LaCl3·7H2O/NaI/benzyl alcohol: A novel reagent system for regioselective hydration of glycals: Application in the synthesis of 1,6-dideoxynojirimycin

Article abstract of DOI:10.1016/S0040-4039(03)01175-4

Glycals can be readily hydrated using the LaCl₃·7H₂O/NaI/PhCH₂OH reagent system. In one case, having an exo methylene group, such hydration gives an intermediate which is readily converted into 1,6-dideoxynojirimycin, a potential enzyme inhibitor.

Full text of DOI:10.1016/S0040-4039(03)01175-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5001–5004
LaCl ·7H O/NaI/benzyl alcohol: a novel reagent system for
3
2
regioselective hydration of glycals: application in the synthesis of
ꢀ
1
,6-dideoxynojirimycin
Shikha Rani, Aditi Agarwal and Yashwant D. Vankar*
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, India
Received 11 March 2003; revised 1 May 2003; accepted 9 May 2003
Abstract—Glycals can be readily hydrated using the LaCl ·7H O/NaI/PhCH OH reagent system. In one case, having an exo
3
2
2
methylene group, such hydration gives an intermediate which is readily converted into 1,6-dideoxynojirimycin, a potential enzyme
inhibitor. © 2003 Elsevier Science Ltd. All rights reserved.
1
5
2
-Deoxysugars are an integral part of several biologi-
to II. A recent report in this area by Piancatelli et al.
using Hg(OAc) /NaBH led us to investigate whether
cally important natural products such as anthracyclin
antibiotics, aureolic acids, avermectins, ortho-
somycins and cardiac glycosides. Recently 2-deoxy-
glucose has been proposed as a potent drug against
ageing. Furthermore, both 2-deoxy-O-glycosides I ,
as well as 1-hydroxy-2-deoxysugars II
2
4
2
3
4
any other reagent would permit such a transformation
especially since mercury salts are toxic in nature and
5
6
1
6
there is current emphasis on green chemistry.
7
8
9,14a
(Fig. 1) func-
In this paper we wish to report LaCl ·7H O/NaI/
3
2
tion as important building blocks in organic synthesis.
Both of these types of compounds have been obtained
from glycals and a few reagents have been developed
for the direct addition of alcohols to glycals without a
PhCH OH as a new reagent system for the regioselec-
2
tive hydration of glycals. This combination was arrived
at after much experimentation. Initially, we attempted
17
to use LaCl ·7H O in the hope that the water of
3
2
1
0
competing Ferrier reaction. These include the use of
hydration would participate in addition to glycals
1
1a
11b
MeOH·HCl,
Ph PBr ,
the cation exchange resin
3
2
under the influence of LaCl as the Lewis acid. How-
3
1
1c
11d
and BCl3 (or BBr3).
AG50WX2
More recently
ever, under these conditions there was no reaction at all
and the glycals were recovered unchanged. Since the
12
from our group, ceric ammonium nitrate and subse-
quently from Yadav’s group, CeCl ·7H O/NaI were
1
3
13,18
3
2
NaI/CeCl ·7H O combination has been reported
to
3
2
also found to be useful reagents for this purpose. One
can, in principle, convert a 2-deoxy-O-glycoside I (Fig.
be a reactive reagent system for a number of useful
transformations, we performed reactions with
LaCl ·7H O along with a molar equivalent of NaI but
1
) into a 1-hydroxy-2-deoxy-sugar II, by the hydrolysis
3
2
of the appropriate O-glycoside I, at the anomeric car-
bon. However, there are only a few methods in the
literature which permit the direct hydration of glycals
again the glycals were found to be unreactive. In an
attempt to compare the reactivity of LaCl ·7H O with
1
4
3
2
CeCl ·7H O, and to assess subsequent anomeric selec-
3
2
tivity, we reacted tri-O-acetyl glucal with LaCl ·7H O/
3
2
NaI in methanol. We expected the formation of
1
2
-deoxy-O-glycoside I (R=Ac, R =Me) analogous to
13
the results reported with CeCl ·7H O. However, the
3
2
present reaction was slow and after 30 h at 40°C, to our
1
surprise, one of the products was II (R=Ac, R =H) in
4
5% yield along with the corresponding Ferrier product
Figure 1.
in 42% yield. Screening several alcohols indicated that a
combination of LaCl ·7H O/NaI/PhCH OH in a 1:1:1
ꢀ
Transformations in Carbohydrate Chemistry, Part 7. For Part 6,
3
2
2
see Ref. 1.
Corresponding author.
ratio was ideal for the optimum hydration of the glycals
without the formation of any O-glycoside or Ferrier
*
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01175-4

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002
S. Rani et al. / Tetrahedron Letters 44 (2003) 5001–5004
Table 1. Hydration of glycals with LaCl ·7H O/NaI/PhCH OH
3
2
2
product. Both acetyl as well as benzyl protected glycals
gave the hydrated products in good to excellent yields.
Our results are summarised in Table 1. Furthermore,
hydration of 3 using the present reagent system gave 4,
in 84% yield in 3 h which, was condensed with benz-
hydrylamine in the presence of NaCNBH3 in acetic
27
the reaction using a catalytic amount of PhCH OH
acid/methanol mixture to give the expected 2,3,4-tri-
28
2
instead of 1 equiv. proceeded very slowly taking almost
O-benzyl-1,6-dideoxynojirimycin derivative 5 in 68%
4
8 h for completion with the formation of about 10% of
yield. This compound can be hydrogenolysed to 1,6-
2
0
24a
the Ferrier product. Surprisingly, the reaction of 3-
deoxy-4,6-di-O-benzyl glucal under the present condi-
tions gave addition of benzyl alcohol rather than water.
At this stage nothing is clear as far as the mechanism of
this reaction is concerned but it appears that a species
such as 1, may be formed, as shown in Scheme 1, which
acts as a source of a proton leading to the formation of
the oxonium ion 2, when reacting with a glycal, which
dideoxynojirimycin 6, as reported. Since the reaction
medium is acidic, formation of the intermediate A (a
hemiacetal) followed by the loss of MeOH should
readily occur. Alternatively, La(III) ions could coordi-
nate with ꢀOMe to facilitate its removal.
In summary, we have developed a new reagent system
which is mild and non-toxic for the hydration of glycals
which has been utilised in the formation of an azasugar
21
in turn is trapped by H O forming II. Alternatively,
2
6
, a potential enzyme inhibitor, in good yield. We
an iodide ion can add to 2, forming the 1-iodo-2-deoxy-
sugar 2A, which is then hydrolysed by water forming II.
We have no evidence for either of the mechanisms
which are mere speculation only.
expect that this reagent system, as well as the synthesis
of 5, will find further use in organic synthesis.
22
The current resurgence of interest in glycobiology has
led to the synthesis of a variety of azasugars as possible
2
3
drugs by way of inhibiting carbohydrate processing
enzymes. In this connection, the synthesis of 1,6-
dideoxynojirimycin 6 (Scheme 2), a potential enzyme
24
inhibitor, has been reported in the literature. It
2
5
occurred to us that a substrate like 3 (Scheme 2) could
be hydrated in an analogous manner to a glycal leading
2
6
to the corresponding keto-aldehyde 4 which could be
condensed with an appropriately protected amine lead-
2
4a
ing to 5, which has been converted
into 1,6-
dideoxynojirimycin 6. Indeed, it was found that
Scheme 1.

S. Rani et al. / Tetrahedron Letters 44 (2003) 5001–5004
5003
Scheme 2.
General experimental procedure
9. (a) Muller, T.; Schneider, R.; Schmidt, R. R. Tetrahedron
Lett. 1994, 35, 4763–4766; (b) Leasage, S.; Perlin, A. S.
Can. J. Chem. 1978, 56, 2889–2896.
10. (a) Ferrier, R. J. Adv. Carbohydr. Chem. Biochem. 1969,
24, 199–266; (b) Ferrier, R. J.; Prasad, N. J. Chem. Soc.
(C) 1969, 570–575.
11. (a) Hadfield, A. F.; Sartorelli, A. C. Carbohydr. Res.
1982, 101, 197–208; (b) Bolitt, V.; Mioskowski, C.; Lee,
S.-G.; Falck, J. R. J. Org. Chem. 1990, 55, 5812–5813; (c)
Sabesan, S.; Neira, S. J. Org. Chem. 1991, 56, 5468–5472;
(d) Toshima, K.; Nagai, H.; Ushiski, Y.; Matsumura, S.
Synlett 1998, 1007–1009.
To a solution of 0.1 mmol of a glycal in 2 mL of
acetonitrile, was added lanthanum chloride heptahy-
drate (37 mg, 0.1 mmol), sodium iodide (15 mg, 0.1
mmol) and benzyl alcohol (11 mg, 0.1 mmol). The
mixture was then stirred at 40°C and the reaction
progress was monitored by TLC. Once the TLC
showed complete consumption of glycal, the solvent
was evaporated from the reaction mixture. The residue
was dissolved in ethyl acetate (15 mL) and washed with
a saturated solution of sodium thiosulfate (15 mL),
water (20 mL×3) and brine (20 mL) and then dried over
1
1
1
2. Pachamuthu, K.; Vankar, Y. D. J. Org. Chem. 2001, 66,
anhydrous Na SO . Removal of the solvent gave the
2
4
7511–7513.
crude product which was purified by column chro-
matography using hexane:ethyl acetate.
3. Yadav, J. S.; Reddy, B. V. S.; Reddy, K. B.; Satya-
narayana, M. Tetrahedron Lett. 2002, 43, 7009–7012.
4. (a) Wild, R.; Schmidt, R. R. Liebigs Ann. 1995, 755–764;
(
b) Barnes, N. J.; Probert, M. A.; Wightman, R. H. J.
Acknowledgements
Chem. Soc., Perkin Trans. 1996, 431–438; (c)
1
Costantino, V.; Imperatore, C.; Fattorusso, E.; Mangoni,
A. Tetrahedron Lett. 2000, 41, 9177–9180; (d) Nieschalk,
J.; O’Hagen, D. J. Fluorine Chem. 1998, 91, 159–163; (e)
Bartolozzi, A.; Capozzi, G.; Menichetti, S.; Nativi, C.
Org. Lett. 2000, 2, 251–253.
We thank the Department of Science and Technology,
New Delhi for financial support in the form of a project
(
SP/S1/G-29/2001). S.R. and A.A. thank the Council of
Scientific and Industrial Research, New Delhi for
1
1
1
5. Bettelli, E.; Cherubini, P.; D’Andrea, P.; Passacantilli, P.;
Piancatelli, G. Tetrahedron 1998, 54, 6011–6018.
6. Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002,
Senior Research Fellowships.
35, 686–694.
References
7. For some reactions using LaCl ·7H O, see: (a) Sasai, A.;
3
2
Suzuki, T.; Itoh, N.; Shibasaki, M. Tetrahedron Lett.
993, 34, 851–854; (b) Lu, J.; Bai, Y. J.; Wang, Z. I.;
Yang, B. Q.; Ma, H. R. Tetrahedron Lett. 2000, 41,
075–9078.
1
. Reddy, B. G.; Vankar, Y. D. Tetrahedron Lett. 2003, 44,
765.
. (a) Kelly, T. R. Annu. Rep. Med. Chem. 1979, 14, 288–
1
4
2
9
2
98; (b) Andrews, F. L.; Larsen, D. S. Tetrahedron Lett.
1
8. Di Deo, M.; Marcantoni, E.; Torregiani, E.; Bartoli, G.;
1
994, 35, 8693–8696.
Bellucci, M. C.; Bosco, M.; Sambri, L. J. Org. Chem.
3
4
. Remers, W. R. The Chemistry of Antitumor Antibiotics;
2
000, 65, 2830–2833 and references cited therein.
19. Physical data: 1,4,6-tri-O-benzyl-2,3-dideoxy- -arabino-
hexopyranose, IIe: [h] =+73.7 (c 1.9, CH Cl ). IR (neat)
400 MHz): l
Wiley: New York, 1979.
. Fisher, M. H.; Mrozik, H. In Macrolide Antibiotics;
Omura, S., Ed.; Academic Press: New York, 1984; pp.
D
D
2
2
−
1
1
5
53–606.
wmax: 1025, 1221 cm . H NMR (CDCl
3
5
6
. Wright, D. E. Tetrahedron 1979, 35, 1207–1237.
1.45–2.20 (m, 4H, H-2, H-2%, H-3, H-3%), 3.52–3.60 (m,
1H, H-4), 3.66–3.81 (m, 2H, H-6, H-6%), 3.83–3.87 (m,
. Henderson, F. G. In Digitalis; Fish, C.; Surawicz, B.,
Eds.; Grune and Stratton: New York, 1969; pp. 3–21.
. Lane, M. A.; Ingram, D. K.; Roth, G. S. Sci. Am. August
1H, H-5), 4.38–4.74 (m, 6H, 3×CH
1H, H-1), 7.21–7.36 (m, 15H, 3×CH C H ). C NMR
2 6 5
Ph), 4.90–4.94 (m,
2
13
7
8
2
002, 24–29.
. (a) Hanessian, S. Total Synthesis of Natural Products:
The Chiron Approach’ Pergamon Press: Oxford, 1983;
(100 MHz, a/b anomers): l 24.05, 27.09, 28.89, 29.81,
68.54, 69.18, 69.79, 70.11, 70.77, 71.07, 72.80, 72.86,
73.39, 78.08, 127.48, 127.52, 127.59, 127.65, 127.75,
127.83, 127.96, 128.25, 128.28, 137.76, 138.01, 138.23,
‘
pp. 40–183; (b) Grisebach, H. Adv. Carbohydr. Chem.
Biochem. 1978, 35, 81–126.
+
138.32, 138.37, 138.47. MS (m/z): 441 (M+Na ), 442,

5
004
S. Rani et al. / Tetrahedron Letters 44 (2003) 5001–5004
26, 272, 91. Anal. calcd for C H O : C, 77.48; H, 7.22.
Ichikawa, Y.; Porco, J. A., Jr.; Wong, C.-H. J. Am.
3
27
30
4
Found: C, 77.42; H, 7.18. 4,6-Di-O-acetyl-2,3-dideoxy-
D
-
Chem. Soc. 1991, 113, 6187–6196.
arabino-hexopyranose, IIf: [h] =+75.7 (c 0.7, CH Cl ).
24. (a) Dhavale, D. D.; Saha, N. N.; Desai, V. N. J. Org.
Chem. 1997, 62, 7482–7484; (b) Di, J.; Rajanikanth, B.;
Szarek, W. A. J. Chem. Soc., Perkin Trans. 1 1992,
2151–2152; (c) Pistia, G.; Hollingsworth, R. I. Carbohydr.
Res. 2000, 328, 467–472; (d) Bordier, A.; Compain, P.;
Martin, O. R.; Ikeda, K.; Asano, N. Tetrahedron: Asym-
metry 2003, 14, 47–51; (e) Defoin, A.; Sarazin, H.; Stre-
ith, J. Helv. Chim. Acta 1996, 79, 560–567.
D
2
2
−
1 1
IR (neat) wmax: 3467, 1745, 1729 cm . H NMR (CDCl
3
4
2
3
00 MHz): l 1.41–2.26 (m, 4H, H-2, H-2%, H-3, H-3%),
.06 (s, 3H, COCH ), 2.10 (s, 3H, COCH ), 4.12–4.24 (m,
3
3
H, H-5, H-6, H-6%), 4.66–4.88 (m, 1H, H-4), 5.31 (s, 1H,
13
H-1). C NMR (100 MHz, a/b anomers): l 20.79, 21.00,
2
6
1
1.04, 23.12, 26.87, 28.74, 29.62, 30.95, 63.25, 63.29,
7.22, 67.87, 68.53, 75.06, 85.34, 90.85, 95.82, 170.11,
71.04. MS (m/z): 250 (M+NH ): 250. Anal. calcd for
+
4
25. Das, S. K.; Mallet, J.-M.; Sinay, P. Angew. Chem., Int.
C H O : C, 51.72; H, 6.94. Found: C, 51.65; H, 6.89.
Ed. Engl. 1997, 36, 493–496.
10
16
6
2
0. This reaction has been repeated several times but no
26. Spectral data for the keto aldehyde 4: [h] =−19.3 (c 2.7,
D
−
1
1
addition of water was observed and on each occasion
product IIe was obtained (Table 1). This result is
undoubtedly very surprising but at present we have no
explanation for its formation.
CH
2
Cl ). IR (neat) wmax: 3441, 1729 cm . H NMR
2
(CDCl
400 MHz): l 2.09 (s, 3H, COCH ), 3.91 (d, 1H,
3
3
H-2, J=5.2 Hz), 4.07 (d, 1H, H-4, J=3.2 Hz), 4.09–4.12
(m, 1H, H-3), 4.48–4.76 (m, 6H, 3×CH Ph), 7.18–7.37
(m, 15H, 3×CH ), 9.74 (s, 1H, CHO). C NMR
(100 MHz, relevant and important peaks only): l 27.93
(CH ), 200.24 (-CO-CH ) and 210.51 (-CHO). MS (m/z):
455 (M+Na ), 406, 341, 306, 118, 102, 91. Anal. calcd for
: C, 74.98; H, 6.53. Found: C, 74.81; H, 6.49.
2
13
2
2
1. We thank the referee for suggesting the possibility of iodo
sugar formation followed by hydrolysis.
2. (a) McAuliffe, J. C.; Hindsgaul, O. Chemistry & Industry
C H
2 6 5
3
3
+
1
1
997, 170, 3rd March; (b) Kobata, A. Acc. Chem. Res.
993, 26, 319–324.
C H O
27 28 5
2
3. (a) Lillelund, V. H.; Jensen, H. H.; Liang, X.; Bols, M.
Chem. Rev. 2002, 102, 515–554; (b) Takebayashi, M.;
Hiranuma, S.; Kanie, Y.; Kajimoto, T.; Kanie, O.;
Wong, C.-H. J. Org. Chem. 1999, 64, 5280–5291; (c)
Kajimoto, T.; Liu, K. K.-C.; Pederson, R. L.; Zhong, Z.;
27. Condensation of benzhydrylamine was performed as per
a procedure reported in Ref. 24a (vide supra).
28. Minor products formed during this reaction were not
obtained in pure form and hence could not be character-
ised.