Photochemical Deracemization of Lactams with Deuteration Enabled by Dual Hydrogen Atom Transfer DOI
Xiaoyu Yan,

Yubing Pang,

Yutong Zhou

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

Photochemical deracemization has emerged as one of the most straightforward approaches to access highly enantioenriched compounds in recent years. While excited-state events such energy transfer, single electron and ligand-to-metal charge transfer have been leveraged promote stereoablation, relying on hydrogen atom which circumvent limitations imposed by triplet redox potential racemic substrates, remain underexplored. Conceptually, attractive method for tertiary stereocenter might be abstraction followed donation. However, implementing a strategy poses significant challenges, primarily because products are also reactive if chiral catalyst is unable differentiate between two enantiomers. Herein we report distinct dual photochemical δ- γ-lactams, achieving high enantioenrichment deuterium incorporation despite inherent reactivity products. Mechanistic studies reveal that benzophenone enables nonselective while tetrapeptide-derived thiol dictates enantioselectivity donation step. More importantly, pyridine-based alcohol was found play crucial roles facilitating well enhancing

Language: Английский

Deuterium in drug discovery: progress, opportunities and challenges DOI Open Access
Rita Maria Concetta Di Martino, Brad D. Maxwell, Tracey Pirali

et al.

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(7), P. 562 - 584

Published: June 5, 2023

Language: Английский

Citations

259
Lewis Base–Boryl Radicals Enabled Borylation Reactions and Selective Activation of Carbon–Heteroatom Bonds DOI

Tianyu Peng,

Feng‐Lian Zhang, Yi‐Feng Wang

et al.

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 56(2), P. 169 - 186

Published: Dec. 26, 2022

ConspectusThe past decades have witnessed tremendous progress on radical reactions. However, in comparison with carbon, nitrogen, oxygen, and other main group element centered radicals, the synthetic chemistry of boron radicals was less studied, mainly due to high electron-deficiency instability such 3-center-5-electron species. In 1980s, Roberts co-workers found that coordination a Lewis base (amines or phosphines) center could form 4-center-7-electron boryl (Lewis base-boryl LBRs) are be more stable. only limited applications were developed. 2008, Curran achieved breakthrough discovery N-heterocyclic carbene (NHC) which enable range reduction polymerization Despite these exciting findings, powerful valuable LBRs would expected, given structures reactivities easily modulated, provide ample opportunities discover new this Account, summary our key contributions LBR-enabled borylation reactions selective activation inert carbon-heteroatom bonds will presented.Organoboron compounds shown versatile chemical society, their syntheses rely principally ionic The development mechanistically different allows synthesizing products inaccessible by traditional methods. For purpose, we progressively developed series NHC-boryl mediated chemo-, regio-, stereoselective alkenes alkynes, wide variety structurally diverse organoboron molecules successfully prepared. utility borylated also demonstrated. Furthermore, disclosed photoredox protocol for oxidative generation enabled useful defluoroborylation arylboration reactions.Selective bond is an ideal way convert simple starting materials value-added products, while cleavage bonds, particular chemoselectivity control when multiple identical present similar environments, remains long-standing challenge. We envisaged finely tuning properties might solution address Recently, 4-dimethylaminopyridine (DMAP)-boryl promoted sequential C-F functionalization trifluoroacetic acid derivatives, α-C-F selectively snipped via spin-center shift mechanism. This strategy enables facile conversion abundantly available highly mono- difluorinated molecules. Encouraged finding, further three-step sequence construct all-carbon quaternary centers from trichloromethyl groups, where three C-Cl cleaved rational choice suitable precursors each step. dehydroxylative alkylation α-hydroxy carboxylic derivatives achieved, allowing efficient some biomass platform value products.

Language: Английский

Citations

73
Formation and degradation of strongly reducing cyanoarene-based radical anions towards efficient radical anion-mediated photoredox catalysis DOI Creative Commons
Yonghwan Kwon,

Jungwook Lee,

Yeonjin Noh

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 6, 2023

Cyanoarene-based photocatalysts (PCs) have attracted significant interest owing to their superior catalytic performance for radical anion mediated photoredox catalysis. However, the factors affecting formation and degradation of cyanoarene-based PC (PC•‒) are still insufficiently understood. Herein, we therefore investigate PC•‒ under widely-used photoredox-mediated reaction conditions. By screening various PCs, elucidate strategies efficiently generate with adequate excited-state reduction potentials (Ered*) via supra-efficient generation long-lived triplet excited states (T1). To thoroughly behavior in actual reactions, a reductive dehalogenation is carried out as model identified dominant photodegradation pathways PC•‒. Dehalogenation coexistent depending on rate electron transfer (ET) substrate strongly depends electronic steric properties PCs. Based understanding both PC•‒, demonstrate that efficient highly reducing allows catalyzed aryl/alkyl halides at loading low 0.001 mol% high oxygen tolerance. The present work provides new insights into reactions reactions.

Language: Английский

Citations

73
Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis DOI

Qinglong Shi,

Xiu‐Wen Kang, Zhiyong Liu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2748 - 2756

Published: Jan. 12, 2024

Controlling the enantioselectivity of hydrogen atom transfer (HAT) reactions has been a long-standing synthetic challenge. While recent advances on photoenzymatic catalysis have demonstrated great potential non-natural photoenzymes, all transformations are initiated by single-electron reduction substrate, with only one notable exception. Herein, we report an oxidation-initiated enantioselective hydrosulfonylation olefins using novel mutant gluconobacter ene-reductase (GluER-W100F-W342F). Compared to known systems, our approach does not rely formation electron donor–acceptor complex between substrates and enzyme cofactor simplifies reaction system obviating addition regeneration mixture. More importantly, GluER variant exhibits high reactivity broad substrate scope. Mechanistic studies support proposed mechanism reveal that tyrosine-mediated HAT process is involved.

Language: Английский

Citations

39
Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp3)–C(sp3) Bond Formation DOI Creative Commons
Ting Wan, Luca Capaldo, Davide Ravelli

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 145(2), P. 991 - 999

Published: Dec. 30, 2022

Herein, we present a comprehensive study on the use of N-heterocyclic carbene (NHC)-ligated boryl radicals to enable C(sp3)–C(sp3) bond formation under visible-light irradiation via Halogen-Atom Transfer (XAT). The methodology relies an acridinium dye generate boron-centered from corresponding NHC-ligated boranes single-electron transfer (SET) and deprotonation. These subsequently engage with alkyl halides in XAT step, delivering desired nucleophilic radicals. strategy is very mild accommodates broad scope halides, including medicinally relevant compounds biologically active molecules. key role operative reaction mechanism has been elucidated through combination experimental, spectroscopic, computational studies. This stands as significant advancement chemistry radicals, which had long restricted radical reductions, enabling C–C photoredox conditions.

Language: Английский

Citations

54
Catalytic Asymmetric Hydrogen Atom Transfer: Enantioselective Hydroamination of Alkenes DOI
Benjamin G. Hejna, Jacob M. Ganley, Huiling Shao

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(29), P. 16118 - 16129

Published: July 11, 2023

We report a highly enantioselective radical-based hydroamination of enol esters with sulfonamides jointly catalyzed by an Ir photocatalyst, Brønsted base, and tetrapeptide thiol. This method is demonstrated for the formation 23 protected β-amino-alcohol products, achieving selectivities up to 97:3 er. The stereochemistry product set through selective hydrogen atom transfer from chiral thiol catalyst prochiral C-centered radical. Structure–selectivity relationships derived structural variation both peptide olefin substrate provide key insights into development optimal catalyst. Experimental computational mechanistic studies indicate that hydrogen-bonding, π–π stacking, London dispersion interactions are contributing factors recognition enantioinduction. These findings further asymmetric catalysis contribute understanding noncovalent relevant such transformations.

Language: Английский

Citations

37
Recent Advances in Deuteration Reactions† DOI
Hao Li, Shabbir Muhammad, Wu Li

et al.

Chinese Journal of Chemistry, Journal Year: 2023, Volume and Issue: 42(10), P. 1145 - 1156

Published: Dec. 26, 2023

Comprehensive Summary The deuteration of organic compounds has attracted more attentions in recent years for the potential applications new drug discovery and synthetic chemistry. For this purpose, many efficient deuterium labeling methodologies have been developed, including hydrogen isotope exchange (HIE), reductive deuteration, dehalogenative that allow synthesis selectively deuterated compounds. In last few years, great breakthroughs selective achieved interest molecules is rising. review, we summarized developments since 2021. Several types key processes incorporation reactions, H/D exchange, are introduced discussed. Key Scientists 2000s, Derdau Atzrodt's group made contributions to directing assisted noble‐metal catalyzed arenes labeled During same period, Sajiki co‐workers completed a series reactions by heterogeneous platinum‐group metal catalysts. Since 2015, Gregory Pieters developed ruthenium catalysts exchange. 2016, Chirik's presence homogeneous iron complex. David MacMillan coworkers photocatalyzed HIE α‐amino C(sp 3 )–H bonds. From 2020, nanoelectrodes were designed deuterations unactivated unsaturated bonds Zhang's group. Recently, Beller's several strategies isotopic using earth‐abundant Our review latest important

Language: Английский

Citations

34
Photocatalytic Umpolung Strategy for the Synthesis of α-Amino Phosphine Oxides and Deuterated Derivatives DOI
Chunhua Ma, Xiaofeng Li,

Xiya Chen

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(44), P. 8016 - 8021

Published: Oct. 30, 2023

Direct, economical, and green synthesis of deuterated α-amino phosphine oxides remains an elusive challenge in synthetic chemistry. Herein, we report a visible-light-driven umpolung strategy for synthesizing from isocyanide using 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene as the photocatalyst D2O deuterium source. Moreover, streamlined sustainable methodology can be applied modification amino acids, natural products, drugs. The strong antiproliferative activity desired products indicates that method could provide novel privileged scaffold antitumor drug development.

Language: Английский

Citations

31
Radical Reactions in Organic Synthesis: Exploring in-, on-, and with-Water Methods DOI Creative Commons
Chryssostomos Chatgilialoglu, Sebastián Barata‐Vallejo, Thanasis Gimisis

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(3), P. 569 - 569

Published: Jan. 23, 2024

Radical reactions in water or aqueous media are important for organic synthesis, realizing high-yielding processes under non-toxic and environmentally friendly conditions. This overview includes (i) a general introduction to chemistry media, (ii) synthetic approaches in, on, with as well heterogeneous phases, (iii) of carbon-centered radicals (or deuterium oxide) activated through coordination various Lewis acids, (iv) photocatalysis (v) applications bioinspired by naturally occurring processes. A wide range chemical strategies different experimental conditions have been reviewed that lead functional group translocation transformation reactions, leading the preparation complex molecules. These results reveal how solvent/medium/reagent radical has matured over last two decades, further discoveries anticipated near future.

Language: Английский

Citations

11
Anti-Markovnikov hydro- and deuterochlorination of unsaturated hydrocarbons using iron photocatalysis DOI

Kang‐Jie Bian,

David Nemoto, Ying Chen

et al.

Nature Synthesis, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

Citations

2