Rapid and Modular Access to Quaternary Carbons from Tertiary Alcohols via Bimolecular Homolytic Substitution

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16330 - 16336

Published: July 20, 2023

Quaternary carbons are ubiquitous in bioactive molecules; however, synthetic methods for the construction of this motif remain underdeveloped. Here, we report synthesis quaternary from tertiary alcohols, a class structurally diverse, bench-stable feedstocks, via merger photoredox catalysis and iron-mediated SH2 bond formation. This alcohol-bromide cross-coupling is enabled by novel halogen-atom transfer (XAT) reagent, which first reductively activated XAT reagent to be reported. A wide variety sterically congested products can accessed through mild practical protocol including derived both alkylation benzylation fragments. We further demonstrate utility method expedited liver receptor agonist two-step conversion ketones esters products, enables modular control up three four substituents on center.

Language: Английский

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Emerging Trends in Copper-Promoted Radical-Involved C–O Bond Formations

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(32), P. 17527 - 17550

Published: Aug. 2, 2023

The C–O bond is ubiquitous in biologically active molecules, pharmaceutical agents, and functional materials, thereby making it an important group. Consequently, the development of bond-forming reactions using catalytic strategies has become increasingly research topic organic synthesis because more conventional methods involving strong base acid have many limitations. In contrast to ionic-pathway-based methods, copper-promoted radical-mediated formation experiencing a surge interest owing renaissance free-radical chemistry photoredox catalysis. This Perspective highlights appraises state-of-the-art techniques this burgeoning field. contents are organized according different reaction types working models.

Language: Английский

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Radical reactions enabled by polyfluoroaryl fragments: photocatalysis and beyond

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(9), P. 4741 - 4785

Published: Jan. 1, 2024

The review summarizes advances in the radical chemistry of polyfluorinated arenes under photocatalytic conditions. fluoroaryl fragment serves as enabling motif for reaction design and efficient generation reactive intermediates.

Language: Английский

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Tethering Three Radical Cascades for Controlled Termination of Radical Alkyne peri-Annulations: Making Phenalenyl Ketones without Oxidants

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(6), P. 4187 - 4211

Published: Feb. 5, 2024

Although Bu3Sn-mediated radical alkyne peri-annulations allow access to phenalenyl ring systems, the oxidative termination of these cascades provides only a limited selection possible isomeric phenalenone products with product selectivity controlled by intrinsic properties new cyclic systems. In this work, we report an oxidant-free strategy that can overcome limitation and enable selective full set isomerically functionalized phenalenones. The key preferential is preinstallation "weak link" undergoes C–O fragmentation in final cascade step. Breaking bond assisted entropy, gain conjugation product, release stabilized fragments. This expanded exo-dig cyclization oligoalkynes, which provide π-extended Conveniently, introduce functionalities (i.e., Bu3Sn iodide moieties) amenable further cross-coupling reactions. Consequently, variety polyaromatic diones, could serve as phenalenyl-based open-shell precursors, be synthesized.

Language: Английский

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Three-Component Synthesis of Multiple Functionalized Allenes via Copper/Photoredox Dual Catalyzed 1,4-Alkylcyanation of 1,3-Enynes

Organic Letters, Journal Year: 2024, Volume and Issue: 26(9), P. 1834 - 1839

Published: Feb. 22, 2024

Efficient access to multiple functionalized allenes via a three component 1,4-alkylcyanation of enynes with cyclic alcohol derivatives in the presence trimethylsilyl cyanide (TMSCN) under copper/photoredox dual catalysis has been developed. Both easily transformable aldehyde and cyano groups were introduced tetra-substituted through light-induced C–C bond cleavage butanol pentanol derivatives. The reactions proceeded smoothly mild conditions broad functional tolerance.

Language: Английский

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Direct Synthesis of α‐Aryl‐α‐Trifluoromethyl Alcohols via Nickel Catalyzed Cross‐Electrophile Coupling

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(47)

Published: Sept. 26, 2022

A nickel-catalyzed reductive cross-electrophile coupling between the redox-active N-trifluoroethoxyphthalimide and iodoarenes is documented. The protocol reproduces a formal arylation of trifluoroacetaldehyde under mild conditions in high yields (up to 88 %) with large functional group tolerance (30 examples). combined computational experimental investigation revealed pivotal solvent assisted 1,2-Hydrogen Atom Transfer (HAT) process generate nucleophilic α-hydroxy-α-trifluoromethyl C-centered radical for Csp

Language: Английский

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Recent Advances in N-O Bond Cleavage of Oximes and Hydroxylamines to Construct N-Heterocycle

Molecules, Journal Year: 2023, Volume and Issue: 28(4), P. 1775 - 1775

Published: Feb. 13, 2023

Oximes and hydroxylamines are a very important class of skeletons that not only widely exist in natural products drug molecules, but also synthon, which have been used industrial production. Due to weak N-O σ bonds oximes hydroxylamines, they can be easily transformed into other functional groups by bond cleavage. Therefore, the synthesis N-heterocycle using as nitrogen sources has attracted wide attention. Recent advances for through transition-metal-catalyzed radical-mediated cyclization classified type rings summarized. In this paper, recent cleavage reviewed. We hope review provides new perspective on field, reference develop environmentally friendly sustainable methods.

Language: Английский

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CH‐Functionalization of Heterocycles with the Formation of C−O, C−N, C−S/Se, and C−P Bonds by Intermolecular Addition of Heteroatom‐Centered Radicals

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(11), P. 1714 - 1755

Published: April 12, 2023

Abstract In the last decade, free radicals have found a wide application in functionalization of unsaturated compounds, such as alkenes, alkynes, and arenes, via free‐radical addition to carbon‐carbon π‐bonds. these processes, intermolecular attack on aromatic substrates represents challenge due relatively high resistance π‐system reactions comparison alkene C=C bonds. The heterocycles is especially interesting diversity their structures chemical properties well importance for medicinal chemistry, agrochemistry, materials science. Addition C‐centered widely known Minisci‐type well‐reviewed. this paper, we summarized main achievements less explored group processes: by heteroatom‐centered (O‐, N‐, S‐/Se‐, P‐radicals) with emphasis papers published after 2010. Literature analysis revealed strong trend towards usage electrochemistry photoredox‐catalysis generation recent years. remaining fundamental problem field lack experimental support proposed mechanisms frequent existence several plausible reaction pathways. progress mechanistic studies can significantly improve prediction optimal conditions depending structure.

Language: Английский

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Metal-free photoinduced C(sp3)–H/C(sp3)–H cross-coupling to access α‑tertiary amino acid derivatives

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

Published: Oct. 6, 2023

The cross-dehydrogenative coupling (CDC) reaction is the most direct and efficient method for constructing α-tertiary amino acids (ATAAs), which avoids pre-activation of C(sp3)-H substrates. However, use transition metals harsh conditions are still significant challenges these reactions that urgently require solutions. This paper presents a mild, metal-free CDC construction ATAAs, compatible with various benzyl C-H substrates, functionalized alkyl good regioselectivity. Notably, our exhibits excellent functional group tolerance late-stage applicability. According to mechanistic studies, one-step synthesized bench-stable N-alkoxyphtalimide generates highly electrophilic trifluoro ethoxy radical serves as key intermediate in process acts hydrogen atom transfer reagent. Therefore, additive-free offers promising strategy synthesis ATAAs under mild conditions.

Language: Английский

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N ‐Hydroxyphthalimide

Encyclopedia of Reagents for Organic Synthesis, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: Jan. 3, 2025

Abstract image [ 524‐38‐9 ] C 8 H 5 NO 3 (MW 163.11) InChI = 1S/C8H5NO3/c10‐7‐5‐3‐1‐2‐4‐6(5)8(11)9(7)12/h1‐4,12H InChIKey CFMZSMGAMPBRBE‐UHFFFAOYSA‐N (reagent for the formation of O ‐alkyl hydroxylamines, catalytic precursor to phthalimido‐ N ‐oxyl radical (PINO), capable mild and selective abstraction hydrogen from a wide variety CH bonds with free radicals exploitation in synthetic schemes, oxidation bonds) Physical Data: mp 233 °C; d 1.58 g cm −3 ; refractive index 1.522 (at 589 nm); p K 6.3 at 25 °C 2 O; OH BDE 88 kcal mol −1 1 NMR (DMSO‐d 6 ) 7.84 (s, 4 , CH), 10.9 OH); 13 168, 134, 128, 123; EPR derived (PINO) triplet, 2.0073, A 4.23 G; MASS (EI) ( m/z 163 M + 147, 133, 105, 104, 77, 76, 50. Solubility: 0.33 L benzene; 50.5 soluble AcOH, CH CN, COOEt. Preparative Methods: ‐hydroxyphthalimide is easily prepared by reaction phthalic anhydride hydroxylamine hydrochloride or sulphate basic conditions. Handling, Storage Precaution: white crystalline solid, stable air, does not need particular precautions storage, irritant eyes skin very toxic after inhalation.

Language: Английский

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