WCl6,9a,11 FeCl3,12 and DCC/SnCl413), metal triflates (e.g.,
TMSOTf,14 Sc(NTf2)3,15 and Bi(OTf)316), and N-bromosuc-
cinimide (NBS).17 Many of these are acidic in nature.
Therefore, existing acid-sensitive groups such as THP ether
and acetonide groups are not always fully compatible, and
the catalysts cannot be recovered and reused. In addition,
the preparation of the prerequisite 1,1-dimethoxyacetals
somewhat limits their practical applications. In marked
contrast, the direct condensation between the parent alde-
hydes and alcohols is much less used. A few methods such
as the use of concentrated H2SO4 as a catalyst and dehydrat-
ing agent,18 or p-TSA in refluxed arenes,19 or stoichiometric
efficient formation of acetals from aldehydes and diols
catalyzed by vanadyl triflate.
The direct condensation between benzaldehyde derivatives
and 1,2-ethandiol 2a (1.1-1.2 equiv) was first tested as a
model reaction with various vanadyl and oxometallic species
(3-5 mol %) in CH2Cl2. Among them, only vanadyl triflate
(VO(OTf)2‚xH2O) could effect clean and complete conver-
sion (in 20 min) at ambient temperature. The product 4a was
isolated in pure form (97% yield) by straight aqueous wash
to remove both the catalyst and the residual diol (Scheme
1). Notably, such a simple and mild protocol was unprec-
20
ZnCl2 have been documented, but the substrate scope is
somewhat limited.
Scheme 1. Test Acetal Formations between Aromatic
4,6-O-Benzylidene acetal-protected monosaccharides are
important precursors in the synthesis of complex carbohy-
drates.21 So far, the most well-adopted procedure involves
the use of a 1,1-dimethoxyacetal and the saccharide catalyzed
by p-TSA or camphorsulfonic acid (CSA) in polar solvents.
The direct condensation requires the use of ZnCl2 in neat
aldehyde.20,22 An ideal atom-efficient catalytic version of this
process at ambient temperature remains to be realized.
Aldehydes and Simple 1,2- and 1,3-Diols
For the past three years, we have unraveled several water-
tolerant vanadyl and other oxometallic species as recoverable,
amphoteric catalysts for nucleophilic acyl substitutions
(NAS) of anhydrides23a,b and methyl esters23c (including
transesterification) with protic nucleophiles (alcohols, amines,
and thiols); these catalysts have high functional group
compatibility and chemoselectivity. In continuation of our
work in this area of catalysis (including Mukaiyama aldol
additions, oxidative couplings of 2-naphthols, and DNA
photocleavages),24 herein we describe a new moisture-
tolerant, environmentally benign protocol for the atom-
edented with other metal-mediated catalysis. A couple of
other more polar diol substrates such as 1-benzoylated
glycerol 2b and pentaerythritol 3 were further examined.
These two cases were performed in CH3CN due to the poor
solubility of the substrates in CH2Cl2. The reactions were
complete in 20-22 h, and the corresponding benzaldehyde
acetals (5 and 6) were similarly isolated both in 92% yield.
With the preliminary success of using vanadyl triflate for
the acetalization of benzaldehyde with simple diols, we
turned our attention to functionalized monosaccharides as
diol surrogates. S-Tolyl-thioglycoside 7 was first tested under
previous standard reaction conditions (5 mol % VO(OTf)2‚
xH2O, 1.1-1.3 equiv of PhCHO). Among several different
solvents examined, only CH3CN led to satisfactory results
due to the reasonably good substrate solubility and intact
catalytic activity.25
A series of monosaccharides (7-13) bearing O-, S-, and
Se-glycosidic (OMe, S-Tol, SePh) bonds with varying C2-
substituents (OH, OBn, N3, and NPhth) were further em-
ployed for the optimal catalytic protocol (Table 1). In all
cases, the absolute configuration at the glycosidic positions
was retained without any anomerization, bond cleavage, or
oxidation of sulfides and selenides. The acetalization was
completely regio- and chemoselective. Only 4,6-O-ben-
zylidene products were obtained in D-gluco- (7-9) and
D-galactopyranosides (10-12). No 3,4- or 2,3-O-benzylidene
products were observed in the cases of 7a, 8-10a, 11a, and
12.
(10) Gemal, A. L.; Luche, J.-L. J. Org. Chem. 1979, 44, 4187.
(11) Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synth. Commun. 1999,
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(12) Zajac, W. W.; Byrne, K. J. J. Org. Chem. 1970, 35, 3375.
(13) Anderson, S. H.; Uh, H.-S. Synth. Commun. 1973, 3, 125.
(14) (a) Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980,
21, 1357. (b) Masaaki, K.; Wataru, H. J. Org. Chem. 2003, 68, 3413.
(15) Ishihara, K.; Karumi, Y.; Kubota, M.; Yamamoto, H. Synlett 1996,
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(16) Leonard, N. M.; Oswald, M. C.; Freiberg, D. A.; Nattier, B. A.;
Smith, R. C.; Mohan, R. S. J. Org. Chem. 2002, 67, 5202.
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(b) Karimi, B.; Ebrahimian, G. R.; Seradj, H. Org. Lett. 1999, 1, 1737.
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7036.
(20) Fletcher, H. G., Jr. Methods Carbohydr. Chem. 1963, 2, 307.
(21) Carbohydrates in Chemistry and Biology; Ernst, B., Hart, G. W.,
Sinay¨, P., Eds.; Wiley-VCH: Weinheim, Germany, 2000; Vol. 1.
(22) Ziegler, T. Carbohydrate Chemistry; Boons, G.-J., Ed.; Blackie
Academic & Professional: London, 1998; pp 21-45.
(23) (a) Chen, C.-T.; Kuo, J.-H.; Li, C.-H., Barhate, N. B.; Hon, S.-W.;
Li, T.-W.; Chao, S.-D.; Liu, C.-C.; Li, Y.-C.; Chang, I.-H.; Lin, J.-S.; Lin,
C.-J.; Chou, Y.-C. Org. Lett. 2001, 3, 3729. (b) Chen, C.-T.; Kuo, J.-H.;
Pawar, V. D.; Munot, Y. S.; Weng, S.-S.; Ku, C.-H.; Liu, C.-Y. J. Org.
Chem. 2005, 70, 1188. (c) Chen, C.-T.; Kuo, J.-H.; Ku, C.-H.; Weng, S.-
S.; Liu, C.-Y. J. Org. Chem. 2005, 70, 1328.
(24) (a) Chen, C.-T.; Hon, S.-W.; Weng, S.-S. Synlett 1999, 816. (b)
Hon, S.-W.; Li, C.-H.; Kuo, J.-H.; Barhate, N. B.; Liu, Y.-H.; Wang, Y.;
Chen, C.-T. Org. Lett. 2001, 3, 869. (c) Barhate, N. B..; Chen, C.-T. Org.
Lett. 2002, 4, 2529. (d) Chen, C.-T.; Lin, J.-S.; Kuo, J.-H.; Weng, S.-S.;
Cuo, T.-S.; Lin, Y.-W.; Cheng, C.-C.; Huang, Y.-C.; Yu, J.-K.; Chou, P.-
T. Org. Lett. 2004, 6, 4471. (e) See also: Chen, C.-T.; Pawar, V. D.; Munot,
Y. S.; Chen, C.-C.; Hsu, C.-J. Chem. Commun. 2005, 2483.
(25) (a) Solvent effects are as follows: CH2Cl2 (24 h, 32%), THF (24 h,
46%), dioxane (24 h, 51%). (b) A brief survey on the effects of vanadyl
and oxometallic species on the test reaction in CH3CN revealed that vanadyl
triflate was the most reactive one. Other catalysts such as VO(OTs)2‚xH2O
(14 h, 71%), MoOCl4 (14 h, 68%), and MoO2Cl2 (14 h, 75%) showed
moderate activities.
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Org. Lett., Vol. 7, No. 15, 2005