Remarkable β-selectivity in the synthesis of β-1-C- arylglucosides: Stereoselective reduction of acetyl-protected methyl 1-C-arylglucosides without acetoxy-group participation

Article abstract of DOI:10.1021/jo071051i

(Chemical Equation Presented) An efficient and practical process to generate β-C-arylglucoside derivatives was achieved. The process described involves Lewis acid mediated ionic reduction of a peracetylated 1-C-aryl methyl glucoside derived from the addit

Full text of DOI:10.1021/jo071051i

with a high degree of selectivity despite concerns that participa-
tion by a C-2 acetoxy group might interfere with hydride
delivery from the R-face as well as ring deactivation may not
allow an efficient reduction process. We have discovered, also
unexpectedly, the critical role of water during the Lewis acid
mediated reductions with silanes. This simple change from the
traditional use of benzyl ethers to ester protecting groups enables
a new and more efficient synthetic method of â-1-C-arylglu-
cosides.
Remarkable â-Selectivity in the Synthesis of
â-1-C-Arylglucosides: Stereoselective Reduction
of Acetyl-Protected Methyl 1-C-Arylglucosides
without Acetoxy-Group Participation
Prashant P. Deshpande,*,‡ Bruce A. Ellsworth,*,†
Frederic G. Buono,‡ Annie Pullockaran, Janak Singh,
Thomas P. Kissick, Ming-H. Huang, Hildegard Lobinger,§
Theodor Denzel,§ and Richard H. Mueller‡
One popular method to prepare this class of compounds,
developed by Kishi3 and extended to the synthesis of C-
arylglucosides by Kraus,4,5 involves addition of an aryllithium
reagent to a 2,3,4,6-tetra-O-benzyl-D-gluconolactone followed
by the reduction of the resulting lactol with Et3SiH.2 We wished
to avoid the use of 2,3,4,6-tetra-O-benzyl-D-glucose as the
carbohydrate synthon for several reasons: the starting material
is expensive, thereby limiting its usefulness for a commercial
process; the starting material must be oxidized at C-1 to a lactone
that is syrupy, thus posing stability concerns, and this same C-1
position is reduced later in the sequence; the intermediate lactol
does not always give high selectivity in the reduction process;6
and more critically, hydrogenolytic deprotection conditions are
incompatible with our desired range of functional groups.7,8
Several of these concerns are resolved by the use of per-tri-
methylsilyl-D-gluconolactone 1 and the subsequent use of acetate
protecting groups. This lactone was previously used by Horton
and co-workers9 in the synthesis of 1-C-methyl glucose deriva-
tive 4 due to the ease of trimethylsilyl ether protection/
deprotection, and relative stability of this group under strongly
basic alkyllithium addition conditions.9 In that synthesis the
intermediate peracetylated lactol (2) was reduced under Raney
Ni conditions via a proposed episulfonium intermediate 3,
Process Research and DeVelopment, Bristol-Myers Squibb,
1 Squibb DriVe, New Brunswick, New Jersey 08903,
Bristol-Myers Squibb, Princeton, New Jersey 08543,
Bristol-Myers Squibb, Regensburg, Germany, and Department of
Metabolic Disease DiscoVery Chemistry, Bristol-Myers Squibb,
Hopewell, New Jersey 08534
prashant.deshpande@bms.com
ReceiVed June 13, 2007
An efficient and practical process to generate â-C-arylglu-
coside derivatives was achieved. The process described
involves Lewis acid mediated ionic reduction of a peracety-
lated 1-C-aryl methyl glucoside derived from the addition
of an aryl-Li to selectively protected δ-D-gluconolactone. The
reduction of the 2-acetoxy-1-C-oxacarbenium ion intermedi-
ates proceeds with a high degree of selectivity to give â-C-
arylglucosides without 2-acetoxy group participation. Fur-
thermore, during the reduction process we also identified an
unprecedented critical role of water. By changing from the
usual benzyl ether protecting groups because of cost and
chemical compatibility concerns, the new process is made
additionally efficient and highly selective.
(2) For recent reviews of C-arylglucoside, synthetic methods, see: (a)
Postema, M. H. D. Tetrahedron 1992, 48, 8545-8599. (b) Jaramillo, C.;
Knapp, S. Synthesis 1993, 1-20. (c) Du, Y.; Linhardt, R.-J. Tetrahedron
1998, 54, 9913-9959. (d) Postema, M. H. D. C-Glycoside Synthesis; CRC
Press: Boca Raton, FL, 1995. (e) Levy, D. E.; Tang, C. The Chemistry of
C-glycosides; Pergamon: Oxford, UK, 1995. (f) Lee D. Y. W.; He, M.
Curr. Top. Med. Chem. 2005, 5, 1333-50.
(3) (a) Lewis, M. D.; Cha, K.; Kishi, Y. J. Am. Chem. Soc. 1982, 104,
4976-4978. (b) Babirad, S. A.; Wang, Y.; Kishi, Y. J. Org. Chem. 1987,
52, 1370-1372.
(4) Kraus, G. A.; Molina, M. T. J. Org. Chem. 1988, 53, 752-753.
(5) For other references in the area see: (a) Lancelin, J.-M.; Zollo, P.
H. A.; Sinay, P. Tetrahedron Lett. 1983, 24, 4833-4836. (b) Czernecki,
S.; Ville, G. J. Org. Chem. 1989, 54, 610-612. (c) Dondoni, A.; Marra,
A.; Schermann, M.-C. Tetrahedron Lett. 1993, 34, 7323-7326. (d) Xie, J.;
Durrat. F.; Valery, J.-M. J. Org. Chem. 2003, 68, 7896-7898. (e) Larson,
C. H.; Ridgway, B. H.; Shaw, J. T.; Smith, D. M.; Woerpel. K. A. J. Am.
Chem. Soc. 2005, 127, 10879-10884 and refereces cited therein.
(6) Ellsworth, B. A.; Doyle, A. G.; Patel, M.; Carceres-Cortes, J.; Meng,
W.; Deshpande, P. P.; Pullockaran, A.; Washburn, W. N. Tetrahedron:
Asymmetry 2003, 14, 3243-3247.
â-1-C-Arylglucosides belong to a class of natural products
that are known for their biological activity and medicinal
properties, and stereochemical control is the major challenge
of their chemical synthesis.1,2 We report a new synthesis of â-C-
arylglucosides where we observed that ester-protected glucosides
bearing a 1-C-aryl group can be reduced under ionic conditions
(7) Ellsworth, B.; Washburn, W. N.; Sher, P. M.; Wu, G.; Meng, W.
U.S. patent 6515117, 2004.
‡ Bristol-Myers Squibb, New Brunswick.
(8) Tetra-O-acetylglucopyranosyl bromide serves as an inexpensive donor
for C-arylglucoside synthesis eliminating an oxidation/reduction protocol
at C-1; however, bromide displacement requires 9 equiv of an aryl Grignard
reagent to give C-arylglucosides in moderate yield. (a) Panigot, M. J.;
Humphries, K. A.; Curley, R. W. J. Carbohydr. Chem. 1994, 13, 303-
321. (b) Lee, D. Y. W.; Zhang, W.-Y.; Karnati, V. V. R. Tetrahedron Lett.
2003, 44, 6857-6859.
Bristol-Myers Squibb, Princeton.
§ Bristol-Myers Squibb, Regensburg.
† Bristol-Myers Squibb, Hopewell.
(1) (a) Hacksell, U.; Daves, G. D., Jr. Prog. Med. Chem. 1985, 22, 1-65.
(b) Suzuki, K.; Matsumoto, T. Recent Progress in the Chemical Synthesis
of Antibiotics and Related Microbial Products; Lukas, G., Ed.; Springer-
Verlag: Berlin, Germany, 1993; Vol. 2, pp 352-403. (c) Franz, G.; Grun,
M. Planta Med. 1983, 47, 131-140.
(9) Horton, D.; Priebe, W. Carbohydr. Res. 1981, 94, 27-41.
10.1021/jo071051i CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/13/2007
9746
J. Org. Chem. 2007, 72, 9746-9749

SCHEME 1. Synthesis of an Alkyl Glucoside 4
SCHEME 2. Synthesis of an 1-C-Aryl Methyl Glucoside 6
SCHEME 3. Synthesis of â-C-Arylglucoside 7
TABLE 1. Selectivities of the Reduction of Peracetylated
Scheme 1;10 this methodology is not applicable for the synthesis
of the targeted pharmaceutically important aryl-substituted sugar
derivatives.
1-C-Arylglucosides 6a-i (Scheme 3)
compd 6
R
7: â:R ratioa
a
b
c
d
e
f
g
h
4-Me
3-Me
2-Me
4-OMe
4-Cl
3,4,5-(OMe)3
3-i-Pr
aryl ) 2-naphthyl
4-Me
30:1
20:1
20:1
>65:1
22:1
22:1
24:1
19:1
48:1
Starting with lactone 1, we prepared several 1-C-aryl methyl
glucosides 5 according to a modification of Barrett’s protocol11
to study the Lewis acid-mediated silane reduction. First, we
significantly improved the yields of the addition of a variety of
aryl lithiums to persilylated gluconolactone (1) by replacing THF
with THF/toluene or THF/heptanes solvent combinations. We
observed that lower solvent polarity12a,b and low temperature
provided significant improvements in the yield as enolization
and de-silylation were suppressed.12c Subsequent in situ trans-
ketalization with methanesulfonic acid/methanol prevented the
formation of open chain carbohydrate derivatives while con-
comitantly removing the TMS protecting groups.9 The resulting
methyl 1-C-arylglucosides 5 were protected to give the corre-
sponding tetraacetates 6a-h in a one pot process (Scheme 2).
Acetate groups are well-known to stabilize proximal carbe-
nium ion intermediates by anchimeric assistance, and this
strategy is often used to control selectivity in the formation of
1,2-trans-glucosides.13,14 They also participate in substitution
reactions and silane-mediated reductions under cationic con-
ditions.15-17 Since we wanted to perform a cationic reduction
i (6-deoxy)
a The content of the R isomer was estimated by HPLC and LCMS.
with 1,2-syn-hydride delivery, the choice of an acetyl group
may seem unusual. However, the steric and electronic effects
of the 1-C-aryl group may outweigh the neighboring effect of
the acetate group on the oxocarbenium ion intermediate.
We report that, in the case of methyl tetra-O-acetyl-1-C-
arylglucosides 6a-h (Scheme 3 and Table 1), a C-2-acetoxy
group does not participate to any extent to direct delivery of
the hydride from the â-face of the oxocarbenium ion intermedi-
ate (Scheme 3). When peracetylated glucosides (6a-h) were
subjected to BF3‚Et2O-mediated reduction with triethylsilane in
acetonitrile, we observed a highly selective reduction from the
R-face to give â-1-C-aryl-1-deoxyglucosides 7 (Table 1) in good
yields.
(10) Wolfrom, M. L.; Hung, Y.-L.; Horton, D. J. Org. Chem. 1965, 30,
3394-3400.
(11) To prepare spirocyclic C-arylglycosides see: (a) Barrett A. G. M.;
Pena, M.; Willardsen A. J. J. Chem. Soc., Chem. Commun. 1995, 11, 1147-
1148. (b) Barrett A. G. M.; Pena, M.; Willardsen, A. J. J. Org. Chem. 1996,
61, 1082-1100. (c) Chafiq, H.; Hitchcock, S. A.; Esteban, A. R.; Sanchez-
Martinez EP 0997472A2, 2000.
Initially, the reactions carried out on small scale advanced
to completion, furnishing â-isomers 7a-e18 and 7f-i with high
selectivity. However, on a multikilogram scale, we noticed that
the reaction stalled and the reduction was incomplete, although
its selectivity was not affected. Further investigations revealed
(12) Barrett11a,b and Chafiq11c and co-workers observed ∼30-35% yields.
(a) Lecomte, V.; Stephan, E.; Bideau, F. L.; Jaouen, G. Tetrahedron Lett.
2002, 43, 3463-3465. (b) Lecomte, V.; Stephan, E. L.; Jaouen, G.
Tetrahedron 2003, 59, 2169-2176. (c) Deshpande, P. P.; Ellsworth, B.
A.; Singh, J.; Denzel, T. W.; Lai, C.; Crispino, G.; Randazzo, M.;
Gougoutas, J. Z. U.S. patent 2004138439 A1 20040715, 2004.
(13) Boons, G.-J. Contemp. Org. Synth. 1996, 3, 173-200.
(14) Nukada, T.; Berces, A.; Zgierski, M. Z.; Whitfield, D. M. J. Am.
Chem. Soc. 1998, 120, 13291-13295.
(15) Minehan, T. G.; Kishi, Y. Tetrahedron Lett. 1997, 38, 6815-6818.
(16) Sherman, J. S.; Gray, G. R. Carbohydrate Res. 1992, 231, 221-
235. Jeffery, A.; Nair, V. Tetrahedron Lett. 1995, 36, 3627-3630.
(17) Beignet, J.; Tiernan, J.; Woo, C. H.; Kariuki, B. M.; Cox, L. R. J.
Org. Chem. 2004, 69, 6341-6356.
J. Org. Chem, Vol. 72, No. 25, 2007 9747

the â-C-aryl-glycosylated product 7i. Evidently, the C-6 acetoxy
group played no role in the â selectivity of compound 7.
Therefore, in the case of peracetylated 1-C-arylglucosides,
neighboring groups do not participate to stabilize the oxocar-
benium ion during the reduction reaction. A similar observation
was also reported by Giannis and Sandhoff24 during the
allylation of peracetylated glucopyranoses with allylsilane and
BF3‚Et2O.
Our results provide sufficient evidence for a predominantly
axial hydride attack that is most likely due to the known
stereoelectronic preference of glucosides.25 Thus, we are able
to produce â-C-arylglucosides as the major products.
This communication describes an efficient, general, and
practical process to generate peracetylated C-arylglucoside
derivatives. Our initial concern that the Lewis acid-mediated
silyl hydride reduction of peracetylated substrates, such as
compound 6, might not reduce efficiently and not provide good
â-selectivity due to C-2 ester neighboring group participation26
proved unfounded. We also show that the less expensive and
more readily available triethylsilane can be used for the
reduction to obtain peracetylated C-arylglucosides with >96%
selectivity for the â-anomer, unlike the reduction of benzyl
protected phenyl-glucosides,6 where sterically hindered silanes
are required to achieve high selectivity. We show also the
unprecedented role of water in the reduction reaction with a
plausible explanation.
Since the trimethylsilyl-protected lactone (1) can be prepared
in one step by using very inexpensive starting materials, this
process is more practical for the synthesis of commercial
C-arylglucoside products. This method allows the use of a
greater diversity of aryl substituents, avoiding chemical incom-
patibilities with hydrogenolytic deprotections used in the 2,3,4,6-
tetra-O-benzyl-D-gluconolactone2 route, and providing improved
stereoselectivity in the reduction process as compared to tetra-
O-benzyl-protected 1-C-arylglucosides. These advantages have
made it the route of choice for us on any scale.7
FIGURE 1. Substituent effects on reduction rate (eq 1).
that the presence of water in the reaction mixture was critical
for this reduction process.19 On laboratory scale, the reactions
did not stall, presumably as a result of the presence of
adventitious water. We established that 1 mole of water and
>2 equiv of BF3‚Et2O were required to drive the reduction to
completion.
We propose that the addition of water to BF3‚Et2O generates
a strong Bronsted acid, such as F3B-O+H2, that may accelerate
the formation of an oxocarbenium ion intermediate.20 This
reagent combination appears to be essential to compensate for
the inductive deactivating effect of the acetoxy substituents. This
proposal is consistent with our previous observations6 that
reduction of tetrabenzyl-1-C-arylglucopyranose lactols does not
require added water since stronger coordination of the Lewis
acid is expected with the lactol (as compared to methyl ketal
6). The reduction of the electron-rich p-methoxy-substituted
analogue (6d) performed well under anhydrous conditions since
oxocarbenium ion formation may be facilitated by the p-MeO-
aryl group in this case.
We also established that the reduction selectiVity of C-
arylglucosides does not strongly depend on the nature of the
aryl substituent. For example, benzylic cation destabilizing and
stabilizing substituents in compounds 6e (R ) Cl) and 6d (R
) OMe) provided products 7e12e and 7d,12c,d respectively, with
high â-stereoselectivity and in good yield. The reductions were
also followed by reaction calorimetry21 to determine the in-
fluence of aryl substituents on the reaction rate. As is evident
from the plots in Figure 1, electron-withdrawing groups, as in
6e, cause a slower reaction than analogues carrying electron-
rich groups (e.g., 6d). The overall reactivity trend was p-OMe
> 3,4,5-tri-OMe > p-Me > 2-naphthyl > m-Me > p-Cl (Figure
1).
Experimental Section
(I) General Procedure for the Syntheses of Methyl 1-C-
Arylglucoside Tetraacetates 6a-i. A dry, three-necked, round-
bottomed flask equipped with a magnetic stirrer and internal
temperature probe was charged with aryl bromide (39.6 mmol)
under nitrogen gas atmosphere. Dry THF (15 mL) and toluene (60
mL) were added and the resulting solution was cooled with stirring
to -78 °C. n-BuLi (10 M in hexanes, 4.75 mL) was added, keeping
(21) (a) Mathew, S. P.; Gunathilagan, S.; Roberts, S. M.; Blackmond,
D. G. Org. Lett. 2005, 7, 4847-4850. (b) Blackmond, D. G. Angew. Chem.,
Int. Ed. 2005, 44, 4302-4320.
The C-6 protecting group is also known to influence reactivity
at the anomeric center of carbohydrates,22 so compound 6i
(Table 1), lacking a C-6 acetoxy substituent, was prepared
following a literature method23 and subjected to our reduction
conditions. We still observed high selectivity (48:1) to form
(22) (a) Eby, R.; Schuerch, C. Carbohydr. Res. 1974, 34, 79-90. (b)
Tokimoto, H.; Fujimoto, Y.; Fukase, K.; Kusumoto, S. Tetrahedron:
Asymmetry 2005, 16, 441-447.
(23) (a) Koos, M.; Gajdos, J. Molecules 1997, 2, M39. (b) Koto, S.;
Morishima, N.; Mori, Y.; Tanaka, H.; Hayashi, S.; Iwai, Y.; Zen, S. Bull.
Chem. Soc. Jpn. 1987, 60, 2301- 2303.
(18) (a) Marquez, F.; Arriandiaga, M. V.; Urbieta, M. T. An. Quim.,
Ser. C 1983, 79 (3, Suppl. 1), 428-31. (b) Panigot, M. J.; Curley, R. W.,
Jr. J. Carbohydr. Chem. 1994, 13, 293-302. (c) Frick, W.; Schmidt, R. R.
Lieb. Ann. Chem. 1989, 6, 565-70. (d) Chen, S.; Gao, Y.; Cai, M. Huaxue
Tongbao 1985, 19-21. (e) Caddick, S.; Motherwell, W. B.; Wilkinson, J.
A. J. Chem. Soc., Chem. Commun. 1991, 10, 674-5.
(19) The reduction of compound 7e was studied with varying concentra-
tions of water (0.4, 0.7, 1.0, 1.3, and 1.6 equiv). The conversions for these
concentrations were 89%, 97.6%, 97.8%, 92.9%, and 71.5%, respectively,
with no change in the â-selectivity.
(20) Akiyama, T.; Takaya, J.; Kagoshima, H. Chem. Lett. 1999, 947-
948.
(24) Giannis, A.; Sandhoff, K. Tetrahedron Lett. 1985, 26, 1479-1482.
(25) (a) Deslongchamps, P. Stereoelectronic Effects in Organic Chem-
istry; Pergamon: New York, 1983; pp 209-221. (b) Rolf, D.; Bennek, J.
A.; Gray, G. R. J. Carbohydr. Chem. 1983, 2, 373-83. (c) Pothier, N.;
Goldstein, S.; Deslongchamps, P. HelV. Chim. Acta 1992, 75, 604-620.
(d) Juaristi, E.; Cuevas, G. Tetrahedron 1992, 48, 5019-5087.
(26) Participation from a C-2 substituent during glycosidation is well-
known: (a) Koenigs, W.; Knorr, E. Ber. 1901, 34, 957. (b) Hanessian, S.;
Banoub, J. Carbohydr. Res. 1977, 53, C13-C16. (c) Varela, O.; Marino,
C.; Ledermeker, R. M. Carbohydr. Res. 1986, 155, 247-51. (d) Tosin,
M.; Murphy, P. V. Org. Lett. 2002, 4, 3675-3678. (e) Urban, D.;
Skrydstrup, T.; Beau, J. M. J. Org. Chem. 1998, 63, 2507-2516.
9748 J. Org. Chem., Vol. 72, No. 25, 2007

the internal temperature <-65 °C. After 1 h at -78 °C, the
lithiation reaction was complete by HPLC (an aliquot was quenched
into methanol and diluted with acetonitrile for HPLC).
mmol) was added. To this solution was added BF3‚Et2O (0.3 mL,
2.4 mmol) over 5 min, and the mixture was allowed to warm to 15
°C over 20 min. Upon completion, the reaction was quenched with
aqueous saturated NaHCO3 (3 mL); the pH of the aqueous layer
was 7. The organic layer was washed with brine (5 mL) and the
solution was dried (MgSO4). The mixture was filtered and the
solvent was evaporated to give the corresponding product (7a-i).
4-(2,3,4,6-Tetra-O-acetyl-â-D-glucopyranosyl)toluene (7a):18a
1H NMR (400 MHz, CDCl3) δ 1.79 (s, 3H), 1.99 (s, 3H), 2.01
(s,3H), 2.07 (s, 3H), 2.31(s, 3H), 3.83 (m,1H), 4.12 (m,1H), 4.26
(dd, J ) 12.3, 4.9 Hz, 1H), 4.34 (d, J ) 9.8 Hz, 1H), 5.13 (t, J )
9.5 Hz, 1H), 5.21 (t, J ) 9.6 Hz, 1H), 5.31 (t, J ) 9.3 Hz, 1H),
7.12 (d, J ) 8.0 Hz, 2H), 7.21 ppm (d, J ) 8.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 20.37, 20.59, 20.62, 20.72, 21.17, 62.33,
68.56, 72.49, 74.26, 75.99, 80.09, 127.03, 129.08, 133.12, 138.63,
168.86, 169.46, 170.33, 170.69 ppm. Compound 7a: HRMS calcd
for C21H26O9 (M + NH4) 440.1921, found 440.1905.
In a second round-bottomed flask, persilylated gluconolactone9
(47.5 to 55.4 mmol) was stirred in toluene (50 mL) and cooled to
-78 °C. The solution of aryl lithium from above was then
cannulated into this solution, keeping the internal temperature <-65
°C. After 2 h at -78 °C, the reaction mixture was warmed to -50
°C. A solution of methanesulfonic acid (6 mL, 92.5 mmol) in
methanol (100 mL) was added and the mixture was then slowly
warmed to room temperature. After18 h, saturated aqueous NaHCO3
was added slowly and the aqueous layer was extracted with EtOAc
(2 × 200 mL). The EtOAc extracts were combined with the organic
layer, washed with saturated NaHCO3 solution and brine, and dried
(MgSO4). The mixture was filtered, and the solvent was removed
on a rotary evaporator. The product was dried under pump vacuum
to give the methyl glucoside. The crude material was used in the
next reaction. DMAP (26 mg, 0.2 mmol), Hunig’s base (22 mL,
123 mmol), and acetic anhydride (11 mL, 117 mmol) were added
sequentially to a solution of the crude methyl 1-C-arylglucoside
(∼22 mmol) in toluene (120 mL) under nitrogen atmosphere at
ambient temperature. After stirring for 6 h the reaction was complete
by HPLC. A 1 N H3PO4 solution was added to the reaction mixture
to neutralize to pH 6.5-7 and the aqueous layer was extracted
further with EtOAc (100 mL). The organic extracts were combined
and washed with brine (50 mL), dried (MgSO4), and filtered. The
filtrate was evaporated and the product was purified by silica gel
column chromatography, using EtOAc/heptane as the eluents. The
fractions containing the desired product were combined and
concentrated, and the material was dried under vacuum to yield
the peracetylated methyl 1-C-arylglucosides (6a-i, ∼70-80%
yields based on aryl bromide).
3-(2,3,4,6-Tetra-O-acetyl-â-D-glucopyranosyl)toluene (7b):18a
1H NMR (400 MHz, CDCl3) δ ppm 1.8 (s, 3 H), 2.00 (s, 3 H),
2.06 (s, 3 H), 2.09 (s, 3 H), 2.34 (s, 3H), 3.81-3.83 (ddd, J )
10.0, 4.72, 2.42 Hz, 1 H), 4.16 (dd, J ) 12.3 and 2.2 Hz, 1 H), 4.3
(dd, J ) 4.8, 8.5 Hz, 1 H), 4.37 (d, J ) 9.7 Hz, 1 H), 5.14 (t, J )
9.7 Hz, 1 H), 5.23 (t, J = 9.7 Hz, 1 H), 5.33 (t, J = 9.7 Hz, 1 H),
7.12 (d, J ) 7.9 Hz, 2 H), 7.16 (s, 1 H), 7.22 (t, J ) 7.9 Hz, 1 H).
13C NMR (100 MHz, CDC13) δ ppm 20.4, 20.6, 20.8, 21.4, 62.4,
68.7, 72.6, 74.3, 76.1, 80.3, 124.3, 127.7, 128.3, 129.7, 136.1, 138.1,
166.9, 169.5, 170.4, 170.7. HRMS calcd for C21H26O9 (M+H) )
423.1655, found 423.1673.
Acknowledgment. We thank Professors Eric Carreira and
Donna Blackmond, Samuel J. Danishefsky, and Dr. David
Kronenthal for helpful discussions and thoughtful review of this
manuscript.
(II) General Procedure for the Reduction of Methyl 1-C-
Arylglucosides (6a-i) to 7a-i. A solution of methyl glucoside 6
(1.0 mmol) in CH3CN (5 mL) was prepared at room temperature
under nitrogen atmosphere and the water content was adjusted to
1 mol equiv (Karl Fischer analysis) by addition of needed water.
The solution was cooled in an ice bath and Et3SiH (0.5 mL, 3.2
1
Supporting Information Available: General methods and H
and 13C NMR are for compounds 6a-i, 7c-i, and 8. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO071051I
J. Org. Chem, Vol. 72, No. 25, 2007 9749