Ceric ammonium nitrate-catalyzed tetrahydropyranylation of alcohols and synthesis of 2-deoxy-O-glycosides

Full text of DOI:10.1021/jo0103322

J . Org. Chem. 2001, 66, 7511-7513
7511
Sch em e 1
Cer ic Am m on iu m Nitr a te-Ca ta lyzed
Tetr a h yd r op yr a n yla tion of Alcoh ols a n d
Syn th esis of 2-Deoxy-O-Glycosid es
Kandasamy Pachamuthu and Yashwant D. Vankar*
Department of Chemistry, Indian Institute of Technology
Kanpur, Kanpur 208 016, India
Ta ble 1. Tetr a h yd r op yr a n yla tion of Alcoh ols Ca ta lyzed
by Cer ic Am m on iu m Nitr a te (CAN)
vankar@iitk.ac.in
Received March 29, 2001
Protection of alcohols as tetrahydropyranyl (THP)
ethers is useful in organic synthesis mainly because of
their stability under a variety of basic conditions includ-
ing Grignard reagents, metal hydrides, alkyllithiums, etc.
Apart from the commonly used protic and Lewis acids,1
other reagents such as iodotrimethylsilane,2 triphe-
nylphosphine hydrobromide,3 montmorillonite K-10,4 het-
eropoly acids,5 and more recently tantalum chloride,6
LiClO4,7 and LiBF4 in acetonitrile8 have also been
reported in the preparation of THP ethers.
Ceric ammonium nitrate (CAN) has been employed as
a useful mild oxidizing agent in organic synthesis.9 A few
years ago we reported10 a reagent system composed of
NaNO2/CAN (2.5:1) in CH3CN for converting olefins into
vicinal nitroamides in one step. To further explore the
potential of this reagent system, we studied its behavior
on olefins such as 3,4-dihydro-2H-pyran 1 (Scheme 1),
but the reaction was not clean. To study the effect of
solvent, this reaction was carried out in methanol which,
to our surprise, was found to add on to 1 to form the
corresponding THP ether 2. Reexamination of the reac-
tion conditions revealed that a variety of alcohols reacted
with 2 equiv of dihydropyran in the presence of only a
catalytic amount of CAN (2 mol %) in CH3CN at room
temperature, forming the corresponding THP ethers in
good to excellent yields in 5-15 min.11 Our results are
summarized in Table 1. At the end of the reaction (TLC
monitoring), the reaction mixture was directly concen-
trated in a vacuum followed by purification by column
chromatography. Alternatively, we have also found that
a
This THP ether was a mixture of two anomers in the ratio of
58/42 and the reaction was carried out in CH3CN:CH2Cl2 (3:1)
mixture.
CAN adsorbed on silica gel (column grade) is also equally
effective. In this case 2 mol % of CAN adsorbed on 250
mg of SiO2 (100-200 mesh) is used for the reaction which
could be simply filtered off, after the reaction is over, and
solvent evaporated to obtain a pure product. Further
chromatographic purification was not needed in the cases
studied by us.
It is noteworthy that alcohols bearing acid-sensitive
groups, such as a ketal (entries 8, 10), an epoxide moiety
(entry 11), a cyclopropane unit (entry 12), and an acetal
(entry 18), are not affected by the acidic nature15 of the
catalyst. Further, it is also important to note that a
TBDMS group remains unaffected (entry 13) under the
present reaction conditions (2 mol % CAN in CH3CN)
especially since it has been reported in the literature12
that TBDMS and THP ethers are cleaved by CAN.
However, such a cleavage is observed by using a sto-
* To whom correspondence should be addressed. Fax: 91-512-
590007.
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; Wiley: New York, 1991. (b) Paquette, L. A.
Encyclopedia of Reagents for Organic synthesis; J ohn Wiley & Sons
Ltd. England. 1995.
(2) Olah, G. A.; Hussain, A.; Singh, B. P. Synthesis 1985, 703.
(3) Bolitt, V.; Mioskowski, C.; Shin, D.-S.; Falck, J . R. Tetrahedron
Lett. 1988, 29, 4583.
(4) Hoyer, S.; Laszlo, P.; Orlovic, M.; Polla, E. Synthesis 1986, 655.
(5) Molnar, A.; Beregszaszi, T. Tetrahedron Lett. 1996, 37, 8597.
(6) Chandrasekhar, S.; Takhi, M.; Ravindra Reddy, Y.; Mohapatra,
S.; Rama Rao, C.; Reddy, V. Tetrahedron 1997, 53, 14997.
(7) Sobhana Babu, B.; Balasubramanian, K. K. Tetrahedron Lett.
1998, 39, 9287.
(8) Sobhana Babu, B.; Balasubramanian, K. K. Synlett 1999, 8, 1261.
(9) Hwu, J . R.; Chen, K.-L.; Ananthan, S. Chem. Commun. 1994,
1425 and references therein.
(10) Reddy, M. V. R.; Mehrotra, B.; Vankar, Y. D. Tetrahedron Lett.
1995, 36, 4861.
(11) Under special experimental conditions [mildly basic with borate/
HCl buffer (pH 8)] using CAN, acetals and ketals are hydrolyzed to
the corresponding carbonyl compounds, see Marko´, I. E.; Ates, A.;
Gautier, A.; Leroy, B.; Plancher, J .-M.; Quesnel, Y.; Vanherck, J .-C.
Angew. Chem., Int. Ed. 1999, 38, 3207.
(12) Gupta, A. D.; Singh, R.; Singh, V. K. Synlett 1996, 69.
(13) Barco, A.; Pollini, G. P.; Traverso, G. Farmaco, Ed. Sci. 1970,
25, 669; Chem Abstr. 1970, 73, 98346.
(14) Manfredini, S.; Baraldi, P. G.; Bazzanimi, R.; Guarneri, M.;
Simoni, D. Tetrahedron Lett. 1994, 35, 5709.
(15) The pH of the solution was found to be 1.1 throughout the
reaction.
10.1021/jo0103322 CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/06/2001

7512 J . Org. Chem., Vol. 66, No. 22, 2001
Notes
Ta ble 2. Syn th esis of 2-Deoxy-O-Glycosid es via Cer ic
Am m on iu m Nitr a te Ca ta lyzed Ad d ition of Alcoh ols to
Glyca ls
Sch em e 2
ichiometric amount of CAN in MeOH as solvent, other
solvents such as CH3CN-H2O (19:1) or benzene-MeOH
(2:1) give poor results of the THP or TBDMS ethers
cleavage.
In an effort to further explore the scope of this reaction,
we have found that glycals 3 and 4 (Scheme 2) undergo
addition of alcohols to form the corresponding 2-deoxy-
O-glycosides 5 and 6, respectively. Because of the im-
portance of 2-deoxy sugars16 as structural units in many
biologically active natural products such as anthracyclins,
aureolic acids, compactin, enediynes, etc., several ap-
proaches have been reported in the literature to construct
2-deoxy-R-(or â)-O-glycosides stereoselectively. Stereose-
lective routes to R or â-2-deoxy-O-glycosides are known
from preformed17 2-deoxy sugars bearing a leaving group
at the anomeric center. Besides these, there have been
some direct approaches also where alcohols are added to
glycals under protic or Lewis acid catalysis.
However, because of the competing Ferrier reaction,18
not all the acids or Lewis acids permit addition of alcohols
to glycals. In this regard, acids such as MeOH‚HCl,19
cation-exchange resin AG 50WX2,20 Ph3P/HBr,21 BCl3 (or
BBr3)22 have been systematically studied to obtain 2-deoxy-
O-glycosides. In all these cases, varying R/â ratio of the
glycosides are observed with R products being the major
ones.
In the present study, CAN (2 mol %) led to the
formation of 2-deoxy-O-glycosides in good yields along
with formation of the corresponding Ferrier products 7,
albeit, in only trace amounts. Further, in most cases, R-O-
glycosides were formed as the major products. Our results
are summarized in Table 2. One disaccharide was also
synthesized using the present methodology (entry 8,
Table 2). Although galactal 3 and glucal 4 both reacted
readily with a variety of alcohols, reactions with 3 were
cleaner. Initial experiments with glucal 4 using only 2
mol % of CAN, as used for galactal based reactions,
indicated the formation of more amount of the Ferrier
product23 (entries 9-12, Table 2). On the other hand,
when 4 equiv of CAN in CH3CN were used in these
a
Isolated yield of the corresponding Ferrier products in paren-
b
theses. R/â ratio of the corresponding Ferrier products in paren-
theses. c Experiments conducted with 4 equiv of CAN. Com-
d
pounds 6d and 7d were inseparable.
reactions, 2-deoxy products were formed as the major
products along with only trace amount of the Ferrier
products. These 2-deoxy-O-glycosides were formed as a
mixture of two anomers in which R-anomer was the major
one in the cases studied (entries 13, 14). Except for the
studies using BBr3 (or BCl3),22 the results from other
catalysts are comparable with the present work in terms
of the R/â ratio. Mechanistically, it is therefore proposed
that CAN reacts with alcohols generating HNO3 (a
Brønsted acid) which presumably activates glycals (or
dihydropyran) and then the alkoxide moiety is trans-
ferred leading to the formation of 2-deoxy-O-glycosides
(or THP ethers) as shown in Figure 1.
(16) J u¨tten, R.; Greven, R. Polysaccharides in Medicinal Applica-
tions; Dumitriu, S., Ed.; Marcell Dekker: New York, 1996; pp 339-
410. (b) Wright, D. E. Tetrahedron 1979, 35, 1207. (c) Kirschning, A.;
Bechthold, A. F. W.; Rohr, J . Topics Curr. Chem. 1997, 188, 1.
(17) Schene, H.; Waldmann, H. Synthesis 1999, 1411. (b) Capozzi,
G.; Mannocci, F.; Meichetti, S.; Nativi, C. Chem. Commun. 1997, 2291.
(c) Toshima, K.; Kasumi, K.; Matsumura, S. Synlett 1999, 1332. (d)
Roush, W. R.; Narayan, S. Org. Lett. 2000, 1, 899 and references
therein.
(18) Ferrier, R. J . Adv. Carbohydr. Chem. Biochem. 1996, 24, 199.
(b) Ferrier, R. J .; Prasad N. J . Chem. Soc. C 1999, 570.
(19) Hadfield, A. F.; Sartorelli, A. C. Carbohydr. Res. 1982, 101, 197.
(20) Sabesan, S.; Neira, S. J . Org. Chem. 1991, 56, 5468.
(21) Bolitt, V.; Mioskowski, C.; Lee, S.-G.; Falck, J . R. J . Org. Chem.
1990, 55, 5812.
(22) Toshima, K.; Nagai, H.; Ushiski, Y.; Matsumura, S. Synlett
1998, 1007.
(23) For a recent report on the use of CAN for effecting the Ferrier
reaction see: (a) Linker, T.; Sommermann, T.; Gimisis, T.; Chatgila-
loglu, C. Tetrahedron Lett. 1998, 39, 9637, and (b) Yadav, J . S.; Reddy,
B. V. S.; Pandey, S. K. New J . Chem. 2001, 25, 538.
The present procedure is simple requiring only 2 mol
% of CAN which is easy to handle and is relatively cheap.
Also, it is noteworthy that tert-butyl alcohol undergoes
addition in these reactions. We therefore expect that our
findings to procure THP ethers as well as 2-deoxy-O-
glycosides using CAN will be useful in organic synthesis.

Notes
J . Org. Chem., Vol. 66, No. 22, 2001 7513
THP eth er 2m : 1H NMR δ 0.03, 0.01 (2s, 6H), 0.90 (s, 9H),
1.5-2.0 (m, 6H), 3.4-3.89 (m, 4H), 4.57 (m, 2H), 7.26-7.40 (m,
5H). 13C NMR δ -5.54, -4.81, 18.29, 18.94, 19.35, 25.4, 25.79,
25.85, 30.5, 61.82, 67.8, 79.17, 99.0, 126.27-142.5 (6C). MS
(FAB) m/z (relative intensity): 337 (2) [M+ + 1]. Anal. Calcd for
C
19H32O3Si : C, 67.81; H, 9.58. Found: C, 67.80; H, 9.32.
Gen er a l P r oced u r e for th e Syn th esis of 2-Deoxy Su ga r s.
A glycal (1 mmol) and an alcohol (1 mmol) were combined with
a catalytic amount (2 mol %) of CAN in anhydrous CH3CN (4
mL) and stirred at ambient temperature. After 3-5 h, the
reaction mixture was extracted with ether and washed with
NaHCO3 and brine, dried over anhydrous Na2SO4, and concen-
trated in
a vacuum. The residue was purified by column
chromatography to obtain products as a mixture of R and â
anomers which were characterized by spectroscopic and analyti-
cal means and compared the data wherever available in the
literature (5a ,24 5b,25 5e,26 5h ,27 6a ,24 6c,28 6d ,29 7a ,30 7b31).
Attempts to separate the anomers were not successful.
Allyl 2-d eoxy-3,4,6-tr i-O-ben zyl-r/â-D-ga la ctop yr a n osid e
5c: 1H NMR δ 2.0-2.04 and 2.2-2.28 (m, 2H), 3.46-3.64 (m,
2H), 3.90-4.0 (m, 4H), 4.14 (dd, 1H, J ) 4.87, 9.75 Hz), 4.4-
4.90 (m, 6H), 5.02 (d, J ) 1.95 Hz, H-1) 5.17-5.27 (m, 2H), 5.85-
5.95 (m, 1H), 7.25-7.35 (m, 15H). 13C NMR δ 31.10, 67.87, 69.50,
69.88, 70.44, 72.94, 73.43, 74.26, 74.75, 97.06 (C-1), 117.03,
127.29-128.38 (18 C), 134.26. Characteristic signals for the
â-anomer: 1H NMR:δ 4.64 (dd, J ) 3.7, 9.3 Hz, H-1). 13C NMR:
δ 103 (C-1). MS (FAB) m/z (relative intensity) 475 (3) [M+ + 1],
474 (100) [M+]. Anal. Calcd for C30 H34 O5: C, 75.92; H, 7.22.
Found: C, 75.80; H, 7.31.
F igu r e 1.
Ack n ow led gm en t. We thank the Department of
Science & Technology, New Delhi, for financial as-
sistance through a project (DST/SP/S1/G-07/1997). One
of us (K.P.) thanks the Council of Scientific and Indus-
trial Research, New Delhi, for senior research fellow-
ship.
Exp er im en ta l Section
Gen er a l. Infrared spectra were recorded on Bruker FT/IR
Vector 22 spectrometers. 1H and 13C NMR spectra were recorded
on J EOL LA-400 NMR spectrometer in solutions of CDCl3 using
tetramethylsilane as the internal standard. FAB mass spectra
were obtained using J EOL SX 102/DA-6000 spectrometer.
Elemental analyses were carried out in Coleman automatic C,
H, N, O analyzer.
Acetonitrile was distilled from P2O5 followed by distillation
from CaH2 prior to use. Ceric ammonium nitrate was purchased
from Merck (India) Ltd., Bombay, and was dried at 80 °C.
Gen er a l P r oced u r e for th e P r ep a r a tion of Tetr a h yd r o-
p yr a n yl Eth er s. To a stirred solution of an alcohol (5 mmol)
and CAN (0.1 mmol, 2 mol %) in dry CH3CN (5 mL) is added a
solution of 3,4-dihydro-2H-pyran (10 mmol) in dry CH3CN (2
mL) dropwise over a period of 5 min. After the addition, stirring
is continued for another 5-15 min and the solvent removed on
a rotary evaporator under reduced pressure. The residue is
passed through a pad of silica gel to obtain the pure product.
Usin g SiO2. To a stirred solution of CAN (55 mg, 0.1 mmol)
in dry CH3CN (5 mL) were added 250 mg of SiO2 (100-200
mesh), an alcohol (5 mmol), and 3,4-dihydro-2H-pyran (10 mmol)
in dry CH3CN sequentially. After the reaction was over, it was
filtered and the filtrate evaporated to yield the pure product.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectral data of 2h -l, 2n , 2p , 2q, 5b, 5d , 5f, 5g, and 7c. This
information is available free of charge via the Internet at
http://pubs.acs.org.
J O0103322
(24) Truelove, J . E.; Hussain, A. A.; Kostenbauder, H. B. J . Pharm.
Sci. 1980, 69, 231.
(25) Toshima, K.; Kasumi, K.; Matsumura, S. Synlett 1999, 813.
(26) Schene, H.; Waldmann, H. Synthesis 1999, 1411.
(27) Hao, L.; Meijin, C.; Kang, Z. Tetrahedron Lett. 1997, 38, 6143.
(28) Takeuchi, K.; Higuchi, S.; Mukaiyama, T. Chem. Lett. 1997,
969.
(29) Hashimoto, S.-I.; Ai, S.; Sakamoto, H.; Hakajima, M.; Yanagiya,
Y.; Ikegami, S. Synlett 1995, 1271.
(30) Descotes, G.; Martin, J . C. Carbohydr. Res. 1977, 56, 168.
(31) Lesueur, C.; Nouguier, R.; Bertrand, M. P.; Hoffmann, P.; De
Mesmaeker, A. Tetrahedron 1994, 50, 5369.