Recent Advances in Alkenyl sp² C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(24), P. 17479 - 17646

Published: Oct. 14, 2022

Alkenes and their derivatives are featured widely in a variety of natural products, pharmaceuticals, advanced materials. Significant efforts have been made toward the development new practical methods to access this important class compounds by selectively activating alkenyl C(sp2)–H bonds recent years. In comprehensive review, we describe state-of-the-art strategies for direct functionalization sp2 C–H C–F until June 2022. Moreover, metal-free, photoredox, electrochemical also covered. For clarity, review has divided into two parts; first part focuses on currently available using different alkene as starting materials, second describes bond easily accessible gem-difluoroalkenes material. This includes scope, limitations, mechanistic studies, stereoselective control (using directing groups well metal-migration strategies), applications complex molecule synthesis where appropriate. Overall, aims document considerable advancements, current status, emerging work critically summarizing contributions researchers working fascinating area is expected stimulate novel, innovative, broadly applicable functionalizations coming

Language: Английский

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Pd/NHC-Controlled Regiodivergent Defluorinative Allylation of gem-Difluorocyclopropanes with Allylboronates

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(11), P. 6495 - 6505

Published: May 17, 2022

Controlling the selectivity of synthetically useful reactions has been a longstanding objective organic chemistry. We report regiodivergent synthetic protocol allowing access to diverse fluorinated 1,5-dienes through Pd/NHC-catalyzed ring-opening allylation gem-difluorocyclopropanes. Density functional theory (DFT) calculations on regioselectivity-determining transition states provided critical insight into design NHC ligand for switching regioselectivity. Consistent with DFT predictions, N-heterocyclic carbene (NHC) ligands bulky ortho substituents favored branched allylation, IHept providing > 20:1 branched/linear less hindered such as IMes thermodynamically more stable linear products. were able carry out late-stage modification various complex molecules using this protocol. Our ligand-controlled approach provides efficient regioisomeric from same starting materials and constitutes valuable addition toolbox diversity-oriented synthesis.

Language: Английский

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Chemo‐, Stereo‐ and Regioselective Fluoroallylation/Annulation of Hydrazones with gem‐Difluorocyclopropanes via Tunable Palladium/NHC Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(23)

Published: April 4, 2023

Defluorinative manipulation of polyfluorinated molecules has shown great promise due to its granting synthetic versatility inert C-F bonds. The development chemo-, stereo- and regioselective strategies realize highly efficient formation either the linear/branched or E/Z products from gem-difluorocyclopropanes (gem-F2 CPs) is a challenging task. Herein, we have realized palladium/NHC-catalyzed fluoroallylation/annulation hydrazones with gem-F2 CPs that incorporate hydrazone N2 moiety into products. thermodynamically unstable fluorinated E-allylation aryl ketone were obtained for first time, while di-alkyl yielded monofluorinated branched selectivity under similar reaction conditions. With aldehyde hydrazones, two kinds pyrazoles via defluorinative allylation/annulation cascade, in which different carbon atoms could be incorporated pyrazole rings regiospecifically. DFT calculations revealed divergent was kinetically controlled final C-C bond proceeded through 7-membered TS.

Language: Английский

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Cross-Electrophile Coupling: Principles, Methods, and Applications in Synthesis

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Cross-electrophile coupling (XEC), defined by us as the cross-coupling of two different σ-electrophiles that is driven catalyst reduction, has seen rapid progression in recent years. As such, this review aims to summarize field from its beginnings up until mid-2023 and provide comprehensive coverage on synthetic methods current state mechanistic understanding. Chapters are split type bond formed, which include C(sp

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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Asymmetric Synthesis of 2,2‐Difluorotetrahydrofurans through Palladium‐Catalyzed Formal [3+2] Cycloaddition

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(44), P. 23641 - 23645

Published: Sept. 8, 2021

The asymmetric synthesis of 2,2-difluorinated tetrahydrofurans was accomplished via enantioselective formal [3+2] cycloaddition catalyzed by palladium. reaction between gem-difluoroalkenes and racemic vinyl epoxides or vinylethylene carbonates resulted in the formation enantioenriched 2,2-difluorotetrahydrofurans with an enantioselectivity up to 98 %. Notably, used readily available (R)-BINAP as ligand at a low loading yielded wide variety difluorinated products moderate high yields. Both chiral diastereomers could be obtained single sequence.

Language: Английский

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Ligand-controlled regioselective and chemodivergent defluorinative functionalization of gem-difluorocyclopropanes with simple ketones

Chemical Science, Journal Year: 2021, Volume and Issue: 12(47), P. 15511 - 15518

Published: Jan. 1, 2021

Modulating the reaction selectivity is highly attractive and pivotal to rational design of synthetic regimes. The defluorinative functionalization

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 Progress in Transition-Metal-Catalyzed Reductive Cross-Coupling Reactions Using Diboron Reagents as Reductants

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(23), P. 15469 - 15480

Published: Nov. 16, 2023

Transition-metal-catalyzed reductive cross-coupling reactions have been developed as one of the important tools for constructing C–C bonds. These involve direct coupling two distinct electrophiles promoted by transition metals and reductants. Notably, these methods offer advantages over conventional because they circumvent need air- moisture-sensitive organometallic reagents while being simple to operate exhibiting good compatibility with various functional groups. In recent years, diboron gained prominence reductants alongside traditional metal reductants, such Zn, Mn, Mg. This Review aims provide an insightful overview nickel/copper/iron-catalyzed using illustrate their possible reaction mechanisms.

Language: Английский

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Copper-Catalyzed Hydroamination of gem-Difluoroalkenes Access to Diversified α-Difluoromethyl Amines

Organic Letters, Journal Year: 2023, Volume and Issue: 25(3), P. 533 - 537

Published: Jan. 13, 2023

The difluoromethyl group (CF2H) is of great importance in medicinal chemistry. We report herein an efficient method for the synthesis diversified α-difluoromethyl amines through copper-catalyzed hydroamination gem-difluoroalkenes, where C-N bond formed via a α-CF2H transition-metal intermediate. This new reaction proceeds Cu-H insertion to gem-difluoroalkenes and gives valuable alkyl-CF2H-containing compounds, which overcome much more challenged β-F elimination from α-fluoroalkyl organocopper species. exhibits broad substrate scope with readily available starting materials commercial catalysis.

Language: Английский

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