Allyl protecting group mediated intramolecular aglycon delivery (IAD) of glycosyl fluorides

Article abstract of DOI:10.1007/s007060200020

Stereospecific 1,2-cis-glycosylation of 2-O-allyl protected glucosyl and mannosyl fluorides can be achieved via a sequence of allyl isomerization, N-iodosuccinimide mediated tethering, and intramolecular aglycon delivery (IAD). Fluoride is advantageous as

Full text of DOI:10.1007/s007060200020

Monatshefte fuÈr Chemie 133, 449±466 ꢀ2002)
Allyl Protecting Group Mediated
Intramolecular Aglycon Delivery ꢀIAD)
of Glycosyl Fluorides
Ian Cumpstey1, Antony J. Fairbanks1;Ã, and Alison J. Redgrave2
1
Dyson Perrins Laboratory, University of Oxford, Oxford OX1 3QY, United Kingdom
2
GlaxoSmithKline, Medicines Research Centre, Stevenage SG1 2NY, United Kingdom
Summary. Stereospeci®c 1,2-cis-glycosylation of 2-O-allyl protected glucosyl and mannosyl
¯uorides can be achieved via a sequence of allyl isomerization, N-iodosuccinimide mediated
tethering, and intramolecular aglycon delivery ꢀIAD). Fluoride is advantageous as an anomeric
leaving group since extended reaction times can be employed to tether hindered aglycon alcohols
without competitive anomeric activation. TinꢀII) chloride mediated intramolecular glycosylation
furnishes the desired ꢀ-glucosides and ꢁ-mannosides in an entirely stereoselective manner.
Keywords. Carbohydrates; Glycosides; Glycosylation; Stereoselectivity; Intramolecular aglycon
delivery ꢀIAD).
Introduction
Intramolecular aglycon delivery ꢀIAD) is an attractive synthetic approach for the
formation of 1,2-cis-glycosidic linkages. The technique of temporarily tethering
together glycosyl donor and glycosyl acceptor via the 2-hydroxyl group of the
glycosyl donor was originally pioneered for the synthesis of ꢁ-mannosides by
Hindsgaul [1] and Stork [2] and more recently to greater effect by Ogawa [3]. The
principle of the approach is that the glycosylation reaction, which ensues after
tethering, must be intramolecular in nature. This therefore enforces the formation
of a 1,2-cis-glycosidic linkage since the nucleophile must be delivered to the
anomeric centre formally syn to the 2-hydroxyl group.
As part of our ongoing interest in the synthesis of oligosaccharides containing
1,2-cis-linkages we recently reported the development of an N-iodosuccinimide
ꢀNIS) mediated one-pot modi®cation of the original Hindsgaul methodology [4, 5].
Subsequently we have developed 2-O-allyl protected thioglycosides as glycosyl
donors for IAD [6]. Herein, an enol ether at position 2 of the glycosyl donor is
accessed in near quantitative yield by isomerization of a 2-O-allyl protecting
group. Subsequent tethering and intramolecular glycosylation then yield the 1,2-
cis-glycoside. However, whereas good yields were obtained for NIS mediated
Ã
Corresponding author. E-mail: antony.fairbanks@chemistry.ox.ac.uk

450
I. Cumpstey et al.
tethering of thioglycoside donors with a variety of simple aglycon alcohols, in the
cases of more hindered carbohydrate alcohols where tethering occurred more
slowly, limitations arose due to competitive activation of the anomeric leaving
group. The use of an orthogonal anomeric leaving group which cannot be activated
during tethering could provide a solution to this problem. Reported herein are full
details of investigations into the use of glycosyl ¯uorides as donors for allyl
mediated IAD [7].
Results and Discussion
As substrates for IAD investigations the manno ꢀ1) and gluco glycosyl ꢀ2) ¯uorides
bearing allyl protection of the 2-hydroxyl were prepared from their respective
orthoesters. Thus, DAST opening of 3 [8] and 4 [9] followed by an n-propylamine
mediated deacetylation of acetates 5 and 6 gave alcohols 7 and 8 [10]. Finally,
reprotection of the 2-hydroxyl group by treatment with allyl bromide and sodium
hydride in DMF furnished the desired donors 1 and 2 in excellent overall yields
ꢀ1: 78% yield over three steps from 3; 2: 84% yield over three steps from 4;
Scheme 1).
The extremely ef®cient allyl isomerization following Boons' protocol [11]
proceeded as smoothly as had been previously observed in the cases of 2-O-allyl
protected thioglycosides [6]; thus, enol ethers 9 and 10 were furnished in excellent
yields ꢀ96% and 98%, respectively; Scheme 2).
Studies then turned to an investigation of tethering reactions of 9 and 10 with a
variety of aglycon alcohols. Previous work had demonstrated that N-iodosucci-
nimide ꢀNIS) was a suitable reagent for this type of tethering reaction, whereas
attempted acid catalyzed tethering had proved unsuccessful. Therefore, NIS-
mediated tethering of the manno vinyl ether 9 was carried out with a variety of
alcohols 11a±f,h under our established reaction conditions [12]. Pleasingly, the
desired mixed acetals 12a±f,h were obtained in good to excellent yields ꢀTable 1).
The tethering yields for simple non-carbohydrate and primary carbohydrate
alcohols are excellent. Also notable are the cases of the secondary carbohydrate
alcohols 11e and 11f and the steroid 11h, whereby longer reaction times and thus
Scheme 1. ꢀi) DAST, DCM, 0ꢀC; 5: 98%, 6: 84%; ꢀii) n-PrNH2, MeOH, THF, 45ꢀC; 7: 83%, 8: 91%
from 4; ꢀiii) allyl bromide, NaH, DMF, 0ꢀC; 1: 96%, 2: 93%

Intramolecular Aglycon Delivery of Glycosyl Fluorides
451
Scheme 2. ꢀi) Wilkinson's catalyst, BuLi, THF, 70ꢀC; 9: 96% from 1, 10: 98% from 2; ꢀꢀii) ROH
ꢀ
Ê
13a±h, NIS, DCE, À40 C to r.t., 4 A sieves; ꢀiii) AgOTf, DTBMP, SnCl2, DCE or MeCN, 50 C; then
TFA, H2O or NIS, H2O
more ef®cient tethering were possible than during previous studies on thioglyco-
sides where competitive anomeric activation occurred. However, it should be noted
that in the case of the more hindered alcohols 11d±f,h an increasing amount of the
succinimide trapped material 16 ꢀFig. 1) was also isolated. Formation of 16 occurs
by competitive nucleophilic attack by succinimide rather than the desired alcohol,
and therefore indicates a potential limitation of the use of NIS as tethering reagent
in these cases.
In the gluco series, tethering of enol ether 10 with alcohols 11a±e,g,h
proceeded likewise to give the mixed acetals 14a±e,g,h. Whereas excellent yields
were obtained for alcohols 11a±c, slightly lower yields were observed than in the
manno series for some of the more bulky carbohydrates 11d,e. Overall it is clear
that in general tethering is marginally less ef®cient in the gluco series. The steroid
11h was only partially soluble in dichloroethane ꢀDCE), but a change of the solvent
to THF produced an acceptable 68% yield of mixed acetals 14h. Again some
succinimide trapped material, in the gluco series compound 17, was observed in
the cases of the more hindered alcohols.
Attention then turned to activation of the glycosyl ¯uorides and intramolecular
glycosylation. Although activation of glycosyl ¯uorides can be carried out by
the use of any number of different Lewis acids [13], in order to ensure com-
plete stereoselectivity it is crucial that the mixed acetal tether, which itself could
be susceptible to Lewis acid catalyzed cleavage, remains intact so that IAD
can operate. Therefore, a series of several different reaction conditions often em-
ployed for the activation of glycosyl ¯uorides were investigated, including
Cp2HfCl2=AgClO4=DTBMP [14], BF3 Á OEt2 [15], and BF3 Á OEt2=2,6-di-tert-
butyl-4-methylpyridine ꢀDTBMP). Whereas some of the desired products were
usually observed, in these cases product formation was either accompanied by
hydrolysis of the tether to various extents, the formation of ꢀ=ꢁ mixtures of
products ꢀpresumably arising from intermolecular glycosylation following the
hydrolysis of the tether), or occasionally the formation of an intractable mixture of
products. Optimum results were obtained using the Mukaiyama activation

452
I. Cumpstey et al.
Table 1. Tethering and glycosylation yields
Alcohol
Product=yield of mixed
acetalsa
Product=yield of
glycosylationc
11a
11b
MeOH
12a=97%
14a=99%
13a=76%e
15a=89%e
12b=99%
14b=99%
13b=70%e
15b=66%e
11c
12c=98%
14c=91%
13c=61%d,f
15c=63%d
11d
11e
12d=80%
14d=79%
13d=49%,e 75%d
15d=44%,e 46%d
12e=83%
14e=52%
13e=55%d,f
15e=66%d,g
11f
12f=37%
14g=39%
13f=50%d
15g=45%d
11g
11h
12h=72%
14h=68%b
13h=59%d
15h=87%d
Isolated yields; reactions carried out in DCE except where otherwise stated; b reaction carried out in
THF; c isolated yields, acid treatment with TFA except where otherwise stated; d reaction carried out
a
e
in DCE; reaction carried out in acetonitrile; no acid treatment; treatment with NIS, H2O
f
g
Fig. 1. Succinimide trapped materials

Intramolecular Aglycon Delivery of Glycosyl Fluorides
453
conditions [16], i.e. tinꢀII) chloride in combination with silver tri¯ate, addition of
the hindered base DTBMP, and heating to 50ꢀC so that the reaction proceeded at
an ef®cient rate. Under these conditions all mixed acetals furnished the desired
ꢁ-mannosides 13a±f,h and ꢀ-glucosides 15a±e,g,h stereospeci®cally as the pure
1,2-cis-anomers in all cases in good to excellent yields ꢀTable 1).
Two features of the intramolecular glycosylation reaction are worth mention-
ing. The ®rst is that the ef®ciency of glycosylation is solvent dependent. For
example, it was observed that whereas the glycosylation of the manno mixed
acetals 12c was slow in acetonitrile and occurred at the same time as partial
hydrolysis of the tether, an otherwise identical experiment employing DCE as
solvent proceeded very quickly ꢀca. 2 h) and without hydrolysis. Subsequent
glycosylation reactions were therefore carried out with DCE as the solvent.
The second important feature worthy of special consideration is the potential
formation of side-products by nucleophilic trapping of the oxonium ion produced
subsequent to the intramolecular glycosylation reaction. Indeed the question as to
the possible fate of this type of oxonium ion has recently arisen in the Ogawa=Ito
para-methoxybenzyl ꢀPMB) IAD system [17]. In our earlier work on thioglyco-
sides [5], byproducts were observed after glycosylation that were identi®ed as
mixed acetals such as 18 ꢀFig. 2). These presumably arose from trapping of the
oxonium ion produced subsequent to the glycosylation reaction by an external
alcohol acting as a nucleophile. In the thioglycoside cases, treatment of the crude
reaction mixture with tri¯uoroacetic acid ꢀTFA) during work-up resulted in the
hydrolysis of any such mixed acetals and in an increased the yield of the desired
1,2-cis-glycoside.
Analysis of the intramolecular glycosylation reactions of the tethered glycosyl
¯uorides by TLC revealed that varying amounts of byproducts were also sometimes
produced. Interestingly, the formation of these byproducts was generally more
prevalent in the gluco rather than the manno series. Treatment of these materials
with TFA following the standard procedure developed earlier always yielded further
1,2-cis-glycoside product, but it was notable that by-product hydrolysis was much
faster than had previously been observed in the thioglycoside work. Therefore, in the
case of alcohol 11e, which possesses an acid sensitive protecting group which could
be cleaved by acid treatment, rather than adopting this acid work-up procedure in
order to optimize the yield of disaccharide product, the identity of this by-product
was investigated. Rather surprisingly, the minor byproducts were identi®ed as the
enol ethers 19 [18]. Treatment of these enol ethers 19 with NIS=H2O proved an
excellent alternative to the standard acidic work-up procedure since it rapidly
resulted in the formation of the desired glycoside 15e, without any cleavage of the
acid sensitive 4,6-benzylidene protecting group ꢀScheme 3).
Fig. 2. Trapping after glycosylation

454
I. Cumpstey et al.
Scheme 3. ꢀi) NIS, THF, H2O; then Et3N, ꢁ 70%
In summary it has been demonstrated that glycosyl ¯uorides are excellent
glycosyl donors for the allyl mediated IAD approach to 1,2-cis-glycosides, and that
tethering and stereospeci®c intramolecular glycosylation may be achieved for a
variety of primary and secondary carbohydrate alcohols. In particular, the use of
glycosyl ¯uorides is advantageous in that tethering ef®ciency can be increased in
the case of bulky secondary carbohydrate alcohols by the use of extended reaction
times. Comparison with alternative methods of IAD indicates that allyl mediated
IAD is superior to the original approaches of Stork and Hindsgaul in terms of both
simplicity of application and yield and can therefore be considered as com-
plementary to the Ogawa PMB approach. Although tethering is more ef®cient in
the PMB system, the allyl system has the advantages that there is no requirement
for cyclic 4,6-protection of the glycosyl donor in order to produce good yields for
the glycosylation step and that the technique is also applicable for the formation of
ꢀ-gluco linkages. The current disadvantages of allyl IAD are competitive trapping
by succinimide during attempted tethering with the most hindered alcohol ac-
ceptors and the formation of mixed acetal or enol ether side products by further
reaction of the oxonium ion produced after intramolecular glycosylation has
occurred. Further investigations into the use of allyl derived vinyl ethers for 1,2-
cis-glycosylation procedures are currently in progress, and the results will be
reported in due course.
Experimental
General
Melting points were recorded on a Ko¯er hot block and are uncorrected. Proton nuclear magnetic
resonance spectra were recorded on Bruker DPX 400 ꢀ400 MHz) or Bruker AMX 500 ꢀ500 MHz)
spectrometers. Carbon nuclear magnetic resonance spectra were recorded on Bruker AC 200
ꢀ50.3 MHz), Bruker DPX 400 ꢀ100.6 MHz), or Bruker AMX 500 ꢀ125.7 MHz) spectrometers.
Multiplicities were assigned using the DEPT sequence. All chemical shifts are quoted on the ꢂ-scale
in ppm. Infrared spectra were recorded on a Perkin-Elmer 150 Fourier transform spectrophotometer.
Low resolution mass spectra were recorded on a Micromass Platform 1 APCI using atmospheric
pressure chemical ionisation ꢀAPCI). High resolution mass spectra ꢀelectrospray) were performed on
a Waters 2790-Micromass LCT electrospray ionization mass spectrometer or by the EPSRC
Mass Spectrometry Service Centre, Department of Chemistry, University of Wales, Swansea, on
a MAT900 XLT electrospray ionization mass spectrometer. Optical rotations were measured on a
Perkin-Elmer 241 polarimeter with a path length of 1 dm. Concentrations are given in g=100 cm3.
Microanalyses were performed by the microanalytical services of Elemental Microanalysis
Ltd, Devon; the results agreed with the calculated values within experimental error. Thin layer

Intramolecular Aglycon Delivery of Glycosyl Fluorides
455
chromatography ꢀTLC) was carried out on Merck Kieselgel 0.22±0.25 mm thickness glass-backed
sheets pre-coated with 60F254 silica. Plates were developed using 5% w=v ammonium molybdate in
2 M H2SO4. Flash column chromatography was carried out using Sorbsil C60 40=60 silica. Solvents
and reagents were dried and puri®ed before use according to standard procedures; MeOH was
distilled from NaH, CH3CN and CH2Cl2 were distilled from CaH2, and THF was distilled from a
solution of sodium benzophenone ketyl immediately before use. Anhydrous DMF and anhydrous
dichloroethane ꢀDCE) were purchased from Aldrich. Petrol refers to the fraction of light petroleum
ether boiling in the range of 40±60ꢀC. All procedures requiring anhydrous conditions were
performed under an Ar atmosphere in glassware which was ¯ame-dried before use.
2-O-Allyl-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ1; C30H33FO5)
Alcohol 7 ꢀ960 mg, 2.12 mmol) was dissolved in anhydrous DMF ꢀ5 cm3) and cooled to 0ꢀC. Allyl
bromide ꢀ0.36 cm3, 4.24 mmol) was added; then, NaH ꢀ60% in mineral oil, 170 mg, 4.24 mmol) was
added portionwise. After 1 h, TLC ꢀethyl acetate:petrol ˆ 1:3) indicated formation of a single
product ꢀRf ˆ 0.5) and complete consumption of starting material ꢀRf ˆ 0.2). The reaction mixture
was quenched with 100 cm3 H2O and extracted with 2 Â 100 cm3 CH2Cl2. The combined organic
extracts were dried ꢀMgSO4), ®ltered, and concentrated in vacuo. The residue was puri®ed by ¯ash
column chromatography ꢀpetrol:ethyl acetate ˆ 5:1) to afford allylated glycosyl ¯uoride 1 ꢀ1.01 g,
96%) as a colourless oil.
27
1
‰ꢀŠ ˆ ‡35:2 ꢀc ˆ 1.4, CHCl3); H NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 3.71 ꢀ1H, dd, J5,6 ˆ 1.9 Hz,
D
J6;6 ˆ 10:9 Hz, H-6), 3.67 ꢀ1H, dd, J5;6 ˆ 4:5 Hz, H-60), 3.84±3.85 ꢀ1H, m, H-2), 3.86±3.98 ꢀ2H, m,
0
0
H-3, H-5), 4.02 ꢀ1H, at, J ˆ 9.5 Hz, H-4), 4.17 ꢀ1H, dd, Jgem ˆ 13.1 Hz, J ˆ 6.0 Hz, OCHH0), 4.25
ꢀ1H, dd, J ˆ 5.7 Hz, OCHH0), 4.51, 4.88 ꢀ2H, ABq, JAB 10.8 Hz, PhCH2), 4.54, 4.68 ꢀ2H, ABq,
JAB ˆ 12.3 Hz, PhCH2), 4.73 ꢀ2H, s, PhCH2), 5.24 ꢀ1H, dd, Jgem ˆ 1.5 Hz, JZ ˆ 10.3 Hz,
OCH2CHˆCHEHZ), 5.31 ꢀ1H, dd, JE ˆ 17.2 Hz, OCH2CHˆCHEHZ), 5.64 ꢀ1H, dd, J1,2 ˆ 1.8 Hz,
J1,F ˆ 50.6 Hz, H-1), 5.93 ꢀ1H, ddat, OCH2CHˆCH2), 7.16±7.41 ꢀ15H, m, Ar±H); ppm; 13C NMR
ꢀCDCl3, 100 MHz): ꢂ ˆ 68.5 ꢀt, C-6), 72.6, 72.6 ꢀ2  t, PhCH2, OCH2CHˆCH2), 73.3 ꢀdd, 2JC-2,F
ˆ
35.3 Hz, C-2), 73.4, 75.2 ꢀ2 Â t, 2 Â PhCH2), 73.9 ꢀd, C-4), 74.0 ꢀd, C-5), 79.0 ꢀd, C-3), 106.4 ꢀdd,
1JC-1,H-1 ˆ 182.2 Hz, 1JC-1,F ˆ 222.6 Hz, C-1), 118.1 ꢀt, OCH2CHˆCH2), 127.6, 127.7, 127.8, 127.9,
127.9, 128.1, 128.1, 128.3, 128.3, 128.5, 128.7 ꢀ11  d, Ar±CH), 134.5 ꢀd, OCH2CHˆCH2), 138.0,
‡
‡
138.0, 138.1 ꢀ3  s, Ar±C); ppm; MS ꢀAPCI ): m=z ˆ 515 ꢀM ‡ Na , 100%); HRMS: calcd. for
‡
C30H37NO5F ꢀMNH4 ): 510.2656, found: 510.2657.
2-O-Allyl-3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl ¯uoride ꢀ2; C30H33FO5)
Alcohol 8 ꢀ3.94 g, 8.70 mmol) was dissolved in anhydrous DMF ꢀ10 cm3) and cooled to 0ꢀC. Allyl
bromide ꢀ1.5 cm3, 17.4 mmol) was added; then, NaH ꢀ60% in mineral oil, 696 mg, 17.4 mmol) was
added portionwise. After 1 h, TLC ꢀethyl acetate:petrol ˆ 1:3) indicated formation of a single
product ꢀRf ˆ 0.4) and complete consumption of starting material ꢀRf ˆ 0.2). The reaction was
quenched with MeOH ꢀ6 cm3) and concentrated in vacuo. The residue was partitioned between
CH2Cl2 ꢀ2 Â 100 cm3) and H2O ꢀ100 cm3). The combined organic layers were dried ꢀMgSO4),
®ltered, and concentrated in vacuo. The residue was puri®ed by ¯ash column chromatography
ꢀpetrol:ethyl acetate ˆ 6:1) to afford allylated glycosyl ¯uoride 2 ꢀ3.99 g, 93%) as a colourless oil.
22
1
‰ꢀŠ ˆ ‡9:2 ꢀc ˆ 0.5, CHCl3); H NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 3.49 ꢀ1H, ddd, J1,2 ˆ 6.9 Hz,
D
0
J2,3 ˆ 8.6 Hz, J2,F ˆ 12.3 Hz, H-2), 3.59 ꢀ1H, ddd, J4,5 ˆ 9.5 Hz, J5,6 ˆ 2.6 Hz, J5;6 ˆ 3:7 Hz, H-5),
3.64 ꢀ1H, at, J ˆ 8.7 Hz, H-3), 3.69±3.77 ꢀ3H, m, H-4, H-6, H-60), 4.20 ꢀ1H, dd, Jgem ˆ 12.4 Hz,
J ˆ 5.8 Hz, OCHH0), 4.34 ꢀ1H, dd, J ˆ 5.7 Hz, OCHH0), 4.54, 4.93 ꢀ2H, ABq, JAB ˆ 10.8 Hz,
PhCH2), 4.55, 4.64 ꢀ2H, ABq, JAB ˆ 12.2 Hz, PhCH2), 4.80, 4.93 ꢀ2H, ABq, JAB ˆ 10.8 Hz, PhCH2),
5.21 ꢀ1H, dd, J1,F ˆ 52.8 Hz, H-1), 5.22 ꢀ1H, dd, Jgem ˆ 1.6 Hz, JZ ˆ 10.3 Hz, OCH2CHˆCHEHZ),
5.32 ꢀ1H, dd, JE ˆ 17.3 Hz, OCH2CHˆCHEHZ), 5.95 ꢀ1H, ddt, OCH2CHˆCH2), 7.14±7.38 ꢀ15H, m,

456
I. Cumpstey et al.
Ar±H) ppm; 13C NMR ꢂC ꢀCDCl3, 100 MHz): ꢂ ˆ 68.3, 73.3, 73.5, 75.0, 75.5 ꢀ5  t, 3  PhCH2,
OCH2CHˆCH2, C-6), 74.7, 76.8, 83.4 ꢀ3  d, C-3, C-4, C-5), 81.2 ꢀdd, 2JC-2,F ˆ 21.5 Hz, C-2), 109.7
1
ꢀdd, JC-1,F ˆ 215.5 Hz, C-1), 117.6 ꢀt, OCH2CHˆCH2), 127.7, 127.8, 127.8, 127.9, 127.9, 128.4,
128.4 ꢀ7  d, Ar±CH), 134.3 ꢀd, OCH2CHˆCH2), 137.8, 137.8, 138.2 ꢀ3  s, Ar±C) ppm; MS
‡
‡
ꢀAPCI ): m=z ˆ 515 ꢀM ‡ Na , 10%).
2-O-Acetyl-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ5; C29H31FO6)
Orthoester 3 ꢀ16.7 g, 32.8 mmol) was dissolved in 80 cm3 freshly distilled CH2Cl2. The mixture was
cooled to 0ꢀC, and ꢀdiethylamino)-sulfur tri¯uoride ꢀDAST, 5.1 cm3, 37.7 mmol) was added. The
reaction mixture was stirred at 0ꢀC. After 7 h, TLC ꢀpetrol:ethyl acetate ˆ 3:1) indicated formation of
a product ꢀRf ˆ 0.5) and complete consumption of starting material ꢀRf ˆ 0.3). The reaction was
diluted with diethyl ether ꢀ200 cm3) and then washed with H2O ꢀ2 Â 200 cm3). The combined
organics were dried ꢀMgSO4), ®ltered, and concentrated in vacuo. The residue was puri®ed by ¯ash
column chromatography ꢀpetrol:ethyl acetate ˆ 5:1, 1% Et3N) to afford acetylated glycosyl ¯uoride
5 ꢀ15.8 g, 98%) as a pale yellow oil.
23
D
1
‰ꢀŠ ˆ ‡13:3 ꢀc ˆ 1.0, CHCl3); IR ꢀthin ®lm): ꢃ ˆ 1751 ꢀs, CˆO) cmÀ1; H NMR ꢀ400 MHz,
CDCl3): ꢂ ˆ 2.17 ꢀ3H, s, CH3), 3.72 ꢀ1H, d, J6;6 ˆ 10:9 Hz, H-6), 3.82 ꢀ1H, dd, J5;6 ˆ 2:7 Hz, H-60),
3.97±3.99 ꢀ3H, m, H-3, H-4, H-5), 4.49, 4.87 ꢀ2H, ABq, JAB ˆ 10.7 Hz, PhCH2), 4.52, 4.69 ꢀ2H,
ABq, JAB ˆ 12.1 Hz, PhCH2), 4.57, 4.72 ꢀ2H, ABq, JAB ˆ 10.9 Hz, PhCH2), 5.48 ꢀ1H, br s, H-2),
5.62 ꢀ1H, dd, J1,2 ˆ 1.9 Hz, J1,F ˆ 49.1 Hz, H-1), 7.15±7.38 ꢀ15H, m, Ar±H) ppm; 13C NMR ꢀCDCl3,
100 MHz): ꢂ ˆ 21.0 ꢀq, CH3), 67.0 ꢀdd, 2JC-2,F ˆ 39.9 Hz, C-2), 68.2 ꢀt, C-6), 72.1, 73.5, 75.3 ꢀ3  t,
0
0
3
1
3  PhCH2), 73.3 ꢀd, C-4), 73.8 ꢀdd, JC-5,F ˆ 2.0 Hz, C-5), 77.2 ꢀd, C-3), 105.5 ꢀdd, JC-1,H
ˆ
1
182.6 Hz, JC-1,F ˆ 221.0 Hz, C-1), 127.8, 127.8, 127.9, 128.0, 128.1, 128.4, 128.5 ꢀ7  d, Ar±CH),
‡
‡
137.6, 138.0, 138.1 ꢀ3  s, Ar±C), 170.1 ꢀs, CˆO) ppm; MS ꢀAPCI ) ˆ 517 ꢀM ‡ Na , 18%);
‡
HRMS: calcd. for C29H35NO6F ꢂMNH4 †: 512.2448, found: 512.2451.
2-O-Acetyl-3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl ¯uoride ꢀ6; C29H31FO6)
Orthoester 4 ꢀ1.0 g, 1.92 mmol) was dissolved in 8 cm3 freshly distilled CH2Cl2. The mixture was
cooled to 0ꢀC, and DAST ꢀ0.33 cm3, 2.50 mmol) was added. The reaction mixture was stirred at 0ꢀC.
After 3.5 h, TLC ꢀCH2Cl2: ether ˆ 14:1) indicated formation of a product ꢀRf ˆ 0.8) and complete
consumption of starting material ꢀRf ˆ 0.7). The reaction was quenched with ice-water ꢀ200 cm3) and
extracted with diethyl ether ꢀ2 Â 200 cm3). The combined organics were dried ꢀMgSO4), ®ltered, and
concentrated in vacuo. The residue was puri®ed by ¯ash column chromatography ꢀpetrol:ethyl
acetate ˆ 4:1) to afford acetylated glycosyl ¯uoride 6 ꢀ796 mg, 84%) as a colourless oil.
22
D
1
‰ꢀŠ ˆ ‡15:3 ꢀc ˆ 1.25, CHCl3); IR ꢀthin ®lm): ꢃ ˆ 1750 ꢀs, CˆO) cmÀ1; H NMR ꢀ400 MHz,
CDCl3): ꢂ ˆ 2.02 ꢀ3H, s, CH3), 3.67±3.75 ꢀ4H, m, H-3, H-5, H-6, H-60), 3.86 ꢀ1H, at, J ˆ 9.0 Hz, H-
4), 4.56, 4.78 ꢀ2H, ABq, JAB ˆ 11.2 Hz, PhCH2), 4.56, 4.63 ꢀ2H, ABq, JAB ˆ 12.1 Hz, PhCH2), 4.71,
4.78 ꢀ2H, ABq, JAB ˆ 11.6 Hz, PhCH2), 5.09±5.15 ꢀ1H, m, H-2), 5.27 ꢀ1H, dd, J1,2 ˆ 6.1 Hz,
J1,F ˆ 52.9 Hz, H-1), 7.16±7.36 ꢀ15H, m, Ar±H) ppm; 13C NMR ꢀCDCl3, 100 MHz): ꢂ ˆ 20.8 ꢀq,
CH3), 68.4, 73.6, 74.4, 74.9 ꢀ4 Â t, C-6, 3 Â PhCH2), 72.5 ꢀdd, C-2), 75.0, 81.5, 81.6 ꢀ3 Â d, C-3, C-4,
C-5), 106.7 ꢀdd, C-1), 127.7, 127.8, 127.8, 127.9, 128.0, 128.4, 128.4, 128.9 ꢀ8 Â d, Ar±CH), 137.6,
137.8 ꢀ2  s, Ar±C), 169.4 ꢀs, CˆO) ppm; 19F NMR ꢀCDCl3, 376 MHz): ꢂ ˆ À136.8 ꢀdd,
‡
‡
‡
,
J1,F ˆ 52.9 Hz, J2,F ˆ 10.2 Hz) ppm; MS ꢀAPCI ): m=z ˆ 533 ꢀM ‡ K , 100%), 517 ꢀM ‡ Na
15%), 475 ꢀM-F, 5%).
3,4,6-Tri-O-benzyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ7; C27H29FO5)
Acetate 5 ꢀ2.0 g, 4.04 mmol) was dissolved in MeOH ꢀ5 cm3), THF ꢀ10 cm3), and n-propylamine
ꢀ5 cm3), and the reaction mixture was stirred at 45ꢀC. After 15 h, TLC ꢀethyl acetate:petrol ˆ 1:3)

Intramolecular Aglycon Delivery of Glycosyl Fluorides
457
indicated formation of a product ꢀRf ˆ 0.2) and complete consumption of starting material ꢀRf ˆ 0.4).
The mixture was concentrated in vacuo and puri®ed by ¯ash column chromatography ꢀpetrol:ethyl
acetate ˆ 3:1, 1% Et3N) to afford alcohol 7 ꢀ1.56 g, 83%) as a colourless oil.
23
1
‰ꢀŠ ˆ ‡34:2 ꢀc ˆ 0.5, CHCl3); H NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 3.70 ꢀ1H, dd, J5,6 ˆ 1.6 Hz,
D
J6;6 ˆ 10:8 Hz, H-6), 3.78 ꢀ1H, dd, J5;6 ˆ 3:5 Hz, H-60), 3.87±3.90 ꢀ1H, m, H-3), 3.94±3.96 ꢀ2H, m,
0
0
H-4, H-5), 4.12±4.13 ꢀ1H, m, H-2), 4.54, 4.67 ꢀ2H, ABq, JAB ˆ 12.2 Hz, PhCH2), 4.54, 4.83 ꢀ2H,
ABq, JAB ˆ 10.8 Hz, PhCH2), 4.71, 4.74 ꢀ2H, ABq, JAB ˆ 11.4 Hz, PhCH2), 5.68 ꢀ1H, dd,
J1,2 ˆ 1.7 Hz, J1,F ˆ 49.5 Hz, H-1), 7.17±7.37 ꢀ15H, m, Ar±H) ppm; 13C NMR ꢀCDCl3, 100 MHz):
ꢂ ˆ 67.1 ꢀdd, 2JC-2,F ˆ 39.0 Hz, C-2), 68.2 ꢀd, C-6), 72.4, 73.5, 75.2 ꢀ3  t, 3  PhCH2), 73.2 ꢀd, C-4),
3
3
1
73.4 ꢀdd, JC-5,F ˆ 2.7 Hz, C-5), 79.1 ꢀdd, JC-3,F ˆ 1.8 Hz, C-3), 107.2 ꢀdd, JC-1,H-1 ˆ 181.9 Hz,
1JC-1,F ˆ 217.7 Hz, C-1), 127.7, 127.8, 127.9, 127.9, 128.0, 128.1, 128.4, 128.6 ꢀ8  d, Ar±CH),
137.6, 137.9, 138.0 ꢀ3 Â s, Ar±C) ppm.
3,4,6-Tri-O-benzyl-ꢁ-D-glucopyranosyl ¯uoride ꢀ8; C27H29FO5)
Orthoester 4 ꢀ5.00 g, 9.62 mmol) was dissolved in 20 cm3 freshly distilled CH2Cl2 in a ¯ame-dried
¯ask, cooled to 0ꢀC under Ar, and DAST ꢀ1.65 cm3, 12.5 mmol) was added. After 7.5 h, TLC ꢀethyl
acetate:petrol ˆ 1:3) indicated formation of a product ꢀRf ˆ 0.45) and complete consumption of
starting material ꢀRf ˆ 0.5). The reaction was quenched with water ꢀ200 cm3) and extracted with
diethyl ether ꢀ2 Â 150 cm3). The organic extracts were dried ꢀMgSO4), ®ltered, and concentrated
in vacuo. The residue was dissolved in THF ꢀ10 cm3), MeOH ꢀ5 cm3), and n-propylamine ꢀ5 cm3)
and stirred at 45ꢀC. After 16.5 h, TLC ꢀethyl acetate:petrol ˆ 1:3) indicated formation of a single
product ꢀRf ˆ 0.2). The mixture was concentrated in vacuo. The residue was puri®ed by ¯ash column
chromatography ꢀpetrol:ethyl acetate ˆ 4:1) to afford alcohol 8 ꢀ3.94 g, 91%) as a white crystalline
solid.
22
D
M.p.: 84ꢀC ꢀdiethyl ether=petrol; Ref. [10]: 80±82ꢀC); ‰ꢀŠ ˆ ‡31:5 ꢀc ˆ 0.55 in CHCl3; Ref.
22
D
[10]: ‰ꢀŠ ˆ ‡25:2); 1H NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 3.59±3.80 ꢀ6H, m, H-2, H-3, H-4, H-5, H-6,
H-60), 4.54, 4.62 ꢀ2H, ABq, JAB ˆ 12.0 Hz, PhCH2), 4.57, 4.78 ꢀ2H, ABq, JAB ˆ 11.1 Hz, PhCH2),
4.81, 4.85 ꢀ2H, ABq, JAB ˆ 11.5 Hz, PhCH2), 5.17 ꢀ1H, d, J1,2 ˆ 6.5 Hz, J1,F ˆ 53.0 Hz, H-1), 7.17±
7.40 ꢀ15H, m, Ar±H) ppm.
2-O-Prop-10-enyl-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ9; C30H33FO5)
Wilkinson's catalyst ꢀ185 mg, 0.20 mmol) was dissolved in 4 cm3 freshly distilled THF, and the
solution was degassed. n-Butyllithium ꢀ1.6 M solution in hexanes, 0.19 cm3, 0.30 mmol) was added,
and the mixture was stirred for 1 h. Allylated mannosyl ¯uoride 1 ꢀ975 mg, 1.98 mmol) was
dissolved in 4 cm3 freshly distilled THF and heated to 70ꢀC. The catalyst solution was added via a
cannular under Ar. After 1 h, TLC ꢀethyl acetate:petrol ˆ 1:3) indicated formation of a single product
ꢀRf ˆ 0.51) and complete consumption of starting material ꢀRf ˆ 0.49). The reaction was allowed to
cool, diluted with CH2Cl2 ꢀ20 cm3), and concentrated in vacuo. The residue was puri®ed by ¯ash
column chromatography ꢀpetrol:ethyl acetate ˆ 6:1, 1% Et3N) to afford vinyl ethers 9 ꢀ934 mg, 96%)
as a pale yellow oil.
1
Partial data: H NMR ꢀ400 MHz, CDCl3): Z:E ˆ 2.7:1; E-isomer: ꢂ ˆ 1.55 ꢀ3H, dd, J ˆ 1.7 Hz,
J ˆ 6.8 Hz, OCHˆCHCH3), 5.02 ꢀ1H, dq, JE ˆ 12.4 Hz, OCHˆCHCH3), 5.66 ꢀ1H, dd, J1,2 ˆ 1.9 Hz,
J1,F ˆ 50.2 Hz, H-1), 6.12 ꢀ1H, dq, OCHˆCHCH3) ppm; Z-isomer: ꢂ ˆ 1.63 ꢀ3H, dd, J ˆ 1.6 Hz,
J ˆ 6.9 Hz, OCHˆCHCH3), 5.62 ꢀ1H, dd, J1,2 ˆ 2.0 Hz, J1,F ˆ 50.5 Hz, H-1), 5.97 ꢀ1H, dq,
JZ ˆ 6.0 Hz, OCHˆCHCH3) ppm; 13C NMR ꢀCDCl3, 100 MHz): E-isomer: ꢂ ˆ 12.3 ꢀq,
1
OCHˆCHCH3), 102.4 ꢀd, OCHˆCHCH3), 105.6 ꢀdd, JC-1,F ˆ 221.7 Hz, C-1), 145.5 ꢀd,
OCHˆCHCH3) ppm; Z-isomer: ꢂ ˆ 9.4 ꢀq, OCHˆCHCH3), 104.2 ꢀd, OCHˆCHCH3), 106.1 ꢀdd,
‡
‡
,
1JC-1,F ˆ 220.7 Hz, C-1), 144.5 ꢀd, OCHˆCHCH3) ppm; MS ꢀAPCI ): m=z ˆ 515 ꢀM ‡ Na
‡
100%); HRMS: calcd. for C30H37NO5F ꢂMNH4 †: 510.2656, found: 510.2663.

458
I. Cumpstey et al.
2-O-Prop-10-enyl-3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl ¯uoride ꢀ10; C30H33FO5)
Wilkinson's catalyst ꢀ390 mg, 0.42 mmol) was dissolved in 8 cm3 freshly distilled THF, and the
solution was degassed. n-Butyl lithium ꢀ1.6 M solution in hexanes, 0.4 cm3, 0.63 mmol) was added,
and the mixture was stirred for 1 h. Allylated glucosyl ¯uoride 2 ꢀ2.06 g, 4.19 mmol) was dissolved in
8 cm3 freshly distilled THF and heated to 70ꢀC. The catalyst solution was added via a cannular under
Ar. After 45 min, the reaction was allowed to cool, diluted with 20 cm3 CH2Cl2, and concentrated in
vacuo. The residue was puri®ed by ¯ash column chromatography ꢀpetrol:ethyl acetate ˆ 5:1, 1%
Et3N) to afford vinyl ethers 10 ꢀ2.02 g, 98%) as a pale yellow oil.
1
Partial data: H NMR ꢀ400 MHz, CDCl3): E:Z ˆ 1:2.3; E-isomer: ꢂ ˆ 1.58 ꢀ3H, dd, J ˆ 1.6 Hz,
J ˆ 7.0 Hz, OCHˆCHCH3), 5.08 ꢀ1H, dq, JE ˆ 12.2 Hz, OCHˆCHCH3), 5.23 ꢀ1H, dd, J1,2 ˆ 6.3 Hz,
J1,F ˆ 52.5 Hz, H-1), 6.23 ꢀ1H, d, OCHˆCHCH3) ppm; Z-isomer: ꢂ ˆ 1.65 ꢀ3H, dd, J ˆ
1.7 Hz, J ˆ 6.8 Hz, OCHˆCHCH3), 4.51 ꢀ1H, aquin, J ˆ 6.6 Hz, OCHˆCHCH3), 5.25 ꢀ1H, m,
J1,2 ˆ 6.4 Hz, J1,F ˆ 52.7 Hz, H-1), 6.16 ꢀ1H, dd, JZ ˆ 6.1 Hz, OCHˆCHCH3) ppm; 13C NMR ꢀCDCl3,
1
100 MHz): E-isomer: ꢂ ˆ 12.2 ꢀq, OCHˆCHCH3), 102.1 ꢀd, OCHˆCHCH3), 108.4 ꢀdd, JC-1,F
ˆ
217.0 Hz, C-1), 146.4 ꢀd, OCHˆCHCH3) ppm; Z-isomer: ꢂ ˆ 9.3 ꢀq, OCHˆCHCH3), 101.5 ꢀd,
1
‡
OCHˆCHCH3), 108.5 ꢀdd, JC-1,F ˆ 213.3 Hz, C-1), 145.6 ꢀd, OCHˆCHCH3) ppm; MS ꢀES ):
‡
‡
m=z ˆ 510 ꢀM ‡ NH4 , 100%); HRMS: calcd. for C30H37NO5F ꢂMNH4 †: 510.2656, found: 510.2663.
General procedure for NIS mediated tethering
3
Ê
NIS ꢀ3 equiv.) and powdered molecular sieves ꢀ4 A) were stirred in 1 cm dry DCE under Ar at
À40ꢀC. The alcohol ꢀ1.5±3 equiv.) was added via a cannular under Ar in 1.5 cm3 dry DCE. The vinyl
ether ꢀ0.1 mmol) was added via a cannular under Ar in 1.5 cm3 dry DCE, and the mixture was
allowed to warm slowly to room temperature. After 1±24 h, the mixture was diluted with DCM,
washed with aqueous Na2S2O3 solution, dried, ®ltered and concentrated in vacuo. The resulting
residue was puri®ed by ¯ash column chromatography to give the mixed acetals.
2-O-52-Iodo-1-methoxypropyl)-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl
¯uoride ꢀ12a; C31H36FIO6)
Vinyl ethers 9 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11a ꢀ0.010 ml, 0.24 mmol) gave
‡
‡
mixed acetals 12a ꢀ102 mg, 97%) as a colourless oil; MS ꢀAPCI ): m=z ˆ 673 ꢀM ‡ Na , 15%).
2-O-51-Cyclohexyloxy-2-iodopropyl)-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl
¯uoride ꢀ12b; C36H44FIO6)
Vinyl ethers 9 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11b ꢀ0.034 cm3, 0.33 mmol) gave
‡
‡
mixed acetals 12b ꢀ115 mg, 99%) as a colourless oil; MS ꢀAPCI ): m=z ˆ 741 ꢀM ‡ Na , 5%).
2-O-51-51,2:3,4-di-O-isopropylidene-ꢀ-D-galactopyranos-6-O-yl)-2-iodopropyl)-
3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ12c; C42H52FIO11)
Vinyl ethers 9 ꢀ178 mg, 0.36 mmol), NIS ꢀ243 mg, 1.1 mmol), and 11c ꢀ212 mg, 0.82 mmol) gave
‡
‡
mixed acetals 12c ꢀ311 mg, 98%) as a colourless oil; MS ꢀES ): m=z ˆ 917 ꢀM ‡ K , 25%), 901
‡
‡
ꢀM ‡ Na , 100%), 896 ꢀM ‡ NH4 , 32%).
2-O-52-Iodo-1-5methyl 2,3,4-tri-O-benzyl-ꢀ-D-mannopyranosid-6-O-yl)-
propyl)-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ12d; C58H64FIO11)
Vinyl ethers 9 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11d ꢀ151 mg, 0.33 mmol) gave
mixed acetals 12d ꢀ140 mg, 80%) as a colourless oil; MS ꢀAPCIÀ): m=z ˆ 1117 ꢀM ‡ ClÀ, 92%).

Intramolecular Aglycon Delivery of Glycosyl Fluorides
459
2-O-52-Iodo-1-5methyl 2-O-benzyl-4,6-O-benzylidene-ꢀ-D-mannopyranosid-3-O-yl)-
propyl)-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ12e; C51H56FIO11)
Vinyl ethers 9 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11e ꢀ121 mg, 0.33 mmol) gave
mixed acetals 12e ꢀ134 mg, 83%) as a colourless oil; MS ꢀAPCIÀ): m=z ˆ 1025 ꢀM ‡ ClÀ, 15%).
2-O-52-Iodo-1-5methyl 2,3,6-tri-O-benzyl-ꢀ-D-mannopyranosid-4-O-yl)-
propyl)-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ12f; C58H64FIO11)
Vinyl ethers 9 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11f ꢀ226 mg, 0.49 mmol) gave
mixed acetals 12f ꢀ65 mg, 37%) as a colourless oil; MS ꢀAPCIÀ): m=z ˆ 1117 ꢀM ‡ ClÀ, 8%).
2-O-51-5Cholestan-3-ꢁ-yloxy)-2-iodopropyl)-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl
¯uoride ꢀ12h; C57H80FIO6)
Vinyl ethers 9 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11h ꢀ136 mg, 0.33 mmol) gave
mixed acetals 12h ꢀ118 mg, 72%) as a colourless oil; MS ꢀAPCIÀ): m=z ˆ 1041 ꢀM ‡ ClÀ, 18%).
General procedure for intramolecular glycosylation
2,6-Di-tert-butyl-4-methylpyridine ꢀDTBMP, 2 equiv.), silver tri¯ate ꢀ2 equiv.), anhydrous tinꢀII)
3
Ê
chloride ꢀ2 equiv.), and powdered molecular sieves ꢀ4 A) were stirred in 1 cm dry DCE under Ar at
50ꢀC. The mixed acetals ꢀ0.1 mmol) were added via a cannular under argon in 3 cm3 dry DCE, and
the reaction was stirred at 50ꢀC until TLC indicated disappearance of starting material. TFA ꢀ2 cm3)
and H2O ꢀ1 cm3) were added, and the solution was stirred for further 30 min. Diethyl ether was
added, and the mixture ®ltered through Celite1, washed with saturated aqueous NaHCO3 and brine,
dried ꢀMgSO4), ®ltered, and concentrated in vacuo. The resulting residue was puri®ed by ¯ash
column chromatography to give the pure 1,2-cis-glycoside.
Methyl 3,4,6-tri-O-benzyl-ꢁ-D-mannopyranoside ꢀ13a; C28H32O6)
Mixed acetals 12a ꢀ102 mg, 0.157 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ64 mg, 0.314 mmol),
silver tri¯uoromethanesulfonate ꢀ81 mg, 0.314 mmol), and anhydrous tinꢀII) chloride ꢀ60 mg,
0.314 mmol) gave ꢁ-mannoside 13a ꢀ55 mg, 76%) as a colourless oil.
24
‰ꢀŠ ˆ À13 ꢀc ˆ 0.75, CHCl3; Ref. [4]: [ꢀ]D ˆ À13 ꢀc ˆ 1.0, CHCl3)); 1H NMR ꢀ500 MHz,
D
0
CDCl3): ꢂ ˆ 3.47 ꢀ1H, ddd, J4,5 ˆ 9.5 Hz, J5,6 ˆ 5.0 Hz, J5;6 ˆ 1:3 Hz, H-5), 3.57 ꢀ3H, s, OCH3),
3.57±3.60 ꢀ1H, m, H-3), 3.74 ꢀ1H, dd, J6;6 ˆ 10:8 Hz, H-6), 3.80 ꢀ1H, dd, H-60), 3.88 ꢀ1H, at,
0
J ˆ 9.4 Hz, H-4), 4.11 ꢀ1H, d, J2,3 ˆ 3.0 Hz, H-2), 4.35 ꢀ1H, s, H-1), 4.55, 4.90 ꢀ2H, ABq,
JAB ˆ 10.8 Hz, PhCH2), 4.58, 4.65 ꢀ2H, ABq, JAB ˆ 12.3 Hz, PhCH2), 4.69, 4.78 ꢀ2H, ABq,
JAB ˆ 11.7 Hz, PhCH2), 7.22±7.40 ꢀ15H, m, Ar±H) ppm; 13C NMR ꢀ125 MHz, CDCl3): 1JC-1,H-1
ˆ
156.7 Hz.
Cyclohexyl 3,4,6-tri-O-benzyl-ꢁ-D-mannopyranoside ꢀ13b; C33H40O6)
Mixed acetals 12b ꢀ112 mg, 0.156 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ64 mg, 0.312 mmol),
silver tri¯uoromethanesulfonate ꢀ80 mg, 0.312 mmol), and anhydrous tinꢀII) chloride ꢀ59 mg,
0.312 mmol) gave ꢁ-mannoside 13b ꢀ50 mg, 60% plus a further 8 mg ꢀ10%) by subsequent acid
treatment of the combined minor products; overall yield: 58 mg, 70%) as a colourless oil.
24
‰ꢀŠ ˆ À20 ꢀc ˆ 0.4, CHCl3; Ref. [4]: [ꢀ]D ˆ À19 ꢀc ˆ 1.6, CHCl3)); 1H NMR ꢀ500 MHz,
D
CDCl3): ꢂ ˆ 1.20±2.02 ꢀ10H, m, cyclohexyl-H), 2.50 ꢀ1H, br s, OH-2), 3.43±3.45 ꢀ1H, m, H-5), 3.58
ꢀ1H, br d, J3,4 ˆ 8.6 Hz, H-3), 3.61±3.81 ꢀ3H, m, H-6, H-60, OCH), 3.86 ꢀ1H, at, J ˆ 9.3 Hz, H-4),

460
I. Cumpstey et al.
4.08 ꢀ1H, br s, H-2), 4.56 ꢀ1H, s, H-1), 4.58, 4.63 ꢀ2H, ABq, JAB ˆ 12.1 Hz, PhCH2), 4.58, 4.91 ꢀ2H,
ABq, JAB ˆ 10.7 Hz, PhCH2), 4.69, 4.80 ꢀ2H, ABq, JAB ˆ 11.7 Hz, PhCH2), 7.23±7.41 ꢀ15H, m,
1
Ar±H) ppm; 13C NMR ꢀ125 MHz, CDCl3): JC-1,H-1 ˆ 155.3 Hz.
3,4,6-Tri-O-benzyl-ꢁ-D-mannopyranosyl-51 ! 6)-1,2:3,4-di-O-isopropylidene-
ꢀ-D-galactopyranose ꢀ13c; C39H48O11)
Mixed acetals 12c ꢀ124 mg, 0.14 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ57 mg, 0.28 mmol),
silver tri¯uoromethanesulfonate ꢀ72 mg, 0.28 mmol), and anhydrous tinꢀII) chloride ꢀ53 mg,
0.28 mmol) gave ꢁ-manno disaccharide 13c ꢀ60 mg, 61%) as a colourless oil.
22
D
1
‰ꢀŠ ˆ À50:7 ꢀc ˆ 0.55, CHCl3; Ref. [4]: [ꢀ]D ˆ À53 ꢀc ˆ 1.3, CHCl3)); H NMR ꢀ400 MHz,
CDCl3): ꢂ ˆ 1.32, 1.34, 1.44, 1.54 ꢀ12H, 4  s, 4  CH3), 3.42 ꢀ1H, ddd, J4,5 ˆ 9.8 Hz, J5,6 ˆ 2.2 Hz,
0
J5;6 ˆ 4:6 Hz, H-5b), 3.56 ꢀ1H, dd, J2,3 ˆ 3.1 Hz, J3,4 ˆ 9.2 Hz, H-3b), 3.70±3.78 ꢀ3H, m, H-6a, H-6b,
H-60b), 3.92 ꢀ1H, at, J ˆ 9.5 Hz, H-4b), 4.03 ꢀ1H, dat, J ˆ 2.2 Hz, J5,6 ˆ 7.8 Hz, H-5a), 4.13 ꢀ1H, dd,
J5;6 ˆ 2:7 Hz, J6;6 ˆ 11:2 Hz, H-60a), 4.22 ꢀ1H, dd, J3,4 ˆ 7.9 Hz, J4,5 ˆ 1.9 Hz, H-4a), 4.22 ꢀ1H, d,
H-2b), 4.32 ꢀ1H, dd, J1,2 ˆ 5.0 Hz, J2,3 ˆ 2.4 Hz, H-2a), 4.5 ꢀ1H, s, H-1b), 4.52, 4.90 ꢀ2H, ABq, JAB
10.8 Hz, PhCH2), 4.54, 4.64 ꢀ2H, ABq, JAB ˆ 12.1 Hz, PhCH2), 4.60 ꢀ1H, dd, H-3a), 4.66, 4.78 ꢀ2H,
ABq, JAB ˆ 12.0 Hz, PhCH2), 5.55 ꢀ1H, d, H-1a), 7.18±7.39 ꢀ15H, m, Ar±H) ppm; 13C NMR
0
0
1
ꢀ125 MHz, CDCl3): JC-1b,H-1b ˆ 160.0 Hz.
Methyl 3,4,6-tri-O-benzyl-ꢁ-D-mannopyranosyl-51 ! 6)-2,3,4-tri-O-benzyl-
ꢀ-D-mannopyranoside ꢀ13d; C55H60O11)
Mixed acetals 12d ꢀ136 mg, 0.126 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ52 mg, 0.25 mmol),
silver tri¯uoromethanesulfonate ꢀ65 mg, 0.312 mmol), and anhydrous tinꢀII) chloride ꢀ48 mg,
0.312 mmol) gave ꢁ-manno disaccharide 13d ꢀ125 mg, 75%) as a colourless oil.
24
‰ꢀŠ ˆ ‡16:0 ꢀc ˆ 1.1 in CHCl3; Ref. [2]: [ꢀ]D ˆ ‡ 16.5 ꢀc ˆ 1.0, CHCl3)); 1H NMR ꢀ500 MHz,
D
0
CDCl3): ꢂ ˆ 3.30 ꢀ3H, s, CH3), 3.40 ꢀ1H, ddd, J4,5 ˆ 9.7 Hz, J5,6 ˆ 4.7 Hz, J5;6 ˆ 2:4 Hz, H-5b), 3.52
ꢀ1H, dd, J2,3 ˆ 3.0 Hz, J3,4 ˆ 9.2 Hz, H-3b), 3.70±3.76 ꢀ3H, m, H-6b, H-60b, H-6a), 3.78±3.81 ꢀ3H, m,
H-2a, H-4a, H-5a), 3.90±3.92 ꢀ1H, m, H-3a), 3.92 ꢀ1H, at, J ˆ 9.4 Hz, H-4b), 4.06 ꢀ1H, d, H-2b), 4.23
ꢀ1H, dd, J6;6 ˆ 10:0 Hz, H-60a), 4.37 ꢀ1H, s, H-1b), 4.56, 4.93 ꢀ2H, ABq, JAB ˆ 11.4 Hz, PhCH2),
0
4.56, 4.63 ꢀ2H, ABq, JAB ˆ 13.0 Hz, PhCH2), 4.57, 4.91 ꢀ2H, ABq, JAB ˆ 11.0 Hz, PhCH2), 4.62
ꢀ2H, s, PhCH2), 4.69, 4.79 ꢀ2H, ABq, JAB ˆ 12.3 Hz, PhCH2), 4.71, 4.76 ꢀ2H, ABq, JAB ˆ 12.7 Hz,
PhCH2), 4.72 ꢀ1H, d, J1,2 ˆ 1.7 Hz, H-1a), 7.22±7.41 ꢀ30H, m, Ar±H) ppm; 13C NMR ꢀ125 MHz,
1
CDCl3): JC-1b,H-1b ˆ 157.9 Hz.
Methyl 3,4,6-tri-O-benzyl-ꢁ-D-mannopyranosyl-51 ! 3)-2-O-benzyl-4,6-O-
benzylidene-ꢀ-D-mannopyranoside ꢀ13e; C48H52O11)
Mixed acetals 12e ꢀ126 mg, 0.127 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ52 mg, 0.25 mmol),
silver tri¯uoromethanesulfonate ꢀ65 mg, 0.25 mmol), and anhydrous tinꢀII) chloride ꢀ48 mg,
0.25 mmol) gave ꢁ-manno disaccharide 13e ꢀ56 mg, 55%) as a colourless oil.
22
D
1
‰ꢀŠ ˆ ‡5:1 ꢀc ˆ 0.35, CHCl3); IR ꢀthin ®lm): ꢃ ˆ 3479 ꢀbr, OH) cmÀ1; H NMR ꢀ400 MHz,
CDCl3): ꢂ ˆ 3.27 ꢀ1H, dt, J4,5 ˆ 9.6 Hz, J5,6 ˆ 3.5 Hz, H-5b), 3.32 ꢀ3H, s, OCH3), 3.39 ꢀ1H, dd,
J2,3 ˆ 3.1 Hz, J3,4 ˆ 9.0 Hz, H-3b), 3.70 ꢀ2H, d, H-6b, H-60b), 3.79±3.87 ꢀ3H, m, H-2a, H-5a, H-6a),
3.89 ꢀ1H, at, J ˆ 9.1 Hz, H-4b), 3.94 ꢀ1H, d, H-2b), 4.19 ꢀ1H, at, J ˆ 9.7 Hz, H-4a), 4.26 ꢀ1H, s, H-1b),
4.28 ꢀ1H, dd, J5,6 ˆ 4.2 Hz, J6;6 ˆ 9:6 Hz, H-60a), 4.49, 4.58 ꢀ2H, ABq, JAB ˆ 12.0 Hz, PhCH2), 4.49
0
ꢀ1H, dd, J2,3 ˆ 3.3 Hz, J3,4 ˆ 10.2 Hz, H-3a), 4.55, 4.87 ꢀ2H, ABq, JAB ˆ 10.8 Hz, PhCH2), 4.62, 4.77
ꢀ2H, ABq, JAB ˆ 12.2 Hz, PhCH2), 4.63, 4.73 ꢀ2H, ABq, JAB ˆ 12.2 Hz, PhCH2), 4.77 ꢀ1H, d,
J1,2 ˆ 1.4 Hz, H-1a), 5.61 ꢀ1H, s, PhCH), 7.21±7.49 ꢀ25H, m, Ar±H) ppm; 13C NMR ꢀCDCl3,

Intramolecular Aglycon Delivery of Glycosyl Fluorides
461
100 MHz): ꢂ ˆ 54.9 ꢀq, OCH3), 64.0, 68.4, 71.8, 74.0, 75.1, 75.9, 77.2, 80.8 ꢀ8  d, C-2b, C-3b, C-4b,
C-5b, C-2a, C-3a, C-4a, C-5a), 68.8, 68.9, 71.1, 73.0, 73.5, 75.1 ꢀ6 Â t, C-6b, C-6a, 4 Â PhCH2), 96.4
1
1
ꢀd, JC-1,H-1 ˆ 158.9 Hz, C-1b), 99.7 ꢀd, JC-1,H-1 ˆ 168.6 Hz, C-1a), 101.8 ꢀd, PhCH), 126.0, 127.4,
127.6, 127.7, 127.7, 127.8, 128.0, 128.0, 128.1, 128.2, 128.2, 128.3, 128.4, 128.4, 129.0 ꢀ15 Â d, Ar±
CH), 137.3, 137.6, 138.1, 138.3, 138.5 ꢀ5  s, Ar±C); MS ꢀAPCIÀ): m=z ˆ 839 ꢀM ‡ ClÀ, 100%);
‡
‡
‡
MS ꢀES ): m=z ˆ 822 ꢀM ‡ NH4 , 100%); HRMS: calcd. for C48H56NO11 ꢂMNH4 †: 822.3853,
found: 822.3864.
Methyl 3,4,6-tri-O-benzyl-ꢁ-D-mannopyranosyl-51 ! 4)-2,3,6-tri-O-benzyl-
ꢀ-D-mannopyranoside ꢀ13f; C55H60O11)
Mixed acetals 12f ꢀ65 mg, 0.06 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ25 mg, 0.12 mmol), silver
tri¯uoromethanesulfonate ꢀ31 mg, 0.12 mmol), and anhydrous tinꢀII) chloride ꢀ23 mg, 0.12 mmol)
gave ꢁ-manno disaccharide 13f ꢀ27 mg, 50%) as a colourless oil.
22
D
1
‰ꢀŠ ˆ ‡21:4 ꢀc ˆ 0.35, CHCl3); IR ꢀthin ®lm): ꢃ ˆ 3416 ꢀbr, OH) cmÀ1; H NMR ꢀ400 MHz,
0
CDCl3): ꢂ ˆ 3.29 ꢀ1H, ddd, J4,5 ˆ 9.7 Hz, J5,6 ˆ 2.2 Hz, J5;6 ˆ 4:5 Hz, H-5b), 3.34 ꢀ3H, s, OCH3),
0
3.39 ꢀ1H, dd, J2,3 ˆ 3.3 Hz, J3,4 ˆ 9.2 Hz, H-3b), 3.62 ꢀ1H, dd, J6;6 ˆ 11:2 Hz, H-6b), 3.65 ꢀ1H, dd,
H-60b), 3.75±3.80 ꢀ3H, m, H-2a, H-5a, H-6a), 3.86 ꢀ1H, at, J ˆ 9.5 Hz, H-4b), 3.88 ꢀ1H, dd,
J5;6 ˆ 3:7 Hz, J6;6 ˆ 11:0 Hz, H-60a), 3.97 ꢀ1H, dd, J2,3 ˆ 3.2 Hz, H-3a), 4.01 ꢀ1H, d, H-2b), 4.32
ꢀ1H, at, J ˆ 9.2 Hz, H-4a), 4.43, 4.56 ꢀ2H, ABq, JAB ˆ 12.1 Hz, PhCH2), 4.48, 4.54 ꢀ2H,
ABq, JAB ˆ 12.0 Hz, PhCH2), 4.51, 4.86 ꢀ2H, ABq, JAB ˆ 11.1 Hz, PhCH2), 4.57, 4.71 ꢀ2H, ABq,
JAB ˆ 11.7 Hz, PhCH2), 4.59, 4.70 ꢀ2H, ABq, JAB ˆ 11.8 Hz, PhCH2), 4.68, 4.72 ꢀ2H, ABq,
JAB ˆ 12.9 Hz, PhCH2), 4.69 ꢀ1H, s, H-1b), 4.77 ꢀ1H, d, J1,2 ˆ 1.9 Hz, H-1a), 7.19±7.36 ꢀ30H, m, Ar±
H) ppm; 13C NMR ꢀCDCl3, 100 MHz): ꢂ ˆ 54.7 ꢀq, OCH3), 67.4 ꢀd, C-2b), 69.0 ꢀt, C-6b), 69.4 ꢀt, C-
6a), 70.9 ꢀd, C-5a), 70.8, 72.2, 72.5, 73.2, 73.3, 75.0 ꢀ6 Â t, 6 Â PhCH2), 72.9 ꢀd, C-4a), 73.8 ꢀd, C-4b),
0
0
1
74.8 ꢀd, C-2a), 75.5 ꢀd, C-5b), 79.0 ꢀd, C-3a), 81.8 ꢀd, C-3b), 98.9 ꢀd, JC-1,H-1 ˆ 172.5 Hz, C-1a),
1
100.0 ꢀd, JC-1,H-1 ˆ 161.5 Hz, C-1b), 127.3, 127.4, 127.4, 127.5, 127.5, 127.5, 127.5, 127.6, 127.7,
127.9, 128.0, 128.1, 128.2, 128.2 ꢀ14 Â d, Ar±CH), 137.9, 138.1, 138.2, 138.2, 138.3, 138.4 ꢀ6 Â s,
Ar±C) ppm; MS ꢀAPCIÀ): m=z ˆ 931 ꢀM ‡ ClÀ, 100%); MS ꢀES ): m=z ˆ 914 ꢀM ‡ NH4 , 100%);
‡
‡
‡
HRMS: calcd. for C55H64NO11 ꢂMNH4 †: 914.4479, found: 914.4473.
Cholestan-30-ꢁ-yl 3,4,6-tri-O-benzyl-ꢁ-D-mannopyranoside ꢀ13h; C54H76O6)
Mixed acetals 12h ꢀ121 mg, 0.12 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ49 mg, 0.24 mmol),
silver tri¯uoromethanesulfonate ꢀ61 mg, 0.24 mmol), and anhydrous tinꢀII) chloride ꢀ46 mg,
0.24 mmol) gave ꢁ-mannoside 13h ꢀ58 mg, 59%) as colourless crystals.
24
M.p.: 100±102ꢀC ꢀEtOH); ‰ꢀŠ ˆ À4:9 ꢀc ˆ 0.75, CHCl3); IR ꢀthin ®lm): ꢃ ˆ 3435 ꢀbr, OH)
D
cmÀ1; 1H NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 0.58±2.00 ꢀ31H, m, steroid CH, CH2), 0.66, 0.81 ꢀ6H, 2  s,
2  CH3), 0.87 ꢀ3H, d, J ˆ 6.6 Hz, CH3), 0.88 ꢀ3H, d, J ˆ 6.8 Hz, CH3), 0.91 ꢀ3H, d, J ˆ 6.5 Hz,
0
CH3), 2.11 ꢀ1H, br s, OH-2), 3.43 ꢀ1H, ddd, J4,5 ˆ 9.7 Hz, J5,6 ˆ 5.6 Hz, J5;6 ˆ 1:9 Hz, H-5), 3.57
0
ꢀ1H, dd, J2,3 ˆ 3.2 Hz, J3,4 ˆ 9.1 Hz, H-3), 3.69 ꢀ1H, dd, J6;6 ˆ 10:7 Hz, H-6), 3.70±3.77 ꢀ1H, m,
steroid OCH), 3.80 ꢀ1H, dd, H-60), 3.84 ꢀ1H, at, J ˆ 9.3 Hz, H-4), 4.06 ꢀ1H, d, H-2), 4.56, 4.91 ꢀ2H,
ABq, JAB ˆ 10.9 Hz, PhCH2), 4.57 ꢀ1H, s, H-1), 4.58, 4.63 ꢀ2H, ABq, JAB ˆ 12.1 Hz, PhCH2), 4.68,
4.79 ꢀ2H, ABq, JAB ˆ 11.9 Hz, PhCH2), 7.21±7.40 ꢀ15H, m, Ar±H) ppm; 13C NMR ꢀCDCl3,
100 MHz): ꢂ ˆ 12.0, 12.2, 18.7, 22.5, 22.8 ꢀ5  q, 5  steroid CH3), 21.2, 23.8, 24.2, 28.2, 28.8, 29.2,
32.1, 34.2, 36.2, 37.0, 39.5, 40.0 ꢀ12 Â t, 12 Â steroid CH2), 28.0, 35.6, 35.8, 44.6, 54.4, 56.2, 56.5
ꢀ7 Â d, 7 Â steroid CH), 35.4, 42.6 ꢀ2 Â s, 2 Â steroid C), 68.8 ꢀd, C-2), 69.4 ꢀt, C-6), 71.3, 73.4, 75.2
ꢀ3 Â t, 3 Â PhCH2), 74.3 ꢀd, C-4), 75.1 ꢀd, C-5), 77.5 ꢀd, steroid OCH), 81.7 ꢀd, C-3), 97.2 ꢀd,
1JC-1,H-1 ˆ 155.6 Hz, C-1), 127.5, 127.7, 127.8, 127.9, 128.1, 128.3, 128.4, 128.5 ꢀ8  d, Ar±CH),
137.9, 138.2, 138.3 ꢀ3 Â s, Ar±C) ppm.

462
I. Cumpstey et al.
2-O-52-Iodo-1-methoxypropyl)-3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl
¯uoride ꢀ14a; C31H36FIO6)
Vinyl ethers 10 ꢀ300 mg, 0.61 mmol), NIS ꢀ410 mg, 1.83 mmol), and 11a ꢀ0.037 cm3, 0.92 mmol) gave
‡
‡
mixed acetals 14a ꢀ399 mg, >99%) as a colourless oil; MS ꢀAPCI ): m=z ˆ 673 ꢀM ‡ Na , 15%).
2-O-51-Cyclohexyloxy-2-iodopropyl)-3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl
¯uoride ꢀ14b; C36H44FIO6)
Vinyl ethers 10 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11b ꢀ0.034 cm3, 0.33 mmol) gave
‡
‡
mixed acetals 14b ꢀ116 mg, 99%) as a colourless oil; MS ꢀAPCI ): m=z ˆ 741 ꢀM ‡ Na , 5%).
2-O-51-51,2:3,4-Di-O-isopropylidene-D-galactopyranos-6-O-yl)-2-iodopropyl)-
3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl ¯uoride ꢀ14c; C42H52FIO11)
Vinyl ethers 10 ꢀ80 mg, 0.36 mmol), NIS ꢀ109 mg, 0.49 mmol), 11c ꢀ84 mg, 0.82 mmol) gave mixed
acetals 14c ꢀ130 mg, 91%) as a colourless oil; MS ꢀAPCIÀ): m=z ˆ 913 ꢀM ‡ ClÀ, 4%); MS
‡
‡
ꢀAPCI ): m=z ˆ 901 ꢀM ‡ Na , 5%).
2-O-52-Iodo-1-5methyl 2,3,4-tri-O-benzyl-ꢀ-D-mannopyranosid-6-O-yl)propyl)-
3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl ¯uoride ꢀ14d; C58H64FIO11)
Vinyl ethers 10 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11d ꢀ151 mg, 0.33 mmol) gave
mixed acetals 14d ꢀ139 mg, 79%) as a colourless oil; MS ꢀAPCIÀ): m=z ˆ 1117 ꢀM ‡ ClÀ, 92%).
2-O-52-Iodo-1-5methyl 2-O-benzyl-4,6-O-benzylidene-ꢀ-D-mannopyranosid-
3-O-yl)propyl)-3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl ¯uoride ꢀ14e; C51H56FIO11)
Vinyl ethers 10 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11e ꢀ121 mg, 0.33 mmol) gave
‡
‡
mixed acetals 14e ꢀ83 mg, 52%) as a colourless oil; MS ꢀES ): m=z ˆ 1029 ꢀM ‡ K , 74%), 1013
‡
‡
ꢀM ‡ Na , 100%), 1008 ꢀM ‡ NH4 , 15%).
2-O-52-Iodo-1-5methyl 2,3,6-tri-O-benzyl-ꢀ-D-glucopyranosid-4-O-yl)propyl)-
3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl ¯uoride ꢀ14g; C58H65FIO11)
Vinyl ethers 10 ꢀ80 mg, 0.16 mmol), NIS ꢀ109 mg, 0.49 mmol), and 11g ꢀ221 mg, 0.48 mmol) gave
‡
‡
mixed acetals 14g ꢀ69 mg, 39%) as a colourless oil; MS ꢀES ): m=z ˆ 1121 ꢀM ‡ K , 22%), 1105
‡
‡
ꢀM ‡ Na , 100%), 1100 ꢀM ‡ NH4 , 21%).
2-O-51-5Cholestan-3-ꢁ-yloxy)-2-iodopropyl)-3,4,6-tri-O-benzyl-ꢁ-D-glucopyranosyl
¯uoride ꢀ14h; C57H80FIO6)
Vinyl ethers 10 ꢀ71 mg, 0.13 mmol), NIS ꢀ103 mg, 0.40 mmol), and 11h ꢀ84 mg, 0.82 mmol) in THF
‡
‡
ꢀ3 cm3) gave mixed acetals 14h ꢀ99 mg, 68%) as a colourless oil; MS ꢀES ): m=z ˆ 1045 ꢀM ‡ K ,
‡
100%), 1029 ꢀM ‡ Na , 90%).
Methyl 3,4,6-tri-O-benzyl-ꢀ-D-glucopyranoside ꢀ15a; C28H32O6)
Mixed acetals 14a ꢀ77 mg, 0.118 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ48 mg, 0.236 mmol),
silver tri¯uoromethanesulfonate ꢀ61 mg, 0.236 mmol), and anhydrous tinꢀII) chloride ꢀ45 mg,

Intramolecular Aglycon Delivery of Glycosyl Fluorides
463
0.236 mmol) gave ꢀ-methyl glucoside 15a ꢀ49 mg, 89%) as a white solid which was recrystallized
from diethyl ether=petrol.
22
D
M.p.: 78±81ꢀC ꢀdiethyl ether=petrol; Ref. [4]: 83±84ꢀC); ‰ꢀŠ ˆ ‡70:8 ꢀc ˆ 1.2, CHCl3; Ref.
1
[4]: [ꢀ]D ˆ ‡ 90 ꢀc ˆ 1.1, CHCl3)); H NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 2.11 ꢀ1H, d, JOH,2 ˆ 7.4 Hz,
OH-2), 3.40 ꢀ3H, s, OCH3), 3.60±3.76 ꢀ6H, m, H-2, H-3, H-4, H-5, H-6, H-60), 4.47, 4.79 ꢀ2H, ABq,
JAB ˆ 10.7 Hz, PhCH2), 4.49, 4.62 ꢀ2H, ABq, JAB ˆ 12.1 Hz, PhCH2), 4.78 ꢀ1H, d, J1,2 ˆ 3.2 Hz, H-
1), 4.83, 4.88 ꢀ2H, ABq, JAB ˆ 11.2 Hz, PhCH2), 7.11±7.36 ꢀ15H, m, Ar±H) ppm.
Cyclohexyl 3,4,6-tri-O-benzyl-ꢀ-D-glucopyranoside ꢀ15b; C33H40O6)
Mixed acetals 14b ꢀ77 mg, 0.118 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ65 mg, 0.318 mmol),
silver tri¯uoromethanesulfonate ꢀ82 mg, 0.318 mmol), and anhydrous tinꢀII) chloride ꢀ60 mg,
0.318 mmol) gave ꢀ-glucoside 15b ꢀ56 mg, 66%) as a white solid which was recrystallized from
diethyl ether=petrol.
22
D
M.p.: 92±94ꢀC ꢀdiethyl ether=petrol); ‰ꢀŠ ˆ ‡90:0 ꢀc ˆ 0.3, CHCl3; Ref. [4]: [ꢀ]D ˆ ‡ 60
ꢀc ˆ 0.6, CHCl3)); 1H NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 1.24±1.92 ꢀ10H, m, cyclohexyl-H), 2.06 ꢀ1H, d,
J ˆ 2.7 Hz, OH-2), 3.61±3.75 ꢀ5H, m, H-2, H-3, H-4, H-6, cyclohexyl OCH), 3.77 ꢀ1H, dd,
J5;6 ˆ 3:9 Hz, J6;6 ˆ 10:7 Hz, H-60), 3.87±3.90 ꢀ1H, m, H-5), 4.49, 4.83 ꢀ2H, ABq, JAB ˆ 10.7 Hz,
PhCH2), 4.51, 4.65 ꢀ2H, ABq, JAB ˆ 12.0 Hz, PhCH2), 4.84, 4.99 ꢀ2H, ABq, JAB ˆ 11.0 Hz, PhCH2),
5.03 ꢀ1H, d, J1,2 ˆ 3.5 Hz, H-1), 7.14±7.42 ꢀ15H, m, Ar±H) ppm.
0
0
3,4,6-Tri-O-benzyl-ꢀ-D-glucopyranosyl-51 ! 6)-1,2:3,4-di-O-isopropylidene-
D-galactopyranose ꢀ15c; C39H48O11)
Mixed acetals 14c ꢀ124 mg, 0.14 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ58 mg, 0.28 mmol),
silver tri¯uoromethanesulfonate ꢀ73 mg, 0.28 mmol), and anhydrous tinꢀII) chloride ꢀ54 mg,
0.28 mmol) gave ꢀ-gluco disaccharide 15c ꢀ62 mg, 63%) as a colourless oil.
22
D
1
‰ꢀŠ ˆ ‡27:7 ꢀc ˆ 0.35, CHCl3; Ref. [4]: [ꢀ]D ˆ ‡ 29 ꢀc ˆ 0.9, CHCl3)); H NMR ꢀ400 MHz,
CDCl3): ꢂ ˆ 1.34, 1.35, 1.45, 1.54 ꢀ12H, 4  s, 4  CH3), 3.63±3.79 ꢀ6H, m, H-2b, H-3b, H-4b, H-6b, H-
60b, H-6a), 3.85 ꢀ1H, ddd, J4,5 ˆ 9.9 Hz, J5,6 ˆ 2.2 Hz, J5;6 ˆ 3:0 Hz, H-5b), 3.91 ꢀ1H, dd, J5;6
ˆ
ˆ
0
0
6:7 Hz, J6;6 ˆ 10:2 Hz, H-60a), 4.00 ꢀ1H, atd, J ˆ 6.7 Hz, J4,5 ˆ 1.9 Hz, H-5a), 4.25 ꢀ1H, dd, J3,4
0
7.8 Hz, H-4a), 4.34 ꢀ1H, dd, J1,2 ˆ 4.9 Hz, J2,3 ˆ 2.2 Hz, H-2a), 4.49, 4.83 ꢀ2H, ABq, JAB ˆ 10.3 Hz,
PhCH2), 4.50, 4.64 ꢀ2H, ABq, JAB ˆ 11.7 Hz, PhCH2), 4.63 ꢀ1H, dd, H-3a), 4.82, 4.98 ꢀ2H, ABq,
JAB ˆ 10.7 Hz, PhCH2), 4.93 ꢀ1H, d, H-1b), 5.53 ꢀ1H, d, H-1a), 7.12±7.41 ꢀ15H, m, Ar±H) ppm.
Methyl 3,4,6-tri-O-benzyl-ꢀ-D-glucopyranosyl-51 ! 6)-3,4,6-tri-O-benzyl-
ꢀ-D-mannopyranoside ꢀ15d; C55H60O11)
Mixed acetals 14d ꢀ49 mg, 0.045 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ19 mg, 0.09 mmol),
silver tri¯uoromethanesulfonate ꢀ23 mg, 0.09 mmol), and anhydrous tinꢀII) chloride ꢀ17 mg,
0.09 mmol) gave ꢀ-gluco disaccharide 15d ꢀ18 mg, 44%) as a colourless oil.
22
‰ꢀŠ ˆ ‡65:5 ꢀc ˆ 1.1, CHCl3); 1H NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 3.30 ꢀ3H, s, OCH3), 3.59±3.80
D
ꢀ8H, m, H-2b, H-3b, H-4b, H-5b, H-6b, H-60b, H-5a, H-6a), 3.79 ꢀ1H, dd, J1,2 ˆ 2.0 Hz, J2,3 ˆ 3.0 Hz,
H-2a), 3.91 ꢀ1H, dd, J3,4 ˆ 9.4 Hz, H-3a), 4.04±4.10 ꢀ2H, m, H-4a, H-60a), 4.47, 4.84 ꢀ2H, ABq,
JAB ˆ 10.8 Hz, PhCH2), 4.48, 4.61 ꢀ2H, ABq, JAB ˆ 12.2 Hz, PhCH2), 4.62 ꢀ2H, s, PhCH2), 4.62,
4.98 ꢀ2H, ABq, JAB ˆ 11.1 Hz, PhCH2), 4.70 ꢀ1H, d, H-1a), 4.71, 4.92 ꢀ2H, ABq, JAB ˆ 11.1 Hz,
PhCH2), 4.72 ꢀ2H, s, PhCH2), 5.00 ꢀ1H, d, J1,2 ˆ 2.9 Hz, H-1b), 7.14±7.39 ꢀ30H, m, Ar±H) ppm; 13
C
NMR ꢀCDCl3, 100 MHz): ꢂ ˆ 54.9 ꢀq, CH3), 67.7, 68.4, 72.0, 72.8, 73.4, 75.0, 75.1, 75.2 ꢀ8  t,
6 Â PhCH2, C-6b, C-6a), 70.7, 71.3, 73.8, 74.1, 74.2, 77.0, 79.9, 83.3 ꢀ8 Â d, C-2b, C-3b, C-4b, C-5b,
C-2a, C-3a, C-4a, C-5a), 98.9, 100.6 ꢀ2 Â d, C-1b, C-1a), 127.4, 127.6, 127.6, 127.7, 127.8, 127.8,
127.9, 127.9, 128.0, 128.1, 128.3, 128.3, 128.4 ꢀ13 Â d, Ar±CH), 138.0, 138.2, 138.3, 138.4, 138.9

464
I. Cumpstey et al.
‡
‡
ꢀ5  s, Ar±C) ppm; MS ꢀAPCI ): m=z ˆ 919 ꢀM ‡ Na , 55%); MS ꢀAPCIÀ): m=z ˆ 931 ꢀM ‡ ClÀ,
‡
10%); HRMS: calcd. for C55H61O11 ꢀMH ): 897.4214, found: 897.4229.
Methyl 3,4,6-tri-O-benzyl-ꢀ-D-glucopyranosyl-51 ! 3)-2-O-benzyl-
4,6-O-benzylidene-ꢀ-D-mannopyranoside ꢀ15e; C48H52O11)
Mixed acetals 14e ꢀ77 mg, 0.078 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ32 mg, 0.16 mmol),
silver tri¯uoromethanesulfonate ꢀ40 mg, 0.16 mmol), and anhydrous tinꢀII) chloride ꢀ30 mg,
0.16 mmol) gave ꢀ-gluco disaccharide 15e ꢀ23 mg, 37%) as white crystals.
22
M.p.: 145±147ꢀC ꢀdiethyl ether=petrol); ‰ꢀŠ ˆ ‡42:4 ꢀc ˆ 0.25, CHCl3); IR ꢀthin ®lm):
D
ꢃ ˆ 3462 ꢀbr, OH) cmÀ1; 1H NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 2.65 ꢀ1H, d, JOH,2 ˆ 9.8 Hz, OH-2), 3.34
ꢀ3H, s, OCH3), 3.56 ꢀ1H, at, J ˆ 9.2 Hz, H-4b), 3.65±3.68 ꢀ2H, m, H-6b, H-60b), 3.71 ꢀ1H, atd,
J1,2 ˆ 3.4 Hz, J ˆ 9.6 Hz, H-2b), 3.75 ꢀ1H, at, J ˆ 9.3 Hz, H-3b), 3.81±3.88 ꢀ3H, m, H-2a, H-5a, H-6a),
3.90±3.94 ꢀ1H, m, H-5b), 4.22±4.24 ꢀ2H, m, H-4a, H-60a), 4.28 ꢀ1H, dd, J2,3 ˆ 3.7 Hz, J3,4 ˆ 9.2 Hz,
H-3a), 4.47, 4.85 ꢀ2H, ABq, JAB ˆ 11.0 Hz, PhCH2), 4.48, 4.57 ꢀ2H, ABq, JAB ˆ 12.0 Hz, PhCH2),
4.66, 4.76 ꢀ2H, ABq, JAB ˆ 12.0 Hz, PhCH2), 4.69, 4.82 ꢀ2H, ABq, JAB ˆ 10.9 Hz, PhCH2), 4.69
ꢀ1H, d, J1,2 ˆ 1.4 Hz, H-1a), 5.21 ꢀ1H, d, H-1b), 5.63 ꢀ1H, s, PhCH), 7.14±7.49 ꢀ25H, m, Ar±H) ppm;
13C NMR ꢀCDCl3, 100 MHz): ꢂ ˆ 54.9 ꢀq, OCH3), 63.9, 71.5, 73.8, 76.1, 77.0, 77.6, 78.2, 83.4
ꢀ8 Â d, C-2a, C-3a, C-4a, C-5a, C-2b, C-3b, C-4b, C-5b), 68.7, 68.8, 73.4, 73.5, 74.8, 75.2 ꢀ6 Â t, C-6a,
C-6b, 4 Â PhCH2), 100.0, 100.8, 101.8 ꢀ3 Â d, C-1a, C-1b, PhCH), 125.6, 127.5, 127.6, 127.6, 127.7,
127.8, 127.8, 127.9, 128.0, 128.2, 128.3, 128.3, 128.3, 128.5, 129.1 ꢀ15 Â d, Ar±CH), 137.0, 137.8,
‡
‡
‡
,
137.9, 138.4, 138.7 ꢀ5  s, Ar±C) ppm; MS ꢀES ): m=z ˆ 843 ꢀM ‡ K , 50%), 827 ꢀM ‡ Na
‡
100%); HRMS: calcd. for C48H56NO11 ꢂMNH4 †: 822.3853, found: 822.3842.
Methyl 3,4,6-tri-O-benzyl-ꢀ-D-glucopyranosyl-51 ! 4)-2,3,6-tri-O-benzyl-
ꢀ-D-glucopyranoside ꢀ15g; C55H60O11)
Mixed acetals 14g ꢀ65 mg, 0.06 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ25 mg, 0.12 mmol),
silver tri¯uoromethanesulfonate ꢀ31 mg, 0.12 mmol), and anhydrous tinꢀII) chloride ꢀ23 mg,
0.12 mmol) gave ꢀ-gluco disaccharide 15g ꢀ24 mg, 45%) as a colourless oil.
22
D
1
‰ꢀŠ ˆ ‡35:1 ꢀc ˆ 1.05, CHCl3); IR ꢀthin ®lm): ꢃ ˆ 3418 ꢀbr, OH) cmÀ1; H NMR ꢀ400 MHz,
CDCl3): ꢂ ˆ 3.38 ꢀ3H, s, OCH3), 3.45 ꢀ1H, br d, JOH,2 ˆ 9.1 Hz, OH-2b), 3.55 ꢀ1H, at, J ˆ 9.1 Hz, H-
3b), 3.55 ꢀ1H, dd, J5,6 ˆ 1.8 Hz, J6;6 ˆ 10:6 Hz, H-6a), 3.61±3.66 ꢀ4H, m, H-2b, H-2a, H-3a, H-60a),
0
0
3.68 ꢀ1H, dd, J5,6 ˆ 1.9 Hz, J6;6 ˆ 11:0 Hz, H-6b), 3.69±3.71 ꢀ1H, m, H-5b), 3.86±3.90 ꢀ1H, m, H-
5a), 3.88 ꢀ1H, at, J ˆ 9.5 Hz, H-4b), 3.93 ꢀ1H, dd, J5;6 ˆ 3:9 Hz, H-60b), 3.99 ꢀ1H, at, J ˆ 9.3 Hz, H-
0
4a), 4.44, 4.57 ꢀ2H, ABq, JAB ˆ 12.2 Hz, PhCH2), 4.49, 4.83 ꢀ2H, ABq, JAB ˆ 10.6 Hz, PhCH2), 4.49,
4.59 ꢀ2H, ABq, JAB ˆ 11.6 Hz, PhCH2), 4.57, 4.69 ꢀ2H, ABq, JAB ˆ 11.0 Hz, PhCH2), 4.59, 4.70
ꢀ2H, ABq, JAB ˆ 12.0 Hz, PhCH2), 4.61 ꢀ1H, d, J1,2 ˆ 3.6 Hz, H-1b), 4.79, 5.18 ꢀ2H, ABq,
JAB ˆ 10.6 Hz, PhCH2), 5.19 ꢀ1H, d, J1,2 ˆ 3.1 Hz, H-1a), 7.16±7.36 ꢀ30H, m, Ar±H) ppm; 13C NMR
ꢀCDCl3, 100 MHz): ꢂ ˆ 55.2 ꢀq, OCH3), 68.4 ꢀt, C-6b), 68.7 ꢀt, C-6a), 70.0 ꢀd, C-5b), 71.5 ꢀd, C-5a),
73.0, 73.2, 73.3, 74.9, 75.1, 75.2 ꢀ6 Â t, 6 Â PhCH2), 74.0, 80.2, 83.6 ꢀ3 Â d, C-2b, C-2a, C-3a), 76.9
ꢀd, C-3b), 77.6 ꢀd, C-4b), 80.5 ꢀd, C-4a), 97.7 ꢀd, C-1b), 101.2 ꢀd, C-1a), 127.3, 127.4, 127.5, 127.6,
127.7, 127.8, 127.8, 128.0, 128.1, 128.2, 128.2, 128.3, 128.4 ꢀ13 Â d, Ar±CH), 137.5, 137.7, 137.7,
‡
‡
‡
,
137.9, 138.2, 138.7 ꢀ6  s, Ar±C) ppm; MS ꢀES ): m=z ˆ 935 ꢀM ‡ K , 14%), 919 ꢀM ‡ Na
‡
‡
‡
100%), 916 ꢀ2M ‡ K ‡ H , 21%), 914 ꢀM ‡ NH4 , 14%); HRMS: calcd. for C55H64NO11
‡
ꢂMNH4 †: 914.4479, found: 914.4476.
Cholestan-30-ꢁ-yl 3,4,6-tri-O-benzyl-ꢀ-D-glucopyranoside ꢀ15h; C54H76O6)
Mixed acetals 14h ꢀ41 mg, 0.04 mmol), 2,6-di-tert-butyl-4-methylpyridine ꢀ16 mg, 0.08 mmol),
silver tri¯uoromethanesulfonate ꢀ21 mg, 0.08 mmol), and anhydrous tinꢀII) chloride ꢀ15 mg,
0.08 mmol) gave ꢀ-glucoside 15h ꢀ29 mg, 87%) as white crystals.

Intramolecular Aglycon Delivery of Glycosyl Fluorides
465
24
D
M.p.: 108±109ꢀC; ‰ꢀŠ ˆ ‡98:5 ꢀc ˆ 0.20, CHCl3); IR ꢀthin ®lm): ꢃ ˆ 3487 ꢀbr, OH) cmÀ1; 1H
NMR ꢀ400 MHz, CDCl3): ꢂ ˆ 0.59±1.99 ꢀ31H, m, steroid CH, CH2), 0.66, 0.81 ꢀ6H, 2  s, 2  CH3),
0.88 ꢀ3H, d, J ˆ 6.5 Hz, CH3), 0.89 ꢀ3H, d, J ˆ 6.5 Hz, CH3), 0.91 ꢀ3H, d, J ˆ 6.6 Hz, CH3), 2.10 ꢀ1H,
b r d,JOH,2 ˆ 8.0 Hz, OH-2), 3.57±3.79 ꢀ4H, m, H-2, H-3, H-4, OCH), 3.68 ꢀ1H, dd, J5,6 ˆ 2.0 Hz,
J6;6 ˆ 10:5 Hz, H-6), 3.77 ꢀ1H, dd, J5;6 ˆ 4:0 Hz, H-60), 3.89±3.92 ꢀ1H, m, H-5), 4.49, 4.84 ꢀ2H,
ABq, JAB ˆ 10.7 Hz, PhCH2), 4.51, 4.65 ꢀ2H, ABq, JAB ˆ 11.9 Hz, PhCH2), 4.84, 4.99 ꢀ2H, ABq,
JAB ˆ 11.2 Hz, PhCH2), 5.04 ꢀ1H, d, J1,2 ˆ 3.6 Hz, H-1), 7.14±7.41 ꢀ15H, m, Ar±H) ppm; 13C NMR
ꢀCDCl3, 100 MHz): ꢂ ˆ 12.0, 12.3, 18.6, 22.6, 22.8 ꢀ5  q, 5  steroid CH3), 21.2, 23.8, 24.2, 27.8,
28.2, 28.7, 32.0, 36.0, 36.1, 36.8, 39.5, 40.0 ꢀ12 Â t, 12 Â steroid CH2), 28.0, 35.5, 35.8, 44.9, 54.2,
56.2, 56.4 ꢀ7 Â d, 7 Â steroid CH), 35.4, 42.6 ꢀ2 Â s, 2 Â steroid C), 68.6, 73.4, 75.0, 75.3 ꢀ4 Â t,
3 Â PhCH2, C-6), 70.4, 73.0, 77.3, 77.3, 83.8 ꢀ5 Â d, C-2, C-3, C-4, C-5, steroid OCH), 96.9 ꢀd, C-1),
127.6, 127.7, 127.7, 127.9, 127.9, 128.3, 128.3 ꢀ7 Â d, Ar±CH), 137.9, 138.2, 138.8 ꢀ3 Â s, Ar±C)
ppm.
0
0
Hydrolsis of vinyl ethers 19
Vinyl ethers 19 ꢀ30 mg, 0.04 mmol) were dissolved in 2 cm3 THF and 0.2 cm3 H2O. NIS ꢀ9 mg,
0.04 mmol) was added to the stirred mixture at room temperature. After 50 min, the mixture was
partitioned between 30 cm3 CHCl2 and 30 cm3 of a 10% aqueous solution of Na2S2O3. Triethyl-
amine ꢀ2 cm3) was added to the organic layer which was then concentrated in vacuo and puri®ed by
¯ash column chromatography ꢀpetrol:ethyl acetate ˆ 3:1) to give ꢀ-gluco disaccharide 15e
ꢀ18 mg, ꢁ 70%) as a white solid, identical to that described previously.
Data for succinimide trapped material: 2-O-52-Iodo-1-5succinimid-N-yl)-propyl)-
3,4,6-tri-O-benzyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ16; C34H37FINO7)
Isolated in varying amounts during manno tethering reactions as single diastereomer as a colourless
22
oil; ‰ꢀŠ ˆ ‡60:0 ꢀc ˆ 0.75, CHCl3); IR ꢀthin ®lm): ꢃ ˆ 1709 ꢀs, CˆO) cmÀ1; 1H NMR ꢀ400 MHz,
D
CDCl3): ꢂ ˆ 1.98 ꢀ3H, d, J ˆ 6.8 Hz, CH3), 2.76 ꢀ4H, s, COCH2CH2CO), 3.66±3.73 ꢀ2H, m, H-6, H-
60), 3.90 ꢀ3H, br s, H-3, H-4, H-5), 3.99 ꢀ1H, br s, H-2), 4.51, 4.62 ꢀ2H, ABq, JAB ˆ 12.2 Hz, PhCH2),
4.51, 4.82 ꢀ2H, ABq, JAB ˆ 11.0 Hz, PhCH2), 4.68, 4.90 ꢀ2H, ABq, JAB ˆ 11.0 Hz, PhCH2), 5.12
ꢀ1H, dq, J ˆ 10.2 Hz, CHI), 5.39 ꢀ1H, dd, J1,2 ˆ 2.0 Hz, J1,F ˆ 50.5 Hz, H-1), 5.72 ꢀ1H, d, CHN),
7.15±7.47 ꢀ15H, m, Ar±H) ppm; 13C NMR ꢀCDCl3, 100 MHz): ꢂ ˆ 23.2, 25.0 ꢀd, q, CH3, CHI), 27.9
2
ꢀt, COCH2CH2CO), 68.4, 73.0, 73.4, 75.1 ꢀ4  t, C-6, 3  PhCH2), 72.7 ꢀdd, JC-2,F ˆ 6.6 Hz, C-2),
1
73.6, 74.2, 78.9 ꢀ3  d, C-3, C-4, C-5), 86.4 ꢀd, CHN), 106.3 ꢀdd, JC-1,F ˆ 221.0 Hz, C-1), 127.6,
127.8, 127.8, 128.0, 128.0, 128.3, 128.4, 128.5, 128.6 ꢀ9 Â d, Ar±CH), 137.5, 137.8, 138.0 ꢀ3 Â s,
‡
‡
‡
Ar±C) ppm; MS ꢀES ): m=z ˆ 735 ꢀM ‡ NH4 , 100%); HRMS: calcd. for C34H41N2O7FI ꢂMNH4 †:
735.1943, found: 725.1949.
Acknowledgements
We gratefully acknowledge ®nancial support from the EPSRC and GlaxoSmithKline as well as the
use of the EPSRC National Mass Spectrometry Service at Swansea and the Chemical Database
Service at Daresbury.
References
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‡
I
from the oxonium ion produced subsequently to intramolecular glycosylation
Received August 24, 2001. Accepted November 6, 2001