IPy2BF4-mediated transformation of n-pentenyl glycosides to glycosyl fluorides: A new pair of semiorthogonal glycosyl donors

Article abstract of DOI:10.1021/ol070753r

Bis(pyridinium) iodonium(1) tetrafluoroborate (IPy₂BF ₄), a solid and stable reagent, can be used to transform n-pentenyl orthoesters (NPOEs) and n-pentenyl glycosides (NPGs) into glycosyl fluorides. The latter pair constitutes a new

Full text of DOI:10.1021/ol070753r

ORGANIC
LETTERS
2
007
Vol. 9, No. 15
759-2762
IPy BF -Mediated Transformation of
n-Pentenyl Glycosides to Glycosyl
Fluorides: A New Pair of
2
4
2
Semiorthogonal Glycosyl Donors
J. Crist o´ bal L o´ pez,* Clara Uriel, Alejandra Guillam o´ n-Mart ´ı n,
Seraf ´ı n Valverde, and Ana M. G o´ mez*
Instituto de Qu ´ı mica Org a´ nica General (CSIC), Juan de la CierVa 3,
28006 Madrid, Spain
clopez@iqog.csic.es; anago@iqog.csic.es
Received March 28, 2007
ABSTRACT
2 4
Bis(pyridinium) iodonium(I) tetrafluoroborate (IPy BF ), a solid and stable reagent, can be used to transform n-pentenyl orthoesters (NPOEs)
and n-pentenyl glycosides (NPGs) into glycosyl fluorides. The latter pair constitutes a new set of semiorthogonal glycosyl donors that can be
used in glycosylation strategies, alone or in combination with NPOEs.
The development of efficient methods for accessing synthetic
oligosaccharides is essential to the understanding of their
biological relevance. Major advances in the field have arisen
fluorides8,9 have also proven themselves as useful glycosyl
donors and have played a strategic role in the development
1
10
of the two-stage activation protocol and the orthogonal
1
1
from the development of new glycosyl donors that have, in
turn, contributed to the design of novel strategies in glyco-
method for glycosyl assembly.
In this Letter, we disclose a convenient method for the
conversion of NPGs into glycosyl fluorides and their use as
sylation.2 In this context, n-pentenyl glycosides (NPGs)
,3
4
1
2
are extremely versatile glycosyl donors that have played a
key role in the development of the chemoselectivity-based
a new pair of semiorthogonal glycosyl donors.
(5) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J. Am.
5
armed-disarmed approach for saccharide coupling, includ-
Chem. Soc. 1988, 110, 5583-5584.
6
7
(6) (a) Konradsson, P.; Mootoo, D. R.; McDevitt, R. E.; Fraser-Reid, B.
J. Chem. Soc., Chem. Commun. 1990, 270-272. (b) Konradsson, P.;
Udodong, U. E.; Fraser-Reid, B. Tetrahedron Lett. 1990, 31, 4313-4316.
(c) Fraser-Reid, B.; Wu, Z.; Udodong, U. E.; Ottosson, H. J. Org. Chem.
1990, 55, 6068-6070.
ing its stereoelectronic or torsional variants. Glycosyl
(
(
(
1) Varki, A. Glycobiology 1993, 3, 97-130.
2) Toshima, K.; Tatsuta, K. Chem. ReV. 1993, 93, 1503-1531.
3) (a) Boons, G.-J. Tetrahedron 1996, 52, 1095-1121. (b) Demchenko,
(7) Fraser-Reid, B.; Wu, Z.; Andrews, C. W.; Skowronski, E. J. Am.
Chem. Soc. 1991, 113, 1434-1435.
A. V. Lett. Org. Chem. 2005, 2, 580-589.
(4) Mootoo, D. R.; Date, V.; Fraser-Reid, B. J. Am. Chem. Soc. 1988,
(8) Mukaiyama, T.; Murai, Y.; Shoda, S. Chem. Lett. 1981, 10, 431-
1
10, 2662-2663. (b) Fraser-Reid, B.; Konradsson, P.; Mootoo, D. R. J.
432.
Chem. Soc., Chem. Commun. 1988, 823-825. (c) Fraser-Reid, B.; Udodong,
U. E.; Wu, Z.; Ottosson, H.; Merrit, J. R.; Rao, C. S.; Roberts, C.; Madsen,
R. Synlett 1992, 927-942.
(9) Reviews: (a) Shimizu, M.; Togo, H.; Yokoyama, M. Synthesis 1998,
799-822. (b) Toshima, K. Carbohydr. Res. 2000, 327, 15-26. (c)
Mukaiyama, T. Angew. Chem., Int. Ed. 2004, 43, 5590-5614.
1
0.1021/ol070753r CCC: $37.00
© 2007 American Chemical Society
Published on Web 06/20/2007

For the transformation of NPGs to glycosyl fluorides we
selected bis(pyridinium) iodonium(I) tetrafluoroborate (IPy
2
-
Table 1. Synthesis of Glycosyl Fluorides 10-16 from NPGs
-7 and NPOEs 8, 9 by Treatment with I(Py) BF in the
Presence of HBF (1.2 equiv) in CH Cl as Solvent
13
BF
4
). This commercially available compound, a stable and
1
2
4
1
4
solid reagent that acts as a mild source of iodonium ions,
4
2
2
drew our attention since it effects facile iodofluorination of
alkenes in the presence of an acid.15 Accordingly, we
reasoned that NPGs could be efficiently converted to glycosyl
1
6,17
fluorides
2 4
upon treatment with IPy BF . Our results,
displayed in Table 1, showed that NPGs 1-7 react smoothly
1
8
at low temperature with IPy
of tetrafluoroboric acid19 (HBF
0-16, in good to excellent yields. n-Pentenyl orthoesters
NPOEs) 8, 9 also underwent the same transformation under
2
BF
4
in CH
2
Cl
2
in the presence
4
) to give glycosyl fluorides
1
(
similar reaction conditions. In all cases (Table 1, entries i-ix),
the reaction took place with complete stereoselectivity to
furnish R-glycosyl fluorides exclusively. Partially disarmed
NPG 5 yielded glycosyl fluoride 14 (entry v) uneventfully.
The transformation of disarmed NPG 7 demanded further
acidic treatment, to rearrange a presumed orthoacyl fluoride
2
0
intermediate, to yield the desired fluoride (entry vii). Silyl
protecting groups are compatible with the reaction conditions
employed as illustrated in the reaction of NPG 6 (entry vi).
Finally, NPOEs can also be transformed to glycosyl fluorides,
thus providing an alternative route to acyl substituted
glycosyl fluorides (e.g., 16) otherwise available by reaction
of disarmed NPGs (compare entries vii and viii).
We next decided to explore the orthogonality of NPGs
and glycosyl fluorides. To activate glycosyl fluorides while
leaving NPGs unchanged, we selected ytterbium triflate (Yb-
(
OTf)
3
). This reagent has been reported by Shibasaki and
21
co-workers to promote efficient glycosylation of glycosyl
22
fluorides whereas Jayaprakash and Fraser-Reid have shown
it to be innocuous toward NPGs. On the other hand, we chose
iodonium dicollidine perchlorate (IDCP)23 as a selective
activator for NPGs.
(
10) (a) Nicolaou, K. C.; Ueno, H. In PreparatiVe Carbohydrate
Chemistry; Hanessian, S., Ed.; Marcel Kekker, Inc.: New York, 1997; pp
13-338. (b) Nicolaou, K. C.; Bockovich, N. J.; Carcanague, D. R. J. Am.
Chem. Soc. 1993, 115, 8843.
11) (a) Kanie, O.; Ito, Y.; Ogawa, T. J. Am. Chem. Soc. 1994, 116,
3
(
1
1
4
2073-12074. (b) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1995, 34,
432-1434. (c) Kanie, O.; Ito, Y.; Ogawa, T. Tetrahedron Lett. 1996, 26,
551.4554. (d) Kanie, O. In Carbohydrates in Chemistry and Biology; Ernst,
B., Hart, G. W., Sina y¨ , P., Eds.; Wiley-VCH: Weinheim, Germany, 2000;
Our experiments for orthogonal couplings are displayed
in Scheme 1. Although useless in target-oriented oligosac-
charide synthesis, methyl substituents have been used in
several instances for the sake of simplicity in NMR
interpretation. Armed and disarmed glycosyl fluorides 12 and
Vol. 1, Chapter 16.
(
12) Demchenko, A. V.; De Meo, C. Tetrahedron Lett. 2002, 43, 8819-
822.
13) Barluenga, J.; Gonz a´ lez, J. M.; Campos, P. J.; Asensio, G. Angew.
8
(
Chem., Int. Ed. Engl. 1985, 24, 319-320.
(
14) Barluenga, J. Pure Appl. Chem. 1999, 71, 431-436.
(15) Barluenga, J.; Campos, P. J.; Gonz a´ lez, J. M.; Su a´ rez, J. L. Asensio,
1
4 underwent smooth glycosylation with NPG 17, in the
G. J. Org. Chem. 1991, 56, 2234-2237.
(16) Recently, a combination of NBS and DAST has been used to
presence of Yb(OTf) in CH Cl at room temperature, to give
3
2
2
transform NPGs into glycosyl fluorides: (a) Clausen, M. H.; Madsen, R.
Chem.sEur. J. 2003, 9, 3821-3832. See also: (b) Konradsson, P.; Fraser-
Reid, B. J. Chem. Soc. Chem. Commun. 1989, 1124-1125.
disaccharides 18 and 19 (Scheme 1a,b). On the other hand,
armed NPGs 1, 4, and 6 reacted with fluorides 20 and 22,
in the presence of IDCP at room temperature in CH Cl , to
2 2
give disaccharides 21, 23, and 24 as anomeric mixtures
(Scheme 1c,d,e). The method works well with disarmed
glycosyl fluorides (Scheme 1b). However, disarmed NPGs
(
17) Yokoyama, M. Carbohydr. Res. 2000, 327, 5-14.
(18) Although CH2Cl2 has been reported as a solvent for the crystal-
lization of IPy2BF4 (see ref 14), we have not observed any solubility
problems in the reactions described in this paper.
(19) Usually, an acid is required to neutralize the supply of pyridine
molecules from IPy2BF4, thus avoiding the incorporation of pyridine itself
as the nucleophile (see ref 14).
(
66.
(
20) Griffith, M. H. E.; Hindsgaul, O. Carbohydr. Res. 1991, 211, 163-
(22) Jayaprakash, K. N.; Fraser-Reid, B. Synlett 2004, 301-305.
(23) (a) Lemieux, R. U.; Morgan, A. R. Can. J. Chem. 1965, 43, 2190-
2197. (b) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J.
Am. Chem. Soc. 1988, 110, 5583-5584.
1
21) Hosono, S.; Kim, W.-S.; Sasai, H.; Shibasaki, M. J. Org. Chem.
1
995, 60, 4-5.
2760
Org. Lett., Vol. 9, No. 15, 2007

semiorthogonal glycosyl donors. Accordingly, NPOE 8 was
made to compete with glycosyl fluoride 12 for glycosyl
acceptor 26 under a variety of experimental conditions
(Scheme 2). Thus, treatment of the above mixture with NIS
Scheme 1. Orthogonal Glycosyl Couplings between NPGs
and Glycosyl Fluorides at Room Temperature, in CH
2 2
Cl as
Solvent
Scheme 2. Coupling of NPOEs with Glycosyl Fluorides
3 2 2
(2 equiv) and Yb(OTf) (1 equiv) in CH Cl at -20 °C, gave
disaccharide 27 along with recovered glycosyl fluoride 12
(85%) (Scheme 2a).
On the contrary, fluoride 12 could not be activated
selectively over NPOE 8 under a series of reaction conditions
2
5
26
27
18
(
SnF
4
,
2
TMSOTf, CpTiCl
2
/AgClO
4
,
Yb(OTf)
3
,
3
BF ‚
8
OEt
2
), the problem being the preferential activation of
NPOE 8 (Scheme 2b). Along this line, disaccharide 25
unavailable from the reaction of disarmed NPG 7 with
(
glycosyl fluoride 23 (Scheme 1f,g)) could now be efficiently
prepared by glycosylation of fluoride acceptor 22 with NPOE
8
(Scheme 2c).
Finally, the knowledge gained from these experiments was
applied to the one-pot synthesis of saccharides. Accordingly,
glycosylation of fluoride 22 with NPOE 8 (NIS/Yb(OTf)
3
,
Scheme 3. One-Pot Assembly of Trisaccharide 29 by
Sequential Glycosyation of NPOE 8 and Fluoride 22 with NPG
(e.g., 7), which would give rise to disaccharides containing
17
acyl substituents at the nonterminal saccharide (e.g., 25,
Scheme 1f), failed to react upon treatment with IDCP and
gave a complex reaction mixture when treated with NIS/
BF
3
‚Et O at -30 °C from which the sought disaccharide
2
could only be isolated in 25% yield (Scheme 1g).
To overcome this drawback we decided to investigate the
possible incorporation of NPOEs (synthetically equivalent
24
to disarmed NPGs but more reactive ) to this set of
(24) Mach, M.; Schlueter, U.; Mathew, F.; Fraser-Reid, B.; Hazen, K.
C. Tetrahedron 2002, 58, 7345-7354.
Org. Lett., Vol. 9, No. 15, 2007
2761

-
20 °C) was followed by the addition of NPG 17 and further
NPOEs that can be activated in the presence of glycosyl
fluorides or NPGs could be used in combination with them
in one-pot synthetic protocols for the preparation of
saccharides.
Yb(OTf) at room temperature to furnish n-pentenyl trisac-
charide 29, in 72% yield (Scheme 3).
In summary, we have reported a novel method for the
preparation of glycosyl fluorides from NPGs or NPOEs by
3
3
0
treatment with IPy
2
BF
4
. We have also shown that NPGs and
Acknowledgment. This research was supported with
funds from the Direcci o´ n General de Ense n˜ anza Superior
(Grants: PPQ2003-00396, CTQ2006-15279-C03-02). C.U.
thanks the CSIC for financial support. We thank Prof. J.
Barluenga (University of Oviedo, Spain) for a generous gift
glycosyl fluorides constitute a new pair of semiorthogonal
1
2,29
glycosyl donors,
and we have determined appropriate
reaction conditions for their selective activation. Furthermore,
(
25) (a) Kreuzer, M.; Thiem, J. Carbohydr. Res. 1986, 149, 347-361.
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2 4
BF .
(
7
b) J u¨ nnemann, J.; Lundt, I.; Thiem, J. Liebigs Ann. Chem. 1991, 759-
64.
(
26) Hashimoto, S.; Hayashi, M.; Noyori, R. Tetrahedron Lett. 1984,
Supporting Information Available: Experimental pro-
2
5, 1379-1382.
1
13
cedures and characterization data and copies of H, C, and
two-dimension NMR spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
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