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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Fluorinated Pyrazoles: From Synthesis to Applications

Chemical Reviews, Journal Year: 2020, Volume and Issue: 121(3), P. 1670 - 1715

Published: Dec. 31, 2020

Fluorinated pyrazoles play an important role in medicinal chemistry, drug discovery, agrochemistry, coordination and organometallic chemistry. Since the early 1990s, their popularity has grown exponentially. Moreover, more than 50% of all contributions on topic have been published last 5 years. In this review, analysis novel synthetic approaches to fluorinated that appeared recent years is performed. A particular emphasis devoted a detailed consideration reaction mechanisms. addition, reasons led ever-increasing various areas science are discussed. At end several potentially interesting but yet mostly unknown classes outlined.

Language: Английский

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A Practical and Scalable Approach to Fluoro‐Substituted Bicyclo[1.1.1]pentanes

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(29)

Published: May 31, 2022

After more than 20 years of trials, a practical scalable approach to fluoro-substituted bicyclo[1.1.1]pentanes (F-BCPs) has been developed. The physicochemical properties the F-BCPs have studied, and core was incorporated into structure anti-inflammatory drug Flurbiprofen in place fluorophenyl ring.

Language: Английский

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Enantioselective, Catalytic Vicinal Difluorination of Alkenes

Angewandte Chemie International Edition, Journal Year: 2018, Volume and Issue: 57(50), P. 16431 - 16435

Published: Sept. 26, 2018

Abstract The enantioselective, catalytic vicinal difluorination of alkenes is reported by I /I III catalysis using a novel, C 2 ‐symmetric resorcinol derivative. Catalyst turnover via in situ generation an ArI F species enabled Selectfluor oxidation and addition inexpensive HF–amine complex. HF:amine ratio employed this process provides handle for regioselective orthogonality as function Brønsted acidity. Selectivity reversal from the 1,1‐difluorination pathway (geminal) to desired 1,2‐difluorination (vicinal) disclosed (>20:1 both directions). Validation with electron deficient styrenes facilitates chiral bioisosteres venerable CF 3 unit that pervasive drug discovery (20 examples, up 94:06 e.r.). An achiral variant reaction also presented p ‐TolI (up >95 % yield).

Language: Английский

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Photocatalytic E → Z Isomerization of Polarized Alkenes Inspired by the Visual Cycle: Mechanistic Dichotomy and Origin of Selectivity

The Journal of Organic Chemistry, Journal Year: 2017, Volume and Issue: 82(19), P. 9955 - 9977

Published: June 27, 2017

Iteratively executed with exquisite spatial and temporal control, the selective isomerization of polarized alkenes underpins a plethora complex biological processes ranging from natural product biosynthesis through to mammalian visual cycle. However, nature's proficiency conceals inherent difficulties in replicating this contra-thermodynamic transformation laboratory. Recently, we disclosed first highly Z-selective alkenes, employing cinnamoyl chromophore as retinal surrogate under UV-irradiation (402 nm) (−)-riboflavin (vitamin B2) an inexpensive, organic photocatalyst (J. Am. Chem. Soc. 2015, 137, 11254–11257). This study was inspired by propensity crystalline eyes vertebrates invert intrinsic directionality isomerization. Herein, extend methodology include bioinspired, catalytic E → Z α,β-unsaturated nitriles, thereby mimicking intermediate Opsin-derived, protonated Schiff base cycle simple alkenes. Replacement iminium motif cyano group is well tolerated gives additional degree versatility for postisomerization functionalization. Broad substrate scope demonstrated (up 99:1 Z:E) together evidence mechanistic dichotomy via both singlet triplet energy transfer mechanisms. Kinetic studies, temperature dependent photostationary state correlations investigation substituent-based electronic perturbation alkene identified polarization combined increased Z-isomer activation barriers selectivity governing factors catalysis. demonstrates importance internal structural preorganization on composition explicates augmented Z-selectivity upon hydrogen-alkyl exchange at β-position alkene.

Language: Английский

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The formation of all-cis-(multi)fluorinated piperidines by a dearomatization–hydrogenation process

Nature Chemistry, Journal Year: 2019, Volume and Issue: 11(3), P. 264 - 270

Published: Jan. 21, 2019

Language: Английский

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Informing Molecular Design by Stereoelectronic Theory: The Fluorine Gauche Effect in Catalysis

Accounts of Chemical Research, Journal Year: 2018, Volume and Issue: 51(7), P. 1701 - 1710

Published: June 12, 2018

The axioms of stereoelectronic theory constitute an atlas to navigate the contours molecular space. All too rarely lauded, advent and development has been one organic chemistry's greatest triumphs. Inevitably, however, in absence a comprehensive treatise, many field's pioneers do not receive veneration that they merit. Rather their legacies are pillars persist teaching research. This ubiquity continues afford practitioners chemistry with abundance opportunities for creative endeavor reaction design, conceiving novel activation modes, preorganizing intermediates, or stabilizing productive transition states products. Antipodal steric governance, which mitigates destabilizing nonbonding interactions, control allows well-defined, often complementary, conformations be populated. Indeed, prevalence hyperconjugative interactions biosynthetic processes renders this approach preorganization decidedly biomimetic and, by extension, expansive. In Account, evolution application simple donor-acceptor model based on fluorine gauche effect is delineated. Founded reinforcing involving C(sp3)-H bonding orbitals C(sp3)-X antibonding [σC-H → σC-X*], general stratagem used conjunction array secondary noncovalent achieve acyclic conformational (ACC) structures interest. These effects range from 1,3-allylic strain (A1,3) through electrostatic charge-dipole cation-π interactions. Synergy between these ensures rotation about strategic C(sp3)-C(sp3) bonds subject requirement antiperiplanarity (180°). Logically, generic [X-CH2-CH2-Y] system (X, Y = electron withdrawing groups) two synclinal (i.e., gauche) significantly As such, models didactically predictively powerful achieving topological preorganization. case effect, low demand remaining substituents at C(sp3) hybridized center placed predictable area space: An exit vector analogy thus appropriate. Furthermore, intrinsic chemical stability C-F bond advantageous, it may considered as inert steering group: juxtaposition size electronegativity fluorinated molecules unique among organo-halogen series. Cognizant replacement atom difluoroethylene motif another group preserves conformation, was reasoned β-fluoroamines would intriguing candidates investigation. burgeoning field Lewis base catalysis, particularly via iminium ion activation, provided timely platform explore postulated fluorine-iminium effect. Necessarily, requires process intramolecularization generate deficient neighboring Examples include protonation, condensation salts, acylation. process, akin substrate binding, obvious parallels enzymatic since perturbs dynamics [ synclinal-endo, antiperiplanar, synclinal-exo]. Account details conformationally small [X-Cα-Cβ-F] logical design illustrates synthetic value enantioselective catalysis.

Language: Английский

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Fluorinated carbohydrates as chemical probes for molecular recognition studies. Current status and perspectives

Chemical Society Reviews, Journal Year: 2020, Volume and Issue: 49(12), P. 3863 - 3888

Published: Jan. 1, 2020

Fluorinated carbohydrates have become indispensable in glycosciences. This contribution provides an overview of how fluorine introduction modifies physical and chemical properties along with selected examples its applications.

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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Catalytic, Vicinal Difluorination of Olefins: Creating a Hybrid, Chiral Bioisostere of the Trifluoromethyl and Ethyl Groups

ACS Catalysis, Journal Year: 2016, Volume and Issue: 6(10), P. 7167 - 7173

Published: Sept. 14, 2016

Contemporaneous reports describing the vicinal difluorination of olefins relying on I(I)/I(III) catalysis have augmented arsenal dihalogenation methods and provided a solution to this longstanding challenge in olefin functionalization. In both studies, success was contingent situ generation ArIF2 from simple aryl iodide, HF source, suitable terminal oxidant. The first report by Jacobsen co-workers employed resorcinol-derived iodide/m-CPBA oxidant combination, while laboratory relied p-iodotoluene Selectfluor. complementarity these approaches ensures that wide variety electronically distinct are viable substrates for transformation. This perspective describes our development catalytic as means efficiently construct hybrid, chiral bioisostere trifluoromethyl ethyl groups broader context molecular design highlights key other laboratories accelerated study.

Language: Английский

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