A highly reactive and stereoselective β-mannopyranosylation system: Mannosyl 4-pentenoate/PhSeOTf

Article abstract of DOI:10.1002/anie.200602642

(Chemical Equation Presented) Controlled linkage: PhSeOTf-promoted glycosylations of a variety of acceptor alcohols with 4,6-O-benzylidene-2,3-di- O-benzylmannopyranosyl pentenoate afford β-mannopyranosides in high yields and with excellent stereoselectiv

Full text of DOI:10.1002/anie.200602642

Communications
Glycosylation
DOI: 10.1002/anie.200602642
A Highly Reactive and Stereoselective
b-Mannopyranosylation System: Mannosyl
4-Pentenoate/PhSeOTf**
Ju Yuel Baek, Tae Jin Choi, Heung Bae Jeon, and
Kwan Soo Kim*
Although many efficient methods for the stereoselective
construction of glycosyl linkages are available,[1] the stereo-
specific formation of the 1,2-cis-b-d-mannopyranosyl linkage
still poses a great challenge. Several diverse and innovative
strategies for b-mannopyranosylation have been developed,[2]
and recently, Crich and co-workers have made a significant
[*] J. Y. Baek, T. J. Choi, H. B. Jeon, Prof. Dr. K. S. Kim
Center for Bioactive Molecular Hybrids and
Department of Chemistry
Yonsei University
Seoul 120-749 (Korea)
Fax: (+82)2-365-7608
E-mail: kwan@yonsei.ac.kr
[**] This work was supported by a grant from the Korea Science and
Engineering Foundation through the Center for Bioactive Molecular
Hybrids (CBMH).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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breakthrough in b-mannoside synthesis by employing 4,6-O-
benzylidene-protected mannopyranosyl sulfoxides or thio-
mannopyranosides as glycosyl donors.[3] The effect of the 4,6-
O-acetal group on the construction of b-mannosyl linkages
was further confirmed with other mannosyl donors by us[4]
and other workers.[5] Nevertheless, the effect of protecting
groups at the 2-O and 3-O positions of the donor,[6] anomeric
leaving groups, and acceptors on the stereoselectivity in this
b-mannosylation of a 4,6-O-acetal-substituted sugar is not yet
fully understood. More importantly, the b selectivity with
certain glycosyl acceptors has never been satisfactory.[7] In the
continuation of our effort to develop an efficient b-manno-
pyranosylation method, our attention focused on the use of
4,6-O-benzylidene mannosyl pentenoate 1 as a glycosyl donor
in the presence of phenylselenyl triflate (PhSeOTf). Glycosyl
pentenoates are not really newbut have been reported as
glycosyl donors with iodonium dicollidine perchlorate
(IDCP) and N-iodosuccinimide/trifluoromethanesulfonic
acid (NIS–TfOH) promoters by the research groups led by
Kunz[8] and Fraser-Reid[9] independently. However, no
detailed studies on the stereoselectivity and no application
to oligosaccharide synthesis have been reported,[10] except
that sialyl 4-pentenoate is reported to be inferior to 4-
pentenyl sialoside as a glycosyl donor.[11] Herein we describe
the use of 1 as the glycosyl donor and PhSeOTf as the
promoter for the synthesis of b-mannopyranosides and the
efficient construction of an oligosaccharide.
Scheme 2. Synthesis of 4,6-O-benzylidene mannosyl pentenoate 1.
various promoters (Table 1). The glycosylation with PhSeOTf
at À788C to 08C afforded exclusively b-disaccharide 4 in 90%
yield (Table 1, entry 1). When PhSeBr was used, however, the
Table 1: Glycosylation with donor
1
using various promoters.
Entry
Promoter
Yield [%][a]
b/a[a]
1
2
3
4
PhSeOTf
PhSeBr
IDCP
90
0
31
41
b only
–
b only
NIS–TfOH
7:1[b]
[a] Determined after isolation of product. [b] Ratio was determined by
1H NMR spectroscopy. Bz=benzoyl.
reaction did not proceed at all (Table 1, entry 2). The use of
IDCP gave b-disaccharide 4 exclusively but only in 31% yield
(Table 1, entry 3), whereas the use of NIS–TfOH provided a
mixture of b-disaccharide 4 and its a anomer in a 7:1 ratio and
in 41% yield (Table 1, entry 4). These results indicated that
PhSeOTf is much more efficient and stereoselective than
other known promoters for glycosylation when used in
combination with 1.
We envisioned that treatment of mannosyl pentenoate 1
with PhSeOTf in the presence of 2,4,6-tri-tert-butylpyrimidine
(TTBP)[12] would induce the lactonization of 1 via selenonium
ion A to generate g-phenylselenylmethyl-g-butyrolactone and
oxocarbenium ion B, which might be in equilibrium with
triflate C (Scheme 1). Subsequent reaction of B or C with a
glycosyl acceptor would provide mannopyranoside D.
We also examined the glycosylation of 3 with 4-
pentenyl 4,6-O- benzylidene mannoside 5 in order to
compare the glycosyl 4-pentenoate with the well-
known 4-pentenyl glycoside[13] as the glycosyl donor
(Scheme 3). Reaction of pentenyl mannoside 5 and
acceptor 3 in the presence of PhSeOTf, however,
unexpectedly afforded a mixture of isomeric oxy-
selenides 6, probably generated by addition of the
alcohol 3 to the selenonium ion A (see Scheme 1).
We used mannosyl pentenoate 1 and PhSeOTf to
examine glycosylations of a number of other glycosyl
acceptors (Table 2). Glycosylation was carried out
with 5 equiv of PhSeBr and AgOTf in the presence
of 4-Š molecular sieves (MS) and TTBP at À788C in
CH2Cl2. Glycosylation proceeded smoothly with 1.5
or 2 equiv of PhSeBr and AgOTf, but 5 equiv of the
Scheme 1. Plausible mechanism of glycosylation with glycosyl pentenoate 1 as
the donor and with PhSeOTf as a promoter. Bn=benzyl, Tf=trifluoromethane-
sulfonyl.
4,6-O-Benzylidene mannosyl pentenoate 1 (a/
b = 10:1) was readily prepared from the corre-
sponding 1-hydroxy sugar 2[5c] by simple treatment
with commercially available 4-pentenoic acid in
the presence of 1,3-diisopropylcarbodiimide
(DIC) and a catalytic amount of 4-dimethylami-
nopyridine (DMAP) as shown in Scheme 2.
We initially examined the glycosylation of
glycosyl acceptor 3 with pentenoate 1 and with
Scheme 3. Reaction of 4-pentenyl 4,6-O-benzylidene mannoside 5 as a donor with the acceptor
3.
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Table 2: Glycosylations of various acceptors 7–16 with donor 1 in
CH2Cl2.
However, glycosylation of 12 gave a mixture of a- and b-
disaccharide 22 (b/a = 17:1) in 90% yield (Table 2, entry 6).
Interestingly, diacetone galactose 13, mannosylation of which
is known to be less stereoselective than that of other glycosyl
acceptors under Crichꢀs sulfoxide conditions[3e] and Schmidtꢀs
tricholoroacetimidate conditions,[5a] reacted with 1 under the
present conditions to afford b-disaccharide 23 exclusively in
82% yield (Table 2, entry 7). Glycosylations of azido sugar 14,
hindered tertiary alcohol 15, and the simple primary alcohol
1-octanol (16) also afforded only b-mannopyranosides in high
yields (Table 2, entries 8–10). Moreover, toluene was also
found to be a good solvent in the present PhSeOTf-mediated
mannosylation method; the results with toluene were almost
same as those with CH2Cl2 (Table 2) unlike the sulfoxide
method for b-mannopyranosylation.[3a] The stereochemistries
at newly generated anomeric centers of unknown disaccha-
rides 19, 20, and 24 were determined unequivocally on the
basis of 1H and 13C NMR spectroscopic data, in particular the
C1’,H1’ coupling constants: 1J(C1’,H1’) = 159.4 Hz in com-
pound 19, 1J(C1’,H1’) = 160.0 Hz in compound 20, and
1J(C1’,H1’) = 160.8 Hz in compound 24.
Entry
1
Glycosyl acceptor
Prod.
Yield [%][a,b]
b/a[a,b]
90
(87)
b only
(b only)
17
88
(89)
b only
(b only)
2
3
4
5
6
18
19
20
21
22
89
(87)
b only
(b only)
87
(87)
b only
(b only)
Like Seeberger et al. indicated,[5c] we observed that the
mannosylation of more reactive primary alcohol acceptors
showed poorer b stereoselectivity with known 4,6-O-benzyl-
idene-substituted mannosyl donors. Therefore, we investi-
gated the efficiency of the present mannosyl pentenoate/
PhSeOTf method for the preparation of b-mannopyranoside
32 (which we needed to make a self-assembled b-mannoside
monolayer on a gold surface) from primary alcohol 31 and
compared the results with those from other mannosylation
methods (Table 3). The glycosylation of 31 with the penten-
oate donor 1 afforded b-mannopyranoside 32 exclusively in
87% yield (Table 3, entry 1). While the glycosylation with the
trichloroacetimidate donor 27 gave a mixture of a- and b-
mannopyranoside 32 (b/a = 2:1, 1J(C1’-H1’) = 161.8 Hz for b-
85
(85)
b only
(b only)
90
(89)
17:1
(4:1)
82
b only
(b only)
5.6:1[c]
2.1:1[d]
(85)
86[c]
88[d]
7
8
23
24
87
b only
1
mannoside and J(C1’-H1’) = 169.6 Hz for a-mannoside) in
85% yield (Table 3, entry 2), the use of 2’-carboxybenzyl
glycoside 28[4] as the mannosyl donor provided the undesired
a anomer of 32 as the major product in good yield (Table 3,
entry 3). On the other hand, glycosylations with thioglycoside
29 and with glycosyl sulfoxide 30 as glycosyl donors afforded a
mixture of a- and b-mannopyranoside 32 (b/a = 1:2 for 29,
11:1 for 30) in yields of 70% and 81%, respectively (Table 3,
entries 4 and 5). Accordingly, the present method appears to
be more efficient than other known methods for the b-
mannosylation of simple primary alcohols.
89
(88)
b only
(b only)
9
25
26
89
(89)
b only
(b only)
10
[a] Determined after isolation of product. [b] Yields and ratios in
parentheses are those from reactions in toluene as a solvent. [c] The
result by Crich’s sulfoxide method, see Ref. [3e]. [d] The result with 3-O-
allyl-2-O-benzyl-4,6-O-benzylidene mannopyranosyl trichloroacetimidate
by Schmidt’s method, see Ref. [5a]. TBDMS=tert-butyldimethylsilyl.
We applied this newglycosylation method to the synthesis
of trisaccharide 36, which has both a- and b-mannopyranosyl
linkages, to showits effectiveness for oligosaccharide syn-
thesis (Scheme 4). Mannosyl pentenoate donors 33 and 37
were readily prepared from d-mannose via the corresponding
1-hydroxy sugars (see the Supporting Information). Reaction
of 4,6-O-benzylidene mannosyl donor 33 and acceptor 3
under the present glycosylation conditions using PhSeOTf
afforded only b-disaccharide 34 in 85% yield. Subsequent
removal of the p-methoxybenzyl (PMB) group of 34 with 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gave alcohol
35. Glycosylation of the disaccharide 35 as an acceptor with
benzoyl-protected mannosyl pentenoate 37 as a donor under
promoters guarantees high yield and stereoselectivity even
when the promoter deteriorates slightly or the generation of
PhSeOTf is incomplete. Although the glycosylation of various
acceptors with 1 was so efficient that the glycosyl donor was
consumed within 20 min at À788C based on TLC, the reaction
mixture was further warmed to 08C to ensure completion of
the reaction. Glycosylations of primary alcohol acceptors 7–9
with 1 afforded exclusively b-disaccharides 17–19 in high
yields (Table 2, entries 1–3). The complete conversion of
acceptors 10 and 11 to give the corresponding b-disaccharides
20 and 21 was also easily achieved (Table 2, entries 4 and 5).
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Table 3: Glycosylation of acceptor 31 with various donors, 1, and 27–30.
and PhSeOTf. This method for the b-mannopyranosylation
was found to be comparable to and even better than other
known methods for the mannosylation of the simple reactive
primary alcohol. The versatility of the present methodology
was readily demonstrated by the efficient synthesis of
trisaccharide 36, which has both a- and b-mannopyranosyl
linkages, with perfect stereoselectivity in high yields.
Entry Glycosyl
donor
Promoter Yield b/a[a] Reaction
[%][a]
conditions
Received: July 3, 2006
Revised: August 7, 2006
Published online: October 13, 2006
1
1
PhSeOTf 85 b
Present
TTBP
only work
Keywords: b-mannopyranosylation · glycosides ·
.
glycosyl pentenoate · glycosylation · phenylselenyl triflate
2
TMSOTf 87
2:1
Ref. [5a]
[1] For selected reviews on glycosylation, see: a) R. R. Schmidt,
Angew.Chem. 1986, 98, 213 – 236; Angew.Chem.Int.Ed.Engl.
1986, 25, 212 – 235; b) P. Sinaþ, Pure Appl.Chem. 1991, 63, 519 –
528; c) K. Toshima, K. Tatsuta, Chem.Rev. 1993, 93, 1503 – 1531;
d) G.-J. Boons, Tetrahedron 1996, 52, 1095 – 1121; e) B. G. Davis,
Tf2O
3
91
1:6
1:2
Ref. [4]
DTBMP[b]
J.Chem.Soc.Perkin Trans.1
2000, 2137 – 2160; f) A. V.
Demchenko, Lett.Org.Chem. 2005, 2, 580 – 589.
BSP[c]
Tf2O
[2] For selected reviews on b-mannosylation, see: a) H. Paulsen,
Angew.Chem. 1982, 94, 184 – 201; Angew.Chem.Int.Ed.Engl.
1982, 21, 155 – 173; b) F. Barresi, O. Hindsgaul in Modern
Methods in Carbohydrate Synthesis (Eds.: S. H. Khan, R. A.
OꢀNeill), Harwood , Amsterdam, 1996, pp. 251 – 276; c) V.
Pozsgay in Carbohydrates in Chemistry and Biology, Vol.1
(Eds.: B. Ernst, G. W. Hart, P. Sinaþ), Wiley-VCH, Weinheim,
2000, pp. 319 – 343; d) J. J. Gridley, H. M. I. Osborn, J.Chem.
4
5
70
81
Ref. [3g]
TTBP
Tf2O
TTBP
11:1 Ref. [3b]
[a] Determined after isolation of product. [b] DTBMP=2,6-di-tert-butyl-4-
methylpyridine. [c] BSP=benzenesulfinylpiperidine. TMS=tert-butyldi-
methylsilyl.
Soc.Perkin Trans.1
Synlett 2003, 1225 – 1240.
[3] a) D. Crich, S. Sun, J.Org.Chem. 1996, 61, 4506 – 4507; b) D.
Crich, S. Sun, J.Org.Chem. 1997, 62, 1198 – 1199; c) D. Crich, S.
2000, 1471 – 1491; e) A. V. Demchenko,
Sun, J.Am.Chem.Soc.
1997, 119, 11217 –
11223; d) D. Crich, S. Sun, J.Am.Chem.Soc.
1998, 120, 435 – 436; e) D. Crich, S. Sun,
Tetrahedron 1998, 54, 8321 – 8348; f) D. Crich,
W. Cai, Z. Dai, J.Org.Chem. 2000, 65, 1291 –
1297; g) D. Crich, M. Smith, J.Am.Chem.Soc.
2001, 123, 9015 – 9020.
[4] K. S. Kim, J. H. Kim, Y. J. Lee, Y. J. Lee, J.
Park, J.Am.Chem.Soc. 2001, 123, 8477 – 8481.
[5] a) R. Weingart, R. R. Schmidt, Tetrahedron
Lett. 2000, 41, 8753 – 8758; b) S.-i. Tanaka, M.
Takashina, H. Tokimoto, Y. Fujimoto, K.
Tanaka, K. Fukase, Synlett 2005, 2325 – 2328;
c) J. D. C. CodØe, L. H. Hossain, P. H. See-
berger, Org.Lett. 2005, 7, 3251 – 3254.
[6] a) A. A. H. Abdel-Rahman, E. Jonke, E. S. H.
El Ashry, R. R. Schmidt, Angew.Chem. 2002,
114, 3100 – 3103; Angew.Chem.Int.Ed. 2002,
41, 2972 – 2974; b) D. Crich, P. Jayalath, Org.
Lett. 2005, 7, 2277 – 2280; c) D. Crich, P.
Jayalath, T. K. Hutton, J.Org.Chem.
71, 3064 – 3070.
2006,
Scheme 4. Synthesis of trisaccharide 36.
[7] For examples, see: Refs. [3e,g,4,5a].
[8] H. Kunz, P. Wernig, M. Schultz, Synlett 1990,
631 – 632.
[9] J. C. Lopez, B. Fraser-Reid, J.Chem.Soc.Chem.Commun. 1991,
159 – 161.
[10] 3-n-Pentenoyl glycals were used for the synthesis of 2,3-
unsaturated disaccharides: a) J. C. Lopez, B. Fraser-Reid, J.
Chem.Soc.Chem.Commun. 1992, 94 – 96; b) J. C. Lopez, A. M.
the same reaction conditions smoothly provided the diaste-
reomerically pure a-trisaccharide 36 in 82% yield.
In conclusion, we have described a highly reactive and
stereoselective procedure for the b-mannopyranosylation
employing 4,6-O-benzylidene mannopyranosyl pentenoate 1
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Communications
Gomez, S. Valverde, B. Fraser-Reid, J.Org.Chem. 1995, 60,
3851 – 3858.
[11] K. Ikeda, J. Fukuyo, K. Sato, M. Sato, Chem.Pharm.Bull. 2005,
53, 1490 – 1493.
[12] D. Crich, M. Smith, Q. Tao, J. Picione, Synthesis 2001, 323 – 326.
[13] For reviews, see: a) B. Fraser-Reid, U. E. Udodong, Z. Wu, H.
Ottosson, J. R. Merritt, C. S. Rao, C. Roberts, R. Madsen, Synlett
1992, 927 – 942; b) B. Fraser-Reid, R. Madsen in Preparative
Carbohydrate Chemistry (Ed.: S. Hanessian), Marcel Dekker,
NewYork, 1997, pp. 339 – 356.
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