Fluorine-directed 1,2-trans glycosylation of rare sugars

Aiguabella, Nuria; Holland, Mareike C.; Gilmour, Ryan

doi:10.1039/c6ob00025h

Cited by 27 publications

(23 citation statements)

References 25 publications

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“…Replacement of a protected hydroxyl group by fluorine in a glycosyl donor can influence anomeric stereoselectivity through multiple effects like destabilization of cationic transition states by the inductive effect of fluorine, stabilization of transient oxocarbenium ion conformers by electrostatic interaction with the C–F bond dipole, or attenuation of the hydrogen-bond acceptor capacity with respect to the parent oxygen substituent . However, except for an in-depth study of 2-deoxy-2-fluoro-hexopyranosyl trichloroacetimidate donors by Bucher and Gilmour, − there have been no systematic studies investigating anomeric diastereoselectivity of fluorinated donors.…”

Section: Introductionmentioning

confidence: 99%

Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors

et al. 2019

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Control of anomeric stereoselectivity in glycosylation with deoxofluorinated glycosyl donors is critical for assembly of fluorinated oligosaccharides. Here, we report the synthesis of benzylated 3-fluoro and 4fluoro analogues of phenyl 1-thioglucosazide and galactosazide donors and evaluation of their stereoselectivity in glycosylation of a series of model carbohydrate acceptors using the Tf 2 O/Ph 2 SO promoter system. Lowtemperature NMR revealed formation of covalent α-triflate and both anomers of oxosulfonium triflates under selected glycosylation conditions. This study demonstrates how the stereoselectivity depends on acceptor reactivity and glycosyl donor configuration. Reactive acceptors favor formation of 1,2-transβ-glycosides with both D-gluco and D-galacto donors, whereas poorly reactive acceptors favor formation of 1,2-cis-α-glycosides with D-galacto donors but are unselective with D-gluco donors.

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Section: Introductionmentioning

confidence: 99%

Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors

et al. 2019

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“…A competent bioisostere for both H and OH, 10 fluorine can be exploited as an electronically matched bioisostere of the hydroxyl group [OH → F], or to induce localized partial charge inversion when substituted for hydrogen [H δ+ → F δ-]. 11 In the arena of natural product chemistry, modulating and augmenting bioactivity can often be achieved through single site fluorination in remarkably complex architectures. 12 This aspect of organofluorine chemistry is inextricably linked to the stability of the C(sp 3 )−F bond: This is at variance with the remaining members of the organohalogen series.…”

Section: Introductionmentioning

confidence: 99%

“…The conspicuous under-representation of fluorine in the rich tapestry of halogenated natural products further underscores the potential of organofluorine compounds in generating new materials with specifically engineered properties. A competent bioisostere for both H and OH, fluorine can be exploited as an electronically matched bioisostere of the hydroxyl group [OH → F], or to induce localized partial charge inversion when substituted for hydrogen [H δ+ → F δ‑ ] . In the arena of natural product chemistry, modulating and augmenting bioactivity can often be achieved through single site fluorination in remarkably complex architectures .…”

Section: Introductionmentioning

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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“…The intrinsic α-selectivity observed in α-deoxygenated donors can be understood by comparing their diastereoselectivity with that observed in donors with fluorine at C-2. Gilmour and co-workers 185 contrasted the behavior of the 2-deoxy trichloroacetimidate 76 , which affords α-glycosides as result of the anomeric effect, with that of donor 77 with a fluorine substituent at C-2 (Scheme 33). The presence of fluorine reverses the stereoselectivity leading to the 1,2- trans glycoside.…”

Section: Installation Of Glycosidic Linkages In Deoxy Sugarsmentioning

confidence: 99%