Stereoselective Glycosylations – Additions to Oxocarbenium Ions

Hagen, Bas; Vorm, Stefan van der; Hansen, Thomas; Marel, Gijs A. van der; Codée, Jeroen D. C.

doi:10.1002/9783527696239.ch1

Cited by 8 publications

(15 citation statements)

References 75 publications

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“…This structure (see Table 2) places all substituents in a position that allows for maximum stabilization of the thiacarbenium ion. As empirically established by Woerpel and co-workers 20−24 and supported by previous computational studies, 15,16,25−28 an oxocarbenium ion is best stabilized by an equatorial OMe substituent at C2 to allow for electron density donation by the axial C2–H2 bond, while the electron density of the ether group at C3 is nearest and most stabilizing to the electron-depleted anomeric center when placed axially. The same holds true for C5-OMe, which is positioned closest to the positive charge, when taking up the axial- gg -orientation in the E 3 envelope.…”

Section: Resultssupporting

confidence: 61%

Synthesis, Reactivity, and Stereoselectivity of 4-Thiofuranosides

et al. 2019

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Thiosugars, sugars that have their endocyclic oxygen substituted for a sulfur atom, have been used as stable bioisosteres of naturally occurring glycans because the thiosugar glycosydic linkage is supposed to be stabilized toward chemical and enzymatic hydrolysis. We have performed an in-depth investigation into the stability and reactivity of furanosyl thiacarbenium ions, by assessing all four diastereoisomeric thiofuranosides experimentally and computationally. We show that all furanosyl thiacarbenium ions react in a 1,2-cis-selective manner with triethylsilane, reminiscent of their oxo counterparts. The computed conformational space occupied by the thiacarbenium ions is strikingly similar to that of the corresponding furanosyl oxycarbenium ions, indicating that the stereoelectronic substituent effects governing the stability of furanosyl oxocarbenium ions and thiacarbenium ions are very similar. While the thio-ribo-furanose appears to be less reactive than its oxo counterpart, the thio-ara-, lyxo-, and xylo-furanosides appear to be more reactive than their oxygen equivalents. These differences are accounted for using the conformational preference of the donors and the carbocation intermediates. The lower reactivity of the thio-ribo furanosides in (Lewis) acid-mediated reactions and the similarity of the thia- and oxocarbenium ions make thio-ribo-furanosides excellent stabilized analogues of the naturally occurring ribo-furanose sugars.

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Section: Resultssupporting

confidence: 61%

Synthesis, Reactivity, and Stereoselectivity of 4-Thiofuranosides

et al. 2019

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“…Many substitution patterns have been studied by the Woerpel laboratory, and both Woerpel and van der Marel, Codée, and their coworkers have published extensive reviews to which the reader is referred for broader coverage of this important topic. 24,68,72…”

Section: Facial Selectivity Of Nucleophilic Attack On Putative Glycmentioning

confidence: 99%

“…The reader is referred to several other books and reviews for complementary perspectives of the field. 9–24 The concepts of stereodirecting neighboring group participation and anchimeric assistance in glycosylation are not covered in this review.…”

Section: Introductionmentioning

confidence: 99%

The Experimental Evidence in Support of Glycosylation Mechanisms at the S_N1–S_N2 Interface

et al. 2018

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A critical review of the state-of-the-art evidence in support of the mechanisms of glycosylation reactions is provided. Factors affecting the stability of putative oxocarbenium ions as intermediates at the S1 end of the mechanistic continuum are first surveyed before the evidence, spectroscopic and indirect, for the existence of such species on the time scale of glycosylation reactions is presented. Current models for diastereoselectivity in nucleophilic attack on oxocarbenium ions are then described. Evidence in support of the intermediacy of activated covalent glycosyl donors is reviewed, before the influences of the structure of the nucleophile, of the solvent, of temperature, and of donor-acceptor hydrogen bonding on the mechanism of glycosylation reactions are surveyed. Studies on the kinetics of glycosylation reactions and the use of kinetic isotope effects for the determination of transition-state structure are presented, before computational models are finally surveyed. The review concludes with a critical appraisal of the state of the art.

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“… 2 Which mechanism dominates, and, consequently, what product distribution is observed, depends on complex interactions between donor, acceptor, protecting groups, and reagents. 3 While many useful methods successfully leverage these interactions to generate certain glycosidic linkages in a stereoselective manner, 4 − 25 a general solution for the construction of broad classes of linkages has yet to emerge. 26 Here, we show that by matching the electronics of the leaving group to the reactivity of the glycosyl donor, it is possible to obtain S N 2-type glycosylations that afford products with high β-selectivity for a range of acceptors.…”

Section: Introductionmentioning

confidence: 99%

Matching Glycosyl Donor Reactivity to Sulfonate Leaving Group Ability Permits S_N2 Glycosylations

et al. 2019

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Here we demonstrate that highly β-selective glycosylation reactions can be achieved when the electronics of a sulfonyl chloride activator and the reactivity of a glycosyl donor hemiacetal are matched. While these reactions are compatible with the acid- and base-sensitive protecting groups that are commonly used in oligosaccharide synthesis, these protecting groups are not relied upon to control selectivity. Instead, β-selectivity arises from the stereoinversion of an α-glycosyl arylsulfonate in an S N 2-like mechanism. Our mechanistic proposal is supported by NMR studies, kinetic isotope effect (KIE) measurements, and DFT calculations.

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Stereoselective Glycosylations – Additions to Oxocarbenium Ions

Cited by 8 publications

References 75 publications

Synthesis, Reactivity, and Stereoselectivity of 4-Thiofuranosides

Synthesis, Reactivity, and Stereoselectivity of 4-Thiofuranosides

The Experimental Evidence in Support of Glycosylation Mechanisms at the S_N1–S_N2 Interface

Matching Glycosyl Donor Reactivity to Sulfonate Leaving Group Ability Permits S_N2 Glycosylations

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Stereoselective Glycosylations – Additions to Oxocarbenium Ions

Cited by 8 publications

References 75 publications

Synthesis, Reactivity, and Stereoselectivity of 4-Thiofuranosides

Synthesis, Reactivity, and Stereoselectivity of 4-Thiofuranosides

The Experimental Evidence in Support of Glycosylation Mechanisms at the SN1–SN2 Interface

Matching Glycosyl Donor Reactivity to Sulfonate Leaving Group Ability Permits SN2 Glycosylations

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The Experimental Evidence in Support of Glycosylation Mechanisms at the S_N1–S_N2 Interface

Matching Glycosyl Donor Reactivity to Sulfonate Leaving Group Ability Permits S_N2 Glycosylations