Enantioselective Epoxidation of Alkenes Catalyzed by 2-Fluoro-<i>N</i>-Carbethoxytropinone and Related Tropinone Derivatives

Armstrong, Alan; Ahmed, Ghafoor; Dominguez‐Fernandez, Belen; Hayter, Barry R.; Wailes, J. Steven

doi:10.1021/jo026322y

Cited by 79 publications

(26 citation statements)

References 40 publications

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“…This example is nonetheless instructive since it demonstrates that a seemingly innocent H → F substitution likely disfavors the proposed spiro-transition state that underpins selectivity . Seminal studies by Armstrong , and Denmark , have validated fluorinated tropinone scaffolds as efficient catalysts for the stereoselective epoxidation of alkenes. Selectivities derive from the rigid alkaloid framework in which the amine moiety inhibits alkene approach to the top face of the transient dioxirane generated upon oxidation.…”

Section: C(sp3)–f Centers In Cyclic Scaffoldsmentioning

confidence: 99%

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

2018

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

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Section: C(sp3)–f Centers In Cyclic Scaffoldsmentioning

confidence: 99%

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

2018

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“…A significant activating effect by a-fluorine substitution has been observed [2][3][4][5] and then extensively studied [6][7][8][9][10][11][12][13][14][15]. We have recently shown that, during epoxidation of methyl p-methoxycinnamate (Scheme 1), enantiopure tri-substituted cyclohexanones 1-3 were more efficient, leading to higher ee% and higher yields, when the halogen was axial (1a-3a) than when the halogen was equatorial (1e-3e) [7].…”

Section: Introductionmentioning

confidence: 99%

Effect of α-fluorination on asymmetric epoxidation of trans-olefins using α-fluorinated cyclohexanone dioxiranes

Solladié‐Cavallo

Jierry

Norouzi‐Arasi

et al. 2004

Journal of Fluorine Chemistry

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“…Katalysatoren auf Basis chiraler Ketone für die asymmetrische Epoxidierung kçnnen weitgehend in drei Typen unterteilt werden (Schema 11): 1) C 2 -symmetrische Kataly-satoren; [26] 2) bicyclische Katalysatoren [27] und 3) von Kohlenhydraten abgeleitete Katalysatoren. [28] Es wurde eine umfassende Übersicht zu den Entwicklungen der veranschaulichten Katalysatortypen bis 2007 und ihrer Rolle in enantioselektiven Epoxidierungen verçffentlicht.…”

Section: Verfahren Zur Epoxidierung Von Nichtaktivierten Alkenen Und unclassified

“…[29] 26,29,30] Der von Fructose abgeleitete Katalysator 42 (Schema 12) war einer der ersten Katalysatoren für die hochenantioselektive Epoxidierung. [31] (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Mol-%) und eine geringere Aufgabe von Oxone (1.5 ¾quiv.) ermçglichte und zu hçheren Umwandlungen führte.…”

Section: Verfahren Zur Epoxidierung Von Nichtaktivierten Alkenen Und unclassified

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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Enantioselective Epoxidation of Alkenes Catalyzed by 2-Fluoro-N-Carbethoxytropinone and Related Tropinone Derivatives

Cited by 79 publications

References 40 publications

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

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

Effect of α-fluorination on asymmetric epoxidation of trans-olefins using α-fluorinated cyclohexanone dioxiranes

Organokatalytische asymmetrische Epoxidierungen – Reaktionen, Mechanismen und Anwendungen

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