Functional Analysis of an Aspartate‐Based Epoxidation Catalyst with Amide‐to‐Alkene Peptidomimetic Catalyst Analogues

Jakobsche, Charles E.; Peris, Gorka; Miller, Scott J.

doi:10.1002/ange.200802223

Cited by 42 publications

(15 citation statements)

References 53 publications

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“…The advantage of using a DG lies in the ability to functionalize nonpolar bonds (such as in alkenes) while maintaining beneficial polar interactions between the substrate and chiral source; however, DGs have rarely been used in organocatalysis. In this context, the Miller research group reported the epoxidation reaction of allylic alcohols, using an amino acid catalyst capable of hydrogen bonding with the alcohol DG, and conducted elegant studies delineating the importance of hydrogen-bonding interactions for this and related systems (7)(8)(9) (Fig. 1).…”

mentioning

confidence: 99%

A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

Wang

Drljevic

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

115

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We report a catalytic enantioselective electrophilic fluorination of alkenes to form tertiary and quaternary C(sp3)-F bonds and generate β-amino-and β-aryl-allylic fluorides. The reaction takes advantage of the ability of chiral phosphate anions to serve as solid-liquid phase transfer catalysts and hydrogen bond with directing groups on the substrate. A variety of heterocyclic, carbocyclic, and acyclic alkenes react with good to excellent yields and high enantioselectivities. Further, we demonstrate a one-pot, tandem dihalogenation-cyclization reaction, using the same catalytic system twice in series, with an analogous electrophilic brominating reagent in the second step.asymmetric | organocatalysis | hydrogen-bonding

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mentioning

confidence: 99%

A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

Wang

Drljevic

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

115

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“…Coupled with its electronegativity, fluorine’s small size has made it an attractive choice for isosteric substitutions of hydrogen or other functional groups, especially those containing oxygen. In this regard, fluoroalkene isosteres of peptide amide bonds have become increasingly prevalent as structural and mechanistic probes in both biological5 and chemical studies 6…”

mentioning

confidence: 99%

“…Given our interest in fluoroolefins as mechanistic probes,6 we sought to expand the methodology for Au-catalyzed nucleophilic fluorination of alkynes by developing new avenues for regiocontrol that would expand both the utility and substrate scope of the reaction. Specifically, we envisioned a classical heteroatom-directed reaction that might confer a high degree of selectivity for a broad range of substrates 11.…”

mentioning

confidence: 99%

Regio- and Stereoselective Synthesis of Fluoroalkenes by Directed Au(I) Catalysis

2009

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Au-catalyzed hydrofluorination reactions of a range of functionalized alkynes are reported. In the presence of an appropriate directing group, localized with particular spacing from the pendant alkyne, regioselective and predictable conversion of the alkyne to the Z-vinyl fluoride may be achieved. In selected cases, yields and selectivities are excellent. Additional experiments with two directing groups installed have established some initial principles with respect to a hierarchy of directing groups and their capacity for influencing hydrofluorination regioselectivity.Fluorine is an element of special interest in organic chemistry. Its electronegativity, highest of all the known elements, contributes to its special properties, which include formation of strong bonds to carbon, 1 low atomic polarizability, 2 and strong inductive characteristics. 3 The field of medicinal chemistry has especially benefited from the development of chemical techniques for incorporating fluorine into organic molecules. Fluorine is now routinely introduced to impart metabolic stability to medicinal compounds. 4 Coupled with its electronegativity, fluorine's small size has made it an attractive choice for isosteric substitutions of hydrogen or In light of the importance of fluoroalkenes, many efforts towards efficient regio-and stereoselective syntheses of these moieties have been reported. 7 Of these, we were especially intrigued by a methodology developed by Sadighi and coworkers employing a Au(I) catalyst 8 to add HF across an alkyne. 9 Using Et 3 N•3HF as a nucleophilic fluorine source, KHSO 4 as an additive, and various co-catalysts, trans-hydrofluorination was achieved in good yields (Scheme 1). Modest regioselectivity for alkyl/aryl alkyne substrates was improved by adding electron-withdrawing groups to the aromatic ring substituents. Although other alkyne hydrohalogenations using Au-catalysis have been reported, these reactions utilize electrophilically activated halogens, for the most part excluding fluorine. 10 Also, the substrate scope of these reactions has been limited to propargyl acetates.Given our interest in fluoroolefins as mechanistic probes, 6 we sought to expand the methodology for Au-catalyzed nucleophilic fluorination of alkynes by developing new avenues for regiocontrol that would expand both the utility and substrate scope of the reaction. Specifically, we envisioned a classical heteroatom-directed reaction that might confer a high degree of selectivity for a broad range of substrates. 11 Here we report the realization of this design in the carbonyl-directed hydrofluorination of alkynes under Au(I) catalysis. We demonstrate that this concept is broadly applicable and engenders regioselectivies that exceed those originally reported for this reaction system. As such, this methodology could facilitate access to new compounds for fundamental research and the development of pharmaceuticals.We commenced our investigations by examining ester 1. We were intrigued to observe that hydrofluorination of this subst...

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“…[18] Es wird angenommen, dass Wasserstoffbrücken zwischen dem Katalysator und dem Alken für einen hohen Grad an Stereoinduktion entscheidend sind, da Substrate ohne ersichtliche Mçglichkeiten für Wasserstoffbrücken fast keine Enantioselektivität zeigten. [18] Es wird angenommen, dass Wasserstoffbrücken zwischen dem Katalysator und dem Alken für einen hohen Grad an Stereoinduktion entscheidend sind, da Substrate ohne ersichtliche Mçglichkeiten für Wasserstoffbrücken fast keine Enantioselektivität zeigten.…”

Section: Elektrophile Epoxidierung Von Alkenen Und Mechanistische Betunclassified

“…Der Mechanismus der tripeptidkatalysierten asymmetrischen Epoxidierung wird immer noch erforscht. [18] [19] Dieses Verfahren wurde später erfolgreich genutzt, um das schwierige Problem der regio-und enantioselektiven Epoxidierung von Polyenen, wie des Sesquiterpens Farnesol und von verwandten Verbindungen, anzugehen (Schema 6). [20] Unter Verwendung des Katalysators 20 wurden eine nahezu perfekte Regioselektivität bezüglich der Doppelbindung neben der allylischen OH-Gruppe und eine hohe Enantioselektivität von 87 % ee erzielt.…”

Section: Epoxidierung Von Elektronenarmen Ab-ungesättigten Aldehydenunclassified

Organokatalytische asymmetrische Epoxidierungen – Reaktionen, Mechanismen und Anwendungen

Davis¹,

Stiller²,

Naicker³

et al. 2014

Angewandte Chemie

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Chirale Epoxide sind vielseitige Bausteine in der Synthese komplexer organischer Gerüste. Durch die hohe Spannung ihres dreigliedrigen Rings können Epoxide eine Reihe von nucleophilen Ringöffnungsreaktionen eingehen. Nach der Entwicklung der Sharpless‐Epoxidierung folgten zahlreiche wichtige Fortschritte, und das rasch aufstrebende Feld der asymmetrischen Organokatalyse stellt nun Katalysatoren für die Epoxidierung eines breiten Spektrums an ungesättigten Carbonylverbindungen bereit. In diesem Kurzaufsatz sind jüngste Entwicklungen auf dem Gebiet organokatalytischer asymmetrischer Epoxidierungen zusammengefasst. Die vorgeschlagenen Reaktionsmechanismen werden beschrieben, und Anwendungen werden beschrieben.

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Functional Analysis of an Aspartate‐Based Epoxidation Catalyst with Amide‐to‐Alkene Peptidomimetic Catalyst Analogues

Cited by 42 publications

References 53 publications

A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

Regio- and Stereoselective Synthesis of Fluoroalkenes by Directed Au(I) Catalysis

Organokatalytische asymmetrische Epoxidierungen – Reaktionen, Mechanismen und Anwendungen

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