for chemical biology studies drug discovery.We previously characterized sequential reduction mechanism that accounts chemoselectivity cross-electrophile coupling This catalytic cycle begins with nickel(I)-mediated generation from alkyl halides, followed by carbon capture nickel(II) complexes, concludes reductive elimination. These steps resonate mechanistic proposals cross-coupling, photoredox, electrocatalytic Herein, our insights each step involving radicals, including initiation, propagation, termination, nuances kinetics, origins selectivity, ligand effects.Radical C(sp3) electrophiles via one-electron oxidative addition low-valent nickel intermediates provides basis stereoconvergent couplings. Our electroanalytical elucidate concerted halogen atom abstraction mechanism, where electron transfer is coupled halide dissociation. Using pathway, have developed stereoselective dehydroalanine, peptides. In application, chiral ligands modulate stereochemical outcome through asymmetric protonation nickel-enolate intermediate.The expands scope promotes elimination formation high-valent nickel(III) species, governs chemo- stereoselectivity. We discovered nickel(II)-aryl efficiently traps radicals barrier ranging 7 9 kcal/mol, fast contrast, nickel(II)-alkyl captures form which was EPR spectroscopy. However, subsequent slow resulted minimal product formation. The observed high diastereoselectivity inspired investigations C-aryl C-acyl glycosylation redox auxiliary readily couples natural carbohydrates produces glycosyl upon photoredox activation. Nickel-catalyzed bromoarenes carboxylic acids leads diverse non-natural glycosides can facilitate discovery.Stoichiometric on well-defined d8-nickel complexes showcased means promote elimination, association, oxidation, addition.In final section, address influence electronic structure activity organonickel intermediates. Synthesis series characterization their structures led us postulate correlates coordination geometry. data reveal change shift potentials reaction intermediates, potentially altering Moreover, coordinating additives solvents may stabilize during adjusting activity, consistent known conditions.

Language: Английский

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