Highly stereoselective glycosyl-chloride-mediated synthesis of 2-deoxyglucosides

Article abstract of DOI:10.1002/chem.201203418

Cl intermediates: The glycosylation of per-O-benzylated 2-deoxy- and 2,6-dideoxythioglycosides, promoted by the combination of para-toluenesulfenyl chloride (p-TolSCl) and silver triflate (AgOTf), furnished the products in high yields and high stereoselec

Full text of DOI:10.1002/chem.201203418

DOI: 10.1002/chem.201203418
Highly Stereoselective Glycosyl-Chloride-Mediated Synthesis of 2-
Deoxyglucosides
Ved Prakash Verma[a, b] and Cheng-Chung Wang*[a]
Dedicated to Professor Chin-Hsing Chou on the occasion of his 65th birthday
The presence of 2-deoxy- or 2,6-dideoxyglycosides, either
2-acetamido moiety is believed to play a decisive role.[13] To
further confirm this structure–activity relationship, we
wanted to synthesize O-glycopeptides 1 and 2, which were
decorated with 2-deoxy-glucoside. Therefore, easy access to
a- or b-2-deoxyglucosyl-l-serine (3) and -threonine (4) is
critical (Figure 1).
as a single structural element or as the components of oligo-
saccharides in either a or b linkages, is essential to the activ-
ity of many natural products, especially for antibiotics and
anticancer agents.[1] However, the stereoselective 2-deoxy-
glycosylation reaction remains a long-standing challenge in
carbohydrate chemistry. Owing to the lack of C2 functional-
ity, which governs the stereoselectivity of the reaction and
stabilizes the intermediary oxonium ion, glycosylation reac-
tions that involve these glycosides are usually held back by
poor stereoselectivity and the high susceptibility of 2-deoxy-
glycosides to acid hydrolysis.[2,3] Although numerous strat-
egies and conditions, including the use of glycal precursors,[4]
have been developed[3] and the anomeric effect leads to the
preferential formation of a-anomers, moderate yields and
poor stereoselectivities are usually encountered in the syn-
thesis of 2-deoxyglucosides.
Figure 1. Retrosynthesis of glycoproteins or peptides 1 and 2.
To control the stereoselectivity of this reaction, indirect
methods that introduce iodine,[5] bromine,[6] or fluorine
atoms,[7] as well as thio[8] or seleno[9] groups at the C2 posi-
tion, are typically adopted. The 1,2-migration–glycosylation
of thioglycosides[10] and the reduction of the C2 oxygen[11] or
nitrogen[12] moieties also provide alternatives. These indirect
approaches are reliable but need additional synthetic steps
to remove these stereo-governing groups. Direct methods,
without the need for modifying the C2 functionality, are
more concise but usually lead to anomeric mixtures.[3]
Thioglycoside is one of the most commonly used glycosyl
donors,[14] owing to its high stability as well as its high reac-
tivity in the presence of numerous promoters. The relative
reactivity values (RRVs) of thioglycosides with different
protecting patterns are quantifiable for one-pot multiple gly-
cosylation reactions.[15] Recently, 2-deoxyglycosyl donors
that were equipped with a conformation-constraining group
or a directing functionality at the C6 position were reported
to provide good stereoselectivity.[16] For ease of preparation,
we chose a direct synthesis of 2-deoxyglycosides by using
easily prepared per-O-benzylated 2-deoxythioglucoside 5.[17]
However, the stereoselective glycosylation of highly reactive
compound 5 without the assistance of any conformation-
constraining and directing group is considered to be more
challenging.[3]
The O-glycosylation of serine and threonine is an omni-
present post-translational modification of proteins and pep-
tides. Studies have shown that even the decoration of a pep-
tide with a single N-acetylglucosamine or N-acetylgalactos-
ACHTUNGTRENNUNGamine group can alter its secondary structure, in which the
The iterative one-pot synthesis of oligosaccharides, estab-
lished by Huang, Ye, and co-workers in 2004[18] by using
para-toluenesulfenyl triflate (p-TolSOTf) as the promoter,[19]
which is generated in situ by mixing para-toluenesulfenyl
chloride (p-TolSCl) and silver triflate (AgOTf), has allowed
the activation of the thioglycosides in the absence of accept-
ors. Multiple glycosyl bonds can be constructed in the same
reaction vessel by using the thioglycosides as both the
donors and the acceptors. Numerous oligosaccharides have
been prepared by using this preactivation procedure[20] and
the a-glycosyl triflate is believed to be a plausible intermedi-
[a] Dr. V. P. Verma, Dr. C.-C. Wang
Institute of Chemistry
Academia Sinica
Nankang, Taipei 115 (Taiwan)
Fax : (+886) 2-27831237
E-mail: wangcc@chem.sinica.edu.tw
[b] Dr. V. P. Verma
Genomics Research Center
Academia Sinica
Nankang, Taipei 115 (Taiwan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203418.
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Chem. Eur. J. 2013, 19, 846 – 851

COMMUNICATION
Table 1. Preactivated direct glycosylations of 2-deoxythioglucopyranoside
5.
ate that stabilizes the transient oxocarbenium cation before
the formation of the glycosyl bond.
First, we tried to control the stereoselectivity of the 2-de-
oxyglycosyl bond formation by utilizing the configuration of
the a-glycosyl-triflate intermediate under these conditions.
Thus, we treated compound 5 (a/b=2:1) with AgOTf
(1.1 equiv) and p-TolSCl (1.0 equiv) in CH2Cl2 at À788C.
The acceptor was introduced 15 min after the addition of p-
TolSCl, when compound 5 had been fully consumed (by
TLC). After serine and threonine derivatives 6a and 6b
were added as the acceptor and the mixture was stirred for
a further 2 to 3 h, we isolated our desired a-2-deoxygluco-
syl-l-serine (7a) and -l-threonine derivatives (7b) in excel-
lent yields and a selectivity (7a: 84%, a only; 7b: 92%, a/
b=15:1; Table 1, entries 1 and 2). Encouraged by these re-
sults, we further extended the scope of this 2-deoxyglycosy-
lation reaction to monosaccharide acceptors. As shown in
Table 1, entries 3–7, acceptors that contained secondary hy-
droxy group, that is, compounds 6c, 6d, and 6g, gave their
corresponding products (7c, 7d, and 7g) in good yields and
excellent a selectivity, although those with primary hydroxy
groups (6e and 6 f) showed slightly lower selectivity. Fur-
thermore, a good yield and high a selectivity could also be
obtained when 2-naphthol (6h) was used as the acceptor;
the use of other non-sugar alcohols, such as MeOH (6i), 2-
adamantanol (6j), 1-adamantanol (6k), and benzyl alcohol
(6l), as the acceptors also resulted in excellent yields and
a selectivity (Table 1, entries 9–12).
Entry
1
Acceptor
Product
Yield
[%][a]
a/b[b]
84
92
a only
2
3
15:1
66
85
a only
4
5
a only
79
70
5:1
Being curious of these good results, we started to investi-
gate the mechanism of this reaction (Scheme 1) and we
tried to characterize the intermediate in this reaction before
6
15:1
7
68
82
a only
a only
8[22]
Scheme 1. Proposed reaction mechanism.
the addition of the acceptor by using NMR spectroscopy at
À788C. We expected to observe the signals for a glycosyl-
triflate intermediate because the in situ generated p-Tol-
SOTf was commonly believed to be the promoter of this re-
action.[18–20] However, instead of glycosyl triflate 9, subzero
NMR spectroscopy revealed a mixture of para-tolyl disul-
fide and a-glycosyl chloride 8,[21] which could even be care-
fully isolated by using column chromatography on silica gel
at room temperature; its physical data were in agreement
with literature values (see the Supporting Information).[21]
As well as 2-deoxyglucoside 5, we also found that para-tolyl
per-O-benzylated thioglucoside, -galactoside, and -manno-
side all afforded their corresponding glycosyl chlorides (data
9
82
92
10:1
15:1
10
11
12
66
88
a only
a only
[a] Yield of isolated product. [b] Determined from the yields of both iso-
mers.
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847

V. P. Verma and C.-C. Wang
not shown). Without adding the acceptor, glycosyl chloride
8 and AgOTf (1.1 equiv) could not be consumed and the
precipitation of AgCl could not be observed (and, hence,
isolated), even after stirring for an additional 3–4 h and
warming to 08C. This result suggested that p-TolSOTf was
not generated at the preactivation stage. After the addition
of the acceptor, the precipitation of AgCl was observed and
isolated and the glycosylation reaction finished within 2–3 h.
We found that glycosyl chloride 8 could be formed in the
presence of a catalytic amount of AgOTf (0.05 equiv), but
that one equivalent of p-TolSCl was necessary. However,
after the addition of the acceptor, the glycosylation reaction
was sluggish unless one equivalent of AgOTf was resup-
plied. We also observed that the precipitation of AgCl oc-
curred immediately after the addition of AgOTf and that
the formation of the product and the precipitation of AgCl
were proportional to the amount of AgOTf that was added.
To confirm that glucosyl chloride 8 was the reaction inter-
mediate, we treated isolated compound 8 with compound
6d and one equivalent of AgOTf at À788C to perform a
standard Koenigs–Knorr reaction; this reaction proceeded
smoothly and afforded disaccharide 7d (67%) with an un-
changed a/b ratio.
As shown in Scheme 1, although we confirmed that a-gly-
cosyl chloride 8 was the intermediate before the addition of
the acceptor, owing to the high a selectivity, we hypothe-
sized that the glycosylation reaction after the introduction
of the acceptor could still be mediated by the corresponding
glycosyl triflate.[23]
Although we did not observe the b-chloride by subzero
NMR spectroscopy, we still could not rule out the possibility
that the b-chloride was the species that reacted with the ac-
ceptors to form the a products, as studied by Lemieux et al.
in halide-ion glycosylation[24] and, lately, further investigated
by Demchenko and co-workers.[25] Notably, the addition of
an equivalent amount of tetrabutylammonium iodide or
chloride as the additive neither accelerated the reaction nor
altered its stereoselectivity.
the remaining TfOH in the reaction mixture neither reacted
with the glucosyl chloride (8) nor activated the remaining
AgOTf to perform further ion exchange to produce AgCl;
thus, the remaining glucosyl chloride (8) remained unreact-
ed.
To analyze the role of the silver ion and the triflate ion,
we individually replaced AgOTf with trimethylsilyl trifluoro-
methanesulfonate (TMSOTf) or silver tetrafluoroborate
(AgBF4). We found that the transformation of compound 5
into compound 8 by using p-TolSCl was smoothly catalyzed
by 0.1 equivalents of both TMSOTf and AgBF4 at À788C in
15 min. However, after the introduction of an acceptor (6d),
the reaction that was further promoted by an equimolar
amount of TMSOTf was sluggish. After stirring overnight,
no precipitation was observed, chloride 8 was not consumed,
and only 21% of compound 7d and the hydrolyzed donor
could be isolated, although the stereoselectivity remained
fully a-selective. In contrast, for the reaction that was fur-
ther promoted by one equivalent of AgBF4, again, com-
pound 8 remained intact before the introduction of acceptor
6d, AgCl precipitation was found after the addition of com-
pound 6d, and the reaction finished in 2–3 h. Disaccharide
7d (82%) was isolated but the a/b ratio was changed into
1.2:1.
Based on these studies, we can preliminarily conclude
that the precipitation of AgCl provides an indispensable
driving force for this reaction to proceed through a chloride/
triflate counterion-exchange pathway. In this case, the de-
pendence of a/b selectivity on the counterions, that is, tri-
flate and tetrafluroborate, supports the formation of transi-
ent ion pairs. Moreover, this ion exchange does not occur
simply between glycosyl chloride and AgOTf. An equimolar
amount of acceptor is also required to promote this reac-
tion.
Even with these studies in hand, we could still only con-
servatively propose that the glycosyl bond was formed be-
tween the acceptor and oxocarbenium cation 9 in an SN1
manner and that the very high a selectivity could simply be
attributed to the anomeric effect, although we found that
the counterion did affect the stereoselectivity of the reac-
tion. Alternatively, as very recently reported by Crich
et al.,[23] the a-glycosyl bond could be formed in equilibria
between the b-glycosyl triflate, the b-contact ion pair (b-
CIP), and the solvent-separated ion pair (SSIP). However,
these hypotheses need to be further confirmed. Recently, a
highly a-selective sialylation reaction, by using a conforma-
tion-constrained sialic-acid donor under this preactivation
system, was reported, but the plausible intermediate was not
identified or discussed.[27] Although the selectivity could be
attributed to the conformation-constraining group, we infer
that this reaction might also proceed through the corre-
sponding sialyl-chloride pathway.
Indeed, the triflate ion seems unlikely to directly replace
the chloride from a nucleophilic-strength perspective. As
mentioned above, we found that compound 8 remained un-
reactive, even with an equimolar amount of AgOTf, until
the acceptor was introduced. After the introduction of the
acceptor, the AgCl precipitated, which provided the driving
force for the activation of glucosyl chloride.[26] Then, the
counterions were exchanged and, hence, the transient oxo-
carbenium cation (9) could be generated. In a test reaction,
we introduced one equivalent of AgOTf but only 0.4 equiva-
lents of the acceptor (6d). The disaccharide (7d) was
formed but, surprisingly, glucosyl chloride 8 was still ob-
1
served as one of the major compounds in the H NMR spec-
trum, even after 5 h. Therefore, we inferred that the Koe-
nigs–Knorr reaction between AgOTf and the glycosyl chlor-
ide needs the participation of an equimolar amount of the
acceptor, otherwise this AgOTf-mediated Koenigs–Knorr
glycosylation cannot proceed. Such a reaction seems unlike-
ly to be promoted by the proton from the acceptor because
It has been reported that the 4,6-O-benzylidene-directed
glycosylation reaction favors b selectivity for 2-deoxygluco-
sylation.[16a–c] Therefore, we tested the selectivity by using 3-
O-benzyl-4,6-O-benzylidene-2-deoxythioglucoside (10; a/b=
3:1) as the donor in this system (Table 2). Again, the corre-
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Glycosyl-Chloride-Mediated Synthesis of 2-Deoxyglucosides
COMMUNICATION
Table 2. Preactivated direct glycosylations of 4,6-O-benzylidene-2-deoxy-
thioglucopyranoside 10.
9, the glycosylation reactions with MeOH (6i) and 2-ada-
mantanol (6j) gave b-major products 11i and 11j (a/b=
1:8.5 and 1:3, respectively). Therefore, we deduce that ac-
ceptors with weaker nucleophilicity cannot efficiently form
glycosyl bonds in the equilibria between a-covalent glycosyl
triflate and the SSIP; therefore, it still reacts with the SSIP
or within the equilibria between the SSIP, the b-contact ion
pair (b-CIP), and the covalent b-triflate to give the a-anom-
ers as the major products.[23] Again, this hypothesis needs to
be confirmed.
The glycosylation reactions of 2,6-dideoxysugars are
known to be more difficult, owing to their lack of an addi-
tional stabilizing oxygen moiety at the C6 position, which
not only makes their reactivity higher but also renders the
control of stereoselectivity more difficult.[28] A direct synthe-
sis of b-linked 2,6-deoxyoligosaccharides has been achieved
several years ago by Takahashi and co-workers.[29] We ap-
plied our preactivation conditions to 2,6-dideoxythioglyco-
side 12 (a/b=1:1; Table 3). Despite its higher reactivity,
good-to-excellent yields and good stereoselectivities were
achieved. Notably, the glycosylation of serine derivative 6a
(Table 3, entry 1) gave glycosyl serine 13a in 81% yield with
an a/b ratio of 12:1; the reactions of secondary monosac-
charide acceptor 6c (Table 3, entry 2) and primary hydroxy
compound 6e (Table 3, entry 3) afforded disaccharides 13c
Entry
Acceptor
Product
Yield
[%][a]
a/b[b]
1
2
83
86
81
2:1
5:1
1:3
3
4
82
66
2:1
1:6
5
6
Table 3. Preactivated direct glycosylations of 2,6-dideoxythioglucopyra-
noside 12.
74
a only
7
8
80
76
20:1
Entry
1
Acceptor
Product
Yield
[%][a]
a/b[b]
1:8.5
81
88
12:1
9
65
1:3
[a] Yield of isolated product. [b] Determined from the yields of both iso-
mers.
2
3
5:1
5:1
sponding a-glycosyl chloride can be observed and isolated
(see the Supporting Information). Indeed, a different trend
in stereoselectivity was observed. For secondary compound
6c and primary monosaccharide acceptor 6e (Table 2, en-
tries 3 and 5), b-major disaccharides 11c (81%, a/b=1:3)
and 11e (66%, a/b=1:6) were isolated in good yields. Re-
garding the glycosylation of l-serine and threonine deriva-
tive 6a and 6b and secondary compound 6d (Table 2,
entry 1, 2, and 4), although compounds 11a (83%, a/b=
2:1), 11b (86%, a/b=5:1), and 11d (82%, a/b=2:1) were
still the major products, an increased ratio the of b products
was observed compared to the previous “a-only” results
(Table 1). However, for 4,6-O-benzylidene-2-deoxyglucose
acceptor 6g and 2-naphthol (6h), still almost-completely a-
selective products 11g (74%, a only) and 11h (80%, a/b=
20:1) could be furnished. However, in Table 2, entries 8 and
82
88
4
b only
5
6
86
68
4:1
10:1
[a] Yield of isolated product. [b] Determined from the yields of both iso-
mers.
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V. P. Verma and C.-C. Wang
tion of an equimolar amount
of the acceptor. However,
whether other Koenigs–Knorr
promoters, such as Ag2O,
Ag2CO3, Hg(CN)2, and HgBr2,
act in the same way in this re-
action requires further clarifi-
cation. These results also
imply that thioglycosides are
often the precursors to glyco-
syl halides as the “real” donors
when halide-containing pro-
moter systems are used. We
have preliminarily studied the
Scheme 2. Iterative synthesis of trisaccharide 14: a) p-TolSCl (0.9 equiv) was used and the yield of compound
14 was calculated based on p-TolSCl.
and 13e in 88 and 82% yield, respectively, both with good
a/b ratios (5:1). The reaction with phenol-type acceptor 6h
furnished the rearranged “b-only” product (13h-r) in excel-
lent yield (88%), thus suggesting complete a-selectivity
during the glycosylation process. Glycosylation with MeOH
(6i) resulted in excellent yield (94%) with moderate stereo-
selectivity (a/b=4:1; Table 3, entry 5). Finally, the sterically
hindered compound 6j gave the product (Table 3, entry 6)
in a lower yield (68%) but higher selectivity (a/b=10:1).
To test the applicability of this method to the synthesis of
oligosaccharides and the stereoselectivity for a donor with
longer sugar units, trisaccharide 14 was synthesized in two
steps (Scheme 2). Preactivation glycosylation of compound 5
with compound 6m afforded disaccharide 7m with complete
a selectivity in 70%. Notably, this a selectivity remained
when disaccharide donor 7m and acceptor 6d were coupled
under this promoter system and gave trisaccharide 14 in
77% yield.
In summary, we have developed an efficient, simple, and
highly stereoselective glycosylation of 2-deoxy- and 2,6-di-
deoxy-thioglycosides without the need for a 2,3-O-confor-
mation-constraining group by using a p-TolSCl/AgOTf pro-
moter system in a preactivation manner. The reaction re-
mained highly a-selective when this system was applied to a
disaccharide donor. In fact, the glycosyl chloride was the in-
termediate before the addition of the acceptor, which sug-
gested that p-TolSOTf was not formed, as is commonly be-
lieved, in this very useful preactivation system for iterative
thioglycoside couplings. In fact, although p-TolSCl and
AgOTf were mixed together, the thioglycosides were first
turned into their corresponding glycosyl chlorides by p-
TolSCl. Such a transformation could be catalyzed by a
Lewis acid, such as AgOTf, TMSOTf, or AgBF4. After the
addition of the acceptor, the glycosylation reaction between
the glycosyl chloride and the acceptor was further promoted
by an equimolar amount of a Koenigs–Knorr donor, such as
AgOTf or AgBF4 (but not TMSOTf), through an ion-ex-
change pathway that was driven by the formation of AgCl.
The stereoselectivity could be influenced by the counterions,
which indirectly suggested the formation of transient oxocar-
benium cation 9. Furthermore, we also found, to the best of
our knowledge, for first time, that the AgOTf-mediated
Koenigs–Knorr glycosylation reaction requires the participa-
preactivation of thioglycosides by using NBS-TfOH and
NCS-TfOH combinations as the promoters and we observed
that the corresponding glycosyl bromide and -chloride were
formed as the intermediates, respectively, before the addi-
tion of the acceptor. In our laboratory, further research of
this mechanism is underway, as well as the syntheses of nat-
ural products and peptides that contain 2-deoxysugars.
Experimental Section
General procedure: A suspension of the donor (100 mg), molecular
sieves (4 ꢁ, 300 mg), and AgOTf (1.1 equiv) in CH2Cl2 (4 mL) was stir-
red at À788C under a N2 atmosphere for 1 h. para-Toluenesulfenyl chlor-
ide (1.0 equiv) was added into the reaction mixture at À788C and the
mixture was stirred for 15 min at the same temperature. Next, the accept-
or (1.2 equiv, dissolved in 0.5 mL CH2Cl2) was added into the reaction
mixture and the mixture was stirred for a further 2–3 h at the same tem-
perature. Upon the completion of the reaction, it was quenched with
Et3N and filtered through a pad of Celite. The filtrate was evaporated in
vacuo to furnish the crude product, which was purified by flash column
chromatography on silica gel to give the final product.
Acknowledgements
This work was supported by the National Science Council of Taiwan
(NSC 99–2113M-001–010-MY2 and NSC 101–2113M-001–011-MY2) and
Academia Sinica.
Keywords: glycosides · glycosyl chloride · glycosylation ·
Koenigs–Knorr reaction
[1] a) J. M. Langenhan, N. R. Peters, I. A. Guzei, M. Hoffman, J. S.
Thorson, Proc. Natl. Acad. Sci. USA 2005, 102, 12305–12310;
b) P. T. Daniel, U. Koert, J. Schuppan, Angew. Chem. 2006, 118,
886–908; Angew. Chem. Int. Ed. 2006, 45, 872–893; c) A. K. V. Iyer,
M. Zhou, N. Azad, H. Elbaz, L. Wang, D. K. Rogalsky, Y. Rojanasa-
kul, G. A. OꢂDoherty, J. M. Langenhan, ACS Med. Chem. Lett. 2010,
1, 326–330.
[2] W. Overend, C. Rees, J. Sequeira, J. Chem. Soc. 1962, 3429–3440.
[3] a) C. H. Marzabadi, R. W. Franck, Tetrahedron 2000, 56, 8385–8417;
b) D. Hou, T. L. Lowary, Carbohydr. Res. 2009, 344, 1911–1940, and
references therein.
[4] a) V. Bolitt, C. Mioskowski, S.-G. Lee, J. R. Falck, J. Org. Chem.
1990, 55, 5812–5813; b) B. D. Sherry, R. N. Loy, F. D. Toste, J. Am.
850
www.chemeurj.org
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Chem. Soc. 2004, 126, 4510–4511; c) H.-C. Lin, J.-F. Pan, Y.-B.
Chen, Z.-P. Lin, C.-H. Lin, Tetrahedron 2011, 67, 6362–6368; d) E. I.
Balmond, D. M. Coe, M. C. Galan, E. M. McGarrigle, Angew.
Chem. 2012, 124, 9286–9289; Angew. Chem. Int. Ed. 2012, 51, 9152–
9155.
[15] a) Z. Zhang, I. R. Ollmann, X.-S. Ye, R. Wischnat, T. Baasov, C.-H.
Wong, J. Am. Chem. Soc. 1999, 121, 734–753; b) X.-S. Ye, C.-H.
Wong, J. Org. Chem. 2000, 65, 2410–2431.
[16] a) R. Pongdee, B. Wu, G. A. Sulikowski, Org. Lett. 2001, 3, 3523–
3525; b) D. Crich, O. Vinogradova, J. Org. Chem. 2006, 71, 8473–
8480; c) K. S. Kim, J. Park, Y. J. Lee, Y. S. Seo, Angew. Chem. 2003,
115, 475–478; Angew. Chem. Int. Ed. 2003, 42, 459–462; d) Y.-S.
Lu, Q. Li, L.-H. Zhang, X.-S. Ye, Org. Lett. 2008, 10, 3445–3448;
e) J. Park, T. J. Boltje, G.-J. Boons, Org. Lett. 2008, 10, 4367–4370;
f) Y.-S. Lu, Q. Li, Y.-H. Wang, X.-S. Ye, Synlett 2010, 1519–1524.
[17] J. S. Yadav, B. V. Subba Reddy, E. Vijaya Bhasker, S. Raghavendra,
A. V. Narsaiah, Tetrahedron Lett. 2007, 48, 677–680.
[18] X. Huang, L. Huang, H. Wang, X.-S. Ye, Angew. Chem. 2004, 116,
5333–5336; Angew. Chem. Int. Ed. 2004, 43, 5221–5224.
[19] a) F. Dasgupta, P. J. Garegg, Carbohydr. Res. 1988, 177, c13-c17;
b) V. Martichonok, G. M. Whitesides, J. Org. Chem. 1996, 61, 1702–
1706; c) D. Crich, S. Sun, Tetrahedron 1998, 54, 8321–8348; d) D.
Crich, W. Cai, J. Org. Chem. 1999, 64, 4926–4930.
[20] a) L. Huang, X. Huang, Chem. Eur. J. 2007, 13, 529–540; b) A.
Miermont, Y. Zeng, Y. Jing, X.-S. Ye, X. Huang, J. Org. Chem. 2007,
72, 8958–8961; c) Z. Wang, L. Zhou, K. El-Boubbou, X.-S. Ye, X.
Huang, J. Org. Chem. 2007, 72, 6409–6420; d) B. Sun, B. Srinivasan,
X. Huang, Chem. Eur. J. 2008, 14, 7072–7081; e) Z. Wang, Y. Xu, B.
Yang, G. Tiruchinapally, B. Sun, R. Liu, S. Dulaney, J. Liu, X.
Huang, Chem. Eur. J. 2010, 16, 8365–8375.
[21] J. M. Nogueira, S. H. Nguyen, C. S. Bennett, Org. Lett. 2011, 13,
2814–2817.
[22] A rearranged isomer, 7h-r, was isolated (94% yield) if the reaction
was stirred for another 15 h.
[5] a) J. Thiem, H. Karl, J. Schwentner, Synthesis 1978, 696–697; b) J.
Thiem, in Trends in Synthetic Carbohydrate Chemistry, (Eds: D.
Horton, L. D. Hawkins, G. J. McGarvey), ACS Symposium Series
386, American Chemical Society, Washington, DC, 1989, Chapter 8,
pp. 131–149; c) W. R. Roush, K. Briner, D. P. Sebesta, Synlett 1993,
264–266; d) W. R. Roush, C. E. Bennett, J. Am. Chem. Soc. 1999,
121, 3541–3542; e) W. R. Roush, B. W. Gung, C. E. Bennett, Org.
Lett. 1999, 1, 891–893.
[6] a) K. Tatsuta, K. Fujimoto, M. Kinoshita, S. Umezawa, Carbohydr.
Res. 1977, 54, 85–104; b) J. Thiem, M. Gerken, J. Org. Chem. 1985,
50, 954–958; c) J. Thiem, B. Schottmer, Angew. Chem. 1987, 199,
591–592; Angew. Chem. Int. Ed. Engl. 1987, 26, 555–557.
[7] a) C. Bucher, R. Gilmour, Angew. Chem. 2010, 122, 8906–8910;
Angew. Chem. Int. Ed. 2010, 49, 8724–8728; b) E. Durantie, C.
Bucher, R. Gilmour, Chem. Eur. J. 2012, 18, 8208–8215.
[8] a) Y. Ito, T. Ogawa, Tetrahedron Lett. 1987, 28, 2723–2726; b) G.
Grewal, N. Kaila, R. W. Franck, J. Org. Chem. 1992, 57, 2084–2092;
c) R. W. Franck, N. Kaila, Carbohydr. Res. 1993, 239, 71–83; d) S.
Ramesh, R. W. Franck, Chem. Commun. 1989, 960–961.
[9] a) A. G. M. Barrett, T. Miller, Tetrahedron Lett. 1988, 29, 1873–
1874; b) M. Perez, J.-M. Beau, Tetrahedron Lett. 1989, 30, 75–78;
c) D. P. Sebesta, W. R. Roush, J. Org. Chem. 1992, 57, 4799–4802;
d) K. C. Nicolaou, J. Pastor, S. Barluenga, N. Winssinger, Chem.
Commun. 1998, 1947–1948.
[10] a) F.-I. Auzanneau, D. R. Bundle, Carbohydr. Res. 1991, 212, 13–24;
b) H. M. Zuurmond, P. A. M. van der Klein, G. A. van der Marel,
J. H. van Boom, Tetrahedron 1993, 49, 6501–6514; c) Z. Yang, B.
Yu, Carbohydr. Res. 2001, 333, 105–114; d) B. Yu, Z. Yang, Org.
Lett. 2001, 3, 377–379; e) F. Sajtos, L. Lazar, A. Borbas, I. Bajza, A.
Liptak, Tetrahedron Lett. 2005, 46, 5191–5194; f) L. Lꢃzꢃr, I. Bajza,
Z. Jakab, A. Liptꢃk, Synlett 2005, 2242–2244; g) D. Hou, T. L.
Lowary, Org. Lett. 2007, 9, 4487–4490; h) D. Hou, T. L. Lowary, J.
Org. Chem. 2009, 74, 2278–2289.
[11] a) M. K. Gurjar, P. K. Ghosh, Indian J. Chem. 1988, 27B, 1063–
1064; b) M. Trumtel, A. Veyrieres, P. Sinay, Tetrahedron Lett. 1989,
30, 2529–2532; c) J. C. Castro-Palomino, R. R. Schmidt, Synlett
1998, 501–503.
[12] G. Capozzi, A. Dios, R. W. Franck, A. Geer, C. Marzabadi, S. Meni-
chetti, C. Nativi, M. Tamarez, Angew. Chem. 1996, 108, 805–807;
Angew. Chem. Int. Ed. Engl. 1996, 35, 777–779.
[13] a) S. E. OꢂConnor, B. Imperiali, Chem. Biol. 1998, 5, 427–437;
b) D. H. Live, R. A. Kumar, X. Beebe, S. J. Danishefsky, Proc. Natl.
Acad. Sci. USA 1996, 93, 12759–12761; c) E. E. Simanek, D. H.
Huang, L. Pasternack, T. D. Machajewski, O. Seitz, D. S. Millar,
H. J. Dyson, C.-H. Wong, J. Am. Chem. Soc. 1998, 120, 11567–
11575.
[23] M. Huang, G. E. Garrett, N. Birlirakis, L. Bohe, D. A. Pratt, D.
Crich, Nat. Chem. 2012, 4, 663–667.
[24] R. U. Lemieux, K. B. Hendriks, R. V. Stick, K. James, J. Am. Chem.
Soc. 1975, 97, 4056–4062.
[25] S. Kaeothip, J. P. Yasomanee, A. V. Demchenko, J. Org. Chem. 2012,
77, 291–299.
[26] a) R. U. Lemieux, T. Takeda, B. Y. Chung, ACS. Symp. Ser. 1976, 39,
90–155; b) S. Hanessian, J. Banoub, Carbohydr. Res. 1977, 53, C13-
C16.
[27] B. Sun, H. Jiang, Tetrahedron Lett. 2011, 52, 6035–6038.
[28] M. Shan, E. U. Sharif, G. A. OꢂDoherty, Angew. Chem. 2010, 122,
9682–9685; Angew. Chem. Int. Ed. 2010, 49, 9492–9495.
[29] H. Tanaka, A. Yoshizawa, T. Takahashi, Angew. Chem. 2007, 119,
2557–2559; Angew. Chem. Int. Ed. 2007, 46, 2505–2507.
[14] a) P. J. Garegg, Adv. Carbohydr. Chem. Biochem. 1997, 52, 179–205;
b) J. D. C. Codꢄe, R. Litjens, L. J. van den Bos, H. S. Overkleeft,
G. A. van der Marel, Chem. Soc. Rev. 2005, 34, 769–782.
Received: September 24, 2012
Revised: October 20, 2012
Published online: December 11, 2012
Chem. Eur. J. 2013, 19, 846 – 851
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