Stereoselective glycosylations using (R)- or (S)-(ethoxycarbonyl)benzyl chiral auxiliaries at C-2 of glycopyranosyl donors

FULL PAPER

DOI: 10.1002/ejoc.200600440

Stereoselective Glycosylations Using (R)- or (S)-(Ethoxycarbonyl)benzyl Chiral

Auxiliaries at C-2 of Glycopyranosyl Donors

Jin-Hwan Kim,^[a]Hai Yang,^[a]Vishal Khot,^[a]Dennis Whitfield,*^[b]and Geert-Jan Boons*^[a]

Keywords: Carbohydrates / Glycosylation / Anomeric control / Chiral auxiliary

The stereoselective introduction of a glycosidic bond pres-

ents the greatest challenge to complex oligosaccharide syn-

thesis. Important developments such as automated polymer-

supported oligosaccharide synthesis will not realize their full

potential until this problem is addressed. In this paper, a

novel approach for stereoselective glycosylations is de-

scribed whereby a chiral auxiliary at C-2 of a glycosyl donor

controls the anomeric outcome of a glycosylation. It was

found that participation of an (S)-ethoxycarbonylbenzyl aux-

iliary led to the formation of 1,2-cis glycosides, probably

through a trans-fused dioxolenium ion intermediate. On the

other hand, the use of an auxiliary with (R) configuration

gave 1,2-trans glycosides, and this glycosylation proceeds

through a cis-fused dioxolenium ion intermediate. The auxil-

iary could conveniently be removed by Birch reduction.

Computational studies support the formation of the proposed

ethoxy-carbonium ion intermediate with all pseudo-equato-

rial substituents.

Germany, 2006)

The last two decades have witnessed dramatic improve-

ments in the methods available for the synthesis of complex

oligosaccharides. New anomeric leaving groups such as an-

omeric fluorides, trichloroacetimidates, and thioglycosides

have been introduced which can be prepared under mild

conditions, are sufficiently stable for purification, may be

stored for a considerable period of time and undergo glyco-

sylations under mild conditions. These beneficial features

permit the synthesis of complex oligosaccharides by highly

convergent strategies in which most synthetic efforts are di-

rected towards the preparation of monomeric glycosyl ac-

ceptors and donors, which can be assembled into complex

structures using a minimum number of synthetic steps. The

synthesis of complex oligosaccharides has been further

streamlined by one-pot multi-step glycosylations^[5,6]and

automated polymer-supported syntheses,^[7–9]which reduces

the need for time-consuming purification protocols.

Despite these important developments, the problem re-

mains that there is no general method for the preparation

of complex oligosaccharides of biological importance. One

of the main stumbling blocks in complex oligosaccharide

synthesis is the formation of mixtures of α/β-anomers dur-

ing glycosylations. Separation of these anomers requires

time-consuming purification protocols resulting in loss of

material. The formation of anomeric mixtures also severely

limits the use of one-pot multi-step glycosylations or poly-

mer-supported syntheses.

Introduction

It is now well established that protein- and lipid-bound

saccharides play essential roles in many molecular processes

impacting eukaryotic biology and disease.^[1–3]Examples of

such processes include fertilization, embryogenesis, neu-

ronal development, hormone activities, the proliferation of

cells and their organization into specific tissues. Remark-

able changes in cell-surface carbohydrates occur with tumor

progression, an event that appears to be intimately associ-

ated with the dreaded state of metastasis. Furthermore,

carbohydrates are capable of inducing a protective antibody

response, which is a major contributor to the survival of an

organism during infection. In plants, oligosaccharides have

been found to control development and defense mecha-

nisms.

A major obstacle to advances in glycobiology is the lack

of pure and structurally well-defined carbohydrates and gly-

coconjugates. These compounds are often found in low con-

centrations and in microheterogeneous forms, greatly com-

plicating their isolation and characterization. In many

cases, well-defined oligosaccharides can only be obtained

by chemical synthesis.^[4]

[a] Complex Carbohydrate Research Center, University of Geor-

gia,

315 Riverbend Road, Athens, GA 30602, USA

E-mail: gjboons@ccrc.uga.edu

Currently, the most reliable method for stereoselective

glycosylations is based on neighboring-group participation

by a 2-O-acyl functionality (Scheme 1, a).^[10]In these reac-

tions, a promoter activates an anomeric leaving group re-

sulting in its departure and the formation of an oxacarben-

[b] National Research Council of Canada, Institute for Biological

Sciences,

100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada

E-mail: dennis.whitfield@nrc-cnrc.gc.ca

Supporting information for this article is available on the

WWW under http://ww w .eurjoc.org or from the author.

Eur. J. Org. Chem. 2006, 5007–5028

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Scheme 1. Conventional and new approaches for stereoselective glycosylation. (a) Classical neighboring-group participation by C-2 ester

leading to 1,2-trans glycosides. (b) Neighboring-group participation by an (S) auxiliary at C-2 leading to 1,2-cis glycosides. (c) Neigh-

boring-group participation by an (R) auxiliary at C-2 leading to 1,2-trans glycosides.

ium ion. Subsequent neighboring-group participation of the the auxiliary will participate, leading to the formation of

2-O-acyl protecting group will give a more stable dioxolen- either a trans- or cis-decalin system. It is expected that an

ium ion. This bicyclic intermediate will only be formed as auxiliary with (S) stereochemistry will lead only to the for-

a 1,2-cis isomer because the alternate 1,2-trans configura- mation of trans-decalin because the alternate cis-fused sys-

tion will experience considerable ring strain. An alcohol can tem will place the phenyl substituent in an axial position

attack the anomeric center of the dioxolenium ion from inducing unfavorable steric interactions (Scheme 1, b). Sub-

only one face leading to the stereospecific formation of a sequent displacement of the anomeric moiety of the trans-

1,2-trans glycoside. Thus, in the case of glucosyl-type do- decalin intermediate will lead to the formation of a 1,2-

nors, β-linked products will be formed while mannosyl do- cis glycoside. Alternatively, the use of an auxiliary with (R)

nors will give α-glycosides.

stereochemistry will lead to the formation of a 1,2-trans gly-

The introduction of 1,2-cis-glycosidic linkages, such as α- coside because in this case the trans-decalin system will ex-

glucosides and α-galactosides, requires glycosyl donors with perience unfavorable steric interactions. Therefore glycosy-

a non-assisting functionality at C-2. Invariably, the use of lation will only take place from the cis-decalin intermediate

these glycosyl donors leads to the formation of mixtures of (Scheme 1, c).

anomers.^[11,12]Thus, the stereoselective formation of 1,2-cis

glycosides is the principal challenge of complex oligosac-

charide synthesis.

Here, we describe a novel strategy for stereoselective gly-

cosylations using a chiral auxiliary at C-2 of a glycosyl do-

Results and Discussion

nor (Scheme 1b, c). The auxiliary is a C-1 substituted ethyl

Ethyl mandelate was explored as a first-generation chiral

moiety that contains a nucleophilic group (Nu). Upon for- auxiliary because both enantiomers of this compound are

mation of an oxacarbenium ion, the nucleophilic moiety of readily available. Furthermore, esters are well-established as

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appropriate participating functionalities in glycosylations and 17R/S, were prepared which have a benzoyl ester, an

and the benzylic nature of the auxiliary will make it possible allyl carbonate or an allyl ether at C-3, respectively. These

to remove it under reductive conditions. Glucosyl donors glycosyl donors were expected to be convenient for complex

5R and 5S, containing a (R)- or (S)-ethoxycarbonylbenzyl oligosaccharide synthesis because the C-6 acetyl ester can

moiety, could be prepared from the readily available epox- be removed in the presence of a benzoyl group, whereas the

ide 1.^[13]Thus, reaction of 1 with ethyl (R)-mandelate in the allyl- or allyloxycarbonyl-protecting group can be cleaved

presence of BF₃·OEt₂led to a trans-diaxial opening of the without affecting the acetyl group at C-6. The glycosyl do-

epoxide to give 2R in a yield of 48%. Next, acetolysis of nors could easily be prepared from the key intermediates

the 1,6-anhydro bridge of 2R with acetic anhydride and 2R/S. Thus benzoylation of the individual diastereoisomers

TMSOTf gave compound 3R in an almost quantitative 2R/S followed by acetolysis of the 1,6-anhydro-bridge of the

yield. The anomeric acetyl group of 3R was selectively re- resulting 6R/S gave the acetates 7R/S, which were converted

moved with hydrazinium acetate to give hemiacetal 4R, into the trichloroacetimidates 9R/S by a standard two-step

which was converted into the trichloroacetimidate 5R using procedure. The allyloxycarbonyl (Alloc) protected deriva-

trichloroacetonitrile in the presence of DBU.^[14]The glyco- tives 13R/S could be prepared by a similar approach by first

syl donor 5S was prepared by a similar protocol using ethyl reacting 2R/S with allyloxycarbonyl chloride in the presence

(S)-mandelate as the starting material (Scheme 2).

of N,N,NЈ,NЈ-tetramethylethylenediamine (TMEDA) to

It is well known that the protecting-group pattern of a give 10R/S, which were converted into the anomeric trichlo-

glycosyl donor can influence the anomeric outcome of a roacetimidates by standard chemical manipulation. The gly-

glycosylation. Therefore, the glucosyl donors 9R/S, 13R/S cosyl donors 17R/S, which have an allyl ether at C-3, could

Scheme 2. Preparation of glycosyl donors 5R/S, 9R/S, 13R/S and 17R/S.

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J.-H. Kim, H. Yang, V. Khot, D. Whitfield, G.-J. Boons

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be synthesized by decarboxylation of the allyloxycarbonyl within 15 min, indicating that the glycosyl donor 5S is

moiety of 10R/S using Pd(PPh₃)₄to give the allyl ethers highly reactive. Dilution of the reaction mixture led to a

14R/S, followed by introduction of an anomeric trichlo- small increase in anomeric selectivity, whereas higher reac-

roacetimidate using standard manipulations.

tion temperatures led to reductions of α-anomeric selectiv-

Having a number of differently protected glycosyl donors ity. As expected, the coupling of 5R with 23 under similar

at hand, attention was focused on glycosylations with the reaction conditions gave 28R as mainly the β-anomer albeit

glycosyl acceptors 23–27. Thus, coupling of 5S with 23 with somewhat lower selectivity (Table 1, Entry 2).

using a catalytic amount of trimethylsilyl triflate (TMSOTf)

The fact that an inversion of configuration of the asym-

in dichloromethane (DCM) at –78 °C gave the disaccharide metric center of the auxiliary led to a reversal of the stereo-

28S mainly as the α-glycoside in high yield (Table 1, Entry chemical outcome of the glycosylation supports the pro-

1). At this low temperature, the reaction was completed posed mode of participation outlined in Scheme 1 (b, c). In

Table 1. Stereoselective glycosylations with glucosyl donor 5R/S, 9R/S, 13R/S and 17R/S.

Entry

Glycosyl donor

Glycosyl acceptor

Product

α/β Ratio (yield, %)^[a]

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

5S

5R

23

28S

28R

29S

29R

30S

30R

31S

31R

32S

32R

33S

33R

34S

34R

35S

35R

36S

36R

37S

37R

38S

38R

20:1 (89%)

1:5 (91%)

12:1 (92%)

1:3 (88%)

10:1 (95%)

1:8 (94%)

18:1 (94%)

1:1 (89%)

4:1 (93%)

1:6 (96%)

7:1 (88%)

1:3 (94%)

α (93%)

5S

24

25

26

27

23

24

23

24

23

24

5R

5S

5R

5S

5R

5S

5R

9S

9R

9S

9R

β (84%)

13S

13R

13S

13R

17S

17R

17S

17R

6:1 (81%)

1:9 (85%)

10:7 (79%)

β (90%)

1:3 (87%)

1:4 (80%)

4:1 (95%)

1:5 (75%)

1

[a] Product ratios were determined by H NMR analysis of the crude reaction products.

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order to demonstrate the generality of the approach, 5R

and 5S were glycosylated with a range of glycosyl acceptors.

As can be seen in Table 1, TMSOTf-mediated coupling of

5S with the glycosyl acceptors 24, 25, 26 and 27 gave the

disaccharides 29S, 30S, 31S and 32S, respectively, with high

α-selectivity (Table 1, Entries 3, 5, 7 and 9). In each case,

the use of glycosyl donor 5R led to a reversal of anomeric

selectivity and the disaccharides 29R, 30R, 31R and 32R

were isolated in excellent yields with modest to good β-an-

omeric selectivity (Table 1, Entries 4, 6, 8 and 10).

In order to determine the influence of the protecting-

group pattern of the glycosyl donor on the anomeric out-

come of glycosylations, the trichloroacetimidates 9S/R, 13S/

R and 17S/R were coupled with the acceptors 23 and 24,

which have a secondary and primary alcohol, respectively.

As can be seen in Table 1, the glycosylations with the glyco-

syl donors 9S and 13S gave the corresponding disaccha-

rides 33S, 34S, 35S and 36S in excellent yields with good

to exclusive α-anomeric selectivity (Table 1, Entries 11, 13,

15 and 17). When the corresponding 9R and 13R were em-

ployed as glycosyl donors an expected reversal of anomeric

selectivity was observed, and the disaccharides 33R, 34R,

35R and 36R were isolated as mainly β-anomers (Table 1,

Entries 12, 14, 16 and 18). Surprisingly, the glycosylations

of 17S/R, which have an allyl ether at C-3, with the glycosyl

acceptors 23 and 24 gave the corresponding disaccharides

37S/R and 38S/R with modest anomeric selectivity (Table 1,

Entries 19–22). These results indicate that an ester protect-

ing group at C-3 is important for efficient participation of

the (S)-ethoxycarbonylbenzyl auxiliary.

Scheme 3. Deprotection of disaccharide 31Sα.

To be useful for target synthesis, it is important that the

auxiliary can be removed under mild conditions. The auxil-

iary was designed in such a way that it contains a substi-

tuted benzyl ether, and therefore should be removable by

catalytic hydrogenation over Pd/C or by Birch reduction.

Indeed, saponification of the benzoyl ester of 31Sα by treat-

ment with NaOMe in methanol followed by removal of the

benzyl ethers and chiral auxiliary using sodium in liquid

ammonia led to a clean formation of the deprotected com-

pound 42 (Scheme 3). On the other hand, catalytic hydro-

genation over Pd/C was sluggish probably due to steric hin-

drance at the benzylic carbon.

Scheme 4. Preparation of glycosyl donor 22R/S.

Finally, it was investigated whether the novel methodol-

ogy can also be applied to galactosyl donors. For this pur-

Gratifyingly, TMSOTf-mediated glycosylation of 22S

pose, the galactosyl trichloroacetimidates 22R/S were pre- with the glycosyl acceptors 23 and 26 gave the correspond-

pared by starting from the readily available 1,6:2,3-di-anhy- ing disaccharides 39S and 40S with good α-anomeric selec-

dro-β--talopyranose (18). Thus, a trans-diaxial opening of tivity, whereas the use of the glycosyl donor 22R, which has

the epoxide of 18 with ethyl (R)-mandelate in the presence a (R)-mandelate at C-2, gave 39R and 40R with modest β-

of BF₃·OEt₂gave 19R in a yield of 51%. Treatment of 19R selectivity (Table 2).

with acetic anhydride and TMSOTf resulted in the opening

The anomeric selectivities summarized in Table 1 and

of the 1,6-anhydro bridge to give compound 20R in an al- Table 2 show that glycosylations with glycosyl donors hav-

most quantitative yield, which was converted into the trich- ing an (S)-ethoxycarbonylbenzyl moiety at C-2 give pre-

loroacetimidate 22R by selective removal of the anomeric dominantly α-glycosides, whereas the donors containing an

acetyl group using hydrazinium acetate to give the hemiace- auxiliary with opposite stereochemistry give mainly β-gly-

tal 21R, followed by treatment with trichloroacetonitrile in cosides. It was, however, observed that the β-anomeric selec-

the presence of DBU. The glycosyl donor 22S (Scheme 4) tivities were somewhat lower. These glycosylations are pro-

was prepared by a similar protocol using ethyl (S)-mandel- posed to proceed through a cis-decalin intermediate, which

ate as the starting material.

places the phenyl substituent of the auxiliary in an equato-

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Table 2. Stereoselective glycosylations with galactosyl donor glycosylation methodology with Density Functional

22R/S.

Theory (DFT) quantum-mechanical calculations (see Ex-

perimental Section). These intuitive models suggest that

(R)-configured auxiliaries, like all equatorial dioxolenium

ion species, should have a cis-decalin that is more stable

than the corresponding trans-decalin species and the ring-

opened parent oxacarbenium ion (Scheme 1, c). Similarly,

the (S)-configured auxiliary should have an all equatorial

trans-decalin dioxolenium ion that is more stable than its

cis isomer and its ring-opened oxacarbenium ion

(Scheme 1, b). These postulates are the basis of the model,

which also assumes that glycosylation reactions proceed

through fully cationic intermediates without significant per-

turbation by solvent or counterions.^[16]Such a method as-

sumes the limitation that the effects of solvents and coun-

terions are equivalent for all ions calculated. Other inherent

limitations of the DFT program and the model system

studied are the basis set imperfections, truncated protecting

groups and incomplete consideration of correlation, all of

which lead to relatively large errors estimated at up to

5 kJmol^–1based on experience with similar systems.

Specifically, this study focused on the following cations:

3,6-di-O-acetyl-4-O-methyl-2-O-(R)-methoxycarbonylben-

zyl--glucopyranosyl (43R) and its 2-O-(S) isomer (43S).

Entry

Glycosyl

donor

Glycosyl

acceptor

Product

α/β Ratio

(yield, %)^[a]

1

2

3

4

22S

22R

22S

22R

23

26

39S

39R

40S

40R

10:1 (75%)

1:4 (79%)

6:1 (78%)

1:2 (82%)

[a] Product ratios were determined by ¹H NMR analysis of the

crude reaction products.

rial orientation (Scheme 1, c). It is, however, important to These cations are derived from 5R/S with the ethoxy re-

note that a cis-decalin does experience unfavorable gauche placed by methoxy and the 4-O-benzyl replaced by O-

interactions. The (S)-ethoxycarbonylbenzyl auxiliary, which methyl. A drawback of these truncations is that they limit

reacts through a trans-decalin intermediate, does not experi- the conformational degrees of freedom and thus simplify

ence these unfavorable interactions rationalizing its more the computational studies. Previous studies of -gluco-con-

efficient anomeric control.

figured pyranosyl oxacarbenium ions have consistently

In general, participation by conventional C-2 ester leads found two stable conformers for both the 2,3,4,6-tetra-O-

to the exclusive formation of 1,2-trans glycosides. Although methyl^[17]and the 2-O-acetyl-3,4,6-tri-O-methyl^[18]analogs

the glycosyl donors that have an ethyl (S)-mandelate at C-2 of 43R and 43S. In both cases, the two conformers can be

4

5

led to disaccharides with high α-anomeric selectivity, small characterized as H₃and S₁conformations. With respect

amounts of the unwanted β-anomers were formed. The for- to the dioxolenium ions related to the 2-O-acetyl analog,

4

3

mation of the unwanted anomer was significant when gly- two conformers characterized as H₅and S₁were found.

cosyl donor 17S was used, which has an allyl ether at C-3. Finally, the possibility of 3-O-acetyl participation, as found

Participation by an ethoxycarbonylbenzyl moiety is proba- experimentally and computationally for -fucopyranosyl

bly slower than that of a conventional ester because of donors,^[19]was considered. Thus, for both 43R and 43S

slower six-membered than five-membered ring formation. seven distinct conformers were considered: B0 and B1 (oxa-

Thus, it is possible that in the case of an ethoxycarbonyl- carbenium ions), C0_axand C1_ax(dioxolenium ions with C-

benzyl-participating group, some glycosylation takes place 1···O-7 axial), C0_eqand C1_eq(dioxolenium ions with C-

from the oxacarbenium ion leading to anomeric mixtures. 1···O-7 equatorial) and 3Ac (dioxolenium ions formed from

This proposal is supported by the observation that dilution 3-O-acetyl participation), where O-7 is the former carbonyl

of the reaction mixture resulted in an improvement of an- oxygen of the auxiliary (see Figure 1, a–l and Figure 2, a,b,

omeric selectivity. The oxacarbenium ion is disfavored by for ball-and-stick representations).

electron withdrawing substituent such as an ester at C-3,

The relative energies of these 14 species are tabulated in

which may facilitate the participation. Differences in sta- Table 3. For 43R with the (R)-configured auxiliary, the

bility of the intermediate oxacarbenium ion may rationalize trends are consistent with the model, specifically the (R)-

the more efficient participation of glycosyl donors 5S, 9S C0_axand (R)C1_ax(cis-decalin type) are more stable by

and 13S compared to 17S.

Ͼ20 kJmol^–1than either the (R)C0_eqor (R)C1_eq(trans-de-

Computational Studies: Recent advances in computer calin type). In particular, the (R)C0_eqion that most re-

hardware and software have made it possible to study pro- sembles the disfavored case in Scheme 1, c, is strongly desta-

tected monosaccharides by high-level quantum-mechanical bilized even with respect to either the (R)3Ac or (R)B0 ions.

methods.^[15]Of particular interest are intermediates or tran- The (R)B1 is more stable than intuitive arguments would

sition states that are not easily amenable to study by experi- suggest. It should be noted that this conformer allows O-2

mental methods. In this section, we present an assessment to be pseudo-equatorial and O-3, O-4 and C-6 to be

of the intuitive models which form the basis of the new pseudo-axial. This preference for O-2 of pyranosyl oxacar-

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Glycopyranosyl Donors with Chiral Auxiliaries

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Figure 2. Ball-and-stick representations of 3-O-acetyl neighboring-

group participation, a) (R)3Ac b) (S)3Ac.

benium ions to be pseudo-equatorial has been noted before

and was estimated to provide an approximate stabilization

of 15 kJmol^–1.^[20]For the diastereomer 43S the results are

in accordance to the model but with smaller distinctions. In

this case, only one of the two trans-decalin isomers (S)C1_eq

is more stable than the (S)C0_axand (S)C1_axisomers by only

about 7 kJmol^–1. The (S)C0_axisomer shows an interaction

between the phenyl of the auxiliary and the acetate at O-3,

perhaps leading to its destabilization (see Figure 1, f).

Table 3. Relative energies of oxacarbenium ions 43R and 43S.

Conformers

∆E

Conformers

∆E

kJmol^–1

RB0

0

SB0

–17.2

–31.3

–43.8

–35.9

–33.4

–50.1

–46.7

RB1

–51.2

–72.8

–62.8

–17.4

–41.6

–43.9

SB1

RC0_ax

RC1_ax

RC0_eq

RC1_eq

R3Ac

SC0_ax

SC1_ax

SC0_eq

SC1_eq

S3Ac

Table 4 depicts the ring dihedrals, which exhibit many of

the expected trends. Notably τ₅(C-5–O-5···C-1–C-2) is ne-

arly planar in the B0 and B1 oxacarbenium ions.^[21]How-

ever, once the dioxolenium ion is formed, this torsion angle

changes dramatically, reflecting the hybridization change at

C-1. Also shown is the ω_H(CH-5–C-5···C-6–O-6) torsion

angle which was varied over the three staggered rotamers

for all 14 species. Only the lowest energy rotamers are

shownand these adopt the standard gg (ω_Habout 180°) or

gt (ω_Habout –60°) conformations typical of -glucopyr-

anoses.^[22]The unfavorable tg (ω_Habout 60°) rotamer was

consistently about 10 kJmol^–1higher in energy. No evi-

dence for pronounced O-6 participation was found in any

of the calculated species. The O-acetyl and the O-methyl

substituents were in each case found in conformations near

their expected minimum-energy conformations.^[23]In the di-

oxolenium ions, two possible conformers are inherently

possible, one with the O-methyl carbon syn to O-7 and its

anti isomer. These extremes correspond to the trans and cis

isomers of normal O-esters. In all cases except for the high

Figure 1. Ball-and-stick representations of a) (R)B0 b) (S)B0 c) (R)

B1 d) (S)B1 e) (R)C0_axf) (S)C0_axg) (R)C1_axh) (S)C1_axi) (R)-

C0_eqj) (S)C0_eqk) (R)C1_eql) (S)C1_eq.

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Table 4. Ring dihedrals for six-membered sugar rings.

Conformers

τ₁[°]

τ₂[°]

τ₃[°]

τ₄[°]

τ₅[°]

τ₆[°]

ω_H[°]

C1–O7 [Å]

C1C2–C3C4 C2C3–C4C5 C3C4–C5O5 C4C5–O5C1 C5O5–C1C2 O5C1–C2C3 O6C6–C5H5

RB0

–58.5

–12.5

–46.1

–8

–54.2

–35.3

53.6

–56.8

–13.7

–47.9

–13.1

–56.7

–34.8

53.9

64.7

–34.7

55.9

–33.6

46.6

–20.1

–8.9

63.8

–26.5

58

42.7

48.8

–20.8

–9.8

–37.8

61.5

–55.8

54.3

–46.1

59.6

–37.2

–36.5

53.6

–54.3

–64.1

–46.22

59.1

7.3

–41

–4.1

–8.5

–39.4

–14.1

–68.7

–20.1

11.7

1.7

–3.4

–35

–29.8

–66.6

–22.2

11.3

30.4

37.5

38.7

34.6

68.5

60.8

179.4

–50.5

179.4

–63.1

168.4

–58.8

173.8

–179.4

–63.2

175.5

176.4

168.5

–61.9

173.8

2.499

2.724

1.681

1.722

1.511

1.583

1.694^[a]

2.674

2.85

1.745

1.844

1.508

1.699

1.694^[a]

RB1

RC0_ax

RC1_ax

RC0_eq

RC1_eq

R3Ac

SB0

47.8

–30.8

55.6

–38.6

37.9

3.6

–40.1

42.1

59.3

54

–58

25.7

31.9

38.4

5.7

68.4

61.7

–57.7

SB1

SC0_ax

SC1_ax

SC0_eq

SC1_eq

S3Ac

–36.8

37.9

–36.4

[a] Former carbonyl oxygen of O-3 acetate to C-1 bond length.

energy isomer (R)C0_eq(Figure 1, i), the syn isomers were

Table 5 depicts the coefficients which correspond to the

Ͼ10 kJmol^–1more stable than the anti isomers. This adds canonical vector representation of six-membered rings that

a further subtlety to the ring-closure step as presumably quantitatively describe the conformations based on the 38

only the trans ester can cyclize (see Scheme 5).

standard IUPAC conformations.^[24]This method uses chair

(¹C₄), boat (^1,4B) and skew-boat (²S_O) canonical vectors as

an orthogonal basis set. In cases where intermediate half

chair or envelope conformations are populated, appropriate

permutations of the C, B and S vectors lead to a new set

of three vectors where the H or E conformer has the highest

coefficient. The residual coefficients of the two less popu-

lated canonical vectors quantitatively show both the direc-

tion and magnitude of the distortion from the principle ca-

nonical vector. For example, conformation (R)B0 is close to

half a chair and half a boat, therefore adopting an envelope

(E₃) with some distortion towards ⁴H₅and a very little

4

towards C₁. It is important to note that its (S) isomer is

an almost perfect E₃envelope. In fact, all (R)/(S) pairs show

the same ring conformation with the exception of the (R)-

C1_ax/(S)C1_axpair. It was predicted in Scheme 1b that the

(S)C0_axand (S)C1_axions (cis-decalin type) were to be de-

stabilized, which perhaps results in distortions. Figure 3 de-

picts the positions of all fourteen isomers in conformational

space on a spherical representation.

The B0 conformers are predominantly E₃which is close

4

in conformational space to the H₃found for its analogs.

5

Similarly, the B1 conformations are S₁as found for the

analogs. Taken together, these results suggest that the col-

lection of protecting groups has only a small influence on

ring conformation. Because four of the decalin-type diox-

olenium species are found to have chair conformers, they

Scheme 5. Schematic representation of the relationship between cis

and trans ester conformation and the syn or anti conformation in

the dioxolenium ions. Also depicted is the sugar-like numbering

used for the six-membered rings of the dioxolenium ions.

conform to the intuitive model. Of the remaining four, three

5

Table 4 also shows the C-1···O-7 or C-1–O (3Ac, C=O) have S₁conformers with only the (S)C1_axadopting the E₅

bond lengths, which might have been expected to correlate conformation. All of these conformations are quite distinct

with relative energies. All bond lengths are close to 1.6 Å from the fused five-membered ring dioxolenium species dis-

as observed in similar species.^[16]No correlation with ener- cussed above.

gies is apparent, so the main determinant of relative ener-

While 5-membered ring dioxolenium ions are typically

gies appears to be subtle interactions between protecting planar,^[25]the situation for the six-membered rings consid-

groups and the extra stabilization provided by dioxolenium ered here is less clear. One report found a half-chair confor-

ion formation.

mation.^[26]The ring dihedrals for the eight isomers consid-

5014

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Eur. J. Org. Chem. 2006, 5007–5028

Glycopyranosyl Donors with Chiral Auxiliaries

Table 5. Coefficients for canonical vector representation of the conformations of the six-membered rings of the sugar.

FULL PAPER

Conformers

Chair

Boat

Skew-boat

Half chair envelope

Boat or other

Skew-boat or other

RB0

⁴C₁0.563

¹C₄0.219

⁴C₁0.788

¹C₄0.172

⁴C₁0.944

¹C₄0.004

¹C₄0.158

⁴C₁0.513

¹C₄0.198

⁴C₁0.766

⁴C₁0.596

⁴C₁0.946

⁴C₁0.005

¹C₄0.157

B_O,30.466

B_O,30.043

^1,4B 0.140

^O,3B 0.037

B_1,40.185

B_O,30.141

B_2,50.778

B_O,30.495

^2,5B 0.100

B_2,50.043

B_2,50.436

B_1,40.167

B_O,30.119

B_2,50.768

¹S₅0.067

⁵S₁0.818

^OS₂0.011

⁵S₁0.734

^OS₂0.007

⁵S₁0.984

¹S₃0.026

¹S₅0.094

⁵S₁0.707

¹S₃0.188

¹S₃0.106

²S_O0.027

⁵S₁0.989

¹S₃0.035

E₃0.932

⁵S₁0.818

⁴C₁0.788

⁵S₁0.734

⁴C₁0.944

⁵S₁0.984

B_2,50.778

E₃0.989

⁵S₁0.707

⁴C₁0.766

E₅0.872

⁴C₁0.946

⁵S₁0.989

B_2,50.768

⁴H₅0.134

¹C₄0.219

^1,4B 0.140

¹C₄0.172

B_1,40.185

B_O,30.141

¹C₄0.158

¹S₅0.094

E_O0.199

¹S₃0.188

⁴H₃0.212

B_1,40.167

B_O,30.119

¹C₄0.157

⁴C₁0.030

B_O,30.043

^OS₂0.011

^O,3B 0.037

^OS₂0.007

¹C₄0.004

¹S₃0.026

⁴C₁0.019

¹C₄0.098

B_2,50.043

⁴C₁0.054

²S_O0.027

⁴C₁0.005

¹S₃0.035

RB1

RC0_ax

RC1_ax

RC0_eq

RC1_eq

R3Ac

SB0

SB1

SC0_ax

SC1_ax

SC0_eq

SC1_eq

S3Ac

mation in all cases, strongly suggesting that considerable

positive charge is delocalized onto the former ester atoms.

In support of this concept the LUMOs for the two lowest

energy species (R)C0_axand (S)C1_eqare shown in Figure 4.

These figures are consistent with considerable charge delo-

calization to the fused ring. Note that the parent B-type

species have LUMOs concentrated on C-1···O-5 of the

sugar ring and the five-membered dioxolenium ions have

LUMOs with considerable p character on the former car-

bonyl carbon. The species considered in this work more

closely resembles the five-membered dioxolenium species,

but with a more delocalized charge.

The mechanism of nucleophilic attack on these new six-

membered ring-fused dioxolenium ions remains to be ad-

dressed, in addition to a number of other issues including

the lifetimes of these species and barriers to their formation

and interconversions. All of these issues require detailed ex-

perimental and theoretical studies in order to arrive at suit-

able conclusions, as presently only speculations based on

results with five-membered fused dioxolenium ions can be

Figure 3. Spherical representation of the conformational space of

six-membered rings with the 14 isomers of 43R and 43S. Blue sym-

bols represent (S)-configured auxiliaries and red symbols represent

isomeric (R)-configuration. Squares B0, pentagons B1, triangles

C0_ax, diamonds C0_eq, filled circles C1_eq, inverted triangles C1_axand

half filled circles 3-Ac.

ered here and the corresponding canonical vector coeffi- made. For example, five-membered dioxolenium ions can be

cients are tabulated in Table 6 and Table 7. In order to con- isolated and studied.^[27]Given that our calculations suggest

form with the sugar numbering used for the descriptors, the these species are stable, it is likely that they would have a

former carbonyl oxygen is considered the ring oxygen and significant lifespan under some experimental conditions.

the former carbonyl carbon C-1, C-2 has the phenyl substit- The lifespan issue is one plausible explanation for the ob-

uent etc. with clockwise numbering. All rings are half chairs served difference between 3-O-acetyl- vs. 3-O-allyl-substi-

with the (R)-auxiliary diastereomers having ³H₄or the tuted donors. Although our calculations show that such

closely related E₄and ³E conformers, whereas the (S)-auxil- ions are predicted to be stable, the large conformational

4

iary diastereomers all exhibit the H₃conformation. Using shift (see Figure 3) to obtain the requisite ring conforma-

the above sugar numbering, τ₅has a nearly planar confor- tion (Figure 2, a,b) and the lesser stability of these ions

Table 6. Ring dihedrals for six-membered rings of the dioxolenium ions (see text for numbering).

Conformers

τ₁[°]

C1C2–C3C4

τ₂[°]

C2C3–C4C5

τ₃[°]

C3C4–C5O5

τ₄[°]

C4C5–O5C1

τ₅[°]

C5O5–C1C2

τ₆[°]

O5C1–C2C3

RC0_ax

SC0_ax

RC1_ax

SC1_ax

RC0_eq

SC0_eq

RC1_eq

SC1_eq

44.9

33

44.2

–70.1

–67.2

–70.1

–58.7

69.3

68.7

74.6

51.7

56.2

49.1

–21.3

–26.7

–14.5

–3

25.9

22

0.2

–3.3

–8.8

7.8

–8.2

4.4

–9.5

2.9

–3.6

–33.4

19.5

3.6

61.6

25

–49.8

–40.2

–40.9

–41.2

–55.2

–57.2

–60.9

–60.4

22.8

21

7

8.8

0.6

0.1

74.5

Eur. J. Org. Chem. 2006, 5007–5028

www.eurjoc.org

5015

J.-H. Kim, H. Yang, V. Khot, D. Whitfield, G.-J. Boons

FULL PAPER

Table 7. Coefficients for canonical vector representation of the conformations of the six-membered rings of the dioxolenium ions (see

text for numbering).

Conformers

Chair

Boat

Skew-boat

Half chair envelope Boat or other

Skew-boat or other

RC0_ax

SC0_ax

RC1_ax

SC1_ax

RC0_eq

SC0_eq

RC1_eq

SC1_eq

¹C₄0.549

¹C₄0.491

¹C₄0.480

¹C₄0.526

⁴C₁0.633

⁴C₁0.520

⁴C₁0.535

⁴C₁0.523

^2,5B 0.077

B_1,40.540

^2,5B 0.066

^O,3B 0.456

B_2,50.049

B_2,50.147

B_2,50.176

B_2,50.167

³S₁0.571

^OS₂0.067

³S₁0.647

¹S₅0.068

¹S₃0.505

¹S₃0.605

¹S₃0.671

¹S₃0.686

³H₄1.098

E₄0.983

^2,5B 0.077

^OS₂0.067

³S₁0.167

¹H₂0.137

⁴C₁0.127

B_2,50.147

B_2,50.176

B_2,50.167

³S₁0.022

B_1,40.048

^2,5B 0.066

¹C₄0.002

B_2,50.049

¹S₃0.085

¹S₃0.136

¹S₃0.163

³H₄0.959

³E 0.912

⁴H₃1.010

⁴H₃1.041

⁴H₃1.071

⁴H₃1.047

Figure 4. LUMOs of lowest energy isomers a) (R)C0_axand b) (S)C1_eq.

when compared to the six-membered dioxolenium species

(Table 3) suggests that there could be a significant kinetic

barrier to their formation.^[28]Because O-allyl is expected to

be activating as compared to O-acetyl,^[29]the corresponding

B0 and B1 species should be more reactive and plausibly

could react before either the six-membered dioxolenium

species or the 3-Ac species form to any appreciable extent.

Thus, it logically follows that more electron-withdrawing

species at O-3 then acetyl could lead to more stereospecific

glycosylations, obviously at the expense of reactivity.

Clearly, a more complete set of protecting-group strategies

should be studied before any firm conclusions can be made.

Experimental Section

The DFT calculations were carried out with the Amsterdam Den-

sity Functional (ADF) program system, ADF2000.^[30]The atomic

orbitals were described as an uncontracted double-ζ Slater function

basis set with a single-ζ polarization function on all atoms which

were taken from the ADF library. The 1s electrons on carbon and

oxygen were assigned to the core and treated by the frozen core

approximation. A set of s, p, d, f, and g Slater functions centered

on all nuclei were used to fit the electron density, and to evaluate

the Coulomb and exchange potentials accurately in each SCF cycle.

The local part of the V_xcpotential (LDA) was described using the

VWN parametrization,^[31]in combination with the gradient-cor-

rected (CGA) Becke’s functional^[32]for the exchange and Perdew’s

function for correlation (BP86).^[33]The CGA approach was applied

self-consistently in geometry optimizations. Second derivatives

were evaluated numerically by a two-point formula. The solvation

parameters were dielectric constant ε = 9.03, ball radius 2.4 Å, with

atomic radii of 1.7 (C ), 1.4 (O) and 1.2 Å (H).

Conclusions

For the first time it has been shown that the anomeric

selectivity of a glycosylation can be controlled by a chiral All input structures were generated using the Hyperchem 7.0 pro-

gram package. Initial conformations were made using standard

geometries according to ref.^[23]above, and all side chains were mini-

mized after extensive conformational searching using semi empiri-

cal methods. Side-chain conformations were further tested using

DFT above. In particular all 3 rotamers about C-5···C-6 were con-

sidered and the conformation about the former carbonyl bond in

the six-membered dioxolenium species were varied between the two

minimum. Ball-and-stick representations were made using Hyper-

chem 7.0 from the ADF output. The spherical representations of

the conformations were plotted using Gnu-plot. The LUMOs were

plotted from the ADF output using the Molekel program.

auxiliary. This new method for anomeric control is in par-

ticular suited for the introduction of α-glucosides. It is to

be expected that a systematic optimization of the structure

of the auxiliary will lead to a stereospecific glycosylation

protocol. In particular, an improved auxiliary may be ob-

tained by increasing its nucleophilicity or reducing the flexi-

bility of rotatable bonds. Only such a method will make

it possible for polymer supported and one-pot multi-step

oligosaccharide syntheses to realize their potential for rou-

tine use for a large number of oligosaccharide targets.

5016

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Eur. J. Org. Chem. 2006, 5007–5028

Glycopyranosyl Donors with Chiral Auxiliaries

FULL PAPER

General Procedures: All reactions were carried out under a positive

pressure of argon unless otherwise noted. All chemicals were pur-

chased from commercial suppliers and used without further purifi-

cation unless otherwise noted. Dichloromethane was distilled from

calcium hydride under nitrogen. Toluene was distilled from molten

sodium under nitrogen. Dimethylformamide (DMF) was distilled

from barium oxide under nitrogen. Column chromatography was

performed on silica gel 60 (EM Science, 70–230 mesh). Reactions

were monitored by TLC on kieselgel 60 F₂₅₄(EM Science), and

the compounds were detected by examination under UV light and

visualized by dipping the plates in a cerium sulfate/ammonium

molybdate solution followed by heating. Organic solutions were

concentrated by rotary evaporation below 40 °C under reduced

pressure. Molecular sieves (3 Å and 4 Å) were crushed and acti-

vated in vacuo at 400 °C for 5 h. Optical rotations were measured

83.17, 81.24, 79.89, 76.18, 72.57, 71.81, 67.31, 61.67, 13.82 ppm.

HR MALDI-TOF MS: m/z calcd. for C₂₃H₂₆O₇[M + Na]⁺

437.1577, found 437.1548.

1,3,6-Tri-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-α/β-

D

-glucopyranose (3S): Trimethylsilyl trifluoromethanesulfonate

(24 µL, 0.13 mmol) was added to a solution of 2S (6.52 g,

6.52 mmol) in acetic anhydride (10 mL) at 0 °C. After the reaction

mixture was stirred at 0 °C for 20 min, it was quenched with an

aqueous saturated solution of NaHCO₃, and the resulting mixture

was extracted with DCM (2 × 30 mL). The organic phase was

washed with water (30 mL) and brine (30 mL) and dried (MgSO₄),

filtered and the filtrate was concentrated in vacuo. The residue was

purified by silica gel column chromatography (20% ethyl acetate in

hexane) to afford 3Sα (2.69 g, 74%): colorless syrup, R_f= 0.57

(ethyl acetate/hexane, 1:1). [α]²_D⁰= +164 (c = 2.1, CHCl₃). ¹H NMR

(300 MHz, CDCl₃): δ = 7.22–7.35 (m,10 H, aromatic), 6.44 (d, J =

3.6 Hz, 1 H, 1-H), 5.57 (t, J = 9.6 Hz, 1 H, 3-H), 4.96 (s, 1 H,

ϾCHPh), 4.55 (d, J = 11.1 Hz, 1 H, CHHPh), 4.48 (d, J = 11.1 Hz,

1 H, CHHPh), 4.25 (d, J = 3.0 Hz, 2 H, 6-H_a, 6-H_b), 4.08–4.20 (m,

2 H, COOCH₂CH₃), 3.97–4.02 (m, 1 H, 5-H), 3.61 (dd, J = 3.6,

9.9 Hz, 1 H, 2-H), 3.55 (t, J = 9.6 Hz, 1 H, 4-H) 2.18 (s, 3 H,

COCH₃), 2.05 (s, 3 H, COCH₃), 1.88 (s, 3 H, COCH₃), 1.20 (t, J

= 7.2 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃):

δ = 170.46, 169.93, 169.47, 169.23, 137.02, 135.82, 128.83, 128.54,

128.13, 128.09, 127.22, 89.40, 81.44, 76.27, 75.48, 74.58, 73.21,

70.71, 62.37, 61.48, 20.97, 20.86, 20.77, 13.93 ppm. HR MALDI-

TOF MS: m/z calcd. for C₂₉H₃₄O₁₁[M + Na]⁺581.1999, found

1

with a “Jasco P-1020” polarimeter. H NMR and ¹³C NMR spec-

tra were recorded with a Varian Inova 300 spectrometer and a Var-

ian Inova 500 spectrometer equipped with Sun workstations.

Chemical shifts are reported in parts per million (ppm) downfield

from tetramethylsilane. Data are presented as follows: chemical

shift, multiplicity (s = singlet, d = doublet, t = triplet, dd = double

of doublet, m = multiplet and/or multiple resonances), integration,

coupling constant in Hertz (Hz). High-resolution mass spectrome-

try was run in a JMS SX/SX102A tandem mass spectrometer,

equipped with FAB source. The matrix used was DHB and the

internal standards ultramark 1621 and PEG.

1,6-Anhydro-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-β-

D-gluco-

pyranose (2S): BF₃–OEt₂(543 µL, 4.27 mmol) was added dropwise 581.1983. 3S(β) (0.69 g, 19%): colorless syrup, R_f= 0.62 (ethyl ace-

to a mixture of 1,6:2,3-di-anhydro-4-O-benzyl-β--mannopyranose

(1) (5 g, 21.3 mmol), ethyl (S)-mandelate (11.5 g, 63.9 mmol) and

activated molecular sieves (4 Å, 2 g) in toluene (20 mL) at room

temperature. After stirring for 1 h, the reaction mixture was

quenched with aqueous saturated NaHCO₃solution (30 mL) and

then diluted with ethyl acetate (30 mL). The organic phase was

dried (MgSO₄), filtered and the filtrate was concentrated in vacuo.

The residue was purified by silica gel column chromatography

tate/hexane, 1:1). [α]²_D⁰= +120 (c = 1.2, CHCl₃). ¹H NMR

(300 MHz, CDCl₃): δ = 7.19–7.38 (m,10 H, aromatic), 5.73 (d, J =

8.1 Hz, 1 H, 1-H), 5.37 (t, J = 9.0 Hz, 1 H, 3-H), 4.99 (s, 1 H,

ϾCHPh), 4.51 (d, J = 11.1 Hz, 1 H, CHHPh), 4.46 (d, J = 11.1 Hz,

1 H, CHHPh), 4.29 (dd, J = 2.4, 12.3 Hz, 1 H, 6-H_a), 4.21 (dd, J

= 4.5, 12.3 Hz, 1 H, 6-H_b), 4.05–4.17 (m, 2 H, COOCH₂CH₃),

3.71–3.76 (m, 1 H, 5-H), 3.49–3.56 (m, 2 H, 4-H, 2-H), 2.15 (s, 3

H, COCH₃), 2.04 (s, 3 H, COCH₃), 1.60 (s, 3 H, COCH₃), 1.83 (t,

(20% ethyl acetate in hexane) to afford 2S (4.23 g, 48%): colorless J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃):

syrup, R_f= 0.34 (ethyl acetate/hexane, 1:1). [α]²_D⁰= +40.3 (c = 1.0,

δ = 170.51, 170.20, 169.43, 168.53, 137.04, 136.65, 128.71, 128.54,

CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.25–7.48 (m, 10 H, 128.15, 128.07, 127.18, 93.51, 83.08, 80.00, 77.20, 75.47, 74.71,

aromatic), 5.54 (s, 1 H, 1-H), 5.22 (s, 1 H, ϾCHPh), 4.63 (d, J = 74.31, 73.50, 62.44, 61.37, 20.97, 20.82, 20.62, 13.98 ppm. HR

12.3 Hz, 1 H, CHHPh), 4.61 (d, J = 12.3 Hz, 1 H, CHHPh), 4.54

(d, J = 5.4 Hz, 1 H, 5-H), 4.13–4.23 (m, 2 H, COOCH₂CH₃), 3.88

(t, J = 4.8 Hz, 1 H, 3-H), 3.73 (d, J = 7.5 Hz, 1 H, 6-H_a), 3.61 (dd,

J = 5.4, 7.2 Hz, 1 H, 6-H_b), 3.33 (d, J = 4.8 Hz, 1 H, 2-H), 3.29

(d, J = 4.8 Hz, 1 H, 4-H), 2.61 (br, 1 H, OH), 1.21 (t, J = 7.2 Hz,

3 H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 171.07,

137.79, 136.01, 128.73, 128.59, 128.43, 127.78, 127.75, 127.50,

101.80, 80.49, 80.17, 80.02, 75.48, 71.80, 71.25, 66.85, 61.43, 14.01

ppm. HR MALDI-TOF MS: m/z calcd. for C₂₃H₂₆O₇[M + Na]⁺

437.1577, found 437.1532.

MALDI-TOF MS: m/z calcd. for C₂₉H₃₄O₁₁[M + Na]⁺581.1999,

found 581.1947.

1,3,6-Tri-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-α/β-

D-glucopyranose (3R): Compound 3R was synthesized according to

the procedure described for the synthesis of compound 3S. 3Rα:

Colorless syrup, R_f= 0.55 (ethyl acetate/hexane, 1:1). [α]²_D⁰= +99.9

1

(c = 2.0, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 7.26–7.37 (m,

10 H, aromatic), 6.29 (d, J = 3.6 Hz, 1 H, 1-H), 5.58 (t, J = 9.9 Hz,

1 H, 3-H), 4.98 (s, 1 H, ϾCHPh), 4.66 (d, J = 10.8 Hz, 1 H,

CHHPh), 4.55 (d, J = 10.8 Hz, 1 H, CHHPh), 4.26 (d, J = 2.7 Hz,

1,6-Anhydro-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-β-D-gluco- 2 H, 6-H_a, 6-H_b), 4.09–4.21 (m, 2 H, COOCH₂CH₃), 3.96–4.01 (m,

pyranose (2R): Compound 2R was synthesized from compound 1

and ethyl (R)-mandelate according to the procedure described for

the synthesis of compound 2S: Colorless syrup, R_f= 0.35 (ethyl

acetate/hexane, 1:1). [α]²_D⁰= –10.3 (c = 1.2, CHCl₃). ¹H NMR

1 H, 5-H), 3.68 (dd, J = 3.6, 9.9 Hz, 1 H, 2-H), 3.66 (t, J = 9.9 Hz,

1 H, 4-H), 2.18 (s, 3 H, COCH₃), 2.05 (s, 3 H, COCH₃), 2.01 (s, 3

H, COCH₃), 1.20 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C

NMR (75 MHz, CDCl₃): δ = 170.46, 170.05, 169.94, 169.04,

(300 MHz, CDCl₃): δ = 7.26–7.45 (m, 10 H, aromatic), 5.34 (s, 1 137.19, 135.85, 128.72, 128.54, 128.49, 128.11, 128.07, 127.01,

H, 1-H), 5.11 (s, 1 H, ϾCHPh), 4.83 (d, J = 12.0 Hz, 1 H, CHHPh),

4.67 (d, J = 12.0 Hz, 1 H, CHHPh), 4.51 (d, J = 5.1 Hz, 1 H, 5-

H), 4.06–4.23 (m, 2 H, COOCH₂CH₃), 3.99 (t, J = 6.3 Hz, 1 H, 3-

H), 3.57–3.65 (m, 2 H, 6-H_a, 6-H_b), 3.34 (d, J = 6.3 Hz, 1 H, 2-H),

3.24 (d, J = 6.3 Hz, 1 H, 4-H), 1.17 (t, J = 7.2 Hz, 1 H, CO-

OCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 171.84, 138.04,

88.72, 79.66, 75.89, 75.06, 74.65, 72.95, 70.84, 62.36, 61.25, 21.15,

20.76, 14.00 ppm. HR MALDI-TOF MS: m/z calcd. for C₂₉H₃₄O₁₁

[M + Na]⁺581.1999, found 581.1989. 3R(β): colorless syrup, R_f=

0.60 (ethyl acetate/hexane, 1:1). [α]²_D⁰= –38 (c = 1.0, CHCl₃). ¹H

NMR (300 MHz, CDCl₃): δ = 7.26–7.34 (m,10 H, aromatic), 5.59

(d, J = 8.1 Hz, 1 H, 1-H), 5.44 (t, J = 9.3 Hz, 1 H, 3-H), 5.10 (s, 1

135.85, 128.65, 128.46, 128.27, 127.70, 127.56, 127.06, 101.78, H, ϾCHPh), 4.63 (d, J = 11.1 Hz, 1 H, CHHPh), 4.54 (d, J =

Eur. J. Org. Chem. 2006, 5007–5028

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5017

J.-H. Kim, H. Yang, V. Khot, D. Whitfield, G.-J. Boons

FULL PAPER

11.1 Hz, 1 H, CHHPh), 4.20–4.30 (m, 2 H, 6-H_a, 6-H_b), 4.05–4.21 128.15, 126.81, 92.96, 79.72, 76.37, 74.89, 74.58, 72.74, 71.21,

(m, 2 H, COOCH₂CH₃), 3.55–3.74 (m, 3 H, 5-H, 2-H, 4-H), 2.15 62.28, 61.25, 21.13, 20.74, 14.03. 5R(β): R_f= 0.71 (ethyl acetate/

(s, 3 H, COCH₃), 2.03 (s, 3 H, COCH₃), 1.85 (s, 3 H, COCH₃), hexane, 1:1) ppm. [α]²_D⁰= +47 (c = 1.3, CHCl₃). ¹H NMR

1.20 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, (300 MHz, CDCl₃): δ = 8.66 (s, 1 H, NH), 7.26–7.37 (m,10 H,

CDCl₃): δ = 170.51, 170.11, 169.94, 168.45, 137.18, 136.47, 128.61, aromatic), 5.83 (d, J = 7.5 Hz, 1 H, 1-H), 5.45 (s, 1 H, ϾCHPh),

128.57, 128.51, 128.15, 128.09, 126.80, 93.57, 82.00, 79.10, 75.33, 5.44 (t, J = 9.6 Hz, 1 H, 3-H), 4.68 (d, J = 11.4 Hz, 1 H, CHHPh),

75.00, 74.46, 73.65, 62.45, 61.29, 21.19, 20.82, 20.65, 14.06 ppm.

HR MALDI-TOF MS: m/z calcd. for C₂₉H₃₄O₁₁[M + Na]⁺

581.1999, found 581.1983.

4.58 (d, J = 11.4 Hz, 1 H, CHHPh), 4.33 (d, J = 12.3 Hz, 1 H, 6-

H_a), 4.26 (dd, J = 2.4, 12.3 Hz, 1 H, 6-H_b), 4.08–4.22 (m, 3 H,

COOCH₂CH₃, 5-H), 3.73–3.82 (m, 2 H, 2-H, 4-H), 2.19 (s, 3 H,

COCH₃), 2.02 (s, 3 H, COCH₃), 1.20 (t, J = 7.2 Hz, 3 H, CO-

OCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.54, 170.42,

170.36, 160.30, 137.29, 136.14, 128.76, 128.54, 128.44, 128.13,

126.83, 97.85, 79.90, 77.24, 77.20, 74.96, 74.26, 73.32, 62.41, 61.15,

21.28, 20.82, 14.08 ppm.

3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-α/β-D-

glucopyranosyl Trichloroacetimidate (5S): Hydrazinium acetate

(254 mg, 2.76 mmol) was added to a solution of 3S (1.40 g,

2.51 mmol) in DMF (10 mL) at room temperature. After stirring

the reaction mixture for 18 h, it was quenched with an aqueous

saturated solution of NaHCO₃. The mixture was extracted with

ethyl acetate (30 mL), and the organic phase was washed with an

aqueous saturated solution of NH₄Cl (30 mL) and dried (MgSO₄),

filtered and the filtrate was concentrated in vacuo. The residue was

purified by silica gel column chromatography (20% ethyl acetate in

hexane) to afford 4S (1.23 g, 95%). Trichloroacetonitrile (2.38 mL)

and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (143 µL) were added

to a solution of 4S (1.23 g, 2.38 mmol) in dichloromethane (10 mL)

at 0 °C. After stirring the reaction mixture for 1 h, it was concen-

trated in vacuo. The residue was purified by silica gel column

chromatography (20 % ethyl acetate in hexane) to afford 5Sα

(1.21 g, 77%): R_f= 0.65 (ethyl acetate/hexane, 1:1). [α]²_D⁰= +107.4

1,6-Anhydro-3-O-benzoyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

zyl]-β-D-glucopyranose (6R): Tetramethyl ethylenediamine (117 µL,

0.78 mmol) was added to a solution of 2R (250 mg, 0.60 mmol)

and benzoyl chloride (139 µL, 1.20 mmol) in dichloromethane

(10 mL) at 0 °C. After stirring the reaction mixture for 1 h at 0 °C,

it was warmed to room temperature and stirring was continued for

2 h. The reaction mixture was quenched with an aqueous saturated

solution of NaHCO₃(10 mL), and then diluted with dichlorometh-

ane (10 mL). The organic phase was dried (MgSO₄), filtered and

the filtrate was concentrated in vacuo. The residue was purified by

flash silica gel column chromatography (hexane/ethyl acetate, 3:1)

to afford 6R (296 mg, 95%): colorless syrup, R_f= 0.65 (ethyl ace-

tate/hexane, 1:1). [α]²_D⁰= –27 (c = 0.6, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.98 (d, J = 8.0 Hz, 2 H), 7.26–7.60 (m, 13 H), 5.51

(s, 1 H), 5.38 (s, 1 H), 5.29 (d, J = 5.5 Hz, 1 H), 4.94 (dd, J =

12.5 Hz, 1 H, CHHPh), 4.77 (dd, J = 12.5 Hz, 1 H, CHHPh), 4.65

(d, J = 5.5 Hz, 1 H), 4.15 (m, 2 H, COOCH₂CH₃), 3.97 (d, J =

7.5 Hz, 1 H), 3.76 (t, J = 7.0 Hz, 1 H), 3.46 (s, 1 H), 3.40 (s, 1 H),

1.19 (t, J = 8.5 Hz, 3 H, COOCH₂CH₃) ppm. HR MALDI-TOF

MS: m/z calcd. for C₃₀H₃₀O₈[M + Na]⁺541.1838, found 541.1827.

1

(c = 2.1, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 8.68 (s, 1 H,

NH), 7.23–7.38 (m,10 H, aromatic), 6.68 (d, J = 3.6 Hz, 1 H, 1-

H), 5.65 (t, J = 9.6 Hz, 1 H, 3-H), 5.03 (s, 1 H, ϾCHPh), 4.56 (d,

J = 11.1 Hz, 1 H, CHHPh), 4.51 (d, J = 11.1 Hz, 1 H, CHHPh),

4.32 (dd, J = 2.1, 12.0 Hz, 1 H, 6-H_a), 4.24 (dd, J = 3.9, 12.0 Hz,

1 H, 6-H_b), 4.08–4.19 (m, 3 H, COOCH₂CH₃, 5-H), 3.72 (dd, J =

3.6, 9.9 Hz, 1 H, 2-H), 3.61 (t, J = 9.9 Hz, 1 H, 4-H), 2.04 (s, 3 H,

COCH₃), 1.87 (s, 3 H, COCH₃), 1.20 (t, J = 7.2 Hz, 3 H, CO-

OCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.46, 170.25,

169.31, 161.20, 137.01, 135.78, 128.77, 128.57, 128.48, 128.27,

128.20, 127.05, 93.93, 81.80, 76.67, 75.35, 74.47, 73.35, 71.10,

62.35, 61.51, 20.85, 20.78, 14.01. 5S(β) (0.24 g, 15%): R_f= 0.69

(ethyl acetate/hexane, 1:1) ppm. [α]²_D⁰= +126.7 (c = 1.5, CHCl₃).

¹H NMR (300 MHz, CDCl₃): δ = 8.73 (s, 1 H, NH), 7.19–7.43

(m,10 H, aromatic), 6.03 (d, J = 6.9 Hz, 1 H, 1-H), 5.32 (t, J =

8.1 Hz, 1 H, 3-H), 5.32 (s, 1 H, ϾCHPh), 4.52 (d, J = 11.4 Hz, 1

H, CHHPh), 4.46 (d, J = 11.4 Hz, 1 H, CHHPh), 4.32 (dd, J =

2.1, 12.0 Hz, 1 H, 6-H_a), 4.21 (dd, J = 3.9, 12.0 Hz, 1 H, 6-H_b),

4.02–4.15 (m, 2 H, COOCH₂CH₃), 3.78–3.83 (m, 1 H, 5-H), 3.65–

3.71 (m, 2 H, 2-H, 4-H), 2.00 (s, 3 H, COCH₃), 1.75 (s, 3 H,

COCH₃), 1.14 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR

(75 MHz, CDCl₃): δ = 170.49, 169.82, 169.56, 160.26, 137.08,

136.46, 128.86, 128.59, 128.50, 128.10, 127.99, 97.61, 81.06, 75.10,

74.92, 74.04, 72.89, 62.36, 61.24, 20.86, 20.80, 13.95 ppm.

1,6-Anhydro-3-O-benzoyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-β-D-glucopyranose (6S): Compound 6S was synthesized ac-

cording to the procedure described for the synthesis of compound

6R. R_f= 0.51 (ethyl acetate/hexane, 1:1). [α]²_D⁰= –37 (c = 0.7,

CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 7.21–8.03 (m, 15 H,

Ar), 5.78 (s, 1 H, 1-H), 5.36 (s, 1 H, ϾCHPh), 5.27 (s, 1 H, 3-H),

4.71 (d, J = 12.0 Hz, 1 H, CHHPh), 4.61 (d, J = 12.0 Hz, 1 H,

CHHPh), 4.16–4.22 (m, 2 H, COOCH₂CH₃), 4.05 (d, J = 7.5 Hz,

1 H, 6-H_b), 3.84 (t, J = 7.0 Hz, 1 H, 6-H_a), 3.52 (s, 1 H, 2-H), 3.42

(s, 1 H, 4-H), 1.22 (t, J = 7.5 Hz, 3 H, COOCH₂CH₃) ppm. HR

MALDI-TOF MS: m/z calcd. for C₃₀H₃₀O₈[M + Na]⁺541.1838,

found 541.1843.

1,6-Di-O-acetyl-3-O-benzoyl-4-O-benzyl-2-O-[(R)-ethoxycarbonyl-

benzyl]-α/β-D-glucopyranose (7R): Trimethylsilyl trifluoromethanes-

ulfonate (0.2 µL, 0.01 mmol) was added to a solution of 6R

(215 mg, 0.41 mmol) in acetic anhydride (3 mL) at 0 °C. After stir-

ring the reaction mixture for 30 min at 0 °C, it was quenched with

an aqueous saturated solution of NaHCO₃(10 mL) and then di-

luted with dichloromethane (10 mL). The organic phase was dried

(MgSO₄), filtered and the filtrate was concentrated in vacuo. The

3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-α/β-D-

glucopyranosyl Trichloroacetimidate (5R): Compound 5R was syn-

thesized according to the procedure described for the synthesis of

compound 5S. 5Rα: R_f= 0.67 (ethyl acetate/hexane, 1:1). [α]²_D⁰

+61.0 (c = 1.8, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 8.39 (s,

=

1

1 H, NH), 7.26–7.37 (m,10 H, aromatic), 6.49 (d, J = 3.3 Hz, 1 H, residue was purified by flash silica gel column chromatography

1-H), 5.70 (t, J = 9.6 Hz, 1 H, 3-H), 5.04 (s, 1 H, ϾCHPh), 4.68 (20% ethyl acetate in hexane) to afford 7R (244 mg, 96%). 7Rα:

(d, J = 11.1 Hz, 1 H, CHHPh), 4.57 (d, J = 11.1 Hz, 1 H, CHHPh),

4.11–4.34 (m, 5 H, 6-H_a, 6-H_b, 5-H, COOCH₂CH₃), 3.77 (dd, J = = 0.4, CHCl₃). H NMR (500 MHz, CDCl₃): δ = 7.13–8.18 (m, 15

colorless syrup, R_f= 0.62 (ethyl acetate/hexane, 1:1). [α]²_D⁰= +97 (c

1

3.6, 9.9 Hz, 1 H, 2-H), 3.71 (t, J = 9.9 Hz, 1 H, 4-H), 2.17 (s, 3 H,

COCH₃), 2.03 (s, 3 H, COCH₃), 1.21 (t, J = 7.2 Hz, 3 H, CO-

OCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.42, 169.97,

H, Ar), 6.26 (d, J = 3.5 Hz, 1 H, 1-H), 5.87 (t, J = 10.0 Hz, 1 H,

3-H), 4.98 (s, 1 H, ϾCHPh), 4.60 (d, J = 11.0 Hz, 1 H, CHHPh),

4.49 (d, J = 11.0 Hz, 1 H, CHHPh), 4.27–4.28 (m, 1 H, 6-H_b),

169.90, 160.77, 137.15, 135.91, 128.54, 128.47, 128.29, 128.19, 4.03–4.05 (m, 1 H, 5-H), 3.94–3.97 (m, 2 H, COOCH₂CH₃), 3.89

5018

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Eur. J. Org. Chem. 2006, 5007–5028

Glycopyranosyl Donors with Chiral Auxiliaries

FULL PAPER

(dd, J = 3.5 Hz, 10.0 Hz, 1 H, 2-H), 3.84–3.88 (m, 1 H, 6-H_a), 3.77

(t, J = 10.0 Hz, 1 H, 4-H), 2.07 (s, 3 H, COCH₃), 2.05 (s, 3 H,

COCH₃), 0.97 (t, J = 7.5 Hz, 3 H, COOCH₂CH₃) ppm. HR

MALDI-TOF MS: m/z calcd. for C₃₄H₃₆O₁₁[M + Na]⁺643.2155,

found 643.2138.

NaHCO₃(10 mL) and then diluted with dichloromethane (10 mL).

The organic phase was dried (MgSO₄), filtered and the filtrate was

concentrated in vacuo. The residue was purified by flash silica gel

column chromatography (hexane/ethyl acetate, 3:1) to afford 10R

(217 mg, 87%): colorless syrup, R_f= 0.58 (ethyl acetate/hexane,

1:1). [α]²_D⁰= +17 (c = 0.8, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ

= 7.26–7.48 (m, 10 H, Ar), 5.89–5.97 (m, 1 H, CH=CH₂), 5.41 (s,

1 H, 1-H), 5.36 (d, J = 17.0 Hz, 1 H, CHH=CH), 5.29 (d, J =

10.5 Hz, 1 H, CHH=CH), 5.21 (s, 1 H, ϾCHPh), 4.96 (s, 1 H),

4.84 (d, J = 12.5 Hz, 1 H, CHHPh), 4.70 (d, J = 12.0 Hz, 1 H,

CHHPh), 4.64 (d, J = 6.0 Hz, 2 H), 4.59 (d, J = 5.5 Hz, 1 H), 4.14–

4.19 (m, 2 H, COOCH₂CH₃), 3.85 (d, J = 12.5 Hz, 1 H), 3.67 (dd,

J = 10.0, 12.0 Hz, 1 H), 3.37 (d, J = 8.5 Hz, 2 H, 2-H, 6-H_b), 1.19

(t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR MALDI-TOF MS:

m/z calcd. for C₂₇H₃₀O₉[M + Na]⁺521.1787, found 521.1762.

1,6-Di-O-acetyl-3-O-benzoyl-4-O-benzyl-2-O-[(S)-ethoxycarbonyl-

benzyl]-α/β-D-glucopyranose (7S): Compound 7S was synthesized

according to the procedure described for the synthesis of com-

pound 7R. 7Sα: R_f= 0.55 (ethyl acetate/hexane, 1:1). [α]²_D⁰= –47 (c

1

= 0.3, CHCl₃). H NMR (300 MHz, CDCl₃): δ = 7.08–7.99 (m, 15

H, Ar), 6.54 (d, J = 3.6 Hz, 1 H, 1-H), 5.82 (t, J = 9.6 Hz, 1 H, 3-

H), 4.95 (s, 1 H, ϾCHPh), 4.52 (d, J = 10.8 Hz, 1 H, CHHPh),

4.43 (d, J = 10.8 Hz, 1 H, CHHPh), 4.28–4.29 (m, 2 H, 6-H_a, 6-

H_b), 4.07–4.15 (m, 3 H, 5-H, COOCH₂CH₃), 3.76 (dd, J = 3.5,

9.6 Hz, 1 H, 2-H), 3.70 (t, J = 9.6 Hz, 1 H, 4-H), 2.20 (s, 3 H,

COCH₃), 2.07 (s, 3 H, COCH₃), 1.15 (t, J = 7.0 Hz, 3 H, CO-

OCH₂CH₃) ppm. HR MALDI-TOF MS: m/z calcd. for C₃₄H₃₆O₁₁

[M + Na]⁺643.2155, found 643.2098.

3-O-Allyloxycarbonyl-1,6-anhydro-4-O-benzyl-2-O-[(S)-ethoxycar-

bonylbenzyl]-β-D-glucopyranose (10S): Compound 10S was synthe-

sized according to the procedure described for the synthesis of

compound 10R. Colorless syrup, R_f= 0.53 (ethyl acetate/hexane,

6-O-Acetyl-3-O-benzoyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

zyl]-α/β-D-glucopyranosyl Trichloroacetimidate (9R): Hydrazinium

1:1). [α]²_D⁰= –35 (c = 0.7, CHCl₃). H NMR (500 MHz, CDCl₃): δ

1

= 7.21–7.81 (m, 10 H, Ar), 5.90–5.91 (m, 1 H, CH=CH₂), 5.70

(s, 1 H, 1-H), 5.39–5.40 (m, 1 H, CHH=CH), 5.35–5.36 (m, 1 H,

CHH=CH), 5.29 (s, 1 H, ϾCHPh), 4.80–4.83 (m, 1 H), 4.61–4.66

(m, 2 H, OCHHCH=CH₂, OCHHCH=CH₂), 4.62 (d, J = 12.0 Hz,

1 H, CHHPh), 4.55 (d, J = 12.0 Hz, 1 H, CHHPh), 4.15–4.23 (m,

3 H, COOCH₂CH₃), 3.91 (d, J = 7.5 Hz, 1 H), 3.83 (dd, J = 6.0,

8.0 Hz, 1 H), 3.72 (dd, J = 6.0, 7.5 Hz, 1 H), 3.45–3.46 (m, 1 H),

1.23 (t, J = 7.5 Hz, 3 H, COOCH₂CH₃) ppm. HR MALDI-TOF

MS: m/z calcd. for C₂₇H₃₀O₉[M + Na]⁺521.1787, found: 521.1782.

acetate (33 mg, 0.36 mmol) was added to a solution of compound

7R (205 mg, 0.33 mmol) in DMF (5 mL) at room temperature. Af-

ter stirring for 18 h, the reaction mixture was quenched with an

aqueous saturated solution of NaHCO₃(10 mL), and diluted with

ethyl acetate (10 mL). The organic phase was dried (MgSO₄) and

concentrated in vacuo. The residue was purified by flash silica gel

column chromatography (hexane/ethyl acetate; 3:1) to afford 8R

(168 mg, 88%). Trichloroacetonitrile (290 µL) and 1,8-diazabicy-

clo[5.4.0]undec-7-ene (DBU, 17 µL) were added to a solution of

8R (168 mg, 0.29 mmol) in dichloromethane (5 mL) at 0 °C. The

reaction mixture was stirred at 0 °C for 1 h and after which it was

concentrated under reduced pressure. The residue was purified by

flash silica gel column chromatography (hexane/ethyl acetate, 3:1)

to afford 9R. (199 mg, 95%). 9Rα: yellowish syrup, R_f= 0.65 (ethyl

acetate/hexane, 1:1). [α]²_D⁰= +104 (c = 0.8, CHCl₃). ¹H NMR

(300 MHz, CDCl₃): δ = 8.46 (s, 1 H, =NH), 7.13–8.18 (m, 15 H,

Ar), 6.47 (d, J = 3.6 Hz, 1 H, 1-H), 5.97 (t, J = 9.6 Hz, 1 H, 3-H),

5.04 (s, 1 H, ϾCHPh), 4.61 (d, J = 10.5 Hz, 1 H, CHHPh), 4.51

(d, J = 10.5 Hz, 1 H, CHHPh), 4.28–4.31 (m, 1 H, 5-H), 4.17–4.20

(m, 1 H, 6-H_a), 4.12 (q, J = 7.2 Hz, 2 H, COOCH₂CH₃), 3.99 (dd,

J = 3.6, 9.9 Hz, 1 H, 2-H), 3.92–3.94 (m, 1 H, 6-H_b), 3.83 (t, J =

9.9 Hz, 1 H, 4-H), 2.04 (s, 3 H, COCH₃), 1.20 (t, J = 7.2 Hz, 3 H,

COOCH₂CH₃) ppm.

1,6-Di-O-acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(R)-ethoxy-

carbonylbenzyl]-α-D-glucopyranose (11R): Trimethylsilyl trifluoro-

methanesulfonate (0.2 µL, 0.01 mmol) was added to a solution of

10R (175 mg, 0.35 mmol) in acetic anhydride (3 mL) at 0 °C. The

reaction mixture was stirred at 0 °C for 30 min. After which it was

quenched with an aqueous saturated solution of NaHCO₃(10 mL)

and then diluted with dichloromethane (10 mL). The organic phase

was dried (MgSO₄), filtered and the filtrate was concentrated in

vacuo. The residue was purified by flash silica gel column

chromatography (hexane/ethyl acetate, 3:1) to afford 11R (206 mg,

98%): colorless syrup, R_f= 0.59 (ethyl acetate/hexane, 1:1). [α]²_D⁰

= –67 (c = 2.0, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 7.26–

7.38 (m, 10 H, Ar), 6.21 (d, J = 3.0 Hz, 1 H, 1-H), 5.93–6.03 (m,

1 H, CH=CH₂), 5.39 (t, J = 9.5 Hz, 1 H, 3-H), 5.29 (dd, J = 7.5,

18.0 Hz, 1 H, CH=CHH), 5.25 (dd, J = 10.5, 18.0 Hz, 1 H,

CH=CHH), 5.00 (s, 1 H, ϾCHPh), 4.72 (d, J = 11.0 Hz, 1 H,

CHHPh), 4.68–4.73 (m, 2 H, OCHHCH=CH₂, OCHHCH=CH₂),

4.55 (d, J = 11.0 Hz, 1 H, CHHPh), 4.21–4.28 (m, 2 H, 6-H_a, 6-

H_b), 4.15 (q, J = 7.0 Hz, 2 H, COOCH₂CH₃), 3.95–3.97 (m, 1 H,

5-H), 3.73 (dd, J = 3.0, 9.5 Hz, 1 H, 2-H), 3.66 (t, J = 9.5 Hz, 1

H, 4-H), 2.02 (s, 6 H, COCH₃), 1.19 (t, J = 7.0 Hz, 3 H, CO-

OCH₂CH₃) ppm. HR MALDI-TOF MS: m/z calcd. for C₃₁H₃₆O₁₂

[M + Na]⁺623.2104, found 623.2124.

6-O-Acetyl-3-O-benzoyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-α/β-D-glucopyranosyl Trichloroacetimidate (9S): Compound 9S

was synthesized according to the procedure described for the syn-

thesis of compound 9R. 9Sα: R_f= 0.58 (ethyl acetate/hexane, 1:1).

[α]²_D⁰= +72 (c = 1.1, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ =

8.68 (s, 1 H, =NH), 7.06–7.62 (m, 15 H, Ar), 6.75 (d, J = 3.0 Hz,

1 H, 1-H), 5.94 (t, J = 9.5 Hz, 1 H, 3-H), 4.99 (s, 1 H, ϾCHPh),

4.34 (dd, J = 2.0, 12.0 Hz, 1 H, 6-H_a), 4.28 (dd, J = 3.5, 12.0 Hz,

1 H, 6-H_b), 4.19–4.21 (m, 1 H, 5-H), 4.11 (q, J = 7.0 Hz, 2 H,

COOCH₂CH₃), 3.86 (dd, J = 3.0, 9.5 Hz, 1 H, 2-H), 3.76 (t, J =

9.5 Hz, 1 H, 4-H), 2.05 (s, 3 H, COCH₃), 1.15 (t, J = 7.0 Hz, 3 H)

ppm.

1,6-Di-O-acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(S)-ethoxy-

carbonylbenzyl]-α-D-glucopyranose (11S): Compound 11S was syn-

thesized according to the procedure described for the synthesis of

1,6-Anhydro-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(R)-ethoxycar- compound 11R. R_f= 0.68 (ethyl acetate/hexane, 1:1). [α]²_D⁰= +43.8

1

bonylbenzyl]-β-

D-glucopyranose (10R): Tetramethyl ethylenediamine

(c = 0.6, CHCl₃). H NMR (500 MHz, CDCl₃): δ = 7.26–7.38 (m,

(98 µL, 0.65 mmol) was added to a solution of 2R (207 mg, 10 H, Ar), 6.48 (d, J = 3.5 Hz, 1 H, 1-H), 5.82–5.87 (m, 1 H,

0.50 mmol) and allyloxycarbonyl chloride (106 µL, 1.0 mmol) in

dichloromethane (10 mL) at 0 °C. Then the reaction mixture was

warmed to room temperature and stirred for 2 hours. The reaction

CH=CH₂), 5.37 (t, J = 9.5 Hz, 1 H, 3-H), 5.30–5.35 (m, 1 H,

CHH=CH), 5.23 (d, J = 11.0 Hz, 1 H, CHH=CH), 5.03 (s, 1 H,

ϾCHPh), 4.63 (d, J = 11.0 Hz, 1 H, CHHPh), 4.50 (d, J = 11.0 Hz,

mixture was quenched with an aqueous saturated solution of 1 H , C H H P h ) , 4 . 4 8 – 4 . 5 2 ( m , 2 H , O C H H C H = C H ₂,

Eur. J. Org. Chem. 2006, 5007–5028

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5019

J.-H. Kim, H. Yang, V. Khot, D. Whitfield, G.-J. Boons

FULL PAPER

OCHHCH=CH₂), 4.25 (m, 2 H, 6-H_a, 6-H_b), 4.09–4.19 (m, 2 H, (m, 1 H, OCHHCH=CH₂), 4.08–4.15 (m, 2 H, COOCH₂CH₃),

COOCH₂CH₃), 3.97–3.99 (m, 1 H, 5-H), 3.65 (dd, J = 3.5, 9.5 Hz, 3.95–4.03 (m, 1 H, OCHH=CH₂), 3.82–3.83 (m, 1 H, 6-H_a), 3.71–

1 H, 2-H), 3.60 (t, J = 9.5 Hz, 1 H, 4-H), 2.18 (s, 3 H, COCH₃), 3.73 (m, 1 H, 5-H), 3.62–3.65 (m, 1 H, 6-H_b), 3.40 (d, J = 2.0 Hz,

2.03 (s, 3 H, COCH₃), 1.20 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) 1 H, 2-H), 3.32–3.34 (m, 1 H, 4-H), 1.21 (t, J = 7.5 Hz, 3 H, CO-

ppm. HR MALDI-TOF MS: m/z calcd. for C₃₁H₃₆O₁₂[M + Na]⁺

623.2104, found 623.2111.

OCH₂CH₃) ppm. HR MALDI-TOF MS: m/z calcd. for C₂₆H₃₀O₇

[M + Na]⁺477.1889, found 477.1865.

6-O-Acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(R)-ethoxycar-

1,6-Di-O-acetyl-3-O-allyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

bonylbenzyl]-α-D-glucopyranosyl Trichloroacetimidate (13R): Hy- zyl]-α-D-glucopyranose (15R): Trimethylsilyl trifluoromethanesul-

drazinium acetate (28 mg, 0.30 mmol) was added to a solution of

compound 11R (165 mg, 0.27 mmol) in DMF (5 mL) at room tem-

fonate (2 µL, 0.01 mmol) was added to a solution of compound

14R (390 mg, 0.86 mmol) in acetic anhydride (10 mL) at 0 °C. After

perature. After stirring for 18 h, the reaction mixture was then stirring the reaction mixture for 30 min at 0 °C, it was quenched

quenched with an aqueous saturated solution of NaHCO₃(10 mL), with an aqueous saturated solution of NaHCO₃and diluted with

and diluted with ethyl acetate (10 mL). The organic phase was dichloromethane. After washing with an aqueous saturated solu-

dried (MgSO₄) and concentrated in vacuo. The residue was purified

by flash silica gel column chromatography (hexane/ethyl acetate,

3:1) to afford 12R (130 mg, 86%). Trichloroacetonitrile (230 µL)

and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 14 µL) were added

to a solution of 12R (130 mg, 0.23 mmol) in dichloromethane

(5 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 1 h.

The reaction mixture was concentrated in vacuo and the residue

was purified by flash silica gel column chromatography (hexane/

tion of NaHCO₃(10 mL), the organic layer was dried (MgSO₄),

concentrated in vacuo, and the residue was purified by flash silica

gel column chromatography (hexane/ethyl acetate; 4:1) to afford

compound 15R (450 mg, 94%). R_f= 0.70 (ethyl acetate/hexane,

1:1). [α]²_D⁰= +119.72 (c = 1.9, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.26–7.42 (m, 10 H, Ar), 6.05–6.09 (m, 1 H,

CH=CH₂), 6.02 (d, J = 3.5 Hz, 1 H, 1-H), 5.11 (s, 1 H, ϾCHPh),

4.91 (d, J = 10.5 Hz, 1 H, CHHPh), 4.62 (dd, J = 6.5, 13.0 Hz, 1

ethyl acetate, 3:1) to afford 13R. (155 mg, 95%): R_f= 0.74 (ethyl H, CHH=CH), 4.57 (d, J = 10.5 Hz, 1 H, CHHPh), 4.56 (dd, J =

acetate/hexane, 1:1). [α]²_D⁰= +53 (c = 1.0, CHCl₃). ¹H NMR

(500 MHz, CDCl₃): δ = 8.41 (s, 1 H, =NH), 7.26–7.47 (m, 10 H,

Ar), 6.43 (d, J = 3.5 Hz, 1 H, 1-H), 5.92–5.99 (m, 1 H, CH=CH₂),

5.50 (t, J = 10.0 Hz, 1 H, 3-H), 5.38–5.41 (m, 1 H, CH=CHH),

5 . 0 , 1 0 . 5 H z , 1 H , C H H = C H ) , 4 . 3 6 – 4 . 3 9 ( m , 2 H ,

OCHHCH=CH₂, OCHHCH=CH₂), 4.22–4.27 (m, 2 H, 6-H_a, 6-

H_b), 4.10–4.15 (m, 2 H, COOCH₂CH₃), 3.91 (t, J = 9.5 Hz, 1 H,

3-H), 3.83–3.85 (m, 1 H, 5-H), 3.60 (dd, J = 3.5, 9.5 Hz, 1 H, 2-

5.24–5.26 (m, 1 H, CH=CHH), 5.06 (s, 1 H, ϾCHPh), 4.74 (d, J H), 3.49 (t, J = 9.5 Hz, 1 H, 4-H), 2.05 (s, 3 H,COCH₃), 2.00 (s, 3

= 10.5 Hz, 1 H, CHHPh), 4.70–4.75 (m, 2 H, OCHHCH=CH₂, H, COCH₃), 1.20 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR

OCHHCH=CH₂), 4.57 (d, J = 10.5 Hz, 1 H, CHHPh), 4.24–4.27 MALDI-TOF MS: m/z calcd. for C₃₀H₃₆O₁₀[M + Na]⁺579.2206,

(m, 2 H, 6-H_a, 6-H_b), 4.14–4.17 (m, 2 H, COOCH₂CH₃), 4.10 (d,

J = 13.5 Hz, 1 H, 5-H), 3.82 (dd, J = 3.0, 9.5 Hz, 1 H, 2-H), 3.71

(t, J = 9.5 Hz, 1 H, 4-H), 2.02 (s, 3 H, COCH₃), 1.20 (t, J = 7.0 Hz,

3 H, COOCH₂CH₃) ppm.

found 579.2198.

1,6-Di-O-acetyl-3-O-allyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-α-

D-glucopyranose (15S): Compound 15S was synthesized ac-

cording to the procedure described for the synthesis of compound

6-O-Acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(S)-ethoxycar- 15R. ¹H NMR (500 MHz, CDCl₃): δ = 7.26–7.43 (m, 10 H, Ar),

bonylbenzyl]-α-

D

-glucopyranosyl Trichloroacetimidate (13S): Com-

6.46 (d, J = 3.0 Hz, 1 H, 1-H), 5.89–5.96 (m, 1 H, CH=CH₂), 5.26

(dd, J = 0.5, 17.0 Hz, 1 H, CHH=CH), 5.16–5.19 (m, CHH=CH),

5.19 (s, ϾCHPh), 4.85 (d, J = 11.0 Hz, 1 H, CHHPh), 4.55 (d, J =

11.0 Hz, 1 H, CHHPh), 4.36 (dd, J = 5.5, 10.0 Hz, 1 H,

O C H H C H = C H ₂) , 4 . 2 9 ( d d , J = 5 . 5 , 1 1 . 5 H z , 1 H ,

OCHHCH=CH₂), 4.10–4.26 (m, 4 H, COOCH₂CH₃, 6-H_a, 6-H_b),

3.87–3.89 (m, 1 H, 5-H), 3.87 (t, J = 10.0 Hz, 1 H, 3-H), 3.57 (dd,

J = 3.5, 9.5 Hz, 1 H, 2-H), 3.47 (t, J = 10.0 Hz, 1 H, 4-H), 2.15 (s,

pound 13S was synthesized according to the procedure described

for the synthesis of compound 13R. R_f= 0.68 (ethyl acetate/hexane,

1:1). [α]²_D⁰= +10 (c = 0.4, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ

= 8.70 (s, 1 H, =NH), 7.25–7.37 (m, 10 H, Ar), 6.72 (d, J = 3.6 Hz,

1 H, 1-H), 5.73–5.85 (m, 1 H, CH=CH₂), 5.46 (t, J = 9.9 Hz, 1 H,

3-H), 5.29 (d, J = 17.1 Hz, 1 H, CH=CHH), 5.20 (d, J = 11.4 Hz,

1 H, CH=CHH), 5.10 (s, 1 H, ϾCHPh), 4.65 (d, J = 11.1 Hz, 1 H,

CHHPh), 4.53 (d, J = 11.1 Hz, 1 H, CHHPh), 4.42–4.47 (m, 2 H, 3 H, COCH₃), 2.02 (s, 3 H, COCH₃), 1.19 (t, J = 7.5 Hz, 3 H,

OCHHCH=CH₂, OCHHCH=CH₂), 4.26–4.29 (m, 2 H, 6-H_a, 6- COOCH₂CH₃) ppm. MALDI-TOF MS: m/z calcd. for C₃₀H₃₆O₁₀

H_b), 4.07–4.16 (m, 3 H, 5-H, COOCH₂CH₃), 3.75 (dd, J = 3.6,

9.9 Hz, 1 H, 2-H), 3.66 (t, J = 9.9 Hz, 1 H, 4-H), 2.02 (s, 3 H,

COCH₃), 1.19 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm.

[M + Na]⁺579.2206, found 579.2221.

6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-α-

D-glucopyranosyl Trichloroacetimidate (17R): Hydrazinium acetate

1,6-Anhydro-3-O-allyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-

β-D-glucopyranose (14R): Tetrakis(triphenylphosphane)palladium

(76 mg, 0.83 mmol) was added to a solution of compound 15R

(458 mg, 0.82 mmol) in DMF (5 mL) at room temperature. After

the reaction mixture was stirred for 18 h, it was quenched with an

aqueous saturated solution of NaHCO₃, and then diluted with

ethyl acetate. The organic phase was dried (MgSO₄), and the sol-

vent was removed in vacuo. The residue was purified by flash col-

umn chromatography (hexane/ethyl acetate, 2:1) to afford 16R

(388 mg, 92%). Trichloroacetonitrile (0.75 mL) and 1,8-diazabicy-

clo[5.4.0]undec-7-ene (DBU, 45 µL) were added to a solution of

16R (388 mg, 0.75 mmol) in dichloromethane (10 mL) at 0 °C. Af-

ter stirring the reaction mixture at 0 °C for 1 h, it was concentrate

(27 mg, 0.02 mmol) was added to a solution of compound 10R

(580 mg, 1.16 mmol) in benzene (10 mL) at room temperature. The

reaction mixture was stirred for 3 h at 70 °C, and then cooled to

room temperature. After filtration, the mixture was concentrated

under reduced pressure and the residue was purified by flash silica

gel column chromatography (hexane/ethyl acetate, 4:1) to afford

compound 14R (448 mg, 85%); Colorless syrup, R_f= 0.56 (ethyl

acetate/hexane, 1:1). [α]²_D⁰= +40 (c = 0.6, CHCl₃). ¹H NMR

(500 MHz, CDCl3): δ = 7.26–7.6 (m, 10 H, Ar), 5.85–5.90 (m, 1

H, CH=CH₂), 5.43 (s, 1 H, 1-H), 5.27 (dd, J = 1.0, 7.6 Hz, 1 H, in vacuo. The residue was purified by flash silica gel column

CHH=CH), 5.18 (dd, J = 1.0, 10.5 Hz, 1 H, CHH=CH), 5.13 (s, 1

H, ϾCHPh), 4.72 (d, J = 12.5 Hz, 1 H, CHHPh), 4.66 (d, J =

chromatography (20 % ethyl acetate in hexane) to afford 17R

(458 mg, 93%); R_f= 0.80 (ethyl acetate/hexane, 1:1). [α]²_D⁰= –94 (c

12.5 Hz, 1 H, CHHPh), 4.57 (d, J = 5.5 Hz, 1 H, 3-H), 4.22–4.9 = 0.5, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 8.45 (s, 1 H,

5020

www.eurjoc.org

Eur. J. Org. Chem. 2006, 5007–5028

Glycopyranosyl Donors with Chiral Auxiliaries

FULL PAPER

=NH), 7.26–7.43 (m, 10 H, Ar), 6.22 (d, J = 3.6 Hz, 1 H, 1-H), 72.17, 71.99, 67.72, 64.01, 61.44, 14.05 ppm. HR MALDI-TOF

6.02–6.15 (m, 1 H, CH=CH₂), 5.37 (d, J = 17.4 Hz, 1 H, MS: m/z calcd. for C₂₃H₂₆O₇[M + Na]⁺437.1577, found 437.1524.

CH=CHH), 5.22 (d, J = 10.2 Hz, 1 H, CH=CHH), 5.13 (s, 1 H,

1,3,6-Tri-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-α/β-

ϾHPh), 4.92 (d, J = 10.8 Hz, 1 H, CHHPh), 4.66 (dd, J = 5.7,

D

-galactopyranose (20S): Trimethylsilyl trifluoromethanesulfonate

12.6 Hz, 1 H, OCHHCH=CH₂), 4.59 (d, J = 10.8 Hz, 1 H,

CHHPh), 4.40 (dd, J = 5.7, 12.6 Hz, 1 H, OCHHCH=CH₂), 3.96–

4.24 (m, 6 H, COOCH₂CH₃, 3-H, 5-H, 6-H_a, 6-H_b), 3.69 (dd, J =

3.3, 9.6 Hz, 1 H, 2-H), 3.54 (t, J = 9.3 Hz, 1 H, 4-H), 1.99 (s, 3 H,

COCH₃), 1.21 (t, J = 6.9 Hz, 3 H, COOCH₂CH₃) ppm.

(5 µL, 0.03 mmol) was added to a solution of compound 19S

(281 mg, 0.68 mmol) in acetic anhydride (10 mL) at 0 °C. After stir-

ring the reaction mixture at 0 °C for 20 min, it was quenched with

an aqueous saturated solution of NaHCO₃. The organic phase was

washed with water (30 mL) and brine (30 mL) and dried (MgSO₄),

filtered and the filtrate was concentrated in vacuo. The residue was

purified by flash silica gel column chromatography (20% ethyl ace-

tate in hexane) to afford 20S (357 mg, 94%). 20Sα: Colorless syrup,

R_f= 0.57 (ethyl acetate/hexane, 1:1). [α]²_D⁰= –49 (c = 0.15, CHCl₃).

6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-α-

D-glucopyranosyl Trichloroacetimidate (17S): Compound 17S was

synthesized according to the procedure described for the synthesis

of compound 17R. R_f= 0.83 (ethyl acetate/hexane, 1:1). [α]²_D⁰= +64

(c = 0.5, CHCl₃). H NMR (500 MHz, CDCl₃): δ = 8.68 (s, 1 H, ¹H NMR (500 MHz, CDCl₃): δ = 7.21–7.39 (m, 10 H, Ar), 6.56

=NH), 7.26–7.44 (m, 10 H, Ar), 6.68 (d, J = 3.5 Hz, 1 H, 1-H), (d, J = 3.5 Hz, 1 H, 1-H), 5.21 (dd, J = 3.0, 10.5 Hz, 1 H, 3-H),

5.86–5.94 (m, 1 H, CH=CH₂), 5.26 (s, 1 H, ϾCHPh), 5.23 (dd, J 5.04 (s, 1 H, ϾCHPh), 4.59 (d, J = 11.0 Hz, 1 H, CHHPh), 4.48

1

= 1.5, 19.0 Hz, 1 H, CH=CHH), 5.14 (d, J = 11.0 Hz, 1 H,

CH=CHH), 4.86 (d, J = 11.0 Hz, 1 H, CHHPh), 4.57 (d, J =

(d, J = 11.0 Hz, 1 H, CHHPh), 4.17 (q, J = 7.5 Hz, 2 H, CO-

OCH₂CH₃), 4.10–4.16 (m, 3 H, 6-H_a, 2-H, 5-H), 4.02–4.05 (m, 2

11.0 Hz, 1 H, CHHPh), 4.26–4.30 (m, 4 H, 5-H, 6-H_a, H, 6-H_b, 4-H), 2.15 (s, 3 H, COCH₃), 2.00 (s, 3 H, COCH₃), 1.91

OCHHCH=CH₂, OCHHCH=CH₂), 4.14 (q, J = 6.5 Hz, 1 H, CO- (s, 3 H, COCH₃), 1.20 (t, J = 7.5 Hz, 3 H, COOCH₂CH₃) ppm.

OCH₂CH₃), 3.99–4.01 (m, 1 H, 6-H_b), 3.96 (t, J = 9.0 Hz, 1 H, 3- ¹³C NMR (75 MHz, CDCl₃): δ = 170.39, 170.35, 170.28, 169.29,

H), 3.65 (dd, J = 3.0, 9.5 Hz, 1 H, 2-H), 3.53 (t, J = 9.5 Hz, 1 H,

4-H), 2.01 (s, 3 H, COCH₃), 1.19 (t, J = 6.5 Hz, 3 H, CO-

OCH₂CH₃) ppm.

137.32, 136.21, 128.76, 128.51, 128.47, 128.14, 128.10, 127.35,

90.44, 81.51, 75.28, 74.49, 72.66, 70.09, 62.23, 61.52, 21.02, 20.84,

20.78, 14.00 ppm. HR MALDI-TOF MS: m/z calcd. for C₂₉H₃₄O₁₁

[M + Na]⁺581.1999, found 581.1913.

1,6-Anhydro-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-β-D-galac-

topyranose (19S): BF₃–OEt₂(218 µL, 1.7 mmol) was added drop-

wise to a mixture of 1,6:2,3-di-anhydro-4-O-benzyl-β--talopyr-

anose (18, 2.0 g, 8.58 mmol), ethyl (S)-mandelate (4.6 g, 43 mmol)

and activated molecular sieves (4 Å, 2 g) in toluene (50 mL) at

room temperature. After stirring for 1 h, the reaction mixture was

quenched with an aqueous saturated solution of NaHCO₃(50 mL)

and then diluted with ethyl acetate (50 mL). The organic phase was

dried (MgSO₄), filtered and the filtrate was concentrated in vacuo.

The residue was purified by flash silica gel column chromatography

(20% ethyl acetate in hexane) to afford 19S (1.81 g, 51%): colorless

syrup, R_f= 0.31 (ethyl acetate/hexane, 1:1). [α]²_D⁰= +52 (c = 1.0,

1,3,6-Tri-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-α/β-

D-galactopyranose (20R): Compound 20R was synthesized accord-

ing to the procedure described for the synthesis of compound 20S.

20Rα: R_f= 0.53 (ethyl acetate/hexane, 1:1). [α]²_D⁰= –70 (c = 1,

CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 7.31–7.37 (m, 10 H,

Ar), 6.23 (d, J = 4.0 Hz, 1 H, 1-H), 5.33 (dd, J = 2.5, 10.5 Hz, 1

H, 3-H), 5.03 (s, 1 H, ϾCHPh), 4.74 (d, J = 11.0 Hz, 1 H, CHHPh),

4.55 (d, J = 11.5 Hz, 1 H, CHHPh), 4.13–4.18 (m, 3 H, 6-H_a, 2-H,

4-H), 4.10 (q, J = 7.0 Hz, 2 H, COOCH₂CH₃), 3.97–4.03 (m, 2 H,

6-H_b, 5-H), 2.16 (s, 3 H, COCH₃), 2.04 (s, 3 H, COCH₃), 1.99 (s,

3 H, COCH₃), 1.20 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C

CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 7.21–7.41 (m, 10 H, NMR (75 MHz, CDCl₃): δ = 170.99, 170.91, 170.88, 169.48,

Ar), 5.60 (s, 1 H, 1-H), 5.03 (s, 1 H, ϾCHPh), 4.61 (d, J = 11.5 Hz,

1 H, CHHPh), 4.56 (d, J = 11.5 Hz, 1 H, CHHPh), 4.39 (t, J =

4.5 Hz, 1 H, 5-H), 4.24 (d, J = 7.5 Hz, 1 H, 6-H_a), 4.15 (q, J =

137.26, 136.20, 128.73, 128.56, 128.45, 128.14, 128.06, 126.95,

91.43, 80.11, 75.89, 74.92, 71.66, 71.12, 62.34, 60.21, 22.02, 21.84,

21.63, 14.15 ppm. HR MALDI-TOF MS: m/z calcd. for C₂₉H₃₄O₁₁

7.0 Hz, 2 H, COOCH₂CH₃), 4.05 (dd, J = 1.5, 3.5 Hz, 1 H, 3-H), [M + Na]⁺581.1999, found 581.1981.

3.81 (t, J = 4 Hz, 1 H, 4-H), 3.59 (s, 1 H, 2-H), 3.58 (d, J = 9.0 Hz,

3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-α/β-D-

1 H, 6-H_b), 2.79 (d, J = 2.0 Hz, 1 H, OH), 1.18 (t, J = 7.0 Hz, 3

H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.48,

137.15, 135.98, 128.54, 128.47, 128.40, 128.09, 127.65, 127.05,

127.00, 100.34, 80.14, 77.91, 71.99, 71.86, 71.69, 67.22, 63.73,

61.25, 13.87 ppm. HR MALDI-TOF MS: m/z calcd. for C₂₃H₂₆O₇

[M + Na]⁺437.1577, found 437.1526.

galactopyranosyl Trichloroacetimidate (22S): Hydrazinium acetate

(80 mg, 0.87 mmol) was added to a solution of compound 20S

(440 mg, 0.79 mmol) in DMF (15 mL) at room temperature. After

stirring the reaction mixture for 18 h, it was quenched with an

aqueous saturated solution of NaHCO₃. The organic phase was

washed with an aqueous saturated solution of NH₄Cl (30 mL) and

1,6-Anhydro-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-β-D-galac- dried (MgSO₄), filtered and the filtrate was concentrated in vacuo.

topyranose (19R): Compound 19R was synthesized from compound

18 and (R)-ethyl mandelate according to the procedure described

for the synthesis of compound 19S: Colorless syrup, R_f= 0.49

(ethyl acetate/hexane, 1:1). [α]²_D⁰= –131 (c = 1.0, CHCl₃). ¹H NMR

(500 MHz, CDCl₃): δ = 7.33–7.47 (m, 10 H, Ar), 5.31 (s, 1 H, 1-

The residue was purified by flash silica gel column chromatography

(20% ethyl acetate in hexane) to afford 21S (391 mg, 96%). Trichlo-

roacetonitrile (0.39 mL) and 1,8-diazabicyclo[5.4.0]undec-7-ene

(DBU, 45 µL) were added to a solution of 21S (391 mg, 0.76 mmol)

in dichloromethane (10 mL) at 0 °C. After stirring the reaction

H), 4.99 (s, 1 H, ϾCHPh), 4.72 (d, J = 12.0 Hz, 1 H, CHHPh), mixture at 0 °C for 1 h, it was concentrated under reduced pressure.

4.65 (d, J = 12.0 Hz, 1 H, CHHPh), 4.41 (t, J = 4.5 Hz, 1 H, 3-H), The residue was purified by silica gel column chromatography

4.24 (d, J = 7.0 Hz, 1 H, 6-H_a), 4.21–4.22 (m, 1 H, 5-H), 4.16 (q, (20% ethyl acetate in hexane) to afford 22S (452 mg, 90%). 22Sα:

J = 7.5 Hz, 2 H, COOCH₂CH₃), 3.95 (t, J = 4.5 Hz, 1 H, 4-H), R_f= 0.69 (ethyl acetate/hexane, 1:1). [α]²_D⁰= +92 (c = 1, CHCl₃).

3.57–3.60 (m, 2 H, 6-H_b, 2-H), 2.79 (d, J = 2.0 Hz, 1 H, OH), 2.68 ¹H NMR (500 MHz, CDCl₃): δ = 8.67 (s, 1 H, NH), 7.55–7.40 (m,

(br, 1 H, OH), 1.20 (t, J = 7.5 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C

NMR (75 MHz, CDCl₃): δ = 170.33, 137.36, 136.03, 128.95,

10 H, Ar), 6.79 (d, J = 3.0 Hz, 1 H, 1-H), 5.28 (dd, J = 2.5, 10.5 Hz,

1 H, 3-H), 5.12 (s, 1 H, ϾCHPh), 4.63 (d, J = 11.5 Hz, 1 H,

128.75, 128.70, 128.33, 127.86, 127.43, 100.23, 80.73, 77.80, 72.22, CHHPh), 4.50 (d, J = 11.5 Hz, 1 H, CHHPh), 4.24–4.26 (m, 1 H,

Eur. J. Org. Chem. 2006, 5007–5028

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5021

J.-H. Kim, H. Yang, V. Khot, D. Whitfield, G.-J. Boons

FULL PAPER

5-H), 4.22 (dd, J = 3.0, 10.0 Hz, 1 H, 2-H), 4.12–4.17 (m, 1 H, 4-

5.14 (t, J = 9.5 Hz, 1 H, 3Ј-H), 4.98 (d, J = 11.0 Hz, 1 H, CHHPh),

H), 4.14 (q, J = 7.0 Hz, 2 H, COOCH₂CH₃), 4.11–4.12 (m, 1 H, 4.73 (d, J = 11.0 Hz, 1 H, CHHPh), 4.69 (d, J = 11.0 Hz, 1 H,

6-H_b), 4.07 (dd, J = 6.5, 11.0 Hz, 1 H, 6-H_a), 1.98 (s, 3 H, COCH₃), CHHPh), 4.60 (d, J = 11.0 Hz, 1 H, CHHPh), 4.57 (d, J = 12.0 Hz,

1.91 (s, 3 H, COCH₃), 1.20 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) 1 H, CHHPh), 4.53 (d, J = 4.0 Hz, 1 H, 1-H), 4.51 (d, J = 12.0 Hz,

ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.64, 170.34, 170.30,

1 H, CHHPh), 4.49 (d, J = 12.0 Hz, 1 H, CHHPh), 4.14–4.19 (m,

161.15, 137.30, 136.23, 128.63, 128.55, 128.40, 128.19, 128.16, 4 H, 6Ј-H_a, 6Ј-H_b, 1Ј-H, CHHPh), 4.03–4.10 (m, 2 H, CO-

127.07, 94.90, 81.95, 75.24, 74.38, 73.17, 73.10, 70.42, 62.34, 61.52,

20.86, 20.75, 14.04 ppm.

OCH₂CH₃), 3.89 (t, J = 9.5 Hz, 1 H, 4-H), 3.77 (t, J = 9.5 Hz, 1

H, 3-H), 3.54 (t, J = 9.5 Hz, 1 H, 4Ј-H), 3.45 (dd, J = 4.0, 9.5 Hz,

1 H, 2-H), 3.32 (s, 3 H, OCH₃), 3.28 (dd, J = 2.0, 11.5 Hz, 1 H, 6-

H_a), 3.20–3.26 (m, 2 H, 2Ј-H, 5Ј-H), 3.16 (d, J = 10.5 Hz, 1 H, 5-

H), 2.91 (dd, J = 1.5, 11.0 Hz, 1 H6-H_b), 2.17 (s, 3 H, COCH₃),

1.88 (s, 3 H, COCH₃), 1.18 (t, J = 7.5 Hz, 3 H, COOCH₂CH₃)

ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 170.65, 170.60, 170.30,

139.44, 138.30, 137.59, 137.35, 136.88, 128.64, 128.49, 128.33,

128.30, 128.25, 128.22, 128.13, 128.05, 128.00, 127.95, 127.88,

127.81, 127.73, 127.20, 127.09, 101.93, 98.21, 81.02, 80.19, 80.01,

78.47, 75.85, 75.07, 74.85, 74.21, 73.47, 73.31, 72.53, 69.33, 66.98,

62.97, 60.99, 55.16, 21.36, 20.70, 14.07 ppm. HR MALDI-TOF

MS: m/z calcd. for C₅₅H₆₂O₁₅[M + Na]⁺985.3986, found

985.3898.

3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-α/β-D-

galactopyranosyl Trichloroacetimidate (22R): Compound 22R was

synthesized according to the procedure described for the synthesis

of compound 22S. 22Rα: R_f= 0.69 (ethyl acetate/hexane, 1:1).

1

[α]²_D⁰= +48 (c = 0.33, CHCl₃). H NMR (500 MHz, CDCl₃): δ =

8.44 (s, 1 H, NH), 7.28–7.40 (m, 10 H, Ar), 6.41 (d, J = 3.5 Hz, 1

H, 1-H), 5.44 (dd, J = 2.5, 10 Hz, 1 H, 3-H), 5.08 (s, 1 H, ϾCHPh),

4.75 (d, J = 11.5 Hz, 1 H, CHHPh), 4.56 (d, J = 11.5 Hz, 1 H,

CHHPh), 4.25 (dd, J = 4.0, 8.0 Hz, 1 H, 2-H), 4.22–4.24 (m, 1 H,

6-H_a), 4.14 (q, J = 7.0 Hz, 2 H, COOCH₂CH₃), 4.10–4.11 (m, 1 H,

4-H), 4.09 (d, J = 2.0 Hz, 1 H, 6-H_b), 4.06 (dd, J = 6.0, 11.0 Hz, 1

H, 5-H), 2.15 (s, 3 H, COCH₃), 1.96 (s, 3 H, COCH₃), 1.19 (t, J =

7.5 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ

= 170.46, 170.31, 169.96, 160.76, 137.38, 136.32, 128.67, 128.53,

128.46, 128.24, 128.15, 127.07, 94.24, 90.98, 80.82, 75.22, 74.44,

73.00, 71.59, 70.59, 62.32, 61.19, 21.09, 20.71, 14.06 ppm.

3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-α-

D-glu-

copyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α- -galactopyranose

D

(29Sα): [α]²_D⁰= +169 (c = 1.5, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.23–7.40 (m, 10 H, aromatic), 5.61 (t, J = 9.5 Hz, 1

H, 3Ј-H), 5.51 (d, J = 5.0 Hz, 1 H, 1-H), 5.09 (d, J = 3.5 Hz, 1 H,

1Ј-H), 5.08 (s, 1 H, ϾCHPh), 4.61 (dd, J = 2.5, 8.0 Hz, 1 H, 3-H),

4.54 (d, J = 11.5 Hz, 1 H, CHHPh), 4.50 (d, J = 11.5 Hz, 1 H,

CHHPh), 4.35 (dd, J = 2.0, 8.0 Hz, 1 H, 4-H), 4.30 (dd, J = 2.5,

5.0 Hz, 1 H, 2-H), 4.26–4.28 (m, 2 H), 4.03–4.18 (m, 4 H), 3.76–

3.81 (m, 2 H), 3.50 (t, J = 9.5 Hz, 1 H, 4Ј-H), 3.47 (dd, J = 3.5,

9.5 Hz, 1 H, 2Ј-H), 2.05 (s, 3 H, COCH₃), 1.94 (s, 3 H, COCH₃),

1.55 (s, 3 H, CH₃), 1.46 (s, 3 H, CH₃), 1.36 (s, 3 H, CH₃), 1.32 (s,

3 H, CH₃), 1.20 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR

(75 MHz, CDCl₃): δ = 170.72, 170.42, 169.61, 137.49, 135.96,

128.79, 128.59, 128.48, 128.10, 127.96, 127.32, 109.25, 108.78,

97.41, 96.29, 80.45, 76.67, 75.96, 73.51, 73.24, 70.85, 70.69, 70.66,

68.17, 67.49, 66.44, 62.95, 61.31, 26.16, 26.13, 24.97, 24.65, 20.10,

20.90, 14.05 ppm. HR MALDI-TOF MS: m/z calcd. for C₃₉H₅₀O₁₅

[M + Na]⁺781.3047, found 781.3033.

General Procedure for the Glycosylations: A mixture of glycosyl do-

nor 5R or 5S (20 mg, 0.03 mmol), glycosyl acceptor (0.036 mmol)

and activated molecular sieves (4 Å) in dichloromethane (10 mL)

was stirred at room temperature for 1 h under argon. After cooling

the mixture to –78 °C, trimethylsilyl trifluoromethanesulfonate

(2.2 µL, 0.012 mmol) was added, and the reaction mixture was

stirred at –78 °C for 1 h and then warmed to 0 °C over a period of

1 h. The reaction mixture was quenched with an aqueous saturated

solution of NaHCO₃(10 mL). The organic phase was dried

(MgSO₄), filtered and the filtrate was concentrated in vacuo. The

residue was purified by silica gel column chromatography (dichlo-

romethane/hexane/ethyl acetate, 2:2:1).

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-α-D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glucopyrano-

side (28Sα): [α]²_D⁰= +251 (c = 1.3, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.16–7.37 (m, 25 H, aromatic), 5.81 (d, J = 3.5 Hz, 1

H, 1Ј-H), 5.54 (t, J = 9.5 Hz, 1 H, 3Ј-H), 5.06 (d, J = 11.5 Hz, 1

H, CHHPh), 4.93 (d, J = 11.5 Hz, 1 H, CHHPh), 4.91 (s, 1 H,

ϾCHPh), 4.67 (d, J = 12.5 Hz, 1 H, CHHPh), 4.61 (d, J = 3.5 Hz,

1 H, 1-H), 4.56 (d, J = 12.5 Hz, 1 H, CHHPh), 4.51 (s, 2 H,

CH₂Ph), 4.50 (d, J = 11.0 Hz, 1 H, CHHPh), 4.43 (d, J = 11.0 Hz,

1 H, CHHPh), 4.00–4.08 (m, 6 H, 3-H, 6-H_a, 6Ј-H_a, 6Ј-H_b, CO-

OCH₂CH₃), 3.85–3.93 (m, 3 H, 5Ј-H, 4-H, 6-H_b), 3.64 (d, J =

10.0 Hz, 1 H, 5-H), 3.59 (dd, J = 3.5, 9.0 Hz, 1 H, 2-H), 3.43 (t, J

= 9.5 Hz, 1 H, 4Ј-H), 3.39 (dd, J = 3.5, 9.5 Hz, 1 H, 2Ј-H), 3.38 (s,

3 H, OCH₃), 1.97 (s, 3 H, COCH₃), 1.92 (s, 3 H, COCH₃), 1.12 (t,

J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃):

δ = 170.47, 170.09, 169.52, 139.36, 137.98, 137.54, 135.82, 128.71,

128.47, 128.43, 128.24, 128.17, 128.01, 127.93, 127.89, 127.45,

127.41, 126.92, 97.67, 95.28, 81.60, 80.53, 80.23, 77.21, 76.42,

76.04, 74.15, 73.84, 73.38, 73.26, 73.20, 71.75, 69.28, 68.85, 68.79,

62.75, 61.26, 55.13, 21.04, 20.86, 13.98 ppm. HR MALDI-TOF

MS: m/z calcd. for C₅₅H₆₂O₁₅[M + Na]⁺985.3986, found

985.3965.

3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-β-

D-glu-

copyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α- -galactopyranose

D

(29Sβ): [α]²_D⁰= –98 (c = 0.6, CHCl₃). ¹H NMR (500 MHz, CDCl₃):

δ = 7.19–7.43 (m, 10 H, aromatic), 5.55 (s, 1 H, ϾCHPh), 5.54 (d,

J = 5.0 Hz, 1 H, 1-H), 5.34 (t, J = 9.5 Hz, 1 H, 3Ј-H), 4.61 (dd, J

= 2.5, 7.5 Hz, 1 H, 3-H), 4.60 (d, J = 7.5 Hz, 1 H, 1Ј-H), 4.50 (d,

J = 11.5 Hz, 1 H, CHHPh), 4.42 (d, J = 11.5 Hz, 1 H, CHHPh),

4.33 (dd, J = 2.5, 5.0 Hz, 1 H, 2-H), 4.04–4.29 (m, 7 H), 3.73 (dd,

J = 9.0, 11.5 Hz, 1 H), 3.54–3.57 (m, 1 H, 5-H), 3.42 (t, J = 9.5 Hz,

1 H, 4Ј-H), 3.23 (dd, J = 7.5, 9.5 Hz, 1 H, 2Ј-H), 2.03 (s, 3 H,

COCH₃), 1.86 (s, 3 H, COCH₃), 1.60 (s, 3 H, CH₃), 1.45 (s, 3 H,

CH₃), 1.34 (s, 6 H, 2 × CH₃), 1.18 (t, J = 7.0 Hz, 3 H, CO-

OCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.67, 170.57,

169.62, 137.26, 136.73, 128.58, 128.52, 128.50, 128.33, 128.05,

127.99, 109.50, 108.53, 104.06, 96.41, 80.19, 76.60, 76.01, 74.85,

74.37, 72.63, 71.30, 70.86, 70.35, 70.16, 67.00, 62.96, 60.98, 26.03,

26.00, 24.95, 24.52, 20.96, 20.88, 14.02 ppm. HR MALDI-TOF

MS: m/z calcd. for C₃₉H₅₀O₁₅[M + Na]⁺781.3047, found

781.3028.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-α-

copyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α- -galactopyranose

(29Rα): [α]²_D⁰= +54 (c = 0.5, CHCl₃). ¹H NMR (500 MHz, CDCl₃):

CDCl₃): δ = 7.20–7.38 (m, 25 H, aromatic), 5.14 (s, 1 H, ϾCHPh), δ = 7.28–7.53 (m, 10 H), 5.66 (t, J = 9.5 Hz, 1 H), 5.48 (d, J =

D-glu-

zyl]-β-

D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-

D-glucopyrano-

D

side (28Rβ): [α]²_D⁰= +91 (c = 0.9, CHCl₃). ¹H NMR (500 MHz,

5022

www.eurjoc.org

Eur. J. Org. Chem. 2006, 5007–5028

Glycopyranosyl Donors with Chiral Auxiliaries

FULL PAPER

4.5 Hz, 1 H), 5.07 (s, 1 H), 4.91 (d, J = 4.0 Hz, 1 H), 4.64 (d, J =

11.5 Hz, 1 H), 4.57 (d, J = 11.5 Hz, 1 H), 4.51 (d, J = 10.0 Hz, 1

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

zyl]-α-D-glucopyranosyl]-(1Ǟ3)-2-O-benzyl-4,6-O-benzylidene-α-D-

1

H), 3.96–4.34 (m, 8 H), 3.57–3.73 (m, 4 H), 2.12 (s, 3 H), 2.07 (s, glucopyranoside (30Rα): [α]²_D⁰= +114 (c = 0.4, CHCl₃). H NMR

3 H), 1.56 (s, 3 H), 1.44 (s, 3 H), 1.33 (s, 3 H), 1.27 (s, 3 H), 1.23

(500 MHz, CDCl₃): δ = 7.03–7.39 (m, 20 H), 5.68 (t, J = 9.5 Hz, 1

H), 5.59 (d, J = 3.5 Hz, 1 H), 5.01 (s, 1 H), 4.85 (s, 1 H), 4.66 (d,

(t, J = 7.0 Hz, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.71,

170.16, 170.06, 137.55, 136.51, 128.71, 128.67, 128.30, 127.10, J = 4.0 Hz, 1 H), 4.63 (d, J = 11.5 Hz, 1 H), 4.59 (d, J = 11.5 Hz,

109.25, 108.80, 96.79, 96.26, 79.45, 77.22, 76.92, 75.76, 73.78, 1 H), 4.58 (d, J = 11.0 Hz, 1 H), 4.48 (d, J = 11.0 Hz, 1 H), 4.38

72.87, 70.79, 70.62, 68.25, 66.93, 66.17, 62.89, 61.25, 26.15, 26.12,

24.93, 24.73, 21.18, 20.89, 14.10 ppm. HR MALDI-TOF MS: m/z

calcd. for C₃₉H₅₀O₁₅[M + Na]⁺781.3047, found 781.3108.

(d, J = 10.5 Hz, 1 H), 4.26 (t, J = 9.5 Hz, 1 H), 4.08–4.14 (m, 2

H), 4.00–4.05 (m, 2 H), 3.96 (dd, J = 3.0, 12.5 Hz, 1 H), 3.72–3.77

(m, 1 H), 3.52–3.63 (m, 3 H), 3.50 (dd, J = 3.5, 10.0 Hz, 1 H), 3.45

(t, J = 10.0 Hz, 1 H), 3.37 (s, 3 H), 2.13 (s, 3 H), 2.04 (s, 3 H), 1.10

(t, J = 7.0 Hz, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.65,

170.37, 170.32, 137.97, 137.31, 137.11, 136.07, 129.18, 128.64,

128.53, 128.40, 128.35, 128.29, 128.21, 128.07, 127.96, 127.76,

126.29, 126.15, 126.11, 101.30, 98.29, 95.13, 82.46, 77.70, 77.57,

76.28, 75.31, 73.97, 73.11, 73.06, 72.97, 68.99, 68.05, 62.58, 61.64,

60.93, 55.29, 21.29, 20.88, 14.07 ppm. HR MALDI-TOF MS: m/z

calcd. for C₄₈H₅₄O₁₅[M + Na]⁺893.3360, found 893.3384.

3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-β-

D-glu-

copyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α- -galactopyranose

D

(29Rβ): [α]²_D⁰= +126 (c = 1.3, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.49–7.51 (m, 2 H), 7.26–7.35 (m, 8 H), 5.66 (s, 1 H),

5.53 (d, J = 4.5 Hz, 1 H), 5.36 (t, J = 9.5 Hz, 1 H), 4.68 (d, J =

11.5 Hz, 1 H), 4.57 (dd, J = 3.5, 8.0 Hz, 1 H), 4.55 (d, J = 11.5 Hz,

1 H), 4.50 (d, J = 8.0 Hz, 1 H), 4.29–4.32 (m, 2 H), 4.24 (dd, J =

5.0, 12.0 Hz, 1 H), 4.12–4.19 (m, 2 H), 4.02–4.09 (m, 3 H), 3.62–

3.70 (m, 2 H), 3.56–3.59 (m, 1 H), 3.47 (dd, J = 8.0, 9.5 Hz, 1 H),

2.26 (s, 3 H), 2.07 (s, 3 H), 1.54 (s, 3 H), 1.43 (s, 3 H), 1.37 (s, 3

H), 1.34 (s, 3 H), 1.19 (t, J = 7.5 Hz, 3 H) ppm. ¹³C NMR

(75 MHz, CDCl₃): δ = 171.28, 170.68, 170.50, 137.49, 136.96,

128.54, 128.30, 128.03, 127.36, 109.50, 108.65, 103.91, 96.25, 79.54,

77.94, 75.72, 75.11, 74.55, 72.87, 71.44, 70.76, 70.48, 69.98, 67.19,

62.91, 60.73, 26.13, 25.97, 25.12, 24.49, 21.35, 20.90, 14.14 ppm.

HR MALDI-TOF MS: m/z calcd. for C₃₉H₅₀O₁₅[M + Na]⁺

781.3047, found 781.3053.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

zyl]-β-D-glucopyranosyl]-(1Ǟ3)-2-O-benzyl-4,6-O-benzylidene-α-D-

glucopyranoside (30Rβ): [α]²_D⁰= +168 (c = 1.5, CHCl₃). ¹H NMR

(500 MHz, CDCl₃): δ = 7.16–7.49 (m, 20 H), 5.67 (s, 1 H), 5.55 (s,

1 H), 5.33 (t, J = 9.5 Hz, 1 H), 4.95 (d, J = 8.5 Hz, 1 H), 4.61 (d,

J = 11.0 Hz, 1 H), 4.51 (d, J = 11.0 Hz, 1 H), 4.42 (d, J = 4.0 Hz,

1 H), 4.06–4.25 (m, 7 H), 3.98 (d, J = 11.0 Hz, 1 H), 3.71–3.78 (m,

2 H), 3.62 (d, J = 9.5 Hz, 1 H), 3.58 (d, J = 9.5 Hz, 1 H), 3.47 (dd,

J = 8.0, 9.5 Hz, 1 H), 3.37–3.43 (m, 2 H), 3.27 (s, 3 H), 2.22 (s, 3

H), 1.93 (s, 3 H), 1.17 (t, J = 7.0 Hz, 3 H) ppm. ¹³C NMR

(75 MHz, CDCl₃): δ = 171.03, 170.70, 170.54, 137.78, 137.51,

137.30, 137.01, 129.07, 128.49, 128.41, 128.38, 128.35, 128.22,

128.01, 127.99, 127.28, 126.13, 102.63, 101.25, 98.26, 80.85, 80.14,

79.62, 78.68, 77.20, 75.84, 74.95, 74.38, 73.20, 72.39, 68.93, 63.04,

61.99, 60.89, 55.21, 21.39, 20.81, 14.12 ppm. HR MALDI-TOF

MS: m/z calcd. for C₄₈H₅₄O₁₅[M + Na]⁺893.3360, found

893.3356.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-α-D-glucopyranosyl]-(1Ǟ3)-2-O-benzyl-4,6-O-benzylidene-α-D-

glucopyranoside (30Sα): [α]²_D⁰= +101 (c = 1.0, CHCl₃). ¹H NMR

(500 MHz, CDCl₃): δ = 6.64–7.57 (m, 20 H), 5.59 (t, J = 9.5 Hz, 1

H), 5.59 (s, 1 H), 5.41 (d, J = 3.0 Hz, 1 H), 4.87 (s, 1 H), 4.71 (d,

J = 3.5 Hz, 1 H), 4.59 (s, 2 H), 4.45 (d, J = 11.0 Hz, 1 H), 4.38 (d,

J = 11.0 Hz, 1 H), 4.22–4.32 (m, 3 H), 4.08–4.12 (m, 2 H), 4.06 (d,

J = 11.5 Hz, 1 H), 3.82–3.86 (m, 2 H), 3.66–3.74 (m, 3 H), 3.40 (s,

3 H), 3.35 (t, J = 9.5 Hz, 1 H), 3.16 (dd, J = 4.0, 10.0 Hz, 1 H),

2.06 (s, 3 H), 1.98 (s, 3 H), 1.22 (t, J = 7.5 Hz, 3 H) ppm. ¹³C

NMR (75 MHz, CDCl₃) δ = 170.60, 169.73, 169.64, 137.85, 137.39,

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-α-

D-glucopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzoyl-α-D-glucopyr-

anoside (31Sα): [α]²_D⁰= –65 (c = 3.2, CHCl₃). H NMR (500 MHz,

1

137.34, 134.93, 129.52, 128.72, 128.64, 128.54, 128.48, 128.40, CDCl₃): δ = 7.87–8.01 (m, 6 H, aromatic), 7.25–7.54 (m, 19 H,

128.32, 128.04, 127.95, 127.84, 127.75, 127.14, 102.41, 98.34, 94.94,

82.60, 77.74, 77.53, 75.42, 73.72, 73.48, 73.01, 72.95, 72.78, 69.17,

67.78, 62.51, 61.81, 61.14, 55.33, 21.08, 20.81, 14.09 ppm. HR

MALDI-TOF MS: m/z calcd. for C₄₈H₅₄O₁₅[M + Na]⁺893.3360,

found: 893.3347.

aromatic), 6.19 (t, J = 10.0 Hz, 1 H, 3-H), 5.67 (t, J = 10.0 Hz, 1

H, 3Ј-H), 5.43 (t, J = 10.0 Hz, 1 H, 4-H), 5.29 (dd, J = 3.5, 10.0 Hz,

1 H, 2-H), 5.23 (d, J = 3.5 Hz, 1 H, 1-H), 5.08 (d, J = 3.0 Hz, 1

H, 1Ј-H), 5.05 (s, 1 H, ϾCHPh), 4.58 (d, J = 11.0 Hz, 1 H,

CHHPh), 4.53 (d, J = 11.0 Hz, 1 H, CHHPh), 4.42 (t, J = 10.0 Hz,

1 H, 5-H), 4.32 (d, J = 11.0 Hz, 1 H, 6Ј-H_a), 4.20–4.26 (m, 2 H,

6Ј-H_b, 5Ј-H), 4.07–4.12 (m, 2 H, COOCH₂CH₃), 3.92 (dd, J = 8.0,

10.0 Hz, 1 H, 6-H_a), 3.66 (d, J = 8.0 Hz, 1 H, 6-H_b), 3.57 (dd, J =

3.0, 10.0 Hz, 1 H, 2Ј-H), 3.52 (t, J = 10.0 Hz, 1 H, 4Ј-H), 3.50 (s,

3 H, OCH₃), 2.10 (s, 3 H, COCH₃), 1.86 (s, 3 H, COCH₃), 1.15 (t,

J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃):

δ = 170.82, 170.67, 169.59, 165.81, 165.48, 137.50, 136.17, 133.42,

133.29, 133.04, 129.96, 129.68, 129.29, 129.16, 128.92, 128.54,

128.48, 128.42, 128.39, 128.25, 128.01, 127.96, 126.86, 97.31, 96.61,

81.59, 78.32, 76.13, 73.82, 73.20, 72.21, 70.58, 69.84, 68.74, 68.59,

67.33, 62.91, 61.39, 55.64, 20.89, 14.01 ppm. HR MALDI-TOF

MS: m/z calcd. for C₅₅H₅₆O₁₈[M + Na]⁺1027.3364, found

1027.3344.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-β-D-glucopyranosyl]-(1Ǟ3)-2-O-benzyl-4,6-O-benzylidene-α-D-

glucopyranoside (30Sβ): [α]²_D⁰= –73 (c = 0.7, CHCl₃). ¹H NMR

(500 MHz, CDCl₃): δ = 7.14–7.52 (m, 20 H), 5.54 (s, 1 H), 5.35 (s,

1 H), 5.24 (t, J = 9.5 Hz, 1 H), 5.09 (d, J = 8.0 Hz, 1 H), 4.88 (d,

J = 12.0 Hz, 1 H), 4.59 (d, J = 12.0 Hz, 1 H), 4.55 (d, J = 4.0 Hz,

1 H), 4.40 (d, J = 11.0 Hz, 1 H), 4.37 (d, J = 11.0 Hz, 1 H), 4.34

(t, J = 9.0 Hz, 1 H), 4.23 (dd, J = 4.5, 10.0 Hz, 1 H), 4.15–4.18 (m,

2 H), 4.01–4.09 (m, 2 H), 3.81 (dd, J = 4.5, 9.5 Hz, 1 H), 3.71–3.75

(m, 2 H), 3.57 (t, J = 9.5 Hz, 1 H), 3.42 (t, J = 9.0 Hz, 1 H), 3.34–

3.37 (m, 2 H), 3.32 (s, 3 H), 1.93 (s, 3 H), 1.66 (s, 3 H), 1.18 (t, J

= 7.5 Hz, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.65,

170.36, 169.56, 138.03, 137.39, 137.31, 137.02, 129.10, 128.67,

128.60, 128.57, 128.48, 128.45, 128.25, 128.15, 128.01, 127.93, Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

126.24, 101.94, 101.45, 98.40, 82.18, 80.64, 79.97, 79.17, 76.28,

75.44, 74.95, 74.16, 73.24, 72.17, 69.06, 62.96, 62.06, 61.08, 55.26,

20.88, 20.82, 14.07 ppm. HR MALDI-TOF MS: m/z: calcd. for

C₄₈H₅₄O₁₅[M + Na]⁺893.3360, found 893.3328.

zyl]-β-D-glucopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzoyl-α-D-glucopyr-

anoside (31Sβ): [α]²_D⁰= +16 (c = 0.5, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.84–7.98 (m, 6 H, aromatic), 7.17–7.54 (m, 19 H,

aromatic), 6.17 (t, J = 10.0 Hz, 1 H, 3-H), 5.41 (t, J = 10.0 Hz, 1

Eur. J. Org. Chem. 2006, 5007–5028

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5023

J.-H. Kim, H. Yang, V. Khot, D. Whitfield, G.-J. Boons

FULL PAPER

H, 3Ј-H), 5.23–5.32 (m, 4 H, 4-H, 2-H, 1-H, ϾCHPh), 4.60 (d, J (d, J = 11.0 Hz, 1 H), 4.82 (d, J = 11.0 Hz, 1 H), 4.76 (d, J =

= 7.5 Hz, 1 H, 1Ј-H), 4.48 (d, J = 11.0 Hz, 1 H, CHHPh), 4.38– 12.5 Hz, 1 H), 4.65 (d, J = 13.0 Hz, 1 H), 4.63 (d, J = 13.0 Hz, 1

4.43 (m, 2 H, 5-H, CHHPh), 4.22 (dd, J = 2.5, 12.0 Hz, 1 H, 6Ј- H), 4.61 (d, J = 3.5 Hz, 1 H), 4.54 (d, J = 9.5 Hz, 1 H), 4.48 (d, J

H_a), 4.11–4.19 (m, 3 H, 6Ј-H_b, 5Ј-H, COOCH₂CH₃), 3.98 (dd, J = = 9.5 Hz, 1 H), 4.26 (d, J = 12.0 Hz, 1 H), 4.20 (dd, J = 4.5,

2.5, 11.0 Hz, 1 H, 6-H_a), 3.82 (dd, J = 8, 11.0 Hz, 1 H, 6-H_b), 3.55–

12.0 Hz, 1 H), 3.96–4.07 (m, 4 H), 3.72–3.83 (m, 4 H), 3.65 (dd, J

3.58 (m, 1 H), 3.54 (s, 3 H, OCH₃), 3.39 (t, J = 9.5 Hz, 1 H, 4Ј-H), = 4.0, 9.5 Hz, 1 H), 3.49 (t, J = 10.5 Hz, 1 H), 3.47 (dd, J = 3.0,

3.26 (dd, J = 7.5, 9.5 Hz, 1 H, 2Ј-H), 1.95 (s, 3 H, COCH₃), 1.70

(s, 3 H, COCH₃), 1.18 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm.

¹³C NMR (75 MHz, CDCl₃): δ = 170.62, 170.26, 169.48, 165.84,

10.0 Hz, 1 H), 3.37 (s, 3 H), 2.02 (s, 3 H), 1.90 (s, 3 H), 1.13 (t, J

= 7.5 Hz, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.78,

170.62, 169.46,138.98, 138.52, 138.42, 137.42, 135.93, 128.61,

165.79, 165.44, 137.18, 137.02, 133.53, 133.37, 133.10, 129.93, 128.54, 128.49, 128.35, 128.34, 128.28, 128.10, 128.07, 128.00,

129.88, 129.66, 129.24, 129.09, 128.91, 128.59, 128.52, 128.50, 127.88, 127.71, 127.54, 127.46, 127.06, 98.01, 97.00, 82.16, 81.55,

128.43, 128.27, 128.07, 128.01, 127.83, 103.64, 96.93, 81.40, 78.61, 80.18, 77.76, 76.17, 75.72, 75.04, 74.08, 73.07, 73.36, 70.82, 68.44,

76.16, 74.68, 74.32, 72.60, 72.09, 70.30, 70.08, 69.77, 68.90, 62.99,

65.59, 62.88, 61.30, 55.15, 20.96, 20.86, 14.03 ppm. HR MALDI-

61.17, 55.89, 20.85, 20.67, 14.12 ppm. HR MALDI-TOF MS: m/z: TOF MS: m/z calcd. for C₅₅H₆₂O₁₅[M + Na]⁺985.3986, found

calcd. for C₅₅H₅₆O₁₈[M + Na]⁺: 1027.3364; found: 1027.3378.

985.3998.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-α-

anoside (31Rα): [α]²_D⁰= +144 (c = 0.7, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.84–7.98 (m, 6 H, aromatic), 7.09–7.54 (m, 19 H, CDCl₃): δ = 7.17–7.37 (m, 25 H), 5.27 (s, 1 H), 5.26 (t, J = 9.5 Hz,

aromatic), 6.14 (t, J = 9.5 Hz, 1 H, 3-H), 5.68 (t, J = 9.5 Hz, 1 H, 1 H), 4.99 (d, J = 10.5 Hz, 1 H), 4.89 (d, J = 11.0 Hz, 1 H), 4.79–

3Ј-H), 5.34 (t, J = 9.5 Hz, 1 H, 4-H), 5.19 (s, 1 H, 1-H), 5.18 (dd, 4.82 (m, 2 H), 4.66 (d, J = 11.5 Hz, 1 H), 4.59 (d, J = 3.3 Hz, 1

D

-glucopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzoyl-α-

D

-glucopyr-

zyl]-β-

D-glucopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzyl-α-D-glucopyrano-

side (32Sβ): [α]²_D⁰= –198 (c = 1.3, CHCl₃). ¹H NMR (500 MHz,

J = 3.5, 9.5 Hz, 1 H, 2-H), 4.96 (s, 1 H, ϾCHPh), 4.68 (d, J =

3.5 Hz, 1 H, 1Ј-H), 4.61 (d, J = 11.0 Hz, 1 H, CHHPh), 4.54 (d, J

= 11.0 Hz, 1 H, CHHPh), 4.24–4.28 (m, 2 H, 5-H, 5Ј-H), 4.20 (dd,

J = 4.5, 12.5 Hz, 1 H, 6Ј-H_a), 4.08–4.13 (m, 3 H, 6Ј-H_b, CO-

OCH₂CH₃), 3.75 (dd, J = 8.5, 10.5 Hz, 1 H, 6-H_a), 3.61 (dd, J =

H), 4.57 (d, J = 11.0 Hz, 1 H), 4.47 (d, J = 11.5 Hz, 1 H), 4.40–

4.44 (m, 2 H), 4.28 (d, J = 12.0 Hz, 1 H), 4.13 (dd, J = 4.5, 12.0 Hz,

1 H), 3.95–4.07 (m, 4 H), 3.84–3.88 (m, 1 H), 3.58 (dd, J = 6.0,

11.0 Hz, 1 H), 3.48–3.53 (m, 2 H), 3.41 (s, 3 H), 3.35–3.42 (m, 2

H), 3.28 (t, J = 8.5 Hz, 1 H), 1.97 (s, 3 H), 1.71 (s, 3 H), 1.02 (t, J

3.5, 9.5 Hz, 1 H, 2Ј-H), 3.55 (t, J = 9.5 Hz, 1 H, 4Ј-H), 3.49 (s, 3 = 7.0 Hz, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.58,

H, OCH₃), 3.33 (d, J = 10.5 Hz, 1 H, 6-H_b), 2.06 (s, 3 H, COCH₃), 170.05, 169.48, 138.73, 138.17, 138.16, 137.24, 136.83, 128.67,

2.01 (s, 3 H, COCH₃), 1.17 (t, J = 7.5 Hz, 3 H, COOCH₂CH₃) 128.50, 128.47, 128.35, 128.16, 128.04, 127.96, 127.94, 127.89,

ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.63, 170.11, 169.89,

127.83, 127.61, 103.47, 98.03, 81.88, 81.23, 79.90, 78.31, 77.90,

165.76, 165.36, 137.56, 136.77, 133.51, 133.31, 133.06, 129.94, 76.12, 75.75, 75.01, 74.70, 74.34, 73.40, 72.59, 69.81, 69.28, 62.79,

129.90, 129.66, 129.23, 129.12, 128.85, 128.58, 128.48, 128.41, 61.07, 55.37, 20.91, 20.79, 13.96 ppm. HR MALDI-TOF MS: m/z

128.25, 128.01, 127.95, 127.03, 96.60, 96.48, 80.01, 77.90, 75.91, calcd. for C₅₅H₆₂O₁₅[M + Na]⁺985.3986, found 985.3876.

73.88, 72.19, 72.14, 70.46, 69.72, 68.56, 68.52, 66.56, 62.82, 61.26,

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

55.62, 21.03, 20.86, 14.02 ppm. HR MALDI-TOF MS: m/z calcd.

zyl]-β-D-glucopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzyl-α-D-glucopyrano-

for C₅₅H₅₆O₁₈[M + Na]⁺1027.3364, found 1027.3405.

side (32Rβ): [α]²_D⁰= +94 (c = 1.4, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.09–7.39 (m, 25 H), 5.53 (s, 1 H), 5.32 (t, J = 9.5 Hz,

1 H), 4.96 (d, J = 11.0 Hz, 1 H), 4.82 (d, J = 12.0 Hz, 1 H), 4.76

(d, J = 11.0 Hz, 1 H), 4.70 (d, J = 12.0 Hz, 1 H), 4.68 (d, J =

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

zyl]-β-

D-glucopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzoyl-α-D-glucopyr-

anoside (31Rβ): [α]²_D⁰= +164 (c = 1.6, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.84–7.99 (m, 6 H, aromatic), 7.25–7.53 (m, 19 H, 11.0 Hz, 1 H), 4.61 (d, J = 3.0 Hz, 1 H), 4.55 (t, J = 11.0 Hz, 2 H),

aromatic), 6.17 (t, J = 9.5 Hz, 1 H, 3-H), 5.70 (s, 1 H, ϾCHPh),

5.36 (t, J = 9.5 Hz, 2 H, 3Ј-H, 4-H), 5.28 (s, 1 H, 1-H), 5.27 (dd, J

4.22–4.33 (m, 3 H), 4.17 (dd, J = 4.5, 11.0 Hz, 1 H), 4.12 (dd, J =

7.5, 11.0 Hz, 1 H), 4.02–4.07 (m, 2 H), 3.96 (t, J = 9.0 Hz, 1 H),

= 4.0, 9.5 Hz, 1 H, 2-H), 4.66 (d, J = 10.5 Hz, 1 H, CHHPh), 4.53 3.76–3.80 (m, 1 H), 3.63 (t, J = 9.5 Hz, 1 H), 3.51 (dd, J = 3.5,

(d, J = 10.5 Hz, 1 H, CHHPh), 4.52 (d, J = 9.5 Hz, 1 H, 1Ј-H), 10.0 Hz, 1 H), 3.39–3.48 (m, 3 H), 3.31 (s, 3 H), 3.29 (t, J = 9.5 Hz,

4.38 (t, J = 9.5 Hz, 1 H, 5-H), 4.13–4.21 (m, 3 H, 6Ј-H_a, CO-

OCH₂CH₃), 4.06 (dd, J = 7.5, 10.5 Hz, 1 H, 6Ј-H_b), 4.00 (d, J =

10.0 Hz, 1 H, 6-H_b), 3.74 (dd, J = 9.0, 10.0 Hz, 1 H, 6-H_a), 3.55–

3.61 (m, 2 H, 4Ј-H, 5Ј-H), 3.45 (s, 3 H, OCH₃), 3.42 (t, J = 9.5 Hz,

1 H, 2Ј-H), 2.24 (s, 3 H, COCH₃), 1.85 (s, 3 H, COCH₃), 1.14 (t,

1 H), 2.22 (s, 3 H), 1.99 (s, 3 H), 1.15 (t, J = 7.0 Hz, 3 H) ppm.

¹³C NMR (75 MHz, CDCl₃): δ = 170.86, 170.63, 170.56, 138.78,

138.14, 138.12, 137.51, 136.59, 128.53, 128.49, 128.41, 128.34,

128.15, 128.05, 127.97, 127.70, 127.60, 127.0, 103.48, 97.99, 81.85,

79.89, 79.76, 78.17, 77.99, 75.73, 74.89, 74.76, 74.57, 73.33, 72.88,

J = 7.5 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): 69.70, 68.58, 62.75, 60.87, 55.29, 21.35, 20.81, 14.10 ppm. HR

δ = 170.97, 170.56, 170.44, 165.86, 165.74, 165.51, 137.37, 136.66, MALDI-TOF MS: m/z calcd. for C₅₅H₆₂O₁₅[M + Na]⁺985.3986,

133.58, 133.41, 133.13, 129.93, 129.84, 129.63, 129.16, 129.03, found 985.3993.

128.72, 128.59, 128.53, 128.49, 128.44, 128.28, 128.06, 128.00,

127.14, 103.45, 96.85, 79.65, 78.21, 75.86, 74.94, 74.52, 72.78,

72.07, 70.27, 69.93, 68.88, 63.01, 60.88, 55.69, 21.31, 20.57, 14.08

ppm. HR MALDI-TOF MS: m/z calcd. for C₅₅H₅₆O₁₈[M + Na]⁺

1027.3364, found 1027.3352.

Methyl [6-O-Acetyl-3-O-benzoyl-4-O-benzyl-2-O-[(S)-ethoxycar-

bonylbenzyl]-α-D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glu-

copyranoside (33Sα): [α]²_D⁰= +38 (c = 1.0, CHCl₃). ¹H NMR

(500 MHz, CDCl₃): δ = 6.80–7.52 (m, 30 H, Ar), 5.83 (d, J =

3.5 Hz, 1 H, 1-H), 5.75 (t, J = 9.5 Hz, 1 H, 3Ј-H), 5.04 (d, J =

12.0 Hz, 1 H, CHHPh), 4.92 (d, J = 12.0 Hz, 1 H, CHHPh), 4.90

(d, J = 12.0 Hz, 1 H, CHHPh), 4.88 (s, 1 H, ϾCHPh), 4.69 (d, J

= 12.0 Hz, 1 H, CHHPh), 4.61 (d, J = 12.0 Hz, 1 H, CHHPh), 4.56

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-α-

D-glucopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzyl-α-D-glucopyrano-

side (32Sα): [α]²_D⁰= –112 (c = 2.8, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.18–7.37 (m, 25 H), 5.63 (t, J = 10.0 Hz, 1 H), 5.32 (d, J = 12.0 Hz, 1 H, CHHPh), 4.55 (d, J = 3.5 Hz, 1 H, 1Ј-H),

(d, J = 3.0 Hz, 1 H), 5.04 (s, 1 H), 4.97 (d, J = 12.5 Hz, 1 H), 4.87 4.43 (d, J = 12.0 Hz, 1 H, CHHPh), 4.32 (d, J = 12.0 Hz, 1 H,

5024

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Eur. J. Org. Chem. 2006, 5007–5028

Glycopyranosyl Donors with Chiral Auxiliaries

FULL PAPER

CHHPh), 4.04–4.06 (m, 2 H, 6-H_a, 6-H_b), 3.83–3.97 (m, 4 H), 3.71 Methyl [6-O-Acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(S)-

(t, J = 9.5 Hz, 1 H, 4-H), 3.60–3.63 (m, 3 H), 3.51 (t, J = 9.5 Hz, ethoxycarbonylbenzyl]-β- -glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-ben-

1 H, 4Ј-H), 3.46 (dd, J = 3.5, 9.5 Hz, 1 H, 2Ј-H), 3.43 (dd, J = 3.5, zyl-α-

-glucopyranoside (35Sβ): [α]²_D⁰= +33 (c = 0.2, CHCl₃). ¹H

D

9.5 Hz, 1 H, 2-H), 3.32 (s, 3 H, OCH₃), 1.91 (s, 3 H, COCH₃), 0.98

(t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR MALDI-TOF MS:

m/z calcd. for C₆₀H₆₄O₁₅[M + Na]⁺1047.4142, found 1047.4138.

NMR (500 MHz, CDCl₃): δ = 7.19–7.38 (m, 25 H, Ar), 5.76–5.82

(m, 1 H), 5.21 (d, J = 10.0 Hz, 1 H), 5.04 (s, 1 H), 4.96 (d, J =

11.0 Hz, 1 H), 4.87 (t, J = 9.5 Hz, 1 H), 4.70–4.75 (m, 3 H), 4.59–

4.62 (m, 2 H), 4.43–4.52 (m, 4 H), 4.37–4.39 (m, 2 H), 4.03–4.13

(m, 7 H), 3.81 (t, J = 9.5 Hz, 1 H), 3.67–3.70 (m, 2 H), 3.51 (dd, J

= 3.5, 9.5 Hz, 1 H), 3.42 (t, J = 9.5 Hz, 1 H), 3.38 (s, 3 H, COCH₃),

3.22 (dd, J = 8.5, 9.5 Hz, 1 H), 3.13–3.15 (m, 1 H), 2.04 (s, 3 H,

COCH₃), 1.18 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR

MALDI-TOF MS: m/z calcd. for C₅₇H₆₄O₁₆[M + Na]⁺1027.4092,

found 1027.4088.

Methyl [6-O-Acetyl-3-O-benzoyl-4-O-benzyl-2-O-[(R)-ethoxycar-

bonylbenzyl]-α-D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glu-

copyranoside (33Rα): Selected ¹H NMR (300 MHz, CDCl₃): δ =

5.84 (d, J = 3.6 Hz, 1 H, 1Ј-H), 3.39 (s, 3 H, CH₃), 2.03 (s, 3 H,

COCH₃), 1.22 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm.

Methyl [6-O-Acetyl-3-O-benzoyl-4-O-benzyl-2-O-[(R)-ethoxycar-

bonylbenzyl]-β-D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glu-

Methyl [6-O-Acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(R)-

copyranoside (33Rβ): Selected ¹H NMR (300 MHz, CDCl₃): δ =

5.62 (d, J = 7.5 Hz, 1 H, 1Ј-H), 3.37 (s, 3 H, CH₃), 1.96 (s, 3 H,

COCH₃), 1.18 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm.

ethoxycarbonylbenzyl]-β-

D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-ben-

zyl-α-D

-glucopyranoside (35Rβ): [α]²_D⁰= +10 (c = 0.2, CHCl₃). ¹H

NMR (500 MHz, CDCl₃): δ = 7.20–7.37 (m, 25 H, Ar), 5.92–6.05

(m, 1 H, CH=CH₂), 5.39 (dd, J = 1.5, 17.1 Hz, 1 H, CHH=CH),

5.24 (dd, J = 1.5, 10.5 Hz, 1 H, CHH=CH), 5.09 (s, 1 H, ϾCHPh),

4.91 (t, J = 9.3 Hz, 1 H, 3Ј-H), 4.70–4.74 (m, 3 H), 4.70 (d, J =

11.0 Hz, 1 H, CHHPh), 4.66 (d, J = 11.0 Hz, 1 H, CHHPh), 4.57

(d, J = 11.0 Hz, 1 H, CHHPh), 4.50 (d, J = 9.3 Hz, 1 H, 1Ј-H),

4.48 (d, J = 11.0 Hz, 1 H, CHHPh), 4.05–4.19 (m, 5 H, 5-H, 6Ј-

H_a, 6Ј-H_b, OCHHCH=CH₂, OCHHCH=CH₂), 3.86 (t, J = 9.3 Hz,

1 H, 3-H), 3.73 (t, J = 9.3 Hz, 1 H, 2Ј-H), 3.54 (t, J = 9.3 Hz, 1 H,

4Ј-H), 3.43 (dd, J = 3.6, 9.3 Hz, 1 H), 3.31 (s, 3 H, OCH₃), 3.26–

3.32 (m, 1 H, 4-H), 3.13–3.16 (m, 1 H, 5Ј-H), 3.08 (d, J = 9.6 Hz,

1 H, 6-H_a), 2.92 (d, J = 10.5 Hz, 1 H, 6-H_b), 1.86 (s, 3 H, COCH₃),

1.17 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR MALDI-TOF

MS: m/z calcd. for C₅₇H₆₄O₁₆[M + Na]⁺1027.4092, found:

1027.4116.

6-O-Acetyl-3-O-benzoyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-α-D-glucopyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α-D-gal-

actopyranose (34Sα): [α]²_D⁰= +44 (c = 0.6, CHCl₃). ¹H NMR

(500 MHz, CDCl₃): δ = 7.12–8.02 (m, 15 H, Ar), 5.88 (t, J =

9.5 Hz, 1 H, 3Ј-H), 5.52 (d, J = 5.0 Hz, 1 H, 1-H), 5.17 (d, J =

3.5 Hz, 1 H, 1Ј-H), 5.03 (s, 1 H, ϾCHPh), 4.61 (dd, J = 2.5, 7.5 Hz,

1 H, 3-H), 4.53 (d, J = 11.0 Hz, 1 H, CHHPh), 4.40 (d, J = 11.0 Hz,

1 H, CHHPh), 4.38 (dd, J = 2.5, 8.5 Hz, 1 H, 4-H), 4.29–4.32 (m,

3 H, 2-H, 6-H_a, 6-H_b), 4.13–4.15 (m, 1 H, 5Ј-H), 4.11–4.13 (m, 1

H, 5-H), 4.08 (q, 2 H, COOCH₂CH₃), 3.81–3.83 (m, 2 H, 6Ј-H_a,

6Ј-H_b), 3.64 (t, J = 9.5 Hz, 1 H, 4Ј-H), 3.60 (dd, J = 3.5, 9.5 Hz, 1

H, 2Ј-H), 2.06 (s, 3 H, COCH₃), 1.56 (s, 3 H, CH₃), 1.46 (s, 3 H,

CH₃), 1.37 (s, 3 H, CH₃), 1.32 (s, 3 H, CH₃), 1.12 (t, J = 7.5 Hz,

3 H, COOCH₂CH₃) ppm. HR MALDI-TOF MS: m/z calcd. for

C₄₄H₅₂O₁₅[M + Na]⁺843.3204, found 843.3192.

6-O-Acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(S)-ethoxycar-

bonylbenzyl]-α-

D-glucopyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-

6-O-Acetyl-3-O-benzoyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

zyl]-β-D-glucopyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α-D-gal-

α-

D

-galactopyranose (36Sα): ¹H NMR (500 MHz, CDCl₃): δ =

actopyranose (34Rβ): [α]²_D⁰= –32 (c = 0.2, CHCl₃). ¹H NMR

(500 MHz, CDCl₃): δ = 7.13–8.22 (m, 15 H, Ar), 5.63 (s, 1 H,

ϾCHPh), 5.63 (t, J = 9.5 Hz, 1 H, 3Ј-H), 5.53 (d, J = 5.0 Hz, 1 H,

1-H), 4.60 (d, J = 10.5 Hz, 1 H, CHHPh), 4.58 (d, J = 7.5 Hz, 1

H, 1Ј-H), 4.55–4.57 (m, 1 H, 5Ј-H), 4.48 (d, J = 10.5 Hz, 1 H,

CHHPh), 4.34 (dd, J = 2.5, 12.5 Hz, 1 H, 3-H), 4.31 (dd, J = 2.5,

5.0 Hz, 1 H, 2-H), 4.26 (dd, J = 4.0, 12.5 Hz, 1 H, 4-H), 4.14–4.15

(m, 1 H, 6Ј-H_a), 4.05 (dd, J = 4.0, 11.0 Hz, 1 H, 6-H_a), 4.01–4.03

(m, 1 H, 6-H_b), 3.94 (q, J = 7.0 Hz, 2 H, COOCH₂CH₃), 3.79 (dd,

J = 2.0, 9.5 Hz, 1 H, 2Ј-H), 3.73 (t, J = 9.5 Hz, 1 H, 4Ј-H), 3.61–

3.65 (m, 2 H, 5-H, 6Ј-H_b), 2.07 (s, 3 H, COCH₃), 1.52 (s, 3 H,

CH₃), 1.42 (s, 3 H, CH₃), 1.34 (s, 3 H, CH₃), 1.32 (s, 3 H, CH₃),

0.97 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR MALDI-TOF

MS: m/z calcd. for C₄₄H₅₂O₁₅[M + Na]⁺843.3204, found

843.3197.

7.25–7.40 (m, 10 H, Ar), 5.81–5.88 (m, 1 H, CH=CH₂), 5.51 (d, J

= 5.0 Hz, 1 H, 1-H), 5.40 (t, J = 10.0 Hz, 1 H, 3Ј-H), 5.31 (d, J =

17.0 Hz, 1 H, CH=CHH), 5.21 (d, J = 11.0 Hz, 1 H, CH=CHH),

5.16 (d, J = 3.0 Hz, 1 H, 1Ј-H), 5.12 (s, 1 H, ϾCHPh), 4.61–4.63

(m, 2 H, 3-H, 5-H), 4.49–4.52 (m, 2 H, OCHHCH=CH₂,

OCHHCH=CH₂), 4.38 (d, J = 8.5 Hz, 1 H, 4-H), 4.30 (d, J =

5.0 Hz, 1 H), 4.24–4.31 (m, 3 H, 2-H, 6-H_a, 6-H_b), 4.14 (q, 2 H,

COOCH₂CH₃), 4.03–4.07 (m, 1 H, 5Ј-H), 3.77–3.88 (m, 2 H, 6Ј-

H_a, 6Ј-H_b), 3.54 (t, J = 10.0 Hz, 1 H, 4Ј-H), 3.51 (dd, J = 3.0,

10.0 Hz, 1 H, 2Ј-H), 2.03 (s, 3 H, COCH₃), 1.53 (s, 3 H, CH₃), 1.46

(s, 3 H, CH₃), 1.36 (s, 3 H, CH₃), 1.32 (s, 3 H, CH₃), 1.19 (t, J =

7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR MALDI-TOF MS: m/z

calcd. for C₄₁H₅₂O₁₆[M + Na]⁺823.3153, found 823.3175.

6-O-Acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(S)-ethoxycar-

bonylbenzyl]-β-

Methyl [6-O-Acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(S)- α-

-galactopyranose (36Sβ): [α]²_D⁰= –60 (c = 0.3, CHCl₃). ¹H NMR

ethoxycarbonylbenzyl]-α- -glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-ben-

zyl-α-

-glucopyranoside (35Sα): [α]²_D⁰= +52 (c = 0.3, CHCl₃). ¹H

NMR (500 MHz, CDCl₃): δ = 7.20–7.38 (m, 25 H, Ar), 5.88 (d, J

D-glucopyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-

D

(500 MHz, CDCl₃): δ = 7.22–7.33 (m, 10 H, Ar), 5.91–5.96 (m, 1

H, CH₂=CH), 5.61 (s, 1 H, ϾCHPh), 5.55 (d, J = 5.0 Hz, 1 H, 1-

H), 5.37 (d, J = 17.5 Hz, 1 H, CHH=CH), 5.26 (d, J = 11.0 Hz, 1

D

= 3.5 Hz, 1 H), 5.28–5.91 (m, 1 H), 5.30–5.38 (m, 3 H), 5.23 (d, J H, CHH=CH), 5.14 (t, J = 10.0 Hz, 1 H, 3Ј-H), 4.59–4.64 (m, 5

= 11.0 Hz, 1 H), 5.06 (d, J = 11.5 Hz, 1 H), 5.03 (d, J = 11.5 Hz, H, 3-H, 1Ј-H, OCHHCH=CH₂, OCHHCH=CH₂, CHHPh), 4.20

1 H), 4.99 (s, 1 H), 4.68 (d, J = 11.0 Hz, 1 H), 4.60 (d, J = 4.0 Hz,

1 H), 4.51–4.58 (m, 6 H), 4.45 (d, J = 11.0 Hz, 1 H), 4.10 (t, J =

(d, J = 11.0 Hz, 1 H, CHHPh), 4.33 (dd, J = 2.0, 5.0 Hz, 1 H, 2-

H), 4.16–4.19 (m, 2 H, 6Ј-H_b, 6-H_a), 4.05–4.07 (m, 2 H, 6Ј_a-H, 6-

7.5 Hz, 2 H), 3.96–4.04 (m, 3 H), 3.84–3.93 (m, 3 H), 3.59–3.63 (m, H_b), 3.46 (t, J = 9.5 Hz, 1 H, 4Ј-H), 3.28 (t, J = 9.5 Hz, 1 H, 2Ј-

2 H), 3.44 (dd, J = 8.5, 10.0 Hz, 1 H), 3.37 (s, 3 H, CH₃), 1.95 (s, H), 2.00 (s, 3 H, COCH₃), 1.60 (s, 3 H, CH₃), 1.55 (s, 6 H, CH₃),

3 H, COCH₃), 1.10 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR 1.45 (s, 3 H, CH₃), 1.17 (t, J = 7.5 Hz, 3 H, COOCH₂CH₃) ppm.

MALDI-TOF MS: m/z calcd. for C₅₇H₆₄O₁₆[M + Na]⁺1027.4092,

HR MALDI-TOF MS: m/z calcd. for C₄₁H₅₂O₁₆[M + Na]⁺

found 1027.4103.

823.3153, found: 823.3136.

Eur. J. Org. Chem. 2006, 5007–5028

www.eurjoc.org

5025

J.-H. Kim, H. Yang, V. Khot, D. Whitfield, G.-J. Boons

FULL PAPER

6-O-Acetyl-3-O-allyloxycarbonyl-4-O-benzyl-2-O-[(R)-ethoxycar-

J = 11.0 Hz, 1 H, CHHPh), 4.62 (dd, J = 2.1, 7.5 Hz, 1 H), 4.54

(d, J = 11.0 Hz, 1 H, CHHPh), 4.39 (dd, J = 2.0, 7.5 Hz, 1 H,

O C H H C H = C H ₂) , 4 . 3 1 ( d d , J = 2 . 4 , 4 . 8 H z , 1 H ,

bonylbenzyl]-β-

D-glucopyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-

α-

D

-galactopyranose (36Rβ): [α]²_D⁰= –25 (c = 0.6, CHCl₃). ¹H NMR

(500 MHz, CDCl₃): δ = 7.26–7.54 (m, 10 H, Ar), 5.95–6.01 (m, 1 OCHHCH=CH₂), 4.27–4.29 (m, 1 H), 4.18–4.22 (m, 2 H), 4.11–

H, CH=CH₂), 5.63 (s, 1 H, ϾCHPh), 5.52 (d, J = 5.0 Hz, 1 H, 1- 4.15 (m, 2 H, COOCH₂CH₃), 4.02–4.04 (m, 1 H), 3.89 (t, J =

H), 5.41 (dd, J = 1.0, 17.0 Hz, 1 H, CH=CHH), 5.24 (d, J =

10.0 Hz, 1 H, CH=CHH), 5.14 (t, J = 9.5 Hz, 1 H, 3Ј-H), 4.73–

4.75 (m, 2 H, OCHHCH=CH₂, OCHHCH=CH₂), 4.74 (d, J =

11.0 Hz, 1 H, CHHPh), 4.54 (d, J = 11.0 Hz, 1 H, CHHPh), 4.50

9.0 Hz, 2 H, 3Ј-H, 5Ј-H), 3.79–3.81 (m, 2 H), 3.43 (t, J = 9.0 Hz,

1 H, 4Ј-H), 3.38 (dd, J = 3.3, 9.0 Hz, 1 H, 2Ј-H), 2.02 (s, 3 H,

COCH₃), 1.53 (s, 3 H, CH₃), 1.47 (s, 3 H, CH₃), 1.39 (s, 3 H, CH₃),

1.33 (s, 3 H, CH₃), 1.19 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm.

(d, J = 7.5 Hz, 1 H, 4-H), 4.28–4.31 (m, 2 H, 2-H, 6-H_a), 4.21–4.25 HR MALDI-TOF MS: m/z calcd. for C₄₀H₅₂O₁₄[M + Na]⁺

(m, 1 H, 6-H_b), 4.13–4.17 (m, 3 H, 5-H, COOCH₂CH₃), 4.01 (d, J 779.3255, found: 779.3243.

= 7.0 Hz, 1 H, 1Ј-H), 3.67 (t, J = 9.5 Hz, 1 H, 4Ј-H), 3.61 (dd, J =

6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-β-

7.0, 9.5 Hz, 1 H, 2Ј-H), 3.53–3.56 (m, 2 H, 3-H, 5Ј-H), 2.03 (s, 3

D

-glucopyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α-D-galactopy-

H, COCH₃), 1.51 (s, 3 H, CH₃), 1.40 (s, 3 H, CH₃), 1.34 (s, 3 H,

CH₃), 1.31 (s, 3 H, CH₃), 1.17 (t, J = 7.5 Hz, 3 H, COOCH₂CH₃)

ppm. HR MALDI-TOF MS: m/z calcd. for C₄₁H₅₂O₁₆[M + Na]⁺

823.3153, found 823.3146.

1

ranose (38Sβ): [α]²_D⁰= +56 (c = 1.0, CHCl₃). H NMR (500 MHz,

CDCl₃): δ = 7.26–7.56 (m, 10 H, Ar), 5.90–6.03 (m, 1 H,

CH=CH₂), 5.77 (s, 1 H, ϾCHPh), 5.58 (d, J = 4.8 Hz, 1 H, 1-H),

5.29 (dd, J = 1.8, 17.4 Hz, 1 H, CHH=CH), 5.18 (dd, J = 1.8,

10.5 Hz, 1 H, CH=CHH), 4.83 (d, J = 10.5 Hz, 1 H, CHHPh),

4.60–4.63 (m, 2 H), 4.47 (d, J = 10.5 Hz, 1 H, CHHPh), 4.46 (d, J

= 7.5 Hz, 1 H, 1Ј-H), 4.34 (dd, J = 2.1, 4.8 Hz, 1 H, 2-H), 4.16–

4.25 (m, 4 H, COOCH₂CH₃, 4-H, 6-H_a), 4.03–4.09 (m, 1 H, 6-H_b,

6Ј-H_b), 3.68 (dd, J = 9.0, 11.1 Hz, 1 H, 5Ј-H), 3.59 (t, J = 9.0 Hz,

1 H, 3Ј-H), 3.41–3.43 (m, 1 H, 6Ј-H_a), 3.33 (d, J = 9.0 Hz, 1 H, 4Ј-

H), 3.23 (dd, J = 7.5, 9.0 Hz, 1 H, 2Ј-H), 1.99 (s, 3 H, COCH₃),

1.61 (s, 3 H, CH₃), 1.46 (s, 3 H, CH₃), 1.34 (s, 3 H, CH₃), 1.33 (s,

3 H, CH₃), 1.18 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR

MALDI-TOF MS: m/z calcd. for C₄₀H₅₂O₁₄[M + Na]⁺779.3255,

found 779.3263.

Methyl [6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(S)-ethoxycarbonyl-

benzyl]-α-D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glucopyr-

anoside (37Sα): [α]²_D⁰= +128 (c = 1.1, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.22–7.38 (m, 25 H, Ar), 5.92–5.98 (m, 1 H), 5.85 (d,

J = 3.3 Hz, 1 H), 5.28–5.29 (m, 1 H), 5.23 (s, 1 H), 5.09–5.17 (m,

2 H), 5.03 (d, J = 12.0 Hz, 1 H), 4.81 (d, J = 12.0 Hz, 1 H), 4.67

(d, J = 12.0 Hz, 1 H), 4.59 (d, J = 3.6 Hz, 1 H), 4.53 (d, J =

12.0 Hz, 1 H), 4.51–4.53 (m, 2 H), 4.50 (d, J = 12.0 Hz, 1 H), 4.24–

4.29 (m, 2 H), 3.98–4.12 (m, 6 H), 3.75–3.84 (m, 4 H), 3.57–3.64

(m, 3 H), 3.40–4.31 (m, 1 H), 3.36 (s, 3 H, OCH₃), 1.96 (s, 3 H,

COCH₃), 1.17 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR

MALDI-TOF MS: m/z calcd. for C₄₁H₅₂O₁₆[M + Na]⁺823.3153,

found 823.3141.

6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-α-

D-glucopyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α-D-galactopy-

1

Methyl [6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(S)-ethoxycarbonyl-

benzyl]-β-D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glucopyr-

ranose (38Rα): Selected H NMR (300 MHz, CDCl₃): δ = 5.42 (s,

1 H, 1Ј-H), 1.93 (s, 3 H, COCH₃), 1.20 (t, J = 7.2 Hz, 3 H, CO-

OCH₂CH₃) ppm.

anoside (37Sβ): [α]²_D⁰= +61 (c = 0.2, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.25–7.41 (m, 25 H), 5.25 (s, 1 H), 5.70–5.79 (m, 1 H),

5.11 (dd, J = 1.5, 15.6 Hz, 1 H), 5.04–5.05 (m, 1 H), 4.98 (d, J =

12.0 Hz, 1 H), 4.78 (d, J = 5.0 Hz, 1 H), 4.76 (d, J = 12.0 Hz, 1

H), 4.75 (d, J = 12.0 Hz, 1 H), 4.70 (d, J = 12.0 Hz, 1 H), 4.69 (d,

J = 12.0 Hz, 1 H), 4.61 (d, J = 3.6 Hz, 1 H), 4.60 (d, J = 12.0 Hz,

1 H), 4.49 (d, J = 12.0 Hz, 1 H), 4.44 (d, J = 12.0 Hz, 1 H), 4.37

(d, J = 7.5 Hz, 1 H, 1Ј-H), 4.04–4.21 (m, 1 H), 4.02–4.14 (m, 7 H),

3.82 (t, J = 9.5 Hz, 1 H), 3.60–3.73 (m, 1 H), 3.67–3.70 (m, 1 H),

3.51 (dd, J = 3.5, 9.5 Hz, 1 H), 3.39 (s, 3 H, OCH₃), 3.29–3.31 (m,

1 H), 3.18–3.26 (m, 2 H), 1.84 (s, 3 H, COCH₃), 1.18 (t, J = 7.0 Hz,

3 H, COOCH₂CH₃) ppm. HR MALDI-TOF MS: m/z calcd. for

C₅₆H₆₄O₁₄[M + Na]⁺983.4194, found: 983.4174.

6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylbenzyl]-β-

D-glucopyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α-D-galactopy-

ranose (38Rβ): [α]²_D⁰= –24 (c = 0.2, CHCl₃). H NMR (500 MHz,

CDCl₃): δ = 7.26–7.58 (m, 10 H, Ar), 6.13 (m, 1 H, CH=CH), 5.71

(s, 1 H, ϾCHPh), 5.54 (d, J = 4.5 Hz, 1 H, 1-H), 5.36 (d, J =

17.0 Hz, 1 H, CHH=CH), 5.20 (d, J = 10.5 Hz, 1 H, CHH=CH),

4.94 (d, J = 10.5 Hz, 1 H, 1Ј-H), 4.81 (dd, J = 5.5 Hz, 1 H,

OCHHCH=CH₂), 4.57 (t, J = 9.5 Hz, 1 H, 2Ј-H), 4.55 (d, J =

3.5 Hz, 1 H, 3-H), 4.39 (d, J = 7.5 Hz, 1 H, OCHHCH=CH₂), 4.31

(d, J = 11.0 Hz, 1 H, CHHPh), 4.26 (d, J = 11.0 Hz, 1 H, CHHPh),

4.24 (d, J = 4.5 Hz, 1 H, 2-H), 4.20 (q, J = 7.0 Hz, 2 H, CO-

OCH₂CH₃), 4.12 (t, J = 9.5 Hz, 1 H, 3Ј-H), 4.01–4.02 (m, 2 H, 6-

H_b, 5Ј-H), 3.57–3.62 (m, 2 H, 6-H_a, 6Ј-H_a), 3.49–3.53 (m, 2 H, 5-

H, 6Ј-H_b), 3.43–3.45 (m, 2 H, 4-H, 4Ј-H), 2.02 (s, 3 H, COCH₃),

1.53 (s, 3 H, CH₃), 1.41 (s, 3 H, CH₃), 1.34 (s, 3 H, CH₃), 1.31 (s,

3 H, CH₃), 1.18 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR

MALDI-TOF MS: m/z calcd. for C₄₀H₅₂O₁₄[M + Na]⁺779.3255,

found 779.3271.

1

Methyl [6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(R)-ethoxycarbonyl-

benzyl]-α-D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glucopyr-

anoside (37Rα): Selected ¹H NMR (300 MHz, CDCl₃): δ = 5.57 (d,

J = 3.6 Hz, 1 H, 1Ј-H), 3.34 (s, 3 H, CH₃), 1.78 (s, 3 H, COCH₃),

1.16 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm.

Methyl [6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(R)-ethoxycarbonyl-

benzyl]-β-D-glucopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glucopyr-

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

anoside (37Rβ): Selected ¹H NMR (300 MHz, CDCl₃): δ = 4.46 (d,

J = 7.5 Hz, 1 H, 1Ј-H), 3.43 (s, 3 H, CH₃), 1.98 (s, 3 H, COCH₃),

1.19 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm.

zyl]-α-D-galactopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glucopyr-

anoside (39Sα): [α]²_D⁰= +191 (c = 1.0, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.17–7.34 (m, 25 H, Ar), 5.93 (d, J = 3.5 Hz, 1 H, 3Ј-

H), 5.19–5.22 (m, 1 H, 4Ј-H), 5.04 (s, 1 H, ϾCHPh), 5.03 (d, J =

6-O-Acetyl-3-O-allyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylbenzyl]-α-

D

-glucopyranosyl-(1Ǟ6)-1,2:3,4-di-O-isopropylidene-α-

ranose (38Sα): [α]²_D⁰= +30 (c = 0 ppm.3, CHCl₃); ¹H NMR

(500 MHz, CDCl₃): δ = 7.26–7.46 (m, 10 H, Ar), 5.90–6.00 (m, 1 (d, J = 11.5 Hz, 1 H, CHHPh), 4.54 (s, 1 H, 1Ј-H), 4.53 (d, J =

H, CH=CH₂), 5.52 (d, J = 5.1 Hz, 1 H, 1-H), 5.30 (s, 1 H, 11.5 Hz, 1 H, CHHPh), 4.42 (d, J = 11.5 Hz, 1 H, CHHPh), 4.10

ϾCHPh), 5.28–5.30 (m, 1 H, CHH=CH), 5.20 (dd, J = 1.8, (t, J = 9.5 Hz, 1 H, 4-H), 3.92–4.06 (m, 7 H, 2Ј-H, 1-H, 6-H_b, 6Ј-

19.8 Hz, 1 H, CHH=CH), 5.14 (d, J = 3.3 Hz, 1 H, 1Ј-H), 4.83 (d, H_a, 6Ј-H_b, COOCH₂CH₃), 3.87–3.89 (m, 1 H, 5Ј-H), 3.78 (dd, J =

D

-galactopy- 11.5 Hz, 1 H, CHHPh), 4.98 (d, J = 11.5 Hz, 1 H, CHHPh), 4.68

(d, J = 11.5 Hz, 1 H, CHHPh), 4.60 (t, J = 9.5 Hz, 1 H, 3-H), 4.57

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Glycopyranosyl Donors with Chiral Auxiliaries

FULL PAPER

4.5, 11.0 Hz, 1 H, 6-H_a), 3.65 (d, J = 9.5 Hz, 1 H, 5-H), 3.59 (dd,

J = 3.0, 9.5 Hz, 1 H, 2-H), 3.37 (s, 3 H, CH₃), 1.91 (s, 3 H,

COCH₃), 1.85 (s, 3 H, COCH₃), 1.09 (t, J = 7.0 Hz, 3 H, CO-

OCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.41, 170.17,

COCH₃), 1.16 (t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. ¹³C NMR

(75 MHz, CDCl₃): δ = 170.63, 170.25, 170.13, 165.38, 164.64,

164.38, 129.94, 129.90, 129.67, 129.27, 129.15, 128.96, 128.50,

128.44, 128.40, 128.24, 128.20, 128.06, 126.96, 97.95, 96.63, 82.05,

170.05, 139.26, 138.21, 138.01, 137.53, 136.21, 128.62, 128.42, 75.35, 75.14, 74.85, 73.02, 72.20, 70.62, 69.69, 68.71, 68.14, 66.96,

128.29, 128.19, 127.98, 127.90, 127.54, 127.46, 127.29, 127.07, 63.02, 61.39, 55.47, 20.87, 20.79, 14.03 ppm. HR MALDI-TOF

127.00, 97.61, 96.33, 81.56, 81.13, 80.36, 77.22, 75.03, 74.84, 73.95,

73.32, 73.27, 73.09, 72.54, 69.35, 68.22, 62.49, 61.24, 55.13, 20.93,

20.68, 14.02 ppm. HR MALDI-TOF MS: m/z calcd. for C₅₅H₆₂O₁₅

[M + Na]⁺985.3986, found 985.3975.

MS: m/z calcd. for C₅₅H₅₆O₁₈[M + Na]⁺1027.3364, found

1027.3354.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-β-D-galactopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzoyl-α-D-glucopyr-

anoside (40Sβ): [α]²_D⁰= +155 (c = 1.0, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.09–7.98 (m, 25 H, Ar), 6.16 (t, J = 9.5 Hz, 1 H, 3-

H), 5.37 (t, J = 9.5 Hz, 1 H, 4-H), 5.36 (s, 1 H, ϾCHPh), 5.23 (dd,

J = 3.5, 9.5 Hz, 1 H, 2-H), 5.22 (s, 1 H, 1-H), 4.92 (dd, J = 3.0,

10.0 Hz, 1 H, 3Ј-H), 4.57 (d, J = 7.5 Hz, 1 H, 1Ј-H), 4.48 (d, J =

12.0 Hz, 1 H, CHHPh), 4.40–4.43 (m, 1 H, 5-H), 4.39 (d, J =

12.0 Hz, 1 H, CHHPh), 4.19 (q, J = 7.0 Hz, 2 H, COOCH₂CH₃),

4.12 (dd, J = 7.0, 11.0 Hz, 1 H, 6Ј-H_a), 4.01 (dd, J = 2.0, 11.0 Hz,

1 H, 6-H_b), 3.95 (dd, J = 6.5, 11.0 Hz, 1 H, 6Ј-H_b), 3.82 (d, J =

2.0 Hz, 1 H, 4Ј-H), 3.78 (dd, 1 H, 6-H_a), 3.72 (dd, J = 7.5, 9.5 Hz,

1 H, 2Ј-H), 3.63 (t, J = 6.5 Hz, 1 H, 5Ј-H), 3.54 (s, 3 H, CH₃), 1.89

(s, 3 H, COCH₃), 1.75 (s, 3 H, COCH₃), 1.20 (t, J = 7.0 Hz, 3

H, COOCH₂CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.51,

170.36, 170.23, 165.84, 165.75, 165.54, 137.45, 137.05, 133.50,

133.35, 133.07, 129.93, 129.86, 129.65, 129.25, 129.09, 128.82,

128.52, 128.47, 128.42, 128.31, 128.26, 128.09, 127.99, 127.86,

103.88, 96.77, 81.51, 74.06, 73.62, 72.18, 71.74, 70.33, 70.07, 69.53,

68.85, 62.15, 61.21, 55.82, 20.70, 20.60, 14.14 ppm. HR MALDI-

TOF MS: m/z calcd. for C₅₅H₅₆O₁₈[M + Na]⁺1027.3364, found

1027.3382.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-β-D-galactopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glucopyr-

anoside (39Sβ): [α]²_D⁰= +253 (c = 1.0, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.15–7.37 (m, 25 H, Ar), 5.06 (s, 1 H, ϾCHPh), 4.95

(d, J = 10.5 Hz, 1 H, CHHPh), 4.83 (d, J = 11.5 Hz, 1 H, CHHPh),

4.73 (d, J = 10.5 Hz, 1 H, CHHPh), 4.71 (d, J = 12.5 Hz, 1 H,

CHHPh), 4.66 (dd, J = 4.5, 10.0 Hz, 1 H, 3Ј-H), 4.65 (d, J =

11.5 Hz, 1 H, CHHPh), 4.60 (d, J = 4.0 Hz, 1 H, 1-H), 4.51 (d, J

= 12.0 Hz, 1 H, CHHPh), 4.48 (d, J = 12.0 Hz, 1 H, CHHPh), 4.39

(d, J = 12.0 Hz, 1 H, CHHPh), 4.36 (d, J = 8.0 Hz, 1 H, 1Ј-H),

3.97–4.15 (m, 7 H, 4-H, 6-H_a, 6-H_b, 6Ј-H_a, 6Ј-H_b, COOCH₂CH₃),

3.81 (t, J = 9.0 Hz, 1 H, 3-H), 3.76–3.76 (m, 1 H, 4Ј-H), 3.66–3.69

(m, 2 H, 2Ј-H, 5Ј-H), 3.52 (dd, J = 4.0, 9.5 Hz, 1 H, 2-H), 3.38 (s,

3 H, CH₃), 3.30 (t, J = 7.0 Hz, 1 H, 5-H), 1.97 (s, 3 H, COCH₃),

1.64 (s, 3 H, COCH₃), 1.19 (t, J = 6.5 Hz, 3 H, COOCH₂CH₃)

ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.42, 170.26, 170.17,

139.06, 138.49, 138.04, 137.83, 136.99, 128.52, 128.48, 128.34,

128.19, 128.09, 127.99, 127.89, 127.82, 127.77, 127.48, 127.23,

101.46, 98.52, 82.80, 80.08, 78.89, 77.95, 75.49, 75.13, 74.58, 74.10,

73.66, 73.26, 71.53, 69.76, 68.17, 61.82, 60.97, 55.26, 20.79, 20.57,

14.15 ppm. HR MALDI-TOF MS: m/z calcd. for C₅₅H₆₂O₁₅[M +

Na]⁺985.3986, found 985.3877.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

zyl]-α-D-galactopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzoyl-α-D-glucopyr-

anoside (40Rα): Selected ¹H NMR (300 MHz, CDCl₃): δ = 4.73 (s,

1 H, 1Ј-H), 3.61 (s, 3 H, CH₃), 2.04 (s, 3 H, COCH₃), 1.99 (s, 3 H,

COCH₃), 1.19 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃) ppm.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

zyl]-β-D-galactopyranosyl]-(1Ǟ4)-2,3,6-tri-O-benzyl-α-D-glucopyr-

1

anoside (39Rβ): [α]²_D⁰= –53 (c = 0.7, CHCl₃); H NMR (500 MHz,

CDCl₃): δ = 7.18–7.38 (m, 25 H, aromatic), 5.05 (s, 1 H, ϾCHPh),

4.93 (d, J = 11.0 Hz, 1 H, CHHPh), 4.81 (dd, J = 3.3, 9.9 Hz, 1

H, 3Ј-H), 4.80 (d, J = 11.0 Hz, 1 H, CHHPh), 4.74 (d, J = 12.0 Hz,

1 H, CHHPh), 4.69 (d, J = 12.0 Hz, 1 H, CHHPh), 4.61 (d, J =

12.0 Hz, 1 H, CHHPh), 4.54 (d, J = 12.0 Hz, 1 H, CHHPh), 4.53

(d, J = 12.0 Hz, 1 H, CHHPh), 4.52 (d, J = 12.0 Hz, 1 H, CHHPh),

4.50 (d, J = 3.0 Hz, 1 H, 1-H), 4.11 (d, J = 9.0 Hz, 1 H, 1Ј-H),

4.02–4.20 (m, 6 H, 6Ј-H_a, 6Ј-H_b, 5Ј-H, CHHPh, COOCH₂CH₃),

3.88 (t, J = 9.0 Hz, 1 H, 4-H), 3.78 (d, J = 3.0 Hz, 1 H, 4Ј-H),

3.66–3.72 (m, 2 H, 2Ј-H, 3-H), 3.43 (dd, J = 3.0, 9.5 Hz, 1 H, 2-

H), 3.31 (s, 3 H, CH₃), 3.27–3.29 (m, 1 H, 6-H_a), 2.94–3.02 (m, 2

H, 5-H, 6-H_b), 2.16 (s, 3 H, COCH₃), 1.97 (s, 3 H, COCH₃), 1.18

(t, J = 7.0 Hz, 3 H, COOCH₂CH₃) ppm. HR MALDI-TOF MS:

m/z calcd. for C₅₅H₆₂O₁₅[M + Na]⁺985.3986, found 985.3971.

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(R)-ethoxycarbonylben-

zyl]-β-D-galactopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzoyl-α-D-glucopyr-

anoside (40Rβ): Selected ¹H NMR (300 MHz, CDCl₃): δ = 4.49 (d,

J = 7.5 Hz, 1 H, 1Ј-H), 3.46 (s, 3 H, CH₃), 2.26 (s, 3 H, COCH₃),

1.82 (s, 3 H, COCH₃), 1.17 (t, J = 7.2 Hz, 3 H, COOCH₂CH₃)

ppm.

Methyl α-D-Glucopyranosyl-(1Ǟ6)-α-D-glucopyranoside (42): So-

dium methoxide (3.0 mg, 0.055 mmol) was added to a solution of

31Sα (55 mg, 0.055 mmol) in methanol (5 mL). The reaction mix-

ture was stirred for 1 d, then quenched with Amberlite IRC-50 ion

exchange resin (weakly acidic). After filtration, the filtrate was con-

centrated in vacuo. The residue was purified by column chromatog-

raphy on Iatrobeads (dichloromethane/methanol, 2:1) to afford 41

(30 mg, 93%). A solution of 41 (30 mg, 0.052 mmol) in THF

(3 mL) was added to liquid ammonia (5 mL) at –78 °C. Sodium (Ϸ

20 mg) was then added until a persistent blue color was obtained.

Solid NH₄Cl (0.1 g) was then added and the solvents were evapo-

Methyl [3,6-Di-O-acetyl-4-O-benzyl-2-O-[(S)-ethoxycarbonylben-

zyl]-α-D-galactopyranosyl]-(1Ǟ6)-2,3,4-tri-O-benzoyl-α-D-glucopyr-

anoside (40Sα): [α]²_D⁰= +249 (c = 1.1, CHCl₃). ¹H NMR (500 MHz,

CDCl₃): δ = 7.25–7.98 (m, 25 H, Ar), 6.16 (t, J = 9.5 Hz, 1 H, 3-

H), 5.48 (t, J = 9.5 Hz, 1 H, 4-H), 5.30 (dd, J = 3.0, 11.0 Hz, 1 H, rated. The crude reaction mixture was purified by column

3Ј-H), 5.26 (dd, J = 3.5, 9.5 Hz, 1 H, 2-H), 5.23 (d, J = 3.5 Hz, 1 chromatography on Iatrobeads (dichloromethane/methanol/H₂O,

H, 1-H), 5.21 (d, J = 4.0 Hz, 1 H, 1Ј-H), 5.12 (s, 1 H, ϾCHPh), 15:5:1) to afford 42 (18 mg, 97%): R_f= 0.34 (dichloromethane/

1

4.64 (d, J = 11.0 Hz, 1 H, CHHPh), 4.48 (d, J = 11.0 Hz, 1 H,

CHHPh), 4.37 (t, J = 8.5 Hz, 1 H, 5-H), 4.20 (t, J = 6.5 Hz, 1 H, (500 MHz, D₂O): δ = 4.87 (d, J = 4.0 Hz, 1 H), 4.73 (d, J = 3.5 Hz,

5Ј-H), 4.12–4.13 (m, 1 H, 2Ј-H), 4.09 (q, J = 7.0 Hz, 2 H, CO- 1 H), 3.90 (dd, J = 4.5, 9.0 Hz, 1 H), 3.76 (dd, J = 2.0, 12.5 Hz, 1

OCH₂CH₃), 4.05–4.08 (m, 1 H, 4Ј-H), 4.03–4.04 (m, 2 H, 6Ј-H_a, H), 3.33–3.73 (m, 10 H), 3.34 (s, 3 H) ppm. ¹³C NMR (75 MHz,

6Ј-H_b), 3.93 (dd, J = 7.5, 11.0 Hz, 1 H, 6-H_a), 3.75 (d, J = 10.0 Hz, D₂O): δ = 99.56, 98.04, 73.56, 73.25, 72.02, 71.66, 71.34, 70.25,

1 H, 6-H_b), 3.44 (s, 3 H, CH₃), 2.00 (s, 3 H, COCH₃), 1.88 (s, 3 H, 69.70, 69.59, 65.67, 60.65, 55.38 ppm.

methanol/H₂O, 15:5:1). [α]²_D⁰= +26.9 (c = 1.0, CH₃OH). H NMR

Eur. J. Org. Chem. 2006, 5007–5028

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FULL PAPER

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Acknowledgments

This research was supported by the NIH Research Resource Center

for Biomedical Complex Carbohydrates (P41-RR-5351). The au-

thors gratefully acknowledge the use of the RSCC computer situ-

ated in the RIKEN Computer Center, Wako-shi, Saitama, Japan

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Received: May 19, 2006

Published Online: August 15, 2006

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Article Doi

Stereoselective glycosylations using (R)- or (S)-(ethoxycarbonyl)benzyl chiral auxiliaries at C-2 of glycopyranosyl donors

DOI: 10.1002/ejoc.200600440

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