Hydrogen Bonding Phase-Transfer Catalysis with Potassium Fluoride: Enantioselective Synthesis of β-Fluoroamines

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(7), P. 2878 - 2883

Published: Jan. 28, 2019

Potassium fluoride (KF) is an ideal reagent for fluorination because it safe, easy to handle and low-cost. However, poor solubility in organic solvents coupled with limited strategies control its reactivity has discouraged use asymmetric C–F bond formation. Here, we demonstrate that hydrogen bonding phase-transfer catalysis KF provides access valuable β-fluoroamines high yields enantioselectivities. This methodology employs a chiral N-ethyl bis-urea catalyst brings solid into solution as tricoordinated urea-fluoride complex. operationally simple reaction affords enantioenriched fluoro-diphenidine (up 50 g scale) using 0.5 mol % of recoverable catalyst.

Language: Английский

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Electrochemical Vicinal Difluorination of Alkenes: Scalable and Amenable to Electron‐Rich Substrates

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(3), P. 1155 - 1160

Published: Nov. 7, 2019

Fluorinated alkyl groups are important motifs in bioactive compounds, positively influencing pharmacokinetics, potency and conformation. The oxidative difluorination of alkenes represents an strategy for their preparation, yet current methods limited alkene-types tolerance electron-rich, readily oxidized functionalities, as well safety scalability. Herein, we report a method the number unactivated that is tolerant electron-rich functionality, giving products otherwise unattainable. Key to success electrochemical generation hypervalent iodine mediator using "ex-cell" approach, which avoids substrate decomposition. more sustainable conditions give good excellent yields up decagram scales.

Language: Английский

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Hyperconjugation

Wiley Interdisciplinary Reviews Computational Molecular Science, Journal Year: 2018, Volume and Issue: 9(2)

Published: Sept. 6, 2018

This review outlines the role of hyperconjugative interactions in structure and reactivity organic molecules. After defining common patterns, we discuss main factors controlling magnitude effects, including orbital symmetry, energy gap, electronegativity, polarizability. The danger underestimating contribution are illustrated by a number spectroscopic, conformational, structural effects. stereoelectronic nature hyperconjugation offers useful ways for control molecular stability reactivity. New manifestations effects continue to be uncovered theory experiments. article is categorized under: Structure Mechanism > Molecular Structures Software Modeling Reaction Mechanisms Catalysis

Language: Английский

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Fluorinated Rings: Conformation and Application

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(25), P. 7193 - 7213

Published: Jan. 29, 2021

The introduction of fluorine atoms into molecules and materials across many fields academic industrial research is now commonplace, owing to their unique properties. A particularly interesting feature the impact substitution on relative orientation a C-F bond when incorporated organic molecules. In this Review, we will be discussing conformational behavior fluorinated aliphatic carbo- heterocyclic systems. preference each system associated with various interactions introduced by such as charge-dipole, dipole-dipole, hyperconjugative interactions. contribution interaction stabilization alicyclic system, which manifests itself in low conformations, discussed detail. novelty demonstrated presenting most recent applications.

Language: Английский

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Expanding organofluorine chemical space: the design of chiral fluorinated isosteres enabled by I(i)/I(iii) catalysis

Chemical Science, Journal Year: 2021, Volume and Issue: 12(32), P. 10686 - 10695

Published: Jan. 1, 2021

Short aliphatic groups are prevalent in bioactive small molecules and play an essential role regulating physicochemistry molecular recognition phenomena.

Language: Английский

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Regio‐ and Enantioselective Intermolecular Aminofluorination of Alkenes via Iodine(I)/Iodine(III) Catalysis**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(32)

Published: May 18, 2022

The regio- and enantio-selective, intermolecular vicinal fluoroamination of α-trifluoromethyl styrenes has been achieved by enantioselective I

Language: Английский

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Electrochemical difunctionalization of alkenes and alkynes for the synthesis of organochalcogens involving C–S/Se bond formation

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 11(2), P. 597 - 630

Published: Nov. 23, 2023

This review highlights the recent progress in electrochemical difunctionalization of alkenes and alkynes involving C–S/Se bond formation to access organochalcogen frameworks.

Language: Английский

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Regioselective, catalytic 1,1-difluorination of enynes

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(11), P. 1515 - 1522

Published: Oct. 16, 2023

Fluorinated small molecules are prevalent across the functional small-molecule spectrum, but scarcity of naturally occurring sources creates an opportunity for creative endeavour in developing routes to access these important materials. Iodine(I)/iodine(III) catalysis has proven be particularly well-suited this task, enabling abundant alkene substrates readily intercepted by situ-generated λ3-iodanes and processed high-value (di)fluorinated products. These organocatalysis paradigms often emulate metal-based processes engaging π bond and, case styrenes, facilitating fluorinative phenonium-ion rearrangements generate difluoromethylene units. Here we demonstrate that enynes competent proxies thereby mitigating recurrent need aryl substituents, highly versatile homopropargylic difluorides generated operationally simple manner. The scope method is disclosed, together with application target synthesis (>30 examples, up >90% yield).

Language: Английский

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Stereodivergent Synthesis of the Vicinal Difluorinated Tetralin of Casdatifan Enabled by Ru-Catalyzed Transfer Hydrogenation

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

We disclose a stereodivergent strategy to prepare vicinal difluorinated tetralins from γ-substituted tetralones via combination of catalyst-controlled transfer hydrogenation and substrate-controlled fluorinations. This process is easily scalable amenable highly functionalized substrates, as demonstrated here in the late-stage synthesis casdatifan, clinical-stage inhibitor hypoxia-inducible factor-2α. Analysis physicochemical properties which features cis-vicinal difluoride, revealed higher level facial polarization compared its trans-vicinal difluoride isomers.

Language: Английский

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Catalytic Geminal Difluorination of Styrenes for the Construction of Fluorine-rich Bioisosteres

Organic Letters, Journal Year: 2018, Volume and Issue: 20(24), P. 8073 - 8076

Published: Dec. 11, 2018

A geminal difluorination of alkenes based on I(I)/I(III) catalysis is disclosed, which compatible with a range electronically and substitutionally diverse styrenes (27 examples, up to 89% yield). Employing inexpensive p-TolI as the organocatalyst, turnover enabled by Selectfluor-mediated oxidation generate ArIF2 species in situ. Extension include α-substituted bearing fluorine-containing groups disclosed provides an expansive platform for generation fluorine-rich architectures.

Language: Английский

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