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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Nontraditional Fragment Couplings of Alcohols and Carboxylic Acids: C(sp³)–C(sp³) Cross-Coupling via Radical Sorting

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(14), P. 6185 - 6192

Published: March 30, 2022

Alcohols and carboxylic acids are among the most commercially abundant, synthetically versatile, operationally convenient functional groups in organic chemistry. Under visible light photoredox catalysis, these native synthetic handles readily undergo radical activation, resulting open-shell intermediates can subsequently participate transition metal catalysis. In this report, we describe C(sp3)–C(sp3) cross-coupling of alcohols through dual combination N-heterocyclic carbene (NHC)-mediated deoxygenation hypervalent iodine-mediated decarboxylation. This mild practical Ni-catalyzed radical-coupling protocol was employed to prepare a wide array alkyl–alkyl cross-coupled products, including highly congested quaternary carbon centers from corresponding tertiary or acids. We demonstrate applications methodology alcohol C1-alkylation formal homologation, as well late-stage functionalization drugs, natural biomolecules.

Language: Английский

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Using Data Science To Guide Aryl Bromide Substrate Scope Analysis in a Ni/Photoredox-Catalyzed Cross-Coupling with Acetals as Alcohol-Derived Radical Sources

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(2), P. 1045 - 1055

Published: Jan. 5, 2022

Ni/photoredox catalysis has emerged as a powerful platform for C(sp2)–C(sp3) bond formation. While many of these methods typically employ aryl bromides the C(sp2) coupling partner, variety aliphatic radical sources have been investigated. In principle, reactions enable access to same product scaffolds, but it can be hard discern which method because nonstandardized sets are used in scope evaluation. Herein, we report Ni/photoredox-catalyzed (deutero)methylation and alkylation halides where benzaldehyde di(alkyl) acetals serve alcohol-derived sources. Reaction development, mechanistic studies, late-stage derivatization biologically relevant chloride, fenofibrate, presented. Then, describe integration data science techniques, including DFT featurization, dimensionality reduction, hierarchical clustering, delineate diverse succinct collection that is representative chemical space substrate class. By superimposing examples from published on this space, identify areas sparse coverage high versus low average yields, enabling comparisons between prior art new method. Additionally, demonstrate systematically selected quantify population-wide reactivity trends reveal possible functional group incompatibility with supervised machine learning.

Language: Английский

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Multimetallic-Catalyzed C–C Bond-Forming Reactions: From Serendipity to Strategy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(12), P. 6596 - 6614

Published: March 13, 2023

The use of two or more metal catalysts in a reaction is powerful synthetic strategy to access complex targets efficiently and selectively from simple starting materials. While capable uniting distinct reactivities, the principles governing multimetallic catalysis are not always intuitive, making discovery optimization new reactions challenging. Here, we outline our perspective on design elements using precedent well-documented C–C bond-forming reactions. These strategies provide insight into synergy compatibility individual components reaction. Advantages limitations discussed promote further development field.

Language: Английский

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Reductive Deoxygenative Functionalization of Alcohols by First‐Row Transition Metal Catalysis

Chinese Journal of Chemistry, Journal Year: 2023, Volume and Issue: 41(13), P. 1637 - 1652

Published: Jan. 23, 2023

Comprehensive Summary Alcohols are among the most accessible functionalities. Catalytic deoxygenative functionalization of alcohols is highly synthetically appealing. While significant progress has been made on reactions with nucleophiles, electrophilic coupling partners remain a real challenge. This manuscript highlights advance in this direction, which mainly achieved by first‐row transition metals. The low‐valent titanium catalyst shown unique reactivity to homolytically cleave C—OH bonds. formed carbon radicals could either undergo reduction give protonation products or couple fragments form C—C chemistry initially realized using stoichiometric amount reagents and later extended catalytic variants. Nickel features variety oxidation states ranging from Ni 0 IV , both two‐electron oxidative addition single‐electron process involved their activation an electrophile. These properties enable nickel catalyze reductive R–X electrophiles. reaction first reported allylic alcohols, then benzylic and, very recently non‐activated alcohols. Recent effort resulted many invaluable methodologies that improve efficiency for construction aliphatic use cobalt copper catalysts not only expands substrate scope these but also shows new selectivity issues.

Language: Английский

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Diversifying Amino Acids and Peptides via Deaminative Reductive Cross-Couplings Leveraging High-Throughput Experimentation

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(10), P. 5684 - 5695

Published: Feb. 28, 2023

A deaminative reductive coupling of amino acid pyridinium salts with aryl bromides has been developed to enable efficient synthesis noncanonical acids and diversification peptides. This method transforms natural, commercially available lysine, ornithine, diaminobutanoic acid, diaminopropanoic alanines homologated derivatives varying chain lengths. Attractive features include ability transverse scales, tolerance pharma-relevant (hetero)aryls biorthogonal functional groups, the applicability beyond monomeric short macrocyclic peptide substrates. The success this work relied on high-throughput experimentation identify complementary reaction conditions that proved critical for achieving a broad scope range substrates including

Language: Английский

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Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(9), P. 6078 - 6144

Published: April 17, 2024

Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods their functionalization require them to first be converted into a more activated derivative, while recent years have seen vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This Review discusses how transition metal catalysis can used toward this goal. These broadly classified three categories. Deoxygenative functionalizations, representing derivatization C–O bond, enable alcohol act as leaving group formation new C–C bonds. Etherifications, characterized by O–H represent classical reactivity has been modernized include mild reaction conditions, diverse partners, high selectivities. Lastly, chain reactions described, wherein acts mediator formal C–H alkyl backbone. Each these classes transformation will discussed context intermolecular arylation, alkylation, related reactions, illustrating alcohols harnessed

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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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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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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