Cationic palladium(II)-catalyzed stereoselective glycosylation with glycosyl trichloroacetimidates

Article abstract of DOI:10.1021/jo702436p

(Chemical Equation Presented) The development of a new method for stereoselective glycosylation with glycosyl trichloroacetimidate donors employing cationic palladium(II), Pd(CH₃CN)₄(BF ₄)₂, is described. This p

Full text of DOI:10.1021/jo702436p

Cationic Palladium(II)-Catalyzed Stereoselective Glycosylation with
Glycosyl Trichloroacetimidates
Jaemoon Yang, Colleen Cooper-Vanosdell, Enoch A. Mensah, and Hien M. Nguyen*
Department of Chemistry and Biochemistry, Montana State UniVersity, Bozeman, Montana 59717
hmnguyen@chemistry.montana.edu
ReceiVed NoVember 20, 2007
The development of a new method for stereoselective glycosylation with glycosyl trichloroacetimidate
donors employing cationic palladium(II), Pd(CH3CN)4(BF4)2, is described. This process employs
Pd(CH3CN)4(BF4)2 as an efficient activator, providing access to a variety of disaccharides and glyco-
peptides. This reaction is highly stereoselective and proceeds under mild conditions with low catalyst
loading. Interestingly, this palladium catalysis directs â-glucosylations in the absence of classical
neighboring group participation.
Introduction
anhydrous and low temperature (up to -78 °C) conditions,
especially if glycosyl donors and acceptors are incorporated with
acid-labile protecting groups. Additionally, high catalyst loading
is often required since these Lewis acids are oxophilic. This
has resulted in the continued development of activating reagents
and conditions for the activation of trichloroacetimidates. It
begins with the use of stoichiometric amounts of AgOTf as a
promoter to provide glycosides with excellent yields.8 Two other
improvements utilizing LiClO4 and LiOTf as promoters have
been described. The first method requires a large excess of
LiClO4.9 The second method employs a catalytic amount of
LiOTf to provide the desired glycoside products as a mixture
of R- and â-isomers.10 Recently, several moisture-stable activat-
ing reagents such as I2/Et3SiH,11 HClO4/silica,12 4 Å acid-
washed molecular sieves,13 and Amberlyst 1514 have been shown
to successfully activate glycosyl trichloroacetimidates.
Since the first paper on Schmidt’s glycosylation method was
published in 1980,1 trichloroacetimidates have been among the
most widely used glycosyl donors. Their popularity comes from
their relative ease of synthesis by base-catalyzed addition of
trichloroacetonitrile to the anomeric hydroxy group.2 The
glycosyl trichloroacetimidates are often formed in high yield
with excellent anomeric selectivity. The glycosyl trichloroace-
timidates are generally activated with strong and moisture-
sensitive Lewis acids such as BF3‚OEt2,1a,3 TMSOTf,2a,4 TB-
SOTf,5 Tf2O,6 and ZnBr.7 These Lewis acids operate under
* To whom correspondence should be addressed. Tel: 406-994-7753. Fax:
406-994-5407.
(1) (a) Schmidt, R. R.; Michel, J. Angew. Chem., Int. Ed. 1980, 19, 731-
732. For a comprehensive review, see: (b) Schmidt, R. R.; Kinzy, W. AdV.
Carbohydr. Chem. Biochem. 1994, 50, 21-123. (c) Schmidt, R. R.; Jung,
K.-H. AdV. Carbohydr. Chem. Biochem. 2000, 5-59.
(2) (a) Schmidt, R. R. Angew. Chem., Int. Ed. 1986, 25, 212-235. (b)
Hoos, R.; Huixin, Vasella, J., A.; Weiss, P. HelV. Chim. Acta 1996, 79,
1757-1784. (c) Patil, V. J. Tetrahedron Lett. 1996, 37, 1481-1484.
(3) (a) Schmidt, R. R.; Michel, J. J. Carbohydr. Chem. 1985, 4, 141-
169. (b) Zimmermann, P.; Bommer, R.; Ba¨r, T.; Schmidt, R. R. J.
Carbohydr. Chem. 1988, 7, 435-452.
(4) (a) Schmidt, R. R.; Behrendt, M.; Toepfer, A. Synlett 1990, 694-
696. (b) Schaubach, R.; Hemberger, J.; Kinzy, W. Liebigs. Ann. Chem.
1991, 607-614. (c) Paulsen, H.; Wilkens, R.; Reck, F.; Brockhausen, I.
Liebigs. Ann. Chem. 1992, 1303-1313. (d) Kulkarni, S. S.; Hung, S.-C.
Lett. Org. Chem. 2005, 2, 670-677.
(5) Haase, W. C.; Seeberger, P. H. Curr. Org. Chem. 2000, 4, 481-
511.
(6) Dobarro-Rodriguez, A.; Trumtel, M.; Wessel, H. P. J. Carbohydr.
Chem. 1992, 11, 255-263.
(7) Ubran, F. J.; Moore, B. S.; Breitenbach, R. Tetrahedron Lett. 1990,
31, 4421-4424.
We report herein a commercially available cationic Pd(II),
Pd(CH3CN)4(BF4)2, catalyzed stereoselective glycosylation with
(8) Douglas, S. P.; Whitfield, D. M.; Krepinsky, J. J. J. Carbohydr. Chem.
1993, 12, 131-136.
(9) Waldmann, H.; Bo¨hm, Schmid, G., U.; Ro¨ttele, H. Angew. Chem.,
Int. Ed. 1994, 33, 1944-1996.
(10) Lubineau, A.; Drouillat, B. J. Carbohydr. Chem. 1997, 16, 1179-
1186.
(11) Adinolfi, M.; Barone, G.; Iadonisi, A.; Schiattarella, M. Synlett 2002,
269-270.
(12) Mukhopadhyway, B.; Maurer, S. V.; Rudolph, N.; van Well, R.
M.; Russell, D. A.; Field, R. A. J. Org. Chem. 2005, 70, 9059-9062.
(13) (a) Adinolfi, M.; Barone, G.; Iadonisi, A.; Schiattarella, M. Org.
Lett. 2003, 5, 987-989. (b) Adinolfi, M.; Barone, G.; Iadonisi, A.;
Schiattarella, M. J. Org. Chem. 2005, 70, 5316-5319.
(14) Tian, Q.; Zhang, S.; Yu, W.; He, M.-B.; Yang, J.-S. Tetrahedron
2007, 63, 2142-2147.
10.1021/jo702436p CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/10/2008
794
J. Org. Chem. 2008, 73, 794-800

Palladium(II)-Catalyzed StereoselectiVe Glycosylation
TABLE 1. Efficiency of Pd(II) Catalysts in Glycosylationa
TABLE 2. Glycosylation with D-Mannose Donorsa
Pd(II)
(mol %) additive (h)
time yieldb
entry
Pd(II) source
(%)
R/âc
1
2
3
4
Pd(CH3CN)4(BF4)2
Pd(CH3CN)4(BF4)2
Pd(CH3CN)4(BF4)2
Pd(PhCN)2Cl2
5
3
5
5
none
3
5
4
8
85
70
83
R only
R only
R only
none
DTBPd
none
<5
a All reactions were carried out in CH2Cl2 (0.15 M) for 3-8 h with 1.3
equiv of BnOH. b Isolated yield. c 1H NMR ratio. d DTBP )2,6-di-tert-
butylpyridine.
glycosyl trichloroacetimidate donors. The cationic palladium(II)
species acts a Lewis acid catalyst because it has vacant
coordination sites.15 Pd(CH3CN)4(BF4)2 is air- and moisture-
stable and easy to handle; thus, it can be used over a wide range
of temperatures and conditions. As compared with neutral Pd(II)
species, cationic Pd(II) catalyst exhibits higher activity.15
Results and Discussion
The efficacy of Pd(CH3CN)4(BF4)2 as a glycosylation activa-
tor was first investigated with 2,3:4,6-bis(di-O-isopropylidene)-
R-D-mannopyranosyl donor 1 (1 equiv) and freshly distilled
benzyl alcohol (1.3 equiv) in the presence of 5 mol % of
Pd(CH3CN)4(BF4)2 at 25 °C for 3 h in freshly distilled CH2Cl2
(Table 1, entry 1). The desired glycoside 2 was isolated in 85%
yield exclusively as R-anomer. The â-anomer was not detected
by 1H NMR. To determine if HBF4, which may generate from
the cationic palladium catalyst, is the source of catalysis the
glycosylation of benzyl alcohol was performed with trichloro-
acetimidate donor 1 (entry 3) in the presence of 2,6-di-tert-
butylpyridine (20 mol %) as an acid scavenger. In the event,
the formation of the desired glycoside 2 from 1 proceeded in
comparable yield to that of entry 1. As a control experiment, a
similar glycosylation was attempted with neutral Pd(II) species,
Pd(PhCN)2Cl2 (entry 4); however, less than 5% yield of 2 was
detected. These results clearly suggest that Pd(CH3CN)4(BF4)2
is responsible for D-mannopyranosyl trichloroacetimidate 1
activation, and it does so with the formation of 2 in good yield.
With optimized reaction conditions in hand, we set out to
define the scope of cationic Pd(II)-catalyzed glycosylation. A
number of nucleophilic acceptors, incorporating a variety of
protecting groups such as isopropylidene ketals, ester function-
ality, and tert-butyl carbamate group, were examined with
glycosyl donor 1 (Table 2, entries 1-4). With the use of primary
and secondary hydroxyl of carbohydrate nucleophiles 4 and 5,
disaccharides 10 and 11 were isolated in 93% and 94% yield,
respectively (entries 1 and 2). Notably, the efficiency of the
reaction is illustrated by the ability to provide 10 and 11
exclusively as R-anomers. When Boc-Ser-OMe (6) was probed
as potential nucleophile (entry 3), glycopeptide 12 was obtained
in 90% yield exclusively as R-anomer. When 2,3,4,6-tetra-O-
benzyl-R-D-mannopyranosyl trichloroacetimidate 3 was em-
ployed as glycosyl donor, disaccharides 14-16 were isolated
a All reactions were carried out in CH2Cl2 (0.15 M) for 3-5 h with 1.3
equiv of acceptors and 5 mol % of Pd(CH3CN)4(BF4)2. b Isolated yield.
c 1H NMR ratio.
in excellent yields nearly exclusively as R-anomers (Table 1,
entries 5-7). Compared to other methods,16 higher yield and
better R-selectivity were observed with the cationic palla-
dium(II)-catalyzed glycosylation with D-mannose donors.
Since the cationic palladium(II)-catalyzed reaction showed
excellent R-selectivity with mannose donors at the newly formed
glycosidic bond, we examined this chemistry with 2,3,4,6-tetra-
O-benzyl-D-glycopyranosyl trichloroacetimidate donor 17 (Table
3). Compared to other glycosylation methods,17 significantly
(16) (a) Chretien, F.; Chapleur, Y.; Castro, B.; Gross, B. J. Chem. Soc.,
Perkin Trans. 1 1980, 381-384. (b) Dasgupta, F.; Garegg, P. Carbohydr.
Res. 1990, 202, 225-238. (c) Suzuki, K.; Maeta, H.; Suzuki, T.; Matsumoto,
T. Tetrahedron Lett. 1989, 30, 6879-6882.
(15) Mkiami, K.; Hatano, M.; Akiyama, K. Top. Organomet. Chem. 2005,
14, 270-321 and references therein.
J. Org. Chem, Vol. 73, No. 3, 2008 795

Yang et al.
TABLE 5. Glycosylation with C(2)-Acyl Glycosyl Donorsa
TABLE 3. Glycosylation with D-Glucose Donora
a All reactions were carried out in CH2Cl2 (0.15 M) with 1.3 equiv of
acceptors and 5 mol % of Pd(CH3CN)4(BF4)2. b Isolated Yield. c 1H NMR
ratio. d Dihydrocholesterol.
TABLE 4. Glycosylation with L-Rhamnose Donora
a All reactions were carried out in CH2Cl2 (0.15 M) with 1.3 equiv of
acceptors and 5 mol % of Pd(CH3CN)4(BF4)2. b Isolated yield. c 1H NMR
ratio. d Dihydrocholesterol
a All reactions were carried out in CH2Cl2 (0.15 M) with 1.3 equiv of
acceptors and 5 mol % of Pd(CH3CN)4(BF4)2. b Isolated Yield. c 1H NMR
ratio.
chemistry could be applied to the â-glucosylations in the absence
of neighboring group participation. It has been reported that
glycosylation of perbenzylated-D-glycopyranosyl n-pentenyl
donor with nucleophilic acceptor 4 provided disaccharide 20
in 80% yield with R/â ) 1:1.4.17a Coupling of perbenzylated-
D-glycopyranosyl phosphite donor with glycosyl acceptor 19
has been reported to provide disaccharide 22 in 89% yield with
better â-selectivity was observed when the glycosylations of
nucleophiles 4, 8, and 19 were performed with trichloroace-
timidate 17. Disaccharides 20-22 were isolated in good yields
with good â-selectivity (Table 3). These results were encourag-
ing because they clearly showed that this cationic palladium
R/â ) 1:1.17b
.
On the other hand, use of R-L-rhamnopyranosyl trichloro-
acetimidate 18 as glycosyl donor provided disaccharides
23-26 in good yields exclusively as R-anomers (Table 4). These
results are encouraging because they clearly showed that this
cationic palladium chemistry could be applied to the ether
(17) (a) Houdier, S.; Vottero, P. J. A. Carbohydr. Res. 1992, 232, 349-
352. (b) Watanabe, Y.; Nakamoto, C.; Yamamoto, T.; Ozaki, S. Tetrahedron
1994, 50, 6523-6536. (c) Yamanoi, T.; Iwai, Y.; Inazu, T. J. Carbohydr.
Chem. 1998, 17, 819-822.
796 J. Org. Chem., Vol. 73, No. 3, 2008

Palladium(II)-Catalyzed StereoselectiVe Glycosylation
FIGURE 1. Cationic Pd(II)-catalyzed stereoselective formation of R-glycosides.
FIGURE 2. Cationic Pd(II)-catalyzed stereoselective formation of â-glycosides.
protecting groups to provide the desired products with excellent
R-selectivity.
loading to provide access to a variety of disaccharides and
glycopeptides in good yields with excellent stereoselectivity at
the anomeric carbon. The advantage of the cationic palladium
catalyst is its ability to direct â-glucosylations in the absence
of classical neighboring group participation.
The remaining glycosyl donors that needed to be tested in
the cationic palladium(II)-catalyzed glycosylation reaction were
the C(2)-acyl protecting group substrates (Table 5). It is expected
that 1,2-trans stereochemical control would be observed at the
newly formed glycosidic bond due to the neighboring group
participation of the C(2)-acyl functionalities.1b Accordingly,
coupling of glycosyl donors 27-29 with a variety of nucleo-
philes provided disaccharides 30-38 in good yields with
excellent â-selectivity.
A possible mechanism for Pd(CH3CN)4(BF4)2-catalyzed ste-
reoselective formation of R-glycosides is outlined in Figure 1.
Cationic palladium(II),18 Pd(CH3CN)4(BF4)2, reversibly coor-
dinates to the imidate nitrogen of 39 to form complex 40 which
subsequently undergoes ionization to generate oxocarbenium
intermediate 41. In the case of D-mannose donors 1 and 3 as
well as L-rhamnose donor 18, oxocarbenium ions such as 41
are important reactive intermediates. Due to the steric and
anomeric effects that are present in D-mannose and L-rhamnose
substrates, axial addition of nucleophiles to 41 should be
favored, thus providing the corresponding R-glycoside products
42.
Experimental Section
General Glycosylation Procedure with Pd(CH3CN)4(BF4)2:
Benzyl 2,3,4,6-Bis(di-O-isopropylidene)-R-D-mannopyranoside
(2). A 10 mL oven-dried Schlenk flask was charged with R-D-
mannopyranosyl trichloroacetimidate 1 (81 mg, 0.20 mmol, 1
equiv), freshly distilled benzyl alcohol (27 µL, 0.26 mmol, 1.3
equiv), and CH2Cl2 (1 mL). Pd(CH3CN)4(BF4)2 (4.4 mg, 0.01 mmol,
5 mol %) was then added to the solution. The resulting mixture
was stirred at 25 °C for 3 h, diluted with benzene (1 mL), and
purified by silica gel flash chromatography (6/1, hexane/ethyl
acetate) to give 2 (59.2 mg, 85%) as a white solid: mp ) 48-49
1
°C; H NMR (CDCl3, 500 MHz) δ 7.35 - 7.26 (m, 5H), 5.05 (s,
1H), 4.77 (dd, J ) 6.0, 3.5 Hz, 1H), 4.64 (d, J ) 6.0 Hz, 1H), 4.62
(d, J ) 11.5 Hz, 1H), 4.47 (d, J ) 11.5 Hz, 1H), 4.39 (ddd, J )
7.5, 6.5, 4.5 Hz, 1H), 4.09 (dd, J ) 9.0, 6.5 Hz, 1H), 3.98 - 3.94
(m, 2H), 1.44 (s, 3H), 1.43 (s, 3H), 1.37 (s, 3H), 1.30 (s, 3H); 13
C
NMR (CDCl3, 125 MHz) δ 137.3, 128.5, 128.0, 127.8, 112.6, 109.2,
105.6, 85.1, 80.4, 76.7, 73.1, 69.1, 66.9, 26.9, 25.8, 25.2, 24.5; IR
(film, cm-1) ν 3031, 2986, 2937, 1455, 1372, 1210, 1077, 1021,
699; HRMS (ESI) calcd for C19H26O6Na [M + Na] 373.1622, found
373.1694.
However, the possible mechanism outlined in Figure 1 is not
consistent with D-glucose donor 17. To rationalize the highly
observed â-selectivity, we speculate that the reaction might
operate via a seven-membered ring intermediate 43 wherein the
C(2)-OBn group of 17 is datively bound to the cationic
palladium catalyst (Figure 2). Formation of 43 directs the
stereochemistry, leading to the formation of â-glycoside 44.
2,3,4,6-Bis(di-O-isopropylidene)-R-D-mannopyranosyl-(1f6)-
1,2,3,4-bis(di-O-isopropylidene)-R-D-galactopyranoside (10). 1H
and 13C NMR of disaccharide 10 have been reported:16a 1H NMR
(CDCl3, 500 MHz) δ 5.50 (d, J ) 5.0 Hz, 1H), 4.99 (s, 1H), 4.75
(dd, J ) 6.0, 3.5 Hz, 1H), 4.60 (d, J ) 6.0 Hz, 1H), 4.56 (dd, J )
8.0, 2.5 Hz, 1H), 4.34 (ddd, J ) 8.0, 6.0, 4.0 Hz, 1H), 4.28 (dd, J
) 5.5, 2.5 Hz), 4.17 (dd, J ) 8.0, 2.0 Hz, 1H), 4.06 (dd, J ) 8.5,
6.0 Hz, 1H), 3.99 (d, J ) 9.0, 4.5 Hz, 1H), 3.93 (dd, J ) 8.5, 4.0
Hz, 1H), 3.91 (dd, J ) 7.0, 2.0 Hz, 1H), 3.70 (dd, J ) 10.5, 6.5
Hz, 1H), 3.60 (dd, J ) 10.5, 7.0 Hz, 1H), 1.50 (s, 3H), 1.42 (s,
3H), 1.41 (s, 3H), 1.40 (s, 3H), 1.34 (s, 3H), 1.30 (s, 3H), 1.29 (s,
Conclusions
In conclusion, we have developed a moisture-tolerant cationic
palladium(II), Pd(CH3CN)4(BF4)2, as an efficient activator of
R-glycosyl trichloroacetimidate donors. The cationic palla-
dium(II)-catalyzed glycosylation reaction is highly stereoselec-
tive and proceeds under mild conditions with low catalyst
3H), 1.28 (s, 3H); 1H NMR matches with the literature report; 13
C
NMR (CDCl3, 125 MHz) δ 112.6, 109.4, 109.3, 108.6, 106.7, 96.3,
85.0, 80.4, 79.5, 73.0, 70.9, 70.6, 70.5, 66.9, 66.1, 66.0, 26.9, 26.0,
25.9, 25.8, 25.2, 24.9, 24.6, 24.5; 13C NMR matches with the
(18) Yang, J.; Mercer, G. J.; Nguyen, H. M. Org. Lett. 2007, 9, 4231-
4234.
J. Org. Chem, Vol. 73, No. 3, 2008 797

Yang et al.
literature report; IR (film, cm-1) ν 2987, 2937, 1373, 1256, 1211,
1165, 1069, 1001, 846.
(m, 3H), 4.58 (dd, J ) 8.0, 2.0 Hz, 1H), 4.52-4.45 (m, 3H), 4.39
(dd, J ) 14.5, 4.5 Hz, 1H), 4.32 (t, J ) 6.0 Hz, 1H), 4.26-4.21
(m, 3H), 4.17 (ddd, J ) 10.5, 6.5, 3.0 Hz, 1H), 4.12 (d, J ) 8.0
Hz, 1H), 4.00-3.96 (m, 2H), 3.89 (dd, J ) 11.0, 5.0 Hz, 1H),
3.78 (d, J ) 11.0 Hz), 1.51 (s, 3H), 1.50 (s, 3H), 1.23 (s, 3H), 1.09
(s, 3H); 13C NMR (C6D6, 125 MHz) δ 139.4, 139.2, 139.1, 138.9,
128.3, 128.2, 128.1, 127.72, 127.7, 127.4, 127.3, 127.23, 127.2,
109.2, 108.2, 97.8, 96.6, 80.6. 75.7, 75.3, 74.8, 73.3, 72.9, 72.7,
71.9, 71.3, 71.1, 70.7, 69.6, 66.1, 65.9, 26.0, 24.6, 24.3; IR (film,
cm-1) ν 2987, 2916, 1496, 1454, 1381, 1371, 1255, 1211, 1167,
1100, 1070, 1027, 1002; HRMS (ESI) calcd for C46H54O11Na [M
+ Na] 805.3558, found 805.3527.
Benzyl 2,3,4,6-tetra-O-benzyl-R-D-mannopyranosyl-(1f4)-
2,3,-di-O-isopropylidene-R-L-rhamnopyranoside (16): 1H NMR
(C6D6, 500 MHz) δ 7.36-7.15 (m, 25H), 7.40-7.36 (m, 4H), 4.96
(s, 1H), 4.92 (s, 1H), 4.87 (d, J ) 11.0 Hz, 1H), 4.75 (d, J ) 12.5
Hz, 1H), 4.72 (d, J ) 12.5 Hz, 1H), 4.68 (d, J ) 12.5 Hz, 1H),
4.66-4.59 (m, 3H), 4.52 (d, J ) 10.5 Hz, 1H), 4.47 (t, J ) 11.5
Hz, 2H), 4.19 (t, J ) 10.0 Hz, 1H), 4.08 (d, J ) 5.5 Hz, 1H),
4.01-3.97 (m, 2H), 3.87 (dd, J ) 10.5, 3.0 Hz, 1H), 3.83 (dd, J )
9.5, 3.0 Hz, 1H), 3.72-3.71 (m, 1H), 3.65 (dd, J ) 11.0, 1.5 Hz,
1H), 3.59 (dq, J ) 8.5, 6.5 Hz, 1H), 3.32 (dd, J ) 10.0, 7.5 Hz,
1H), 1.44 (s, 3H), 1.23 (s, 3H), 1.02 (d, J ) 6.0 Hz, 3H); 13C NMR
(C6D6, 125 MHz) δ 138.8, 138.6, 138.2, 128.5, 128.3, 128.25, 128.2,
128.1, 128.0, 127.9, 127.8, 127.6, 127.5, 127.4, 127.3, 109.0, 98.9,
96.1, 80.2, 80.1, 76.0, 75.2, 74.7, 74.2, 73.4, 72.6, 72.3, 71.8. 69.1,
68.7, 65.0, 28.1, 26.3, 17.3; IR (film, cm-1) ν 3029, 2984, 2934,
1496, 1454, 1380, 1242, 1219, 1139, 1093, 1051, 1027, 994, 861;
HRMS (ESI) calcd for C50H56O10Na [M + Na] 839.3771, found
839.3762.
2,3,4,6-Tetra-O-benzyl-â-D-glucopyranosyl-(1f6)-1,2,3,4-bis(di-
O-isopropylidene)-R-D-galactopyranoside (20). 1H and 13C NMR
of disaccharide 20 have been reported:20 Rf ) 0.36 (hexane/ethyl
acetate, 4/1); 1H NMR (CDCl3, 500 MHz) δ 7.44-7.14 (m, 20H),
5.58 (d, J ) 5.0 Hz, 1H), 5.07 (d, J ) 11 Hz, 1H), 4.97 (d, J ) 11
Hz, 1H), 4.82 (d, J ) 11 Hz, 1H), 4.79 (d, J ) 11 Hz, 1H), 4.73
(d, J ) 11 Hz, 1H), 4.65-4.58 (m, 2H), 4.55 (s, 1H), 4.51 (d, J )
11 Hz, 1H), 4.47 (d, J ) 7.5 Hz, 1H), 4.33-4.31 (m, 1H), 4.25 (d,
J ) 8 Hz, 1H), 4.17 (dd, J ) 10.5, 3.5 Hz, 1H), 4.1 (m, 1H), 3.83-
3.68 (m, 3H), 3.67-3.58 (m, 2H), 3.49-3.45 (m, 2H), 1.51 (s,
3H), 1.46 (s, 3H), 1.32 (2s, 6H); 1H NMR matches with the
literature report; 13C NMR (CDCl3, 125 MHz) δ 138.7, 138.2, 128.7,
128.4, 128.2, 128.0, 127.9, 127.7, 127.6, 127.55, 127.49, 109.4,
108.6, 104.4, 96.4, 84.6, 81.6, 77.7, 75.7, 75.0, 74.8, 74.4, 73.5,
71.5, 70.8, 70.5, 69.7, 68.8, 67.4, 26.1, 26.0, 25.1, 24.5; 13C NMR
matches with the literature report; J(13CH) ) 156 Hz (104.4 ppm);
179 Hz (96.4 ppm); IR (film, cm-1) ν 2902, 1454, 1381, 1255,
1211.
2,3,4,6-Bis(di-O-isopropylidene)-R-D-mannopyranosyl-(1f3)-
1,2,5,6-bis(di-O-isopropylidene)-R-D-glucofuranoside (11). 1H and
13C NMR of disaccharide 11 have been reported:16a 1H NMR
(CDCl3, 500 MHz) δ 5.79 (d, J ) 3.0 Hz, 1H), 5.19 (s, 1H), 4.73
(dd, J ) 6.0, 3.5 Hz, 1H), 4.58 (d, J ) 5.5 Hz, 1H), 4.53 (d, J )
3.5 Hz, 1H), 4.37 (dd, J ) 110, 6.0 Hz, 1H), 4.18 (m, 2H), 4.09-
3.99 (m, 4H), 3.95-3.92 (m, 2H), 1.45 (s, 3H), 1.42 (s, 6H), 1.37
1
(s, 3H), 1.34 (s, 3H), 1.30 (s, 3H), 1.28 (s, 3H), 1.27 (s, 3H); H
NMR matches with the literature report; 13C NMR (CDCl3, 125
MHz) δ 112.7, 111.9, 109.2, 109.1, 107.7, 105.1, 84.9, 83.6, 80.8,
80.7, 79.3, 73.1, 72.3, 67.4, 66.6, 26.9, 26.8, 26.2, 25.8, 25.3, 25.1,
24.5; 13C NMR matches with the literature report; IR (film, cm-1
)
ν 3365, 3194, 2988, 2938, 1455, 1374, 1213, 1163, 1115, 1078,
1020, 845.
1-O-(Boc-L-Ser)- 2,3,4,6-bis(di-O-isopropylidene)-R-D-man-
1
nopyranoside (12): H NMR (CDCl3, 500 MHz) δ 5.43 (d, J )
9.0 Hz, 1H), 4.91 (s, 1H), 4.75 (dd, J ) 6.0, 3.5 Hz, 1H), 4.53 (d,
J ) 6.0 Hz, 1H), 4.38-4.36 (m, 1H), 4.35 (dd, J ) 11.5, 6.5 Hz,
1H), 4.09 (dd, J ) 8.5, 6.5 Hz, 1H), 4.01 (dd, J ) 8.5, 4.5 Hz,
1H), 3.91-3.87 (m, 2H), 3.80 (dd, J ) 10.5, 3.0 Hz, 1H), 3.74 (s,
3H), 1.44 (s, 9H), 1.43 (s, 6H), 1.36 (s, 3H), 1.29 (s, 3H); 13C
NMR (CDCl3, 125 MHz) δ 170.8, 155.4, 112.7, 109.3, 107.2, 84.9,
80.9, 79.4, 72.9, 68.7, 67.0, 53.9, 52.5, 29.7, 28.3, 26.8, 25.8, 25.2,
24.5; IR (film, cm-1) ν 2983, 2936, 1721, 1507, 1370, 1253, 1211,
1163, 1117, 1066, 1028, 827; HRMS (ESI) calcd for C21H35NO10Na
[M + Na] 484.2153, found 484.2159.
Methyl 2,3,4,6-bis(di-O-isopropylidene)-R-D-mannopyrano-
syl-(1f6)-2,3,4-tri-O-pivaloyl)-R-D-glucopyranoside (13): 1H
NMR (CDCl3, 500 MHz) δ 5.49 (t, J ) 9.5 Hz, 1H), 5.00 (s, 1H),
4.83 (d, J ) 3.5 Hz, 1H), 4.72 (dd, J ) 5.5, 3.5 Hz, 1H), 4.66 (dd,
J ) 10.5, 4.0 Hz, 1H), 4.49 (t, J ) 12.0 Hz, 1H), 4.46 (d, J ) 6.0
Hz, 1H), 4.31-4.27 (m, 1H), 4.06-3.95 (m, 4H), 3.83-3.80 (m,
1H), 3.57 (t, J ) 9.5 Hz, 1H), 3.32 (s, 3H), 1.39 (s, 3H), 1.37 (s,
3H), 1.34 (s, 3H), 1.24 (s, 3H), 1.19 (s, 9H), 1.319 (s, 9H), 1.14 (s,
9H); 13C NMR (CDCl3, 125 MHz) δ 177.9, 177.8, 176.9, 112.7,
109.2, 109,1, 96.3, 85.3, 81.1, 79.4, 73.0, 71.4, 71.1, 68.3, 66.7,
63.0, 55.3, 33.9, 33.8, 38.7, 27.2, 27.1, 26.9, 26.6, 25.8, 25.4, 24.6;
IR (film, cm-1) ν 2978, 2937, 1734, 1481, 1371, 1281, 1159, 1065,
1037, 977; HRMS (ESI) calcd for C34H56O14Na [M + Na]
711.3568, found 711.3609.
Methyl 2,3,4,6-Tetra-O-benzyl-R-D-mannopyranosyl-(1f6)-
2,3,4-tri-O-benzoyl)-R-D-glucopyranoside (14). 1H and 13C NMR
of disaccharide 14 have been reported:16b 1H NMR (CDCl3, 500
MHz) δ 7.97-7.84 (m, 2H), 7.51-7.14 (m, 33H), 6.09 (t, J )
10.0 Hz, 1H), 5.54 (t, J ) 10.0 Hz, 1H), 5.21 (dd, J ) 10.0, 3.5
Hz, 1H), 5.15 (d, J ) 3.5 Hz, 1H), 4.90 (d, J ) 1.0 Hz, 1H), 4.85
(d, J ) 10.5 Hz, 1H), 4.70 (d, J ) 12.5 Hz, 1H), 4.66 (d, J ) 12.5
Hz, 1H), 4.53 (d, J ) 12.0 Hz, 1H), 4.50-4.42 (m, 3H), 4.37 (d,
J ) 12.0 Hz, 1H), 4.15-4.11 (m, 1H), 3.93 (t, J ) 9.0 Hz, 1H),
3.88-3.83 (m, 3H), 3.68-3.67 (m, 1H), 3.64-3.58 (m, 3H), 3.53-
Methyl 2,3,4,6-Tetra-O-benzyl-â-D-glucopyranosyl-(1f6)-
2,3,4-tri-O-benzoyl-R-D-glucopyranoside (21). 1H and 13C NMR
of disaccharide 20 have been reported:21 Rf ) 0.18 (hexane/ethyl
1
acetate, 6/1); H NMR (CDCl3, 500 MHz) δ 7.96 (d, J ) 7.5 Hz,
1
3.50 (m, 1H), 3.37 (s, 3H); H NMR matches with the literature
2H), 7.92 (d, J ) 7.0 Hz, 2H), 7.84 (d, J ) 7.0 Hz, 2H), 7.51-
7.13 (m, 29H), 6.16 (t, J ) 10 Hz, 1H), 5.48 (t, J ) 10 Hz, 1H),
5.25 (dd, J ) 10, 3.5 Hz, 1H), 5.20 (d, J ) 2.5 Hz, 1H), 5.05 (d,
J ) 10.5 Hz, 1H), 4.90 (d, J ) 11 Hz, 1H), 4.82-4.74 (m, 2H),
4.68 (d, J ) 10 Hz, 1H), 4.53-4.35 (m, 5H), 4.12 (d, J ) 10 Hz,
1H), 3.80 (dd, J ) 10.5, 7 Hz, 1H), 3.64-3.57 (m, 4H), 3.49-
report; 13C NMR (CDCl3, 125 MHz) δ 165.8, 165.1, 138.7, 138.6,
138.4, 138.3, 133.3, 133.2, 133.1, 129.9, 129.6, 129.3, 129.1, 128.6,
128.4, 128.31, 128.3, 128.2, 127.9, 127.8, 127.7, 127.52, 127.5,
127.4, 98.2, 96.9, 79.8, 74.9, 74.8, 74.7, 73.2, 72.5, 72.1, 71.8, 70.5,
69.8, 68.9, 68.1, 66.1, 55.5; 13C NMR matches with the literature
report; IR (film, cm-1) ν 3063, 3031, 2933, 2871, 1730, 1453, 1280,
1265, 1106, 1069, 1027, 916, 825.
1
3.40 (m, 2H), 3.37 (s, 3H); H NMR matches with the literature
report; 13C NMR (CDCl3, 125 MHz) δ 165.84, 165.80, 165.5, 138.6,
138.5, 138.10, 138.07, 133.42, 133.35, 133.08, 130.0, 129.9, 129.7,
129.2, 129.1, 128.9, 128.4, 128.35, 128.26, 128.2, 127.93, 127.87,
127.75, 127.67, 127.57, 127.5, 104.0, 96.8, 84.5, 82.3, 81.7, 77.7,
2,3,4,6-Tetra-O-benzyl-R-D-mannopyranosyl-(1f6)-1,2,3,4-
bis(di-O-isopropylidene)-R-D-galactopyranoside (15). The syn-
thesis of disaccharide 15 has been reported:19 1H NMR (C6D6, 500
MHz) δ 7.46-7.45 (m, 2H), 7.40-7.36 (m, 4H), 7.31-7.29 (m,
2H), 725-7.13 (m, 12H), 5.58 (d, J ) 5.0 Hz, 1H), 5.28 (s, 1H),
5.03 (d, J ) 11.5 Hz, 1H), 4.72 (d, J ) 12.0 Hz, 1H), 4.68-4.64
(20) (a) Kim, K. S.; Lee, Y. J.; Kim, H. Y.; Kang, S. S.; Kwon, S. Y.
Org. Biomol. Chem. 2004, 2, 2408. (b) Houdier, S.; Vottero, P. J. A.
Carbohydr. Res. 1992, 232, 349.
(19) Fraser-Reid, B.; Konradsson, P.; Mootoo, D. R.; Udodong, U. J.
Chem. Soc., Chem. Commun. 1988, 823-825.
(21) Kim, K. S.; Lee, Y. J.; Kim, H. Y.; Kang, S. S.; Kwon, S. Y. Org.
Biomol. Chem. 2004, 2, 2408.
798 J. Org. Chem., Vol. 73, No. 3, 2008

Palladium(II)-Catalyzed StereoselectiVe Glycosylation
75.7, 75.0, 74.9, 74.8, 73.4, 72.1, 70.5, 69.9, 69.0, 68.8, 68.6, 55.5;
13C NMR matches with the literature report; J(13CH) ) 155 Hz
(104.0 ppm); 173 Hz (96.8 ppm); IR (film, cm-1) ν 2916, 1730.
1-O-Dihydrocholesterolyl-2,3,4,6-tetra-O-benzyl-â-D-glucopy-
) 7.5, 1.5 Hz, 1H), 4.13 (d, J ) 5.5 Hz, 1H), 3.95 (t, J ) 6.5 Hz,
1H), 3.84 (dd, J ) 10, 6 Hz, 1H), 3.63-3.56 (m, 2H), 3.29 (dd, J
) 9.5, 7 Hz, 1H), 1.52 (s, 3H), 1.49 (s, 3H), 1.43 (s, 3H), 1.31 (s,
9H), 1.19 (d, J ) 6.5 Hz, 3H), 0.86 (s, 9H), 0.12 (s, 3H), 0.06 (s,
3H); 13C NMR (CDCl3, 125 MHz) δ 109.2, 108.9, 108.5, 97.0,
96.3, 79.1, 76.0, 75.9, 71.0, 70.6, 66.5, 65.9, 65.3, 28.1, 26.4, 26.1,
26.0, 25.9, 24.9, 24.3, 17.6, -4.0, -4.9; IR (film, cm-1) ν 2934,
1382; HRMS (ESI) calcd for C27H48O10SiNa (M + Na) 583.2909,
found 583.2927.
1
ranoside (22â). H and 13C NMR of disaccharide 20 have been
reported:22 Rf ) 0.44 (hexane/ethyl acetate, 9/1); 1H NMR (CDCl3,
500 MHz) δ 7.35-7.15 (m, 20H), 4.96 (d, J ) 11 Hz, 1H), 4.91
(d, J ) 11 Hz, 1H), 4.81 (d, J ) 11 Hz, 1H), 4.77 (d, J ) 11 Hz,
1H), 4.71 (d, J ) 11 Hz, 1H), 4.61-4.51 (m, 3H), 4.51 (d, J ) 8
Hz, 1H), 3.74 (d, J ) 10.5 Hz, 1H), 3.65-3.60 (m, 3H), 3.52 (t, J
) 9.0 Hz, 1H), 3.46-3.40 (m, 2H), 1.98-0.58 (m, 47H); 1H NMR
matches with the literature report; 13C NMR (CDCl3, 125 MHz) δ
138.7, 138.6, 138.3, 138.2, 128.4, 128.33, 128.26, 128.0, 127.9,
127.73, 127.67, 127.62, 127.55, 127.52, 101.9, 84.9, 82.4, 79.1,
78.1, 75.7, 75.0, 74.8, 73.4, 69.3, 56.5, 56.3, 54.4, 44.8, 42.6, 40.1,
39.5, 37.1, 36.2, 35.8, 35.6, 35.5, 34.8, 32.1, 29.7, 28.8, 28.3, 28.0,
24.2, 23.8, 22.8, 22.6, 21.2, 18.7, 12.3, 12.1; 13C NMR matches
with the literature report; IR (film, cm-1) ν 2931, 2866, 1453, 1360.
1-O-Dihydrocholesterolyl-2,3,4,6-tetra-O-benzyl-R-D-glucopy-
4-O-tert-Butyldimethylsilyl-2,3,-di-O-isopropylidene-R-L-rham-
nopyranosyl-(1f3)-1,2,5,6-bis(di-O-isopropylidene)-R-D-gluco-
1
furanoside (26): Rf ) 0.34 (hexane/ethyl acetate, 6/1); H NMR
(CDCl3, 500 MHz) δ 5.86 (d, J ) 3.5 Hz, 1H), 5.08 (s, 1H), 4.53
(d, J ) 3.5 Hz, 1H), 4.40 (d, J ) 3.5 Hz, 1H), 4.26-4.23 (m, 1H),
4.11 (dd, J ) 8.5, 6.5 Hz, 1H), 4.08 (dd, J ) 8.5, 3 Hz, 1H), 4.05
(d, J ) 5.5 Hz, 1H), 3.93-3.87 (m, 2H), 3.84 (dd, J ) 10, 6 Hz,
1H), 3.30 (dd, J ) 10, 7 Hz, 1H), 1.50 (s, 3H), 1.49 (s, 3H), 1.38
(s, 3H), 1.32 (s, 3H), 1.29 (s, 6H), 1.16 (d, J ) 6.5 Hz, 3H), 0.85
(s, 9H), 0.11 (s, 3H), 0.05 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
112.0, 109.1, 109.0, 105.3, 94.6, 81.7, 81.0, 79.2, 76.1, 76.0, 75.5,
71.7, 68.0, 66.4, 28.1, 26.74, 26.69, 26.4, 26.1, 25.8, 25.1, 17.4,
-3.9, -5.0; IR (film, cm-1) ν 2934, 1381, 1372, 1078; HRMS
(ESI) calcd for C27H48O10SiNa (M + Na) 583.2909, found
583.2918.
1
ranoside (22R): Rf ) 0.44 (hexane/ethyl acetate, 9/1); H NMR
(CDCl3, 500 MHz) δ 7.34-7.11 (m, 20H), 4.98 (d, J ) 11 Hz,
1H), 4.91 (d, J ) 3 Hz, 1H), 4.81 (d, J ) 11 Hz, 1H), 4.79 (d, J
) 11 Hz, 1H), 4.74 (d, J ) 12 Hz, 1H), 4.65 (d, J ) 12 Hz, 1H),
4.44 (d, J ) 11.5 Hz, 2H), 3.97 (t, J ) 9 Hz, 1H), 3.86 (t, J ) 9.5
Hz, 1H), 3.71 (dd, J ) 10, 3 Hz, 1H), 3.68-3.51 (m, 4H), 1.96-
0.56 (m, 47H); 13C NMR (CDCl3, 125 MHz) δ 139.0, 138.3, 128.4,
128.34, 128.32, 128.1, 127.9, 127.83, 127.80, 127.65, 127.61, 127.5,
94.7, 82.1, 80.0, 77.9, 76.3, 75.6, 75.1, 73.4, 73.0, 70.0, 68.7, 56.5,
56.3, 54.4, 45.1, 42.6, 40.0, 39.5, 36.9, 36.2, 35.84, 35.78, 35.7,
35.5, 32.1, 28.7, 28.2, 28.0, 27.4, 24.2, 23.8, 22.8, 22.5, 21.2, 18.7,
12.3, 12.1; IR (film, cm-1) ν 2928, 2865, 1453.
Methyl 2-O-Benzoyl-3,4,6-tri-O-benzyl-â-D-glucopyranosyl-
(1f6)-2,3,4-tri-O-benzoyl-R-D-glucopyranoside (30). The syn-
thesis of disaccharide 30 has been reported:23 1H NMR (CDCl3,
500 MHz) δ 8.05-7.78 (m, 8H), 7.56-7.18 (m, 27H), 6.05 (t, J )
10.0 Hz, 1H), 5.30 (t, J ) 9.0 Hz, 1H), 5.27 (d, J ) 7.0 Hz, 1H),
5.06 (dd, J ) 10.0, 3.5 Hz, 1H), 4.85 (d, J ) 3.5 Hz, 1H), 4.80 (d,
J ) 11.0 Hz, 1H), 4.73 (d, J ) 11.0 Hz, 1H), 4.67 (d, J ) 11.0
Hz, 1H), 4.61-4.52 (m, 3H), 4.47 (d, J ) 12.0 Hz, 1H), 4.17 (ddd,
J ) 10.0, 8.5, 1.5 Hz, 1H), 4.07 (dd, J ) 11.0, 1.5 Hz, 1H), 3.84
(d, J ) 9.0 Hz, 1H), 3.77 (t, J ) 9.0 Hz, 1H), 3.73-3.68 (m, 2H),
3.64 (dd, J ) 11.0, 8.0 Hz, 1H), 3.52 (dd, J ) 9.5, 5.5, 3.5 Hz,
1H), 3.01 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 165.71, 165.7,
165.5, 165.3, 133.4, 133.3, 133.1, 133.0, 129.9, 129.8, 129.6, 128.4,
128.3, 128.25, 128.2, 127.9, 127.8, 127.7, 127.63, 127.6, 101.7,
96.3, 82.7, 77.9, 77.3, 77.0, 76.8, 75.3, 75.1, 75.0, 73.7, 73.5, 72.0,
70.5, 69.7, 68.9, 68.7, 68.4, 54.9; IR (film, cm-1) ν 2936, 1728,
1452, 1094, 1069, 1027, 735.
1-O-(Boc-L-Ser)-2-O-benzoyl-3,4,6-tri-O-benzyl-â-D-glucopy-
ranoside (31): 1H NMR (CDCl3, 500 MHz) δ 8.02 (d, J ) 7.5 Hz,
2H), 7.58-7.11 (m, 18H), 5.28 (d, J ) 8.0 Hz, 1H), 5.22 (t, J )
8.5 Hz, 1H), 4.80 (d, J ) 10.5 Hz, 1H), 4.73 (d, J ) 11.5 Hz, 1H),
4.65 (d, J ) 11.0 Hz, 1H), 4.63 (d, J ) 12.0 Hz, 1H), 4.56 (dd, J
) 10.5, 4.5 Hz, 1H), 4.52 (d, J ) 8.0 Hz, 1H), 4.34 (dd, J ) 8.0,
3.5 Hz, 1H), 4.24 (d, J ) 10.0 Hz, 1H), 3.81-3.77 (m, 3H), 3.74
(d, J ) 3.0 Hz, 2H), 3.03 (s, 3H), 3.36 (bs, 1H), 1.36 (s, 9H); 13C
NMR (CDCl3, 125 MHz) δ 170.5, 165.2, 155.4, 137.9, 137.8, 137.7,
133.2, 129.8, 128.4, 128.3, 128.0, 127.9, 127.8, 127.72, 127.7,
101.2, 82.5, 77.7, 75.3, 75.1, 74.9, 73.6, 73.4, 68.9, 68.5, 53.9, 52.5,
28.3; IR (film, cm-1) ν 3437, 3353, 3296, 2951, 2870, 1723, 1601,
1497, 1453, 1365, 1268, 1161, 1094, 1070, 826, 737, 712, 699;
HRMS (ESI) calcd for C43H49NO11Na [M + Na] 778.3203, found
778.3224.
Benzyl 4-O-tert-butyldimethylsilyl-2,3,-di-O-isopropylidene-
R-L-rhamnopyranosyl-(1 f 4)-2,3-di-O-isoproylidene-R-L-rham-
nopyranoside (23): Rf ) 0.42 (hexane/ethyl acetate, 6/1); 1H NMR
(CDCl3, 500 MHz) δ 7.34-7.29 (m, 5H), 5.54 (s, 1H), 5.04 (s,
1H), 4.68 (d, J ) 11.5 Hz, 1H), 4.50 (d, J ) 11.5 Hz, 1H, Bn),
4.21 (t, J ) 6.5 Hz, 1H), 4.12 (d, J ) 5.5 Hz, 1H), 4.10 (d, J ) 5.5
Hz, 1H), 3.91 (t, J ) 6.0 Hz, 1H), 3.74-3.68 (m, 1H), 3.59-3.53
(m, 2H), 3.32 (dd, J ) 9.5, 7.5 Hz, 1H), 1.52 (s, 3H), 1.50 (s, 3H),
1.32 (s, 3H), 1.30 (s, 3H), 1.26 (d, J ) 6 Hz, 3H), 1.19 (d, J ) 6.5
Hz, 3H), 0.88 (s, 9H,), 0.12 (s, 3H), 0.06 (s, 3H); 13C NMR (CDCl3,
125 MHz) δ 137.1, 128.5, 128.2, 127.9, 109.4, 108.7, 96.2, 95.9,
78.9, 78.6, 76.7, 76.5, 76.1, 75.7, 69.1, 66.4, 64.2, 28.1, 27.9, 26.4,
25.9, 17.9, 17.5, -4.0, -4.8; IR (film, cm-1) ν 2934, 1381, 1245,
1221, 1086; HRMS (ESI) calcd for C31H50O9SiNa (M + Na)
617.3116, found 617.3097.
Methyl 4-O-tert-butyldimethylsilyl-2,3,-di-O-isopropylidene-
R-L-rhamnopyranosyl-(1f6)-2,3,4-tri-O-benzoyl-R-D-glucopy-
1
ranoside (24): Rf ) 0.49 (hexane/ethyl acetate, 2/1); H NMR
(CDCl3, 500 MHz) δ 7.97-7.92 (m, 4H), 7.85 (d, J ) 8 Hz, 2H),
7.51-7.34 (m, 7H), 7.27 (t, J ) 8 Hz, 2H), 6.13 (t, J ) 10 Hz,
1H), 5.56 (t, J ) 10 Hz, 1H), 5.24 (dd, J ) 10, 3.5 Hz, 1H), 5.21
(d, J ) 3.5 Hz, 1H), 4.91 (s, 1H), 4.22-4.18 (m, 1H), 4.07 (d, J
) 6 Hz, 1H), 3.86-3.82 (m, 2H), 3.62 (dd, J ) 11.5, 5.5 Hz, 1H),
3.52 (dd, J ) 10, 6.5 Hz, 1H), 3.46 (s, 3H), 3.25 (dd, J ) 9.5, 7.5
Hz, 1H), 1.47 (s, 3H), 1.29 (s, 3H), 1.10 (d, J ) 6 Hz, 3H), 0.87
(s, 9H), 0.11 (s, 3H), 0.04 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
165.82, 165.79, 165.3, 133.5, 133.4, 133.3, 133.0, 129.9, 129.8,
129.7, 128.41, 128.39, 128.3, 108.8, 97.8, 97.0, 78.9, 75.86, 75.80,
72.1, 70.5, 69.7, 68.7, 55.6, 29.7, 28.1, 26.4, 25.9, 17.5, -4.0, -4.9;
IR (film, cm-1) ν 2930, 1732, 1280, 1265; HRMS (ESI) calcd for
C43H54O13SiNa (M + Na) 829.3226, found 829.3221.
2-O-Benzoyl-3,4,6-tri-O-benzyl-â-D-glucopyranosyl-(1f3)-
1,2,5,6-bis(di-O-isopropylidene)-R-D-glucofuranoside (32): 1H
NMR (CDCl3, 500 MHz) δ 7.97 (d, J ) 7.5 Hz, 2H), 7.58-7.11
(m, 18H), 5.35 (d, J ) 4.0 Hz, 1H), 5.19 (t, J ) 8.5 Hz, 1H), 4.80
(d, J ) 11.0 Hz, 1H), 4.73 (d, J ) 11.0 Hz, 1H), 4.65-4.54 (m,
5H), 4.36 (dd, J ) 11.0, 6.0 Hz, 1H), 4.26-4.22 (m, 3H), 4.02
(dd, J ) 9.0, 7.0 Hz, 1H), 3.93 (dd, J ) 9.0, 6.0 Hz, 1H), 3.81-
3.75 (m, 2H), 3.73 (d, J ) 3.0 Hz, 2H), 3.54-3.53 (m, 1H), 1.39
(s, 3H), 1.36 (s, 3H), 1.25 (s, 3H), 1.08 (s, 3H); 13C NMR (CDCl3,
125 MHz) δ 164.8, 138.0, 137.8, 137.7, 133.4, 129.6, 128.53, 128.5,
4-O-tert-Butyldimethylsilyl-2,3,-di-O-isopropylidene-R-L-rham-
nopyranosyl-(1f6)-1,2,3,4-bis(di-O-isopropylidene)-R-D-galac-
topyranoside (25): Rf ) 0.37 (hexane/ethyl acetate, 6/1); 1H NMR
(CDCl3, 500 MHz) δ 5.51 (d, J ) 5 Hz, 1H), 4.96 (s, 1H), 4.58
(dd, J ) 8, 2.5 Hz, 1H), 4.29 (dd, J ) 5, 2.5 Hz, 1H), 4.24 (dd, J
(23) Sato, K.; Akai, S.; Sakai, K.; Kojima, M.; Murakami, H.; Idoji, T.
Tetrahedron Lett. 2005, 46, 7411-7414.
(22) Mukaiyama, T.; Matsubara, K.; Hora, M. Synthesis 1994, 1368.
J. Org. Chem, Vol. 73, No. 3, 2008 799

Yang et al.
128.4, 128.3, 128.1, 127.97, 127.9, 127.8, 127.72, 127.7, 111.8,
108.5, 104.9, 99.7, 82.7, 82.3, 80.7, 80.4, 77.8, 75.7, 75.1, 74.8,
73.7, 73.6, 73.2, 68.5, 65.9; IR (film, cm-1) ν 2987, 2935, 1723,
1600, 1453, 1372, 1266, 1071, 1026, 826, 712, 698; HRMS (ESI)
calcd for C46H52O12Na [M + Na] 819.3351, found 819.3347.
2-3,4,6-Tetra-O-benzoyl-â-D-glucopyranosyl-(1f6)-1,2,5,6-
bis(di-O-isopropylidene)-R-D-glucopyranoside (33). The synthesis
of disaccharide 33 has been reported:24 1H NMR (CDCl3, 500 MHz)
δ 8.01 (d, J ) 8.0 Hz, 2H), 7.95 (d, J ) 8.0 Hz, 2H), 7.88 (d, J )
8.0 Hz, 2H), 7.80 (d, J ) 8.0 Hz, 2H), 7.53-7.24 (m, 12H), 5.88
(t, J ) 9.5 Hz, 1H), 5.65 (t, J ) 9.5 Hz, 1H), 5.51 (dd, J ) 9.5, 8.0
Hz, 1H), 5.40 (d, J ) 5.0 Hz, 1H), 5.01 (d, J ) 8.0 Hz, 1H), 4.62
(dd, J ) 12.0, 3.0 Hz), 4.46 (dd, J ) 12.0, 5.5 Hz, 1H), 4.40 (dd,
J ) 8.0, 2.5 Hz, 1H), 4.18 (dd, J ) 5.0, 2.5 Hz, 1H), 4.15 (ddd, J
) 8.5, 5.0, 3.0 Hz, 1H), 4.07 (dd, J ) 8.0, 1.5 Hz, 1H), 4.00 (dd,
J ) 10.5, 3.5 Hz, 1H), 3.88-3.81 (m, 2H), 1.35 (s, 3H), 1.22, (s,
3H), 1.18 (s, 3H), 1.17 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
166.1, 165.8, 165.2, 165.1, 133.4, 133.1, 133.0, 130.0, 129.8, 129.7,
129.4, 128.9, 128.8, 128.7, 128.4, 128.3, 128.24, 128.2, 109.3,
108.4, 101.2, 96.2, 73.0, 72.2, 71.8, 70.9, 70.5, 70.4, 69.8, 68.3,
67.5, 63.2, 25.9, 25.7, 24.8, 24.2; IR (film, cm-1) ν 1730, 1601,
1452, 1374, 1266, 1094, 1069, 1026, 825, 709.
2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranosyl-(1f6)-1,2,5,6-
bis(di-O-isopropylidene)-R-D-galactopyranoside (36): Rf ) 0.38
1
(benzene/ethyl acetate, 9/1); H NMR (CDCl3, 500 MHz) δ 8.07
(d, J ) 7.5 Hz, 2H), 8.01 (d, J ) 7.5 Hz, 2H), 7.96 (d, J ) 7.5,
2H), 7.76 (d, J ) 7.5 Hz, 2H), 7.59 (t, J ) 7 Hz, 1H), 7.54 (t, J )
7.5 Hz, 1H), 7.46 (m, 3H), 7.41 (t, J ) 8 Hz, 3H) 7.34 (t, J ) 7.5
Hz, 2H), 7.22 (m, 3H), 5.97 (d, J ) 2.5 Hz, 1H), 5.79 (t, J ) 10
Hz, 1H), 5.59 (dd, J ) 10.0, 3.0 Hz, 1H), 5.40 (d, J ) 4 Hz, 1H),
5.0 (d, J ) 8 Hz, 1H), 4.65 (dd, J ) 11.0, 6.5 Hz, 1H), 4.40 (m,
2H), 4.32 (t, J ) 6.6 Hz,1H), 4.19 (d, J ) 2.5 Hz, 1H), (m, 1H),
4.04 (m, 1H), 3.89 (m, 2H), 1.37 (s, 3H), 1.22 (s, 3H), 1.20 (s,
3H), 1.18 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 166.0, 165.6,
165.5, 165.3, 133.5, 133.2, 133.0, 129.9, 129.8, 128.6, 128.4, 128.3,
128.2, 109.3, 108.4, 101.7, 96.2, 71.8, 71.3, 71.0, 70.5, 70.3, 69.7,
68.4, 68.2, 67.4, 62.0, 25.9, 25.7, 24.8, 24.2; ΙR (film, cm-1) ν
3065, 2985, 2935, 1727, 1605, 1453, 1381, 1267, 1103, 1069;
HRMS (ESI) calcd for C46H46O15Na [M + Na] 861.2734, found
895.2766.
Benzyl 2,3,4,6-tetra-O-benzoyl-â-D-galactopyranosyl-(1f4)-
,2,3-O-isopropylidene)-R-L-rhamnopyranoside (37): Rf ) 0.29
(benzene/ethyl acetate, 25/1); 1H NMR (CDCl3, 500 MHz) δ 8.06
(d, J ) 7 Hz, 2H), 8.00 (dd, J ) 7, 4 Hz, 4H), 7.78 (d, J)7 Hz,
2H), 7.61 (t, J ) 7.5 Hz, 1H), 7.54(t, J ) 7.5 Hz, 1H), 7.48 (t, )
7.5 Hz, 3H), 7.41 (t, J ) 7.5 Hz, 3H), 7.35 (m, 9H), 7.31 (t, J )
6 Hz, 2H), 7.26 (m, 3H), 5.96 (d, J ) 2.5 Hz, 1H), 5.71 (t, J )
10.5 Hz, 1H), 5.59 (dd, J ) 10.5, 3.5 Hz, 1H), 5.23 (d, J ) 8 Hz,
1H), 4.98 (s, 1H), 4.62 (m, 2H), 4.42 (m, 2H), 4.29 (t, J ) 6 Hz,
1H), 4.01 (s, 1H), 3.99 (m, 1H), 3.70 (m, 1H), 3.58 (m, 1H), 1.46
(s, 3H), 1.34 (d, J ) 6.5 Hz, 3H), 1.21 (s, 3H); 13C NMR (CDCl3,
125 MHz) δ 165.6, 133.5, 133.3, 133.2, 133.1, 129.9, 128.6, 128.5,
128.4, 128.3, 128.0, 101.2, 96.0, 81.5, 78.0, 76.0, 71.9, 71.4, 70.0,
69.1, 68.3, 64.1, 62.2, 27.9, 26.1, 17.6; ΙR (film, cm-1) ν 3063,
3033, 2964, 2935, 1730, 1602, 1450, 1261, 1095, 1068; HRMS
(ESI) calcd for C50H48O14Na [M + Na] 895.2936, found 895.2929.
1-O-D-Hydrocholesterolyl-2,3,4,6-tetra-O-benzoyl-â-D-galac-
topyranoside (38): Rf ) 0.36 (benzene/ethyl acetate, 40/1); 1HNMR
(CDCl3, 500 MHz) δ 8.09(d, J ) 7.5 Hz, 2H), 8.01(d, J ) 7.5 Hz,
2H), 7.94(d, J ) 7.0 Hz, 2H), 7.77(d, J ) 7.5 Hz, 2H), 7.59 (t, J
) 7.5 Hz, 1H), 7.55 (t, J ) 7.5 Hz, 1H), 7.49 (m, 3H), 7.42 (t, J
) 10 Hz, 3H), 7.36 (m, 3H), 7.22 (m, 2H), 5.96 (d, J ) 2.5 Hz,
1H), 5.74 (t, J ) 10.5 Hz, 1H), 5.56 (dd, J ) 10.5, 3.5 Hz,1H),
4.86 (d, J ) 8 Hz, 1H), 4.66 (dd, J ) 11.5, 7 Hz, 1H), 4.41 (dd,
J ) 11, 6.5 Hz, 1H), 4.30 (t, J ) 6.5 Hz, 1H), 3.61(m, 1H), 2.0-
0.5(m, 47H); 13C NMR (CDCl3, 125 MHz) δ 166.0, 165.7, 165.3,
165.2, 130.1, 129.8, 129.7, 128.8, 128.6, 128.4, 128.3, 128.2, 100.6,
80.5, 71.9, 71.2, 70.0, 68.2, 62.1, 56.4, 56.3, 54.3, 44.7, 42.6, 40.0,
39.5, 36.9, 36.2, 35.8, 35.5, 35.4, 34.7, 32.0, 29.4, 28.6, 28.2, 28.0,
24.2, 23.8, 22.8, 22.6, 21.2, 18.7; ΙR (film, cm-1) ν 3067, 2935,
2863, 1730, 1602, 1450, 1266, 1106, 1068, 1027; HRMS (ESI)
calcd for C61H74O10Na [M + Na] 989.5174, found 989.5133.
Methyl 2-3,4,6-Tetra-O-benzoyl-â-D-glucopyranosyl-(1f6)-
2,3,4-tri-O-benzoyl-R-D-glucopyranoside (34). The synthesis of
disaccharide 34 has been reported:25 1H NMR (CDCl3, 500 MHz)
δ 7.96 (dd, J ) 8.0, 7.0 Hz, 4H), 7.90 (d, J ) 7.0 Hz, 2H), 7.87
(d, J ) 7.5 Hz, 2H), 7.84 (d, J ) 7.5 Hz, 2H), 7.80 (d, J ) 7.5 Hz,
2H), 7.77 (d, J ) 7.5 Hz, 2H), 7.53-7.20 (m, 16H), 6.04 (t, J )
10.0 Hz, 1H), 5.89 (t, J ) 10.0 Hz, 1H), 5.63 (t, J ) 10.0 Hz, 1H),
5.54 (d, J ) 9.5, 7.5 Hz, 1H), 5.29 (t, J ) 9.5 Hz, 1H), 5.06 (dd,
J ) 10.0, 2.5 Hz, 1H), 4.95 (d, J ) 8.0 Hz, 1H), 4.91 (d, J ) 4.0
Hz, 1H), 4.58 (dd, J ) 12.5, 3.0 Hz, 1H), 4.42 (dd, J ) 12.0, 5.0
Hz, 1H), 4.19 (t, J ) 8.0 Hz, 1H), 4.12 (dd, J ) 9.5, 4.0 Hz, 1H),
4.08 (d, J ) 11.0 Hz, 1H), 3.76 (dd, J ) 11.5, 7.5 Hz, 1H), 3.07
(s, 3H); 13C NMR (CDCl3, 125 MHz) δ 166.1, 165.8, 165.6, 165.4,
165.2, 133.4, 133.3, 133.2, 133.1, 133.0, 129.8, 129.7, 129.6, 129.3,
129.2, 129.0, 128.7, 128.4, 128.31, 128.3, 128.2, 101.7, 96.4, 72.8,
72.3, 71.9, 71.8, 70.3, 69.6, 68.9, 68.7, 63.0, 55.0; IR (film, cm-1
)
ν 2929, 1729, 1601, 1451, 1315, 1267, 1108, 1094, 1069, 1026,
911, 708.
Benzyl 2,3,4,6-tetra-O-benzoyl-â-D-glucopyranosyl-(1f4)-2,3-
O-isopropylidene-R-L-rhamnopyranoside (35): 1H NMR (CDCl3,
500 MHz) δ 8.07-7.81 (m, 7H), 7.53-7.17 (m, 18H), 5.89 (t, J )
10.0 Hz, 1H), 5.62 (t, J ) 10.0 Hz, 1H), 5.46 (dd, J ) 10.0, 8.0
Hz, 1H), 5.31 (d, J ) 8.0 Hz, 1H), 4.96 (s, 1H), 4.65 (dd, J ) 5.5,
2.5 Hz, 1H), 4.60 (d, J ) 12.0 Hz, 1H), 4.46 (d, J ) 5.5 Hz, 1H),
4.41 (d, J ) 11.5 Hz, 1H), 4.11 (ddd, J ) 9.5, 5.5, 3.5 Hz, 1H),
4.01-3.96 (m, 2H), 3.63 (dq, J ) 9.5, 6.0 Hz, 1H), 3.56 (dd, J )
10.0, 6.5 Hz, 1H), 1.45 (s, 3H), 1.26 (d, J ) 6.0 Hz, 3H), 1.23 (s,
3H); 13C NMR (CDCl3, 125 MHz) δ 166.1, 165.8, 165.3, 136.9,
133.6, 133.2, 133.1, 130.0, 129.9, 129.8, 129.76, 129.7, 129.6,
129.5, 128.9, 128.8, 128.5, 128.4, 128.3, 128.2, 127.9, 109.2, 100.4,
95.9, 80.7, 78.0, 76.0, 73.1, 72.3, 72.1, 70.0, 69.1, 64.0, 63.2, 29.7,
27.9, 26.2, 17.5; IR (film, cm-1) ν 2983, 2933, 1732, 1601, 1452,
1380, 1266, 1177, 1106, 1092, 1069, 1026, 733, 709, 686; HRMS
(ESI) calcd for C50H48O14Na [M + Na] 895.2936, found 895.2929.
Acknowledgment. We thank Montana State University and
NSF EPSCoR for financial support. We also thank Dr. Gregory
1
J. Mercer for obtaining HRMS and processing H and 13C
spectra for all the compounds.
Supporting Information Available: 1H NMR and 13C NMR
spectra of all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
(24) Gareg, P. J.; Norberg, J. Acta. Chem. Scand. 1979, 116-118.
(25) Guthrie, R. D.; Jenkins, A. D.; Roberts, G. A. F. J. Chem. Soc.,
Perkin. Trans. 1973, 1, 2414-2417.
JO702436P
800 J. Org. Chem., Vol. 73, No. 3, 2008