6-O-benzyl- and 6-O-silyl-N-acetyl-2-amino-2-N,3-O-carbonyl-2- deoxyglucosides: Effective glycosyl acceptors in the glucosamine 4-OH series. Effect of anomeric stereochemistry on the removal of the oxazolidinone group

Article abstract of DOI:10.1021/jo0482559

(Chemical Equation Presented) The 4-OH groups of both α- and β-methyl glycosides of N-acetylglucosamine, protected with an oxazolidinone spanning the nitrogen and O-3, and bearing benzyl or silyl protection on O-6, show excellent reactivity as acceptors i

Full text of DOI:10.1021/jo0482559

6-O-Benzyl- and
6-O-Silyl-N-acetyl-2-amino-2-N,3-O-carbonyl-2-deoxyglucosides:
Effective Glycosyl Acceptors in the Glucosamine 4-OH Series.
Effect of Anomeric Stereochemistry on the Removal of the
Oxazolidinone Group
David Crich* and A. U. Vinod
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
dcrich@uic.edu
Received October 4, 2004
The 4-OH groups of both R- and â-methyl glycosides of N-acetylglucosamine, protected with an
oxazolidinone spanning the nitrogen and O-3, and bearing benzyl or silyl protection on O-6, show
excellent reactivity as acceptors in couplings to a range of glycosyl donors. The enhanced reactivity
of these acceptors is attributed in part to the tied back nature of the oxazolidinone, which reduces
hindrance around the nucleophilic oxygen. The N-acetyloxazolidinone function also reduces the
tendency seen in simple N-acetylglucosamines toward amide glycosylation, and removes the
possibility of problematic hydrogen bonding networks. In the â-, but not the R-, series selective
hydrolysis of the N-acetyloxazolidinone directly to the N-acetylglucosamine was possible with barium
hydroxide, a feature attributed to chelate formation between the acetamide carbonyl group and
the glycosidic oxygen in the â-series.
Introduction
probable.3 In addition to structural effects, it has been
demonstrated that the amide group in N-acetylglucos-
amine derivatives may itself be glycosylated by active
species leading to O-glycosyl imidates.4 Glycosylation of
the acetamide group in this manner, which obviously
depletes the pool of available glycosyl donor as well as
increasing the steric hindrance in the immediate vicinity
of the acetamide, may be one reason underlying the
deleterious effect of even remote acetamido groups on
some glycosylation reactions.5 Yet another possible rea-
son for the failure of many glycosylations of N-acetyl-
glucosamine 4-OH acceptors, at least under the condi-
tions of the sulfoxide method, is the formation of cyclic
oxazines between the acceptor alcohol and the acet-
amide.6 Despite the widespread acknowledgment of the
N-acetylglucosamine acceptor reactivity problem, and the
recent investigations into the specific causes, there are
Hydroxyl groups on the 4-position of otherwise pro-
tected N-acetylglucosamine derivatives are widely ac-
knowledged to be among the most difficult alcohols to
glycosylate.1 On the basis of variable-temperature NMR
studies, we have suggested that the low reactivity of
these alcohols arises from intermolecular hydrogen bond-
ing of the amide group, which effectively increases steric
bulk around the nucleophilic alcohol.2 Such intermolecu-
lar effects should be magnified at lower temperatures and
are, therefore, particularly relevant to many modern
glycosylation reactions, many of which operate signifi-
cantly below room temperature. A recent report on the
efficient glycosylation of the 4-OH group of polymer-
supported N-acetylglucosamine derivatives may be in-
terpreted as lending support to the H-bonding hypothesis
as the polymer obviously isolates the individual mol-
ecules, rendering intermolecular hydrogen bonding im-
(3) Mogemark, M.; Elofsson, M.; Kihlberg, J. J. Org. Chem. 2003,
68, 7281.
(4) Liao, L.; Auzanneau, F.-I. Org. Lett. 2003, 5, 2607.
(5) Lucas, R.; Hamza, D.; Lubineau, A.; Bonnaffe´, D. Eur. J. Org.
Chem. 2004, 2107.
(6) Aguilera, B.; Fernando-Mayoralas, A. J. Org. Chem. 1998, 63,
2719.
(1) (a) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155. (b)
Debenham, J.; Rodebaugh, R.; Fraser-Reid, B. Liebigs Ann./Recl. 1997,
791.
(2) Crich, D.; Dudkin, V. J. Am. Chem. Soc. 2001, 121, 6819.
10.1021/jo0482559 CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/14/2005
J. Org. Chem. 2005, 70, 1291-1296
1291

Crich and Vinod
numerous reports7 of successful couplings either to the
4-OH of N-acetylglucosamine acceptors themselves, or
involving acceptors or donors with proximal or remote
amides and carbamates. From these reports it is obvious
that no single reason for the typical lack of reactivity
holds under all sets of glycosylation conditions.8 What-
ever the reason, or combination of reasons, considerable
effort has been devoted to overcoming this problem with
most studies focusing on masking the amide group.
Among a wide variety of amine protecting groups inves-
tigated in this context, the phthaloyl and azido systems
are the most popular; with the latter being preferred in
terms of reactivity of the 4-OH group as demonstrated,
at least for the sulfoxide method, by a series of competi-
tion reactions.2 A more recent paper has shown, also by
means of competition reactions, that use of the N-trichloro-
ethoxycarbonyl (NTroc) group affords greater glucosamine
4-OH reactivity than the comparable 2-deoxy-2-phthaloyl
and 2-deoxy-2-azido donors in trichloroacetimidate cou-
plings.9 Tetrachlorophthaloyl10 and sulfonamide11 pro-
tected glucosamine 4-OH derivatives also appear to have
considerable potential as acceptor alcohols. With the
exception of the 2-azido-2-deoxy system, which is readily
converted in a single step to the N-acetylglucosamine
function with potassium thioacetate,12 the various N-
protected glucosamine 4-OH derivatives in common use
all require two steps for transformation to the N-
acetylglucosamine after the glycosylation reaction. With
a view to streamlining synthetic protocols we have been
interested in developing other surrogates for the N-
acetylglucosamine that (i) avoid the manipulation of
triflyl azide necessary for the preparation of the 2-azido-
2-deoxyglucose system,13 (ii) enhance the reactivity of the
4-OH group toward glycosylation, and (iii) are readily
cleaved under mild conditions directly to the N-acetyl-
glucosamine function itself in a single reaction step.
Initially, we explored the N,N-diacetylglucosamine and
N-acetyl-N-benzyl groups2 but these failed to meet all of
our criteria, and we therefore turned our attention to the
SCHEME 1. Preparation of the r-Configured
Acceptor 4
N-acetyl-2-N,3-O-carbonyl functionality on which we now
report in full.14
Results and Discussion
We reasoned that an N-acetyloxazolidinone bridging
N-2 and O-3 of glucosamine would (i) prevent hydrogen
bonding by removing the amide NH from play, (ii) reduce
steric hindrance around O-4, and (iii) be readily converted
to the requisite acetamide in a single step after gly-
cosylation. The presence in Nature of both R- and
â-glycosidic linkages to the anomeric center of N-acetyl-
glucosamine,15 together with a series of intriguing reports
on the differing nucleophilicity of pyranosidic alcohols
dependent on their anomeric configuration,16 prompted
us to undertake the synthesis of both R- and â-methyl
glycosides of the N-acetyloxazolidinone protected glycosyl
acceptors. Synthesis of the R-anomer (4) began with the
known 4,6-O-benzylidene protected glucosamine deriva-
tive 117 and oxazolidinone formation by sequential treat-
ment with p-nitrophenyl chloroformate and Amberlyst
IR 120 resin (Scheme 1). Acetylation then gave the
N-acetyloxazolidinone 3, whose benyzlidene group was
successfully cleaved regioselectively in the standard
manner to give the acceptor 4.18
Interestingly, when the same reaction sequence was
applied to the â-series (Scheme 2), beginning with the
known amino alcohol 5,19 cleavage of the benzylidene
acetal with sodium cyanoborohydride and HCl in ether
led to the R-anomer 4 and not to the desired product.
There are numerous successful examples of the reductive
cleavage of benzylidene acetals to benzyl ethers using the
cyanoborohydride/HCl in systems bearing â-glycosidic
bonds18 including contemporaneous ones from our own
laboratories,20 and therefore this anomerization was
(7) (a) Gan, Z.; Cao, S.; Wu, W.; Roy, R. J. Carbohydr. Chem. 1999,
18, 755. (b) Duchaussoy, P.; Lei, P.; Petitou, M.; Sinay¨, P.; Lormeua,
J. C.; Choay, J. Bioorg. Med. Chem. Lett. 1991, 1, 99. (c) Ojeda, R.;
Angulo, J.; Nieto, P. M.; Mart´ın-Lomas, M. Can. J. Chem. 2002, 80,
917. (d) Broddefalk, J.; Forsgren, M.; Sethson, I.; Kihlberg, J. J. Org.
Chem. 1999, 64, 8948. (e) Hamilton Andreotti, A.; Kahne, D. J. Am.
Chem. Soc. 1993, 115, 3352. (f) Thompson, C.; Ge, M.; Kahne, D. J.
Am. Chem. Soc. 1999, 121, 1237. (g) Ikemoto, N.; Schreiber, S. L. J.
Am. Chem. Soc. 1992, 114, 2524. (h) Crich, D.; Sun, S. Tetrahedron
1998, 54, 8321. (i) Sun, B.; Chen, Z.; Eggert, U. S.; Shaw, S. J.; LaTour,
J. V.; Kahne, D. J. Am. Chem. Soc. 2001, 123, 12722. (j) Crich, D.;
Smith, M. J. Am. Chem. Soc. 2001, 123, 9015. (k) Haberman, J. M.;
Gin, D. Y. Org. Lett. 2003, 5, 2539. (l) Qian, X.; Hindsgaul, O. J. Chem.
Soc., Chem. Commun. 1997, 1059.
(8) Presumably, the issue of matching or mismatching of donors with
particular acceptors, juxtaposed with the basic issue of reactivity, plays
a role here. For discussions of matching and mismatching in glycoside
bond formations see: (a) Paulsen, H. In Selectivity, a Goal for Synthetic
Efficiency; Bartmann, W., Trost, B. M., Eds.; Verlag Chemie: Basel,
Switzerland, 1984. (b) Spijker, N. M.; van Boeckel, C. A. A. Angew.
Chem., Int. Ed. Engl. 1991, 30, 180. (c) Fraser-Reid, B.; Lo´pez, J. C.;
Go´mez, A. M.; Uriel, C. Eur. J. Org. Chem. 2004, 1387.
(9) Xue, J.; Khaja, S. D.; Locke, R. D.; Matta, K. L. Synlett 2004,
861.
(14) For a preliminary communication on a part of this work see:
Crich, D.; Vinod, A. U. Org. Lett. 2003, 5, 1297.
(15) (a) Lehman, J. Carbohydrates: Structure and Biology; Thieme:
Stuttgart, Germany, 1998. (b) Dwek, R. A. Chem. Rev. 1996, 96, 683.
(c) Dwek, R. A.; Butters, T. D. Chem. Rev. 2002, 102, 283. (d) Varki,
A.; Cummings, R.; Esko, J.; Freeze, H.; Hart, G.; Marth, J., Eds.
Essentials of Glycobiology; Cold Spring Harbor Press: Cold Spring
Harbor, NY, 1999. (e) Varki, A. Glycobiology 1993, 3, 97. (f) Hecht, S.
M., Ed. Bioorganic Chemistry: Carbohydrates; OUP: New York, 1999.
(16) (a) Magaud, D.; Dolmazon, R.; Anker, D.; Doutheau, A.; Dory,
Y. L.; Deslongchamps, P. Org. Lett. 2000, 2, 2275. (b) Zhu, X.-X.; Cai,
M.-S.; Zhou, R.-L. Carbohydr. Res. 1997, 303, 261. (c) Rochepeau-
Jobron, L.; Jacquinet, J.-C. Carbohydr. Res. 1998, 305, 181.
(17) Bauer, T.; Tarasiuk, J.; Pasiczek, K. Tetrahedron: Asymmetry
2002, 13, 77.
(10) Debenham, J. S.; Fraser-Reid, B. J. Org. Chem. 1996, 61, 432.
(11) Dudkin, V. Y.; Miller, J. S.; Danishefsky, S. J. Tetrahedron Lett.
2003, 44, 1791.
(18) (a) Garegg, P. J. In Preparative Carbohydrate Chemistry;
Hanessian, S., Ed.; Dekker: New York, 1993; p 53. (b) Garegg, P. J.;
Hultberg, H.; Wallin, S. Carbohydr. Res. 1982, 108, 97.
(19) Haller, M. F.; Boons, G. J. Eur. J. Org. Chem. 2002, 2033.
(20) Crich, D.; Banerjee, A.; Yao, Q. J. Am. Chem. Soc. 2004, 126,
14930.
(12) (a) Dudkin, V. Y.; Crich, D. Tetrahedron Lett. 2003, 44, 1787.
(b) Shangguan, N.; Katukojvala, S.; Greenberg, R.; Williams, L. J. J.
Am. Chem. Soc. 2003, 125, 7754.
(13) Vasella, A.; Witzig, C.; Chiara, J.-L.; Martin-Lomas, M. Helv.
Chim. Acta 1991, 74, 2073.
1292 J. Org. Chem., Vol. 70, No. 4, 2005

Effective Glycosyl Acceptors in the Glucosamine 4-OH Series
SCHEME 2. Preparation of the â-Configured
comparable yields and selectivities in all cases but two:
both the 4,6-O-benzylidene protected mannosyl donor 10
(Table 2, entries 1 and 2) and the tetra-O-benzyl pro-
tected glucosyl donor 13 (Table 2, entries 3 and 4)
exhibited a shift in favor of the R-anomeric product on
going from acceptor 4 to acceptor 9. In the case of
mannosyl donor 10 this change is manifested in the
reduced â-selectivty on coupling to 9 (Table 2, entries 1
and 2), whereas with the already R-selective glucosyl
donor 13 the trend is reflected in increased R-selectivity
(Table 2, entries 3 and 4). This pattern is potentially
attributable to the change in steric environment arising
from the difference in protecting groups at O-6 in the two
acceptors and, thus, there would seem to be no reason to
invoke a change in reactivity with anomeric configura-
tion. Anomeric selectivities follow the established pattern
for thioglycoside/BSP couplings,7j,21 or the closely related
sulfoxide method,21,24 likely proceeding via the intermedi-
ate R-glycosyl triflate7j,25 through a displacement that
likely involves a transient contact ion pair.26 Thus, 4,6-
O-benzylidene protected mannosylation was â-selective
(Table 1, entries 1 and 2),7h,j while glucosylation was
somewhat R-selective with the tetrabenzyl donor (Table
1, entries 3 and 4) and even more so with the 4,6-O-
benzylidene protected system (Table 1, entries 5 and
6).7j,27 4,6-O-Benzylidene protected galactosylation was
completely R-selective (Table 1, entries 7 and 8),28 as was
rhamnosylation, with both a standard fully disarmed
donor and a 2,3-O-carbonate protected donor (Table 1,
entries 9 and 10),29 and fucosylation with a perbenzylated
donor (Table 1, entry 11).24 The only system necessitating
comment is the 4,6-O-benzylidene mannosylation (Table
1, entries 1 and 2), which, while â-selective as expected,
was considerably less so than comparable couplings to
other glucosamine 4-OH acceptor alcohols such as the
2-azido-2-deoxyglucose system,2 the phthaloyl protected
glucosamine,2 and even the low-yielding but never-the-
less selective N-acetylglucosamine system itself;7h at the
present time we have no satisfactory explanation for this
deviation from high â-selectivity.
Acceptor 9
unexpected. Presumably, the reaction is assisted here by
the strain imposed on the pyranose ring by the presence
of the trans-fused oxazolidinone ring, which facilitates
ring opening by cleavage of the C1-O5 bond. Repeated
attempts at overcoming this epimerization by controlling
the acidity of the medium were unsuccessful and conse-
quently we turned to an alternative sequence. Thus,
hydrogenolysis of the acetal gave the diol 8, which
underwent clean monosilylation on the primary alcohol
with thexyldimethylsilyl chloride to afford the â-acceptor
9.
With acceptors 4 and 9 in hand, a series of couplings
were carried out with a range of thioglycosides with
preactivation at -60 °C in dichloromethane, using the
combination of 1-benzenesulfinylpiperidine (BSP) and
trifluoromethanesulfonic anhydride7j,21 in the presence of
the hindered base 2,4,6-tri-tert-butylpyrimidine (TTBP).22
As is evident from the results presented in Table 1, both
acceptors performed well with all donors tested.
Among the myriad of other glycosylation methods
available,30 we have briefly surveyed the applicability of
glycosyl acceptor 4 in Kahne’s sulfoxide method (Scheme
3, Table 2, entry 2),21,24 Gin’s dehydrative coupling
sequence (Scheme 3, Table 2, entry 3),21,31 and Schmidt’s
trichloroacetimidate protocol (Scheme 3, Table 2, entry
4)l32 and find that it performs well in all three.
Although the two anomers 4 and 9 behaved analo-
gously in glycosylation reactions, a significant difference
was observed in the deprotections of the two anomeric
series of disaccharides. Thus, in the disaccharides derived
from the R-methyl acceptor 4, it proved impossible to
selectively hydrolyze the oxazolidinone ring without
We attribute the good to excellent yields in each of
these couplings to a combination of the absence of the
NH bond, the reduced nucleophilicity of imides as com-
pared to amides, which attenuates the problem of pro-
tecting group glycosylation, and the relatively unhindered
nature of the acceptor alcohols due to the “tied back”
oxazolidinone protecting group.23 When a direct compari-
son was made between acceptors 4 and 9 both gave
(24) Yan, L.; Kahne, D. J. Am. Chem. Soc. 1996, 118, 9239.
(25) Crich, D.; Sun, S. J. Am. Chem. Soc. 1997, 119, 11217.
(26) Crich, D.; Chandrasekera, N. S. Angew. Chem., Int. Ed. 2004,
40, 5386.
(27) Crich, D.; Cai, W. J. Org. Chem. 1999, 64, 4926.
(28) Crich, D.; de la Mora, M.; Vinod, A. U. J. Org. Chem. 2003, 68,
8142.
(29) Crich, D.; Vinod, A. U.; Picione, J. J. Org. Chem. 2003, 68, 8453.
(30) Barresi, F.; Hindsgaul, O. J. Carbohydr. Chem. 1995, 14, 1043.
(31) Garcia, B. A.; Gin, D. Y. J. Am. Chem. Soc. 2000, 122, 4269.
(32) Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem.
1994, 50, 21.
(21) Crich, D.; Lim, L. B. L. Org. React. 2004, 64, 115.
(22) Crich, D.; Smith, M.; Yao, Q.; Picione, J. Synthesis 2001, 323.
(23) Inspection of coupling constants indicated the 4C1 chair con-
formation to be retained in both the R- and â-methyl series, indicating
that the reactivity is not due to an unusual conformation of the
glucosamine pyranose ring.
J. Org. Chem, Vol. 70, No. 4, 2005 1293

Crich and Vinod
TABLE 1. Glycosylation of Acceptors 4 and 9 by the Thioglycoside/BSP/Tf2O Method
a Anomeric ratios were determined by integration of the 1H NMR spectra of reaction mixtures. b Yields refer to pure isolated products.
1294 J. Org. Chem., Vol. 70, No. 4, 2005

Effective Glycosyl Acceptors in the Glucosamine 4-OH Series
TABLE 2. Alternative Methods for the Formation of 14
from 4
TABLE 3. Removal of the Oxazolidinone in the
r-Methyl Series
anomeric
%
entry donor
mediator, conditions
ratioa (R/â) yieldb
1
2
3
4
13c
29
30
31
BSP, TTBP, Tf2O, -60 °C
TTBP, Tf2O, -60 °C
Ph2SO, Tf2O, TTBP, -40 °C
TMSOTf, -30 °C
6.2:1
78
63
59
82
R only
R only
3.5/1
a Anomeric ratios were determined by integration of the 1H
NMR spectra of reaction mixtures. b Yields refer to pure isolated
products. c Entry 1 is reproduced here from Table 1 for convenient
comparison.
SCHEME 3. Coupling to 4 by Alternative Methods
SCHEME 4. Removal of the Oxazolidinone in the
r-Methyl Series
a Yields refer to pure isolated products. b In this example the
acetylation was conducted with acetic anhydride and pyridine.
SCHEME 5. Removal of the Oxazolidinone in the
â-Methyl Series
competing cleavage of the acetamide.33 Accordingly, a
protocol was developed involving treatment with barium
hydroxide in hot ethanol,34 followed by reacetylation of
the crude reaction mixture with acetic anhydride to give
the required N-acetylglucosamine based disaccharides
(Scheme 4, Table 3).
Remarkably, in the â-series selective cleavage of the
oxazolidinone ring was possible with aqueous ethanolic
barium hydroxide, leading directly to the N-acetyl-
glucosamine-based disaccharides, without the need for
reacetylation, thereby fulfilling the last of our design
criteria (Scheme 5, Table 4).35
While it is clear from Schemes 1 and 2 and the
anomerization observed on exposure of 7 to HCl in ether
that the â-series are intrinsically less stable than the
R-series, as might be expected on simple anomeric effect
grounds, we believe that the root cause of the greater
ease and selectivity of oxazolidinone cleavage in the
â-series is unrelated. As is widely appreciated,36 N-
acyloxazolidinones enjoy two predominant conformations
with the carbonyl dipoles aligned either syn- or anti-
periplanar. In the absence of metal ions the antiperipla-
nar conformation is preferred whereas the syn-confor-
mation is favored in the presence of Lewis acidic metals.
In the R-series both the syn- and anti-conformations are
possible as the glycosidic bond is roughly orthogonal to
the plane of the N-acetyloxazolidinone system (Scheme
6). Presumably, hydrolysis in the presence of the barium
cation involves the formation of a chelate with the syn-
conformation in which both carbonyl groups are acti-
vated, hence the lack of selectivity.
In the â-series the equatorial glycosidic bond is in the
approximate plane of the N-acetyloxazolidinone and
destabilizes both the anti and syn conformations, owing
to the presence of dipolar interactions and steric prob-
lems, respectively, leading to intrinsically higher reactiv-
ity. On addition of the coordinating metal the anti
(33) This behavior is typical of N-acyl oxazolidinones. For example,
see: (a) Shinzo, K.; Tsutomu, Y.; Shiroshi, S. J. Org. Chem. 1989, 54,
513. (b) Scholz, K. H.; Heine, H. G.; Hartmann, W. Tetrahedron Lett.
1978, 19, 1467. (c) Ning, X.; Ciufolini, M. A. Tetrahedron Lett. 1995,
36, 6595.
(34) Kang, S. H.; Choi, H.; Kim, J. S.; Youn, J.-H. Chem. Commun.
2000, 227.
(35) Under these mild conditions, only very low yields of product
were obtained from the R-series. For example, only 22% of 35 could be
isolated from the complex reaction mixture obtained on exposure of
disaccharide 21 to barium hydroxide.
(36) (a) Evans, D. A.; Bartoli, J.; Shih, T. L. J. Am. Chem. Soc. 1981,
103, 2127. (b) Ghosh, A. K.; Fidanze, S.; Senanayake, C. H. Synthesis
1998, 937.
J. Org. Chem, Vol. 70, No. 4, 2005 1295

Crich and Vinod
TABLE 4. Removal of the Oxazolidinone in the
SCHEME 7 N-Acetyl Oxazolidinone Conformations
and Selective Cleavage in the â-Series
â-Methyl Series
glycosidic oxygen will have the effect of transferring the
amide resonance, normally shared by both carbonyls,
mainly toward the acetyl group thereby activating the
oxazolidinone toward hydrolysis (Scheme 7). After hy-
drolysis of the oxazolidinone ring the remaining acet-
amide is free to adopt the usual conformation of this
group, in which the N-H bond is antiperiplanar to the
axial C2-H bond, and the system is free of unfavorable
interactions with the glycosidic bond.37
In work closely related to that presented here, it was
reported that the oxazolidinone-protected thioglycoside
43 serves as a viable glycosyl acceptor in neighboring
group-directed, â-selective couplings to several glycosyl
donors.38 However, glycosylation of the oxazolidinone
N-H bond was an important competing reaction, under-
lining the importance of the N-acetyl group in acceptors
4 and 9. It has also been demonstrated that the carbonate
protected thioglycoside 44 is a viable acceptor in glyco-
sylation reactions,39 and it would seem reasonable at this
stage to suggest that tied back, cyclic protecting groups
for the 2,3-positions will likely generally increase the
reactivity of the 4-OH as an acceptor alcohol in a broad
range of situations.
a Yields refer to pure isolated products.
SCHEME 6 N-Acetyl Oxazolidinone Conformations
and Nonselective Cleavage in the r-Series
Acknowledgment. We thank the NIH (GM 62160)
for support of this work.
Supporting Information Available: Full experimental
details and characterization data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
conformer will be stabilized by chelate formation involv-
ing the acetyl carbonyl and the glycosidic oxygen. Che-
lation involving the two carbonyl groups in the syn
conformation, however, will not be favored as it does not
alleviate the steric clash of the acetyl group with the
equatorial glycosidic bond. The preferential chelation of
the metal between the acetyl carbonyl group and the
JO0482559
(37) Fowler, P.; Bernet, B.; Vasella, A. Helv. Chim. Acta 1996, 79,
269.
(38) Kerns, R. J.; Zha, C.; Benakli, K.; Liang, Y.-Z. Tetrahedron Lett.
2003, 44, 8069.
(39) Zhu, T.; Boons, G.-J. Org. Lett. 2001, 3, 4201.
1296 J. Org. Chem., Vol. 70, No. 4, 2005