Synthetic Advantages of Defluorinative C−F Bond Functionalization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Aug. 22, 2023

Abstract Much progress has been made in the development of methods to both create compounds that contain C−F bonds and functionalize bonds. As such, are becoming common versatile synthetic functional handles. This review summarizes advantages defluorinative functionalization reactions for small molecule synthesis. The coverage is organized by type carbon framework fluorine attached mono‐ polyfluorinated motifs. main challenges, opportunities advances discussed each class organofluorine. Most text focuses on case studies illustrate how defluorofunctionalization can improve routes targets or properties enable unique mechanisms reactions. broader goal showcase incorporating exploiting design routes, improvement specific advent new methods.

Language: Английский

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Synergistic Pd/Cu-Catalyzed 1,5-Double Chiral Inductions

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9241 - 9251

Published: March 19, 2024

Much attention has been focused on the catalytic asymmetric creation of single chiral centers or two adjacent stereocenters. However, construction nonadjacent stereocenters is significant importance but challenging because lack remote induction models. Herein, based a C═C bond relay strategy, we report synergistic Pd/Cu-catalyzed 1,5-double model. All four stereoisomers target products bearing 1,5-nonadjacent involving both allenyl axial and central chirality could be obtained divergently by simply changing combination catalysts with different configurations. Control experiments DFT calculations reveal novel mechanism 1,5-oxidative addition, contra-thermodynamic η3-allyl palladium shift, conjugate nucleophilic substitution, which play crucial roles in control reactivity, regio-, enantio-, diastereoselectivity. It expected that this strategy may provide general protocol for synthesis structural motifs distant

Language: Английский

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A review of frustrated Lewis pair enabled monoselective C–F bond activation

Chemical Science, Journal Year: 2024, Volume and Issue: 15(8), P. 2712 - 2724

Published: Jan. 1, 2024

Frustrated Lewis pair (FLP) bond activation chemistry has greatly developed over the last two decades since seminal report of metal-free reversible hydrogen activation. Recently, FLP systems have been utilized to allow monoselective C-F (at equivalent sites) in polyfluoroalkanes. The problem 'over-defluorination' functionalization polyfluoroalkanes (where multiple fluoro-positions are uncontrollably functionalized) a long-standing chemical fluorocarbon for 80 years. mediated is complementary other solutions address and offers several advantages unique opportunities. This perspective highlights some these opportunities places development into context wider effort overcome 'over-defluorination'.

Language: Английский

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Chemo-, regio-, and stereoselective tetrafunctionalization of fluoroalkynes enables divergent synthesis of 5-7-membered azacycles

Chemical Science, Journal Year: 2024, Volume and Issue: 15(30), P. 12026 - 12035

Published: Jan. 1, 2024

A 1,2,3,4-tetrafunctionalization of polyfluoroalkynes for the divergent construction 5-7-membered ( E )-1,2-difluorovinyl azacycles is developed.

Language: Английский

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Enantio‐ and Diastereoselective Synthesis of Chiral Tetrasubstituted α‐Amino Allenoates Bearing a Vicinal All‐Carbon Quaternary Stereocenter with Dual‐Copper‐Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(31)

Published: June 1, 2023

The skeletons of chiral tetrasubstituted allenes bearing a vicinal all-carbon quaternary stereocenter are importance but still challenging to synthesize. Herein, we report enantio- and diastereoselective γ-additions 1-alkynyl ketimines with dual-copper-catalysis under mild conditions, affording α-amino allenoates in high yields (up 99 % yield) excellent enantioselectivities ee) diastereoselectivities >20 : 1 dr). Importantly, the stereodivergent synthesis products was realized by asymmetric γ-addition reaction Grignard reagent promoted epimerization. Moreover, dual-copper-catalyzed reactions were smoothly applied gram-scale adopted introduce allenyl moieties into bioactive molecules. Mechanistic experiments density functional theory (DFT) calculations demonstrated that catalyzed double copper catalysts.

Language: Английский

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Palladium-Catalyzed Allylic Alkylation Reactions of Nucleophilic Allenones: Asymmetric Allylic Alkylation, Z/E Divergent Allylic Alkylation, and [5 + 2] Annulation

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(13), P. 9940 - 9954

Published: June 19, 2024

Metal-catalyzed allenylic substitution reactions where allenes serve as electrophilic precursors have been recognized a rapid way for novel allene construction. On the contrary, chemistry in which act nucleophiles has far less investigated, especially powerful platform such metal-catalyzed allylic alkylation reactions. We herein describe two unprecedented palladium-catalyzed of an nucleophile. In first reaction, using vinyloxazolidinones allyl precursor, asymmetric allylation trisubstituted allenones worked well to prepare array axially chiral tetrasubstituted allenes. Mechanistic studies and density functional theory (DFT) calculations indicated that weak hydrogen-bonding interaction between acidic C(sp2)–H allenone nitrogen anion π-azaallyl-Pd species is key success stereocontrol. This reaction revealed intriguing reactivity nucleophilic time. second with use allenylethylene carbonates π-oxyallyl-Pd precursors, presented unique under different conditions provide divergent synthetic access (E)- (Z)-allenyl diene products. Interestingly, subsequent sequential intramolecular cyclization/isomerization (Z)-product delivered dihydrooxepine derivatives [5 + 2] annulation

Language: Английский

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Nickel‐Catalyzed Stereo‐ and Enantioselective Cross‐Coupling of gem‐Difluoroalkenes with Carbon Electrophiles by C−F Bond Activation

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(6)

Published: Dec. 10, 2021

Abstract Stereo‐ and enantioselective cross‐electrophile coupling involving C−F bond activation is reported. Treatment of gem‐difluoroalkenes with racemic benzyl electrophiles in the presence a chiral nickel complex using B 2 pin as stoichiometric reductant allows construction C(sp )−C(sp 3 ) under mild conditions, affording broad range monofluoroalkenes bearing stereogenic allylic centers. Initial mechanistic studies indicate that radical chain pathway may be operating, wherein ester group gem‐difluoroalkene promotes through oxidative addition to Ni species .

Language: Английский

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Ligand‐Controlled Palladium‐Catalyzed Regiodivergent Defluorinative Allylation of gem‐Difluorocyclopropanes via σ‐Bond Activation

Chinese Journal of Chemistry, Journal Year: 2022, Volume and Issue: 40(19), P. 2345 - 2355

Published: June 28, 2022

Comprehensive Summary Monofluoroalkenes are important and versatile privileged components in pharmacologically relevant molecules. Here, we report a method for the selective construction of these compounds diversity‐oriented fashion through regiodivergent cross‐coupling gem ‐difluorocyclopropanes with allylboronates by employing palladium catalyst two different ligands, which were used as allyl electrophiles C—C C—F bond activation. In presence 2‐biphenylyl(diphenyl)phosphine ligand, linear‐selective allyl–allyl formation is highly obtained, while utilizing sterically hindered BrettPhos (dicyclohexyl[3,6‐dimethoxy‐2',4',6'‐tris(1‐methylethyl)[1,1'‐biphenyl]‐2‐yl]phosphine) ligand favors generation branched‐selective product. Experimental computational studies investigated key steps reactions, revealing origin ligand‐controlled regiodivergence.

Language: Английский

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Recent advances in the metal-catalyzed asymmetric synthesis of chiral allenes

Organic Chemistry Frontiers, Journal Year: 2022, Volume and Issue: 9(18), P. 5053 - 5073

Published: Jan. 1, 2022

Recent advances in the metal-catalyzed asymmetric synthesis of chiral allenes are summarized. This review is categorized based on starting material, including alkynes, racemic allenes, and conjugated dienes.

Language: Английский

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Synthesis of Stereoenriched Piperidines via Chemo-Enzymatic Dearomatization of Activated Pyridines

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(46), P. 21088 - 21095

Published: Nov. 9, 2022

The development of efficient and sustainable methods for the synthesis nitrogen heterocycles is an important goal chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds precursors. A potential biocatalytic approach this privileged scaffold would be asymmetric dearomatization readily assembled activated pyridines. However, nature yet yield a suitable biocatalyst specifically reaction. Here, by combining biocatalysis, we present general chemo-enzymatic pyridines preparation with precise stereochemistry. key step involves stereoselective one-pot amine oxidase/ene imine reductase cascade convert N-substituted tetrahydropyridines stereo-defined 3- 3,4-substituted piperidines. This has proved useful transformations syntheses antipsychotic drugs Preclamol OSU-6162, as well two intermediates synthetic routes ovarian cancer monotherapeutic Niraparib.

Language: Английский

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