An efficient stereoselective dihydroxylation of glycals using a bimetallic system, RuCl3/CeCl3/NaIO4

Article abstract of DOI:10.1021/jo0526385

A catalytic dihydroxylation reaction on glycals has been developed using a bimetallic oxidizing system to furnish sugar 1,2-diols in a highly setroselective manner.

Full text of DOI:10.1021/jo0526385

SCHEME 1
An Efficient Stereoselective Dihydroxylation of
Glycals using a Bimetallic System,
†
RuCl3/CeCl3/NaIO4
Pallavi Tiwari and Anup Kumar Misra*
Medicinal and Process Chemistry DiVision,
Central Drug Research Institute, Chattar Manzil Palace,
Lucknow-226 001, U.P., India
TABLE 1. Stereoselective cis-Dihydroxylation of Glycals and
Unsaturated Carbohydrate Derivatives using RuCl3/CeCl3‚7H2O/
NaIO4 in EtOAc/CH3CN/H2O at 0 °C
akmisra69@rediffmail.com
ReceiVed December 23, 2005
A catalytic dihydroxylation reaction on glycals has been
developed using a bimetallic oxidizing system to furnish
sugar 1,2-diols in a highly setreoselective manner.
Suitably protected 1,2-dihydroxy carbohydrate derivatives are
useful synthetic intermediates in several organic transformations
such as in the synthesis of polyhydroxylated chiral natural
products,1 O-glycosides2 and C-glycosides.3 They have also used
in the O-glycosylations involving intramolecular aglycon de-
livery.4 Conventionally, sugar-derived 1,2-diols are prepared
using the reaction sequence of conversion of acetobromosugars
to the corresponding sugar ortho esters followed by hydrolysis
of ortho esters to the sugar 1,2-diols.5 Although this method
has been used widely, use of excess s-collidine6 as solvent
during the formation of ortho esters is a serious drawback of
this protocol. Other reported methods for the preparation of
sugar 1,2-diols include (a) osmium-catalyzed (OsO4-NMO)
dihydroxylation of glycals;2a,c (b) conversion of glycals to 1,2-
glycal epoxides using dimethyldioxirane followed by hydrolytic
opening of 1,2-glycal epoxides;7 and (c) reaction of glycals with
a Together with D-gulo-isomer as minor product (∼20%).
† C.D.R.I. communication no. 6921.
(1) Fu¨rstner, A.; Konetzki, I. J. Org. Chem. 1998, 63, 3072.
(2) (a) Sanders, W. J.; Kiessling, L. L. Tetrahedron Lett.1994, 35, 7335.
(b) Shi, L.; Kim, Y.-J.; Gin, D. Y. J. Am.Chem. Soc. 2001, 123, 6939. (c)
Charette, A. B.; Marcoux, J.-F.; Cote, B. Tetrahedron Lett. 1991, 32, 7215.
(d) Trumtel, M.; Tavecchia, P.; Veyrie`res, A.; Sinay¨, P. Carbohydr. Res.
1989, 191, 29.
(3) (a) Vidal, T.; Haudrechy, A.; Langlois, Y. Tetrahedron Lett. 1999,
40, 5677. (b) Hung, S.-C.; Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1996,
35, 2671. (c) Carpintero, M.; Nieto, I.; Fernandez-Mayoralas, A. J. Org.
Chem. 2001, 66, 1768.
(4) (a) Barresi, F.; Hindsgual, O. J. Am. Chem. Soc. 1991, 114, 9376.
(b) Stork, G.; Kim, G. J. Am. Chem. Soc. 1992, 114, 1087. (c) Bols, M.
Chem. Commun. 1992, 913.
(5) (a) Lichtenthaler, F. W.; Schneider-Adams, T. J. Org.Chem. 1994,
59, 6728. (b) Broder, W.; Kunz, H. Carbohydr. Res. 1993, 249, 221. (c)
Schmidt, R. R.; Effenberger, G. Carbohydr. Res. 1987, 171, 59. (d) Wu,
E.; Wu, Q. Carbohydr. Res. 1993, 250, 327.
oxone in acetone.8 There are several drawbacks in the above-
mentioned methods, which include the use of very expensive
and toxic reagents, difficulties in removing the Osmium salt
from the products, use of very unstable epoxidation reagent,
and formation of C-2 epimer. Use of oxone for the dihydroxy-
lation of glycals is very convenient but always resulted in
formation of a C-2 epimeric mixture as major and minor product
in our hands. In view of the importance of 1,2-sugar diols in
the synthesis of oligosaccharides and natural products, a strong
impetus has been given to develop a mild, less toxic, economi-
cally convenient, and user-friendly reaction protocol for their
preparation. Recently, we noted a few reports on the oxidative
use of RuCl3 in a combination of NaIO4 and a Brønsted or Lewis
(6) Lemieux, R. U.; Morgan, A. R. Can. J. Chem. 1965, 43, 2199.
(7) (a) Danishefsky, S. J.; Halcomb, R. L. J. Am. Chem. Soc. 1989, 111,
6661. (b) Iserloh, U.; Dudkin, V.; Wang, Z.-G.; Danishefsky, S. J.
Tetrahedron Lett. 2002, 43, 7027.
(8) Rani, S.; Vankar, Y. D. Tetrahedron Lett. 2003, 44, 907.
10.1021/jo0526385 CCC: $33.50 © 2006 American Chemical Society
Published on Web 02/25/2006
J. Org. Chem. 2006, 71, 2911-2913
2911

SCHEME 2
SCHEME 3
SCHEME 4
acid in a specific solvent mixture in the preparation of cis-1,2-
diols from simple alkenes in a highly stereoselective manner.9
We reasoned that use of RuCl3/CeCl3‚7H2O/NaIO4, a bimetallic
reagent system for the dihydroxylation of glycals, could produce
only sugar 1,2-cis-diols as it does with the simple alkenes. In
this endeavor, we report a highly stereoselective dihydroxylation
of glycals toward the formation of 1,2-sugar diols (Scheme 1).
This methodology has been further extended for the preparation
of disaccharides of uncommon sugars (Table 1, entries 11 and
12).
were quite stable. This stereoselective dihydroxylation has been
applied to the preparation of disaccharides containing mannose,
talose, and gulose using a reaction sequence consisting of Ferrier
rearrangement followed by cis-dihydroxylation. Additionally,
sugar 1,2-di-O-acetates thus obtained can be further converted
to 2-acetoxy glycals by anomeric bromination using 33% HBr-
AcOH and subsequent elimination of HBr on treatment with
DBU. Synthesis of ulosyl bromides for their use in the
glycosylation can also be prepared from the 2-acetoxy glycal
or enol acetate by treatment with N-bromosuccinimide as
reported by Lichtenthaler et al.10 (Scheme 2).
In a first set of experiments, tri-O-acetyl-D-glucal was treated
with RuCl3/CeCl3‚7H2O/NaIO4 in EtOAc/CH3CN/H2O at 0 °C,
varying the quantity of CeCl3‚7H2O and NaIO4. It was observed
that treatment of tri-O-acetyl-D-glucal with a combination of
RuCl3/CeCl3‚7H2O/NaIO4 in a mixed solvent at 0 °C can furnish
3,4,6-tri-O-acetyl-D-glucose-1,2-diol in 15 min. A series of
differentially protected glycals was transformed into 1,2-diols
following the similar reaction condition. An anomeric mixture
of sugar 1,2-diols was isolated, which were further acetylated
for the structural confirmation of the products. From the spectral
analysis, it was found that the stereochemistry at C-2 is
equatorial in every case. In another set of experiments, a variety
of 2,3-unsaturated mono- and disaccharides were also reacted
with reagent combination toward the formation of 2,3-
unprotected mono- and disaccharides. Exclusive formation of
cis-diol was observed depending on the stereochemistry of the
substituents present in the substrates. As expected, no trace of
the formation of other epimer was observed in TLC and spectral
analysis. Under these reaction conditions, common protecting
groups used in the protection of carbohydrates (e.g., benzylidene,
isopropylidene, TBDPS, acetyl, benzyl, benzoyl, pivaloyl, etc.)
The plausible mechanism for the formation of exclusively
single epimeric cis-diol can be explained by considering the
syn-addition of the RuO4 to the olefinic bond from the less
sterically hindered site and hydrolysis of the Ru-complex
activated by CeCl3 (Schemes 3 and 4).
In summary, a mild, stereoselective protocol for the cis-
dihydroxylation of glycals and unsaturated sugar derivatives has
been developed using an economically convenient, less toxic
bimetallic catalyst system. The reaction is very fast and yields
are excellent. The reaction protocol has been further extended
toward the formation of 2-acetoxy glycal derivatives and unusual
disaccharides.
(9) (a) Plietker, B.; Niggemann, M. Org. Lett. 2003, 5, 3353. (b) Plietker,
B.; Niggemann, M. Org. Biomol. Chem. 2004, 2, 1116. (c) Plietker, B.;
Niggemann, M. J. Org. Chem. 2005, 70, 2402.
(10) Lichtenthaler, F. W.; Schneider-Adams, T. J. Org. Chem. 1994, 59,
6728.
(11) Tai, A.-A.; Kulkarni, S. S.; Hung, S.-C. J. Org. Chem. 2003, 68,
8719.
(12) Horton, D.; Luetzow, A. E. Carbohydr. Res. 1968, 7, 101.
2912 J. Org. Chem., Vol. 71, No. 7, 2006

ized by spectroscopic and analytical techniques. Spectral data of
compounds 1b, 5b, 6b, 7b, and 10b are reported in the cited
references. Spectral data for all compounds are reported in
Supporting Information.
Experimental Section
General Reaction Protocol for cis-Dihydroxylation of Glycal
or 2,3-Unsaturated Glycoside. A mixture of NaIO4 (300 mg, 1.4
mmol) and CeCl3‚7H2O (38 mg, 0.1 mmol) in H2O (2 mL) was
stirred at room temperature for a few minutes. The reaction mixture
was cooled to 0 °C, and to the cooled reaction mixture were added
EtOAc (3 mL), CH3CN (6 mL), and RuCl3‚H2O (5.2 mg, 0.025
mmol) successively. After the mixture stirred for 2.0 min, a solution
of substrate (1.0 mmol) in EtOAc (3 mL) was added, and the
resulting heterogeneous mixture was stirred until the full consump-
tion of the starting material (Table 1). After completion of the
reaction (TLC), the reaction mixture was diluted with EtOAc (25
mL). The organic layer was washed with aqueous NaHCO3 and
water, dried (Na2SO4), and concentrated under reduced pressure.
The crude product was purified over SiO2 using hexanes-EtOAc
as eluant. Acetylation of the diol was carried out conventionally
using acetic anhydride and pyridine, and the product was character-
Acknowledgment. Instrumentation facilities from SAIF,
CDRI are gratefully acknowledged. P.T. thanks CSIR, New
Delhi for providing a Senior Research fellowship. This project
was funded by Department of Science and Technology (DST),
New Delhi (SR/FTP/CSA-10/2002), India.
Supporting Information Available: General experimental
1
methods, H NMR and 13C NMR spectral data and spectra of all
products, and 2D HSQC, HMBC, and COSY spectra of compounds
9b, 11b, and 12b. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO0526385
J. Org. Chem, Vol. 71, No. 7, 2006 2913