Radical C(sp3)–H functionalization and cross-coupling reactions

Nature Reviews Chemistry, Journal Year: 2022, Volume and Issue: 6(6), P. 405 - 427

Published: May 17, 2022

Language: Английский

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Arenethiolate as a Dual Function Catalyst for Photocatalytic Defluoroalkylation and Hydrodefluorination of Trifluoromethyls

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(7), P. 4103 - 4109

Published: March 18, 2022

Thiol is known to act as a hydrogen atom transfer catalyst working in synergy with photocatalyst photoredox catalysis, but we report herein that an arene thiolate appropriate substituent can be photoactivated under visible light function both strongly reducing electron-donating redox and HAT enable catalytic C–F activation of trifluoromethyl substrates for selective hydrodefluorination coupling various alkenes the presence formate salts. These reactions demonstrate promising utility arenethiolates dual photocatalysts. The synthetic this method demonstrated by broad scope amenable substrates, including trifluoromethylated (hetero)arenes, trifluoroacetates, trifluoroacetamides, which exhibited high levels chemoselectivity. reaction efficacy allows site-selective late-stage functionalization multitrifluoromethylated bioactive compounds pharmaceuticals

Language: Английский

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The interplay of polar effects in controlling the selectivity of radical reactions

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(9), P. 682 - 695

Published: Aug. 1, 2022

Language: Английский

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Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(31), P. 14288 - 14296

Published: July 27, 2022

The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation unactivated alkenes with industrial chemical, chlorodifluoromethane (ClCF2H, Freon-22). This protocol realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) organophotoredox catalysis under blue light irradiation. A broad scope readily accessible featuring variety functional groups drug natural product moieties could be selectively difluoromethylated good efficiency in metal-free manner. Combined experimental computational studies suggest that the key XAT process ClCF2H both thermodynamically kinetically favored over hydrogen pathway owing formation strong boron–chlorine (B–Cl) bond low-lying antibonding orbital carbon–chlorine (C–Cl) bond.

Language: Английский

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Synthetic Applications of Photocatalyzed Halogen‐Radical Mediated Hydrogen Atom Transfer for C−H Bond Functionalization

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(34)

Published: May 13, 2022

Abstract The opportunity to activate C(sp 3 )−H bonds via homolytic cleavage by means of halogen radicals has long been disregarded in synthetic endeavors due the unpredictable selectivity. Nowadays, photocatalysis established itself as a method choice for generation such reactive intermediates under mild conditions. This Minireview collects recent examples showcasing how photocatalytic manifolds have used tame aggressive Hydrogen Atom Transfer (HAT) purposes. In last section this work, we address site‐selectivity issues posed methodology and show it can be guided through judicious reaction

Language: Английский

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

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

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Visible-light mediated catalytic asymmetric radical deuteration at non-benzylic positions

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 1, 2022

Abstract Site- and enantioselective incorporation of deuterium into organic compounds is broad interest in synthesis, especially within the pharmaceutical industry. While catalytic approaches relying on two-electron reaction manifolds have allowed for stereoselective delivery a formal deuteride (D – ) or deuteron + at benzylic positions, complementary strategies that make use one-electron atom transfer target non-benzylic positions remain elusive. Here we report photochemical approach asymmetric radical deuteration by utilizing readily available peptide- sugar-derived thiols as catalyst inexpensive oxide source. This metal-free platform enables four types deuterofunctionalization reactions exocyclic olefins allows with high levels enantioselectivity incorporation. Computational studies reveal attractive non-covalent interactions are responsible stereocontrol. We anticipate our findings will open up new avenues deuteration.

Language: Английский

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Site-Specific and Degree-Controlled Alkyl Deuteration via Cu-Catalyzed Redox-Neutral Deacylation

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(22), P. 9570 - 9575

Published: May 25, 2022

Deuterated organic compounds have become increasingly important in many areas; however, it remains challenging to install deuterium site-selectively unactivated aliphatic positions with control of the degree deuteration. Here, we report a Cu-catalyzed degree-controlled deacylative deuteration diverse alkyl groups methylketone (acetyl) moiety as traceless activating group. The use N-methylpicolino-hydrazonamide (MPHA) promotes efficient aromatization-driven C–C cleavage. Mono-, di-, and trideuteration at specific sites can be selectively achieved. reaction is redox-neutral broad functional group tolerance. utility this method has been demonstrated forming complete set deuterated ethyl groups, merging Diels–Alder reaction, net devinylative deuteration, synthesis d2-analogue Austedo.

Language: Английский

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Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp³)–C(sp³) Bond Formation

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

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Boryl radical catalysis enables asymmetric radical cycloisomerization reactions

Science, Journal Year: 2023, Volume and Issue: 382(6674), P. 1056 - 1065

Published: Nov. 30, 2023

The development of functionally distinct catalysts for enantioselective synthesis is a prominent yet challenging goal synthetic chemistry. In this work, we report family chiral N-heterocyclic carbene (NHC)-ligated boryl radicals as that enable catalytic asymmetric radical cycloisomerization reactions. can be generated from easily prepared NHC-borane complexes, and the broad availability NHC component provides substantial benefits stereochemical control. Mechanistic studies support cycle comprising sequence addition, hydrogen atom transfer, cyclization, elimination catalyst, wherein subunit determines enantioselectivity cyclization. This catalysis allows construction valuable heterocyclic products simple starting materials.

Language: Английский

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