Stereoselective glycosylation using oxathiane glycosyl donors

Fascione, M. A.; Adshead, Sophie J.; Stalford, S. A.; Kilner, Colin A.; Leach, Andrew G.; Turnbull, W. Bruce

doi:10.1039/b913308a

Cited by 81 publications

(85 citation statements)

References 35 publications

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“…Therefore, it is explained that the lack of a methoxy group (30 → 31) destabilized the sulfonium ion intermediate and stereoselectivity became lower (33 α only → 34 α:β = 5.1:1). In other words, the introduction of a methoxy group instead of a hydrogen atom at the benzylic position stabilizes the sulfonium ion intermediate and enables α-selective glycosylation in excellent selectivity even in the case when electron-donating benzyl groups are introduced as protecting groups of a glycosyl donor (14). Intramolecular formation of sulfonium ions by a chiral auxiliary at the 2-hydroxyl group, and the subsequent α-selective glycosylation protocol, is a great success in chemical glycosylation.…”

Section: Stereoselectivity Of Glycosylation Via Glycosyl Sulfoniummentioning

confidence: 99%

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Sulfonium Ions as Reactive Glycosylation Intermediates

Nokami

2012

TIGG

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Glycosyl sulfonium ions are positively charged organosulfur compounds having the positive charge on a sulfur atom that is covalently attached to the anomeric carbon. These species have received attention because of their potential as glycosylation intermediates. Recently, novel methods for the preparation of glycosyl sulfonium ions have been reported. The reactivity of glycosyl sulfonium ions can be controlled by changing the substituents on the sulfur atom and the protecting groups of the hydroxyl groups. Recent studies have also shown that glycosyl sulfonium ions are unique glycosylation intermediates that have modifiable reactivity.

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Section: Stereoselectivity Of Glycosylation Via Glycosyl Sulfoniummentioning

confidence: 99%

“…4c) (14,15). They prepared β-sulfonium ion 14 by the action of trifluoromethanesulfonic anhydride (Tf 2 O), 1,3,5-trimethoxybenzene, and glycosyl sulfoxide 13 having the decalin structure.…”

Section: B Preparation Of Glycosyl Sulfonium Ionsmentioning

confidence: 99%

Sulfonium Ions as Reactive Glycosylation Intermediates

Nokami

2012

TIGG

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“…On the other hand, neighbouring hydroxyl groups of the donor could show influence on the anomeric preference through their protecting substituents, many of which were routinely exploited in various glycosylation methods, such as 2-O-ester-type [8][9][10] or 2-O-picolyl-type [11][12][13] for 1,2-trans glycosylation, and several sulfide auxiliaries [14][15][16][17][18] as well as intramolecular aglycon delivery IAD-type 19,20 for 1,2-cis glycosylation reactions.…”

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confidence: 99%

The intriguing dual-directing effect of 2-cyanobenzyl ether for a highly stereospecific glycosylation reaction

Hoang

Liu

2014

Nat Commun

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The diverse presence as well as their very specific bio-responses of glycoconjugates found in all living species requires scientists to synthesize the precise structure of these complex oligosaccharides for various studies on glycoscience. Very few approaches were able to offer the sole a-or b-glycosylated products, even at the cost of complicating the preparative route or usage of exotic chiral auxiliaries to drive the stereoselectivity. In this report, the unification of solvent assistance and neighbouring group participation concepts have led us to the use of 2-cyanobenzyl ether as the dual-directing auxiliary for stereospecific construction of a-and b-glycosidic bonds from a single starting material, and both isomers can be obtained in exclusive stereoselectivity. This work demonstrates the difference in reactivities of glycosyl acceptors can be employed to completely drive the stereoselectivity, drawing the parallel comparison with the arming/disarming concept, which has been exclusively confined to glycosyl donors.

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“…1,[7][8][9][10] Despite these advances, however, stereocontrol over the formation of the glycosidic linkage still remains a challenge, particularly in the synthesis of 1,2-cis glycosides. [11][12][13][14][15] Much recent work in this field has focussed on the study of stabilised glycosyl sulfonium ions and their stereodirecting ability, [16][17][18][19][20][21][22] including our recent report of oxathiane ketal-S-oxide glycosyl donors 1 for stereoselective 1,2-cis glycosylations (Scheme 1a).…”

Section: Introductionmentioning

confidence: 99%

“…The resulting 2,4,6-trimethoxyphenyl (TMP)-oxathiane ketal sulfonium ions 2 then afforded -glycosides 3 with complete stereoselectivity following heating at 50 °C. However, although glycosylation reactions with oxathiane ketal sulfonium ions 4 are notable for the formation of glycosides with complete -stereoselectivity, 19,21 the resulting O-2 acyclic ketal formed in the product 5 occasionally decomposed under the reaction conditions, diminishing yields in more challenging glycosylation reactions.…”

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confidence: 99%

Stereoselective glycosylations using oxathiane spiroketal glycosyl donors

Fascione

Webb

Kilner

et al. 2012

Carbohydrate Research

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Novel oxathiane spiroketal donors have been synthesised and activated via an umpolung Sarylation strategy using 1,3,5-trimethoxybenzene and 1,3-dimethoxybenzene.The comparative reactivity of the resulting 2,4,6-trimethoxyphenyl (TMP)-and 2,4-dimethoxyphenyl (DMP)-oxathiane spiroketal sulfonium ions is discussed, and theirstereoselectivity in glycosylation reactions are compared to the analogous TMP-and DMPsulfonium ions derived from a oxathiane glycosyl donors bearing a methyl ketal group. The results show that the stereoselectivity of the oxathiane glycosyl donors is dependent on the structure of the ketal group and reactivity can be tuned by varying the substituent on the sulfonium ion. IntroductionThe chemical synthesis of complex oligosaccharides presents many technical challenges ranging from lengthy reaction sequences through to problematic purification steps. Scheme 1 a) Umpolung S-arylation strategy for oxathiane ketal-S-oxide donors 1. b)Oxathiane ketal donor scaffold 4 and oxathiane spiroketal donor scaffold 6.Attempts to arylate glycosyl oxathianes with benzyne led to the formation of glycosyl 3 acetates. 21 However, oxidation of the oxathiane to give oxathiane ketal-S-oxides 1, and subsequent treatment with Tf 2 O, led to the formation of surprisingly stable activated intermediates which were sufficiently long-lived to undergo electrophilic aromatic substitution in the presence 1,3,5-trimethoxybenzene (TMB). Therefore, conversion of the previously nucleophilic sulfide into an electrophilic S(IV) centre facilitated an "umpolung" approach to S-arylation. The resulting 2,4,6-trimethoxyphenyl (TMP)-oxathiane ketal sulfonium ions 2 then afforded -glycosides 3 with complete stereoselectivity following heating at 50 °C. However, although glycosylation reactions with oxathiane ketal sulfonium ions 4 are notable for the formation of glycosides with complete -stereoselectivity, 19,21 the resulting O-2 acyclic ketal formed in the product 5 occasionally decomposed under the reaction conditions, diminishing yields in more challenging glycosylation reactions.Therefore, in an attempt to circumvent this issue, we set out to design a new oxathiane donor scaffold in which the axial methoxy group was replaced with an O-substituent constrained in a spirocyclic ring (Scheme 1b). It was anticipated that following glycosylation, spiroketal sulfonium ion 6 would afford glycosides 7 bearing an O-2 cyclic ketal which would be more stable than the corresponding O-2 acyclic ketal, but still sufficiently labile to be removed by Lewis acid catalysed cleavage. To this end, we present the synthesis and activation of oxathiane spiroketal-S-oxides via an umpolung S-arylation strategy, and compare theirstereoselectivities in glycosylation reactions with the analogous oxathiane ketal sulfoniumions. We also demonstrate that the stability and -stereoselectivity of oxathiane spiroketal sulfonium ions in glycosylation reactions can be modulated by changing the S-aryl appendage exogenous to the oxathiane ring. Both TMP and 2,4-dimet...

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Stereoselective glycosylation using oxathiane glycosyl donors

Abstract: A bicyclic glycosyl donor is activated as an arylsulfonium ion and used to synthesise alpha-glycosides with high stereoselectivity.

Cited by 81 publications

References 35 publications

Sulfonium Ions as Reactive Glycosylation Intermediates

Sulfonium Ions as Reactive Glycosylation Intermediates

The intriguing dual-directing effect of 2-cyanobenzyl ether for a highly stereospecific glycosylation reaction

Stereoselective glycosylations using oxathiane spiroketal glycosyl donors

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