Reductive Cross-Coupling of Unreactive Electrophiles

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(17), P. 2491 - 2509

Published: Aug. 11, 2022

ConspectusTransition-metal-catalyzed reductive coupling of electrophiles has emerged as a powerful tool for the construction molecules. While major achievements have been made in field cross-couplings between organic halides and pseudohalides, an increasing number reports demonstrates reactions involving more readily available, low-cost, stable, but unreactive electrophiles. This account summarizes recent results our laboratory focusing on this topic. These findings typically include deoxygenative C–C alcohols, alkylation alkenyl acetates, C–Si chlorosilanes, C–Ge chlorogermanes.The alcohols with is synthetically appealing, potential chemistry remains to be disclosed. Our initial study focused reaction allylic aryl bromides by combination nickel Lewis acid catalysis. method offers selectivity that opposite classic Tsuji–Trost reactions. Further investigation benzylic led foundation dynamic kinetic cross-coupling strategy applications nickel-catalyzed arylation cobalt-catalyzed enantiospecific alkenylation alcohols. The titanium catalysis was later established produce carbon radicals directly from unactivated tertiary via C–OH cleavage. development their fragments delivers new methods all-carbon quaternary centers. shown high functionalization leaving primary secondary intact. Alkenyl acetates are inexpensive, environmentally friendly considered most attractive reagents. benzyl ammoniums alkyl mild approaches conversion ketones into aliphatic alkenes.Extensive studies enabled us extend cross-electrophile silicon germanium chemistry. harness ready availability chlorosilanes chlorogermanes suffer challenge low reactivity toward transition metals. Under catalysis, broad range couple well vinyl- hydrochlorosilanes. use partners formation functionalized alkylsilanes. seems less substrate-dependent, various common aryl, alkenyl, In general, functionalities such Grignard-sensitive groups (e.g., acid, amide, alcohol, ketone, ester), acid-sensitive ketal THP protection), fluoride chloride, bromide, tosylate mesylate, silyl ether, amine tolerated. provide access organosilicon organogermanium compounds, some which challenging obtain otherwise.

Language: Английский

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Modular Access to Chiral α-(Hetero)aryl Amines via Ni/Photoredox-Catalyzed Enantioselective Cross-Coupling

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(19), P. 8797 - 8806

Published: May 3, 2022

Chiral α-aryl N-heterocycles are commonly found in natural products, pharmaceutical agents, and chiral catalysts but remain challenging to access via asymmetric catalysis. Herein, we report a general modular approach for the direct enantioselective α-arylation of saturated azacycles acyclic N-alkyl benzamides nickel/photoredox dual This process exploits hydrogen atom transfer ability photoeliminated chlorine radicals convert corresponding α-amino alkyl that then coupled with ubiquitous inexpensive (hetero)aryl chlorides. These coupling reactions require no oxidants or organometallic reagents, feature feedstock starting materials, broad substrate scope, high enantioselectivities, applicable late-stage diversification medicinally relevant complex molecules. Mechanistic studies suggest nickel catalyst uncommonly plays multiple roles, accomplishing radical generation, capture, cross-coupling, induction.

Language: Английский

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Recent Advances in Asymmetric Organometallic Electrochemical Synthesis (AOES)

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

ConspectusIn recent years, our research group has dedicated significant effort to the field of asymmetric organometallic electrochemical synthesis (AOES), which integrates electrochemistry with transition metal catalysis. On one hand, we have rationalized that compounds can serve as molecular electrocatalysts (mediators) reduce overpotentials and enhance both reactivity selectivity reactions. other conditions for catalysis be substantially improved through electrochemistry, enabling precise modulation metal's oxidation state by controlling potentials regulating electron transfer rate via current adjustments. This synergistic approach addresses key challenges inherent in traditional catalysis, particularly those related use redox-active chemical reagents. Furthermore, redox conveniently tuned modifying their ligands, thereby governing reaction regioselectivity stereoselectivity. As a result, AOES emerged powerful promising tool chiral compounds.In this Account, summarize contextualize efforts AOES. Our primary strategy involves leveraging controllability potential regulate organometallics, facilitating desired An efficient platform was established under mild conditions, significantly reducing reliance on been systematically categorized into three sections based distinct electrolysis modes: combined anodic oxidation, cathodic reduction, paired electrolysis. In each section, highlight innovative discoveries tailored unique characteristics respective modes.In many transformations, metal-catalyzed reactions involving reagents utilizing exhibit similar reactivities. However, also observed notable differences certain cases. These findings include following: (1) Enhanced efficiency synthesis: instance, Rh-catalyzed enantioselective functionalization C–H bonds demonstrates superior efficiency. (2) Expanded scope transformations: previously challenging achieved due tunability potentials. A example is reductive coupling aryl chlorides, expands range accessible transformations. Additionally, mechanistic studies explore techniques intrinsic such controlled experiments, impact electrode materials catalyst performance, cyclic voltammetry studies. investigations provide more intuitive understanding behavior catalysts study mechanisms, guide design new catalytic systems.The advancements offer robust environmentally friendly sustainable selective By integrating developed versatile organic not only enhances but reduces environmental impact. We anticipate Account will stimulate further innovation realm AOES, leading discovery systems development synthetic methodologies.

Language: Английский

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Zinc and manganese redox potentials in organic solvents and their influence on nickel-catalysed cross-electrophile coupling

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

Published: Sept. 6, 2024

Language: Английский

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Cross-Electrophile Coupling: Principles, Methods, and Applications in Synthesis

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Cross-electrophile coupling (XEC), defined by us as the cross-coupling of two different σ-electrophiles that is driven catalyst reduction, has seen rapid progression in recent years. As such, this review aims to summarize field from its beginnings up until mid-2023 and provide comprehensive coverage on synthetic methods current state mechanistic understanding. Chapters are split type bond formed, which include C(sp

Language: Английский

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A General, Multimetallic Cross-Ullmann Biheteroaryl Synthesis from Heteroaryl Halides and Heteroaryl Triflates

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(51), P. 21484 - 21491

Published: Dec. 17, 2021

Despite their importance to medicine and materials science, the synthesis of biheteroaryls by cross-coupling remains challenging. We describe here a new, general approach biheteroaryls: Ni- Pd-catalyzed multimetallic cross-Ullmann coupling heteroaryl halides with triflates. An array 5-membered, 6-membered, fused bromides chlorides, as well aryl triflates derived from heterocyclic phenols, proved be viable substrates in this reaction (62 examples, 63 ± 17% average yield). The generality was further demonstrated 96-well plate format at 10 μmol scale. 96 possible products provided >90% hit rate under single set conditions. Further, low-yielding combinations could rapidly optimized "Toolbox Plate" ligands, additives, reductants.

Language: Английский

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Synthesis of Nickel(I)–Bromide Complexes via Oxidation and Ligand Displacement: Evaluation of Ligand Effects on Speciation and Reactivity

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(35), P. 19368 - 19377

Published: Aug. 23, 2023

Nickel’s +1 oxidation state has received much interest due to its varied and often enigmatic behavior in increasingly popular catalytic methods. In part, the lack of understanding about NiI results from common synthetic strategies limiting breadth complexes that are accessible for mechanistic study catalyst design. We report an oxidative approach using tribromide salts allows generation a well-defined precursor, [NiI(COD)Br]2, as well several new complexes. Included among them bearing bulky monophosphines, which structure–speciation relationships established reactivity Suzuki–Miyaura coupling (SMC) is investigated. Notably, these routes also allow synthesis monomeric t-Bubpy-bound complexes, not previously been achieved. These react with aryl halides, can enable challenging investigations present opportunities catalysis synthesis.

Language: Английский

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Nickel-Catalyzed Electroreductive Coupling of Alkylpyridinium Salts and Aryl Halides

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(14), P. 9336 - 9345

Published: June 28, 2023

An electrochemical, nickel-catalyzed reductive coupling of alkylpyridinium salts and aryl halides is reported. High-throughput experimentation (HTE) was employed for rapid reaction optimization evaluation a broad scope pharmaceutically relevant structurally diverse halides, including complex drug-like substrates. In addition, the transformation compatible with both primary secondary distinct conditions. Mechanistic insights were critical to enhance efficiency using salts. Systematic comparisons electrochemical non-electrochemical methods revealed complementary two approaches.

Language: Английский

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Nickel-Catalyzed Atroposelective Cross-Electrophile Coupling of Aryl Halides: A General and Practical Route to Diverse MOP-Type Ligands

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(26), P. 17606 - 17612

Published: May 23, 2024

We report a highly cross- and atroposelective coupling between ortho-(chloro)arylphosphine oxides ortho-(bromo)aryl ethers. This previously unknown asymmetric nickel-catalyzed reaction offers direct route to enantioenriched axially chiral biaryl monophosphine that are difficult access by other means. These products can be readily reduced generate MOP-type ligands bearing complex skeletal backbones. The utility of these in catalysis is also demonstrated.

Language: Английский

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Divergent Transformations of Aromatic Esters: Decarbonylative Coupling, Ester Dance, Aryl Exchange, and Deoxygenative Coupling

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(12), P. 1747 - 1760

Published: May 31, 2024

ConspectusAromatic esters are cost-effective, versatile, and commonly used scaffolds that readily synthesized or encountered as synthetic intermediates. While most conventional reactions involving these nucleophilic acyl substitutions 1,2-nucleophilic additions─where a nucleophile attacks the carbonyl group, decarbonylative transformations offer an alternative pathway by using group leaving group. This transition-metal-catalyzed process typically begins with oxidative addition of C(acyl)–O bond to metal. Subsequently, reaction involves migration CO metal center, nucleophile, reductive elimination yield final product. Pioneering work Yamamoto on nickel complexes development (such Mizoroki–Heck-type olefination) aromatic carboxylic anhydrides catalyzed palladium were conducted de Vries Stephan. Furthermore, reports have surfaced hydrogenation pyridyl methyl Murai ruthenium catalysts well nitro phenyl Gooßen under catalysis. Our has been at forefront developing C–H arylations 1,3-azoles aryl boronic acids catalysts. The key this is use esters, which easy synthesize, stabilize, handle, allowing bond; nickel, facilitates suitable bidentate phosphine ligands can stabilize intermediate. By modification nucleophiles, effectively utilized electrophiles in cross-coupling reactions, encouraging nucleophiles among researchers. Account summarizes our advancements for coupling particularly highlighting utilization diverse such alkenylation, intramolecular etherification, α-arylation ketones, arylation, methylation, arylation dibenzofuran synthesis, along cyanation coupling. We also delve into types distinct from typical including ester dance ring exchanges, deoxygenative transformations, focusing complex. For example, hypothesized undergo 1,2-translocation starting complex, leading sequence ortho-deprotonation/decarbonylation, followed protonation, carbonylation, elimination. exchange likely different In coupling, complex engages forming intermediate undergoes presence appropriate reducing agent. These methodologies poised captivate interest chemists offering unconventional emerging approaches transforming esters. Moreover, we demonstrated potential transform available basic chemicals new compounds through organic synthesis.

Language: Английский

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