TEMPO-Enabled Electrochemical Enantioselective Oxidative Coupling of Secondary Acyclic Amines with Ketones

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(38), P. 15599 - 15605

Published: Sept. 17, 2021

An electrochemical asymmetric coupling of secondary acyclic amines with ketones via a Shono-type oxidation has been described, affording the corresponding amino acid derivatives good to excellent diastereoselectivity and enantioselectivity. The addition an N-oxyl radical as redox mediator could selectively oxidize substrate rather than product, although their potential difference is subtle (about 13 mV). This transformation proceeds in absence stoichiometric additives, including metals, oxidants, electrolytes, which gives it functional group compatibility. Mechanistic studies suggest that proton-mediated racemization product prevented by reduction protons at cathode.

Language: Английский

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Electrochemical Late-Stage Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(19), P. 11269 - 11335

Published: Sept. 26, 2023

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical biological activities. LSF can thus greatly accelerate development medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical synthesis has emerged as an environmentally friendly platform transformation organic compounds. Over past decade, electrochemical late-stage (eLSF) gained major momentum, which is summarized herein up to February 2023.

Language: Английский

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Electrochemical oxidative C(sp3)–H cross-coupling with hydrogen evolution

Nature Synthesis, Journal Year: 2023, Volume and Issue: 2(3), P. 217 - 230

Published: Feb. 16, 2023

Language: Английский

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Green chemistry meets medicinal chemistry: a perspective on modern metal-free late-stage functionalization reactions

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(19), P. 10955 - 10982

Published: Jan. 1, 2021

This review summarizes the most recent advances of metal-free late-stage functionalization (LSF) pharmaceutically relevant molecules. Particular emphasis is placed on C – H activation as well use endogenous functional groups.

Language: Английский

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Electrochemistry for the Chemoselective Modification of Peptides and Proteins

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 144(1), P. 23 - 41

Published: Dec. 30, 2021

Although electrochemical strategies for small-molecule synthesis are flourishing, this technology has yet to be fully exploited the mild and chemoselective modification of peptides proteins. With growing number diverse peptide natural products being identified emergence modified proteins as therapeutic diagnostic agents, methods stand alluring prospects harnessing reactivity polypeptides build molecular complexity. As a inherently tunable reaction platform, electrochemistry is arguably well-suited overcome chemo- regioselectivity issues which limit existing bioconjugation strategies. This Perspective will showcase recently developed approaches protein modification. The article also highlights wealth untapped opportunities production homogeneously biomolecules, with an eye toward realizing enormous potential chemistry.

Language: Английский

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Convergent Synthesis of 1,4-Dicarbonyl Z-Alkenes through Three-Component Coupling of Alkynes, α-Diazo Sulfonium Triflate, and Water

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(11), P. 4952 - 4965

Published: March 11, 2022

We report a general protocol for the convergent synthesis of 1,4-dicarbonyl Z-alkenes form alkynes using α-diazo sulfonium triflate and water. The C═O, C═C, C–H bonds are formed under mild conditions with wide range functional groups tolerated. reaction exhibits excellent Z-selectivity complete regioselectivity. resulting can smoothly undergo follow-up conversion to variety heteroaromatic scaffolds. Moreover, also provides facile access corresponding deuterated heteroarenes high level deuterium incorporation (90–97% D-inc.) by directly D2O, thus rendering method highly valuable. comprehensive mechanistic studies indicate that free carbyne radical intermediate is via photocatalytic single electron transfer process, KH2PO4 plays crucial role in significant improvements on yield selectivity based density-functional theory calculations, providing new direction coupling reactions diazo compounds.

Language: Английский

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Photoinduced Chemo‐, Site‐ and Stereoselective α‐C(sp³)−H Functionalization of Sulfides

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(29)

Published: April 21, 2022

Abstract The ubiquity of sulfur‐containing molecules in biologically active natural products and pharmaceuticals has long attracted synthetic chemists to develop efficient strategies towards their synthesis. strategy direct α‐C(sp 3 )−H modification sulfides provides a streamlining access complex molecules. Herein, we report photoinduced chemo‐, site‐ stereoselective functionalization using isatins as the photoredox reagent coupling partner catalyzed by chiral gallium(III)‐ N,N ′‐dioxide complex. reaction proceeds through verified single‐electron transfer (SET) mechanism with high efficiency, excellent functional group tolerance, well broad substrate scope. Importantly, this cross‐coupling protocol is highly selective for late‐stage methionine‐related peptides, regardless inherent structural similarity complexity diverse residues.

Language: Английский

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Advances in Organic Electrochemical Synthesis

Acta Chimica Sinica, Journal Year: 2022, Volume and Issue: 80(8), P. 1115 - 1115

Published: Jan. 1, 2022

Organic electrochemical synthesis has become a useful and environmentally friendly alternative to traditional organic been applied oxidation, reduction, or redox neutral transformation.By dialing in the electric current electrode potential, it is possible achieve some challenging transformations under mild reaction conditions.With increasing awareness of energy efficiency environmental protection, attracted much attention recent years.However, faces several challenges including passivation, limited types, difficulty controlling reactivity selectivity, so on.This review focuses on solution system, summarizes efforts addressing these through direct electrolysis indirect electrolysis.In electrolysis, strategies include rational design reactions, change modes equipment, merging technology with other novel synthetic technologies.In terms compounds transition metals are mainly used as molecular electrocatalysts shuttle electrons between electrodes substrates control affording chemical transformations.

Language: Английский

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Divergent Acyl and Decarbonylative Liebeskind–Srogl Cross-Coupling of Thioesters by Cu-Cofactor and Pd–NHC (NHC = N-Heterocyclic Carbene) Catalysis

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(3), P. 1848 - 1855

Published: Jan. 17, 2023

Transition-metal-catalyzed cross-coupling reactions of thioesters by selective acyl C(O)–S cleavage have emerged as a powerful platform for the preparation complex molecules. Herein, we report divergent Liebeskind–Srogl Pd–NHC (NHC = N-heterocyclic carbene) catalysis. The reaction provides straightforward access to functionalized ketones highly C(acyl)–S under mild conditions. Most crucially, conditions enable direct functionalization range pharmaceuticals decorated with palette sensitive functional groups, providing attractive products medicinal chemistry programs. Furthermore, decarbonylative C(acyl)–S/C(aryl)–C(O) is reported. Cu metal cofactor directs pathway an or pathway. This reactivity applicable pharmaceuticals. represents mildest Suzuki discovered date. Cu-directed and opens up chemical space in molecule synthesis.

Language: Английский

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Electrochemical NiH‐Catalyzed C(sp³)−C(sp³) Coupling of Alkyl Halides and Alkyl Alkenes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(44)

Published: Sept. 14, 2023

Herein, an electrochemically driven NiH-catalyzed reductive coupling of alkyl halides and alkenes for the construction Csp3 -Csp3 bonds is firstly reported. Notably, serve dual function as substrates hydrogen sources to generate NiH species under electrochemical conditions. The tunable nature this reaction realized by introducing intramolecular coordinating group substrate, where product can be easily adjusted give desired branched products. method proceeds mild conditions, exhibits a broad substrate scope, affords moderate excellent yields with over 70 examples, including late-stage modification natural products drug derivatives. Mechanistic insights offer evidence process. sp3 -carbon-halogen activated through single electron transfer (SET) nickel catalyst in its low valence state, generated cathodic reduction, generation from pivotal transformation.

Language: Английский

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