Selective Arene Hydrogenation for Direct Access to Saturated Carbo‐ and Heterocycles

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(31), P. 10460 - 10476

Published: Jan. 31, 2019

Arene hydrogenation provides direct access to saturated carbo- and heterocycles thus its strategic application may be used shorten synthetic routes. This powerful transformation is widely applied in industry expected facilitate major breakthroughs the sciences. The ability overcome aromaticity while controlling diastereo-, enantio-, chemoselectivity central use of preparation complex molecules. In general, multisubstituted arenes yields predominantly cis isomer. Enantiocontrol imparted by chiral auxiliaries, Brønsted acids, or transition-metal catalysts. Recent studies have demonstrated that highly chemoselective transformations are possible. Such methods underlying strategies reviewed herein, with an emphasis on synthetically useful examples employ readily available

Language: Английский

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Positional and Geometrical Isomerisation of Alkenes: The Pinnacle of Atom Economy

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(39), P. 13654 - 13664

Published: June 25, 2019

Strategies to achieve spatiotemporal regulation of pre-existing alkenes via external stimuli are essential given the ubiquity feedstock olefins in chemistry and their downstream applications. Mirroring 1-0 switch that underpins mammalian vision through selective geometric isomerisation retinal, strategies manipulate 2D space by both positional chemical, thermal light-driven processes being intensively pursued. This minireview highlights current state art activating achieving directionality these fundamental chemical transformations.

Language: Английский

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Strategies for Nucleophilic C(sp³)–(Radio)Fluorination

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 9928 - 9950

Published: April 24, 2023

This Perspective surveys the progress and current limitations of nucleophilic fluorination methodologies. Despite long rich history C(sp3)–F bond construction in chemical research, inherent challenges associated with this transformation have largely constrained to a privileged reaction platform. In recent years, Doyle group─along many others─has pursued study development intent generating deeper mechanistic understanding, developing user-friendly reagents, contributing invention synthetic methods capable enabling radiofluorination. Studies from our laboratory are discussed along developments others field. Fluoride reagent implications identity highlighted. We also outline space inaccessible by technologies series future directions field that can potentially fill existing dark spaces.

Language: Английский

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Systematic Investigation of Lipophilicity Modulation by Aliphatic Fluorination Motifs

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 63(3), P. 1002 - 1031

Published: Jan. 2, 2020

Optimization of compound lipophilicity is a key aspect drug discovery. The aim this work was to compare the modulations induced by 16 distinct known and novel fluoroalkyl motifs on three parent models. Fifty fluorinated compounds, with 28 experimental aliphatic log P values, are involved in discussing various trends. As well as confirming trends, number lipophilicity-reducing introduced. Tactics reduce discussed, such "motif extensions" rearrangements", including concomitant extension carbon chain, one- two-fluorine 'deletions' within perfluoroalkyl groups. Quantum chemical calculations (SMD-MN15) based solvent-dependent three-dimensional (3D) conformational analysis gave excellent correlations superior Clog predictions 2D structural motifs. availability systematic collection data small molecules illustrates relative fluorination

Language: Английский

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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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Mechanism and Origins of Chemo- and Stereoselectivities of Aryl Iodide-Catalyzed Asymmetric Difluorinations of β-Substituted Styrenes

Journal of the American Chemical Society, Journal Year: 2018, Volume and Issue: 140(45), P. 15206 - 15218

Published: Oct. 23, 2018

The mechanism of the aryl iodide-catalyzed asymmetric migratory geminal difluorination β-substituted styrenes (Banik et al. Science 2016, 353, 51) has been explored with density functional theory computations. computed consists (a) activation iodoarene difluoride (ArIF2), (b) enantiodetermining 1,2-fluoroiodination, (c) bridging phenonium ion formation via SN2 reductive displacement, and (d) regioselective fluoride addition. According to computational model, ArIF2 intermediate is stabilized through halogen−π interactions between electron-deficient iodine(III) center benzylic substituents at catalyst stereogenic centers. Interactions ester carbonyl groups (I(III)+···O) are not observed in unactivated complex, but do occur upon hydrogen-bonding external Brønsted acid (HF). 1,2-fluoroiodination occurs alkene complexation electrophilic, cationic I(III) followed by C–F bond anti forming C–I bond. bound olefin adopt a spiro arrangement favored transition structures nearly periplanar disfavored structures. Multiple attractive non-covalent interactions, including slipped π···π stacking, C–H···O, C–H···π found underlie high induction. chemoselectivity for 1,1-difluorination versus 1,2-difluorination controlled mainly (1) steric effect substituent on olefinic double (2) nucleophilicity oxygen substrate.

Language: Английский

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Fluorination and Fluoroalkylation Reactions Mediated by Hypervalent Iodine Reagents

Advanced Synthesis & Catalysis, Journal Year: 2020, Volume and Issue: 362(20), P. 4256 - 4292

Published: Aug. 4, 2020

Abstract This review summarizes the progress in fluorination and fluoroalkylation of electron‐rich systems with diverse fluorine (F) fluoroalkyl (R fn ) reagents employing hypervalent iodine compounds as initiators last few decades. Because strong electrophilicity, high oxidizing properties, low toxicity, air moisture stability, ready availability, ease handling, mild reaction conditions, have been widely utilized modern organic chemistry. In particular, use to initiate C−F C−R =CF 2 H, CF 3 , perfluoroalkyl, OCH SCF SeCF etc) bond formation has increasingly developed. these reactions, behave powerful oxidants or electrophiles activate fluorination/fluoroalkylation reagents, transition‐metal catalysts, substrates situ form electrophilic radical intermediates, which subsequently participate fluorination, difluoromethylation, trifluoromethylation, perfluoroalkylation, trifluoroethoxylation, fluoroalkylthiolation, trifluoromethylselenolation others under conditions. Although great achievements made this area, they are just initial phase still require a wide scope for improvement. It is anticipated that will draw much attention from chemistry community inspire more contributions development new hypervalent‐iodine‐mediated reactions. magnified image

Language: Английский

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Catalytic, Enantioselective 1,2-Difluorination of Cinnamamides

Organic Letters, Journal Year: 2019, Volume and Issue: 21(13), P. 4919 - 4923

Published: April 9, 2019

The enantio- and diastereoselective synthesis of 1,2-difluorides via chiral aryl iodide-catalyzed difluorination cinnamamides is reported. method uses HF-pyridine as a fluoride source mCPBA stoichiometric oxidant to turn over catalyst, affords compounds containing vicinal, fluoride-bearing stereocenters. Selectivity for 1,2-difluorination versus rearrangement pathway resulting in 1,1-difluorination enforced through anchimeric assistance from N- tert-butyl amide substituent.

Language: Английский

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Urea group-directed organocatalytic asymmetric versatile dihalogenation of alkenes and alkynes

Nature Catalysis, Journal Year: 2021, Volume and Issue: 4(8), P. 692 - 702

Published: Aug. 9, 2021

Language: Английский

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