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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Catalytic Asymmetric Diamination of Styrenes

Journal of the American Chemical Society, Journal Year: 2017, Volume and Issue: 139(12), P. 4354 - 4357

Published: March 9, 2017

An enantioselective catalytic vicinal diamination of styrenes is reported, which proceeds under entirely intermolecular reaction control. It relies on a chirally modified aryliodine(I) catalyst and within an iodine(I/III) manifold with conventional 3-chloroperbenzoic acid as terminal oxidant. environmentally benign solvent combination not only adds to the attractiveness process but also slows down rate undesired background reaction. A total 30 examples are presented, consistently provide high enantiomeric excesses in range 91–98%.

Language: Английский

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Enantioselective Iodine(I/III) Catalysis in Organic Synthesis

Advanced Synthesis & Catalysis, Journal Year: 2018, Volume and Issue: 361(1), P. 2 - 25

Published: May 24, 2018

Abstract Chiral aryliodine(III) reagents have provided an advanced concept for enantioselective synthesis and catalysis. With the advent of chiral iodine(I/III) catalysis, many different structures been explored in area. The currently most prominent catalyst design is based on a resorcinol core attachment two lactic side chains bearing ester or amide groups. This enables privileged modular synthesis, which fine‐tuning with respect to specific reaction requirement straightforward. present overview summarizes structural variation optimization such aryliodine catalysts discusses properties active iodine(III) states. status quo oxidation catalysis intramolecular intermolecular control reviewed, aspects individual catalytic cycles are discussed. magnified image

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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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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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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Asymmetric iodine catalysis-mediated enantioselective oxidative transformations

Organic & Biomolecular Chemistry, Journal Year: 2018, Volume and Issue: 16(30), P. 5386 - 5402

Published: Jan. 1, 2018

The implementation of chiral iodine catalysis has tremendously been developed in the field asymmetric synthesis over past decade.

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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