Benzyne arylation of oxathiane glycosyl donors

Fascione, M. A.; Turnbull, W. Bruce

doi:10.3762/bjoc.6.19

Cited by 23 publications

(19 citation statements)

References 37 publications

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“…Triol 9 was then either protected under standard conditions to afford oxathiane ketal donors 11-13, or reduced using a combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and Et 3 SiH, before protection to afford oxathiane ether donors 14 and 15. [26] Activation as methyl sulfonium salts: In a first set of experiments we prepared the S-methyl sulfonium ions for comparison to the S-phenyl sulfonium species reported by Boons et al [18] Woerpel and co-workers had previously noted a significant reactivity difference between ethyl and phenyl sulfonium ions, while studying a model system for neighbouring-group participation by sulfide groups. [21] Although their phenyl sulfonium ion reacted with nucleophiles at À45 8C, the ethyl sulfonium ion was stable up to 0 8C.…”

Section: Resultsmentioning

confidence: 99%

“…[25,26] Thioglycoside 8 was synthesised in a one-pot reaction from the pentaacetate 7, then subsequently deacetylated under ZemplØn conditions and subjected to acidic methanol to afford the unprotected oxathiane ketal 9. Triol 9 was then either protected under standard conditions to afford oxathiane ketal donors 11-13, or reduced using a combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and Et 3 SiH, before protection to afford oxathiane ether donors 14 and 15.…”

Section: Resultsmentioning

confidence: 99%

“…[13,14] In this paper, we explore the factors influencing the stereoselectivity of glycosylation reactions involving bicyclic glycosyl sulfonium ions. Recently, we described the synthesis of oxathiane glycosyl donors 4 and 5 [25,26] (Scheme 1b) that are pre-organised to form bicyclic trans-decalin sulfonium ions 6, which are similar to the Boons intermediate 2. We evaluate changes in reactivity and stereoselectivity arising from different substituents on the oxathiane glycosyl donors.…”

Section: Introductionmentioning

confidence: 99%

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Do Glycosyl Sulfonium Ions Engage in Neighbouring‐Group Participation? A Study of Oxathiane Glycosyl Donors and the Basis for their Stereoselectivity

Fascione

Kilner

Leach

et al. 2011

Chemistry A European J

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Neighbouring-group participation has long been used to control the synthesis of 1,2-trans-glycosides. More recently there has been a growing interest in the development of similar strategies for the synthesis of 1,2-cis-glycosides, in particular the use of auxiliary groups that generate sulfonium ion intermediates. However, there has been some debate over the role of sulfonium ion intermediates in these reactions: do sulfonium ions actually engage in neighbouring-group participation, or are they a resting state of the system prior to reaction through an oxacarbenium ion intermediate? Herein, we describe the reactivities and stereoselectivities of a family of bicyclic thioglycosides in which an oxathiane ring is fused to the sugar to form a trans-decalin-like structure. A methyl sulfonium ion derived from one such glycosyl donor is so stable that it can be crystallised from ethanol, yet it reacts with complete stereoselectivity at high temperature. The importance of a ketal group in the oxathiane ring for maintaining this high stereoselectivity is investigated using a combination of experiment and ab initio calculations. The data are discussed in terms of S(N)1 and S(N)2 type mechanisms. Trends in stereoselectivity across a series of compounds are more consistent with selective addition to oxacarbenium ions rather than a shift between S(N)1 and S(N)2 mechanisms.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Do Glycosyl Sulfonium Ions Engage in Neighbouring‐Group Participation? A Study of Oxathiane Glycosyl Donors and the Basis for their Stereoselectivity

Fascione

Kilner

Leach

et al. 2011

Chemistry A European J

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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%

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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