On the nitrile effect in l-rhamnopyranosylation

Article abstract of DOI:10.1016/j.carres.2006.03.036

It is shown that the use of 5% acetonitrile or propionitrile in dichloromethane functions to increase the β-selectivity of a number of l-rhamnopyranosylation reactions conducted by the thioglycoside method with activation by the 1-benzenesulfinyl piperidi

Full text of DOI:10.1016/j.carres.2006.03.036

Carbohydrate Research 341 (2006) 1467–1475
On the nitrile effect in L-rhamnopyranosylation
David Crich* and Mitesh Patel
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7061, USA
Received 14 February 2006; received in revised form 17 March 2006; accepted 28 March 2006
Available online 27 April 2006
Abstract—It is shown that the use of 5% acetonitrile or propionitrile in dichloromethane functions to increase the b-selectivity of a
number of L-rhamnopyranosylation reactions conducted by the thioglycoside method with activation by the 1-benzenesulfinyl piper-
idine/trifluoromethanesulfonic anhydride couple. The use of more significant quantities of acetonitrile or propionitrile results in the
formation of complex reaction mixtures containing little coupled product, but from which Ritter-type products can be isolated.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Deoxy sugars; Acetonitrile; Nitrilium ion
1. Introduction
(CIP) is the reactive species in our benzylidene acetal
mediated b-mannosylation systems,27 we considered
the key to successful b-L-rhamnosylation to lie in the
use of disarming non-participating protecting groups.
The function of these groups is to destabilize the oxa-
carbenium ion, so as to shift the CIP/glycosyl triflate
equilibrium toward the glycosyl triflate, which is the
established resting state.6,28 In this manner, the concen-
tration of the a-selective solvent-separated ion pair
(SSIP), and of any free oxacarbenium ions is minimized
resulting in enhanced b-selectivity (Scheme 1).
While significant advances have been made in the stereo-
controlled formation of b-mannopyranosides in recent
years, through both direct and indirect methods,1–19
their 6-deoxy congenors, the b-rhamnopyranosides, con-
tinue to pose significant challenges. In the D-series, char-
acterized by the scarcity of D-rhamnose itself,20 we have
successfully devised methods based on stereochemically
controlled b-mannosylation, followed by efficient deoxy-
genation at the 6-position by radical fragmentation of
modified 4,6-O-acetals,21–23 but the L-series, while acces-
sible by indirect methods,24–26 continues to pose signifi-
cant challenges to direct stereocontrolled synthesis. We
report here on our attempts to use the ‘nitrile effect’ to
enhance the b-selectivity of solution-phase rhamnosyl-
ation reactions.
On this basis, following the early work of Schuerch,7
we surveyed of 2-O-sulfonyl protected rhamnosyl do-
nors, ultimately arriving at the 4-O-benzoyl-2-O-sulfon-
yl system 1.6,29 A number of other non-participating
electron-withdrawing protecting groups for O2, includ-
ing phosphates, nitrate, cyanate, and a vinylous ester,
were also surveyed but found to be less successful than
the optimum sulfonate 1.6 Interestingly, 2,3-O-carbonyl
and 2,3-O-alkylidene protected mannosyl and rhamno-
syl thioglycosides were found to be highly a-selective
in a number of homogeneous solution phase glycosyl-
ations.3,30–32 This contrasts with their use in hetero-
genous glycosylations in the form of glycosyl bromides
with activation by insoluble silver salts when they are
b-selective.33–37 We ascribe the a-selectivity of these
2,3-O-carbonates in homogeneous glycosylations to the
half-chair conformation imposed on the pyranose ring,
for which we have provided crystallographic evidence,38
2. Results and discussion
As we have discussed,6 based on our determination that
a transient contact oxacarbenium ion/triflate anion pair
*
Corresponding author. Tel.: +1 312 996 5189; fax: +1 312 996
0431; e-mail: dcrich@uic.edu
We distinguish between direct methods, which afford the desired
glycosidic bond in a single step, and indirect methods, requiring either
prior attachment of the acceptor to the donor, or correction of
stereochemistry after formation of the glycosidic bond.
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.03.036

1468
D. Crich, M. Patel / Carbohydrate Research 341 (2006) 1467–1475
X
X
X
O
O
O
O
O
O
O
O
P
P
P
P
CIP
free
covalent
donor
SSIP
oxacarbenium ion
OR
O
OR
O
O
P
O
P
β-glycoside
Scheme 1. Abbreviated glycosylation mechanism.
α-glycoside
Table 1. The effect of varying quantities of propionitrile and aceto-
nitrile on the formation of 6 from 2 and 4 at ꢀ60 ꢁC
which reduces the energy barrier to oxacarbenium ion
formation: the b-directing effect observed with the bro-
mides and insoluble silver salts is simply a function of
the mode of adsorption onto the promoter surface.31
This understanding of the reactivity of the 2,3-O-car-
bonates led us to the 3,4-O-carbonyl protected thiogly-
coside 2, which exhibits comparable b-selectivity in our
systems to sulfonate 1.31
Entry
Solvent (v/v)
Yield (%) 6
b:a ratio
1
2
3
4
5
6
7
8
EtCN/CH2Cl2 0:100
EtCN/CH2Cl2 100:0
EtCN/CH2Cl2 10:90
EtCN/CH2Cl2 5:95
EtCN/CH2Cl2 2.5:97.5
CH3CN/CH2Cl2 5:95
CH3CN/CH2Cl2 2.5:97.5
CH3CN/CH2Cl2 1.25:98.75
81
<10
69
80
78
76
80
98
6:1
>5:1
6.8:1
7.9:1
6.6:1
7.2:1
8:1
4.5:1
BnO
OBn
O
SPh
CF3
BzO
O
BnO
SPh
OBn
O
O
BnO
O
S
BnO
O
O
O
NH
O
Working with donor 2 and coupling to acceptor 4, we
surveyed the effect of propionitrileà under our BSP/
Tf2O/TTBP conditions,3,4,47 with the formation of
rhamnoside 6 (Table 1). In neat dichloromethane (Table
1, entry 1), 6 was formed in good yield with a 6:1 b:a
ratio. By contrast, in neat propionitrile extensive decom-
position of the donor was observed, most of the
acceptor was recovered unchanged, and <10% of the
coupled product 6 was discernible in the crude reaction
mixture, albeit with a b:a ratio of at least 5:1 (Table 1,
entry 2). This result was somewhat surprising as propio-
nitrile had previously been demonstrated to be a satis-
factory solvent for BSP type coupling reactions with
other simple thioglycosides,3 and in the closely related
sulfoxide couplings,48 but was nevertheless reproducible.
Reducing the amount of propionitrile until it was simply
an additive in the main solvent resulted in the restora-
tion of efficient coupling, and with some increase in
b-selectivity, with a maximum approaching 8:1 for the
solvent ratio of 5/95 (v/v) propionitrile/dichlorometh-
O
CCl3
1
3
2
HO
BnO
BnO
BnO
O
BnO
O
OMe
O
O
O
O
OBn
OBn
BnO
HO
O
BnO
BnO
OBn
OMe
OMe
O
6
4
5
Although donors 1 and 2 gave moderate to excellent
b-selectivity with simple secondary and tertiary alcohols,
and with more reactive carbohydrate acceptors, they
only afford modest selectivity with more typical second-
ary carbohydrate acceptors.6,29,31,39 As a consequence,
we turned our attention to the well-known b-directing
effect of acetonitrile in glycosylation reactions.40–44 We
were encouraged in this endeavor by preliminary results
from the Schmidt group in which it was found that
2,3,4,6-tetra-O-benzyl-a-D-mannopyranosyl trichloro-
acetimidate 3 gave approximately a 1:1 b:a mixture of
anomers in good yield on coupling to methyl 2,3,4-tri-
O-benzyl-a-D-glucopyranoside 4, and to methyl 2,4,6-
tri-O-benzyl-a-D-glucopyranoside 5, in propionitrile at
ꢀ80 ꢁC on activation with trimethylsilyl triflate,44 when
high a-selectivity would have been expected in non-par-
ticipating solvents.45,46
à Propionitrile has a lower freezing point (ꢀ93 ꢁC) than acetonitrile
(ꢀ48 ꢁC), making it the nitrile of choice when used in significant
proportion in low temperature glycosylations. It was demonstrated
by Schmidt that propionitrile and acetonitrile have similar directing
effects in other glycosylation reactions.44

D. Crich, M. Patel / Carbohydrate Research 341 (2006) 1467–1475
1469
ane (Table 1, entry 4). It was subsequently shown that
comparable results could be obtained with low propor-
tions of acetonitrile in dichloromethane (Table 1, entries
6–8), and because of the greater ease of removal, the
mixed acetonitrile/dichloromethane system was selected
for use in further coupling reactions.
generally lower when a nitrile is included in the solvent
mixture, falling to a minimum with the use of pure pro-
pionitrile. In an attempt to shed further light on this
problem, the coupling of donor 1 with the primary
acceptor 4 was conducted in a 70/30 mixture of dichloro-
methane and acetonitrile. Examination of the crude
reaction mixture by 1H NMR spectroscopy revealed
the almost complete absence of the anticipated coupled
product 13 and the formation of one major product,
which was isolated by chromatography on silica gel in
30% yield, and tentatively assigned structure 18. This
assignment is based on the rhamnose anomeric hydro-
gen signal at d 5.13 whose broad singlet nature is typical
for an a-rhamnoside in this series, and on the 3H singlet
at d 1.99, attributed to the imidate methyl group. On
standing in deuteriochloroform, this unstable com-
pound underwent decomposition to acetate 19, thereby
providing further support for product 18, which is obvi-
ously formed by attack of the acceptor on the inter-
mediate nitrilium ion 20. Unfortunately, attempts to
detect the formation of nitrilium ion 20, or its congenor
arising from donor 2, by low temperature NMR spec-
troscopy have so far been unsuccessful. Presumably,
the increased concentration of acetonitrile leads to a
stabilization of nitrilium ion 20 and diverts nucleophilic
attack away from the anomeric center toward the
sp-hydridized carbon. In support of this mechanism,
we note that a variety of glycosyl nitrilium ions have
been captured intramolecularly by this ‘Ritter-like’
capture mode by various nucleophiles and that this
But
O
S
N
N
Ph
N
But
But
BSP
TTBP
A further series of coupling reactions were then
conducted with donor 2 in the 95/5 dichloromethane/
acetonitrile solvent mixture with the results indicated
in Table 2. In each a shift in the ratio of products, favor-
ing the b-anomer, is observed on inclusion of aceto-
nitrile, sometimes improving an already b-selective
reaction, sometimes changing a previously a-selective
reaction into a b-selective one, and other times reducing
a-selectivity.
A similar series of experiments were conducted with
donor 1 with similar consequences (Table 3). A compar-
ison between the results presented in Tables 2 and 3
reveals donor 1 to be generally more b-selective than
donor 2, whether the couplings are conducted in pure
dichloromethane or with the inclusion of acetonitrile.
As is clear from the ensemble of results presented in
Tables 1–3, the isolated yields of coupled products are
Table 2. Coupling reactions with donor 2 in CH2Cl2/CH3CN 95/5 (v/v) and in pure CH2Cl2
Entry
Acceptor
Product
Yielda (%) (b:a ratio)b
CH2Cl2/CH3CN (95/5)
CH2Cl2
HO
O
BnO
O
OMe
O
O
O
O
BnO
BnO
OBn
OBn
1
87 (5.8:1)
76% (7.2:1)
55% (2.1:1)
OBn
BnO
O
OMe
6
4
OBn
O
OBn
O
O
HO
O
BnO
O
O
BnO
2
3
70 (1:1.1)
85 (1:8.1)
BnO
BnO
OMe
OBn
OMe
OMe
O
7
8
OMe
O
O
HO
Ph
O
O
O
O
72% (1:4.2)
77% (1:1.2)
O
O
O
O
OBn
O
9
10
O
O
OBn
O
OH
O
O
O
O
O
Ph
O
4
87 (1:2.1)
BnO
O
OBn
O
OMe
OMe
11
12
a Yields refer to isolated products.
b Ratios were determined on the crude reaction mixtures by integration of the 1H NMR spectra.

1470
D. Crich, M. Patel / Carbohydrate Research 341 (2006) 1467–1475
Table 3. Further coupling reactions with donor 1 in CH2Cl2/CH3CN 95/5 (v/v) and in pure CH2Cl2
Entry
Acceptor
Producta
Yieldb (%) (b:a ratio)c
CH2Cl2/CH3CN (95/5)
CH2Cl2
HO
O
BnO
O
OMe
O
O
BzO
BnO
BnO
BnO
OBn
OBn
1
87 (12.7:1)
88% (16:1)
78% (1.2:1)
OSO2Ar
13
BnO
OMe
4
OMe
OMe
O
O
O
HO
Ph
O
BzO
BnO
2
3
O
85 (1:1.4)
92 (2.6:1)
74 (2.4:1)
O
O
O
OSO2Ar
9
14
O
O
OBn
O
OH
O
BzO
BnO
O
O
Ph
O
O
88% (3.9:1)
42% (3.5:1)
BnO
O
ArSO2
OMe
OMe
11
15
BnO
BnO
OBn
O
BnO
BnO
OBn
O
O
O
BzO
4
HO
OMe
BnO
OMe
OSO2Ar
16
17
a Ar = p-CF3C6H4.
b Yields refer to isolated products.
c Ratios were determined on the crude reaction mixtures by integration of the 1H NMR spectra.
3. Experimental
3.1. General methods
Me
AcO
BnO
O
N
O
O
BnO
BnO
O
BzO
BnO
BnO
BnO
BnO
OMe
OMe
OSO2Ar
All solvents were dried and distilled by standard proce-
dures. Trifluoromethanesulfonic anhydride was distilled
over P2O5. Acceptors and donors were dried at 40 ꢁC
under vacuum for 2 h before use. BSP and TTBP were
dried at room temperature under vacuum for 2 h before
use. Optical rotations were determined with an Autopol
III polarimeter for solutions in CHCl3. NMR spectra
were recorded for CDCl3 solutions with a Bruker
Avance spectrometer at 500 MHz (1H) or 125 MHz
(13C). Chemical shifts are in parts per million downfield
from tetramethylsilane. High resolution mass spectra
were recorded with a Waters Q-TOF2 instrument.
Microanalyses were conducted by Midwest Microlabs,
Indianapolis, IN. The anomeric stereochemistry of all
coupled products was assigned on the basis of the ano-
19
18
Me
N
O
BzO
BnO
OSO2Ar
20
chemistry has been applied in the synthesis of sugar
b-peptide libraries.49,50
Finally, we note the unexpectedly high amounts of a-
anomeric products 10a and 14a observed on coupling of
acceptor 9 to donors 1 and, especially, 2. In our very
extensive studies on the formation of the b-D-mannopyr-
anosides,4 acceptor 9 typically delivers b-selectivities in
excess of 10:1; certainly, it is usually a more b-selective
acceptor than the glucose 4-OH derivative 7. However,
comparison of Table 2, entries 2 and 3, reveals that
the roles are reversed in coupling to L-rhamnopyranosyl
donor 2. We believe this to be a manifestation of stereo-
chemical matching/mismatching,51 a phenomenon that
is gaining increasingly wide recognition in glycosidic
bond forming reactions.52–54
1
meric JCH coupling constants.55
3.2. General procedure for coupling reactions
Tf2O (0.40 mmol) was added dropwise to a stirred solu-
tion of donor (0.27 mmol), BSP (0.35 mmol), and TTBP
(0.80 mmol) in CH3CN (0.5 mL) and CH2Cl2 (7.0 mL)
under argon at ꢀ60 ꢁC. After stirring for 1 h at
ꢀ60 ꢁC, the acceptor (0.80 mmol) in CH2Cl2 (2.5 mL)
was added slowly over a period of 1 min. The reaction

D. Crich, M. Patel / Carbohydrate Research 341 (2006) 1467–1475
1471
mixture was stirred for 3 h at ꢀ60 ꢁC, then quenched at
ꢀ60 ꢁC with saturated NaHCO3, and extracted with
CH2Cl2 (3 · 20 mL). The combined organic layer was
dried (Na2SO4), and the solvent was removed under
reduced pressure. Purification by silica gel column chro-
matography (EtOAc/hexane) afforded the correspond-
ing a/b rhamnosides.
3.2.3. Methyl 2,3,6-tri-O-benzyl-4-O-(2-O-benzyl-3,4-
O-carbonyl-a-L-rhamnopyranosyl)-a-D-glucopyranoside
21
(8a). ½aꢁD ꢀ11.7 (c 1.0, CHCl3), lit.31 ꢀ19.6;
IR: 1811 cmꢀ1 1H NMR (CDCl3): d 7.33–7.21 (m,
;
20H, arom H), 5.09 (d, 1H, 2J = 11.0 Hz, –CH2Ph),
2
5.0 (s, 1H, H-1II), 4.76 (d, 1H, J = 12.0 Hz, –CH2Ph),
4.63–4.56 (m, 4H, H-1I –CH2Ph), 4.52 (d, 1H,
2J = 12.0 Hz, –CH2Ph), 4.45–4.41 (m, 2H, –CH2Ph),
4.25–4.23 (m, 2H, H-3II, H-4II), 4.11–4.08 (m, 1H, H-
5II), 3.93 (s, 1H, H-2II), 3.82–3.80 (m, 2H, H-3I, H-4I),
3.62 (m, 1H, H-5I), 3.58–3.53 (m, 2H, H-2I, H-6I),
3.41–3.38 (dd, 1H, J6a,6b = 11.0 Hz, J5,6a = 3.0 Hz, H-
6I), 3.35 (s, 3H, –OCH3), 0.97 (d, 3H, J5,6 = 6.0 Hz,
H-6II); 13C NMR: d 153.9, 138.2, 137.8, 137.5, 136.9,
128.7, 128.5, 128.4, 128.2, 128.08, 128.01, 127.90,
127.85, 127.75, 127.70, 98.6 (1JCH = 172.8 Hz), 97.9
(1JCH 166.1 Hz), 80.6, 80.2, 79.6, 78.2, 77.9, 77.5, 75.8,
74.1, 73.8, 73.6, 73.3, 72.6, 69.8, 69.0, 68.7, 55.3, 17.3;
ESIMS m/z calcd for C42H46O11Na [M+Na]+:
749.2938. Found: 749.2941.
3.2.1. Methyl 6-O-(2-O-benzyl-3,4-O-carbonyl-a-L-rhamno-
pyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (6a).
21
½aꢁD ꢀ3.6 (c 1.1, CHCl3), lit.31 ꢀ32.7; IR: 1813 cmꢀ1
;
1H NMR (CDCl3): d 7.38–7.21 (m, 20H, arom H), 5.01
(d, 1H, 2J = 11.0 Hz, –CH2Ph), 4.86 (d, 1H,
2J = 11.0 Hz, –CH2Ph), 4.81–4.77 (m, 2H, –CH2Ph),
4.77 (s, 1H, H-1II), 4.74 (d, 1H, J = 12.0 Hz, –CH2Ph),
2
4.68 (d, 1H, 2J = 12.0 Hz, –CH2Ph), 4.60 (d, 1H,
2J = 12.5 Hz, –CH2Ph), 4.54 (d, 1H, J = 4.0 Hz, H-1I),
4.50–4.48 (dd, 1H, J2,3 = 11.5 Hz, J3,4 = 3.0 Hz, H-3II),
2
4.46 (d, 1H, J = 11.0 Hz, –CH2Ph), 4.41–4.36 (t, 1H,
J3,4, J4,5 = 9.5 Hz, H-4II) 4.05 (m, 1H, H-5II), 4.02
(m, 1H, H-2II), 3.98 (t, 1H, J2,3, J3,4 = 10.0 Hz, H-3I),
3.83–3.81 (dd, 1H, J6a,6b = 10.5 Hz, J5,6a = 1.5 Hz,
H-6I), 3.71–3.68 (m, 1H, H-5I), 3.54–3.50 (dd, 1H,
J6a,6b = 11.5 Hz, J5,6b = 5.5 Hz, H-6I), 3.50–3.47 (dd,
3.2.4. Methyl 2,3,6-tri-O-benzyl-4-O-(2-O-benzyl-3,4-
O-carbonyl-b-L-rhamnopyranosyl)-a-D-glucopyranoside
21
(8b). ½aꢁD +18.8 (c 1.0, CHCl3), lit.31 +56.1;
1H, J2,3 = 9.5 Hz, J1,2 = 3.5 Hz, H-2I), 3.37 (t, 1H, J3,4
,
IR: 1811 cmꢀ1 1H NMR (CDCl3): d 7.38–7.25 (m,
;
J4,5 = 10.0 Hz, H-4I), 3.32 (s, 3H, –OCH3), 1.34 (d,
3H, J5,6 = 6.5 Hz, H-6II); 13C NMR: d 153.7, 138.6,
138.0, 136.8, 128.6, 128.52, 128.45, 128.18, 128.11,
128.00,127.98, 127.92, 127.80, 127.74, 127.71, 99.4
(1JCH = 172.3 Hz), 98.0 (1JCH = 167.1 Hz), 82.0, 80.5,
80.0, 77.9, 77.4, 75.8, 75.0, 74.1, 73.4, 72.9, 69.7, 68.6,
66.7, 55.2, 17.7; ESIMS m/z calcd for C42H46O11Na
[M+Na]+: 749.2938. Found: 749.2938.
18H, arom H), 7.11 (m, 2H, arom H), 4.99 (d, 1H,
2J = 11.5 Hz, –CH2Ph), 4.76–4.65 (m, 6H, H-1I, H-1II,
–CH2Ph), 4.61 (d, 1H, 2J = 12.0 Hz, –CH2Ph), 4.52
(d,1H, 2J = 12.0 Hz, –CH2Ph), 4.31–4.25 (m, 2H, H-
4II, –CH2Ph), 3.86 (t, 1H, J2,3, J3,4 = 9.0 Hz, H-3I),
3.82 (dd, 1H, J6a,6b = 10.5 Hz, J5,6a = 1.5 Hz, H-6I),
3.73 (m, 1H, H-6I), 3.69–3.62 (m, 2H, H-4I, H-5I),
3.53–3.48 (m, 4H, H-2I, H-2II, H-3II, H-5II), 3.44 (s,
3H, –OCH3), 1.24 (d, 3H, J5,6 = 6.0 Hz, H-6II); 13C
NMR: d 154.0, 138.6, 138.4, 137.8, 137.5, 128.6, 128.5,
128.4, 128.2, 128.15, 128.09, 128.05, 128.00, 127.87,
127.85, 127.42, 127.37, 101.5 (1JCH = 165.0 Hz), 97.7
(1JCH = 163.1 Hz), 82.2, 81.5, 80.0, 77.9, 76.2, 75.7,
73.44, 73.37, 73.10, 72.98, 70.6, 69.5, 68.8, 55.5, 17.7;
ESIMS m/z calcd for C42H46O11Na [M+Na]+:
749.2938. Found: 749.2923.
3.2.2. Methyl 6-O-(2-O-benzyl-3,4-O-carbonyl-b-L-rhamno-
pyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (6b).
21
½aꢁD +46.6 (c 1.0, CHCl3), lit.31 +52.3; IR: 1810 cmꢀ1
;
1H NMR (CDCl3): d 7.37–7.26 (m, 20H, arom H), 5.0
(d,1H, 2J = 11.0 Hz, –CH2Ph), 4.89–4.80 (m, 5H,
2
–CH2Ph), 4.73 (d, 1H, J = 10.5 Hz, –CH2Ph), 4.68 (d,
1H, 2J = 10.5 Hz, –CH2Ph), 4.66 (s, 1H, H-1II), 4.58
(d, 1H, J = 3.5 Hz, H-1I), 4.48–4.44 (dd, 1H,
J3,4 = 11.5 Hz, J4,5 = 9.0 Hz, H-4II), 4.29–4.27 (dd,
1H, J6a,6b = 11.5 Hz, J5,6a = 3.0 Hz, H-6I), 4.25 (d, 1H,
J2,3 = 2.0 Hz, H-2II), 4.13–4.10 (dd, 1H, J3,4 = 12.0 Hz,
J2,3 = 2.5 Hz, H-3II), 3.99 (t, 1H, J2,3, J3,4 = 9.0 Hz,
H-3I), 3.76–3.69 (m, H-5I, H-6I, H-5II), 3.61 (t, 1H,
3.2.5. Methyl 4-O-(2-O-benzyl-3,4-O-carbonyl-a-L-rhamno-
pyranosyl)-2,3-O-isopropylidene-a-L-rhamnopyranoside
21
1
(10a). ½aꢁD ꢀ68.5 (c 1.0, CHCl3); IR: 1819 cmꢀ1; H
NMR (CDCl3): d 7.36–7.31 (m, 5H, arom H), 5.48
(d, 1H, J1,2 = 1.0 Hz, H-1II), 4.85 (s, 1H, H-1I), 4.76
(d, 1H, 2J = 12.0 Hz, –CH2Ph), 4.70 (d, 1H,
2J = 12.0 Hz, –CH2Ph), 4.45 (m, 2H, H-3II, H-4II),
4.13 (m, 1H, H-2II), 4.06 (m, 3H, H-2I, H-3I, H-5II),
3.58 (m, 1H, H-5I), 3.50 (m, 1H, H-4I), 3.36 (s, 3H,
–OCH3), 1.51 (s, 3H, –C(CH3)2), 1.38 (d, 3H,
J5,6 = 6.0 Hz, H-6II), 1.34 (s, 3H, –C(CH3)2), 1.26
(d, 3H, J5,6 = 6.0 Hz, H-6I); 13C NMR: d 153.7,
136.9, 128.5, 128.1, 127.7, 109.6, 98.1 (1JCH = 174.9 Hz),
97.9 (1JCH = 167.4 Hz), 80.3, 78.4, 78.2, 77.9, 76.1, 74.6,
J3,4, J4,5 = 8.5 Hz, H-4I), 3.46–3.43 (dd, 1H, J2,3
=
10.0 Hz, J1,2 = 4.0 Hz, H-2I), 3.36 (s, 3H, –OCH3),
1.39 (d, 3H, J5,6 = 6.0 Hz, H-6II); 13C NMR: d 153.9,
138.8, 138.3, 138.1 137.2, 128.5, 128.41, 128.39, 128.1,
128.0, 127.9, 127.8, 127.6, 101.2 (1JCH = 157.5 Hz),
98.3 (1JCH = 166.9 Hz), 81.8, 81.6, 80.0, 77.9, 77.6,
75.6, 75.2, 73.8, 73.5, 73.4, 71.0, 70.0, 68.0, 55.3, 17.8;
ESIMS m/z calcd for C42H46O11Na [M+Na]+:
749.2938. Found: 749.2969.

1472
D. Crich, M. Patel / Carbohydrate Research 341 (2006) 1467–1475
72.8, 69.2, 63.5, 54.9, 27.9, 26.3, 17.9, 17.8; ESIMS m/z
calcd for C24H32O10Na [M+Na]+: 503.1893. Found:
503.1892.
H), 5.56 (s, 1H, H-7I), 4.94 (m, 4H, H-1I,
–CH2Ph), 4.79 (s, 1H, H-1II), 4.60 (d, 1H, 2J =
11.5 Hz, –CH2Ph), 4.44 (dd, 1H, J4,5 = 11.5 Hz,
J3,4 = 9.5 Hz, H-4II), 4.32 (m, 1H, H-6I), 4.28 (d, 1H,
J2,3 = 2.0 Hz, H-2II), 4.11 (t, 1H, J1,2, J2,3 = 2.5 Hz,
3.2.6. Methyl 4-O-(2-O-benzyl-3,4-O-carbonyl-b-L-rhamno-
pyranosyl)-2,3-O-isopropylidene-a-L-rhamnopyranoside
H-2I), 4.0 (m, 2H, H-3I, H-4I), 3.92 (dd, 1H, J3,4
=
21
(10b). ½aꢁD +5.6 (c 0.7, CHCl3); IR: 1810 cmꢀ1
;
1H
11.5 Hz, J2,3 = 2.5 Hz, , H-3II), 3.81 (m, 2H, H-5I,
H-6I), 3.60 (m, 1H, H-5II), 3.38 (s, 3H, –OCH3), 1.42
(d, 3H, J5,6 = 6.5 Hz, H-6II); 13C NMR: d 153.9, 138.5,
137.5, 137.4, 129.0, 128.5, 128.2, 128.0, 127.92, 127.86,
NMR (CDCl3): d 7.37–7.30 (m, 5H, arom H), 4.86–
4.79 (q, 2H, 2J = 12.5 Hz, –CH2Ph), 4.83 (s, 1H,
H-1I), 4.75 (d, 1H, J1,2 = 1.0 Hz, H-1II), 4.52–4.48 (dd,
1H, J4,5 = 11.5 Hz, J3,4 = 9.5 Hz, H-4II), 4.37 (t, 1H,
J2,3, J3,4 = 6.0 Hz, H-3I), 4.21 (d, 1H, J2,3 = 1.5 Hz,
H-2II), 4.13–4.11 (m, 2H, H-3II, H-2I), 3.76 (m, 1H,
127.5, 126.0, 101.9 (1JCH = 164.8 Hz), 101.6 (1JCH
=
160.5 Hz), 101.2 (1JCH = 174.8 Hz), 81.5, 79.4, 77.8,
76.4, 73.8, 73.7, 73.2, 71.0, 69.1, 63.7, 54.9, 17.8; ESIMS
H-5II), 3.70 (m, 1H, H-5I), 3.39–3.36 (dd, 1H, J4,5
=
m/z
calcd for C35H38O11Na [M+Na]+: 657.2307.
10.0 Hz, J3,4 = 7.0 Hz, H-4I), 3.37 (s, 3H, –OCH3),
1.48 (s, 3H, –C(CH3)2), 1.44 (d, 3H, J5,6 = 6.0 Hz
H-6II), 1.33 (s, 3H, –C(CH3)2), 1.25 (d, 3H,
J5,6 = 6.5 Hz, H-6I); 13C NMR: d 153.9, 137.1, 128.4,
128.1, 128.0, 109.0, 100.9 (1JCH = 157.1 Hz), 98.2
(1JCH = 166.5 Hz), 83.4, 81.8, 77.9, 76.40, 75.8, 73.6,
73.2, 71.1, 63.9, 54.9, 28.0, 26.1, 17.8, 17.7; ESIMS
m/z calcd for C24H32O10Na [M+Na]+: 503.1888. Found:
503.1885.
Found: 657.2307.
3.2.9. Methyl 6-O-[(4-O-benzoyl-3-O-benzyl-2-O-(2-tri-
fluoromethylbenzenesulfonyl)-a-L-rhamnopyranosyl)]-2,3,
21
4-tri-O-benzyl-a-D-glucopyranoside (13a). ½aꢁD +31.9
(c 1.0, CHCl3), lit.29 ꢀ30.2; H NMR (CDCl3): d 8.22
1
(d, 1H, J = 7.5 Hz, arom H), 7.95 (d, 2H, J = 8.5 Hz,
arom H), 7.73 (d, 1H, J = 8.0 Hz, arom H), 7.59–
7.26 (m, 17H, arom H), 7.14 (m, 1H, arom H), 7.06
(t, 2H, J = 8.0 Hz, arom H), 6.94 (d, 2H, J = 7.5 Hz,
arom H), 5.28 (t, 1H, J3,4, J4,5 = 9.5 Hz, H-4II), 5.12
(d, 1H, J1,2 = 1.5 Hz, H-1II), 5.03–5.01 (m, 2H, H-2II,
–CH2Ph), 4.94 (d, 1H, 2J = 11.0 Hz, –CH2Ph), 4.85
(d, 1H, 2J = 11.0 Hz, –CH2Ph), 4.83 (d, 1H,
2J = 12.0 Hz, –CH2Ph), 4.72 (d, 1H, 2J = 12.5 Hz,
–CH2Ph), 4.62 (d, 1H, J1,2 = 3.0 Hz, H-1I), 4.55 (d,
1H, 2J = 11.0 Hz, –CH2Ph), 4.30–4.23 (q, 2H, J =
12.5 Hz, –CH2Ph), 4.02 (t, 1H, J2,3, J3,4 = 9.5 Hz,
H-3I), 3.90–3.83 (m, 3H, H-6I, H-3II, H-5II), 3.79–3.76
(m, 1H, H-5I), 3.60–3.57 (dd, 1H, J6a,6b = 11.0 Hz,
J5,6a = 6.5 Hz, H-6I), 3.54 (dd, 1H, J2,3 = 9.5 Hz,
J1,2 = 3.0 Hz, H-2I), 3.40–3.36 (m, 4H, H-4I, –OCH3),
1.19 (d, 3H, J5,6 = 6.0 Hz, H-6II); 13C NMR: d 165.3,
138.6, 138.0, 137.9, 137.0, 135.2, 133.5, 133.2, 132.0,
131.6, 129.8, 129.7, 128.52, 128.48, 128.37, 128.31,
128.26, 128.20, 128.16, 128.08, 128.07, 128.00, 127.96,
127.92, 127.8, 127.6, 97.9 (1JCH 172.9 Hz), 97.8 (1JCH
157.3 Hz), 82.0, 79.9, 77.8, 76.8, 75.9, 75.2, 73.6, 73.3,
72.5, 71.5, 70.2, 67.0, 66.8, 55.2, 17.3; ESIMS m/z calcd
for C55H55O13F3NaS [M+Na]+: 1035.3213. Found:
1035.3218.
3.2.7. Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-(2-O-
benzyl-3,4-O-carbonyl-a-L-rhamnopyranosyl)-a-D-manno-
21
pyranoside (12a). ½aꢁD ꢀ69.9 (c 0.9, CHCl3); IR:
1810 cmꢀ1 1H NMR (CDCl3): d 7.52 (dd, 2H, J =
;
8.5 Hz, J = 2.5 Hz, arom H), 7.40–7.30 (m, 13H, arom
H), 5.65 (s, 1H, H-7I), 4.87 (d, 1H, 2J = 11.5 Hz,
–CH2Ph), 4.83 (s, 1H, H-1II), 4.82 (d, 1H, 2J =
12.5 Hz, –CH2Ph), 4.67 (dd, 1H, J3,4 = 11.0 Hz, J2,3
=
2.5 Hz, H-3II), 4.66 (d, 1H, 2J = 12.0 Hz, –CH2Ph),
2
4.63 (d, 1H, J = 12.0 Hz, –CH2Ph), 4.49 (d, 1H, J1,2
=
2.0 Hz, H-1I), 4.45 (m, 1H, H-5II), 4.35 (dd, 1H,
J4,5 = 11.5 Hz, J3,4 = 10.0 Hz, H-4II), 4.25 (dd, 1H,
J6a,6b = 10.0 Hz, J5,6a = 4.5 Hz, H-6I), 4.21 (m, 1H, H-
2II), 4.1 (dd, 1H, J2,3 = 3.5 Hz, J1,2 = 1.5 Hz, H-2I),
4.03 (t, 1H, J3,4, J4,5 = 10.0 Hz, H-4I), 3.94 (dd, 1H,
J3,4 = 9.5 Hz, J2,3 = 3.0 Hz, H-3I), 3.84 (t, 1H, J5,6a
,
J6a,6b = 10.5 Hz, H-6I), 3.76 (m, 1H, H-5I), 3.35 (s, 3H,
–OCH3), 1.11 (d, 3H, J5,6 = 6.0 Hz, H-6II); 13C NMR:
d 153.8, 138.0, 137.4, 137.0, 129.0, 128.6, 128.4, 128.2,
127.9, 127.8, 126.0, 101.6 (1JCH = 162.4 Hz), 98.8
(1JCH = 165.9 Hz), 97.6 (1JCH 169.3 Hz), 80.2, 79.1,
77.9, 75.0, 74.4, 74.0, 73.8, 73.3, 68.9, 68.7, 63.9, 55.0,
17.5; ESIMS m/z calcd for C35H38O11Na [M+Na]+:
657.2307. Found: 657.2306.
3.2.10. Methyl 6-O-[(4-O-benzoyl-3-O-benzyl-2-O-(2-tri-
fluoromethylbenzenesulfonyl)-b-L-rhamnopyranosyl)]-2,3,
21
4-tri-O-benzyl-a-D-glucopyranoside (13b). ½aꢁD +59.0 (c
1
3.2.8. Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-(2-O-
benzyl-3,4-O-carbonyl-b-L-rhamnopyranosyl)-a-D-manno-
1.0, CHCl3), lit.29 +22.9; H NMR (CDCl3): d 8.22 (d,
1H, J = 7.5 Hz, arom H), 7.96–7.94 (dd, 2H, J = 7.5
Hz, J 0.5 Hz, arom H), 7.66 (d, 1H, J = 8.0 Hz, arom
H), 7.59 (t, 1H, J = 7.0 Hz, arom H), 7.46–7.18 (m,
15H, arom H), 7.11 (t, 2H, J = 7.5 Hz, arom H), 7.04
(d, 2H, J = 7.0 Hz, arom H), 5.41 (d, 1H, J2,3 = 3.0 Hz,
H-2II), 5.29 (t, 1H, J3,4, J4,5 = 9.5 Hz, H-4II), 4.98 (d,
21
pyranoside (12b). ½aꢁD +29.3 (c 0.6, CHCl3);
IR: 1811 cmꢀ1
; d 7.49 (dd,
1H NMR (CDCl3):
2H, J = 8.5 Hz, J = 3.0 Hz, arom H), 7.45 (d, 2H,
J = 7.5 Hz, arom H), 7.40–7.37 (m, 4H, arom H),
7.34–7.31 (m, 4H, arom H), 7.27 (m, 3H, arom

D. Crich, M. Patel / Carbohydrate Research 341 (2006) 1467–1475
1473
1H, 2J = 11.0 Hz, –CH2Ph), 4.86–4.82 (m, 2H, –CH2Ph),
4.75 (d, 1H, 2J = 12.0 Hz, –CH2Ph), 4.66 (s, 1H, H-1II),
4.64 (d, 1H, J1,2 = 3.5 Hz, H-1I), 4.56–4.49 (m, 3H,
–CH2Ph), 4.37 (d, 1H, 2J = 12.5 Hz, –CH2Ph), 4.27–
4.24 (dd, 1H, J6a,6b = 11.5 Hz, J5,6a = 3.5 Hz, H-6I),
3.91 (t, 1H, J2,3, J3,4 = 9.0 Hz, H-3I), 3.69–3.63 (m, 3H,
H-5I, H-6I, H-3II), 3.56–3.52 (m, 2H, H-2I, H-5II), 3.43
(t, 1H, J3,4, J4,5 = 9.5 Hz, H-4I), 3.36 (s, 3H, –OCH3),
1.26 (d, 3H, J5,6 = 6.0 Hz, H-6II); 13C NMR: d 165.2,
139.1, 138.6, 138.4, 136.8, 136.5, 133.24, 133.22, 131.9,
130.9, 129.8, 129.6, 128.5, 128.4, 128.34, 128.26, 128.25,
128.17, 128.0, 127.92, 127.86, 127.74, 127.55, 127.52,
98.3 (1JCH 165.9 Hz), 97.8 (1JCH 156.8 Hz), 81.7, 79.6,
77.4, 77.2, 75.6, 74.9, 73.4, 72.5, 71.0, 70.9, 69.9, 67.1,
55.2, 17.6; ESIMS m/z calcd for C55H55O13F3NaS
[M+Na]+: 1035.3213. Found: 1035.3209.
J3,4 = 10.0 Hz, J2,3 = 3.0 Hz, H-3II), 3.56 (m, 1H, H-
5II), 3.49 (m, 1H, H-5I), 3.42–3.39 (m, 1H, H-4I), 3.34
(s, 3H, –OCH3), 1.50 (s, 3H, –C(CH3)2), 1.31 (s, 3H,
–C(CH3)2), 1.30 (d, 3H, J5,6 = 6.0 Hz, H-6II), 1.26 (d,
3H, J5,6 = 6.5 Hz, H-6I); 13C NMR: d 165.2, 136.83,
136.80, 133.3, 132.7, 131.8, 131.2, 129.8, 129.7, 128.4,
128.2, 128.0, 127.85, 127.80, 127.75, 127.70, 127.65,
127.61, 108.9, 98.0 (1JCH = 166.6 Hz), 97.6 (1JCH
=
155.1 Hz), 82.8, 78.0, 76.3, 76.1, 75.7, 72.6, 71.06,
71.05, 63.8, 54.7, 28.1, 26.1, 17.7, 17.5. Anal calcd for
C37H41F3O12S: C, 57.96; H, 5.39. Found: C, 58.03; H,
5.39.
3.2.13. Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-[(4-O-
benzoyl-3-O-benzyl-2-O-(2-trifluoromethylbenzenesulfon-
yl)-a-L-rhamnopyranosyl)]-a-D-mannopyranoside (15a).
21
½aꢁD ꢀ24.3 (c 1.1, CHCl3), lit.29 ꢀ35.6; 1H NMR
3.2.11. Methyl 4-O-[(4-O-benzoyl-3-O-benzyl-2-O-(2-tri-
fluoromethylbenzenesulfonyl)-a-L-rhamnopyranosyl)]-2,3-
(CDCl3): d 8.27 (d, 1H, J = 7.5 Hz, arom H), 7.92 (d,
2H, J = 7.5 Hz, arom H), 7.75 (d, 1H, J = 7.5 Hz, arom
H), 7.57–7.39 (m, 10H, arom H), 7.34 (d, 2H,
J = 7.0 Hz, arom H), 7.26–7.19 (m, 4H, arom H), 7.14
(t, 2H, J = 7.5 Hz, arom H), 6.99 (d, 2H, J = 7.0 Hz,
21
O-isopropylidene-a-L-rhamnopyranoside
(14a). ½aꢁD
+21.5 (c 0.5, CHCl3), lit.29 ꢀ55.2; H NMR (CDCl3):
d 8.26 (d, 1H, J = 7.5 Hz, arom H), 7.94 (d, 2H,
J = 7.5 Hz, arom H), 7.76 (d, 1H, J = 7.5 Hz, arom
H), 7.58–7.50 (m, 3H, arom H), 7.42 (t, 2H,
J = 8.0 Hz, arom H), 7.17 (t, 1H, J = 7.5 Hz, arom
H), 7.1 (t, 2H, arom H), 6.99 (d, 2H, J = 7.5 Hz, arom
1
arom H), 5.66 (s, 1H, H-7I), 5.30 (t, 1H, J3,4
,
J4,5 = 10.0 Hz, H-4II), 5.18 (d, 1H, J1,2 = 1.0 Hz, H-
1II), 5.11 (t, 1H, J1,2, J2,3 = 3.0 Hz, H-2II), 4.82 (d, 1H,
2J = 11.5 Hz, –CH2Ph), 4.72 (s, 1H, H-1I), 4.70 (d,
1H, 2J = 11.5 Hz, –CH2Ph), 4.39–4.30 (m, 4H, H-6I,
H-5II, –CH2Ph), 4.19 (s, 1H, H-2I), 4.02–3.98 (m, 3H,
H-3I, H-4I, H-3II), 3.88 (t, 1H, J5,6a, J6a,6b = 10.0 Hz,
H-6I), 3.81 (m, 1H, H-5I), 3.41 (s, 3H, –OCH3), 1.07
(d, 3H, J5,6 = 6.5 Hz, H-6II); 13C NMR: d 165.4, 138.0,
137.5, 137.1, 135.0, 133.5, 133.1, 132.0, 131.7, 129.9,
129.7, 129.0, 128.4, 128.32, 128.26, 128.23, 128.18,
127.7, 127.6, 126.1, 101.6 (1JCH = 162.3 Hz), 99.0
(1JCH = 170.5 Hz), 96.5 (1JCH = 170.6 Hz), 78.7, 74.5,
74.1, 73.8, 73.1, 72.4, 71.7, 68.8, 67.2, 63.9, 55.1, 17.2;
ESIMS m/z calcd for C48H47F3O13NaS [M+Na]+:
943.2587. Found: 943.2598.
H), 5.48 (d, 1H, J1,2 = 1.5 Hz, H-1II), 5.28 (t, 1H, J3,4
,
J4,5 = 9.5 Hz, H-4II), 5.19 (t, 1H, J1,2, J2,3 = 2.5 Hz,
H-2II), 4.86 (s, 1H, H-1I), 4.39 (d, 1H, 2J = 12.0 Hz,
–CH2Ph), 4.30 (d, 1H, 2J = 12.0 Hz, –CH2Ph), 4.12–
4.11 (m, 2H, H-2I, H-3I), 3.91–3.86 (m, 2H, H-3II,
H-5II), 3.66–3.63 (m, 1H, H-5I), 3.48–3.45 (m, 1H, H-
4I), 3.39 (s, 3H, –OCH3), 1.55 (s, 3H, –C(CH3)2), 1.37
(s, 3H, –C(CH3)2), 1.27 (d, 3H, J5,6 = 6.5 Hz, H-6I),
1.22 (d, 3H, J5,6 = 6.5 Hz, H-6II); 13C NMR: d 165.2,
137.1, 135.5, 133.3, 133.1, 131.9, 131.7, 129.8, 129.7,
128.3, 128.24, 128.20, 128.1, 127.7, 127.5, 109.7, 98.0
(1JCH = 165.4 Hz), 97.2 (1JCH = 171.6 Hz), 79.3, 77.8,
77.1, 76.0, 73.7, 72.4, 71.4, 67.7, 63.9, 55.0, 28.0, 26.4,
17.7, 17.5. Anal calcd for C37H41F3O12S: C, 57.96; H,
5.39. Found: C, 57.66; H, 5.23.
3.2.14. Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-[(4-O-
benzoyl-3-O-benzyl-2-O-(2-trifluoromethylbenzenesulfon-
yl)-b-L-rhamnopyranosyl)]-a-D-mannopyranoside (15b).
21
3.2.12. Methyl 4-O-[(4-O-benzoyl-3-O-benzyl-2-O-(2-tri-
fluoromethylbenzenesulfonyl)-b-L-rhamnopyranosyl)]-2,3-
½aꢁD +51.1 (c 1.0, CHCl3), lit.29 +25.6; 1H NMR
(CDCl3): d 8.35 (m, 1H, arom H), 7.94–7.92 (dd, 2H,
J = 8.0 Hz, 1.0 Hz, arom H), 7.77 (m, 1H, arom H),
7.59–7.26 (m, 15H, arom H), 7.16 (t, 1H, J = 7.5 Hz,
arom H), 7.07 (t, 2H, J = 7.5 Hz, arom H), 6.96
(d, 2H, J = 7.0 Hz, arom H), 5.69 (s, 1H, H-7I), 5.47
21
O-isopropylidene-a-L-rhamnopyranoside
(14b). ½aꢁD
+43.6 (c 0.7, CHCl3), lit.29 +30.7; H NMR (CDCl3):
d 8.28 (m, 1H, arom H), 7.96 (d, 2H, J = 8.0 Hz, arom
H), 7.74 (m, 1H, arom H), 7.59–7.52 (m, 3H, arom
H), 7.43 (t, 2H, J = 7.5 Hz, arom H), 7.16 (t, 1H,
J = 7.0 Hz, arom H), 7.08 (t, 2H, J = 7.5 Hz, arom
H), 7.0 (d, 2H, J = 7.5 Hz, arom H), 5.34 (d, 1H,
J2,3 = 3.0 Hz, H-2II), 5.30 (t, 1H, J3,4, J4,5 = 9.5 Hz,
H-4II), 4.80 (s, 2H, H-1I, H-1II), 4.82 (d, 1H,
2J = 12.5 Hz, –CH2Ph), 4.34 (d, 1H, 2J = 12.0 Hz,
–CH2Ph), 4.16 (t, 1H, J2,3, J3,4 = 6.5 Hz, H-3I), 4.05
(d, 1H, J2,3 = 6.0 Hz, H-2I), 3.70–3.68 (dd, 1H,
1
(d, 1H, J2,3 = 2.5 Hz, H-2II), 5.26 (t, 1H, J3,4
,
J4,5 = 10.0 Hz, H-4II), 4.98 (d, 1H, 2J = 12.0 Hz,
–CH2Ph), 4.89 (s, 1H, H-1II), 4.67 (d, 1H, 2J =
12.0 Hz, –CH2Ph), 4.63 (d, 1H, J1,2 = 1.5 Hz, H-1I),
2
4.44 (d, 1H, J = 12.5 Hz, –CH2Ph), 4.31 (t, 1H, J3,4
,
J4,5 = 9.5 Hz, H-4I), 4.25–4.19 (m, 2H, H-6I, –CH2Ph),
4.15 (m, 1H, H-2I), 4.00–3.98 (dd, 1H, J3,4 = 9.5 Hz,
J2,3 2.5 Hz, H-3I), 3.81 (t, 1H, J5,6a, J6a,6b = 10.0 Hz,

1474
D. Crich, M. Patel / Carbohydrate Research 341 (2006) 1467–1475
H-6I), 3.75 (m, 1H, H-5I), 3.49–3.46 (dd, 1H, J3,4
=
NMR: d 165.2, 139.1, 139.0, 138.4, 136.7, 136.5, 133.2,
132.7, 131.8, 131.0, 129.7, 129.6, 128.40, 128.37,
128.32, 128.25, 128.17, 128.10, 127.9, 127.8, 127.6,
9.5 Hz, J2,3 = 2.5 Hz, H-3II), 3.42 (m, 1H, H-5II), 3.33
(s, 3H, –OCH3), 1.29 (d, 3H, J5,6 = 6.5 Hz, H-6II); 13C
NMR: d 165.2, 138.9, 137.8, 137.0, 136.9, 133.2, 132.6,
132.0, 131.1, 129.8, 129.7, 128.8, 128.5, 128.4, 128.20,
128.17, 127.95, 127.91, 127.86, 127.81, 127.72, 127.65,
127.60, 127.57, 126.1, 101.5 (1JCH = 164.5 Hz), 100.9
(1JCH = 171.8 Hz), 98.6 (1JCH = 161.0 Hz), 79.0, 77.6,
76.6, 76.5, 75.9, 73.6, 72.3, 71.0, 70.8, 68.9, 64.0,
54.7, 17.6; ESIMS m/z calcd for C48H47F3O13NaS
[M+Na]+: 943.2587. Found: 943.2542.
127.55, 127.47, 127.2, 100.2 (1JCH = 155.4 Hz) (1JCH
=
164.5 Hz), 83.4, 78.2, 76.7, 76.2, 75.0, 74.8, 73.5, 73.1,
72.3, 71.9, 71.2, 70.8, 69.4, 54.7, 17.7; ESIMS m/z calcd
for C55H55O13F3KS [M+Na]+: 1035.3213. Found:
1035.3236.
3.3. Methyl 6-O-acetyl-2,3,4-tri-O-benzyl-a-D-gluco-
pyranoside
3.2.15. Methyl 3-O-[(4-O-benzoyl-3-O-benzyl-2-O-(2-tri-
fluoromethylbenzenesulfonyl)-a-L-rhamnopyranosyl)]-2,4,
Tf2O (0.027 mL, 0.16 mmol) was added dropwise to a
stirred solution of donor 1 (70 mg, 0.11 mmol) and
BSP (29 mg, 0.14 mmol), in CH3CN (1.2 mL) and
CH2Cl2 (1.8 mL) under argon at ꢀ60 ꢁC. After stirring
for 1 h at ꢀ60 ꢁC, acceptor 4 (150 mg, 0.32 mmol) in
CH2Cl2 (1.0 mL) was added over a period of 1 min.
The reaction mixture was stirred for 3 h at ꢀ60 ꢁC, then
quenched at ꢀ60 ꢁC with saturated aqueous NaHCO3,
and extracted with CH2Cl2. (3 · 15 mL). The combined
organic layer was dried (Na2SO4), and the solvent was
removed under reduced pressure. Examination of the
crude reaction mixture by 1H NMR spectroscopy
revealed the formation of one very major product,
tentatively assigned as the imidate (18). Purification by
silica gel column chromatography (EtOAc/hexane)
afforded the unstable 18 (30 mg, 27%) and acetate 19
(10 mg, 6%). Compound 18 rapidly decomposed on
standing in CDCl3 to a mixture of 19 and several other
compounds. It was characterized by the following
signals: 1H NMR (300 MHz, CDCl3): d 5.13 (s, 1H,
H-1II), 4.62 (d, 1H, J1,2 = 3.6 Hz, H-1I), 3.42 (s, 3H,
–OCH3), 1.99 (s, 3H, CH3C(OR)=N), 1.17 (d, 3H
J5,6 = 6.3 Hz, H-6II).
21
6-tri-O-benzyl-a-D-mannopyranoside (17a). ½aꢁD +6.9
1
(c 0.7, CHCl3), lit.29 ꢀ23.1; H NMR (CDCl3): d 8.16
(d, 1H, J = 8.5 Hz, arom H), 7.72 (m, 3H, arom H),
7.56–7.07 (m, 21H, arom H), 7.01 (t, 2H, J = 7.5 Hz,
arom H), 6.88 (d, 2H, J = 7.5 Hz, arom H), 5.36
(s, 1H, H-1II), 5.30 (t, 1H, J3,4, J4,5 10.0 Hz, H-4II),
5.03 (s, 1H, H-2II), 4.85 (s, 1H, H-1I), 4.81–4.71 (m,
3H, –CH2Ph), 4.62–4.55 (m, 2H, –CH2Ph), 4.45
2
(d, 1H, J = 11.0 Hz, –CH2Ph), 4.21–4.10 (m, 3H, H-
3I, –CH2Ph), 4.03 (m, 1H, H-5II), 4.00–3.93 (m, 3H,
H-2I, H-4I, H-3II), 3.82 (m, 1H, H-6I), 3.78–3.72 (m,
2H, H-5I, H-6I), 3.34 (s, 3H, –OCH3), 1.13 (d, 3H,
J5,6 = 6.0 Hz, H-6II); 13C NMR: d 165.2, 138.4, 138.3,
138.0, 136.7, 134.9, 133.5, 133.1, 131.9, 131.7, 129.7,
129.6, 128.5, 128.3, 128.1, 127.74, 127.71, 127.69,
127.64, 127.59, 127.54, 127.50, 127.3, 98.7 (1JCH
169.8 Hz), 93.5 (1JCH 171.6 Hz), 76.9, 75.0, 74.8, 73.9,
73.8, 73.6, 73.4, 73.2, 72.2, 71.5, 71.3, 69.0, 67.1, 54.9,
17.3; ESIMS m/z calcd for C55H55O13F3KS [M+K]+:
1051.2953. Found: 1051.2914.
3.2.16. Methyl 3-O-[(4-O-benzoyl-3-O-benzyl-2-O-(2-tri-
fluoromethylbenzenesulfonyl)-b-L-rhamnopyranosyl)]-2,4,
3.3.1. Methyl 6-O-acetyl-2,3,4-tri-O-benzyl-a-D-gluco-
21
21
6-tri-O-benzyl-a-D-mannopyranoside (17b). ½aꢁD +68.9
pyranoside (19). ½aꢁD +18.0 (c 0.8, CHCl3), lit.56
1
1
(c 1.1, CHCl3), lit.29 +35.2; H NMR (CDCl3): d 8.23
+28.6; H NMR (CDCl3): d 7.37–7.26 (m, arom H),
2
(d, 1H, J = 7.0 Hz, arom H), 7.90 (dd, 2H, J = 8.0 Hz,
J = 0.5 Hz, arom H), 7.67 (d, 1H, J = 9.0 Hz, arom
H), 7.56 (t, 1H, J = 7.0 Hz arom H), 7.45–7.24
(m, 19H, arom H), 7.15 (t, 1H, J = 7.5 Hz, arom H),
7.06 (t, 2H, J = 7.5 Hz, arom H), 6.90 (d, 2H,
J = 7.5 Hz, arom H), 5.27 (t, 1H, J3,4, J4,5 = 9.0 Hz,
H-4II), 5.13 (d, 1H, J2,3 = 2.5 Hz, H-2II), 4.88 (d, 1H,
2J = 13.0 Hz, –CH2Ph), 4.77 (t, 2H, 2J = 10.5 Hz,
–CH2Ph), 4.72 (s, 1H, H-1II), 4.71 (d, 1H, 2J =
12.0 Hz, –CH2Ph), 4.65 (d, 1H, J1,2 = 1.5 Hz, H-1I),
5.09 (d, 1H, J = 10.5 Hz, –CH2Ph), 4.89–4.79 (m, 3H,
–CH2Ph), 4.68 (d, 1H, 2J = 12.5 Hz, –CH2Ph), 4.59–
4.55 (m, 2H, –CH2Ph), 4.26–4.24 (m, 2H, H-6), 4.01
(t, 1H, J3,4, J4,5 = 9.5 Hz, H-3), 3.81 (m, 1H, H-5),
3.55–3.52 (dd, 1H, J2,3 = 9.5 Hz, J1,2 = 3.5 Hz, H-2),
3.48 (t, 1H, J4,5, J3,4 = 9.0 Hz, H-4), 3.37 (s, 3H,
–OCH3), 2.02 (s, 3H, CH3CO); 13C NMR: d 170.7,
138.6, 138.0, 137.8, 128.50, 128.48, 128.45, 128.13,
128.09, 128.01, 127.99, 127.92, 127.7, 98.1, 82.0, 79.8,
75.8, 75.0, 73.4, 68.5, 63.0, 55.2, 20.9.
2
4.60–4.57 (m, 2H, –CH2Ph), 4.30 (d, 1H, J = 12.5 Hz,
–CH2Ph), 4.13 (d, 1H, 2J = 12.5 Hz, –CH2Ph), 4.02
(dd, 1H, J3,4 = 9.5 Hz, J2,3 = 2.5 Hz, H-3I), 3.94 (t,
1H, J3,4, J4,5 = 9.5 Hz, H-4I), 3.89 (m, 1H, H-2I), 3.79–
3.75 (m, 3H, H-5I, H-6I), 3.48 (m, 1H, H-5II), 3.41–
3.39 (dd, 1H, J3,4 = 9.5 Hz, J2,3 = 3.0 Hz, H-3II), 3.32
(s, 3H, –OCH3), 1.26 (d, 3H, J5,6 = 6.5 Hz, H-6II); 13C
Acknowledgement
We thank the NIH (GM57335) for support of this work,
and John Picione for first recognizing the a-selective
coupling of donor 2 with acceptor 9.

D. Crich, M. Patel / Carbohydrate Research 341 (2006) 1467–1475
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rides. Supplementary data associated with this article
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