Electrophilic fluorination - Nucleophilic addition reaction mediated by selectfluor: Mechanistic studies and new applications

Article abstract of DOI:10.1021/jo990686h

The electrophilic fluorination-nucleophilic addition reaction with Selectfluor-type reagents upon glycals has been studied and optimized. This reaction leads to selective fluorination at the 2-position with concomitant nucleophilic addition to the anomeric center. To understand the stereochemical outcome of this process, a mechanistic study has led to the discovery that, in the fucose series, Selectfluor adds specifically in a syn manner, yielding a 1-[TEDA-CH₂Cl]-2-fluoro saccharide that anomerizes slowly to a more stable intermediate. The anomeric α/β distribution was studied as a function of reactants and conditions, and it was found that a judicious choice of protective group strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Furthermore, a hypersensitive radical probe was used to probe the reaction, and no product characteristic of a radical process was isolated, suggesting that no single electron transfer occurs during the attack of the glycal on Selectfluor. The importance of solvent effect, Selectfluor counterion, and stepwise procedure has also been discussed. This study has brought an important improvement of yields and a broader range of allowed nucleophiles such as secondary alcohols of carbohydrates, amino acids, phosphates, or phosphonates. This optimized process was further applied to the modification of important bioactive molecules, including the synthesis of fluorinated daunomycin and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.

Full text of DOI:10.1021/jo990686h

5264
J . Org. Chem. 1999, 64, 5264-5279
Electr op h ilic F lu or in a tion -Nu cleop h ilic Ad d ition Rea ction
Med ia ted by Selectflu or : Mech a n istic Stu d ies a n d New
Ap p lica tion s
Ste´phane P. Vincent, Michael D. Burkart, Chung-Ying Tsai, Zhiyuan Zhang, and
Chi-Huey Wong*
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute,
10550 North Torrey Pines Road, La J olla, California 92037
Received April 23, 1999
The electrophilic fluorination-nucleophilic addition reaction with Selectfluor-type reagents upon
glycals has been studied and optimized. This reaction leads to selective fluorination at the 2-position
with concomitant nucleophilic addition to the anomeric center. To understand the stereochemical
outcome of this process, a mechanistic study has led to the discovery that, in the fucose series,
Selectfluor adds specifically in a syn manner, yielding a 1-[TEDA-CH2Cl]-2-fluoro saccharide that
anomerizes slowly to a more stable intermediate. The anomeric R/â distribution was studied as a
function of reactants and conditions, and it was found that a judicious choice of protective group
strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Further-
more, a hypersensitive radical probe was used to probe the reaction, and no product characteristic
of a radical process was isolated, suggesting that no single electron transfer occurs during the
attack of the glycal on Selectfluor. The importance of solvent effect, Selectfluor counterion, and
stepwise procedure has also been discussed. This study has brought an important improvement of
yields and a broader range of allowed nucleophiles such as secondary alcohols of carbohydrates,
amino acids, phosphates, or phosphonates. This optimized process was further applied to the
modification of important bioactive molecules, including the synthesis of fluorinated daunomycin
and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.
In tr od u ction
activity of substrates and stabilize the glycosidic linkage
against hydrolysis.3 Though methods are available for the
synthesis of 2-deoxy-2-fluoro glycosides, they are often
too tedious to be of practical use. Recent procedures
involve the use of molecular fluorine20,21 or solid xenon
difluoride22-24 in reaction with glycals. Hydrolysis of the
resulting 1,2-difluoro saccharide is followed by bromina-
tion and substitution with a nucleophile at the anomeric
position.5,17,25 All of these procedures require the activa-
tion of the 2-deoxy-2-fluoro sugar for glycosylation, which
is a very difficult process because the inductive effect
posed by the 2-fluoro group greatly suppresses the
anomeric reactivity in glycosylation reactions. The poor
overall yield of these reactions prompted us to develop a
more direct approach to the synthesis of fluorinated
glycosides.
Fluorinated carbohydrates have received great atten-
tion recently as evidenced by an abundance of literature
concerning the synthesis,1-5 biological activity, and struc-
ture6,7 of fluorocarbohydrates, particularly 2-deoxy-2-
fluoro glycosides. Their intriguing biological activities
include antiviral therapeutics,8-11 cancer imaging
diagnosis,12-14 and antitumor applications.15 Enzymo-
logically, these molecules have been used to probe the
mechanism and specificity of individual glycosyltrans-
ferases16,17 and glycosidases,18,19 as they can modify the
(1) Burkart, M. D.; Zhang, Z.; Hung, S.-C.; Wong, C.-H. J . Am. Chem.
Soc. 1997, 119, 11743.
(2) Albert, M.; Dax, K.; Ortner, J . Tetrahedron 1998, 54, 4839.
(3) Tsuchiya, T. Adv. Carbohydr. Chem. Biochem. 1990, 48, 91.
(4) Yan, F.; Nguyen, B. V.; Hudlicky, T. Tetrahedron 1997, 53,
11541.
Recently, we reported the first synthesis of fluorinated
carbohydrates via reaction of glycals with 1-chloromethyl-
(5) McCarter, J . D.; Yeung, W.; Chow, J .; Dolphin, D.; Withers, S.
G. J . Am. Chem. Soc. 1997, 119, 5792.
(6) Reif, B.; Wittmann, V.; Engels, J . W. Helv. Chim. Acta 1997,
80, 1952.
(7) Berger, I.; Tereshko, V.; Egli, M. Nucleic Acids Res. 1998, 26,
2473.
(8) Ma, T.; Chu, C. K.; Lin, J .-S. J . Med. Chem. 1997, 40, 2750.
(9) Hagiwara, T.; Kijima-Suda, I.; Ido, T.; Ohrui, H.; Tomita, K.
Carbohydr. Res. 1994, 263, 167.
(10) Germann, C.; Shields, A. F.; Haberkorn, U. J . Nucl. Med. 1998,
39, 1418.
(11) Krawczyk, S. H.; Nassiri, M. R.; Kucera, L. S.; Kern, E. R.; Ptak,
R. G.; Wotring, L. L.; Drach, S. C.; Townsend, L. B. J . Med. Chem.
1995, 38, 4106.
(12) Smith, I. C.; Ogston, K. N.; Eremin, O. Ann. Surg. 1998, 228,
220.
(13) Shreve, P. D.; Steventon, R. S.; Wahl, R. L. Radiology 1998,
207, 431.
(14) Oshida, M.; Uno, K.; Nakajima, N. Cancer 1998, 82, 2227.
(15) Takagi, Y.; Kobayashi, N.; Chang, M. S.; Lim, G.-J .; Tsuchiya,
T. Carbohydr. Res. 1998, 307, 217.
(16) Hayashi, T.; Murray, B.; Wang, R.; Wong, C.-H. Bioorg. Med.
Chem. 1997, 5, 497.
(17) Murray, B. W.; Wittmann, V.; Burkart, M. D.; Hung, S.-C.;
Wong, C.-H. Biochemistry 1997, 36, 823.
(18) Shouming, H.; Withers, S. G. J . Biol. Chem. 1997, 272, 24864.
(19) Monem, V.; Birsan, C.; Warren, R. A.; Withers, S. G.; Rose, D.
R. Biochemistry 1998, 37, 4751.
(20) Diksic, M.; J olly, D. Carbohydr. Res. 1986, 153, 17.
(21) Ido, T.; Wan, C.-N.; Fowler, J . S.; Wolf, A. P. J . Org. Chem.
1977, 42, 2341.
(22) Korytnyk, W.; Valentekovic-Horvat, S. Tetrahedron Lett. 1980,
21, 1493.
(23) Korytnyk, W.; Valentekovic-Horvath, S.; Petrie, C. R. I. Tetra-
hedron Lett. 1982, 38, 2547.
(24) Petrie, C. R., III.; Sharma, M.; Simmons, O. D.; Korytnyk, W.
Carbohydr. Res. 1989, 186, 326.
(25) Shelling, J . G.; Dolphin, D.; Wirz, P.; Cobbledick, R. E.; Einstein,
F. W. B. Carbohydr. Res. 1984, 132, 241.
10.1021/jo990686h CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/16/1999

Fluorination-Nucleophilic Addition Mediated by Selectfluor
J . Org. Chem., Vol. 64, No. 14, 1999 5265
Ta ble 1. Rea ction of Dia cetylfu ca l (2) w ith Selectflu or (1.2 equ iv) a n d Ben zyl Alcoh ol to Yield
3,4-Dia cetyl-2-d eoxy-2-flu or o-1-ben zyl-fu cose 3
temperature
nucleophile
entry
method
equiv (BnOH)
solvent
method
step 1
step 2
R/â ratio
yield (%)
1
2
3
4
5
6
7
8
BF4
BF4
BF4
BF4
OTf
OTf
OTf
OTf
excess
excess
CH3CN
nonstepwise
nonstepwise
stepwise
stepwise
stepwise
nonstepwise
stepwise
nonstepwise
25
25
25
25
25
25
25
25
25
25
25
90
90
90
25
25
0/100
26/74
50/50
17/83
50/50
50/50
40/60
40/60
71
72
2.4
26
72
75
7
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
3
3
3
3
3
3
6
Sch em e 1
acetonitrile yields an anomeric ratio of 1:3 (R/â) in
nitromethane (Table 1, entries 1-2). When the nucleo-
phile is added in stoichiometric amounts with acetonitrile
as solvent (Scheme 2), acetonitrile participates in the
reaction with attack at the anomeric position, and
consequent addition of the nucleophile at the nitrile
carbon gives the fluorinated disaccharide 1. To avoid this
undesirable reaction, nitromethane is used as the solvent
because it dissolves the charged Selectfluor salts and
remains inert during the reaction. Although a base or
proton sponge is necessary with reactions in acetonitrile,
reactions in nitromethane require no additional reagents
to deprotonate the nucleophile. In a general manner, we
observed that the rates of the fluorination-nucleophilic
addition reaction are optimal in nitromethane.
Step w ise ver su s On e-Step Rea ction . When a sto-
ichiometric quantity of nucleophile is used, markedly
improved yields may be obtained through a two-step and
one-pot reaction procedure: an initial reaction of the
glycal with Selectfluor, followed by addition of the nu-
cleophile to the mixture with heating. For most glycals,
the first step must be performed at room temperature.
Increased temperature for the second step improves
yields with all nucleophiles (Table 1, entries 4-6) and
effects anomeric configuration. Mechanistic studies con-
cerning anomeric stereoselectivity are discussed below.
The stepwise procedure allows the formation of a reactive
intermediate comprised of the 1-[TEDA-CH2Cl]-2-deoxy-
2-fluoro saccharide 4, similar to the galactose derivative
described by Albert et al.2 When the glycal has reacted
completely with Selectfluor, the nucleophile is added, and
heat may be applied. This new technique allows a wider
scope of possible nucleophiles that can be chosen inde-
pendent of their reactivity with Selectfluor. Although
alcohols may be used in either the stepwise or one-step
procedure as a result of their poor reactivity with
Selectfluor, other reactive nucleophiles, such as phenols,
amines, phosphates or thiols, benefit from a stepwise
protocol. This new condition greatly expands the possible
functionality to be introduced at the anomeric position.
Selectflu or Cou n ter ion . Using the triflate counte-
rion of Selectfluor (F-TEDA-CH2Cl 2OTf or Selecfluor
triflate)28,30 instead of the more commonly available
tetrafluoroborate salt (F-TEDA-CH2Cl 2BF4) gives fewer
side products and improves yields dramatically.31 The
tetrafluoroborate salt gives the corresponding 1,2-difluoro
saccharide as a major side product, presumably as a
result of the nucleophilic addition of fluoride from the
tetrafluoroborate counterion. We reasoned that a triflate
4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoro-
borate),1 or Selectfluor26 (Scheme 1), which has been
demonstrated to be a reagent for mild fluorination.27,28
We have demonstrated that Selectfluor reacts regio-
selectively with glycals to give specific fluorination at the
2-position with a concomitant functionalization at the
anomeric position in one pot. It also converts the ano-
meric hydroxyl group to the fluorine group in the pres-
ence of dimethyl sulfide and acts as an activator of
thioglycosides in glycosylation reactions. Promise of this
new reagent has encouraged us to investigate the reac-
tion mechanism and to optimize procedures for practical
synthesis.
Here we report the mechanisitic study of this reaction
and its application to the practical synthesis of 2-deoxy-
2-fluoro glycosides, including fluoro disaccharides, fluo-
roglycosyl phosphates, fluorinated natural product gly-
cosides, and the synthesis of glycosyl sulfoxides from
thioglycosides.
Resu lts a n d Discu ssion
Im p r ovem en t of th e Rea ction betw een Glyca l
a n d Selectflu or . In our experience, we have found three
parameters that are crucial to improving the yields and
the use of a greater range of nucleophiles: solvent,
reaction sequence, and reactant counterion. Combination
of each optimal parameter gives an optimized reaction
procedure.
Solven t Effect. In the fluorination-nucleophilic ad-
dition reaction, DMF may be used as solvent when the
desired nucleophile is water. Acetonitrile may be used
when other nucleophiles are present in excess.1 Aceto-
nitrile appears to influence the anomeric stereoselectivity
in a manner similar to the situation in conventional
glycosylation, favoring products with â configuration.29
A reaction which gives exclusively the â product in
(30) Resil Chemical Co., Ltd., PO Box 113, Manchester M20, U.K.
(31) The term “Selectfluor” relates to the family of compounds with
the general formula 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]-
octane (Its bis(triflate) form will be noted, in this paper, F-TEDA‚2OTf
or Selectfluor bistriflate form).
(26) Lal, G. S.; Pez, G. P.; Syvret, R. G. Chem. Rev. 1996, 96, 1737.
(27) Lal, G. S. J . Org. Chem. 1993, 58, 2791.
(28) Banks, R. E. U.S. Patent 5,086,178, 1992.
(29) Schmidt, R. R.; Behrendt, M.; Toepfer, A. Synlett 1990, 694.

5266 J . Org. Chem., Vol. 64, No. 14, 1999
Vincent et al.
Sch em e 2
Ta ble 2
1
counterion would avoid this unwanted side product and
display greater solubility in nitromethane. Table 2 sum-
marizes the importance of the triflate counterion to the
fluorination-nucleophilic addition reaction. In all cases,
Selectfluor triflate provides greater yields than the
tetrafluoroborate salt. Entries 4 and 5 in Table 1 also
demonstrate the synthetic benefit of the triflate reagent
in producing higher yields. These data implicate the
aforementioned side reaction of the tetrafluoroborate salt
responsible for consumption of the R anomer in entry 4.
A previous comparison of the triflate vs tetrafluoroborate
salts for the electrophilic fluorination of aromatic rings
showed little difference in reactivity and product out-
come.32 The dramatic effects seen in the fluorination-
nucleophilic addition reaction illustrate the special na-
ture of glycal chemistry.
Mech a n ism a n d Ster eoselection . The fluorination-
nucleophilic addition reaction may be mechanistically
separated into the two stages of the stepwise procedure.
The first step is reaction of the glycal with Selectfluor to
form the 1-[TEDA-CH2Cl]-2-deoxy-2-fluoro sugar inter-
mediate. The second step is the reaction of this interme-
diate with the nucleophile. Our goal is to understand the
mechanism of each step independently.
lowed the first step via 19F and H NMR in CD3NO2 to
determine the mechanism of Selectfluor attack, the
structure of the intermediate, and the nature of nucleo-
philic addition (Figure 1). The reaction with diacetyl fucal
2 and Selectfluor triflate was chosen because it gave
exclusively equatorially fluorinated products and no 1,2-
difluoro side products. After 15 min of reaction, two peaks
are found by 19F NMR (Figure 1a). The octet corresponds
to the 4C1 (ring-flipped chair) form of the reactive
intermediate, R-1-[TEDA-CH2Cl]-2-deoxy-2-fluoro sugar
intermediate 4 (Scheme 3).2 1H NMR revealed the nature
of the quartet as 2-fluoro diacetylfucal 8, a side product
resulting from elimination of the reactive intermediate.
It should be noted that this elimination occurs only when
1
intermediate 4 is in the C4 conformation because of the
trans-diaxial relationship of the leaving [TEDA-CH2Cl]
moiety and the H-2. In the spectrum from 3 h of reaction
(Figure 1b,g), the glycal 2 was completely consumed
1
(demonstrated by H NMR), yielding only intermediate
4 and the side product of elimination (compound 8).33
Therefore, Selectfluor attacks the glycal in a pure syn-
addition manner.
After 3 h, a second intermediate, 10, began to form
from 4. Isolation and characterization of 10 showed it to
Selectflu or Atta ck : syn -Ad d ition , F lu or in e Ste-
r eocon tr ol, a n d An om er ic Selectivity. We have fol-
(33) In the NMR experiment, the other side reaction is the hydrolysis
of the intermediates, whose structure has been assigned in our previous
article. In the procedure described in the experimental part, this side
reaction was prevented by the use of molecular sieves.
(32) Banks, R. E.; Besheesh, M. K. J . Fluorine Chem. 1996, 76, 161.

Fluorination-Nucleophilic Addition Mediated by Selectfluor
J . Org. Chem., Vol. 64, No. 14, 1999 5267
1
F igu r e 1. Time course of reaction with diacetylfucal and 1.1 equiv Selectfluor triflate in CD3NO2 by 19F NMR (a-e) and H NMR
(f-j); a and f, 15 min after addition; b and g, 3 h after addition; c and h, 24 h after addition; d and i, 24 h after addition of excess
H2O at rt; e and j, after 1 h at 75 °C.
Sch em e 3
1
be the epimerization product of 4, in the C4 (non-ring
flipped chair) conformation of the â-1-[TEDA-CH2Cl]-2-
deoxy-2-fluoro intermediate. It could be assumed that an
anomeric triflate intermediate is involved in this process,
though it is considered unstable at room temperature.34
However this NMR experiment does not show any new
species that could be assigned as a glycosyl triflate. After
24 h (Figure 1c,h), the amount of 10 continued to increase
as 4 decreased in concentration, and 8 did not increase
in concentration (which remained the same as at 15 min).
In a separate experiment, conversion of 4 to 10 reached
95% after 72 h. When excess water was added, interme-
diate 4 was converted completely to the hydrolyzed form
(Figure 1d,i). Only a small percentage of 10 was hydro-
lyzed after 24 h of exposure to water at room tempera-
ture. Heating the mixture to 75° for 30 min resulted in a
complete hydrolysis of 10 (Figure 1e,j). These results
indicate that the syn-adduct 4 slowly epimerizes to the
thermodynamically more stable form 10. The difference
in hydrolysis rates may be explained by the relative
stability of each intermediate. Hence, the stereochemistry
of the carbon-fluorine bond is determined prior to and
independent of nucleophilic addition.
At this point, the mechanism of the second step of the
fluorination-nucleophilic addition reaction may be un-
derstood. Whether the nucleophile adds with pure inver-
sion of stereochemistry (SN2-type mechanism) or an
intermediate oxonium species is involved (SN1-type mech-
anism) must be understood for directed, stereocontrolled
addition of complex nucleophiles.
The first experiment to identify the mechanism of
nucleophilic attack is to determine the effect of steric
hindrance on product distribution. We reasoned that if
the reaction occurs via a pure SN2 mechanism, the R/â
anomeric ratio would remain unchanged when varying
the steric bulk of the nucleophile. Table 3, entry 12, with
methanol providing the least steric bulk, gives a product
R/â anomeric ratio of 40:60. Benzyl alcohol (entry 13)
yields 50:50, and cyclohexanol (entry 14) gives 55:45. tert-
Butyl alcohol (entry 15), the most bulky, gives a 70:30
(34) Crich, D.; Sun, S. J . Am. Chem. Soc. 1998, 120, 435.

5268 J . Org. Chem., Vol. 64, No. 14, 1999
Vincent et al.
Ta ble 3
R/â ratio. These results, conducted under exactly the
same conditions, demonstrate that increasing steric
hindrance of the nucleophile favors an R-selectivity of the
process, indicating that the mechanism of nucleophilic
attack is not a pure SN2 process.
The second experiment to identify the mechanism of
the second step involved addition of benzyl alcohol to 4
and 10 separately (Scheme 3). When benzyl alcohol is
added to a sample of 4 in CD3NO2 and heated to 100° for
15 min, the resultant product proved to be a 1:1 R/â
anomeric mixture. The same procedure conducted with
10 yielded a 3:2 R/â anomeric ratio. This demonstrates
that both intermediates do not share the same transition
state, otherwise the R/â ratio would have been the same
from both epimers. These results can be explained by a
pure SN1 mechanism, with the assumption that both
intermediates (4 and 10) follow independent pathways,
yielding disparate R/â ratios. Alternatively, the results
may be caused by a competition between SN1 and SN2
mechanisms.
Hence, general rules of anomeric selectivity can be
proposed. Allowing the initial syn-adduct (4) to epimerize
to the thermodynamically more stable intermediate (10)
will lead to a higher R-selectivity of the product. Also,
steric bulk of the nucleophile plays a direct role in the
outcome of product anomeric selectivity, with greater
bulk favoring higher R-selectivity.
Another factor that may be utilized to control anomeric
stereoselectivity is the influence of protecting groups
upon attack of the nucleophile. We reasoned that, in a
manner similar to the steric effect of nucleophiles, one
can select hindered protecting groups for the glycal to
favor R products. Figure 2 shows how bulky protecting
groups may be used to favor R products formation. This
principle is well demonstrated in the syntheses of flu-
orinated daunomycinone glycosides 14-16 (Scheme 6)
below. As the protecting group size increases on the fucal
starting material, from acetyl to benzoyl to pivaloyl,
R-selectivity increases consequently.
F igu r e 2. Oxonium intermediate involved in a SN1-type
mechanism.
F lu or in a tion Ster eoselectivity. Knowing that the
mechanism of Selectfluor attack upon the glycal in the
first step occurs via a syn-addition, we proposed to utilize
glycal protecting groups to direct fluorination stereose-
lectivity. In the galactose and fucose series, the protecting
group at the 4-position directs the stereoselectivity of the
fluorine addition, yielding exclusively equatorially flu-
orinated products even with acetate-protected hydroxy-
ls.35 As triacetylglucal typically yields a 40:60 equatorial/
axial ratio, favoring manno- over gluco- forms,1 larger
protecting groups should therefore lead to a larger
proportion of gluco- product. Table 4, entries 16-18,
demonstrates this principle. With glucal protected as the
acetyl, benzoyl, and pivaloyl forms, the products possess
fluorine equatorial/axial ratios of 45:55, 75:25, and 90:
10, respectively. The C-F selectivity has been simply
reversed through modifying the protecting group strat-
egy. It should be noted that purification of equatorial/
axial fluorinated epimers can be extremely difficult.
Therefore, improving the stereoselectivity of fluorination
is an essential improvement to fluoroglycoside synthesis.
In the synthesis of fluorinated oleandrigenin glycoside
19 (Scheme 6), pivaloyl protecting groups are used on the
L-rhamnal starting material for the purpose of directing
(35) A correction to our previous publication:1 in Table 1 entry 4,
the C-F selectivity should be 100% in favor of the equatorial position
in the galactal series.

Fluorination-Nucleophilic Addition Mediated by Selectfluor
Ta ble 4
J . Org. Chem., Vol. 64, No. 14, 1999 5269
both the C-F and the anomeric stereochemistry. We
found that the fluorine equatorial/axial ratio of the
product was 60:40, favoring the expected equatorial
fluorination. Unlike results for fucal or galactal, this
experiment shows the steric influence of both 6- and
3-positions on the stereoselectivity of fluorination when
compared to the case of tripivaloyl glucal above (entry
16, Table 4).
Sin gle-Electr on vs Tw o-Electr on Tr a n sfer Mech -
a n ism . Given our finding that Selectfluor reacts with the
glycal in a syn-addition fashion, it must be emphasized
that this is only a stereochemical observation. The true
mechanism of the first step is uncertain.36 Different
mechanisms have been proposed for reactions involving
N-F fluorinating reagents. Several mechanistic studies
have been conducted, mainly for the fluorination reaction
of carbanionic species.37,38 Reaction mechanisms can be
extremely sensitive to experimental conditions; for in-
stance, reaction with a given radical probe may provide
different results in two different solvents, demonstrating
that the mechanism could not be the same in different
conditions.39 More recently, Ramsden et al. showed that
(36) Differding, E.; Bersier, P. M. Tetrahedron 1992, 48, 1595.
(37) Differding, E.; Wehrli, M. Tetrahedron Lett. 1991, 32, 3819.
(38) Differding, E.; Ruegg, G. Tetrahedron Lett. 1991, 32, 3815.
(39) Ashby, E. C.; Pham, T. N. Tetrahedron Lett. 1987, 28, 3197.

5270 J . Org. Chem., Vol. 64, No. 14, 1999
Vincent et al.
Sch em e 4
reactions involving xenon difluoride could adopt different
pathways depending on the basicity of the solvent used
and the nature of the reaction vessel.40 Because the glycal
reaction with Selectfluor is very sensitive to solvent
variation and obviously very different to the fluorination
reaction of carbanions, we decided to investigate its
mechanism.
The synthesis of 20 was accomplished through a Wittig
reaction of the aldehyde 2145 and methoxymethyl triph-
enylphosphonium chloride (Scheme 4). The methyl vinyl
ether 20 was combined with Selectfluor triflate in the
optimized conditions for fluorosugar synthesis, with
methanol serving as nucleophile. As shown in Scheme
4, if the process proceeds via a heterolytic N-F cleavage,
the cyclopropyl moiety will remain intact, yielding the
R-fluoro acetal 22. If a radical intermediate is involved
in this process it should rearrange and give compounds
such as 23. The mechanism suggested by Umemoto et
al.43 involves a SET and subsequent F• transfer. We found
that the expected fluorinated dimethoxy acetal 22 was
obtained in a 45% yield with no rearrangement occurring
despite complete consumption of 20. With this probe in
hand, we compared other fluorinating reagents using the
same reaction to identify SET mechanisms (Table 5).
With the N-fluoro diphenylsulfonimide (entry 25), the
expected fluorinated acetal 22 was isolated with a 40%
yield along with the rearranged R,â-unsaturated alde-
hyde 24 (compound already described by Mukaiyama et
al.46), suggesting the possible existence of SET (Scheme
5). To explain the formation of compound 24, we propose
two distinct pathways, both involving SET as the first
step. The two possible radical cations could undergo
either a cationic or radical rearrangement. Then, F•
transfer would occur followed by attack of methanol. The
aldehyde is possibly formed during the workup or puri-
fication through hydrolysis of the resulting dimethoxy
acetal or gem-fluoro methoxy compound. If 25 is formed
by the radical pathway, the process involves a nucleo-
philic substitution of the benzylic fluoride by methanol
catalyzed by the acidic diphenylsulfonamide proton.
The reaction with xenon difluoride (entry 27) provided
several products containing olefins and ring-opened
compounds, as seen by crude NMR. These data cor-
roborate the recent finding that xenon difluoride can give
rise to a radical process.40 N-Fluoro pyridinium gave no
reaction under its optimal conditions.
The mechanistic study was begun by probing the
reaction with three radical scavengers: 2,6-di-tert-butyl-
4-methylphenol (BHT), 2,2,6,6-tetramethylpiperidinooxy
(TEMPO), and p-quinone. To Selectfluor and triacetyl
glucal were added 2 equiv of scavenger and excess
methanol as nucleophile. No inhibition was seen with
p-quinone, and methyl-2-deoxy-2-fluoroglucoside was
isolated. BHT elicited slow reactivity with Selectfluor and
decreased yield by 50%. TEMPO inhibited the reaction
completely, and all of the starting material was recov-
ered. In a separate experiment without glycal, TEMPO
reacted independently with Selectfluor. The reactivity of
TEMPO with Selectfluor points to a homolytic cleavage
of the N-F bond, although no monosaccharide products
that would implicate a single-electron transfer (SET) or
another radical mechanism were isolated from any of
these experiments.
Several recent mechanistic studies have attempted to
determine the mechanism of N-F fluorinating
reagents.36-38,41-43 These studies based on kinetics, elec-
trochemistry, or radical trapping inspired our synthesis
of more sensitive molecules based on the hypersensitive
radical probes containing a phenyl-cyclopropyl moiety.44,45
Radicals formed on these molecules trigger the opening
of a cyclopropyl ring at a rate of 1011 sec-1 44,45
We
.
reasoned that if a SET occurs during the reaction
between Selectfluor and a glycal the radical cation formed
would rearrange into a noncyclic olefin.
(40) Ramsden, C. A.; Smith, R. G. J . Am. Chem. Soc. 1998, 120,
6842.
(41) Zupan, M.; Skulj, P.; Stavber, S. Chem. Lett. 1998, 641.
(42) DesMarteau, D. D.; Xu, Z.-Q.; Witz, M. J . Org. Chem. 1992,
57, 629.
(43) Umemoto, T.; Fukami, S.; Tomizawa, G.; Harasawa, K.; Kawa-
da, K.; Tomita, K. J . Am. Chem. Soc. 1990, 112, 8563.
(44) Newcomb, M.; Manek, B. J . Am. Chem. Soc. 1990, 112, 9663.
(45) Fu, H.; Look, G. C.; Zhang, W.; J acobsen, E. N.; Wong, C.-H. J .
Org. Chem. 1991, 56, 6497.
These mechanistic experiments conclude that Select-
fluor proceeds via a two-electron mechanism in reaction
with vinyl ethers, which may be extrapolated to reaction
(46) Ishida, A.; Mukaiyama, T. Bull. Chem. Soc. J pn. 1977, 50, 1161.

Fluorination-Nucleophilic Addition Mediated by Selectfluor
Ta ble 5
J . Org. Chem., Vol. 64, No. 14, 1999 5271
Sch em e 5. P u ta tive Mech a n ism for F or m a tion of Ald eh yd e 25
with glycals. Although these findings support previous
monosaccharide (41%),5 giving an overall yield of 28%
over three steps. By the use of Selectfluor, the reaction
is conducted in one pot with a higher overall yield. In
entry 17, the benzoyl protection of glucal gives the
expected gluco-stereoselectivity as well as R anomeric
selection. A very favorable yield is found in entry 18 even
with an extremely bulky nucleophile. We believe that the
severe steric hindrance of the nucleophile leads to R
anomeric specificity. Increasing the size of nucleophile
also increases R-selectivity as shown in entry 20. 2′-
Deoxy-2′-fluorodisaccharides have been shown to be
specific, mechanism-based inhibitors of glycosidases.5
conclusions,41 these are the first examples of using a
hypersensitive vinyligous ether radical probe to study
fluorination, and they are of particular importance to the
use of Selectfluor in glycal chemistry.
Syn th esis of Im p or ta n t F lu or in a ted Glycosid es.
2′-Deoxy-2′-flu or od isa cch a r id es a n d 2-Deoxy-2-flu -
or o Glycosid es. Given the improved reaction conditions,
Selectfluor salt, and mechanistic knowledge described
above, we began with the synthesis of several glycosides.
Table 4 outlines 2′-deoxy-2′-fluorodisaccharides (entries
17-19) that can be made via Selectfluor triflate in good
yields. Recent publications reporting the synthesis of
fluorinated disaccharides required the synthesis of 1,2-
difluoride from the glycal (69%),23 formation of the
1-bromo-2-fluoride (99%),25 and final coupling with a
Amino acids (entry 22), phenols (entry 21), and amines
(entry 23) also serve as good nucleophiles, which must
be utilized in the stepwise procedure. These reactions
provide a new direction to the synthesis of new fluori-

5272 J . Org. Chem., Vol. 64, No. 14, 1999
Vincent et al.
Ta ble 6
nated glycosides, including fluorinated glycopeptides,
fluorinated nucleotides, and chromophore-labeled fluo-
roglycosides.
series generally must be stored at low temperature and
have the propensity to anomerize.47-49 It had also been
noticed that â-fucosyl phosphates are more stable when
the sugar is protected by benzoyl groups rather than
acetates.47
F lu or o-p h osp h or yla t ion . One-pot synthesis of 2-
deoxy-2-fluoro phosphate saccharides has been a goal of
our Selectfluor chemistry, as they can be used for the
synthesis of glycosyltransfer enzyme inhibitors. As men-
tioned above, nonstepwise procedures result in no desir-
able product formation, presumably through decomposi-
tion of Selectfluor by phosphate acidity. From these
experiments, several conclusions may be drawn concern-
ing the synthesis of fluoroglycosyl phosphates. First, the
reaction is very sensitive to the choice of glycal protection.
Protection with acetate gave the lowest yields (never
exceeding 15% of impure material), whereas benzoyl and
pivaloyl protection gave much better results (Table 6,
entries 29 and 30).47 Additionally, we found that the
nature of phosphate protection can significantly modify
the yield and anomeric distribution of the phosphoryla-
tion in the fucose series (entries 28 and 29). When
diphenyl phosphate is used as a nucleophile, the reaction
is R-specific, whereas a â-selectivity is observed when
using dibenzyl phosphate. This trend may be due to in
situ decomposition of the â products under the reaction
conditions (90-100 °C), as phosphates in the â-L-fucose
Attempts to use deprotonated phosphates (triethyl-
ammonium and pyridinium salts) to enhance the nucleo-
philicity failed completely, yielding no expected fluoro-
glycosyl phosphates. The utility of this fluoro-phos-
phorylation technique is obvious when compared with
standard methods that require at least three steps and
give lower overall yields.17 Reaction of diphenyl phos-
phoric acid with tripivaloyl glucal (Table 6, entry 31) and
galactal (entry 32) gave both R and â anomers with
favorable yields. In keeping with the C-F stereoselec-
tivity described above in the gluco series, protection with
pivaloates gave the expected 90:10 equatorial/axial ratio.
It should be noted that the â phosphate is the major
product of the gluco form, whereas the galacto form favors
the R phosphate.
In an attempt to extend this reaction to other phos-
phorus-based nucleophiles, phosphites were reacted with
the intermediates, but the products decomposed during
(48) Sim, M. M.; Kondo, H.; Wong, C.-H. J . Am. Chem. Soc. 1993,
115, 2260.
(49) Gokhale, U. B.; Hindsgaul, O.; Palcic, M. M. Can. J . Chem.
1990, 68, 1063.
(47) Adelhorst, K.; Whitesides, G. Carbohydr. Res. 1993, 249, 69.

Fluorination-Nucleophilic Addition Mediated by Selectfluor
Sch em e 6
J . Org. Chem., Vol. 64, No. 14, 1999 5273
the course of the reaction. Results were more favorable
with phosphonate addition, giving the expected product
34 in 36% yield with exclusive R-selectivity. This result
compares favorably with standard phosphonate glycoside
syntheses in which direct phosphonylation obtain pro-
duces from 25% to 50% in harsher conditions (170 °C
under vacuum).50
manno configuration at the 2-position consistently exhibit
pure R-configuration (see also Table 4, entries 16 to 19).
The anthracycline antibiotic daunorubicin (daunomy-
cin) is a commonly used chemotherapeutic agent that
displays some undesirable side effects including high
cardiotoxicity.53 With inspiration from the glycal oxida-
tive coupling techniques of Danishefsky to make hybrid
anthracyclines,54 we chose to synthesize the fluorinated
analogue of daunorubicin by the fluorination-nucleo-
philic addition reaction. Several fluorinated analogues in
this family have been previously described.15 Daunoru-
bicin was hydrolyzed in methanol/aqueous HCl to yield
daunomycinone and daunosamine. We chose to substitute
the natural daunosamine with 2-deoxy-2-fluoro fucal to
demonstrate the viability of the one-pot reaction to
bioactive molecules. To study the glycal protecting group
participation in the fluorination-nucleophilic addition
reaction, we investigated acetylated, benzoylated, and
pivaloylated fucal as glycosyl donors. Protected fucal and
Selectfluor triflate were allowed to react at room tem-
perature for 4 h, followed by addition of daunomycinone
and heat to reflux for 1 h. Products 14-16 were isolated
in 60% yield. Daunomycinone serves as an important
example of nucleophile reactivity in the fluorination-
nucleophilic addition reaction. With four unprotected
hydroxyls, only the secondary hydroxyl at C-7 attacks the
reactive intermediate. Protecting group strategy plays an
important role in product outcome. The bulky pivaloyl
protecting groups on the glycal served to direct the
anomeric ratio to 3:1 R/â. The benzoyl fucal gave a 2:1
anomeric ratio, and the acetyl derivative yielded 3:1. As
the natural R-configuration is desired, the pivaloylated
starting material should serve as a future route to
fluorinated analogues of adriamycin and other glycosy-
lated anthracyclines.
Ap p lica tion to Kn ow n Bioa ctive Molecu les: Ca r -
d ia c Glycosid es a n d An th r a cyclin e Glycosid es. To
demonstrate the synthetic utility of the electrophilic
fluorination-nucleophilic addition reaction, two biologi-
cally active natural product glycosides were chosen for
the synthesis of fluorinated analogues. The following two-
step procedure is a useful method of modifying natural
product glycosides through fluorination. The carbohy-
drate is first hydrolyzed, and a glycal is used for the
fluoroglycosylation of the aglycone. Fluorinated ana-
logues of the natural product improve hydrolysis resis-
tance and may display modified biological activity.
We began with oleandrin, a cardiac glycoside from the
leaves of Nerium oleander that is a member of the
digitalis class of cardiotonics. Hydrolysis of oleandrige-
ninin in boiling methanol and 1 N H2SO4 gives the
aglycon, oleandrigenin, and the monosaccharide olean-
drose. Oleandral, or 3-O-methyl-L-rhamnal, may be easily
synthesized from the parent monosaccharide or by other
methods.51,52 For the purposes of this experiment, the
commercially available L-rhamnal is used, first combined
with Selectfluor triflate for 3 h at room temperature,
followed by oleandrigenin and heat to reflux for 1 h
(Scheme 6). Product 19 was isolated in 63% yield. The
C-F stereoselectivity was 60:40 eq/ax and is rationalized
by the steric hindrance of the pivaloyl protecting group.
It should be noted that whereas a 60:40 R/â mixture is
obtained when the fluorine is equatorial, only the natural
R-configuration of oleandrin is observed for the product
with axial fluorine, thus giving an overall 75:25 R/â ratio.
This observation seems to be general for all reactions
involving glucal-type starting materials; products with
Oxid a tion of Th ioglycosid e to Su lfoxid e. The elec-
trophilic nature of Selectfluor was then used to fluorinate
thioglycosides for use as activated glycosylation reagents1
or as precursors to sulfoxides (Scheme 7).34,55-58 The
(50) Vaghefi, M. M.; Bernacki, R. J .; Hennen, W. J .; Robins, R. K.
J . Med. Chem. 1987, 30, 1391.
(51) Tolman, R. L.; Peterson, L. H. Carbohydr. Res. 1989, 189, 113.
(52) Danishefsky, S. J .; Armistead, D. M.; Wincott, F. E.; Selnick,
H. G.; Hungate, R. J . Am. Chem. Soc. 1989, 111, 2967.
(53) Yariv, J .; Kalb, A. J .; Katchalski, E. Nature 1967, 215, 890.
(54) Suzuki, K.; Sulikowski, G. A.; Friesen, R. W.; Danishefsky, S.
J . J . Am. Chem. Soc. 1990, 112, 8895.
(55) Kahne, D.; Walker, S.; Cheng, Y.; van Engen, D. J . Am. Chem.
Soc. 1989, 111, 6881.

5274 J . Org. Chem., Vol. 64, No. 14, 1999
Sch em e 7. P r op osed Mech a n ism for Activa tion of Th ioglycosid e u sin g Selectflu or
Vincent et al.
Ta ble 7. Oxid a tion of Th ioglycosid es by Selectflu or to
th e Cor r esp on d in g Su lfoxid e
system is also applied to the synthesis of the more
reactive compound 44 to avoid the decomposition of the
product.
The advantages of this method are short reaction time,
quantitative conversion, and easy workup. The product
generated from the reagent is not soluble in CH2Cl2 and
can be easily washed away by water. After evaporation
of the solvent, the diastereomeric mixture was obtained
in quantitative yield, and the purity was confirmed by
NMR. We also performed this reaction with thioglyco-
sides bearing a hydroxyl group (38, 40, and 44). Interest-
ingly, when we treated p-methylthiophenol with 0.5 equiv
of Selectfluor in CH3CN-H2O, the disulfide 45 (Table 6)
was the only product. Use of 1.5 equiv of Selectfluor gave
the monosulfoxide 46.
In conclusion, we have conducted a mechanistic study
upon the electrophilic fluorination-nucleophilic addition
reaction of glycals mediated by Selectfluor, which brings
new insights into the nature of the intermediates in-
volved, the factors affecting the stereochemistry of both
fluorination and nucleophilic addition, and the electro-
philic character of this reaction. These results allowed
us to explore a broader range of nucleophiles, giving
fluorinated disaccharides, glycopeptides, glycosyl phos-
phates, or phosphonates and fluorinated analogues of
biologically relevant glycosylated compounds, directly
from glycals, in a one-pot procedure. Additionally, we
found that Selectfluor is a very efficient reagent for the
oxidation of thioglycosides to the corresponding sulfox-
ides.
available methods for the oxidation of thioglycosides to
sulfoxides are based on m-chloroperoxybenzoic acid (MCP-
BA) at low temperature (-78 C)55,56 or H2O2-AcOH.59
The first method may cause overoxidation, requires low
temperature, and is not trivial in product purification.
The second method is relatively inexpensive but less
efficient when dealing with less reactive thioglycosides.
We have found that Selectfluor in CH3CN-H2O (20:1)
can quantitatively oxidize thioglycosides to the corre-
sponding sulfonyl glycosides in minutes, and no purifica-
tion is needed (Scheme 7). The reaction may proceed
through the fluoro-sulfonium cation,1 which reacts with
water to give the sulfoxide.
As shown in Table 7, thioglycosides with different
protecting groups and with about 104-fold reactivity
difference60 can be oxidized quantitatively by Selectfluor.
When a silyl ether (TBS) protected thioglycoside was used
as substrate, the HF released from the reaction also
cleaved the TBS group. To solve this problem, a weak
base (5 equiv of NaHCO3) was added, and the reaction
was carried out in a higher concentration of water, CH3-
CN-H2O (10:1), to neutralize the HF. This modified
Exp er im en ta l Section
Gen er a l P r oced u r e for th e F lu or in a tion -Nu cleop h ilic
Ad d ition Rea ction . To a mixture of glycals (100-200 mg
scale, 1 equiv) and 4 Å dry molecular sieves (200 mg) in dry
nitromethane (4 mL) was added F-TEDA‚2OTf (1.1 equiv).
After 6 h of stirring room temperature under argon, a solution
of the nucleophile (1.1 equiv) in nitromethane (1 mL) is added
quickly, and the solution is stirred at 100 °C for 1 h. The
mixture is poured onto 100 mL of dichloromethane, filtered
through Celite, and concentrated. The resulting mixture is
then chromatographed.
Com p ou n d 1. Eth a n im id ic Acid , N-(2-F lu or o-2-d eoxy-
3,4,6-tr i-O-a cetyl-R-D-ga la ctop yr a n osyl)-1,2:3,4-Di-O-iso-
p r op ylid en e-R-D-ga la ctop yr a n osyl Ester . To a mixture of
tri-O-acetyl-galactal (209 mg, 0.77 mmol), 1,2:3,4-di-O-isopro-
pylidene-R-D-galactopyranose (100 mg, 0.38 mmol), 2,6-di-tert-
butyl-4-methylpyridine (158 mg, 0.77 mmol), and 4 Å molec-
ular sieves (200 mg) in dry acetonitrile (3 mL) was added
F-TEDA‚2BF4 (272 mg, 0.77 mmol). The mixture was stirred
for 18 h at room temperature under argon. To the reaction
mixture was added dichloromethane (25 mL). The resulting
solution was filtered, concentrated, and purified by silica gel
chromatography (hexanes/ethyl acetate, 2:1) to give the title
compound (74.8 mg, 0.13 mmol, in a 54% yield based on
recovered starting material (38%)). 1H NMR (400 MHz, CDCl3)
(56) Pascal, R. A.; Kahne, D. J . Am. Chem. Soc. 1998, 120, 5961.
(57) Liang, R.; Yan, L. L. J .; Ge, M.; Uozumi, Y.; Sekanina, K.;
Horan, N.; Gildersleeve, J .; Thompson, C.; Smith, A.; Biswas, K.; Still,
W. C.; Kahne, D. Science 1996, 274, 1520.
(58) Crich, D.; Sun, S. J . Org. Chem. 1996, 61, 4506.
(59) Kakarla, R.; Dulina, R. G.; Hatzenbuhler, N. T.; Hui, Y. W.;
Sofia, M. J . J . Org. Chem. 1996, 61, 8347.
δ 5.56 (d, J 1-2 ) 5.0 Hz, 1H), 5.52 (dd, J 1′-2′ ) 3.1 Hz, J 1′-F
)
(60) Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.;
Wong, C.-H. J . Am. Chem. Soc. 1999, 121, 734.
2.1 Hz, 1H), 5.40-5.31 (m, 2H), 4.91 (ddd, J 2′-F ) 51.1 Hz,

Fluorination-Nucleophilic Addition Mediated by Selectfluor
J . Org. Chem., Vol. 64, No. 14, 1999 5275
J 2′-3′ ) 10.1 Hz, J 2′-1′ ) 3.1 Hz, 1H), 4.70 (t, J ) 6.7 Hz, 1H),
4.64 (dd, J ) 7.9, 2.4 Hz, 1H), 4.36-4.28 (m, 3H), 4.19-4.03
(m, 4H), 2.15 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H),
1.53 (s, 3H), 1.48 (s, 3H), 1.37 (s, 3H), 1.34 (s, 3H); 13C NMR
(100.6 MHz, CDCl3) δ 170.42, 170.08, 169.92, 164.55, 109.48,
108.60, 96.27, 86.7 (d, J ) 187.4 Hz), 83.33 (d, J ) 22.0 Hz),
71.08, 70.60, 70.50, 69.04 (d, J ) 7.6 Hz), 68.77 (d, J ) 18.6
Hz), 66.77, 65.91, 64.26, 61.65, 25.99, 25.92, 24.89, 24.41,
20.70, 20.65, 20.57, 16.21; 19F NMR (376 MHz, CDCl3) δ
-202.40 (dd, J ) 51.1, 10.6 Hz); HRMS (M + Cs+) calcd for
3H); 19F NMR (376 MHz, CDCl3) δ -199.63 (dd, J F-2H ) 49.6
Hz, J F-3H ) 27.9 Hz); HRMS (M + Cs+) calcd for C21H29FO12
-
Cs 625.0697, found 625.0715.
Com p ou n d 10. 1-Ch lor om eth yl-4-N-(2-d eoxy-2-flu or o-
3,4-d i-O-a cetyl-â-1-L-fu cop yr a n osyl)-1,4-d ia zon ia bicyclo-
[2.2.2]octa n e Bistr ifla te. To a mixture of diacetyl fucal (50
mg scale, 1 equiv) and 4 Å dry molecular sieves (200 mg) in
dry nitromethane (8 mL) was added F-TEDA‚2OTf (1.1 equiv).
After 2 days of stirring at room temperature under argon, 10
mL of AcOEt was added, and the mixture was filtered. The
resulting filtrate was poured onto a mixture of AcOEt/hexane
1:1 (100 mL). After removal of the supernatant, the resulting
C
26H38FNO13Cs 724.1382, found 724.1402.
Com pou n d 5-glu cor. 2-Deoxy-2-flu or o-3,4,6-tr i-O-acetyl-
r-D-glu cosyl-(1-6)-1,2:3,4-d i-O-isop r op ylid en e-r-D-ga la c-
top yr a n ose. The general procedure was applied. Chromato-
graphic conditions, hexane/AcOEt, 2:1. 1H NMR (600 MHz,
CDCl3) δ 5.55 (dt, J 3′-2′ ) 9.6 Hz J 3′-F ) 12.6 Hz J 3′-4′ ) 9.6
Hz, 1H), 5.48 (d, J 1-2 ) 5.0 Hz, 1H), 5.11 (d, J 1′-2′ ) 3.8 Hz,
1H), 5.01 (t, J 3′-4′ ) J 5′-4′ ) 9.6 Hz, 1H), 4.59 (dd, J 3-2 ) 7.9
Hz J 3-4 ) 2.4 Hz, 1H), 4.48 (ddd, J 1′-2′ ) 3.9 Hz J 3′-2′ ) 9.6 Hz
J 2′-F ) 49.3 Hz, 1H), 4.28 (m, 2H), 4.15 (ddd, J 5′-4′ ) 10.2 Hz
J 6′A-5′ ) 2.1 Hz J 6′B-5′ ) 4.0 Hz, 1H), 4.07 (m, 2H), 4.00 (dt,
J 5-6 ) 7.9 Hz J 5-4 ) 2.4 Hz, 1H), 3.81 (AB part of an ABX
system, J 5-6A ) J 5-6B ) 6.2 Hz J AB ) 10.5 Hz, 2H), 2.07 (s,
3H), 2.05 (s, 3H), 2.02 (s, 3H), 1.55 (s, 3H), 1.41 (s, 3H), 1.32
(s, 3H), 1.31 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 170.7, 170.1,
169.7, 109.3, 108.7, 96.5 (d, J C-F ) 25.0 Hz), 96.2, 87.3 (d, J C-F
) 200.0 Hz), 70.8 (d, J ) 20.8 Hz), 70.7, 70.6, 70.5, 68.1, 67.9
(d, J C-F ) 7.5 Hz), 67.2, 66.6, 61.7, 26.1, 25.9, 24.9, 24.3, 20.7,
20.6; 19F NMR (376 MHz, CDCl3) δ -197.85 (dd, J 2-F ) 49.3
Hz, J 3-F ) 12.6 Hz); HRMS (M + Na+) calcd for C24H35FO13
573.1959, found 573.1980.
white solid was washed once with 3 mL of chloroform and
1
dried. H NMR (600 MHz, CD3NO2) δ 5.50 (AB system, J AB
)
10.0 Hz, CH2Cl), 5.47-5.38 (m, 3H 3-H and 1-H), 5.37 (dd,
J 4-F ) 2.3 Hz J 3-4 ) 2.9 Hz, 1H), 4.51-4.25 (m, partially
hidden by the solvent and CH2N), 2.17 (s, 3H), 2.07 (s, 3H),
1.33 (d, J 5-6 ) 6.4 Hz, 3H); 13C NMR (150 MHz, CD3NO2) δ
172.03, 171.43, 122.15 (q, J C-F ) 318.0 Hz, TfO-), 95.64 (d,
J C-F ) 23.0 Hz), 85.51 (d, J C-F ) 186.3 Hz), 15.64 (CH2Cl);
72.52 (d, J ) 19.5 Hz), 70.84 (d, J ) 8.5 Hz), 70.59, 52.96,
51.99, 51.92, 20.62, 20.39, 15.82; 19F NMR (376 MHz, CD3-
NO2) δ -109.6837 (s, TfO-), -196.65 (dd, J 2-F ) 55.9 Hz, J 3-F
) 12.7 Hz); HRMS (M + Na+) calcd for C17H28O5FClN2
393.1593, found 393.1589.
Com p ou n d 11â. 2-Deoxy-2-flu or o-3,4-d i-O-a cet yl-r-1-
m eth yl-L-fu cop yr a n ose. The general procedure was applied.
Chromatographic conditions, hexane/AcOEt, 4:1. 1H NMR (400
MHz, CDCl3) δ 5.27 (ddd, J 4-5 ) 0.8 Hz J 4-F ) 2.7 Hz J 3-4
3.8 Hz, 1H), 5.11 (ddd, J 3-4 ) 3.8 Hz, J F-3 ) 13.5 Hz, J 3-2
9.7 Hz, 1H), 4.49 (ddd, J 1-2 ) 7.6 Hz J 3-2 ) 9.7 Hz J 2-F
)
)
)
Com p ou n d 5-m a n n or. 2-Deoxy-2-flu or o-3,4,6-t r i-O-
a cetyl-r-D-m a n n osyl-(1-6)-1,2:3,4-d i-O-isop r op ylid en e-r-
D-ga la ctop yr a n ose. 1H NMR (400 MHz, CDCl3) δ 5.0 (d, J 1-2
) 5.0 Hz, 1H), 5.32 (t, J 3′-4′ ) J 5′-4′ ) 10.1 Hz, 1H), 5.25 (ddd,
J 3′-2′ ) 2.5 Hz J 3′-F ) 28.3 Hz J 3′-4′ ) 10.1 Hz, 1H), 5.06 (dd,
J 1′-F ) 7.1 Hz J 1′-2′ ) 1.6 Hz, 1H), 4.78 (dt, J 1′-2′ ) J 3′-2′ ) 2.0
Hz J 2′-F ) 49.7 Hz, 1H), 4.63 (dd, J 3-2 ) 2.4 Hz J 3-4 ) 7.9 Hz,
1H), 4.34 (dd, J 3-2 ) 2.4 Hz J 1-2 ) 5.0 Hz, 1H), 4.29 (dd, J 6′a-5′
53.5 Hz, 1H), 4.48 (dd, J 1-2 ) 7.6 Hz J 1-F ) 2.2 Hz, 1H), 3.84
(qd, J 5-6 ) 6.3 Hz J 5-4 ) 0.8 Hz, 1H), 3.61 (s, 3H), 2.16 (s,
3H), 2.06 (s, 3H), 1.24 (d, J 5-6 ) 6.3 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 170.48, 170.07, 101.49 (d, J C-F ) 23.1 Hz),
88.05 (d, J C-F ) 184.9 Hz), 71.45 (d, J ) 17.3 Hz), 70.80 (d, J
) 8.7 Hz), 69.08, 57.21, 20.61, 20.55, 15.84; 19F NMR (376
MHz, CDCl3) δ -204.08 (dd, J 2-F ) 53.3 Hz, J 3-F ) 15.2 Hz);
HRMS (M+H+) calcd for C11H17O6F 265.1087, found 265.1085.
Com p ou n d 12r. 2-Deoxy-2-flu or o-3,4-d i-O-a cetyl-r-1-
(cycloh exyl)-L-fu cop yr a n ose. The general procedure was
) 4.7 Hz J 6′a-6′b ) 12.5 Hz, 1H), 4.22 (dd, J 3-4 ) 7.9 Hz J 5-4
)
1.8 Hz, 1H), 4.11 (m, 2H), 3.97 (dt, J 5-6a ) J 5-6b ) 4.7 Hz J 5-4
) 1.8 Hz, 1H), 3.80 (AB part of ABX, J 5-6a ) J 5-6b ) 4.7 Hz
J 6a-6b) 10.4 Hz, 2H), 2.11 (s, 3H.), 2.10 (s, 3H), 2.05 (s, 3H),
1.56 (s, 3H), 1.44 (s, 3H), 1.34 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ 170.78, 170.16, 169.52, 109.46, 108.72, 97.19 (d, J C-F
) 29.0 Hz), 96.24, 86.84 (d, J C-F ) 178.0 Hz), 70.86, 70.59,
70.46, 69.98 (d, J ) 16.7 Hz), 68.55, 67.06, 66.09, 65.64, 61.99,
26.06, 25.93, 24.89, 24.47, 20.76, 20.66; 19F NMR (376 MHz,
CDCl3) δ -200.85 (dd, J 2-F ) 49.7 Hz, J 3-F ) 28.3 Hz); HRMS
(M + Na+) calcd for C24H35FO13 573.1959, found 573.1942.
Com p ou n d 7-glu cor. 3′,4′,6′-Tr i-O-a cetyl-2′-d eoxy-2′-
flu or o-r-D-glu cop yr a n osyl-(1′-4)-1,6-a n h yd r o-2,3-O-iso-
p r op ylid en e-â-D-m a n n op yr a n ose. The general procedure
was applied. Chromatographic conditions, hexane/AcOEt, 2:1.
The isolated products were an inseparable mixture of the
R-gluco glycoside 7-glu cor and the R-manno glycoside 7-m -
a n n or in a ratio of 45:55.1H NMR (400 MHz, CDCl3) δ 5.56
(dt, J 3′-F ) 11.8 Hz, J 3′-2′ ) 9.6 Hz, J 3′-4′ ) 9.6 Hz, 1H), 5.37-
5.21 (m, 2H), 5.02 (t, J 4′-3′ ) 9.6 Hz, J 4′-5′ ) 9.6 Hz, 1H), 4.76
1
applied. Chromatographic conditions, hexane/AcOEt, 4:1. H
NMR (400 MHz, CDCl3) δ 5.41 (td, J 3-2 ) 9.3 Hz J 3-F ) 9.3
Hz J 3-4 ) 3.5 Hz, 1H), 5.32 (td, J 3-4 ) 3.5 Hz, J F-4 ) 3.5 Hz
J 5-4 ) 1.0 Hz, 1H), 5.17 (d, J 1-2 ) 4.0 Hz), 5.27 (ddd, J 1-2
)
4.0 Hz J 3-2 ) 9.3 Hz J 2-F ) 50.5 Hz, 1H), 4.27 (qd, J 5-6 ) 7.1
Hz J 5-4 ) 1.0 Hz, 1H), 3.61 (h, J ) 3.8 Hz, 1H), 2.16 (s, 3H),
2.04 (s, 3H), 1.87 (m, 2H), 1.76 (m, 2H), 1.33 (m, 6H), 1.12 (d,
J 5-6 ) 7.1 Hz); 13C NMR (125 MHz, CDCl3) δ 170.48, 170.13,
94.86 (d, J C-F ) 19.2 Hz), 85.26 (d, J C-F ) 189.6 Hz), 76.71,
71.87 (d, J ) 7.6 Hz), 68.77 (d, J ) 18.0 Hz), 64.45, 33.27,
31.44, 25.50, 23.98, 23.68, 20.73, 20.60, 15.67; HRMS (M +
Na+) C16H25O6F1 calcd for 355.1533, found 355.1529.
Com p ou n d 12â. 2-Deoxy-2-flu or o-3,4-d i-O-a cetyl-â-1-
(cycloh exyl)-L-fu cop yr a n ose. 1H NMR (400 MHz, CDCl3)
δ 5.25 (td, J 3-4 ) 3.5 Hz, J F-4 ) 3.5 Hz J 5-4 ) 1.1 Hz, 1H),
5.09 (ddd, J 3-2 ) 9.4 Hz J 3-F ) 16.7 Hz J 3-4 ) 3.5 Hz, 1H),
4.63 (dd, J 1-2 ) 7.8 Hz J 1-F ) 3.8 Hz, 1H), 5.27 (ddd, J 1-2
)
7.8 Hz J 3-2 ) 9.4 Hz J 2-F ) 51.3 Hz, 1H), 3.81 (qd, J 5-6 ) 6.5
Hz J 5-4 ) 1.1 Hz, 1H), 3.61 (m, 1H), 2.15 (s, 3H), 2.05 (s, 3H),
1.95 (m, 2H), 1.76 (m, 2H), 1.36 (m, 6H), 1.21 (d, J 5-6 ) 6.5
Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 170.59, 170.14, 94.83
(d, J C-F ) 21.8 Hz), 88.00 (d, J C-F ) 184.8 Hz), 78.08, 71.69
(d, J ) 19.0 Hz), 70.95 (d, J ) 7.6 Hz), 64.46 (5), 33.40, 31.65,
25.49, 24.06, 23.83, 20.67, 20.64, 16.04; 19F NMR (376 MHz,
CDCl3) δ - 203.42 (dd, J 2-F ) 53.3 Hz, J 3-F ) 15.3 Hz); HRMS
(M + Na+) calcd for C16H25O6F 355.1533, found 355.1710.
Com p ou n d 13r. 2-Deoxy-2-flu or o-3,4-d i-O-a cetyl-r-1-
ter t-bu tyl-L-fu cop yr a n ose. The general procedure was ap-
plied. Chromatographic conditions, hexane/AcOEt, 4:1. 1H
NMR (400 MHz, CDCl3) δ 5.40 (td, J 3-2 ) 10.2 Hz J 3-F ) 10.2
Hz J 3-4 ) 3.5 Hz, 1H), 5.32 (td, J 3-4 ) 3.5 Hz, J F-4 ) 3.5 Hz,
(dd, J ) 6.3, 1.3 Hz, 1H), 4.52 (ddd, J 2′-F ) 49.2 Hz, J 2′-3′
9.6 Hz, J 2′-1′ ) 3.9 Hz, 1H), 4.33-4.17 (m, 4H), 4.12 (dd, J 2-3
) 6.3 Hz, J 2-1 ) 3.2 Hz, 1H), 3.99 (dd, J 3-2 ) 7.1 Hz, J 3-4
)
)
1.1 Hz, 1H), 3.93 (s, 1H), 3.75 (t, J 5-6 ) 7.1 Hz, 1H), 2.08 (s,
3H), 2.07 (s, 3H), 2.06 (s, 3H), 1.54 (s, 3H), 1.33 (s, 3H); 19F
NMR (376 MHz, CDCl3) δ -196.60 (dd, J F-2H ) 49.7 Hz, J F-3H
) 11.6 Hz); HRMS (M + Cs+) calcd for C21H29FO12Cs 625.0697,
found 625.0715.
Com p ou n d 7-m a n n or. 3′,4′,6′-Tr i-O-a cetyl-2′-d eoxy-2′-
flu or o-r-D-m a n n op yr a n osyl-(1′-4)-1,6-a n h yd r o-2,3-O-iso-
p r op ylid en e-â-D-m a n n op yr a n ose. 1H NMR (400 MHz,
CDCl3) δ 5.37-5.21 (m, 4H), 4.82 (dd, J ) 6.3, 1.2 Hz, 1H),
4.80 (dt, J 2′-F ) 49.6 Hz, J 2′-1′ ) 2.1 Hz, J 2′-3′ ) 2.1 Hz, 1H),
4.27-4.17 (m, 4H), 4.09 (dd, J ) 6.4, 3.0 Hz, 1H), 3.98 (dd, J
) 7.4, 1.1 Hz, 1H), 3.95 (s, 1H,), 3.75 (t, J 5-6 ) 7.1 Hz, 1H),
2.11 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 1.54 (s, 3H), 1.33 (s,-
J 5-4 ) 2.2 Hz, 1H), 5.30 (d, J 1-2 ) 4.0 Hz), 4.71 (ddd, J 1-2
4.0 Hz J 3-2 ) 10.2 Hz J 2-F ) 51.0 Hz, 1H), 4.27 (qd, J 5-6
)
)
7.0 Hz J 5-4 ) 2.2 Hz, 1H), 2.16 (s, 3H), 2.04 (s, 3H), 1.27 (s,

5276 J . Org. Chem., Vol. 64, No. 14, 1999
Vincent et al.
9H), 1.10 (d, J 5-6 ) 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3)
8.06-7.92 (m, 6H), 7.56-7.39 (m, 9H), 6.07 (dt, J 3′-F ) 11.4
Hz, J 3′-2′ ) 9.6 Hz, J 3′-4′ ) 9.6 Hz, 1H), 5.60 (t, J 4′-3′ ) 9.7 Hz,
J 4′-5′ ) 9.7 Hz, 1H), 5.54 (d, J 1-2 ) 4.8 Hz, 1H), 5.27 (d, J 1′-2′
δ 170.50, 170.18, 90.95 (d, J C-F ) 19.9 Hz), 85.06 (d, J C-F
)
188.6 Hz), 75.75, 71.96 (d, J ) 7.6 Hz), 68.95 (d, J ) 18.0 Hz),
63.99, 28.41, 20.75, 20.59, 15.69; 19F NMR (376 MHz, CDCl3)
δ -203.42 (dd, J 2-F ) 50.8 Hz, J 3-F ) 7.6 Hz); HRMS (MH+)
calcd for C14H23O6F 307.1557, found 307.1554.
) 3.8 Hz, 1H), 4.74 (ddd, J 2′-F ) 49.5, J 2′-3′ ) 9.6 Hz, J 2′-1′
)
3.8 Hz, 1H), 4.65-3.92 (m, 9H), 1.63 (s, 3H), 1.43 (s, 3H), 1.35
(s, 3H), (s, 3H); 19F NMR (376 MHz, CDCl3) δ -197.38 (dd,
J F-2′ ) 51.1 Hz, J F-3′ ) 10.6 Hz); HRMS (M + Cs+) calcd for
Com p ou n d 13â. 2-Deoxy-2-flu or o-3,4-d i-O-a cet yl-r-1-
ter t-bu tyl-L-fu cop yr a n ose. 1H NMR (400 MHz, CDCl3) δ
5.25 (ddd, J 4-5 ) 1.1 Hz J 4-F ) 2.5 Hz J 3-4 ) 3.5 Hz, 1H),
5.12 (ddd, J 3-4 ) 3.5 Hz, J F-3 ) 13.2 Hz, J 3-2 ) 9.7 Hz, 1H),
4.68 (dd, J 1-2 ) 7.6 Hz J 1-F ) 3.8 Hz), 4.58 (ddd, J 1-2 ) 7.6
Hz J 3-2 ) 9.7 Hz J 2-F ) 51.3 Hz, 1H), 3.81 (qd, J 5-6 ) 6.5 Hz
J 5-4 ) 1.1 Hz, 1H), 2.15 (s, 3H), 2.06 (s, 3H), 1.30 (s, 9H), 1.20
(d, J 5-6 ) 6.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 170.60,
170.15, 95.17 (d, J C-F ) 22.8 Hz), 87.90 (d, J C-F ) 183.9 Hz),
75.66, 71.76 (d, J ) 18.0 Hz), 71.00 (d, J ) 7.6 Hz), 68.89,
28.47, 20.67, 20.64, 16.19; 19F NMR (376 MHz, CDCl3) δ
-202.91 (dd, J 2-F ) 50.8 Hz, J 3-F ) 12.7 Hz); HRMS (MH+)
calcd for C14H23O6F 307.1557, found 307.1554.
C
39H41FO13Cs 869.1586, found 869.1611.
Com p ou n d 18-glu coâ. 3′,4′,6′-Tr i-O-b en zoyl-2′-d eoxy-
2′-flu or o-â-D-glu cop yr a n osyl-(1′-6)-1,2:3,4-d i-O-isop r op y-
1
lid en e-r-D-ga la ctop yr a n ose. H NMR (400 MHz, CDCl3) δ
8.01-7.88 (m, 6H), 7.56-7.32 (m, 9H), 5.84 (dt, J 3′-F ) 14.0
Hz, J 3′-2′ ) 9.2 Hz, J 3′-4′ ) 9.2 Hz, 1H), 5.58 (t, J 4′-3′ ) 9.2 Hz,
J 4′-5′ ) 9.2 Hz, 1H), 5.54 (d, J 1-2 ) 5.0 Hz, 1H), 4.98 (dd, J 1′-2′
) 7.6 Hz, J 1′-F ) 2.8 Hz, 1H), 4.62-4.57 (m, 2H), 4.58 (ddd,
J 2′-F ) 50.5 Hz, J 2′-3′ ) 9.2 Hz, J 2′-1′ ) 7.6 Hz, 1H), 4.45 (dd,
J 6b′-6a′ ) 12.1 Hz, J 6b′-5′ ) 5.5 Hz, 1H), 4.31 (dd, J 1-2 ) 5.0
Hz, J 2-3 ) 2.4 Hz, 1H), 4.22 (dd, J 4-3 ) 7.9 Hz, J 4-5 ) 1.5 Hz,
1H), 4.15-4.03 (m, 3H), 3.95-3.90 (m, 1H), 1.55 (s, 3H), 1.42
(s, 3H), 1.33 (s, 3H), 1.31 (s, 3H); 13C NMR (100.6 MHz, CDCl3)
δ 166.03, 165.54, 165.18, 133.46, 133.32, 133.06, 129.80,
129.68, 128.39, 128.33, 128.30, 109.36, 108.75, 100.46 (d, J 1′C-F
) 23.2 Hz), 96.22, 89.55 (d, J 2′C-F ) 191.7 Hz), 73.07 (d, J 3′C-F
) 20.3 Hz), 71.92, 71.17, 70.57, 7034, 69.27 (d, J 4′C-F ) 7.2
Hz), 68.80, 67.68, 63.06, 25.96, 25.89, 24.92, 24.34; 19F NMR
Com p ou n d 16. 7-O-(2-Deoxy-2-flu or o-3,4-O-d ip iva loyl-
r-L-fu cop yr a n osyl)-d a u n om ycin on e. 1H NMR (400 MHz,
CDCl3) δ 14.01 (s, 1H, 6-OH), 13.27 (s, 1H, 11-OH), 8.04 (d,
J 1-2 ) 8.1 Hz, 1H), 7.78 (t, J 1-2 ) 8.1 Hz, 1H), 7.78 (d, J 3-2
)
)
)
)
8.1 Hz, 1H), 5.74 (d, 1H), 5.44 (dd, J 7-8ax ) 3.7 Hz, J
7-8eq
5.9 Hz, 1H, 7-H), 5.38 (t, J 4′-3′ ) 2.9 Hz, 1H), 5.23 (dt, J 3′-4′
2.9 Hz, J 3′-2′ ) 10.3 Hz, 1H), 4.74 (ddd, J 2′-1′ ) 4.1 Hz, J 2′-3′
(376 MHz, CDCl3) δ -195.28 (dd, J F-2′H ) 50.5 Hz, J F-3′H
)
10.3 Hz, J 2′-F ) 49.9 Hz, 1H), 4.41 (m, 1H), 4.20 (s, 1H, 9-OH),
4.08 (s, 3H, 4-OMe), 3.27 (dd, J ) 1.5 Hz, J ax-eq ) 19.1 Hz,
1H, 10 ax-H), 3.01 (d, J ax-eq ) 19.1 Hz, 1H, 10 eq- H), 2.42 (s,
3H, 9-COMe), 2.33 (dd, J ) 3.7 Hz, J ax-eq ) 15.0 Hz, 1H, 8
eq-H), 2.21 (d, J ax-eq ) 15.0 Hz, 1H, 8 ax-H), 1.28 (s, 9H, tBu),
1.18 (d, J 5′-6′ ) 6.6, 3H), 1.12 (s, 9H, tBu); 13C NMR (125 MHz,
CDCl3) δ 211.2 (CO-13), 187.1 (5-C), 186.8 (12-C), 177.3 (CO-
Pv), 177.2 (CO-Pv), 161.0 (4), 156.3, 155.7 (11), 135.7 (2-C),
135.6 (12a-C), 134.7 (10a-C), 133.1 (6a-C), 121.0 (4a-C),
119.8, 118.4 (3-C), 111.63 (5a-C), 111.56 (11a-C), 98.4 (J 1′-F
) 9.5 Hz), 85.1 (J 2′-F ) 192.6 Hz), 76.5 (9-C), 71.2 (J 3′-F ) 7.6
Hz), 69.3 (7-C), 68.4, (J 4′-F ) 18.1 Hz), 66.0 (5′-C), 56.7 (4-
OMe), 35.5 (8), 33.8 (10), 29.7 (Pv), 27.3 (Pv), 26.9 (Pv), 24.9,
(14), 15.8 (6′-C); 19F NMR (376 MHz, CDCl3) δ -205.7 (dd, J
) 9.9, 49.7 Hz); HRMS (M + Cs+) calcd for C37H43FNO13Cs
847.1742, found 847.1773.
14.0 Hz); HRMS (M + Cs+) calcd for C39H41FO13Cs 869.1586,
found 869.1554.
Com p ou n d 18-m a n n or. 3′,4′,6′-Tr i-O-ben zoyl-2′-d eoxy-
2′-flu or o-r-D-m a n n op yr a n osyl-(1′-6)-1,2:3,4-d i-O-isop r o-
p ylid en e-r-D-ga la ctop yr a n ose. 1H NMR (400 MHz, CDCl3)
δ 8.06-7.92 (m, 6H), 7.56-7.39 (m, 9H), 5.96 (t, J 4′-3′ ) 10.1
Hz, J 4′-5′ ) 10.1 Hz, 1H), 5.70 (ddd, J 3′-F ) 28.5, J 3′-4′ ) 10.1
Hz, J 3′-2′ ) 2.6 Hz, 1H), 5.55 (d, J 1-2 ) 4.3 Hz, 1H), 5.19 (dd,
J 1′-F ) 7.0 Hz, J 1′-2′ ) 1.8 Hz, 1H), 5.03 (dt, J 2′-F ) 49.9, J 2′-3′
) 2.2 Hz, J 2′-1′ ) 2.2 Hz, 1H), 4.65-3.96 (m, 7H), 4.26 (dd,
J 4-3 ) 7.9 Hz, J 4-5 ) 1.9 Hz, 1H), 3.86 (dd, J 6b-6a ) 10.4 Hz,
J 6b-5 ) 5.9 Hz, 1H), 1.60 (s, 3H), 1.43 (s, 3H), 1.34 (s, 3H),
1.33 (s, 3H); 19F NMR (376 MHz, CDCl3) δ -201.14 (ddd, J F-2′H
) 49.6 Hz, J F-3′H ) 28.3 Hz, J F-1′H ) 6.2 Hz); HRMS (M +
Cs+) calcd for C39H41FO13Cs 869.1586, found 869.1611.
Com p ou n d 19. (3â,5â,14â,16â,17â)-3-[2-Deoxy-2-flu or o-
3,4-d i-O-p iva loyl-r-L-r h a m n osyl]-16-a cetoxy-14-h yd r oxy-
ca r d -20(22)-en olid e (XX) (3-[2-Deoxy-2-flu or o-3,4-d i-O-
p iva loyl-r-L-r h a m n op yr a n osyl]-olea n d r igen in ). Silica gel
chromatography (9:1 dichloromethane/ethyl acetate) yields
product (33.6 mg, 65%) as a fluffy white solid.1H NMR (400
MHz, CDCl3) δ 5.97 (s, 1H, 21-H), 5.49 (dt, J ) 9.4 Hz J ) 2.4
Hz, 1H, 16-H), 5.32 (dt, J 3′-4′ ) J 2′-3′ ) 9.2 Hz J F-3 ) 14.3 Hz,
1H), 4.95 (ABX, J AB ) 9.2 Hz J AX ) J BX ) 1.6 Hz, 2H, 21-H),
4.84 (dd, J 3′-4′ ) J 5′-4′ ) 9.2 Hz, 1H), 4.60 (dd, J 1′-2′ ) 7.8 Hz
J F-1′ ) 2.7 Hz, 1H), 4.28 (ddd, J 1′-2′ ) 7.8 Hz J 2′-3′ ) 9.2 Hz
J 2′-F ) 50.8 Hz, 1H), 4.06 (s, 1H, 14-OH), 3.59 (m, 1H), 3.20
(d, J ) 8.6 Hz, 1H, 17-H), 2.74 (dd, J ) 9.7 Hz J ) 15.7 Hz,
3H, 15a-H).
Com p ou n d 20. (tr a n s-P h en yl-cyclop r op yl)-m eth oxy-
eth en e. A suspension of triphenyl[(methoxy)-methyl]phos-
phonium chloride (2.78 g, 8.11 mmol) in 10 mL of anhydrous
THF at -78 °C was treated dropwise with a solution of n-BuLi
(4.7 mL, 1.6 M in hexane, 7.52 mmol). The reaction mixture
was stirred for 5 min at -78 °C, the cooling bath was removed,
and the mixture was stirred and allow to warm until it reached
0 °C. The mixture was recooled to -78 °C, and the aldehyde
21 (1.1 g, 7.53 mmol) in 10 mL of THF was added dropwise.
The reaction mixture was stirred 1 h at -78 °C and then 12 h
at room temperature before it was quenched by the addition
of phosphate buffer (pH ) 7.1). The mixture was extracted 3
times with EtOAc, and the combined organic phase was dried
over MgSO4 and concentrated in vacuo. Chromatography on
silica gel (AcOEt/hexane/Et3N, 4:95:1) afforded 20 (0.88 g, 5.06
mmol, 67% yield) as a mixture of E and Z olefin isomers in a
3/2 ratio. Some fractions of pure E isomer have been collected
that allowed the interpretation of the NMR spectra of the
mixture. P u r e E: 1H NMR (500 MHz, CDCl3) δ 7.25 (t, J )
7.7 Hz, 2Hm), 7.13 (dd, J ) 7.3 Hz J ) 9.2 Hz, 1Hp), 7.05 (d, J
Com p ou n d 17r. 2-Deoxy-2-flu or o-3,4,6-tr i-O-p iva loyl-
r-1-(cycloh exyl)-D-glu cop yr a n ose. The general procedure
was applied. Chromatographic conditions, hexane/AcOEt, 3:1.
1H NMR (400 MHz, CDCl3) δ 5.58 (td, J 3-2 ) 9.7 Hz J 3-F
)
11.9 Hz J 3-4 ) 9.7 Hz, 1H), 5.18 (d, J 1-2 ) 3.8 Hz, 1H), 5.02
(t, J 3-4 ) 9.7 Hz, J 5-4 ) 10.0 Hz, 1H), 4.44 (ddd, J 1-2 ) 3.8 Hz
J 3-2 ) 9.7 Hz J 2-F ) 49.9 Hz, 1H), 4.17-4.03 (m, 3H), 3.61
(m, 1H), 1.89 (m, 2H), 1.76 (m, 2H), 1.36 (m, 6H), 1.22 (s, 9H),
1.17 (s, 9H), 1.16 (s, 9H).
Com p ou n d 17â. 2-Deoxy-2-flu or o-3,4,6-tr i-O-p iva loyl-
â-1-(cycloh exyl)-D-glu cop yr a n ose. 1H NMR (600 MHz,
CDCl3) δ 5.35 (td, J 3-2 ) 9.2 Hz J 3-F ) 14.0 Hz J 3-4 ) 9.2 Hz,
1H), 5.01 (t, J 3-4 ) 9.2 Hz, J 5-4 ) 10.0 Hz, 1H), 4.68 (dd, J 1-2
) 7.9 Hz J 1--F ) 2.6 Hz, 1H), 4.25 (ddd, J 1-2 ) 7.9 Hz J 3-2
)
9.2 Hz J 2-F ) 50.8 Hz, 1H), 4.11 (AB part of ABX, J A-B ) 12.2
Hz J A-X ) 1.7 Hz J B-X ) 7.0 Hz, 2H), 3.73 (ddd, J 5-4 ) 10.0
Hz J A-X ) 1.7 Hz J B-X ) 7.0 Hz, 1H), 3.67 (m, 1H), 1.90 (m,
2H), 1.76 (m, 2H), 1.53-1.23 (m, 6H), 1.21 (s, 9H), 1.17 (s, 9H),
1.16 (s, 9H); 13C NMR (150 MHz, CDCl3) δ 178.03, 177.30,
176.65, 98.72 (d, J C-F ) 22.0 Hz), 89.87 (d, J C-F ) 189.0 Hz),
72.49 (d, J ) 19.8 Hz), 72.18, 67.85 (d, J ) 6.6 Hz), 62.26,
38.78, 33.40, 31.64, 27.07, 27.03, 26.98, 25.46, 23.91, 23.76;
19F NMR (376 MHz, CDCl3) δ -196.37 (dd, J 2-F ) 48.2 Hz,
J 3-F ) 12.7 Hz); HRMS (MH+) calcd for C27H45O8F 517.3177,
found 517.3161.
Com p ou n d 18-glu cor. 3′,4′,6′-Tr i-O-ben zoyl-2′-d eoxy-
2′-flu or o-r-D-glu cop yr a n osyl-(1′-6)-1,2:3,4-d i-O-isop r op y-
lid en e-r-D-ga la ctop yr a n ose. The general procedure was
applied. Chromatographic conditions, hexane/AcOEt, 4:1. The
title compound was isolated as an inseparable mixture of the
R-gluco glycoside 18-glu cor and the R-manno glycoside 18-
m a n n or in a ratio of 2:1. The â-gluco glycoside 18-glu coâ was
isolated to purity. 18-glu cor: 1H NMR (400 MHz, CDCl3) δ

Fluorination-Nucleophilic Addition Mediated by Selectfluor
J . Org. Chem., Vol. 64, No. 14, 1999 5277
) 8.1 Hz, 2Ho), 6.42 (d, J trans ) 12.4 Hz, 1H, 1), 4.62 (dd, J trans
) 12.4 Hz, J ) 7.7 Hz, 1H, 4), 3.50 (s, 3H), 1.78 (ddd, J ) 4.8
Hz J ) 4.4 Hz J ) 9.2 Hz, 1H, 4), 1.54 (m, 1H, 3), 1.11 (td, J
) 5.1 Hz J ) 5.1 Hz J B-X ) 5.8 Hz, 1H, 5), 0.99 (td, J ) 5.1
Hz J ) 5.1 Hz J ) 9.2 Hz, 1H, 5); 13C NMR (150 MHz, CDCl3)
δ 147.24, 142.81, 128.26, 125.48, 125.38, 105.40, 56.06 (OMe),
24.74 (4), 22.30 (3), 16.38 (5). Mixtu r e E/Z 3/2: 1H NMR (500
MHz, CDCl3) δ 7.28-7.00 (m, 5H), 6.42 (d, J trans ) 12.4 Hz,
Com p ou n d 26â. 3,4,6-Tr i-O-a cetyl-2-d eoxy-2-flu or o-â-
1-(4-m eth oxyph en yl)-D-galactose. 1H NMR (400 MHz, CDCl3)
δ 7.06-7.02 (m, 2H), 6.86-6.82 (m, 2H), 5.48-4.46 (m, 1H),
5.18 (ddd, J 3-F ) 13.3 Hz, J 3-2 ) 9.8 Hz, J 3-4 ) 3.6 Hz, 1H),
5.01 (dd, J 1-2 ) 7.7 Hz, J 1-F ) 3.9 Hz, 1H), 4.75 (ddd, J 2-F
51.2 Hz, J 2-3 ) 9.8 Hz, J 2-1 ) 7.7 Hz, 1H), 4.23 (dd, J 6a-6b
)
)
11.3 Hz, J 6a-5 ) 6.7 Hz, 1H), 4.14 (dd, J 6b-6a ) 11.3 Hz, J 6b-5
) 6.7 Hz, 1H), 4.02 (td, J 5-6 ) 6.7 Hz, J 5-4 ) 1.0 Hz, 1H), 3.79
(s, 3H), 2.17 (s, 3H), 2.09 (s, 3H), 2.06 (s, 3H); 13C NMR (100.6
MHz, CDCl3) δ 170.33, 170.06, 169.99, 155.89, 150.71, 119.03,
114.52, 100.39 (d, J 1C-F ) 23.7 Hz), 87.50 (d, J 2C-F ) 187.9
Hz), 71.01 (d, J 3C-F ) 18.9 Hz), 70.86, 67.46 (d, J 4C-F ) 8.3
Hz), 61.11, 55.62, 20.65, 20.61, 20.57; 19F NMR (376 MHz,
CDCl3) δ -203.00 (dd, J F-2H ) 51.2 Hz, J F-3H ) 13.3 Hz);
HRMS (M + Na+) calcd for C19H23FO9Na 437.1224, found
437.1209.
0.6H, 1E), 5.93 (d, J cis ) 6.2 Hz, 0.4H, 1Z), 4.62 (dd, J trans
)
12.4 Hz, J ) 7.7 Hz, 0.6H, 2E), 4.03 (dd, J cis ) 6.2 Hz J ) 9.2
Hz, 0.4H, 2Z), 3.58 (s, 1.2H, OMeZ), 3.50 (s, 1.8H, OMeE), 1.98
(m, 0.4H, 3Z), 1.84 (ddd, J ) 4.8 Hz J ) 4.4 Hz J ) 9.2 Hz,
0.4H, 4Z), 1.78 (ddd, J ) 4.8 Hz J ) 4.4 Hz J ) 9.2 Hz, 0.6H,
4E), 1.54 (m, 0.6H, 3E), 1.18 (td, J ) 5.1 Hz J ) 5.1 Hz J ) 9.2
Hz, 0.4H, 5Z), 1.11 (td, J ) 5.1 Hz J ) 5.1 Hz J ) 9.2 Hz,
0.6H, 5E), 0.99 (m, 1H, 5); 13C NMR (150 MHz, CDCl3) 147.24
(1E), 146.22 (1Z), 142.81, 128.26, 128.18, 125.55, 125.48,
125.38, 109.31 (2Z), 105.40 (2E), 59.64 (OMeZ), 56.06 (OMeE),
24.97 (4Z), 24.74 (4E), 22.30 (3E), 19.85 (3Z), 17.36 (5Z), 16.38
(5E).
Com p ou n d 27r. L-Th r eon in e, N-[(p h en ylm et h oxy)-
ca r bon yl]-O-(3,4-d i-O-a cetyl-2-d eoxy-2-flu or o-r-L-fu cop y-
r a n osyl)-, P h en ylm eth yl Ester . The general procedure was
1
applied. Chromatographic conditions, hexane/AcOEt, 3:1. H
Com pou n d 22. 2-(tr a n s-2-P h en yl-cyclopr opyl)-2-flu or o-
eth a n a l d im eth yla ceta l. The general procedure was applied.
Chromatographic conditions, hexane/AcOEt, 9:1; 2 diastere-
oisomers, ratio 6/4. 1H NMR (400 MHz, CDCl3) δ 7.40-7.00
(m, 5H), 4.44 (dd, J ) 5.1 Hz J ) 2.7 Hz, 0.4H), 4.42 (dd, J )
5.7 Hz, J ) 2.7 Hz, 0.6H), 4.11 (ddd, J ) 5.7 Hz J ) 7.3 Hz J
) 47.8 Hz, 0.6H), 4.09 (ddd, J ) 5.2 Hz J ) 7.6 Hz J ) 47.5
Hz, 0.4H), 3.48 (d, J ) 2.4 Hz, 1.2H), 3.46 (d, J ) 4.0 Hz, 1.8H),
2.04 (m, 1H), 1.44 (m, 1H), 1.14 (td, J ) 5.1 Hz J ) 5.1 Hz J
) 9.2 Hz, 0.4H), 1.11 (m, 1.6H); 13C NMR (100 MHz, CDCl3) δ
141.73, 141.61, 128.40, 128.35, 126.22, 125.89, 125.82, 104.56
(d, J ) 26 Hz), 104.45 (d, J ) 27 Hz), 94.26 (d, J ) 176 Hz),
93.80 (d, J ) 175 Hz), 55.36 (d, J ) 117 Hz), 55.07 (d, J ) 126
Hz), 22.26 (d, J ) 23 Hz, 4), 22.02 (d, J ) 23 Hz, 4), 20.36 (d,
J ) 10 Hz), 19.92 (d, J ) 2.9 Hz), 12.49 (d, J ) 8.7 Hz), 11.81
(d, J ) 2.9 Hz); 19F NMR (376 MHz, CDCl3) δ -187.41 (dd),
-189.22 (dd).
Com pou n d 25r. 3′,4′,6′-Tr i-O-ben zoyl-2′-deoxy-2′-flu or o-
r-D-ga la ctop yr a n osyl-(1′-2)-1,6-a n h yd r o-3,4-O-isop r op y-
lid en e-â-D-ga la ctose. The general procedure was applied.
Chromatographic conditions, hexane/AcOEt, 3:1. The title
compound was isolated as an inseparable mixture of the
R-gluco glycoside 25-glu cor and the R-manno glycoside 25-
m a n n or in a ratio of 4:1. 1H NMR (400 MHz, CDCl3) δ 8.15-
7.98 (m, 4H), 7.88-7.84 (m, 2H), 7.65-7.30 (m, 9H), 6.03 (t,
J 4′-F ) 2.4 Hz, J 4′-3′ ) 2.4 Hz, 1H), 5.85 (td, J 3′-F ) 10.3 Hz,
J 3′-2′ ) 10.3 Hz, J 3′-4′ ) 3.4 Hz, 1H), 5.49 (s, 1H), 5.46 (d, J 1′-2′
) 3.8 Hz, 1H), 5.12 (ddd, J 2′-F ) 49.9 Hz, J 2′-3′ ) 10.3 Hz,
J 2′-1′ ) 3.8 Hz, 1H), 4.66 (t, J ) 6.8 Hz, 1H), 4.57-4.49 (m,
3H), 4.36 (dd, J 6b′-6a′ ) 11.4 Hz, J 6b′-5′ ) 5.5 Hz, 1H), 4.35 (d,
J ) 8.0 Hz, 1H), 4.11 (d, J ) 7.6 Hz, 1H), 3.98 (s, 1H), 3.60
(dd, J ) 7.4, 5.2 Hz, 1H), 1.47 (s, 3H), 1.28 (s, 3H); 13C NMR
(100.6 MHz, CDCl3) δ 166.02, 165.48, 165.27, 133.67, 133.29,
133.24, 129.81, 129.74, 128.63, 128.39, 128.27, 108.72, 99.01,
96.57 (d, J 1′C-F ) 20.9 Hz), 85.29 (d, J 2′C-F ) 192.1 Hz), 77.17,
74.56, 71.97, 69.38 (d, J 4′C-F ) 7.4 Hz), 69.13, 68.66 (d, J 3′C-F
) 18.6 Hz), 67.90, 63.08, 62.35, 25.69, 24.15; 19F NMR (376
MHz, CDCl3) δ -203.66 (dd, J F-2′H ) 49.9 Hz, J F-3′H ) 10.1
Hz); HRMS (M + Cs+) calcd for C36H35FO12Cs 811.1167, found
811.1196.
NMR (400 MHz, CDCl3) δ 7.40-7.33 (m, 10H), 5.52 (d, J )
9.7 Hz, 1H), 5.23-5.16 (m, 3H), 5.14 (s, 2H,), 5.11 (td, J 4-F
)
3.5 Hz, J 4-3 ) 3.5 Hz, J 4-5 ) 1.1 Hz, 1H), 5.08 (d, J 1-2 ) 4.0
Hz, 1H), 4.69 (ddd, J 2-F ) 50.1 Hz, J 2-3 ) 10.3 Hz, J 2-1 ) 4.0
Hz, 1H), 4.52 (dd, J ) 9.7, 2.2 Hz, 1H), 4.41 (qd, J ) 6.3, 2.2
Hz, 1H), 3.79 (qd, J 5-6 ) 6.5 Hz, J 5-4 ) 1.1 Hz, 1H), 2.13 (s,
3H), 2.03 (s, 3H), 1.26 (d, J ) 6.3 Hz, 3H), 0.92 (d, J 6-5 ) 6.5
Hz, 3H); 13C NMR (100.6 MHz, CDCl3) δ 170.28, 170.23,
169.84, 156.66, 136.02, 134.99, 128.77, 128.62, 128.53, 128.51,
128.20, 128.13, 94.06 (d, J 1C-F ) 20.4 Hz), 84.81 (d, J 2C-F
190.7 Hz), 73.52, 71.37 (d, J 4C-F ) 7.5 Hz), 68.33 (d, J 3C-F
)
)
18.6 Hz), 67.61, 67.28, 65.14, 58.73, 20.67, 20.53, 15.70, 15.51;
19F NMR (376 MHz, CDCl3) δ -205.10 (dd, J F-2H ) 50.1 Hz,
J F-3H ) 9.7 Hz); HRMS (M + Cs+) calcd for C29H34FNO10Cs
708.1221, found 708.1204.
Com p ou n d 27â. L-Th r eon in e, N-[(p h en ylm eth oxy)ca r -
bon yl]-O-(3,4-d i-O-a cetyl-2-d eoxy-2-flu or o-â-L-fu cop yr a -
n osyl)-, P h en ylm eth yl Ester . 1H NMR (400 MHz, CDCl3) δ
7.39-7.30 (m, 10H), 5.54 (d, J ) 9.7 Hz, 1H), 5.22-5.09 (m,
5H), 4.92 (ddd, J 3-F ) 13.4 Hz, J 3-2 ) 9.7 Hz, J 3-4 ) 3.6 Hz,
1H), 4.46-4.24 (m, 4H), 3.56 (qd, J 5-6 ) 6.4 Hz, J 5-4 ) 0.8
Hz, 1H), 2.13 (s, 3H), 2.04 (s, 3H), 1.35 (d, J ) 6.4 Hz, 3H),
1.15 (d, J 6-5 ) 6.4 Hz, 3H); 13C NMR (100.6 MHz, CDCl3) δ
170.45, 169.98, 169.83, 156.70, 136.15, 135.16, 128.79, 128.65,
128.58, 128.50, 128.13, 127.97, 101.39 (d, J 1C-F ) 22.5 Hz),
87.64 (d, J 2C-F ) 186.9 Hz), 77.95, 71.21 (d, J 3C-F ) 18.3 Hz),
70.56 (d, J 4C-F ) 8.4 Hz), 69.09, 67.50, 67.12, 58.69, 20.61,
20.58, 18.81, 15.89; 19F NMR (376 MHz, CDCl3) δ -203.29
(dd, J F-2H ) 53.6 Hz, J F-3H ) 13.3 Hz); HRMS (M + Cs+) calcd
for C29H34FNO10Cs 708.1221, found 708.1204.
Com p ou n d 28. N-Ben zyl-2-d eoxy-2-flu or o-3,4-d i-O-
a cetyl-r-L-fu cop yr a n osyla m in e. The general procedure was
1
applied. Chromatographic conditions, hexane/AcOEt, 1:3. H
NMR (600 MHz, CDCl3) δ 7.35 (m, 5H, Ph), 5.29 (m, 1H), 5.09
(m, 1H), 4.89 (dt, J 2-1 ) 9.0 Hz, J 2-F ) 51.5 Hz, 1H), 4.18 (dd,
J 1-2 ) 9.0 Hz, J 1-F ) 2.3 Hz, 1H), 4.13 (d, J ) 13.5 Hz, 1H),
3.96 (d, J ) 13.5 Hz, 1H), 2.16 (s, 3H), 2.05 (s, 3H), 1.20 (d, J
) 6.5 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ -199.8 (dd, J )
15.3, 50.9 Hz); HRMS (M + H+) calcd for C17H23FNO5
340.1560, found 340.1570.
Com p ou n d 26. 3,4,6-Tr i-O-a cetyl-2-d eoxy-2-flu or o-1-r-
Com p ou n d 29â. 2-Deoxy-2-flu or o-3,4-d i-O-ben zoyl-â-1-
(d iben zylp h osp h or yl)-L-fu cop yr a n ose. The general proce-
dure was applied. Chromatographic conditions, hexane/AcOEt,
4:1. 1H NMR (600 MHz, CDCl3) δ 8.05 (d, J ) 7.5 Hz, 2H),
7.87 (d, J ) 7.5 Hz, 2H), 7.63 (t, J ) 7.4 Hz, 1H), 7.55-7.25
(m, 15H), 5.69 (broad t, J 3-4 ) J F-4 ) 2.6 Hz, 1H), 5.52 (m,
(4-m eth oxyp h en yl)-D-ga la ctose. The general procedure was
1
applied. Chromatographic conditions, hexane/AcOEt, 3:1. H
NMR (400 MHz, CDCl3) δ 7.07-7.02 (m, 2H), 6.87-6.82 (m,
2H), 5.64-5.58 (m, 2H) 5.56 (td, J ) 3.4 Hz, J ) 3.4 Hz, J )
1.0 Hz, 1H), 4.90 (ddd, J ) 49.6 Hz, J ) 10.2 Hz, J ) 3.8 Hz,
1H), 4.43 (td, J ) 6.7 Hz, J ) 1.0 Hz, 1H), 4.11 (d, J ) 6.7 Hz,
2H), 3.78 (s, 3H), 2.16 (s, 3H), 2.08 (s, 3H), 1.99 (s, 3H); 13C
NMR (100.6 MHz, CDCl3) δ 170.31, 169.99, 155.56, 150.30,
2H), 5.14 (m, 4H), 4.90 (ddd, J ) 7.9 Hz J ) 10.1 Hz J 2-F
)
51.7 Hz, 1H), 4.12 (q, J 5-6 ) 7.0 Hz, 1H), 1.29 (d, J 5-6 ) 7.0
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 165.60, 165.35, 133.60-
120.05, 96.45 (dd, J C-P ) 4.4 Hz J C-F ) 22.0 Hz), 88.30 (dd,
J C-P ) 8.8 Hz J C-F ) 189.0 Hz), 71.57 (d, J ) 19.8 Hz), 71.12
(d, J ) 8.8 Hz), 70.72, 69.64 (d, J C-P ) 4.4 Hz), 69.58 (d, J C-P
) 4.4 Hz), 15.96; 19F NMR (376 MHz, CDCl3) δ -203.55 (dd,
J 2-F ) 53.4 Hz, J 3-F ) 12.7 Hz); 31P NMR (161 MHz, CDCl3)
118.33, 114.60, 96.20 (d, J 1C-F ) 21.0 Hz), 84.89 (d, J 2C-F
)
192.6 Hz), 68.47 (d, J 4C-F ) 7.5 Hz), 68.15 (d, J 3C-F ) 18.9
Hz), 67.12, 61.35, 55.61, 20.65, 20.59, 20.55; 19F NMR (376
MHz, CDCl3) δ -204.39 (dd, J F-2H ) 49.6 Hz, J F-3H ) 9.7 Hz);
HRMS (M + Na+) calcd for C19H23FO9Na 437.1224, found
437.1209.

5278 J . Org. Chem., Vol. 64, No. 14, 1999
Vincent et al.
δ -2.14 (s); HRMS (MH+) calcd for C34H32O9PF 635.1846,
) 18.7 Hz), 65.96 (d, J C-F ) 6.6 Hz), 60.59, 38.83, 38.73, 27.02,
26.98; 31P NMR (161 MHz, CDCl3) δ -12.71 (s); 19F NMR (376
MHz, CDCl3) δ -197.83 (dd, J 2-F ) 48.2 Hz, J 3-F ) 12.7 Hz);
HRMS (M + Cs+) calcd for C33H44O11PF 799.1660 found,
799.1690.
found 635.1824.
1
Com p ou n d 29r. H NMR (600 MHz, CDCl3) δ 8.01 (dd, J
) 8.3 Hz J ) 1.3 Hz, 2H), 7.87 (dd, J ) 8.3 Hz J ) 1.3 Hz,
2H), 7.61 (tt, J ) 7.4 Hz J ) 1.3 Hz, 1H), 7.55-7.25 (m, 15H),
6.13 (dd, J 1-P ) 6.1 Hz J 1-2 ) 3.5 Hz, 1H), 5.75 (td, J 3-2
10.5 Hz J 3-F ) 10.5 Hz J 3-4 ) 3.5 Hz, 1H), 5.68 (td, J 3-4
)
)
Com p ou n d 32-glu coâ. 2-Deoxy-2-flu or o-3,4,6-tr i-O-p iv-
aloyl-â-1-(diph en ylph osph or yl)-D-glu copyr an ose. 1H NMR
(400 MHz, CDCl3) δ 7.41-7.19 (m, 10H), 5.52 (td, J ) 7.6 Hz
J ) 7.6 Hz J ) 3.0 Hz, 1H), 5.37 (td, J ) 9.0 Hz J ) 13.8 Hz
J ) 10.0 Hz, 1H), 5.11 (t, J ) 10.0 Hz, J ) 10.0 Hz, 1H), 4.73
(ddd, J ) 7.6 Hz J ) 9.0 Hz J ) 50.8 Hz, 1H), 4.08 (d, J ) 3.5
Hz, 2H), 4.85 (td, J ) 10.0 Hz J ) 3.5 Hz, 3H), 1.18 (s, 9H),
1.16 (s, 9H), 1.13 (s, 9H); 13C NMR (150 MHz, CDCl3) δ 177.86,
176.99, 176.39, 150.25 (d, J C-P ) 7.7 Hz, phenyl), 150.05 (d,
J C-P ) 7.7 Hz, phenyl), 130-120, 96.56 (dd, J C-P ) 4.4 Hz
J C-F ) 19.8 Hz), 89.48 (dd, J C-P ) 9.9 Hz J C-F ) 192.3 Hz),
73.16, 73.71 (d, J ) 19.8 Hz), 66.56 (d, J C-F ) 7.2 Hz), 61.09,
38.81, 38.78, 38.76, 27.02, 26.97; 19F NMR (376 MHz, CDCl3)
δ -197.33 (dd, J 2-F ) 50.8 Hz, J 3-F ) 12.7 Hz); 31P NMR (161
MHz, CDCl3) δ -13.23 (s); HRMS (M + Cs+) calcd for
J F-4 ) 3.5 Hz, J 5-4 ) 0.9 Hz, 1H), 5.15 (m, 4.5H overlapping
half of the 2-H signal), 5.06 (td, J 1-2 ) 3.1 Hz J 3-2 ) 10.5 Hz
J 2-P ) 3.1 Hz, 0.5H), 4.31 (q, J 5-6 ) 6.5 Hz, 1H), 1.11 (d, J 5-6
) 6.5 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 165.59, 165.43,
133.6-127.9, 94.82 (dd, J C-P ) 4.4 Hz J C-F ) 19.8 Hz), 85.11
(dd, J C-P ) 8.8 Hz J C-F ) 191.2 Hz), 71.79 (d, J ) 6.6 Hz),
69.71 (d, J C-P ) 4.4 Hz), 69.57 (d, J C-P ) 4.4 Hz), 68.69 (d, J
) 17.6 Hz), 67.25, 15.68; 19F NMR (376 MHz, CDCl3) δ -203.55
(dd, J 2-F ) 48.3 Hz, J 3-F ) 10.2 Hz); 31P NMR (161 MHz,
CDCl3) δ -1.81 (s); HRMS (MH+) calcd for C34H32O9PF
635.1846, found 635.1824.
Com p ou n d 30. 2-Deoxy-2-flu or o-3,4-d i-O-ben zoyl-r-1-
(d ip h en ylp h osp h or yl)-L-fu cop yr a n ose. The general pro-
cedure was applied. Chromatographic conditions, hexane/
AcOEt, 4:1. 1H NMR (600 MHz, CDCl3) δ 8.10-7.10 (m, 20H),
6.29 (dd, J ) 6.1 Hz J ) 3.5 Hz, 1H), 5.77 (td, J ) 10.6 Hz J
) 10.6 Hz J ) 3.5 Hz, 1H), 5.71 (dd, J ) 3.5 Hz, J ) 2.6 Hz,
1H), 5.12 (dddd, J ) 3.5 Hz J ) 10.6 Hz J ) 3.5 Hz J ) 49.1
Hz, 1H), 4.32 (q, J ) 10.2 Hz, 1H), 1.08 (d, J ) 10.2 Hz, 3H);
13C NMR (150 MHz, CDCl3) δ 165.54, 165.41, 150.36 (d, J )
7.7 Hz), 150.26 (d, J ) 7.7 Hz, CAr), 133.60-120.05, 95.89 (dd,
J C-P ) 5.5 Hz J C-F ) 22.0 Hz), 84.90 (dd, J C-P ) 7.7 Hz J C-F
) 192.3 Hz), 71.54 (d, J ) 6.6 Hz), 68.64 (d, J ) 17.6 Hz),
67.63, 15.58; 19F NMR (376 MHz, CDCl3) δ -203.53 (dd, J 2-F
) 49.2 Hz, J 3-F ) 14.1 Hz); 31P NMR (161 MHz, CDCl3) δ
-12.54 (s); HRMS (M + Cs+) calcd for C32H28O9PF 739.0509,
found 739.0488.
C
33H44O11PF 799.1660, found 799.1692.
Com p ou n d 33r. 2-Deoxy-2-flu or o-3,4,6-tr i-O-p iva loyl-
r-1-(d ip h en ylp h osp h or yl)-D-ga la ctop yr a n ose. The general
procedure was applied. Chromatographic conditions, hexane/
AcOEt, 4:1. 1H NMR (600 MHz, CDCl3) δ 7.40-7.17 (m, 10H),
6.20 (dd, J 1-P ) 6.5 Hz J 1-2 ) 3.5 Hz, 1H), 5.50 (td, J 3-4 ) 3.5
Hz, J F-4 ) 3.5 Hz, J 5-4 ) 1.3 Hz, 1H), 5.45 (td, J 3-2 ) 10.2 Hz
J 3-F ) 10.2 Hz J 3-4 ) 3.5 Hz, 1H), 4.82 (ddt, J 1-2 ) 3.5 Hz
J 3-2 ) 10.2 Hz J 2-F ) 49.4 Hz J 2-P ) 3.5 Hz, 1H), 4.25 (dd,
J 5-6A ) 8.4 Hz J 5-6B ) 6.2 Hz, 1H), 3.84 (AB part of ABX, J A-B
) 11.1 Hz J A-X ) 8.4 Hz J B-X ) 6.2 Hz, 2H), 1.22 (s, 9H), 1.19
(s, 9H), 1.12 (s, 9H); 13C NMR (150 MHz, CDCl3) δ 177.54,
177.12, 176.40, 130-120, 94.45 (dd, J C-P ) 5.5 Hz J C-F ) 22.0
Hz), 86.90 (dd, J C-P ) 7.8 Hz J C-F ) 192.3 Hz), 68.93, 67.46
(d, J ) 18.7 Hz), 67.20 (d, J C-F ) 7.7 Hz), 60.11, 39.02, 38.84,
38.61, 27.10, 26.98; 19F NMR (376 MHz, CDCl3) δ -204.09 (dd,
J 2-F ) 48.3 Hz, J 3-F ) 7.6 Hz); 31P NMR (161 MHz, CDCl3) δ
-7.57 (s); HRMS (M + Cs+) calcd for C33H44O11PF 799.1660,
found: 799.1688.
Com p ou n d 31. 2-Deoxy-2-flu or o-3,4-d i-O-p iva loyl-r-1-
(d ip h en ylp h osp h or yl)-L-fu cop yr a n ose. The general pro-
cedure was applied. Chromatographic conditions, hexane/
AcOEt, 4:1. 1H NMR (600 MHz, CDCl3) δ 7.40-7.15 (m, 20H),
6.16 (dd, J 1-P ) 5.9 Hz J 1-2 ) 3.5 Hz, 1H), 5.41 (td, J 3-2
)
10.5 Hz J 3-F ) 10.5 Hz J 3-4 ) 3.5 Hz, 1H), 5.30 (t, J 3-4 ) 3.5
Hz, J F-4 ) 3.5 Hz, 1H), 4.82 (dddd, J 1-2 ) 3.5 Hz J 3-2 ) 10.5
Hz J 2-P ) 3.5 Hz J 2-F ) 49.4 Hz, 1H), 4.14 (q, J 5-6 ) 6.5 Hz,
Com p ou n d 33â. 2-Deoxy-2-flu or o-3,4,6-tr i-O-p iva loyl-
â-1-(d ip h en ylp h osp h or yl)-D-ga la ctop yr a n ose. 1H NMR
(600 MHz, CDCl3) δ 7.40-7.17 (m, 10H), 5.50 (td, J 1-P ) 7.6
Hz J 1-F ) 3.8 Hz J 1-2 ) 7.6 Hz, 1H), 5.50 (t, J 3-4 ) 2.7 Hz,
J F-4 ) 2.7 Hz, 1H), 5.45 (ddd, J 3-2 ) 10.2 Hz J 3-F ) 13.2 Hz
J 3-4 ) 2.7 Hz, 1H), 4.60 (ddd, J 1-2 ) 7.6 Hz J 3-2 ) 10.2 Hz
J 2-F ) 51.6 Hz, 1H), 4.10 (dd, J 5-6A ) 6.2 Hz J 5-6B ) 7.6 Hz,
1H), 3.96 (AB part of ABX, J A-B ) 11.1 Hz J A-X ) 6.2 Hz J B-X
) 7.6 Hz, 2H), 1.25 (s, 9H), 1.18 (s, 9H), 1.15 (s, 9H); 13C NMR
(150 MHz, CDCl3) δ 177.74, 177.03, 176.46, 130-120, 96.98
(dd, J C-P ) 4.4 Hz J C-F ) 24.2 Hz), 87.98 (dd, J C-P ) 8.8 Hz
J C-F ) 189.0 Hz), 72.06, 70.60 (d, J ) 17.6 Hz), 66.78 (d, J C-F
) 8.8 Hz), 60.34, 39.04, 38.84, 38.68, 27.10, 27.01, 26.97; 19F
NMR (376 MHz, CDCl3) δ -204.24 (dd, J 2-F ) 50.8 Hz, J 3-F
) 10.2 Hz); 31P NMR (161 MHz, CDCl3) δ -13.17 (s).
1H), 1.25 (s, 9H), 1.18 (s, 9H), 0.95 (d, J 5-6 ) 6.5 Hz, 3H); 13
C
NMR (150 MHz, CDCl3) δ 177.24, 177.09, 129.9-120.0, 95.80
(dd, J C-P ) 5.8 Hz J C-F ) 21.7 Hz), 84.75 (dd, J C-P ) 7.2 Hz
J C-F ) 192.1 Hz), 70.51 (d, J ) 7.2 Hz), 67.97 (d, J ) 18.8
Hz), 67.67, 39.07, 38.81, 27.18, 26.97, 15.37; 19F NMR (376
MHz, CDCl3) δ -204.67 (dd, J 2-F ) 48.2 Hz, J 3-F ) 7.6 Hz);
31P NMR (161 MHz, CDCl3) δ -7.66 (s); HRMS (M + Cs+) calcd
for C28H36O9PF 699.1135, found 699.1155.
Com p ou n d 32-m a n n or. 2-Deoxy-2-flu or o-3,4,6-tr i-O-
pivaloyl-r-1-(diph en ylph osph or yl)-D-m an n opyr an ose. The
general procedure was applied. Chromatographic conditions,
hexane/AcOEt, 4:1. 1H NMR (400 MHz, CDCl3) δ 7.41-7.24
(m, 10H), 6.02 (ddd, J 1-P ) 5.4 Hz J 1-F ) 5.4 Hz J 1-2 ) 2.2
Hz, 1H), 5.53 (t, J 3-4 ) 10.0 Hz, J 5-4 ) 10.0 Hz, 1H), 5.25 (ddd,
J 3-2 ) 2.4 Hz J 3-F ) 27.6 Hz J 3-4 ) 10.0 Hz, 1H), 4.73 (ddd,
J 1-2 ) 2.2 Hz J 3-2 ) 2.4 Hz J 2-F ) 48.9 Hz, 1H), 4.02-3.96
(m, 3H, 5), 1.20 (s, 9H), 1.19 (s, 9H), 1.16 (s, 9H); 13C NMR
(150 MHz, CDCl3) δ 177.99, 177.46, 177.12, 130-120, 95.58
(dd, J C-P ) 5.5 Hz J C-F ) 31.9 Hz), 71.09, 68.86 (d, J ) 16.5
Hz), 63.70, 60.70, 38.90, 27.02, 27.00; 19F NMR (376 MHz,
Com p ou n d 34. 2-Deoxy-2-flu or o-3,4-d i-O-ben zoyl-r-1-
(ben zyl-(t-bu tyla cetyl-p h osp h on yl))-L-fu cop yr a n ose. The
general procedure was applied. Chromatographic conditions,
hexane/AcOEt, 3:1, 2 diastereoisomers. 1H NMR (600 MHz,
CDCl3) δ 8.10-7.10 (m, 15H), 6.29 (dd, J 1-P ) 6.1 Hz J 1-2
)
3.5 Hz, 1H), 5.77 (td, J 3-2 ) 10.6 Hz J 3-F ) 10.6 Hz J 3-4 ) 3.5
Hz, 1H), 5.71 (dd, J 3-4 ) 3.5 Hz, J F-4 ) 2.6 Hz, 1H), 5.12 (dddd,
J 1-2 ) 3.5 Hz J 3-2 ) 10.6 Hz J 2-P ) 3.5 Hz J 2-F ) 49.1 Hz,
1H), 4.32 (q, J 5-6 ) 10.2 Hz, 1H), 1.08 (d, J 5-6 ) 10.2 Hz, 3H);
13C NMR (150 MHz, D2O) δ 165.54, 165.41, 150.36 (d, J ) 7.7
CDCl3) δ -200.78 (ddd, J 2-F ) 48.3 Hz, J 3-F ) 27.9 Hz J 1-F
)
5.1 Hz); 31P NMR (161 MHz, CDCl3) δ -6.89 (s); HRMS (M +
Cs+) calcd for C33H44O11PF 799.1660 found, 799.1690.
Hz), 150.26 (d, J ) 7.7 Hz), 133.60-120.05, 95.89 (dd, J C-P
)
Com p ou n d 32-glu cor. 2-Deoxy-2-flu or o-3,4,6-tr i-O-p iv-
aloyl-r-1-(diph en ylph osph or yl)-D-glu copyr an ose. 1H NMR
(400 MHz, CDCl3) δ 7.41-7.19 (m, 10H), 6.14 (dd, J 1-F ) 6.5
Hz J 1-2 ) 3.5 Hz, 1H), 5.59 (td, J 3-2 ) 9.7 Hz J 3-F ) 11.4 Hz
J 3-4 ) 10.0 Hz, 1H), 5.14 (t, J 3-4 ) 10.0 Hz, J 5-4 ) 10.0 Hz,
1H), 4.73 (ddt, J 1-2 ) 3.5 Hz J 3-2 ) 9.7 Hz J 2-F ) 48.6 Hz
J 2-P ) 3.5 Hz, 1H), 3.91-3.85 (m, 3H), 1.19 (s, 9H), 1.17 (s,
9H), 1.14 (s, 9H); 13C NMR (150 MHz, CDCl3) δ 177.86, 177.09,
176.20, 130-120, 94.79 (dd, J C-P ) 5.5 Hz J C-F ) 22.0 Hz),
86.90 (dd, J C-P ) 7.7 Hz J C-F ) 150.6 Hz), 69.97, 69.46 (d, J
5.5 Hz J C-F ) 22.0 Hz), 84.90 (dd, J C-P ) 7.7 Hz J C-F ) 192.3
Hz), 71.54 (d, J ) 6.6 Hz), 68.64 (d, J ) 17.6 Hz), 67.63, 15.58;
19F NMR (376 MHz, CDCl3) δ -203.32 (s); -203.49 (s); 31P
NMR (161 MHz, CDCl3) δ 22.42 (s), 22.20 (s); HRMS (M +
Cs+) calcd for C33H36O10PF 775.1084, found 775.1104.
Gen er a l P r oced u r e for th e Oxid a tion of Th ioglyco-
sid es. To a stirred solution of thioglycoside (0.2 mmol) in CH3-
CN-H2O (2 mL, 20:1 or 10:1; with or without NaHCO3) was
added a solution of F-TEDA‚2BF4 (0.24 mmol) in CH3CN-H2O.
After a stirring time of 20 min, the mixture was concentrated

Fluorination-Nucleophilic Addition Mediated by Selectfluor
J . Org. Chem., Vol. 64, No. 14, 1999 5279
and redissolved in a mixture of CH2Cl2 and 10% aqueous
NaHCO3 (1:1, 50 mL). The organic phase was washed with
brine, dried with Na2SO4, filtered, and concentrated. The crude
products were checked by 1H NMR and HRMS. All starting
thioglycosides are prepared by the methods described in the
previous paper.60
Com p ou n d 35. p-Meth ylp h en yl 2,3,6-Tr i-O-a cetyl-4-O-
(2,3,4,6-tetr a -O-a cetyl-â-D-ga la ctop yr a n osyl)-1-su lfin yl-â-
D-glu cop yr a n osid e. 1H NMR (400 MHz, CDCl3), for one
diastereomer, δ 5.08 (dd, 1H, J ) 7.8 and 10.4 Hz), 4.95 (dd,
1H, J ) 3.0 and 10.4 Hz), 4.39 (d, 1H, J ) 9.5 Hz); for the
other, 5.074 (dd, 1H, J ) 7.8 and 10.4 Hz), 4.94 (dd, 1H, J )
3.0 and 10.4 Hz), 4.14 (d, 1H, J ) 9.5 Hz); the ratio ) 1:1,
HRMS for C33H42O18SCs (M + Cs+) calcd 891.1146, found
891.1166.
Com p ou n d 40. p-Meth ylp h en yl 4,6-O-Ben zylid in e-2-
d eoxy-2-p h th a lim id o-1-su lfin yl-â-D-glu cop yr a n osid e. 1H
NMR (500 MHz, CDCl3), for one diastereomer, δ 5.56 (s, 1H),
5.40 (d, 1H, J ) 10.0 Hz), 4.78 (t, 1H, J ) 10 Hz), 2.04 (s, 3H);
for the other, 5.55 (s, 1H), 5.23 (d, 1H, J ) 10.0 Hz), 4.64 (t,
1H, J ) 10 Hz), 2.67 (s, 3H); the ratio ) 3:1, HRMS for C28H25
-
NO7SCs (M + Cs+) calcd 652.0406, found 652.0426.
Com p ou n d 41. p -Met h ylp h en yl 2-Azid o-4,6-O-b en -
zylid en e-3-O-ch lor oa cetyl-2-d exoy-1-su lfin yl-â-D-ga la cto-
p yr a n osid e. 1H NMR (500 MHz, CDCl3), for one diastereomer,
δ 5.45 (s, 1H), 3.50 (d, 1H, J ) 1.0 Hz), 2.39 (s, 3H); for the
other, 5.40 (s, 1H), 3.61 (d, 1H, J ) 1.0 Hz), 2.44 (s, 3H); the
ratio ) 4:5, HRMS for C28H22ClN7O6SNa (M + Na+) calcd
514.0816, found 514.0823.
Com p ou n d 42. p-Meth ylp h en yl 3,4,6-Tr i-O-a cetyl-2-
deoxy-2-(2,2,2-tr ich lor oeth oxylcar bon ylam in o)-1-su lfin yl-
â-D-glu cop yr a n osid e. 1H NMR (400 MHz, CDCl3), for one
diastereomer, δ 6.48 (d, 1H, J ) 7.3 Hz), 5.66 (t, 1H, J ) 9.6
Hz), 5.02 (t, 1H, J ) 9.8 Hz); for the other, 5.98 (d, 1H, J )
7.3 Hz), 5.41 (t, 1H, J ) 9.6 Hz), 4.90 (t, 1H, J ) 9.8 Hz); the
ratio ) 1:2, HRMS for C28H26NO10Cl3SCs (M + Cs+) calcd
733.9397, found 733.9371.
Com p ou n d 36. Eth yl 2,3,4,6-tetr a -O-a cetyl-1-su lfin yl-
â-D-ga la ctop yr a n osid e. H NMR (500 MHz, CDCl3), for one
1
diastereomer, δ 5.67 (t, 1H, J ) 10 Hz), 5.20 (dd, 2H, J ) 3.5
and 10.0 Hz), 2.18 (s, 3H); for the other, 5.24 (t, 1H, J ) 10
Hz), 5.16 (dd, 1H, J ) 3.5 and 10.0 Hz), 2.17 (s, 3H); the ratio
) 1:1, HRMS for C15H22O10SCs (M + Cs+) calcd 417.0831,
found 417.084.
Com p ou n d 37. p-Meth ylp h en yl 2,3,4,6-Tetr a -O-ben -
zoyl-1-su lfin yl-â-D-ga la ctop yr a n osid e. 1H NMR (500 MHz,
CDCl3), for one diastereomer, δ 6.13(t, 1H, J ) 10 Hz), 5.85
(d, 1H, J ) 3.0 Hz), 4.65 (d, 1H, J ) 10.0 Hz), 2.31 (s, 3H); for
the other, 5.82 (d, 1H, J ) 3.0 Hz), 5.13 (d, 1H, J ) 10 Hz),
2.37 (s, 3H); the ratio ) 3:1, HRMS for C34H30O9SCs (M + Cs+)
calcd 747.0465, found 747.0485.
Com p ou n d 38. p-Meth ylp h en yl 2,3,4-Tr i-O-ben zoyl-1-
su lfin yl-â-D-ga la ctop yr a n osid e. 1H NMR (500 MHz, CDCl3),
for one diastereomer, δ 6.13(t, 1H, J ) 10 Hz), 5.85 (d, 1H, J
) 3.0 Hz), 4.65 (d, 1H, J ) 10.0 Hz), 2.31 (s, 3H); for the other,
5.82 (d, 1H, J ) 3.0 Hz), 5.13 (d, 1H, J ) 10 Hz), 2.37 (s, 3H);
the ratio ) 3:1, HRMS for C34H30O9SCs (M + Cs+) calcd
747.0465, found 747.0485.
Com p ou n d 39. p-Meth ylp h en yl 2,3,4-Tr i-O-ben zoyl-6-
O-t -b u t yld im e t h ylsilyl-1-su lfin yl-â-D -ga la ct op yr a n o-
sid e. 1H NMR (400 MHz, CDCl3), for one diastereomer, δ 5.99
(t, 1H, J ) 10 Hz), 5.93 (d, 1H, J ) 3.0 Hz), 4.65 (d, 1H, J )
10.0 Hz), 2.36 (s, 3H); for the other, 5.89 (d, 1H, J ) 3.0 Hz),
5.72 (t, 1H, J ) 10 Hz), 4.93 (d, 1H, J ) 10.0 Hz), 2.42 (s, 3H);
the ratio ) 3:1, HRMS for C40H44O9SSiCs (M + Cs+) calcd
861.1530, found 861.1550.
Com p ou n d 43. p-Meth ylp h en yl 3-O-Ben zyl-4,6-O-ben -
zylid in e -2-O-le vu lin yl-1-su lfin yl-â-D -ga la ct op yr a n o-
sid e. 1H NMR (400 MHz, CDCl3), for one diastereomer, δ 4.06
(d, 1H, J ) 3.2 Hz), 3.94 (dd, 1H, J ) 1.6 and 12.5 Hz), 3.67
(dd, 1H, J ) 3.3 and 9.5 Hz), 2.33 (s, 3H); for the other, δ 4.03
(d, 1H, J ) 3.2 Hz), 3.85 (dd, 1H, J ) 1.6 and 12.5 Hz), 3.62
(dd, 1H, J ) 3.3 and 9.5 Hz), 2.38 (s, 3H); the ratio ) 1:2,
HRMS for C28H26NO10Cl3SCs (M + Cs+) calcd 733.9397, found
733.9371.
Com p ou n d 44. p-Meth ylp h en yl 2-O-Ben zyl-4,6-O-ben -
zylid in e-1-su lfin yl-â-D-ga la ctop yr a n osid e. 1H NMR (500
MHz, CDCl3), for one diastereomer, δ 5.38 (s, 1H), 4.46 (t, 1H,
J ) 9.5 Hz), 4.19 (d, 1H, J ) 9.5 Hz), 4.07 (d, 1H, J ) 3.0 Hz),
3.32 (d, 1H, J ) 0.5 Hz), 2.42 (s, 1H); for the other, 5.27 (s,
1H), 4.19 (d, 1H, J ) 9.5 Hz), 3.95 (d, 1H, J ) 3.0 Hz), 3.44 (d,
1H, J ) 0.5 Hz), 2.37 (s, 1H); the ratio ) 3:1, HRMS for
C
27H28O6SNa (M + Na+) calcd 503.1504, found 503.1516.
J O990686H