Platinum-catalyzed ring opening of 1,2-cyclopropanated sugars with O-nucleophiles. Convenient synthesis of 2-C-branched carbohydrates

Article abstract of DOI:10.1021/ja001558+

A new reaction is described catalyzed by Zeise's dimer that allows for ring opening of 1,2-cyclopropanated sugars with O-nucleophiles to give 2-C-branched carbohydrates. A number of O-nucleophiles can participate in the ring opening including alcohols, ph

Full text of DOI:10.1021/ja001558+

J. Am. Chem. Soc. 2000, 122, 9575-9583
9575
Platinum-Catalyzed Ring Opening of 1,2-Cyclopropanated Sugars
with O-Nucleophiles. Convenient Synthesis of 2-C-Branched
Carbohydrates
Ju1rgen Beyer, Philip R. Skaanderup, and Robert Madsen*
Contribution from the Department of Organic Chemistry, Technical UniVersity of Denmark,
DK-2800 Lyngby, Denmark
ReceiVed May 5, 2000
Abstract: A new reaction is described catalyzed by Zeise’s dimer that allows for ring opening of
1,2-cyclopropanated sugars with O-nucleophiles to give 2-C-branched carbohydrates. A number of O-
nucleophiles can participate in the ring opening including alcohols, phenols, and water. A wide range of alcohols
has been employed giving 2-C-branched glycosides ranging from simple methyl glycosides to more complex
disaccharides. A very high diastereoselectivity is obtained at the newly formed C-1 stereocenter. The R-glycoside,
favored by the anomeric effect, is always the major product in the ring opening with alcohols regardless of the
stereochemistry of the starting cyclopropane. When electron-rich phenols are employed as O-nucleophiles,
rearrangement to the glycosyl arene has been observed. In general, the ring opening occurs readily with
unsubstituted sugar cyclopropanes to give 2-C-methyl carbohydrates. However, cyclopropanes with ester or
alkyl substituents are significantly less reactive and some even completely inert to ring opening. When the
ring opening is carried out with PdCl2(PhCN)2 catalyst, a Ferrier-type rearrangement occurs, giving
2,3-unsaturated glycosides containing a 2-C-alkyl substituent.
Introduction
including effective enantioselective methods.7 Relief of the ring
strain in cyclopropanes provides a driving force for many
different ring-opening reactions.8 Cyclopropanations have re-
cently been extended to carbohydrates where several methods
have been developed for stereocontrolled cyclopropanation of
glycals.9 In general, zinc-mediated cyclopropanation under
modified Simmons-Smith conditions takes place from the same
face of the glycal double bond as the C-3 substituent10 while
cyclopropanation with metal carbenes or dihalocarbenes occurs
from the opposite face.11 These 1,2-cyclopropanated sugars have
been shown to undergo ring opening to give 2-C-branched
sugars when subjected to solvolysis in the presence of a
stoichiometric amount of mercury,10c strong acid,11a,b or halo-
nium ions.10a,12 In addition, ring opening under Mitsunobu
conditions has also been reported in a special case.11d We
reasoned that a catalytic ring-opening procedure could be
developed by employing an appropriate transition metal. The
reaction between a transition metal and a cyclopropane is due
to an interaction between a vacant orbital on the metal and the
C-Branched sugars occur widely in nature and have been the
focus of intense studies in carbohydrate chemistry. Many
antibiotics contain C-branched sugars as the glycosidic com-
ponents,1 and they have also been identified as structural
subunits in many other natural products.2,3 As a result, C-
branched sugars have often been used for total synthesis of
natural products2,4 and carbohydrate mimetics.5 However, C-
branched sugars constitute some of the most difficult carbohy-
drates to prepare in a stereocontrolled fashion.1,6 In addition,
many procedures use toxic reagents such as mercury and tin or
strongly basic organolithium and Grignard reagents.
Cyclopropanes are versatile functional groups in organic
synthesis and can be prepared by a variety of procedures
(1) Chapleur, Y.; Che´tien, F. In PreparatiVe Carbohydrate Chemistry;
Hanessian, S., Ed.; Marcel Dekker: New York, 1997; pp 207-262.
Yoshimura, J. AdV. Carbohydr. Chem. Biochem. 1984, 42, 69.
(2) Fraser-Reid, B.; Burgey, C. S.; Vollerthun, R. Pure Appl. Chem. 1998,
70, 285. Fraser-Reid, B. Acc. Chem. Res. 1996, 29, 57. Hanessian, S. Total
Synthesis of Natural Products: The ‘Chiron’ Approach; Pergamon Press:
Oxford, 1983.
(7) Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998, 54, 7919.
(8) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.; Tanko, J.;
Hudlicky, T. Chem. ReV. 1989, 89, 165.
(9) For a very recent review on preparation and ring opening of
cyclopropanated carbohydrates, see: Cousins, G. S.; Hoberg, J. O. Chem.
Soc. ReV. 2000, 29, 165.
(10) (a) Ramana, C. V.; Murali, R.; Nagarajan, M. J. Org. Chem. 1997,
62, 7694. (b) Hoberg, J. O. J. Org. Chem. 1997, 62, 6615. (c) Scott, R. W.;
Heathcock, C. H. Carbohydr. Res. 1996, 291, 205. (d) Hoberg, J. O.; Bozell,
J. J. Tetrahedron Lett. 1995, 36, 6831.
(11) (a) Kim, C.; Hoang, R.; Theodorakis, E. A. Org. Lett. 1999, 1, 1295.
(b) Hoberg, J. O.; Claffey, D. J. Tetrahedron Lett. 1996, 37, 2533. (c)
Timmers, C. M.; Leeuwenburgh, M. A.; Verheijen, J. C.; van der Marel,
G. A.; van Boom, J. H. Tetrahedron: Asymmetry 1996, 7, 49. (d) Henry,
K. J., Jr.; Fraser-Reid, B. Tetrahedron Lett. 1995, 36, 8901.
(12) (a) Ramana, C. V.; Nagarajan, M. Carbohydr. Lett. 1998, 3, 117.
(b) Ramana, C. V.; Nagarajan, M. Synlett 1997, 763. (c) Bertinato, P.;
Sorensen, E. J.; Meng, D.; Danishefsky, S. J. J. Org. Chem. 1996, 61, 8000.
(3) Celmer, W. D. Pure Appl. Chem. 1971, 28, 413.
(4) For some recent examples, see: Sasaki, M.; Inoue, M.; Takamatsu,
K.; Tachibana, K. J. Org. Chem. 1999, 64, 9399. Fernandez-Megia, E.;
Gourlaouen, N.; Ley, S. V.; Rowlands, G. J. Synlett 1998, 991. Horita, K.;
Nagasawa, M.; Sakurai, Y.; Yonemitsu, O. Chem. Pharm. Bull. 1998, 46,
1199. Bamba, M.; Nishikawa, T.; Isobe, M. Tetrahedron 1998, 54, 6639.
Chiba, N.; Takeoka, J.; Ando, K.; Tsutsumi, N.; Ogawa, S. Tetrahedron
1997, 53, 16287. Shimura, T.; Komatsu, C.; Matsumura, M.; Shimada, Y.;
Ohta, K.; Mitsunobu, O. Tetrahedron Lett. 1997, 38, 8341. Sin, N.;
Kallmerten, J. Tetrahedron Lett. 1996, 37, 5645.
(5) Sinay¨, P. Pure Appl. Chem. 1998, 70, 1495. Beau, J.-M.; Gallagher,
T. Top. Curr. Chem. 1997, 187, 1. Kishi, Y. Pure Appl. Chem. 1993, 65,
771.
(6) For recent organometallic approaches from glycals, see: Ferna´ndez,
E.; Ruiz, A.; Claver, C.; Castillo´n, S.; Polo, A.; Piniella, J. F.; Alvarez-
Larena, A. Organometallics 1998, 17, 2857. Linker, T.; Sommermann, T.;
Kahlenberg, F. J. Am. Chem. Soc. 1997, 119, 9377.
10.1021/ja001558+ CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/26/2000

9576 J. Am. Chem. Soc., Vol. 122, No. 40, 2000
Beyer et al.
Scheme 1a
Chart 1
Table 1. Ring Opening with Simple Alcoholsa
a (a) 5% [Pt(C2H4)Cl2]2, CH2Cl2, rt, 74%. (b) 3.7% [Pt(C2H4)Cl2]2,
CH2Cl2, rt, 23% or 3.7% [Pt(C2H4)Cl2]2, BnOH, CH2Cl2, rt, 95%.
σ-orbital of the C-C bond, the latter possessing high π-orbital
character. In particular, platinum has been shown to react
effectively with cyclopropanes to form platinacyclobutanes
which are usually fairly stable and can be isolated.13 However,
if the cyclopropane contains an oxy substituent, platinum has
been shown to catalyze ring opening and subsequent rearrange-
ment reactions.14 Especially the Pt(II)-catalyzed rearrangement
of alkoxy and siloxy cyclopropanes into allylic ethers is
noteworthy.14b,c We anticipated that a 1,2-cyclopropanated sugar
would undergo a similar rearrangement. In fact, when we treated
racemic cyclopropane 1 with Zeise’s dimer [Pt(C2H4)Cl2]2, we
obtained olefin 2 as the only product (Scheme 1). However,
when we carried out the same reaction on D-glucal-derived
cyclopropane 3, we did not observe any of the corresponding
exocyclic olefin, but instead benzyl glycoside 4 was isolated
as the major product. This is presumably formed by reaction of
the intermediate platinacyclobutane with benzyl alcohol which
might have been released during the reaction due to some
decomposition. Indeed, when the reaction was repeated with
benzyl alcohol added from the beginning, 2-C-branched gly-
coside 4 was obtained in 95% yield. This constitutes a new
method for stereocontrolled preparation of 2-C-branched gly-
cosides and to the best of our knowledge the first example of
a Pt-catalyzed ring opening of a cyclopropane with an O-
nucleophile. Herein, we report a detailed study on the scope
and limitations of this new transformation.15 We demonstrate
that the ring opening can take place with a variety of sugar
cyclopropanes and a range of O-nucleophiles including alcohols,
phenols, and water.
a All reactions were carried out in CH2Cl2 at ambient temperature
with 3.7% [Pt(C2H4)Cl2]2 and 2 equiv of the alcohol.
failed to open the cyclopropane in the presence of Zeise’s dimer,
and only benzyl glycoside 4 or unreacted cyclopropane 3 was
isolated from these experiments. As a result, the following
studies were carried out with different cyclopropanated sugars
and alcohol nucleophiles at ambient temperature in CH2Cl2. The
amount of Zeise’s dimer could be lowered to 1 mol % in gram-
scale experiments. However, to be able to weigh out accurate
amounts of catalyst on a smaller scale, the 3.7 mol % used in
Scheme 1 was maintained throughout these studies.
To probe the stereochemical outcome of the ring opening,
we first sought to investigate the reaction with some simple
alcohols. Hence, cyclopropanes 3 and 5-8 (Chart 1) were ring-
opened in the presence of methyl, allyl, benzyl, or tert-butyl
alcohol to give 2-C-methyl glycosides 9-21 (Table 1). The
structures of the R- and â-anomers were verified by their
JC-1,H-1 coupling constants: with JC-1,H-1(R-anomer) always
being about 10 Hz larger than JC-1,H-1(â-anomer).16 In the cases
where the R- and â-anomers could not be separated, the R/â
ratio was determined from 1H NMR by measuring the doublets
from the 2-C-methyl groups. The results in Table 1 show that
the ring opening proceeds well with the simple alcohols. High
yields were generally obtained with methyl, allyl, and benzyl
alcohol while tert-butyl alcohol gave a more moderate yield
(entry 3). The diastereoselectivity at the newly formed C-1
stereocenter was very high in all cases, strongly favoring the
R-glycoside, regardless of the stereochemistry of the starting
cyclopropane. The selectivity is particularly high for cyclopro-
panes 3, 5, and 6 which give products where the anomeric
substituent in the R-glycosides is trans to the 2-C-methyl group
(entries 1-9). This is in accordance with the halonium ion
mediated solvolysis reaction where cyclopropane 3 has been
Results and Discussion
Cyclopropane Ring Opening with Simple Alcohols. Ad-
ditional experiments revealed that the reaction between cyclo-
propane 3 and benzyl alcohol was best carried out in a weakly
coordinating solvent such as CH2Cl2 or toluene while THF gave
slower conversion and MeCN or DMF almost no reaction at
all. Coordination also played an important role for the choice
of catalyst. Platinum catalysts containing more tightly bound
ligands than in Zeise’s dimer gave either slower conversion (e.g.,
PtCl2(PhCN)2) or no reaction at all (e.g., PtCl2(MeCN)2,PtCl2-
(COD), and PtCl2(PPh3)2). A variety of other metal catalysts
including PdCl2(PPh3)2, Pd(PPh3)4, [Ru(CO)3Cl2]2, and [Rh-
(CO)2Cl]2 also failed to open the cyclopropane. However, when
Zeise’s dimer was replaced by the electrophilic palladium
catalyst PdCl2(PhCN)2 a Ferrier-type rearrangement occurred
(vide infra). A variety of other nucleophiles including thiophe-
nol, benzoic acid, benzylamine, aniline, and diethyl malonate
(13) Jennings, P. W.; Johnson, L. L. Chem. ReV. 1994, 94, 2241.
(14) (a) Hoberg, J. O.; Jennings, P. W. Organometallics 1996, 15, 3902.
(b) Ikura, K.; Ryu, I.; Kambe, N.; Sonoda, N. J. Am. Chem. Soc. 1992,
114, 1520. (c) Doyle, M. P.; van Leusen, D. J. Org. Chem. 1982, 47, 5326.
(15) Beyer, J.; Madsen, R. J. Am. Chem. Soc. 1998, 120, 12137.
(16) Bock, K.; Pedersen, C. J. Chem. Soc., Perkin Trans. 2 1974, 293.

Pt-Catalyzed Ring Opening of 1,2-Cyclopropanated Sugars
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9577
Table 2. Ring Opening with Watera
Chart 2
Table 3. Ring Opening with Monosaccharidesa
a All reactions were carried out in THF at 60 °C with 3.7%
[Pt(C2H4)Cl2]2 and 2 equiv of water.
shown to give R-glycosides exclusively.10a,12a For cyclopropanes
7 and 8 the platinum-catalyzed ring opening still gives R-gly-
cosides in good selectivity (entries 10-13). This is on the other
hand in contrast to the halonium ion mediated solvolysis where
7 gives mostly â-glycoside products.10a,12a As a result, the
stereochemical outcome of the platinum-catalyzed ring opening
seems to be largely dictated by the anomeric effect.17 The results
in Table 1 are in keeping with what is often observed in normal
O-glycosylation reactions in a weakly coordinating solvent when
a nonparticipating group is present at C-2. Here mannosyl and
rhamnosyl donors generally give higher R-selectivity in glyco-
sylations than the corresponding galactosyl donors which again
give slightly higher R-selectivity than the glucosyl donors.18
However, in conventional O-glycoside synthesis, competitive
reaction with water is a serious problem if rigorously anhydrous
conditions are not maintained. Surprisingly, no side product
arising from ring opening with water has been observed in the
examples in Table 1. In fact, when the reaction was carried out
in CH2Cl2 or toluene with 2 equiv of water no ring opening
occurred but instead the catalyst “blacked out”. Zeise’s dimer
and its precursor Zeise’s salt are both known to react with water
upon heating to produce metallic platinum, acetaldehyde, and
hydrogen chloride.19
Cyclopropane Ring Opening with Water. A number of
experiments were carried out to find conditions that would allow
the catalyst to react with the cyclopropane before it reacted with
water. It was soon realized that an important factor was to keep
a low water concentration. This was achieved by adding water
in portions during the course of the reaction. In addition, THF
proved to be the best solvent for these experiments with water
and 60 °C seemed to be the optimum reaction temperature.
Therefore, cyclopropanes 3, 5, 7, and 8 could be ring-opened
to give hemiacetals 22-25 (Table 2). The yields were generally
lower than the yields when the simple alcohols in Table 1 were
used as nucleophiles. The major byproducts observed were
dimers of 22-25 and benzyl glycosides 4, 14, 19, and 21.
Hemiacetals of 2-deoxy sugars are fairly acid labile and known
to dimerize easily.20 The benzyl glycosides are probably formed
a All reactions were carried out in CH2Cl2 at ambient temperature
with 3.7% [Pt(C2H4)Cl2]2 and 2 equiv of the monosaccharide.
in the same way as in Scheme 1 from some slight decomposition
and release of benzyl alcohol.
Cyclopropane Ring Opening with Monosaccharides and
Phenols. The ring-opening reaction makes it possible to view
the 1,2-cyclopropanated sugars as special glycosyl donors.
Therefore, it was decided also to investigate the reaction with
some more complex nucleophiles (Chart 2). Reacting cyclo-
propanes 3, 6, and 7 with monosaccharides 26 and 27 gave rise
to 2-C-branched disaccharides 32-35 in acceptable yields (Table
3). The yields were slightly lower than the yields with the simple
primary alcohols in Table 1. In fact, in one experiment (entry
2) benzyl glycoside 4 was isolated in 12% yield as a significant
byproduct. However, the diastereoselectivity follows the same
trend as observed before, giving the R-glycoside as the major
or the only product. Disaccharides 32-35 can be viewed as
special carbohydrate mimetics where the 2-hydroxy group has
been replaced by a hydrophobic methyl group.
Extending the reaction to phenols as nucleophiles gave rise
to O-glycosides and glycosyl arenes (phenyl C-glycosides)
depending on the substituents on the aromatic ring (Table 4).
Reacting cyclopropane 3 with phenol (28) or p-methoxyphenol
(29) gave phenyl O-glycosides 36 and 37, respectively, in
acceptable yields and excellent R-selectivity. However, when
(17) Juaristi, E.; Cuevas, G. The Anomeric Effect; CRC Press: Boca
Raton, 1995.
(18) Schmidt, R. R.; Kinzy, W. AdV. Carbohydr. Chem. Biochem. 1994,
50, 21. Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155.
(19) Chatt, J.; Searle, M. L. Inorg. Synth. 1957, 5, 210. Smidt, J.; Hafner,
W.; Jira, R.; Sedlmeier, J.; Sieber, R.; Ru¨ttinger, R.; Kojer, H. Angew. Chem.
1959, 71, 176.
(20) Hanessian, S. AdV. Carbohydr. Chem. 1966, 21, 143.

9578 J. Am. Chem. Soc., Vol. 122, No. 40, 2000
Table 4. Ring Opening of 3 with Phenolsa
Beyer et al.
Scheme 2a
a (a) 3.7% [Pt(C2H4)Cl2]2, BnOH, toluene, 70 °C, 1.5 h, 75%. (b)
3.7% [Pt(C2H4)Cl2]2, BnOH, toluene, 85 °C, 14 h.
Scheme 3a
a All reactions were carried out in CH2Cl2 at ambient temperature
with 3.7% [Pt(C2H4)Cl2]2 and 2 equiv of the phenol.
the phenol was further substituted with electrondonating groups
as in 30 and 31, glycosyl arenes 38 and 39 were obtained. These
are presumably formed by a Fries-type rearrangement of the
intermediate O-aryl glycoside.21 In the reactions with methoxy-
phenols 29-31 (entries 2-4), about 10-15% of benzyl gly-
coside 4 was also obtained as a byproduct. This follows the
general trend observed so far. When a poor O-nucleophile is
used, some decomposition of the cyclopropanated sugar will
occur with release of benzyl alcohol which is then a better
nucleophile in the ring-opening reaction.
Ring Opening of Substituted Cyclopropanes. Carboalkoxy-
substituted cyclopropanes can be prepared by reaction of the
glycal with ethyl diazoacetate by Rh(OAc)2 catalysis.11 These
were less reactive toward ring opening than the unsubstituted
cyclopropanes, and it was necessary to use toluene at elevated
temperature to get the reaction to proceed. Hereby, furanose
cyclopropane 40 was reacted with benzyl alcohol to produce
2-C-branched benzyl furanoside 41 as a 4/1 R/â mixture.
Although the R-anomer is still the dominating product, the R/â
ratio is lower than that observed for the unsubstituted pyranose
cyclopropanes in Tables 1 and 3. The ring opening of 40 could
also be performed with methanol, but unfortunately in this case
some transesterification with the ethyl ester did occur. This
transesterification turned out to be a major problem when the
ring opening was carried out on pyranose ester substituted
cyclopropane 42. This is even less reactive than furanose
cyclopropane 40, and the higher reaction temperature caused
significant transesterification, giving 43 as a mixture of benzyl
and ethyl glycoside as well as ethyl and benzyl ester.
Cyclopropanated sugars containing substituents other than
ester groups are not known. However, we have discovered that
zinc-mediated cyclopropanation directed by the 3-benzyloxy
group can be extended to prepare new substituted cyclopropanes.
In fact, cyclopropanating tri-O-benzyl-D-glucal and -D-galactal
with ethylidene iodide and diethyl zinc22 gave methyl-substituted
cyclopropanes 44a and 44b, respectively, while cyclopropana-
ting with phenyldiazomethane and zinc(II)chloride23 gave rise
to the corresponding phenyl-substituted cyclopropanes 44c and
a (a) 10% PdCl2(PhCN)2, BnOH, CH2Cl2, rt.
44d. The exo/endo selectivity varied from 2/1 to 5/1. However,
ring opening of these cyclopropanes with benzyl alcohol in
refluxing toluene turned out to be very difficult and gave either
no conversion or only very little benzyl glycoside product. In
addition, when ring-opened benzyl glycosides could be isolated,
they turned out to be a mixture of six- and seven-membered
sugars. This shows that for the substituted cyclopropanes 44
the platinum-catalyzed ring opening is not regioselective for
cyclopropane bond 1 but is also capable of breaking bond 2
(Scheme 2). In view of these results, no further experiments
have been carried out on substituted cyclopropanes.
Ferrier-Type Rearrangement. During the initial studies with
different catalysts, we discovered that when cyclopropane 3 was
treated with a very electrophilic palladium(II) catalyst, PdCl2-
(PhCN)2, a novel rearrangement occurred to give 2,3-unsaturated
benzyl glycoside 45 (Scheme 3). The same rearrangement could
be achieved with D-galactal-derived cyclopropane 5 although
in a lower yield due to some decomposition. None of the
corresponding benzyl glycosides 4 and 14 were observed in
these cases. However, in the rearrangement of 3 benzyl
glycoside 19 could be isolated as a byproduct in 3% yield. This
is mechanistically very interesting because the configuration at
C-2 in 19 has been inverted as compared to the starting
cyclopropane 3. This has never been observed in any of the
ring openings with Zeise’s dimer where the configuration at
C-2 is always retained. The stereochemistry at the anomeric
center in 45 and 46 was determined after hydrogenation of the
(21) Mahling, J.-A.; Schmidt, R. R. Synthesis 1993, 325.
(22) Kawabata, N.; Nakagawa, T.; Nakao, T.; Yamashita, S. J. Org.
Chem. 1977, 42, 3031.
(23) Goh, S. H.; Closs, L. E.; Closs, G. L. J. Org. Chem. 1969, 34, 25.

Pt-Catalyzed Ring Opening of 1,2-Cyclopropanated Sugars
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9579
Scheme 4
Scheme 5
double bond to give 47 and 48, respectively. The chemistry of
cyclopropane C-C single bonds often resembles that of
carbon-carbon double bonds.8 In fact, this palladium-catalyzed
rearrangement is analogous to the acid-induced Ferrier rear-
rangement of normal glycals.24 However, this is the first example
of a similar rearrangement on 1,2-cyclopropanated glycals. It
is very interesting that these seemingly similar platinum(II) and
palladium(II) catalysts ring-open the cyclopropanes to give
vastly different products.
corner attack.28 This gives rise to initial formation of σ-bonded
palladium glycoside 52.29 The same σ-bonded metal species is
observed in mercury(II)-mediated ring openings.10c,30 Further
reaction by â-hydride elimination affords olefin 53 which on
rehydropalladation gives 54.31 Previous studies have shown that
these glycopyranosides with palladium at C-2 undergo a facile
and unusual â-alkoxy elimination to the corresponding glycals.32
The reaction is probably mediated by coordination between
palladium and the exocyclic oxygen at C-1 which also prevents
a competing â-hydride elimination. Therefore, 55 is formed
which then by allylic Ferrier rearrangement gives the product.
In this reaction palladium(II) serves as the Lewis acid.33,34
Although intermediate glycal 55 cannot be observed in these
rearrangements, the fact that 19 can be isolated from the
rearrangement of 3 supports its existence. It should also be noted
that the Ferrier rearrangement generally gives good yields for
derivatives of D-glucal while the rearrangement works poorly
for derivatives of D-galactal.35 The exact same result is observed
for the rearrangement of cyclopropanated glycals 3 and 5.
In conclusion, we have developed a convenient procedure
for platinum-catalyzed ring opening of 1,2-cyclopropanated
Mechanism for Cyclopropane Ring Opening. To gain some
more insight into the mechanism of the platinum-catalyzed ring
opening with O-nucleophiles, we carried out a deuterium
labeling experiment with monodeuterated benzyl alcohol (Scheme
4). The product 49 was found to be completely monodeuterated
at the 2-C-methyl group. This allows us to propose a mechanism
where an intermediate platinacyclobutane is formed by oxidative
addition of the cyclopropane to platinum(II). Platina(IV)-
cyclobutanes have previously been proposed as intermediates
in rearrangements of electron-rich cyclopropanes with Zeise’s
dimer.14a,b However, it should also be noted that platina(IV)-
cyclobutanes formed from electron-rich cyclopropanes have
never actually been isolated or detected spectroscopically. The
best evidence for their formation is a crystal structure on a
platinum complex formed after ring opening of an electron-
rich cyclopropane.25 The structure shows that the cyclopropane
inserts into platinum at an edge because the configuration at
the cyclopropyl carbon is retained.25 Literature data on platina-
(IV)cyclobutanes suggest that the platinum(IV)-carbon σ-bonds
are polarized to give platinum(minus) and carbon(plus).26 In
platinacyclobutane 50 the electron donation from the sugar ring
oxygen will further enhance this polarization. As a result, 50 is
believed to have substantial oxocarbonium ion character as
previously observed for certain palladium species.27 Nucleophilic
attack of the O-nucleophile then gives the glycoside/hemiacetal
with the R-anomer dominating according to the anomeric effect.
Reductive elimination from 51 completes the catalytic cycle to
give the C-branched sugar and regenerating platinum(II).
(28) Blomberg, M. R. A.; Siegbahn, P. E. M.; Ba¨ckvall, J.-E. J. Am.
Chem. Soc. 1987, 109, 4450.
(29) For ring opening of other electron-rich cyclopropanes by palladium-
(II) complexes, see: Park, S.-B.; Cha, J. K. Org. Lett. 2000, 2, 147.
Fujimura, T.; Aoki, S.; Nakamura, E. J. Org. Chem. 1991, 56, 2809.
(30) Barrett, A. G. M.; Tam, W. J. Org. Chem. 1997, 62, 4653. Kocovsky´,
P.; Sˇrogl, J.; Pour, M.; Gogoll, A. J. Am. Chem. Soc. 1994, 116, 186.
Lambert, J. B.; Chelius, E. C.; Bible, R. H.; Hajdu, E. J. Am. Chem. Soc.
1991, 113, 1331. Coxon, J. M.; Steel, P. J.; Whittington, B. I. J. Org. Chem.
1990, 55, 4136.
(31) For other examples of â-hydride elimination-rehydropalladation
sequences, see: Larock, R. C.; Yum, E. K. Tetrahedron 1996, 52, 2743.
Larock, R. C.; Leung, W.-Y.; Stolz-Dunn, S. Tetrahedron Lett. 1989, 30,
6629.
(32) Bedjeguelal, K.; Bolitt, V.; Sinou, D. Synlett 1999, 762. Bedjeguelal,
K.; Joseph, L.; Bolitt, V.; Sinou, D. Tetrahedron Lett. 1999, 40, 87.
Nguefack, J.-F.; Bolitt, V.; Sinou, D. J. Org. Chem. 1997, 62, 1341; 6827.
(33) For Ferrier rearrangement of 3,4,6-tri-O-benzyl-D-glucal with
BF3.OEt2 into benzyl 4,6-di-O-benzyl-2,3-dideoxy-R-D-erythro-hex-2-
enopyranoside, see: Descotes, G.; Martin, J.-C. Carbohydr. Res. 1977, 56,
168.
(34) When we subjected 3,4,6-tri-O-benzyl-D-glucal to Zeise’s dimer or
PdCl2(PhCN)2, we observed in both cases Ferrier rearrangement into benzyl
4,6-di-O-benzyl-2,3-dideoxy-R-D-erythro-hex-2-enopyranoside.
(35) Ferrier, R. J.; Prasad, N. J. Chem. Soc. C 1969, 570. Ciment, D.
M.; Ferrier, R. J. J. Chem. Soc. C 1966, 441.
For the palladium-catalyzed Ferrier-type rearrangement, a
different mechanistic pathway is believed to be operating
(Scheme 5). Contrary to platinum(II), previous theoretical
studies suggest that palladium(II) ring-opens cyclopropanes by
(24) Ferrier, R. J. Methods Carbohydr. Chem. 1972, 6, 307.
(25) Hoberg, J. O.; Larsen, R. D.; Jennings, P. W. Organometallics 1990,
9, 1334.
(26) Ye, Z.; Dimke, M.; Jennings, P. W. Organometallics 1993, 12, 1026.
(27) Hii, K. K.; Claridge, T. D. W.; Brown, J. M. Angew. Chem., Int.
Ed. Engl. 1997, 36, 984.

9580 J. Am. Chem. Soc., Vol. 122, No. 40, 2000
Beyer et al.
(J ) 157.1 Hz). Anal. Calcd for C29H34O5: C, 75.30; H, 7.41. Found:
C, 75.40; H, 7.40.
sugars with O-nucleophiles. The 2-C-branched glycosides thus
obtained are formed with very high R-selectivity regardless of
the stereochemistry of the starting cyclopropane. In addition,
we have discovered a palladium-catalyzed Ferrier-type rear-
rangement of 1,2-cyclopropanated sugars to give 2,3-unsaturated
sugars containing a 2-C-alkyl substituent. All these 2-C-branched
sugars are valuable chiral building blocks in synthetic strategies
toward natural products and carbohydrate mimetics.
Allyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-r-D-mannopyrano-
side (10). Rf ) 0.48. [R]25D +51.5 (c 1.0, CHCl3). 1H NMR (250 MHz)
δ: 7.39-7.29 (m, 15H), 5.89 (m, 1H), 5.25 (dq, J ) 17.2, 1.7 Hz,
1H), 5.16 (dq, J ) 10.4, 1.7 Hz, 1H), 4.84 (d, J ) 10.8 Hz, 1H), 4.76
(d, J ) 1.3 Hz, 1H), 4.67 (d, J ) 12.2 Hz, 1H), 4.64 (d, J ) 11.4 Hz,
1H), 4.59 (d, J ) 11.4 Hz, 1H), 4.49 (d, J ) 12.2 Hz, 1H), 4.44 (d, J
) 10.8 Hz, 1H), 4.15 (ddt, J ) 13.0, 5.1, 1.5 Hz, 1H), 4.06 (m, 1H),
3.93 (ddt, J ) 13.0, 6.1, 1.2 Hz, 1H), 3.79-3.65 (m, 4H), 2.43 (m,
1H), 1.09 (d, J ) 7.3 Hz, 3H). 13C NMR (62.5 MHz) δ: 138.7, 138.5,
138.3, 134.1, 128.3, 128.3, 128.2, 127.9, 127.6, 127.5, 127.5, 127.4,
127.4, 116.9, 101.3 (J ) 167.2 Hz), 79.7, 74.9, 74.2, 73.3, 71.3, 71.0,
69.1, 67.7, 36.7, 11.2. Anal. Calcd for C31H36O5: C, 76.20; H, 7.43.
Found: C, 75.95; H, 7.72.
Experimental Section
General Procedures. All NMR spectra were recorded in CDCl3
using TMS (δ ) 0) as internal reference for 1H NMR spectra and CDCl3
(δ ) 77.0) for 13C NMR spectra. All Rf values were measured in 5/1
hexane/EtOAc.
tert-Butyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-mannopyra-
General Procedure for Platinum-Catalyzed Cyclopropane Ring
Opening with Alcohols and Phenols. Zeise’s dimer36 (21.5 mg, 0.0366
mmol) was dissolved in CH2Cl2 (5 mL) under an atmosphere of
nitrogen. The solution was then transferred by syringe to a flask
containing the cyclopropane (1.0 mmol) and the alcohol (2.0 mmol).
The mixture was stirred under nitrogen at room temperature for 15 h.
After removal of the solvent in vacuo, the crude mixture was purified
by flash chromatography. If R- and â-glycosides could not be separated,
complete NMR data are reported for the R-anomer (major) while for
the â-anomer (minor) the chemical shift and coupling constant for the
anomeric carbon are reported.
General Procedure for Platinum-Catalyzed Cyclopropane Ring
Opening with Water. The cyclopropane (500 mg, 1.16 mmol) was
dissolved in THF (4 mL) followed by addition of Zeise’s dimer (25
mg, 0.0425 mmol) and H2O (14 µL, 0.78 mmol). The solution was
heated under an atmosphere of nitrogen at 60 °C for 24 h during which
time more H2O (14 µL) was added after 1 and 2 h, respectively. The
reaction mixture was concentrated and the residue purified by flash
chromatography.
1
noside (11). Rf ) 0.59. R-Anomer. H NMR (500 MHz) δ: 7.38-
7.15 (m, 15H), 5.00 (d, J ) 1.2 Hz, 1H), 4.83 (d, J ) 10.7 Hz, 1H),
4.68 (d, J ) 12.1 Hz, 1H), 4.64 (d, J ) 11.5 Hz, 1H), 4.56 (d, J )
11.5 Hz, 1H), 4.46 (d, J ) 12.1 Hz, 1H), 4.43 (d, J ) 10.7 Hz, 1H),
4.06 (dd, J ) 9.0, 5.1 Hz, 1H), 3.96 (ddd, J ) 9.0, 5.9, 2.0 Hz, 1H),
3.80-3.76 (m, 2H), 3.63 (dd, J ) 10.5, 2.0 Hz, 1H), 2.22 (m, 1H),
1.23 (s, 9H), 1.08 (d, J ) 7.3 Hz, 3H). 13C NMR (125 MHz) δ: 138.8,
138.5, 138.3, 128.1, 128.1, 127.9, 127.6, 127.5, 127.4, 127.3, 96.4 (J
) 164.0 Hz), 79.7, 74.8, 74.5, 74.4, 73.2, 70.8, 70.7, 69.1, 38.2, 28.4,
11.4. â-Anomer. 13C NMR (125 MHz) δ: 95.9 (J ) 150.8 Hz). Anal.
Calcd for C32H40O5: C, 76.16; H, 7.99. Found: C, 76.52; H, 7.87.
Methyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-r-D-talopyrano-
side (12). Rf ) 0.47. [R]25D +26.2 (c 1.7, CHCl3). 1H NMR (250 MHz)
δ: 7.37-7.19 (m, 15H), 4.97 (d, J ) 11.7 Hz, 1H), 4.64 (bs, 1H),
4.63 (d, J ) 11.9 Hz, 1H), 4.55 (d, J ) 11.8 Hz, 1H), 4.53 (d, J )
11.7 Hz, 1H), 4.52 (d, J ) 11.9 Hz, 1H), 4.44 (d, J ) 11.8 Hz, 1H),
3.96 (t, J ) 6.3 Hz, 1H), 3.85 (m, 2H), 3.66 (d, J ) 6.3 Hz, 2H), 3.33
(s, 3H), 2.27 (m, 1H), 1.26 (d, J ) 7.4 Hz, 3H). 13C NMR (62.5 MHz)
δ: 139.1, 138.6, 138.1, 128.2, 128.0, 127.5, 127.5, 127.4, 127.2, 127.0,
126.9, 103.7 (J ) 171.1 Hz), 76.2, 74.5, 74.0, 73.3, 70.0, 69.6, 69.6,
54.7, 36.2, 12.4. Anal. Calcd for C29H34O5: C, 75.30; H, 7.41. Found:
C, 75.25; H, 7.41.
Tetrahydro-3-methylene-2H-pyran (2). Zeise’s dimer (100 mg,
0.170 mmol) was dissolved during 5 min in CH2Cl2 (10 mL). 2-Oxa-
bicyclo[4.1.0]heptane 137 (330 mg, 3.36 mmol) was then added by
syringe. The solution was stirred at room temperature for 20 h. The
solvent was removed in vacuo and the residue purified by flash
chromatography (pentane/Et2O 5/1) to afford 243 mg (74%) of 2 as a
Allyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-talopyranoside (13).
1
Rf ) 0.54. R-Anomer. H NMR (500 MHz) δ: 7.37-7.21 (m, 15H),
5.91 (m, 1H), 5.24 (dq, J ) 17.2, 1.5 Hz, 1H), 5.16 (dq, J ) 10.5, 1.5
Hz, 1H), 4.96 (d, J ) 11.8 Hz, 1H), 4.81 (s, 1H), 4.64 (d, J ) 11.8
Hz, 1H), 4.55 (d, J ) 11.8 Hz, 1H), 4.53 (d, J ) 11.3 Hz, 2H), 4.45
(d, J ) 11.8 Hz, 1H), 4.16 (ddt, J ) 13.0, 5.2, 1.5 Hz, 1H), 4.01 (dt,
J ) 6.1, 1.5 Hz, 1H), 3.97 (dd, J ) 13.0, 6.1 Hz, 1H), 3.89 (dd, J )
5.2, 3.0 Hz, 1H), 3.86 (m, 1H), 3.69-3.63 (m, 2H), 2.31 (m, 1H),
1.26 (d, J ) 7.4 Hz, 3H). 13C NMR (125 MHz) δ: 139.2, 138.7, 138.2,
134.2, 128.2, 128.0, 127.7, 127.5, 127.5, 127.3, 127.1, 127.0, 117.0,
101.9 (J ) 166.9 Hz), 76.3, 74.7, 74.0, 73.3, 70.1, 69.8, 69.6, 67.8,
36.3, 12.5. â-Anomer. 13C NMR (125 MHz) δ: 101.6 (J ) 156.4 Hz).
Anal. Calcd for C31H36O5: C, 76.20; H, 7.43. Found: C, 76.45; H,
7.40.
1
liquid. H NMR (250 MHz) δ: 4.77 (m, 2H), 4.03 (s, 2H), 3.73 (m,
2H), 2.32 (tt, J ) 6.3, 1.1 Hz, 2H), 1.72 (m, 2H). 13C NMR (62.5
1
MHz) δ: 144.1, 109.1, 72.6, 67.8, 31.6, 28.1. H NMR data are in
accordance with literature values.38
Benzyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-mannopyrano-
1
side (4). Rf ) 0.51. R-Anomer. H NMR (250 MHz) δ: 7.38-7.09
(m, 20H), 4.78 (d, J ) 10.8 Hz, 1H), 4.75 (d, J ) 1.0 Hz, 1H), 4.63
(d, J ) 12.0 Hz, 1H), 4.60 (d, J ) 12.0 Hz, 1H), 4.57 (d, J ) 11.5 Hz,
1H), 4.49 (d, J ) 11.5 Hz, 1H), 4.45 (d, J ) 12.0 Hz, 1H), 4.40 (d, J
) 12.0 Hz, 1H), 4.39 (d, J ) 10.8 Hz, 1H), 4.01 (dd, J ) 8.8, 5.2 Hz,
1H), 3.75 (m, 1H), 3.70 (m, 2H), 3.61 (dd, J ) 10.6, 1.9 Hz, 1H), 2.39
(m, 1H), 1.02 (d, J ) 7.3 Hz, 3H). 13C NMR (62.5 MHz) δ: 138.7,
138.5, 138.3, 137.7, 128.3, 128.0, 127.9, 127.7, 127.6, 127.6, 127.5,
101.4 (J ) 166.9 Hz), 79.8, 75.0, 74.2, 73.4, 71.5, 71.1, 69.1, 68.9,
36.8, 11.3. â-Anomer. 13C NMR (62.5 MHz) δ: 100.4 (J ) 156.7 Hz).
Anal. Calcd for C35H38O5: C, 78.04; H, 7.11. Found: C, 77.99; H,
7.41.
Benzyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-r-D-talopyrano-
side (14). Rf ) 0.62. [R]25D +34.5 (c 2.9, CHCl3). 1H NMR (500 MHz)
δ: 7.36-7.17 (m, 20H), 4.97 (d, J ) 11.8 Hz, 1H), 4.85 (s, 1H), 4.71
(d, J ) 12.0 Hz, 1H), 4.64 (d, J ) 11.8 Hz, 1H), 4.56 (bd, J ) 12.0
Hz, 3H), 4.49 (d, J ) 11.8 Hz, 1H), 4.47 (d, J ) 11.8 Hz, 1H), 4.07
(dt, J ) 6.3, 1.6 Hz, 1H), 3.93 (dd, J ) 5.3, 3.0 Hz, 1H), 3.90 (bs,
1H), 3.68 (m, 2H), 2.35 (m, 1H), 1.27 (d, J ) 7.4 Hz, 3H). 13C NMR
(62.5 MHz) δ: 139.3, 138.8, 138.2, 137.9, 128.3, 128.1, 127.9, 127.7,
127.6, 127.3, 127.2, 127.1, 102.0 (J ) 163.8 Hz), 76.4, 74.7, 74.1,
73.4, 70.2, 70.1, 69.7, 68.9, 36.3, 12.6. Anal. Calcd for C35H38O5: C,
78.04; H, 7.11. Found: C, 78.19; H, 7.38.
Methyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-mannopyrano-
1
side (9). Rf ) 0.56. R-Anomer. H NMR (250 MHz) δ: 7.37-7.14
(m, 15H), 4.84 (d, J ) 10.8 Hz, 1H), 4.66 (d, J ) 12.2 Hz, 1H), 4.65
(d, J ) 11.5 Hz, 1H), 4.61 (s, 1H), 4.53 (d, J ) 11.5 Hz, 1H), 4.51 (d,
J ) 12.2 Hz, 1H), 4.44 (d, J ) 10.8 Hz, 1H), 3.98 (m, 1H), 3.80-3.65
(m, 4H), 3.33 (s, 3H), 2.39 (tq, J ) 7.3, 1.6 Hz, 1H), 1.08 (d, J ) 7.3
Hz, 3H). 13C NMR (62.5 MHz) δ: 138.7, 138.6, 138.4, 128.3, 127.9,
127.7, 127.6, 127.5, 103.2 (J ) 171.2 Hz), 79.8, 74.9, 74.2, 73.4, 71.2,
71.0, 69.2, 54.6, 36.7, 11.2. â-Anomer. 13C NMR (62.5 MHz) δ: 102.8
Methyl 3,4-Di-O-benzyl-2-deoxy-2-C-methyl-L-rhamnopyrano-
1
side (15). Rf ) 0.58. R-Anomer. H NMR (250 MHz) δ: 7.38-7.21
(m, 10H), 4.90 (d, J ) 10.9 Hz, 1H), 4.62 (d, J ) 11.5 Hz, 1H), 4.58
(d, J ) 10.9 Hz, 1H), 4.52 (d, J ) 11.5 Hz, 1H), 4.49 (bs, 1H), 3.95
(dd, J ) 9.3, 5.1 Hz, 1H), 3.68 (m, 1H), 3.28 (t, J ) 9.3 Hz, 1H), 3.30
(s, 3H), 2.38 (m, 1H), 1.29 (d, J ) 6.2 Hz, 3H), 1.06 (d, J ) 7.3 Hz,
3H). 13C NMR (62.5 MHz) δ: 138.6, 138.6, 128.2, 128.2, 127.9, 127.8,
127.5, 127.4, 127.4, 127.3, 102.9 (J ) 165.8 Hz), 80.0, 79.9, 74.9,
(36) Boag, N. M.; Ravetz, M. S. J. Chem. Soc., Dalton Trans. 1995,
3473.
(37) Friedrich, E. C.; Lewis, E. J. J. Org. Chem. 1990, 55, 2491.
(38) Kirmse, W.; Rode, K. Chem. Ber. 1987, 120, 847.

Pt-Catalyzed Ring Opening of 1,2-Cyclopropanated Sugars
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9581
70.8, 67.2, 54.4, 36.7, 18.1, 11.2. â-Anomer. 13C NMR (62.5 MHz) δ:
102.6 (J ) 154.5 Hz). Anal. Calcd for C22H28O4: C, 74.13; H, 7.92.
Found: C, 73.91; H, 8.11.
127.6, 127.5, 127.5, 127.4, 127.3, 127.3, 100.3 (J ) 166.9 Hz), 79.8,
74.2, 73.3, 72.1, 71.6, 69.8, 69.4, 68.8, 35.3, 12.5. â-Anomer. 13C NMR
(62.5 MHz) δ: 103.7 (J ) 158.2 Hz). Anal. Calcd for C35H38O5: C,
78.04; H, 7.11. Found: C, 78.02; H, 7.06.
3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-mannopyranose (22). Rf
) 0.05. R-Anomer. 1H NMR (200 MHz) δ: 7.40-7.12 (m, 15H), 5.15
(d, J ) 2 Hz, 1H), 4.85 (d, J ) 12 Hz, 2H), 4.67-4.40 (m, 5H), 4.14-
3.98 (m, 2H), 3.71-3.59 (m, 3H), 2.41 (m, 1H), 1.06 (d, J ) 8 Hz,
3H). 13C NMR (50 MHz) δ: 138.6, 138.4, 137.9, 128.7, 128.2, 127.8,
127.5, 96.4 (J ) 167 Hz), 79.1, 74.6, 74.4, 73.1, 70.9, 70.9, 69.4, 36.7,
11.2. Data are in accordance with literature values.10c
Allyl 3,4-Di-O-benzyl-2-deoxy-2-C-methyl-L-rhamnopyranoside
1
(16). Rf ) 0.58. R-Anomer. H NMR (500 MHz) δ: 7.37-7.25 (m,
10H), 5.91 (m, 1H), 5.27 (dq, J ) 17.4, 1.4 Hz, 1H), 5.16 (dq, J )
10.3, 1.4 Hz, 1H), 4.91 (d, J ) 10.9 Hz, 1H), 4.65 (s, 1H), 4.64 (d, J
) 11.5 Hz, 1H), 4.59 (d, J ) 10.9 Hz, 1H), 4.55 (d, J ) 11.5 Hz, 1H),
4.11 (ddt, J ) 12.9, 5.1, 1.3 Hz, 1H), 4.01 (dd, J ) 9.0, 5.4 Hz, 1H),
3.92 (ddt, J ) 12.9, 6.1, 1.3 Hz, 1H), 3.73 (m, 1H), 3.29 (t, J ) 9.3
Hz, 1H), 2.42 (m, 1H), 1.29 (d, J ) 6.2 Hz, 3H), 1.07 (d, J ) 6.2 Hz,
3H). 13C NMR (62.5 MHz) δ: 138.7, 138.5, 134.1, 128.2, 127.9, 127.5,
127.3, 116.8, 101.0 (J ) 166.1 Hz), 80.1, 79.4, 75.0, 70.9, 67.5, 67.5,
36.7, 18.1, 11.2. â-Anomer. 13C NMR (62.5 MHz) δ: 100.5 (J ) 154.7
Hz). Anal. Calcd for C24H30O4: C, 75.36; H, 7.91. Found: C, 75.49;
H, 8.16.
3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-talopyranose (23). Rf )
1
0.05. [R]25 +1.4 (c 0.6, CHCl3). R-Anomer. H NMR (200 MHz) δ:
D
7.41-7.20 (m, 15H), 5.17 (bs, 1H), 4.93 (d, J ) 12 Hz, 1H), 4.78-
4.39 (m, 5H), 4.24 (m, 1H), 3.89 (dd, J ) 5, 3 Hz, 1H), 3.83-3.53
(m, 3H), 2.67 (d, J ) 3 Hz, 1H), 2.26 (m, 1H), 1.24 (d, J ) 7 Hz, 3H).
13C NMR (50 MHz) δ: 139.0, 138.7, 137.8, 128.2, 128.0, 127.9, 127.6,
127.3, 127.1, 127.0, 96.9 (J ) 167 Hz), 76.0, 74.9, 73.7, 73.2, 70.3,
70.0, 69.9, 36.5, 12.4. â-Anomer. 13C NMR (50 MHz) δ: 96.3 (J )
159.2 Hz). Anal. Calcd for C28H32O5: C, 74.98; H, 7.19. Found: C,
74.66; H, 7.57.
Benzyl 3,4-Di-O-benzyl-2-deoxy-2-C-methyl-L-rhamnopyranoside
1
(17). Rf ) 0.67. R-Anomer. H NMR (250 MHz) δ: 7.37-7.26 (m,
15H), 4.90 (d, J ) 10.8 Hz, 1H), 4.67 (d, J ) 11.8 Hz, 1H), 4.66 (d,
J ) 11.8 Hz, 1H), 4.60 (s, 1H), 4.59 (d, J ) 10.8 Hz, 1H), 4.54 (d, J
) 11.8 Hz, 1H), 4.42 (d, J ) 11.8 Hz, 1H), 4.03 (dd, J ) 9.2, 5.2 Hz,
1H), 3.78 (m, 1H), 3.31 (t, J ) 9.2 Hz, 1H), 2.44 (m, 1H), 1.30 (d, J
) 6.2 Hz, 3H), 1.06 (d, J ) 7.3 Hz, 3H). 13C NMR (62.5 MHz) δ:
138.6, 138.5, 137.7, 128.2, 127.9, 127.7, 127.6, 127.5, 127.3, 101.2 (J
) 165.6 Hz), 80.1, 79.4, 75.0, 70.9, 68.6, 67.6, 36.8, 18.2, 11.2.
â-Anomer. 13C NMR (62.5 MHz) δ: 100.2 (J ) 155.9 Hz). Anal. Calcd
for C28H32O4: C, 77.75; H, 7.46. Found: C, 77.67; H, 7.36.
3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-glucopyranose (24). Rf
) 0.06. [R]25D +72.4 (c 0.9, CHCl3). Mp 89-90 °C (hexane/EtOAc).
1
R-Anomer. H NMR (200 MHz) δ: 7.50-7.11 (m, 15H), 5.13 (bs,
1H), 4.87 (d, J ) 11 Hz, 1H), 4.82 (d, J ) 11 Hz, 1H), 4.71-4.45 (m,
4H), 4.08 (m, 1H), 3.76-3.47 (m, 4H), 2.72 (bs, 1H), 1.91 (m, 1H),
1.08 (d, J ) 6 Hz, 3H). 13C NMR (50 MHz) δ: 138.1, 128.3, 127.8,
127.6, 95.2 (J ) 163.8 Hz), 82.0, 79.7, 75.3, 74.7, 73.3, 70.8, 69.1,
41.3, 12.8. Anal. Calcd for C28H32O5: C, 74.98; H, 7.19. Found: C,
74.69; H, 7.22.
Methyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-glucopyrano-
1
side (18). Rf ) 0.41. R-Anomer. H NMR (250 MHz) δ: 7.35-7.13
(m, 15H), 4.83 (d, J ) 11.2 Hz, 1H), 4.79 (d, J ) 12.5 Hz, 1H), 4.63
(d, J ) 12.5 Hz, 1H), 4.62 (d, J ) 11.0 Hz, 1H), 4.55 (d, J ) 3.4 Hz,
1H), 4.51 (d, J ) 11.3 Hz, 2H), 3.78-3.58 (m, 5H), 3.32 (s, 3H), 1.92
(m, 1H), 1.03 (d, J ) 6.7 Hz, 3H). 13C NMR (62.5 MHz) δ: 139.7,
138.4, 138.2, 128.3, 127.8, 127.7, 127.6, 102.0 (J ) 165.7 Hz), 82.6,
79.5, 75.3, 74.7, 73.5, 70.9, 69.0, 54.9, 41.3, 12.6. â-Anomer. 13C NMR
(125 MHz) δ: 100.2 (J ) 160.7 Hz). Anal. Calcd for C29H34O5: C,
75.30; H, 7.41. Found: C, 75.45; H, 7.28.
3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-galactopyranose (25).
Rf ) 0.05. [R]25 +57.7 (c 0.5, CHCl3). Mp 112-113 °C (hexane/
D
EtOAc). R-Anomer. 1H NMR (200 MHz) δ: 7.39-7.21 (m, 15H), 5.17
(t, J ) 4 Hz, 1H), 4.88 (d, J ) 11 Hz, 2H), 4.70 (d, J ) 11 Hz, 2H),
4.62-4.28 (m, 2H), 4.15 (t, J ) 6 Hz, 1H), 3.85 (bs, 1H), 3.66-3.41
(m, 2H), 3.08 (m, 1H), 2.74 (bs, 1H), 2.42 (m, 1H), 1.05 (d, J ) 7 Hz,
3H). 13C NMR (50 MHz) δ: 138.6, 138.3, 137.8, 128.3, 128.1, 128.0,
127.7, 127.5, 95.6 (J ) 171.4 Hz), 79.4, 74.2, 73.4, 72.3, 71.8, 70.0,
69.7, 35.3, 12.7. â-Anomer. 13C NMR (50 MHz) δ: 99.4 (J ) 164.1
Hz). Anal. Calcd for C28H32O5: C, 74.98; H, 7.19. Found: C, 74.43;
H, 7.37.
Benzyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-glucopyranoside
1
(19). Rf ) 0.53. R-Anomer. H NMR (500 MHz) δ: 7.37-7.20 (m,
20H), 4.86 (d, J ) 10.9 Hz, 1H), 4.81 (d, J ) 10.9 Hz, 1H), 4.78 (d,
J ) 3.4 Hz, 1H), 4.70 (d, J ) 12.1 Hz, 1H), 4.66 (d, J ) 12.1 Hz,
1H), 4.65 (d, J ) 10.9 Hz, 1H), 4.53 (d, J ) 12.1 Hz, 1H), 4.52 (d, J
) 10.9 Hz, 1H), 4.46 (d, J ) 12.1 Hz, 1H), 3.87 (m, 1H), 3.76 (dd, J
) 10.6, 4.0 Hz, 1H), 3.67 (m, 3H), 1.97 (m, 1H), 1.08 (d, J ) 6.8 Hz,
3H). 13C NMR (125 MHz) δ: 138.7, 138.4, 138.1, 137.9, 128.4, 128.3,
128.3, 127.8, 127.8, 127.7, 127.6, 127.5, 100.2 (J ) 166.0 Hz), 82.7,
79.5, 75.4, 74.8, 73.5, 71.3, 68.9, 68.9, 41.3, 12.7. â-Anomer. 13C NMR
(125 MHz) δ: 103.3 (J ) 158.0 Hz). Anal. Calcd for C35H38O5: C,
78.04; H, 7.11. Found: C, 77.80; H, 6.90.
Methyl 2,3,4-Tri-O-benzyl-6-O-(3,4,6-tri-O-benzyl-2-deoxy-2-C-
methyl-r-D-mannopyranosyl)-r-D-glucopyranoside (32). Rf ) 0.13.
1
[R]25 +48.4 (c 0.3, CHCl3). H NMR (500 MHz) δ: 7.45-7.10 (m,
D
30H), 4.99 (d, J ) 10.8 Hz, 1H), 4.91 (d, J ) 11.1 Hz, 1H), 4.84 (d,
J ) 11.1 Hz, 1H), 4.81 (d, J ) 10.8 Hz, 1H), 4.79 (d, J ) 12.1 Hz,
1H), 4.77 (s, 1H), 4.69 (d, J ) 12.1 Hz, 1H), 4.63 (d, J ) 11.7 Hz,
1H), 4.62 (s, 1H), 4.58 (d, J ) 12.2 Hz, 1H), 4.55 (d, J ) 11.1 Hz,
1H), 4.53 (d, J ) 11.7 Hz, 1H), 4.41 (d, J ) 11.1 Hz, 1H), 4.38 (d, J
) 12.2 Hz, 1H), 3.99 (m, 2H), 3.85 (dd, J ) 11.4, 4.2 Hz, 1H), 3.73
(m, 2H), 3.64 (m, 1H), 3.59 (m, 2H), 3.52 (m, 3H), 3.35 (s, 3H), 2.43
(m, 1H), 1.06 (d, J ) 7.3 Hz, 3H). 13C NMR (62.5 MHz) δ: 138.8,
138.7, 138.5, 138.3, 138.3, 138.1, 128.4, 128.3, 128.3, 128.2, 128.1,
128.0, 127.9, 127.7, 127.6, 127.5, 127.5, 127.4, 127.4, 127.3, 102.4 (J
) 169.2 Hz), 97.9 (J ) 171.0 Hz), 82.2, 80.0, 79.2, 77.6, 77.2, 75.8,
74.9, 74.7, 74.0, 73.2, 71.4, 70.9, 69.7, 69.0, 65.7, 55.1, 36.5, 11.1.
Anal. Calcd for C56H62O10: C, 75.14; H, 6.98. Found: C, 74.92; H,
6.75.
Allyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-galactopyranoside
1
(20). Rf ) 0.48. R-Anomer. H NMR (500 MHz) δ: 7.37-7.21 (m,
15H), 5.87 (m, 1H), 5.25 (dq, J ) 10.5, 1.6 Hz, 1H), 5.14 (dq, J )
17.2, 1.6 Hz, 1H), 4.89 (d, J ) 11.6 Hz, 1H), 4.75 (d, J ) 3.5 Hz,
1H), 4.70 (d, J ) 11.6 Hz, 1H), 4.57 (d, J ) 11.6 Hz, 1H), 4.51 (d, J
) 11.8 Hz, 1H), 4.50 (d, J ) 11.6 Hz, 1H), 4.43 (d, J ) 11.8 Hz, 1H),
4.13 (ddt, J ) 13.3, 5.0, 1.5 Hz, 1H), 3.93 (m, 2H), 3.63-3.55 (m,
4H), 2.44 (m, 1H), 1.05 (d, J ) 6.9 Hz, 3H). 13C NMR (125 MHz) δ:
138.8, 138.3, 138.0, 134.4, 128.3, 128.1, 128.0, 127.7, 127.6, 127.5,
127.3, 116.5, 100.4 (J ) 167.2 Hz), 79.9, 74.3, 73.4, 72.2, 71.7, 69.7,
69.5, 67.9, 35.3, 12.5. â-Anomer. 13C NMR (125 MHz) δ: 103.9 (J )
156.6 Hz). Anal. Calcd for C31H36O5: C, 76.20; H, 7.43. Found: C,
76.30; H, 7.20.
Methyl 2,3,6-Tri-O-benzyl-4-O-(3,4,6-tri-O-benzyl-2-deoxy-2-C-
methyl-r-D-mannopyranosyl)-r-D-glucopyranoside (33). Rf ) 0.26.
1
[R]25 +33.1 (c 2.1, CHCl3). H NMR (500 MHz) δ: 7.33-7.16 (m,
D
30H), 5.10 (d, J ) 1.6 Hz, 1H), 5.06 (d, J ) 11.3 Hz, 1H), 4.79 (d, J
) 10.9 Hz, 1H), 4.71 (d, J ) 12.1 Hz, 1H), 4.61 (d, J ) 3.6 Hz, 1H),
4.60 (d, J ) 12.2 Hz, 1H), 4.60 (d, J ) 11.3 Hz, 1H), 4.55 (d, J )
12.1 Hz, 1H), 4.53 (d, J ) 12.1 Hz, 1H), 4.46 (s, 2H), 4.44 (d, J )
12.1 Hz, 1H), 4.41 (d, J ) 10.9 Hz, 1H), 4.36 (d, J ) 12.2 Hz, 1H),
3.89-3.84 (m, 2H), 3.72-3.64 (m, 6H), 3.58 (dd, J ) 10.5, 3.0 Hz,
1H), 3.52 (dd, J ) 9.7, 3.5 Hz, 1H), 3.44 (d, J ) 10.1 Hz, 1H), 3.39
(s, 3H), 2.22 (m, 1H), 0.81 (d, J ) 7.3 Hz, 3H). 13C NMR (125 MHz)
δ: 138.7, 138.6, 138.3, 137.9, 128.4, 128.3, 128.2, 128.1, 127.9, 127.8,
127.6, 127.5, 127.4, 127.4, 127.3, 127.1, 104.2 (J ) 169.9 Hz), 97.6
Benzyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-galactopyrano-
side (21). Rf ) 0.48. R-Anomer. [R]25D +99.0 (c 1.9, CHCl3). 1H NMR
(250 MHz) δ: 7.37-7.22 (m, 20H), 4.89 (d, J ) 11.6 Hz, 1H), 4.80
(d, J ) 3.5 Hz, 1H), 4.70 (d, J ) 11.6 Hz, 1H), 4.68 (d, J ) 12.2 Hz,
1H), 4.57 (d, J ) 11.6 Hz, 1H), 4.51 (d, J ) 11.8 Hz, 1H), 4.49 (d, J
) 11.6 Hz, 1H), 4.45 (d, J ) 12.2 Hz, 1H), 4.43 (d, J ) 11.8 Hz, 1H),
3.99 (d, J ) 6.2 Hz, 1H), 3.94 (d, J ) 6.2 Hz, 1H), 3.66-3.53 (m,
3H), 2.45 (m, 1H), 1.06 (d, J ) 6.9 Hz, 3H). 13C NMR (62.5 MHz) δ:
138.7, 138.2, 137.9, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7,

9582 J. Am. Chem. Soc., Vol. 122, No. 40, 2000
Beyer et al.
(J ) 167.7 Hz), 82.1, 80.1, 79.4, 76.7, 75.3, 74.6, 74.0, 73.3, 73.2,
73.1, 72.3, 71.0, 69.8, 69.5, 69.1, 55.2, 37.4, 11.2. Anal. Calcd for
C56H62O10: C, 75.14; H, 6.98. Found: C, 75.40; H, 7.07.
117.7, 114.5, 101.1 (J ) 167 Hz), 79.5, 74.9, 74.1, 73.3, 71.8, 71.3,
69.1, 55.6, 37.0, 11.2. Anal. Calcd for C35H38O6: C, 75.79; H, 6.90.
Found: C, 75.55; H, 6.81.
Methyl 2,3,4-Tri-O-benzyl-6-O-(3,4-di-O-benzyl-2-deoxy-2-C-
2-(3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-â-D-mannopyranosyl)-
3,5-dimethoxyphenol (38). Rf ) 0.32. [R]25 +18.8 (c 2.1, CHCl3).
methyl-r-L-rhamnopyranosyl)-r-D-glucopyranoside (34). Rf ) 0.29.
D
1
[R]25 -1.79 (c 1.8, CHCl3). H NMR (500 MHz) δ: 7.24-7.39 (m,
1H NMR (250 MHz) δ: 8.90 (s, 1H), 7.40-7.21 (m, 15H), 6.09 (d, J
) 2.3 Hz, 1H), 6.00 (d, J ) 2.3 Hz, 1H), 5.06 (d, J ) 2.2 Hz, 1H),
4.92 (d, J ) 10.9 Hz, 1H), 4.70 (d, J ) 11.6 Hz, 1H), 4.61 (d, J )
12.0 Hz, 1H), 4.59 (d, J ) 11.6 Hz, 1H), 4.50 (d, J ) 10.9 Hz, 1H),
4.47 (d, J ) 12.0 Hz, 1H), 3.93 (t, J ) 9.5 Hz, 1H), 3.82 (dd, J ) 9.5,
4.8 Hz, 1H), 3.77 (s, 3H), 3.75 (m, 1H), 3.74 (s, 3H), 3.69 (dd, J )
10.3, 2.4 Hz, 1H), 3.51 (dd, J ) 9.5, 2.4 Hz, 1H), 2.50 (m, 1H), 1.01
(d, J ) 7.3 Hz, 3H). 13C NMR (62.5 MHz) δ: 160.4, 158.1, 156.6,
138.4, 137.9, 128.3, 128.2, 127.9, 127.7, 127.5, 127.4, 103.8, 94.1,
90.4, 83.2, 79.1, 78.2, 75.0, 73.2, 73.1, 70.6, 68.2, 55.3, 55.1, 36.7,
6.9. Stereochemistry at C-1 was assigned by NOE experiment. NOE’s
were observed between H-1 and H-3 as well as H-1 and H-5. Anal.
Calcd for C36H40O7: C, 73.95; H, 6.90. Found: C, 74.10; H, 7.05.
2-(3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-mannopyranosyl)-
D
25H), 5.00 (d, J ) 10.9 Hz, 1H), 4.90 (d, J ) 10.5 Hz, 1H), 4.87 (d,
J ) 10.5 Hz, 1H), 4.82 (d, J ) 10.5 Hz, 1H), 4.79 (d, J ) 11.6 Hz,
1H), 4.68 (d, J ) 12.1 Hz, 1H), 4.60 (d, J ) 12.1 Hz, 1H), 4.59 (s,
1H), 4.59 (d, J ) 10.5 Hz, 1H), 4.54 (d, J ) 11.6 Hz, 1H), 4.53 (d, J
) 10.9 Hz, 1H), 4.49 (bs, 1H), 3.99 (t, J ) 9.2 Hz, 1H), 3.93 (dd, J )
9.2, 5.3 Hz, 1H), 3.81 (dd, J ) 10.7, 1.6 Hz, 1H), 3.71-3.75 (m, 2H),
3.51 (dd, J ) 9.6, 3.6 Hz, 1H), 3.44 (t, J ) 9.6 Hz, 1H), 3.43 (dd, J
) 10.7, 5.5 Hz, 1H), 3.34 (s, 3H), 3.26 (t, J ) 9.2 Hz, 1H), 2.28 (m,
1H), 1.25 (d, J ) 6.2 Hz, 3H), 1.02 (d, J ) 7.3 Hz, 3H). 13C NMR
(125 MHz) δ: 138.6, 138.6, 138.2, 138.1, 128.4, 128.3, 128.2, 128.0,
127.9, 127.8, 127.6, 127.6, 127.5, 127.4, 102.1 (J ) 166 Hz), 97.7 (J
) 168 Hz), 82.0, 80.2, 80.0, 79.0, 77.9, 75.7, 75.1, 74.9, 73.2, 71.0,
69.8, 67.5, 65.9, 54.9, 36.9, 18.1, 11.2. Anal. Calcd for C49H56O9: C,
74.60; H, 7.15. Found: C, 74.30; H, 7.09.
3,4,5-trimethoxyphenol (39). R-Anomer. Rf ) 0.23. [R]25 -13.8 (c
D
1.4, CHCl3). 1H NMR (500 MHz) δ: 8.01 (s, 1H, exchanges with D2O),
7.39-7.23 (m, 15H), 6.27 (s, 1H), 5.11 (d, J ) 11.1 Hz, 1H), 4.65 (d,
J ) 12.1 Hz, 1H), 4.53 (d, J ) 11.7 Hz, 1H), 4.53 (d, J ) 11.1 Hz,
1H), 4.52 (s, 1H), 4.48 (d, J ) 12.1 Hz, 1H), 4.43 (d, J ) 11.7 Hz,
1H), 4.39 (t, J ) 6.8 Hz, 1H), 4.03 (dd, J ) 10.1, 7.6 Hz, 1H), 3.85 (s,
3H), 3.81 (s, 3H), 3.78 (m, 1H), 3.77 (s, 3H), 3.66 (dd, J ) 3.2, 0.7
Hz, 1H), 3.61 (t, J ) 2.6 Hz, 1H), 2.58 (m, 1H), 0.78 (d, J ) 7.0 Hz,
3H). 13C NMR (125 MHz) δ: 153.4, 152.6, 151.2, 138.1, 137.9, 137.9,
134.7, 128.4, 128.2, 127.6, 127.5, 127.5, 127.4, 110.5, 97.0, 76.7, 75.1,
73.2, 72.7, 71.4, 71.2, 68.7, 67.1, 60.9, 60.8, 55.7, 33.0, 13.5. Anal.
Calcd for C37H42O8: C, 72.29; H, 6.89. Found: C, 72.07; H, 6.76.
â-Anomer. Rf ) 0.27. [R]25D +18.9 (c 5.2, CHCl3). 1H NMR (500 MHz)
δ: 8.55 (s, 1H, exchanges with D2O), 7.30-7.12 (m, 15H), 6.14 (s,
1H), 4.90 (d, J ) 2.2 Hz, 1H), 4.83 (d, J ) 10.9 Hz, 1H), 4.62 (d, J
) 11.6 Hz, 1H), 4.50 (d, J ) 12.1 Hz, 1H), 4.50 (d, J ) 11.6 Hz, 1H),
4.41 (d, J ) 10.9 Hz, 1H), 4.37 (d, J ) 12.1 Hz, 1H), 3.82 (t, J ) 9.4
Hz, 1H), 3.77 (s, 3H), 3.74 (dd, J ) 9.4, 4.9 Hz, 1H), 3.72 (s, 3H),
3.69 (s, 3H), 3.63 (dd, J ) 10.3, 3.0 Hz, 1H), 3.59 (dd, J ) 10.3, 2.2
Hz, 1H), 3.43 (dt, J ) 9.4, 2.6 Hz, 1H), 2.39 (m, 1H), 0.92 (d, J ) 7.3
Hz, 3H). 13C NMR (125 MHz) δ: 153.2, 152.7, 149.6, 138.3, 138.3,
137.9, 134.6, 128.3, 128.2, 128.2, 127.8, 127.5, 127.5, 127.4, 107.9,
96.6, 83.2, 79.1, 78.6, 75.0, 73.2, 73.0, 70.6, 68.2, 60.7, 60.7, 55.6,
37.9, 6.7. Stereochemistry at C-1 for this â-anomer has been assigned
by NOE experiment. NOE’s were observed between H-1 and H-3 as
well as between H-1 and H-5. Anal. Calcd for C37H42O8: C, 72.29; H,
6.89. Found: C, 72.44; H, 7.06.
Methyl 2,3,4-Tri-O-benzyl-6-O-(3,4,6-tri-O-benzyl-2-deoxy-2-C-
methyl-D-glucopyranosyl)-r-D-glucopyranoside (35). Rf ) 0.19.
R-Anomer. [R]25 +79.6 (c 1.3, CHCl3). Mp 88-89 °C (hexane/
D
1
EtOAc). H NMR (500 MHz) δ: 7.37-7.14 (m, 30H), 4.97 (d, J )
10.8 Hz, 1H), 4.91 (d, J ) 11.0 Hz, 1H), 4.75-4.85 (m, 5H), 4.68-
4.57 (m, 5H), 4.50 (d, J ) 11.0 Hz, 1H), 4.45 (d, J ) 12.1 Hz, 1H),
3.99 (t, J ) 9.3 Hz, 1H), 3.79-3.56 (m, 8H), 3.49 (dd, J ) 9.6, 2.8
Hz, 1H), 3.47 (dd, J ) 9.6, 2.8 Hz, 1H), 3.35 (s, 3H), 1.90 (m, 1H),
1.01 (d, J ) 6.8 Hz, 3H). 13C NMR (125 MHz) δ: 138.7, 138.6, 138.5,
138.2, 138.1, 138.1, 128.4, 128.4, 128.3, 128.3, 128.1, 128.0, 127.9,
127.9, 127.8, 127.7, 127.6, 127.6, 127.5, 127.5, 101.3 (J ) 169.0 Hz),
97.8 (J ) 168.0 Hz), 82.4, 82.1, 80.2, 79.4, 78.0, 75.8, 75.2, 75.0,
74.7, 73.4, 73.3, 71.1, 70.2, 68.8, 65.8, 55.0, 41.2, 12.9. Anal. Calcd
for C56H62O10: C, 75.14; H, 6.98. Found: C, 74.92; H, 6.93. â-Anomer.
1
[R]25 +13.2 (c 1.3, CHCl3). Mp 172-174 °C (hexane/EtOAc). H
D
NMR (500 MHz) δ: 7.36-7.18 (m, 30H), 4.97 (d, J ) 10.8 Hz, 1H),
4.90 (d, J ) 11.1 Hz, 1H), 4.85 (d, J ) 11.0 Hz, 1H), 4.79 (d, J )
10.8 Hz, 1H), 4.78 (d, J ) 11.5 Hz, 2H), 4.65 (d, J ) 12.2 Hz, 1H),
4.63-4.53 (m, 7H), 4.14 (dd, J ) 10.8, 1.8 Hz, 1H), 4.05 (d, J ) 8.6
Hz, 1H), 3.99 (t, J ) 9.3 Hz, 1H), 3.77 (m, 1H), 3.74 (dd, J ) 10.8,
2.8 Hz, 1H), 3.68 (dd, J ) 5.0, 10.8 Hz, 1H), 3.64 (dd, J ) 10.8, 4.2
Hz, 1H), 3.57-3.51 (m, 2H), 3.44 (m, 1H), 3.37 (s, 3H), 3.20 (dd, J )
10.7, 8.9 Hz, 1H); 1.85 (m, 1H), 1.04 (d, J ) 6.5 Hz, 3H). 13C NMR
(125 MHz) δ: 138.7, 138.4, 138.2, 128.4, 128.3, 128.1, 128.1, 127.9,
127.9, 127.7, 127.7, 127.6, 127.6, 127.5, 104.8 (J ) 156.0 Hz), 98.1
(J ) 165.0 Hz), 85.1, 82.2, 79.8, 79.3, 77.8, 75.8, 75.4, 75.1, 74.9,
74.7, 73.4, 73.4, 69.8, 69.3, 67.8, 55.1, 42.5, 12.7. Anal. Calcd for
C56H62O10: C, 75.14; H, 6.98. Found: C, 75.34; H, 7.05.
Benzyl 3,5-Di-O-benzyl-2-deoxy-2-C-(ethoxycarbonylmethyl)-D-
xylofuranoside (41). The reaction was carried out in toluene at 70 °C
for 1.5 h. R-Anomer. Rf ) 0.46. [R]25D +89.9 (c 1.0, CHCl3). 1H NMR
(500 MHz) δ: 7.33-7.23 (m, 15H), 5.29 (d, J ) 5.1 Hz, 1H), 4.75 (d,
J ) 12.0 Hz, 1H), 4.63 (d, J ) 12.0 Hz, 1H), 4.53 (d, J ) 12.0 Hz,
1H), 4.51 (bs, 2H), 4.45 (d, J ) 12.0 Hz, 1H), 4.37 (dd, J ) 11.1, 6.4
Hz, 1H), 4.05 (q, J ) 7.1 Hz, 2H), 4.01 (t, J ) 6.4 Hz, 1H), 3.75 (dd,
J ) 10.4, 4.7 Hz, 1H), 3.64 (dd, J ) 10.4, 6.5 Hz, 1H), 2.75 (m, 1H),
2.65 (dd, J ) 16.4, 10.0 Hz, 1H), 2.47 (dd, J ) 16.4, 5.5 Hz, 1H),
1.18 (t, J ) 7.1 Hz, 3H). 13C NMR (62.5 MHz) δ: 172.2, 138.1, 138.0,
137.8, 128.4, 128.3, 128.2, 128.1, 127.7, 127.6, 127.5, 127.4, 127.3,
101.7, 82.2, 77.2, 73.4, 72.7, 69.3, 69.2, 60.3, 45.8, 32.2, 14.0. Anal.
Calcd for C30H34O6: C, 73.45; H, 6.99. Found: C, 73.24; H, 6.78.
â-Anomer. Rf ) 0.29. [R]25D -55.2 (c 1.1, CHCl3). 1H NMR (500 MHz)
δ: 7.33-7.21 (m, 15H), 4.94 (d, J ) 1.8 Hz, 1H), 4.80 (d, J ) 12.0
Hz, 1H), 4.65 (d, J ) 12.0 Hz, 1H), 4.58 (d, J ) 12.0 Hz, 1H), 4.52
(d, J ) 12.0 Hz, 1H), 4.49 (d, J ) 12.0 Hz, 1H), 4.48 (d, J ) 12.0 Hz,
1H), 4.39 (bq, J ) 5.8 Hz, 1H), 4.09 (q, J ) 7.1 Hz, 2H), 3.90 (dd, J
) 5.8, 3.0 Hz, 1H), 3.82 (dd, J ) 10.3, 4.6 Hz, 1H), 3.76 (dd, J )
10.3, 7.2 Hz, 1H), 2.84 (m, 1H), 2.39 (dd, J ) 15.8, 6.8 Hz, 1H), 2.29
(dd, J ) 15.8, 8.7 Hz, 1H), 1.20 (t, J ) 7.1 Hz, 3H). 13C NMR (125
MHz, CDCl3) δ: 171.3, 138.2, 138.1, 138.0, 128.3, 128.2, 128.1, 127.7,
127.6, 127.5, 127.4, 127.3, 106.4, 81.8, 80.2, 73.4, 71.4, 70.1, 69.1,
60.6, 46.9, 34.7, 14.0. Stereochemistry at C-1 for this â-anomer has
been assigned by NOE experiment. NOE’s were observed between H-1
Phenyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-D-mannopyrano-
1
side (36). Rf ) 0.51. R-Anomer. H NMR (500 MHz) δ: 7.42-7.00
(m, 20H), 5.47 (d, J ) 1.3 Hz, 1H), 4.87 (d, J ) 10.8 Hz, 1H), 4.72
(d, J ) 11.6 Hz, 1H), 4.65 (d, J ) 11.6 Hz, 1H), 4.63 (d, J ) 12.0 Hz,
1H), 4.48 (d, J ) 10.8 Hz, 1H), 4.42 (d, J ) 12.0 Hz, 1H), 4.23 (dd,
J ) 8.5, 5.2 Hz, 1H), 3.92-3.82 (m, 2H), 3.76 (dd, J ) 10.8, 3.6 Hz,
1H), 3.62 (dd, J ) 10.8, 1.8 Hz, 1H), 2.61 (m, 1H), 1.19 (d, J ) 7.3
Hz, 3H). 13C NMR (125 MHz) δ: 156.5, 138.6, 138.4, 138.1, 129.3,
128.3, 128.2, 128.2, 128.2, 127.9, 127.8, 127.6, 127.6, 127.5, 127.5,
127.4, 121.8, 116.3, 100.1 (J ) 168.0 Hz), 79.4, 74.8, 73.9, 73.2, 71.8,
71.2, 68.8, 36.8, 11.1. â-Anomer. 13C NMR (125 MHz) δ: 99.6 (J )
158.0 Hz). Anal. Calcd for C34H36O5: C, 77.84; H, 6.92. Found: C,
78.08; H, 7.21.
p-Methoxyphenyl 3,4,6-Tri-O-benzyl-2-deoxy-2-C-methyl-r-D-
1
mannopyranoside (37). Rf ) 0.41. [R]25 +95.1 (c 1.7, CHCl3). H
D
NMR (500 MHz) δ: 7.41-7.17 (m, 15H), 7.01 (d, J ) 9.1 Hz, 2H),
6.79 (d, J ) 9.1 Hz, 2H), 5.35 (d, J ) 1.1 Hz, 1H), 4.87 (d, J ) 10.8
Hz, 1H), 4.71 (d, J ) 11.5 Hz, 1H), 4.63 (d, J ) 11.5 Hz, 1H), 4.62
(d, J ) 12.0 Hz, 1H), 4.48 (d, J ) 10.8 Hz, 1H), 4.43 (d, J ) 12.0 Hz,
1H), 4.21 (dd, J ) 8.4, 5.2 Hz, 1H), 3.87 (m, 2H), 3.77 (dd, J ) 10.8,
3.7 Hz, 1H), 3.76 (s, 3H), 3.64 (dd, J ) 10.8, 1.7 Hz, 1H), 2.60 (m,
1H), 1.18 (d, J ) 7.3 Hz, 3H). 13C NMR (62 MHz) δ: 154.7, 150.6,
138.7, 138.6, 138.3, 128.4, 128.3, 128.3, 127.9, 127.7, 127.6, 127.5,

Pt-Catalyzed Ring Opening of 1,2-Cyclopropanated Sugars
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9583
and H-3 as well as between H-1 and H-4. Anal. Calcd for C30H34O6:
C, 73.45; H, 6.99. Found: C, 73.31; H, 6.88.
(62.5 MHz) δ: 138.4, 138.3, 138.1, 128.1, 128.1, 128.0, 127.6, 127.5,
127.4, 127.3, 127.3, 127.2, 98.8, 73.3, 72.9, 70.8, 70.5, 69.1, 68.4, 33.9,
32.0, 16.3.
General Procedure for Ferrier-Type Rearrangement. The cy-
clopropane (500 mg, 1.16 mmol) and benzyl alcohol (240 µL, 2.32
mmol) were dissolved in CH2Cl2 (5 mL) followed by addition of PdCl2-
(PhCN)2 (44 mg, 0.118 mmol). The mixture was stirred at room
temperature under an atmosphere of nitrogen for 48 h. After removal
of the solvent in vacuo, the crude mixture was purified by flash
chromatography.
Benzyl 4,6-Di-O-benzyl-2,3-dideoxy-2-C-methyl-r-D-threo-hex-2-
enopyranoside (46). Rf ) 0.48. [R]25D -45.7 (c 0.6, CHCl3). 1H NMR
(250 MHz) δ: 7.40-7.23 (m, 15H), 5.81 (d, J ) 5.2 Hz, 1H), 4.95 (s,
1H), 4.83 (d, J ) 11.8 Hz, 1H), 4.66-4.58 (m, 4H), 4.53 (d, J ) 12.0
Hz, 1H), 4.26 (ddd, J ) 6.8, 5.7, 2.6 Hz, 1H), 3.82 (dd, J ) 10.0, 5.7
Hz, 1H), 3.77-3.69 (m, 2H), 1.79 (s, 3H). 13C NMR (62.5 MHz) δ:
138.6, 138.4, 138.0, 132.1, 128.3, 128.1, 127.7, 127.6, 127.5, 127.3,
121.7, 96.4, 73.4, 70.7, 69.7, 69.7, 69.4, 68.2, 19.2. Anal. Calcd for
C28H30O4: C, 78.11; H, 7.02. Found: C, 77.85; H, 7.18.
Hydrogenation as described above gave 48 as the major product:
Rf ) 0.58. 1H NMR (500 MHz) δ: 7.41-7.25 (m, 15H), 4.80 (d, J )
11.8 Hz, 1H), 4.68 (d, J ) 11.8 Hz, 1H), 4.67 (d, J ) 2.5 Hz, 1H),
4.62 (d, J ) 11.8 Hz, 1H), 4.54 (d, J ) 11.8 Hz, 1H), 4.53 (d, J )
11.8, 1H), 4.40 (d, J ) 11.8 Hz, 1H), 4.18 (dt, J ) 6.0, 2.5 Hz, 1H),
3.73 (dd, J ) 10.1, 5.8 Hz, 1H), 3.71 (dd, J ) 10.1, 6.5 Hz, 1H), 3.61
(bq, J ) 4.0 Hz, 1H), 2.00 (dt, J ) 13.9, 4.7 Hz, 1H), 1.85 (m, 1H),
1.78 (dt, J ) 13.9, 4.4 Hz, 1H), 1.20 (d, J ) 7.3 Hz, 3H). 13C NMR
(62.5 MHz) δ: 138.5, 138.4, 137.5, 128.0, 127.7, 127.5, 127.3, 127.2,
127.1, 101.1 (J ) 164.9 Hz), 73.1, 72.0, 70.4, 69.6, 69.4, 68.6, 31.2,
27.7, 18.2.
Benzyl 4,6-Di-O-benzyl-2,3-dideoxy-2-C-methyl-D-erythro-hex-2-
1
enopyranoside (45). Rf ) 0.49. R-Anomer. H NMR (250 MHz) δ:
7.40-7.20 (m, 15H), 5.74 (bs, 1H), 4.89 (s, 1H), 4.82 (d, J ) 12.0 Hz,
1H), 4.66-4.58 (m, 3H), 4.52 (d, J ) 12.2 Hz, 1H), 4.43 (d, J ) 11.5
Hz, 1H), 4.14 (d, J ) 9.4 Hz, 1H), 3.99 (ddd, J ) 9.4, 4.2, 2.2 Hz,
1H), 3.71 (dd, J ) 10.8, 4.2 Hz, 1H), 3.66 (dd, J ) 10.8, 2.2 Hz, 1H),
1.75 (s, 3H). 13C NMR (62.5 MHz) δ: 138.2, 134.5, 128.2, 127.8,
127.7, 127.5, 127.4, 124.5, 96.8, 73.3, 70.8, 70.7, 69.9, 69.3, 68.9, 18.5.
Anal. Calcd for C28H30O4: C, 78.11; H, 7.02. Found: C, 77.99; H,
7.02.
Hydrogenation at room temperature and 1 atm over Pd/C in EtOAc
containing 1 equiv of Et3N gave 47 as the major product: Rf ) 0.49.
1H NMR (500 MHz) δ: 7.39-7.22 (m, 15H), 4.75 (d, J ) 12.2 Hz,
1H), 4.70 (d, J ) 3.2 Hz, 1H), 4.67 (d, J ) 12.2 Hz, 1H), 4.60 (d, J
) 11.4 Hz, 1H), 4.55 (d, J ) 12.2 Hz, 1H), 4.50 (d, J ) 12.2 Hz, 1H)
4.40 (d, J ) 11.4 Hz, 1H), 3.83-3.68 (m, 3H), 3.58 (ddd, J ) 11.0,
10.4, 4.7 Hz, 1H), 2.00 (ddd, J ) 11.9, 4.7, 4.2 Hz, 1H), 1.90 (m, 1H),
1.64 (dt, J ) 11.9, 11.0 Hz, 1H), 0.97 (d, J ) 6.9 Hz, 3H). 13C NMR
Acknowledgment. We thank the Danish Natural Science
Research Council for financial support.
JA001558+