The 4-(tert-Butyldiphenylsiloxy)-3-fluorobenzyl group: A new alcohol protecting group, fully orthogonal with the p-methoxybenzyl group and removable under desilylation conditions

Article abstract of DOI:10.1021/jo900026e

A new benzyl ether-type protecting group for alcohols, the 4-(tert-butyldiphenylsiloxy)-3-fluorobenzyl group, is introduced. The protecting group is introduced by means of the readily prepared benzyl bromide and is cleaved with tetrabutylammonium fluoride

Full text of DOI:10.1021/jo900026e

The 4-(tert-Butyldiphenylsiloxy)-3-fluorobenzyl Group: A New
Alcohol Protecting Group, Fully Orthogonal with the
p-Methoxybenzyl Group and Removable under Desilylation
Conditions
David Crich,*,†,‡,§ Linfeng Li,† and Michio Shirai‡
Department of Chemistry, Wayne State UniVersity, 5101 Cass AVenue, Detroit, Michigan 48202,
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois
60607, and Centre de Recherche CNRS de Gif-sur-YVette, Institut de Chimie des Substances Naturelles,
AVenue de la Terrasse, 91198 Gif-sur-YVette, France
dcrich@icsn.cnrs-gif.fr
ReceiVed January 7, 2009
A new benzyl ether-type protecting group for alcohols, the 4-(tert-butyldiphenylsiloxy)-3-fluorobenzyl
group, is introduced. The protecting group is introduced by means of the readily prepared benzyl bromide
and is cleaved with tetrabutylammonium fluoride in dimethylformamide under microwave irradiation.
The fluoride substituent provides stability to oxidizing conditions, such that the new protecting group is
fully compatible with the removal of p-methoxybenzyl ethers with DDQ. Applications of the new protecting
group in the direct stereocontrolled synthesis of ꢀ-mannopyranosides are presented.
Introduction
an unanticipated consequence of the steric bulk of silyl ether
protecting groups. Thus, while 4,6-O-benylidene-protected thi-
omannopyranosides, and their sulfoxides, carrying benzyl ethers
at positions 2 and 3 are known to be superb donors in the direct
stereocontrolled formation of ꢀ-mannopyranoside linkages,5 an
analogous system 1 carrying a 3-O-tert-butyldimethylsilyl group
Benzyl and silyl ethers are some of the most widely used
alcohol protecting groups.1 The high degree of mutual orthogo-
nality which they display makes combinations of them attractive
protecting systems for complex polyols, whether in the context
of total synthesis, combinatorial library synthesis, or oligosac-
charide synthesis. In addition to their differing reactivity patterns,
the two types of protecting group differ significantly in their
steric properties. The appreciably greater bulk of the silyl ethers
leads to the much reduced chelating ability of R-siloxycarbonyl
systems2 and contributes to the inverted conformations adopted
by some polylsilylated six-membered ring systems.3 In the
course of a study4 targeted at the synthesis of the common core
pentasaccharide of the N-linked glycoproteins, we uncovered
(3) (a) Walford, C.; Jackson, R. F. W.; Rees, N. H.; Clegg, W.; Heath, S. L.
J. Chem. Soc., Chem. Commun. 1997, 1855–1856. (b) Yamada, H.; Okajima,
K.; Imagawa, H.; Nagata, Y.; Nishizawa, M. Tetrahedron Lett. 2004, 45, 4349–
4351. (c) Yamada, H.; Tanigakiuchi, K.; Nagao, K.; Okajima, K.; Mukae, T.
Tetrahedron Lett. 2004, 45, 9207–9209. (d) Okajima, K.; Mukae, T.; Imagawa,
H.; Kawamura, Y.; Nishizawa, M.; Yamada, H. Tetrahedron 2005, 61, 3497–
3506. (e) Marzabadi, C. H.; Anderson, J. E.; Gonzalez-Outeirino, J.; Gaffney,
P. R. J.; White, C. G. H.; Tocher, D. A.; Todaro, L. J. J. Am. Chem. Soc. 2003,
125, 15163–15173. (f) Jensen, H. H.; Pedersen, C. M.; Bols, M. Chem.sEur. J.
2007, 13, 7576–7581. (g) Okada, Y.; Nagata, O.; Taira, M.; Yamada, H. Org.
Lett. 2007, 9, 2755–2758.
(4) Dudkin, V. Y.; Crich, D. Tetrahedron Lett. 2003, 44, 1787–1789.
(5) (a) Crich, D.; Sun, S. J. Org. Chem. 1997, 62, 1198–1199. (b) Crich, D.;
Sun, S. Tetrahedron 1998, 54, 8321–8348. (c) Crich, D.; Smith, M. J. Am. Chem.
Soc. 2001, 123, 9015–9020. (d) Crich, D.; Lim, L. B. L. Org. React. 2004, 64,
115–251. (e) Crich, D. In Glycochemistry: Principles, Synthesis, and Applications;
Wang, P. G., Bertozzi, C. R., Eds.; Dekker: New York, 2001; pp 53-75. (f)
Crich, D.; Banerjee, A.; Li, W.; Yao, Q. J. Carbohydr. Chem. 2005, 24, 415–
424. (g) Crich, D.; Banerjee, A.; Yao, Q. J. Am. Chem. Soc. 2004, 126, 14930–
14934. (h) Crich, D.; Banerjee, A. Org. Lett. 2005, 7, 1935–1938. (i) Crich, D.;
Yao, Q. J. Am. Chem. Soc. 2004, 126, 8232–8236. (j) Dudkin, V. Y.; Miller,
J. S.; Danishefsky, S. J. J. Am. Chem. Soc. 2004, 126, 736–738.
† Wayne State University.
‡ University of Illinois at Chicago.
§ Institut de Chimie des Substances Naturelles.
(1) (a) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic Synthesis,
4th ed.; Wiley: New York, 2007. (b) Kocienski, P. J. Protecting Groups, 3rd
ed.; Thieme: Stuttgart, 2005.
(2) (a) Kahn, S. D.; Keck, G. E.; Hehre, W. J. Tetrahedron Lett. 1987, 28,
279–280. (b) Keck, G. E.; Castellino, S. Tetrahedron Lett. 1987, 28, 281–284.
(c) Shambayati, S.; Blake, J. F.; Wierschke, S. G.; Jorgensen, W. L.; Schreiber,
S. L. J. Am. Chem. Soc. 1990, 112, 697–703.
2486 J. Org. Chem. 2009, 74, 2486–2493
10.1021/jo900026e CCC: $40.75 2009 American Chemical Society
Published on Web 02/25/2009

4-(tert-Butyldiphenylsiloxy)-3-fluorobenzyl Group
SCHEME 1. Assembly of
4-(tert-Butyldiphenylsiloxy)-3-fluorobenzyl Bromide
in place of a benzyl ether was found to favor the formation of
R-mannosides. This result was even more surprising in view of
the fact that the regioisomeric 3-O-benzyl-2-O-tert-butyldim-
ethylsilyl system 2 showed adequate ꢀ-selectivity. Thus, the
more remote 3-O-silyl group in 1 had a greater influence on
the stereochemical outcome of the glycosylation than the 2-O-
silyl ether adjacent to the reactive site in 2. We rationalized
this effect in terms of a buttressing interaction between the 3-O-
silyl and 2-O-benzyl ethers in 1, which forces the benzyl closer
to the anomeric center leading ultimately to the reduced
stereoselectivity.6,7
SCHEME 2. Orthogonality with p-Methoxybenzyl Ethers
This interesting reactivity pattern alerted us to the need for a
protecting group having the steric characteristics of a benzyl
ether but which is removable under typical desilylation condi-
tions. We report here on the design and successful implementa-
tion of such a system.8
Results and Discussion
A significant range of substituted benzyl ether protecting
groups is reported in the literature,1,9 many of which have been
applied in carbohydrate chemistry.10 However, until the descrip-
tion of the p-siletanylbenzyl ether,11 none could be considered
to be cleavable under typical desilylation conditions.12 In
designing such a protecting group, we first considered the
obvious simple p-siloxybenzyl type systems but dismissed them
on the grounds that they would be too acid sensitive and subject
to cleavage under the same oxidative conditions commonly used
for the removal of p-methoxybenzyl1,13 and naphthylmethyl
ethers.14 Rather, we focused on p-siloxybenzyl systems bearing
an electron-withdrawing substituent intended to provide en-
hanced stability under acidic and oxidative conditions, in much
the same way that a 3-chloro substituent enhances the stability
of the 4-azidobenzyl ethers.15 In view of our requirement for a
system with the steric properties of a simple benzyl ether we
targeted therefore the 3-fluoro-4-siloxybenzyl groups.
Starting from commercially available 3-fluoro-4-hydroxy-
benzoic acid (3), 4-(tert-butyldiphenylsiloxy)-3-fluorobenzyl
bromide (5) was assembled in three convenient steps (Scheme
1).
Before proceeding to applications in oligosaccharide synthesis,
the orthogonality of the new protecting group with p-methoxy-
benzyl ethers was tested. Thus, monoalkylation of 2,2-dibenzyl-
1,3-propanediol 6 with p-methoxybenzyl chloride gave 7, which
was converted to the fully protected 8 on treatment with sodium
hydride in THF in the presence of HMPA, followed by the addition
of 5 (Scheme 2). Exposure of 8 to DDQ in wet dichloromethane
at room temperature resulted in cleavage of the p-PMB ether in
89% yield. On the other hand, exposure of 8 to tetrabutylammo-
nium fluoride in a variety of solvents, including DMF, at room
temperature resulted only in the removal of the silyl ether, giving
phenol 10 in high yield. This result was not totally unexpected in
view of similar observations reported in the literature on saponi-
fication of p-acetoxybenzyl ethers.9b Fortunately, when desilylation
was conducted under microwave irradiation at 90 °C, a satisfactory
85% yield of the desired alcohol 7 was obtained (Scheme 2). The
complete orthogonality of the new protecting group with p-
methoxybenzyl ethers, for which the system had been designed,
was thus established.
(6) (a) Crich, D.; Dudkin, V. Tetrahedron Lett. 2000, 41, 5643–5646. Also
see: (b) Code´e, J. D. C.; Hossain, L. H.; Seeberger, P. H. Org. Lett. 2005, 7,
3251–3254.
(7) We have provided one solution to this problem in the form of the
minimally sterically bulky propargyl ethers. (a) Crich, D.; Jayalath, P. Org. Lett.
2005, 7, 2277–2280. (b) Crich, D.; Jayalath, P.; Hutton, T. K. J. Org. Chem.
2006, 71, 3064–3070. (c) Crich, D.; Wu, B. Org. Lett. 2006, 8, 4879–4882. (d)
Crich, D.; Karatholuvhu, M. S. J. Org. Chem. 2008, 73, 5173–5176.
(8) During the course of this investigation, Seeberger and co-workers reported
their solution to this problem in the form of the triisopropylsilyloxymethyl ether:
(a) Code´e, J. D. C.; Kro¨ck, L.; Castagner, B.; Seeberger, P. H. Chem.sEur. J.
2008, 14, 3987–3994.
(9) (a) Plante, O. J.; Buchwald, S. L.; Seeberger, P. H. J. Am. Chem. Soc.
2000, 122, 7148–7149. (b) Jobron, L.; Hindsgaul, O. J. Am. Chem. Soc. 1998,
121, 5835–5836. (c) Kang, J.; Lim, G. J.; Yoon, S. K.; Kim, M. Y. J. Org.
Chem. 1995, 60, 564–577. (d) Xia, J.; Alderfer, J. L.; Piskorz, C. F.; Matta,
K. L. Chem.sEur. J. 2000, 6, 3442–3451. (e) Gaunt, M. J.; Yu, J.; Spencer,
J. B. J. Org. Chem. 1998, 63, 4172–4173. (f) Lipták, A.; Borbás, A.; Jánossy,
L.; Szilágyi, L. Tetrahedron Lett. 2000, 41, 4949–4953. (g) Reddy, C. R.;
Chittiboyina, A. G.; Kache, R.; Jung, J.-C.; Watkins, E. B.; Avery, M. A.
Tetrahedron 2005, 61, 1289–1295.
(10) Crich, D., Ed. Handbook of Reagents for Organic Synthesis: Reagents
for Glycoside, Nucleotide, and Peptide Synthesis; Wiley: Chichester, 2005.
(11) Lam, H.; House, S. E.; Dudley, G. B. Tetrahedron Lett. 2005, 46, 3283–
3285.
(12) A p-siloxybenzylidene acetal protecting group for diols has been
described: (a) Kaburagi, Y.; Osajima, H.; Shimada, K.; Tokuyama, H.; Fukuyama,
T. Tetrahedron Lett. 2004, 45, 3817–3821. For a siletanylbenzylidene acetal,
see: House, S. E.; Poon, K. W. C.; Lam, H.; Dudley, G. B. J.Org. Chem. 2006,
71, 420–422.
Turning to applications in glycosidic bond formation, treatment
of phenyl 4,6-O-benzylidene-1-thio-R-D-mannopyranoside 11 with
(13) Wuts, P. G. M. In Handbook of Reagents for Organic Synthesis:
Reagents for Glycoside, Nucleotide, and Peptide Synthesis; Crich, D., Ed.; Wiley:
Chichester, 2005; pp 425-428.
(14) Csa´va´s, M.; Szabo´, Z. B.; Borba´s, A.; Lipta´k, A. In Handbook of
Reagents for Organic Synthesis: Reagents for Glycoside, Nucleotide, and Peptide
Synthesis; Crich, D., Ed.; Wiley: Chichester, 2005; pp 459-460.
(15) Egusa, K.; Fukase, K.; Kusumoto, S. Synlett 1997, 675–676.
(16) (a) Garegg, P. J.; Iversen, T.; Oscarson, S. Carbohydr. Res. 1976,
50, C12–C14. (b) Pozsgay, V. Carbohydr. Res. 1979, 69, 284–286. (c)
Lergenmüller, M.; Nukada, T.; Kuramochi, K.; Dan, A.; Ogawa, T.; Ito, Y.
Eur. J. Org. Chem. 1999, 1367–1376. (d) Crich, D.; Li, W.; Li, H. J. Am.
Chem. Soc. 2004, 126, 15081–15086.
J. Org. Chem. Vol. 74, No. 6, 2009 2487

Crich et al.
TABLE 2. Selective Deprotection of Glycosidesa
SCHEME 3. Preparation of Glycosyl Donor 13
TABLE 1. Glycosylation Reactions with Donor 13
a The deprotections were conducted with the anomerically pure
ꢀ-anomer. b Heating in a microwave reactor. c Conventional heating in
DMF solution.
with the results set out in Table 2. As in the model experiments
(Scheme 2), all attempts at debenzylation with TBAF at lower
temperatures resulted only in the cleavage of the silyl group.
In a final demonstration of the ability of the new protecting
group to support ꢀ-mannosylation reactions, donor 13 was
coupled to alcohols 18 and 22 to generate the disaccharides 25
and 26, both with excellent ꢀ-selectivity (Scheme 4), thereby
establishing the viability of this new protecting group for use
in the synthesis of mannans containing both the ꢀ-(1f2)5g and
ꢀ-(1f3)16d linkages.
While the focus of this project has been on the application
of the new benzyl protecting group in glycosylation reactions,
we anticipate that it will also find use in the broader context of
organic synthesis. In particular, we anticipate that the new
protecting group will find application in situations requiring
chelation control and the subsequent cleavage of the protecting
group under desilylation conditions. Finally, we note that while
we have concentrated here on benzyl ethers derived from
bromide 5 based on the tert-butyldiphenylsilyl moiety, we expect
that analogous chemistry will be possible with the corresponding
4-(tert-butyldimethylsiloxy)-3-fluorobenzyl and 4-(triisopropyl-
siloxy)-3-fluorobenzyl systems.
p-methoxybenzyl chloride under phase-transfer conditions16 af-
forded the 2-O-PMB ether 12. Benzylation with 5 and sodium
hydride in DMF then provided the orthogonally protected glycosyl
donor 13 (Scheme 3).
With acceptor 13 in hand, the glycosylation of a series of
four acceptor alcohols was undertaken. These reactions were
carried out in dichloromethane at -60 °C, with prior activation
of the thioglycoside with a combination of 1-benzenesulfinyl
piperidine (BSP),5c,d,f and trifluoromethanesulfonic anhydride
in the presence of the convenient non-nucleophilic base 2,4,6-
tri-tert-butylpyrimidine (TTBP),17 before addition of the alcohol.
Like the action of trifluoromethanesulfonic anhydride on gly-
cosyl sulfoxides,18 this activation protocol converts the thiogly-
coside to a covalent R-glycosyl trifluoromethanesulfonate,5c
which then undergoes SN2-like reaction with the alcohol with
the intermediacy of a transient contact ion pair.19 As is clear
from Table 1, all couplings proceeded in high yield and with
excellent ꢀ-selectivity.20
Experimental Section
General Experimental Details. Experiments conducted using
microwave irradiation were carried out with a Biotage Initiator Exp
(17) Crich, D.; Smith, M.; Yao, Q.; Picione, J. Synthesis 2001, 323–326.
(18) Crich, D.; Sun, S. J. Am. Chem. Soc. 1997, 119, 11217–11223.
(19) Crich, D.; Chandrasekera, N. S. Angew. Chem., Int. Ed. 2004, 43,
5386–5389.
Glycosides 14-17 were then subjected to partial deprotection
by exposure to DDQ at room temperature and by treatment with
TBAF in THF at 90 °C under microwave heating conditions
2488 J. Org. Chem. Vol. 74, No. 6, 2009

4-(tert-Butyldiphenylsiloxy)-3-fluorobenzyl Group
SCHEME 4. Disaccharide Synthesis
US operating at a high absorbance level and with temperature
determination by means of an infrared sensor.
General Procedure for the Removal of 4-(tert-Butyldiphenylsi-
lyloxy)-3-fluorobenzyl Group with Conventional Heating (Method
B). To a stirred solution of the substrate and 4 Å molecular sieves
in DMF (0.05 M) was added TBAF (2 equiv, 1.0 M in THF). The
reaction mixture was heated to 90 °C for 3 h and then cooled to rt,
filtered through Celite, and washed with EtOAc. The filtrate was
diluted with EtOAc and washed with H2O. The aqueous phase was
extracted with EtOAc three times, and the combined organic phase
was dried and concentrated. Purification by column chromatography
on silica gel, eluting with hexane/ethyl acetate mixtures, afforded
the corresponding alcohols.
General Procedure for the Removal of p-Methoxybenzyl Group.
To a stirred solution of the substrate in CH2Cl2/H2O (9/1, 0.05 M)
was added DDQ (2 equiv) in one portion. The reaction mixture
was stirred at rt for 2 h and then diluted with CH2Cl2 and washed
with brine. The organic layer was separated, dried over Na2SO4,
and concentrated. Chromatographic purification on silica gel, eluting
with hexane/ethyl acetate mixtures, afforded the corresponding
alcohols.
2,2-Dibenzyl-3-(4-methoxybenzyloxy)propan-1-ol (7). From 2,2-
Dibenzylpropane-1,3-diol 6. To a stirred solution of 2,2-dibenzyl-
propane-1,3-diol (309 mg, 1.21 mmol) in THF (5 mL) at 0 °C was
added sodium hydride (60%, 63 mg, 1.57 mmol). After 10 min,
PMBCl (213 µL, 1.57 mmol) was added and the reaction mixture
stirred under reflux for 6 h. The reaction mixture was concentrated,
dissolved in CH2Cl2, and washed with saturated NH4Cl and brine.
The organic layer was separated, dried over Na2SO4, and concen-
trated. Chromatographic purification (7.5% ethyl acetate in hexane)
on silica gel gave 7 (369 mg, 81%). From 8: Prepared by the general
procedure for the removal of 4-(tert-butyldiphenylsilyloxy)-3-
fluorobenzyl group using a microwave reactor (method A) with a
yield of 25.4 mg (85%): colorless oil; 1H NMR (500 MHz, CDCl3)
δ 7.32-7.20 (m, 12H), 6.94-6.92 (m, 2H), 4.43 (s, 2H), 3.83 (s,
3H), 3.47 (d, J ) 5.5 Hz, 2H), 3.25 (s, 2H), 2.82 (d, J ) 13.5 Hz,
1H), 2.78 (d, J ) 13.5 Hz, 1H), 2.37 (t, J ) 5.5 Hz, 1H); 13C
NMR (125.9 MHz, CDCl3) δ 159.3, 137.9, 130.7, 130.1, 129.5,
128.1, 126.2, 113.9, 73.7, 73.1, 66.5, 55.4, 43.4, 39.4; HRESIMS
calcd for C25H28O3Na [M + Na]+ 399.1931, found 399.1930.
4-(tert-Butyldiphenylsiloxy)-3-fluorobenzyl Alcohol (4). To a
stirred solution of 3-fluoro-4-hydroxybenzoic acid (2.0 g, 12.8
mmol) and Et3N (10.7 mL, 76.8 mmol) in CH2Cl2 (30 mL) was
added TBDPSCl (8.4 mL, 32.0 mmol) dropwise at room temper-
ature. The reaction mixture was stirred at rt overnight and then
diluted with CH2Cl2 and washed with brine. The organic layer was
separated, dried over Na2SO4, and concentrated. The residue was
then dissolved in dry THF (30 mL) at 0 °C, and LiAlH4 (947 mg,
25.6 mmol) was added portionwise. After 10 min, the cooling bath
was removed, and the reaction mixture was heated to reflux with
stirring for 4 h. The reaction mixture was cooled to room
temperature, and then water was added dropwise until a white solid
precipitated. To this mixture was added Na2SO4, and the mixture
was filtered through Celite. The filter cake was washed with CH2Cl2,
and the filtrate was concentrated and the residue purified by flash
chromatography over silica gel (15% ethyl acetate in hexane) to
afford 4 (2.25 g, 46%): colorless oil; 1H NMR (500 MHz, CDCl3)
δ 7.79-7.77 (m, 4H), 7.46-7.40 (m, 6H), 7.06-7.04 (dd, J )
2.0, 11.0 Hz, 1H), 6.72 (d, J ) 9.0 Hz, 1H), 6.65 (t, J ) 8.5 Hz,
1H), 4.46 (s, 2H), 2.30 (s, 1H), 1.19 (s, 9H); 13C NMR (125.9 MHz,
CDCl3) δ 153.7 (d, J ) 246.7 Hz), 142.8 (d, J ) 12.9 Hz), 135.5,
134.6 (d, J ) 5.0 Hz), 132.6, 130.1, 127.9, 122.5 (d, J ) 2.5 Hz),
121.3, 115.2 (d, J ) 18.9 Hz), 64.3, 26.6, 19.8; HRESIMS calcd
for C23H25O2FSiNa [M + Na]+ 403.1506, found 403.1496.
4-(tert-Butyldiphenylsiloxy)-3-fluorobenzyl Bromide (5). To a
stirred solution of 4 (2.20 g, 5.8 mmol) and PPh3 (2.27 g, 8.7 mmol)
in CH2Cl2 (10 mL) was added CBr4 (2.92 g, 8.8 mmol) portionwise.
The resulting solution was stirred for 1 h at rt before it was
concentrated, and the residue was purified by chromatography over
silica gel (1% ethyl acetate in hexane) to afford 5 (2.32 g, 92%):
1
colorless oil; H NMR (500 MHz, CDCl3) δ 7.76-7.74 (m, 4H),
7.48-7.44 (m, 2H), 7.42-7.38 (m, 4H), 7.12-7.09 (dd, J ) 2.0,
11.0 Hz, 1H), 6.78 (d, J ) 8.0 Hz, 1H), 6.59 (t, J ) 8.5 Hz, 1H),
4.37 (s, 2H), 1.16 (s, 9H); 13C NMR (125.9 MHz, CDCl3) δ 153.5
(d, J ) 246.7 Hz), 143.7 (d, J ) 12.9 Hz), 135.5, 132.3, 131.2 (d,
J ) 6.3 Hz), 130.2, 127.9, 124.7 (d, J ) 2.5 Hz), 121.4, 117.2 (d,
J
) 18.9 Hz), 33.0, 26.5, 19.7; HRESIMS calcd for
2,2-Dibenzyl-1-[4-(tert-butyldiphenylsilyloxy)-3-fluorobenzyloxy]-
3-(4-methoxybenzyloxy)propane (8). To a stirred solution of 7 (157
mg, 0.417 mmol) in HMPA (404 µL, 0.417 mmol) and anhydrous
THF (4 mL) at 0 °C was added n-BuLi (184 µL, 0.459 mmol).
The reaction mixture was stirred at 0 °C for 5 min, and then bromide
5 (222 mg, 0.500 mmol) in THF (1 mL) was added. The ice bath
was removed and the stirring continued for 10 h at rt. The reaction
mixture was diluted with CH2Cl2 and washed with saturated
NaHCO3 and brine. The organic layer was separated, dried over
Na2SO4, and concentrated. The residue was purified by flash
chromatography on silica gel (2.5% ethyl acetate in hexane) to give
C23H24OBrFSiNa [M + Na]+ 465.0662, found 465.0654.
General Procedure for the Removal of 4-(tert-Butyldiphenylsi-
lyloxy)-3-fluorobenzyl Group Using a Microwave Reactor (Method
A). To a stirred solution of the substrate and 4 Å molecular sieves
in THF (0.05 M) was added TBAF (2 equiv, 1.0 M in THF). The
reaction mixture was heated to 90 °C in a microwave reactor for
2 h and then cooled to rt and filtered through Celite. Purification
by column chromatography on silica gel, eluting with hexane/ethyl
acetate mixtures, afforded the corresponding alcohols.
1
(20) The anomeric stereochemistry of the coupled products was assigned
on the basis of the characteristic chemical shift of the mannose H-5 resonance
in the 1H NMR spectrum5b and was confirmed by the measurement of
8 (219 mg, 71%): colorless oil; H NMR (500 MHz, CDCl3) δ
7.78-7.76 (m, 4H), 7.48-7.35 (m, 8H), 7.26-7.16 (m, 10H),
7.12-7.10 (dd, J ) 2.0, 11.0 Hz, 1H), 6.96-6.94 (m, 2H), 6.78
(d, J ) 8.5 Hz, 1H), 6.65 (t, J ) 8.5 Hz, 1H), 4.42 (s, 2H), 4.32
1
anomeric JCH coupling constants. Bock, K.; Pedersen, C. J. Chem. Soc.,
Perkin Trans. 2 1974, 293–297.
J. Org. Chem. Vol. 74, No. 6, 2009 2489

Crich et al.
(s, 2H), 3.85 (s, 3H), 2.93 (s, 2H), 2.89 (s, 2H), 2.853 (s, 2H),
2.849 (s, 2H), 1.18 (s, 9H); 13C NMR (125.9 MHz, CDCl3) δ 159.2,
153.6 (d, J ) 245.5 Hz), 142.7 (d, J ) 11.3 Hz), 138.4, 135.5,
132.6, 132.2 (d, J ) 5.0 Hz), 130.7, 130.6, 130.1, 129.5, 127.8,
126.0, 123.2 (d, J ) 2.6 Hz), 121.0, 115.9 (d, J ) 17.6 Hz), 113.8,
72.7, 72.2, 70.0, 69.7, 55.4, 43.9, 39.0, 26.6, 19.7; HRESIMS calcd
for C48H51O4FSiNa [M + Na]+ 761.3438, found 761.3400.
2,2-Dibenzyl-3-[4-(tert-butyldiphenylsilyloxy)-3-fluorobenzyloxy]-
propan-1-ol (9). Prepared by the general procedure for the removal
of p-methoxybenzyl group from 8 with a yield of 29.6 mg (89%):
18H), 7.06-7.03 (dd, J ) 2.0, 11.5 Hz, 1H), 6.85 (s, 1H), 6.83 (s,
1H), 6.70 (d, J ) 8.0 Hz, 1H), 6.60 (t, J ) 8.5 Hz, 1H), 5.62 (s,
1H), 5.47 (s, 1H), 4.66-4.58 (m, 3H), 4.46 (d, J ) 12.0 Hz, 1H),
4.27-4.20 (m, 3H), 3.97-3.96 (dd, J ) 1.0, 3.0 Hz, 1H), 3.90-3.85
(m, 2H), 3.78 (s, 3H), 1.15 (s, 9H); 13C NMR (125.6 MHz, CDCl3)
δ 159.7, 153.9 (d, J ) 245.6 Hz), 143.0 (d, J ) 12.0 Hz), 137.7,
135.7, 134.1, 132.8, 132.2 (d, J ) 6.5 Hz), 131.9, 130.3, 130.1,
129.8, 129.4, 129.1, 128.4, 128.0, 127.9, 126.3, 123.3 (d, J ) 3.8
Hz), 121.2 (d, J ) 1.9 Hz), 116.0 (d, J ) 18.6 Hz), 114.1, 101.7,
87.3, 79.2, 77.5, 76.1, 72.7, 72.4, 68.7, 65.7, 55.5, 26.7, 19.9;
HRESIMS calcd for C50H51O7FSSiNa [M + Na]+ 865.3007, found
865.2997.
General Glycosylation Procedure Using the BSP/TTBP/Tf2O
System. To a stirred solution of donor (1 equiv), BSP (1.2 equiv),
TTBP (1.5 equiv), and 4 Å molecular sieves in CH2Cl2 (0.05 M in
donor) at -60 °C was added Tf2O (1.2 equiv). After 30 min of
stirring at -60 °C, a 0.15 M solution of the glycosyl acceptor (1.5
equiv) in CH2Cl2 was slowly added. The reaction mixture was
stirred for a further 2 h at -60 °C before saturated NaHCO3 was
added to quench the reaction. The reaction mixture was allowed to
reach room temperature and then filtered through a pad of Celite
and washed with CH2Cl2, after which the filtrate was washed with
saturated NaHCO3 and brine. The organic layer was separated, dried
over Na2SO4, and concentrated. Purification by column chroma-
tography on silica gel, eluting with hexane/ethyl acetate mixtures,
afforded the corresponding coupled products.
1
colorless oil; H NMR (500 MHz, CDCl3) δ 7.74-7.72 (m, 4H),
7.46-7.35 (m, 6H), 7.26-7.16 (m, 10H), 7.05-7.02 (dd, J ) 2.0,
11.5 Hz, 1H), 6.72 (d, J ) 8.5 Hz, 1H), 6.60 (t, J ) 8.5 Hz, 1H),
4.30 (s, 2H), 3.43 (d, J ) 5.5 Hz, 2H), 3.16 (s, 2H), 2.77 (d, J )
13.5 Hz, 1H), 2.73 (d, J ) 13.5 Hz, 1H), 2.12 (t, J ) 5.5 Hz, 1H),
1.14 (s, 9H); 13C NMR (125.9 MHz, CDCl3) δ 153.4 (d, J ) 246.7
Hz), 142.9 (d, J ) 11.3 Hz), 137.8, 135.5, 132.6, 131.5 (d, J ) 5.0
Hz), 130.6, 130.1, 128.0, 127.8, 126.2, 123.2, 121.1 (d, J ) 2.6
Hz), 115.9 (d, J ) 18.8 Hz), 73.7, 72.7, 66.2, 43.4, 39.4, 26.5,
19.7; HRESIMS calcd for C40H43O3FSiNa [M + Na]+, 641.2858,
found 641.2854.
2,2-Dibenzyl-1-(4-hydroxy-3-fluorobenzyloxy)-3-(4-methoxyben-
zyloxy)propane (10). To a stirred solution of 8 (16.2 mg, 21.9 µmol)
in THF (1 mL) was added TBAF (33.0 µL, 1.0 M in THF). The
reaction mixture was stirred at rt for 2 h. The reaction mixture was
concentrated, and chromatographic purification (10% ethyl acetate
in hexane) on silica gel afforded 10 (12.5 mg, 92%): colorless oil;
1H NMR (500 MHz, CDCl3) δ 7.34-7.32 (m, 2H), 7.23-7.13 (m,
10H), 7.05-6.97 (m, 2H), 6.94-6.91 (m, 2H), 5.18 (s, 1H), 4.40
(s, 2H), 4.36 (s, 2H), 3.84 (s, 3H), 2.93 (s, 2H), 2.92 (s, 2H), 2.84
(s, 4H); 13C NMR (125.9 MHz, CDCl3) δ 159.2, 150.9 (d, J )
236.6 Hz), 142.9 (d, J ) 13.8 Hz), 138.4, 131.6 (d, J ) 5.0 Hz),
130.7, 130.6, 129.5, 127.8, 125.9, 124.3 (d, J ) 2.6 Hz), 117.0,
115.1 (d, J ) 17.6 Hz), 113.8, 72.7, 72.1, 69.6, 55.3, 43.9, 39.0;
HRESIMS calcd for C32H33O4FNa [M + Na]+ 523.2255, found
523.2252.
1-Adamantanyl 4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenyl-
siloxy)-3-fluorobenzyl]-2-O-(4-methoxybenzyl)-ꢀ-D-mannopyrano-
side (14ꢀ) and 1-Adamantanyl 4,6-O-Benzylidene-3-O-[4-(tert-
butyldiphenylsiloxy)-3-fluorobenzyl]-2-O-(4-methoxybenzyl)-r-D-
mannopyranoside (14r). Prepared by the general glycosylation
procedure with a yield of 419 mg (85%, ꢀ/R ) 11.7:1). 14ꢀ: white
crystalline solid; mp 139 °C; [R]23D -19.8 (c 2.0, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.75-7.73 (m, 4H), 7.48-7.27 (m, 13H),
7.00 (d, J ) 12.0 Hz, 1H), 6.85 (s, 1H), 6.83 (s, 1H), 6.63 (d, J )
8.5 Hz, 1H), 6.56 (t, J ) 8.5 Hz, 1H), 5.59 (s, 1H), 4.92 (d, J )
12.5 Hz, 1H), 4.87 (d, J ) 12.5 Hz, 1H), 4.76 (s, 1H), 4.48 (d, J
) 12.5 Hz, 1H), 4.36 (d, J ) 12.0 Hz, 1H), 4.28-4.25 (dd, J )
5.0, 10.5 Hz, 1H), 4.16 (t, J ) 9.5 Hz, 1H), 3.93 (t, J ) 10.0 Hz,
1H), 3.77 (s, 3H), 3.72 (d, J ) 3.0 Hz, 1H), 3.52-3.49 (dd, J )
3.0, 10.0 Hz, 1H), 3.33-3.28 (dt, J ) 4.5, 9.5 Hz, 1H), 2.19 (s,
3H), 1.88 (d, J ) 11.0 Hz, 3H), 1.78 (d, J ) 11.5 Hz, 3H), 1.68
Phenyl 4,6-O-Benzylidene-2-O-(4-methoxybenzyl)-1-thio-r-D-
mannopyranoside (12). To a mixture of 11 (1.25 g, 3.5 mmol),
tetrabutylammonium hydrogensulfate (235 mg, 0.69 mmol), and
PMBCl (0.57 mL, 4.2 mmol) in CH2Cl2 (50 mL) was added 1 M
aq NaOH (17 mL). The reaction mixture was stirred under reflux
for 24 h and then allowed to cool to room temperature and diluted
with CH2Cl2. The organic layer was separated. The aqueous phase
was extracted twice with CH2Cl2. The combined organic layer was
washed with saturated NaHCO3 and brine, dried over Na2SO4, and
concentrated. Chromatographic purification (50% hexane in CH2Cl2)
afforded 12 (1.16 g, 70%) as a white crystalline solid: mp 113 °C;
(d, J ) 12.5 Hz, 3H), 1.63 (d, J ) 12.5 Hz, 3H), 1.15 (s, 9H); 13
C
NMR (125.6 MHz, CDCl3) δ 159.4, 153.8 (d, J ) 245.6 Hz), 142.9
(d, J ) 12.1 Hz), 137.9, 135.7, 132.8, 132.4 (d, J ) 6.5 Hz), 130.8,
130.7, 130.3, 129.0, 128.4, 128.0, 126.3, 123.1 (d, J ) 2.8 Hz),
121.1 (d, J ) 1.9 Hz), 115.9 (d, J ) 19.5 Hz), 113.7, 101.6, 95.2
(1JCH ) 153.6 Hz), 78.7, 78.5, 76.1, 75.5, 74.2, 71.7, 69.1, 67.5,
55.5, 42.7, 36.5, 30.9, 26.8; HRESIMS calcd for C54H61O8FSiNa
[R]22 +124.7 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ
D
7.53-7.25 m, 10H), 6.91-6.88 (m, 2H), 5.57 (s, 1H), 5.53 (s, 1H),
4.68 (d, J ) 11.2 Hz, 1H), 4.58 (d, J ) 11.2 Hz, 1H), 4.32-4.26
(dt, J ) 4.8, 9.6 Hz, 1H), 4.24-4.20 (dd, J ) 4.8, 10.4 Hz, 1H),
4.12-4.07 (m, 2H), 3.97 (t, J ) 9.6 Hz, 1H), 3.83 (t, J ) 10.4 Hz,
1H), 3.80 (s, 3H), 2.47 (d, J ) 8.0 Hz, 1H); 13C NMR (100.7 MHz,
CDCl3) δ 159.9, 137.5, 133.9, 132.0, 130.0, 129.5, 129.4, 128.5,
128.0, 126.6, 114.3, 102.4, 86.6, 79.9, 79.8, 73.1, 69.2, 68.7, 64.9,
55.5; HRESIMS calcd for C27H28O6SNa [M + Na]+ 503.1504,
found 503.1500.
[M + Na]+ 907.4017, found 907.4018. 14r: colorless oil; [R]22
D
1
+37.6 (c 0.5, CHCl3); H NMR (500 MHz, CDCl3) δ 7.74-7.72
(m, 4H), 7.49-7.27 (m, 13H), 7.08-7.05 (dd, J ) 2.0, 11.5 Hz,
1H), 6.87 (s, 1H), 6.85 (s, 1H), 6.70 (d, J ) 8.5 Hz, 1H), 6.58 (t,
J ) 8.5 Hz, 1H), 5.62 (s, 1H), 5.09 (d, J ) 2.0 Hz, 1H), 4.71 (d,
J ) 12.0 Hz, 1H), 4.67 (d, J ) 12.0 Hz, 1H), 4.61 (d, J ) 12.0
Hz, 1H), 4.46 (d, J ) 12.0 Hz, 1H), 4.61 (d, J ) 12.0 Hz, 1H),
4.21-4.18 (dd, J ) 5.0, 10.0 Hz, 1H), 4.15 (t, J ) 9.5 Hz, 1H),
3.99-3.93 (dt, J ) 5.0, 10.5 Hz, 1H), 3.94-3.91 (dd, J ) 3.0, 9.5
Hz, 1H), 3.82 (t, J ) 10.0 Hz, 1H), 3.79 (s, 3H), 3.60-3.59 (dd,
J ) 2.0, 3.0 Hz, 1H), 2.11 (s, 3H), 1.70-1.55 (m, 12H), 1.14 (s,
9H); 13C NMR (125.6 MHz, CDCl3) δ 159.6, 153.8 (d, J ) 244.7
Hz), 142.8 (d, J ) 12.3 Hz), 134.0, 135.7, 132.9, 132.7 (d, J ) 6.5
Hz), 130.5, 130.2, 130.1, 129.0, 128.4, 128.0, 126.2, 123.1 (d, J )
Phenyl 4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenylsiloxy)-3-
fluorobenzyl]-2-O-(4-methoxybenzyl)-1-thio-r-D-mannopyrano-
side (13). To a stirred solution of 12 (700 mg, 1.6 mmol) in DMF
(8 mL) at 0 °C was added NaH (60% in mineral oil, 70.8 mg, 1.8
mmol). After 15 min, 5 (857 mg, 1.9 mmol) in DMF (2 mL) was
added and the reaction mixture stirred at rt for 10 h. The reaction
mixture was diluted with EtOAc and washed with H2O. The
aqueous phase was extracted with EtOAc three times, and the
combined organic phase was dried and concentrated. Chromato-
graphic purification (7.5% ethyl acetate in hexane) on silica gel
gave 13 (947 mg, 74%): colorless oil; [R]23D +51.8 (c 1.0, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.75-7.73 (m, 4H), 7.50-7.24 (m,
2.6 Hz), 121.1, 115.8 (d, J ) 19.6 Hz), 114.0, 101.5, 92.7 (1JCH
)
167.9 Hz), 79.8, 77.3, 76.6, 74.9, 73.1, 72.5, 69.2, 64.0, 55.5, 42.5,
36.4, 30.8, 26.7, 19.9; HRESIMS calcd for C54H61O8FSiNa [M +
Na]+ 907.4017, found 907.4019.
2490 J. Org. Chem. Vol. 74, No. 6, 2009

4-(tert-Butyldiphenylsiloxy)-3-fluorobenzyl Group
4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenylsiloxy)-3-fluoroben-
zyl]-2-O-(4-methoxybenzyl)-ꢀ-D-mannopyranosyl-(1f3)-1,2:5,6-di-
isopropylidene-r-D-glucofuranose (15). Prepared by the general
pared by the general glycosylation procedure with a yield of 126.4
mg (62%): colorless oil; [R]24D -7.2 (c 2.0, CHCl3); 1H NMR (500
MHz, CDCl3) δ 7.76-7.74 (m, 4H), 7.47-7.18 (m, 23H),
7.07-7.05 (dd, J ) 2.0, 11.0 Hz, 1H), 6.84-6.82 (m, 2H), 6.70
(d, J ) 8.0 Hz, 1H), 6.62 (t, J ) 8.5 Hz, 1H), 5.49 (s, 1H), 5.21
(d, J ) 10.5 Hz, 1H), 4.82-4.67 (m, 5H), 4.40 (d, J ) 12.5 Hz,
1H), 4.42-4.37 (m, 3H), 4.07-4.01 (m, 3H), 3.89-3.85 (dd, J )
8.5, 10.0 Hz, 1H), 3.78 (s, 3H), 3.70-3.56 (m, 4H), 3.52-3.48
(m, 1H), 3.49 (s, 3H), 3.41 (t, J ) 10.0 Hz, 1H), 3.29-3.26 (dd,
J ) 3.0, 10.0 Hz, 1H), 3.07-3.02 (dt, J ) 5.0, 10.0 Hz, 1H), 1.16
(s, 9H); 13C NMR (125.6 MHz, CDCl3) δ 159.5, 153.9 (d, J )
245.5 Hz), 143.0 (d, J ) 11.7 Hz), 138.9, 137.8, 137.7, 135.7, 132.8,
132.5 (d, J ) 5.7 Hz), 130.7, 130.4, 130.3, 129.1, 128.9, 128.5,
128.4, 128.32, 128.30, 128.1, 127.7, 126.3, 122.9 (d, J ) 2.8 Hz),
121.2, 115.6 (d, J ) 19.6 Hz), 113.8, 101.6, 101.5 (d, J ) 161.9
Hz), 98.9 (d, J ) 173.1 Hz), 78.9, 78.8, 78.5, 76.4, 75.3, 75.0,
73.9, 71.9, 70.5, 68.6, 68.4, 67.5, 63.2, 55.7, 55.5, 26.8, 19.9;
HRESIMS calcd for C65H70N3O12FSiNa [M + Na]+ 1154.4611,
found 1154.4583.
1-Adamantanyl 4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenyl-
siloxy)-3-fluorobenzyl]-ꢀ-D-mannopyranoside (18). Prepared by the
general procedure for the removal of the p-methoxybenzyl group
from 14 with a yield of 97.3 mg (80%): colorless oil; [R]22D -5.3
(c 1.5, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.73-7.71 (m, 4H),
7.48-7.34 (m, 11H), 7.10-7.07 (dd, J ) 2.0, 11.0 Hz, 1H), 6.73
(d, J ) 8.5 Hz, 1H), 6.57 (t, J ) 8.5 Hz, 1H), 5.58 (s, 1H), 4.82
(s, 1H), 4.69 (d, J ) 12.0 Hz, 1H), 4.64 (d, J ) 12.5 Hz, 1H),
4.30-4.27 (dd, J ) 5.0, 10.5 Hz, 1H), 4.11 (t, J ) 9.5 Hz, 1H),
3.92 (d, J ) 3.0 Hz, 1H), 3.87 (t, J ) 10.5 Hz, 1H), 3.60-3.57
(dd, J ) 4.0, 9.5 Hz, 1H), 3.34-3.29 (dt, J ) 5.0, 10.0 Hz, 1H),
2.59 (s, 1H), 2.18 (s, 3H), 1.86 (d, J ) 11.0 Hz, 3H), 1.78 (d, J )
11.5 Hz, 3H), 1.66 (d, J ) 12.5 Hz, 3H), 1.61 (d, J ) 12.5 Hz,
3H), 1.12 (s, 9H); 13C NMR (125.6 MHz, CDCl3) δ 153.9 (d, J )
245.6 Hz), 143.1 (d, J ) 12.2 Hz), 137.7, 135.7, 132.8, 132.0 (d,
J ) 5.6 Hz), 130.3, 129.2, 128.5, 128.0, 126.3, 123.6 (d, J ) 2.8
Hz), 121.3, 116.2 (d, J ) 19.6 Hz), 101.7, 93.5, 78.4, 77.2, 76.1,
71.78, 71.75, 69.0, 66.9, 42.6, 36.4, 30.9, 26.8, 19.9; HRESIMS
calcd for C46H53O7FSiNa [M + Na]+ 787.3442, found 787.3457.
4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenylsiloxy)-3-fluoroben-
zyl]-ꢀ-D-mannopyranosyl-(1f3)-1,2:5,6-diisopropylidene-r-D-glu-
cofuranose (19). Prepared by the general procedure for the removal
glycosylation procedure with a yield of 120.6 mg (82%): colorless
1
oil; [R]23 -31.6 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ
D
7.74-7.72 (m, 4H), 7.48-7.27 (m, 13H), 7.02-6.99 (dd, J ) 2.0,
11.5 Hz, 1H), 6.85 (s, 1H), 6.83 (s, 1H), 6.65 (d, J ) 8.0 Hz, 1H),
6.57 (t, J ) 8.5 Hz, 1H), 5.92 (d, J ) 3.5 Hz, 1H), 5.59 (s, 1H),
4.78 (d, J ) 11.5 Hz, 1H), 4.70 (d, J ) 11.5 Hz, 1H), 4.55 (d, J )
11.5 Hz, 1H), 4.54 (s, 1H), 4.45-4.41 (m, 3H), 4.33-4.27 (m,
3H), 4.18-4.13 (m, 2H), 4.09-4.06 (dd, J ) 6.0, 8.5 Hz, 1H),
3.91 (t, J ) 10.0 Hz, 1H), 3.81 (d, J ) 3.0 Hz, 1H), 3.78 (s, 3H),
3.53-3.50 (dd, J ) 3.0, 10.0 Hz, 1H), 3.32-3.27 (dt, J ) 4.5,
10.0 Hz, 1H), 1.52 (s, 3H), 1.45 (s, 3H), 1.36 (s, 3H), 1.33 (s, 3H),
1.15 (s, 9H); 13C NMR (125.6 MHz, CDCl3) δ 159.6, 153.9 (d, J
) 245.5 Hz), 143.0 (d, J ) 12.2 Hz), 137.6, 135.7, 132.8, 132.1
(d, J ) 5.5 Hz), 130.4, 130.3, 129.1, 128.5, 128.0, 126.2, 123.3 (d,
J ) 3.8 Hz), 121.2, 115.9 (d, J ) 18.6 Hz), 113.9, 112.2, 108.9,
105.2 (d, J ) 183.8 Hz), 101.6, 100.6 (1JCH ) 155.7 Hz), 83.1,
81.2, 80.7, 78.7, 78.1, 75.7, 74.6, 73.3, 72.0, 68.7, 68.0, 66.4, 55.5,
27.0, 26.9, 26.7, 26.5, 25.7, 19.9; HRESIMS calcd for
C56H65O13FSiNa [M + Na]+ 1015.4076, found 1015.4038.
Methyl 4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenylsiloxy)-3-
fluorobenzyl]-2-O-(4-methoxybenzyl)-ꢀ-D-mannopyranosyl-(1f6)-
2,3,4-tri-O-benzyl-r-D-glucopyranoside (16ꢀ) and Methyl 4,6-O-
Benzylidene-3-O-[4-(tert-butyldiphenylsiloxy)-3-fluorobenzyl]-2-O-
(4-methoxybenzyl)-r-D-mannopyranosyl-(1f6)-2,3,4-tri-O-benzyl-
r-D-glucopyranoside (16r). Prepared by the general glycosylation
procedure with a yield of 133.8 mg (79%, ꢀ/R ) 8.2:1). 16ꢀ:
1
colorless oil; [R]23 -1.1 (c 1.0, CHCl3); H NMR (500 MHz,
D
CDCl3) δ 7.74-7.71 (m, 4H), 7.48-7.17 (m, 28H), 7.02-7.00 (dd,
J ) 2.0, 11.5 Hz, 1H), 6.84 (s, 1H), 6.82 (s, 1H), 6.65 (d, J ) 8.5
Hz, 1H), 6.57 (t, J ) 8.5 Hz, 1H), 5.57 (s, 1H), 5.04 (d, J ) 11.0
Hz, 1H), 4.87-4.80 (m, 4H), 4.71 (d, J ) 12.0 Hz, 1H), 4.69 (d,
J ) 12.0 Hz, 1H), 4.61 (d, J ) 4.0 Hz, 1H), 4.55 (d, J ) 12.0 Hz,
1H), 4.51 (d, J ) 12.5 Hz, 1H), 4.40 (d, J ) 12.5 Hz, 1H),
4.28-4.24 (dd, J ) 5.0, 10.5 Hz, 1H), 4.16-4.03 (m, 4H), 3.90 (t,
J ) 10.0 Hz, 1H), 3.80-3.77 (dd, J ) 5.0, 12.0 Hz, 1H), 3.69 (s,
3H), 3.65 (d, J ) 3.0 Hz, 1H), 3.55-3.52 (dd, J ) 4.0, 10.0 Hz,
1H), 3.50-3.45 (m, 2H), 3.41-3.39 (dd, J ) 3.0, 9.5 Hz, 1H),
3.36 (s, 3H), 3.23-3.18 (dt, J ) 5.0, 10.0 Hz, 1H), 1.14 (s, 9H);
13C NMR (125.6 MHz, CDCl3) δ 159.5, 153.9 (d, J ) 245.5 Hz),
143.0 (d, J ) 12.1 Hz), 139.0, 138.6, 138.2, 137.7, 135.7, 132.8,
132.2 (d, J ) 5.5 Hz), 130.5, 130.4, 130.3, 129.1, 128.74, 128.67,
128.6, 128.47, 128.45, 128.4, 128.2, 128.0, 127.9, 126.2, 123.2 (d,
of the p-methoxybenzyl group from 15 with a yield of 17.7 mg
1
(80%): colorless oil; [R]23 -15.2 (c 0.5, CHCl3); H NMR (500
D
MHz, CDCl3) δ 7.75-7.73 (m, 4H), 7.50-7.24 (m, 18H),
7.06-7.03 (dd, J ) 2.0, 11.5 Hz, 1H), 6.85 (s, 1H), 6.83 (s, 1H),
6.70 (d, J ) 8.0 Hz, 1H), 6.60 (t, J ) 8.5 Hz, 1H), 5.62 (s, 1H),
5.47 (s, 1H), 4.66-4.58 (m, 3H), 4.46 (d, J ) 12.0 Hz, 1H),
4.27-4.20 (m, 3H), 3.97-3.96 (dd, J ) 1.0, 3.0 Hz, 1H), 3.90-3.85
(m, 2H), 3.78 (s, 3H), 2.19-1.78 (br s, 1H), 1.15 (s, 9H); 13C NMR
(125.6 MHz, CDCl3) δ 153.9 (d, J ) 245.6 Hz), 143.2 (d, J )
11.2 Hz), 137.5, 135.7, 132.8, 131.7 (d, J ) 5.5 Hz), 130.3, 129.2,
128.5, 128.0, 126.2, 123.6 (d, J ) 3.8 Hz), 121.3, 116.2 (d, J )
18.6 Hz), 112.3, 109.2, 105.4, 101.7, 98.3, 83.1, 80.8, 79.0, 78.6,
76.4, 73.4, 72.1, 70.0, 68.9, 67.3, 67.0, 27.0, 26.9, 26.7, 26.6, 25.7,
19.9; HRESIMS calcd for C48H57O12FSiNa [M + Na]+ 895.3501,
found 895.3481.
J ) 1.8 Hz), 121.2, 115.9 (d, J ) 18.6 Hz), 113.8, 102.2 (1JCH
)
156.7 Hz), 101.6, 98.0 (1JCH ) 169.3 Hz),.82.5, 80.1, 78.8, 78.1,
76.1, 75.0, 74.6, 74.1, 73.6, 71.8, 69.9, 68.8, 68.4, 67.7, 55.40,
55.36, 26.7, 19.9; HRESIMS calcd for C72H77O13FSiNa [M + Na]+
1219.5015, found 1219.4989. 16r: colorless oil; [R]23 +25.5 (c
D
1
0.4, CHCl3); H NMR (500 MHz, CDCl3) δ 7.73-7.71 (m, 4H),
7.46-7.23 (m, 28H), 7.06-7.03 (dd, J ) 2.0, 12.0 Hz, 1H), 6.83
(s, 1H), 6.81 (s, 1H), 6.68 (d, J ) 8.0 Hz, 1H), 6.55 (t, J ) 8.5 Hz,
1H), 5.59 (s, 1H), 5.00 (d, J ) 10.5 Hz, 1H), 4.92 (d, J ) 11.0 Hz,
1H), 4.83-4.77 (m, 3H), 4.69-4.56 (m, 6H), 4.43 (d, J ) 12.0
Hz, 1H), 4.19-4.15 (m, 2H), 4.00 (t, J ) 10.0 Hz, 1H), 3.84-3.62
(m, 10H), 3.50-3.47 (dd, J ) 3.5, 10.0 Hz, 1H), 3.40 (t, J ) 9.5
Hz, 1H), 3.31 (s, 3H), 1.13 (s, 9H); 13C NMR (125.6 MHz, CDCl3)
δ 159.5, 153.7 (d, J ) 245.6 Hz), 142.9 (d, J ) 12.2 Hz), 138.8,
138.30, 138.25, 137.9, 135.7, 132.8, 132.6 (d, J ) 5.7 Hz), 130.2,
129.9, 129.0, 128.73, 128.71, 128.69, 128.4, 128.3, 128.2, 128.1,
128.0, 127.9, 126.3, 123.1 (d, J ) 1.8 Hz), 121.1, 115.8 (d, J )
19.4 Hz), 114.0, 101.7, 99.7 (1JCH ) 171.7 Hz), 98.0 (1JCH ) 169.5
Hz), 82.3, 80.3, 79.3, 78.0, 76.6, 76.1, 75.8, 75.2, 73.5, 73.2, 69.9,
66.4, 64.4, 55.5, 55.3, 26.7, 19.9; HRESIMS calcd for
C72H77O13FSiNa [M + Na]+ 1219.5015, found 1219.5043.
Methyl 4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenylsiloxy)-3-
fluorobenzyl]-ꢀ-D-mannopyranosyl-(1f6)-2,3,4-tri-O-benzyl-r-D-
glucopyranoside (20). Prepared by the general procedure for the
removal of the p-methoxybenzyl group from 16 with a yield of
45.9 mg (84%): colorless oil; [R]24D +15.5 (c 1.0, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.73-7.70 (m, 4H), 7.47-7.20 (m, 26H),
7.10-7.08 (dd, J ) 2.0, 11.0 Hz, 1H), 6.73 (d, J ) 8.5 Hz, 1H),
6.58 (t, J ) 8.5 Hz, 1H), 5.55 (s, 1H), 5.02 (d, J ) 11.0 Hz, 1H),
4.89 (d, J ) 11.0 Hz, 1H), 4.83 (d, J ) 11.0 Hz, 1H), 4.80 (d, J )
12.0 Hz, 1H), 4.68-4.57 (m, 5H), 4.29-4.26 (dd, J ) 5.0, 10.5
Hz, 1H), 4.18 (s, 1H), 4.09-3.99 (m, 3H), 3.91 (d, J ) 3.0 Hz,
1H), 3.84 (t, J ) 9.5 Hz, 1H), 3.81-3.77 (ddd, J ) 2.0, 5.0, 10.0
Hz, 1H), 3.61-3.58 (dd, J ) 5.5, 10.0 Hz, 1H), 3.54-3.51 (dd, J
Methyl 4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenylsiloxy)-3-
fluorobenzyl]-2-O-(4-methoxybenzyl)-ꢀ-D-mannopyranosyl-(1f4)-
2-azido-3,6-di-O-benzyl-2-deoxy-r-D-glucopyranoside (17). Pre-
J. Org. Chem. Vol. 74, No. 6, 2009 2491

Crich et al.
) 3.5, 10.0 Hz, 1H), 3.49-3.46 (dd, J ) 3.0, 9.5 Hz, 1H), 3.44 (t,
J ) 10.0 Hz, 1H), 3.36 (s, 3H), 3.24-3.19 (dt, J ) 5.0, 10.0 Hz,
1H), 2.41 (s, 1H), 1.13 (s, 9H); 13C NMR (125.6 MHz, CDCl3) δ
153.9 (d, J ) 246.6 Hz), 143.2 (d, J ) 12.1 Hz), 138.9, 138.6,
138.3, 137.6, 135.7, 132.8, 131.8 (d, J ) 5.7 Hz), 130.3, 129.2,
128.74, 128.67, 128.5, 128.4, 128.22, 128.17, 128.0, 127.9, 126.2,
123.6 (d, J ) 2.8 Hz), 121.2, 116.2 (d, J ) 18.6 Hz), 101.8, 100.7,
98.1,.82.4, 80.1, 78.5, 77.7, 76.6, 76.0, 75.0, 73.6, 71.8, 70.0, 69.9,
68.8, 68.6, 67.1, 55.4, 26.7, 19.9; HRESIMS calcd for
C64H69O12FSiNa [M + Na]+ 1099.4440, found 1099.4418.
Methyl 4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenylsiloxy)-3-
fluorobenzyl]-ꢀ-D-mannopyranosyl-(1f4)-2-azido-3,6-di-O-benzyl-
2-deoxy-r-D-glucopyranoside (21). Prepared by the general proce-
dure for the removal of the p-methoxybenzyl group from 17 with
a yield of 24.8 mg (82%): colorless oil; [R]23D +24.8 (c 1.0, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.73-7.71 (m, 4H), 7.47-7.18 (m,
19H), 7.07-7.05 (dd, J ) 2.0, 11.0 Hz, 1H), 6.70 (d, J ) 8.0 Hz,
1H), 6.58 (t, J ) 8.5 Hz, 1H), 5.47 (s, 1H), 5.04 (d, J ) 11.0 Hz,
1H), 4.81-4.72 (m, 3H), 4.59 (d, J ) 12.0 Hz, 1H), 4.51 (d, J )
12.0 Hz, 1H), 4.46 (s, 1H), 4.40 (d, J ) 12.0 Hz, 1H), 4.06-3.64
(m, 8H), 3.48-3.43 (m, 2H), 3.43 (s, 3H), 3.41 (t, J ) 10.0 Hz,
1H), 3.29-3.26 (dd, J ) 3.0, 10.0 Hz, 1H), 3.07-3.02 (dt, J )
5.0, 10.0 Hz, 1H), 2.46 (s, 1H), 1.14 (s, 9H); 13C NMR (125.6
MHz, CDCl3) δ 153.9 (d, J ) 245.6 Hz), 143.2 (d, J ) 11.2 Hz),
138.5, 137.7, 137.6, 135.7, 132.7, 131.8 (d, J ) 5.5 Hz), 130.3,
129.2, 128.8, 128.5, 128.4, 128.3, 128.2, 128.0, 127.9, 126.2, 123.3
(d, J ) 2.8 Hz), 121.3, 116.0 (d, J ) 19.5 Hz), 101.7, 100.5, 98.9,
78.9, 78.3, 78.5, 75.3, 75.0, 73.9, 71.8, 70.3, 69.8, 68.6, 68.3, 67.0,
63.4, 55.6, 26.7, 19.9; HRESIMS calcd for C57H62N3O11FSiNa [M
+ Na]+ 1034.4035, found 1034.4011.
73.2, 70.9, 68.7, 67.4, 66.7, 55.5, 26.98, 26.94, 26.5, 25.8;
HRESIMS calcd for C33H42O12Na [M + Na]+ 653.2574, found
653.2556.
Methyl 4,6-O-Benzylidene-2-O-(4-methoxybenzyl)-ꢀ-D-man-
nopyranosyl-(1f6)-2,3,4-tri-O-benzyl-r-D-glucopyranoside (24). Pre-
pared by the general procedure for the removal of 4-(tert-
butyldiphenylsilyloxy)-3-fluorobenzyl group using a microwave
reactor (method A) from 16 with a yield of 13.3 mg (78%): colorless
1
oil; [R]23 -15.0 (c 0.4, CHCl3); H NMR (500 MHz, CDCl3) δ
D
7.47-7.27 (m, 22H), 6.89 (s, 1H), 6.88 (s, 1H), 5.51 (s, 1H), 5.02
(d, J ) 11.0 Hz, 1H), 4.96 (d, J ) 11.0 Hz, 1H), 4.91 (d, J ) 11.0
Hz, 1H), 4.84 (d, J ) 11.0 Hz, 1H), 4.81 (d, J ) 12.0 Hz, 1H),
4.66 (d, J ) 12.0 Hz, 1H), 4.60 (d, J ) 12.0 Hz, 1H), 4.59 (s, 1H),
4.52 (d, J ) 11.5 Hz, 1H), 4.34 (s, 1H), 4.29-4.26 (dd, J ) 5.0,
10.0 Hz, 1H), 4.17-4.15 (dd, J ) 2.0, 10.0 Hz, 1H), 4.04 (t, J )
9.5 Hz, 1H), 3.88-3.75 (m, 7H), 3.71-3.66 (dt, J ) 3.5, 9.5 Hz,
1H), 3.58-3.54 (dd, J ) 5.5, 10.5 Hz, 1H), 3.51-3.49 (dd, J )
3.5, 10.0 Hz, 1H), 3.45 (t, J ) 10.0 Hz, 1H), 3.37 (s, 3H),
3.28-3.23 (dt, J ) 5.0, 10.0 Hz, 1H), 2.35 (d, J ) 9.0 Hz, 1H);
13C NMR (125.6 MHz, CDCl3) δ 159.7, 138.8, 138.5, 138.3, 137.5,
130.4, 130.2, 129.3, 128.72, 128.70, 128.5, 128.43, 128.38, 128.3,
128.2, 128.1, 128.0, 126.4, 114.2, 102.5, 102.2, 98.1, 82.4, 80.2,
79.5, 78.1, 77.9, 76.2, 75.5, 75.1, 73.7, 70.9, 70.0, 68.8, 68.7, 67.3,
55.5, 55.4; HRESIMS calcd for C49H54O12Na [M + Na]+ 857.3513,
found 857.3504.
Methyl 4,6-O-Benzylidene-2-O-(4-methoxybenzyl)-ꢀ-D-man-
nopyranosyl-(1f4)-2-azido-3,6-di-O-benzyl-2-deoxy-r-D-glucopy-
ranoside (25). Prepared by the general procedure for the removal
of the 4-(tert-butyldiphenylsilyloxy)-3-fluorobenzyl group using a
microwave reactor (method A) from 17 with a yield of 21.2 mg
1
(78%): colorless oil; [R]24 -9.0 (c 0.5, CHCl3); H NMR (500
D
1-Adamantanyl 4,6-O-Benzylidene-2-O-(4-methoxybenzyl)-ꢀ-D-
mannopyranoside (22). Compound 22 was prepared by the general
procedure for the removal of the 4-(tert-butyldiphenylsilyloxy)-3-
fluorobenzyl group using microwave reactor (method A) from 14
with a yield of 49.5 mg (74%). Compound 22 was also prepared
by the general procedure for the removal of the 4-(tert-butyldiphe-
nylsilyloxy)-3-fluorobenzyl group with conventional heating (method
MHz, CDCl3) 7.49-7.27 (m, 17H), 6.88-6.86 (m, 2H), 5.43 (s,
1H), 5.19 (d, J ) 11.0 Hz, 1H), 4.91 (d, J ) 11.5 Hz, 1H), 4.81
(d, J ) 3.5 Hz, 1H), 4.76 (d, J ) 12.0 Hz, 1H), 4.70 (d, J ) 11.0
Hz, 1H), 4.57 (d, J ) 11.0 Hz, 1H), 4.48 (s, 1H), 4.44 (d, J ) 11.5
Hz, 1H), 4.08-4.03 (m, 2H), 3.86 (t, J ) 9.5 Hz, 1H), 3.80 (s,
3H), 3.73-3.62 (m, 5H),3.50-3.47 (m, 2H), 3.47 (s, 3H), 3.38 (t,
J ) 10.0 Hz, 1H), 3.07-3.02 (dt, J ) 5.0, 10.0 Hz, 1H); 13C NMR
(125.6 MHz, CDCl3) δ 159.7, 138.7, 137.54, 137.48, 130.4, 130.1,
129.4, 129.0, 128.6, 128.5, 128.43, 128.40, 128.3, 128.2, 127.8,
126.5, 126.3, 114.1, 102.2, 101.8, 98.9, 79.3, 78.9, 78.8, 77.9, 75.9,
75.3, 74.0, 71.0, 70.5, 68.6, 68.3, 67.1, 63.2, 55.7, 55.5; HRESIMS
calcd for C42H47N3O11Na [M + Na]+ 792.3108, found 792.3138.
1-Adamantanyl 4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenyl-
siloxy)-3-fluorobenzyl]-2-O-(4-methoxybenzyl)-r-D-mannopyrano-
syl-(1f3)-4,6-O-benzylidene-2-O-(4-methoxybenzyl)-ꢀ-D-mannopy-
ranoside (26r) and 1-Adamantanyl 4,6-O-Benzylidene-3-O-[4-(tert-
butyldiphenylsiloxy)-3-fluorobenzyl]-2-O-(4-methoxybenzyl)-ꢀ-D-
mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-(4-methoxybenzyl)-
ꢀ-D-mannopyranoside (26ꢀ). Prepared by the general glycosylation
procedure. Radical chromatographic purification (5% ethyl acetate
in toluene) on silica gel provided 26 with a yield of 48.2 mg (71%,
ꢀ/R ) 11.4:1). 26r: colorless oil; [R]24D -12.5 (c 0.2, CHCl3); 1H
NMR (500 MHz, CDCl3) δ 7.69-7.27 (m, 22H), 7.06-7.03 (dd,
J ) 2.0, 11.0 Hz, 1H), 6.91 (s, 1H), 6.89 (s, 1H), 6.74 (s, 1H),
6.72 (s, 1H), 6.63-6.62 (m, 3H), 6.51 (t, J ) 8.5 Hz, 1H), 5.61 (s,
1H), 5.56 (s, 1H), 5.34 (s, 1H), 4.84 (d, J ) 11.5 Hz, 1H), 4.82 (s,
1H), 4.77 (d, J ) 12.5 Hz, 1H), 4.49 (d, J ) 12.5 Hz, 1H), 4.44
(d, J ) 11.5 Hz, 1H), 4.33 (d, J ) 12.0 Hz, 1H), 4.28-4.12 (m,
5H), 3.96-3.78 (m, 5H), 3.72 (s, 3H), 3.72-3.66 (m, 2H), 3.48
(s, 3H), 3.40-3.35 (dt, J ) 5.0, 10.0 Hz, 1H), 2.18 (s, 3H), 1.86
(d, J ) 12.0 Hz, 3H), 1.77 (d, J ) 11.5 Hz, 3H), 1.68-1.59 (m,
6H), 1.10 (s, 9H); 13C NMR (125.6 MHz, CDCl3) δ 159.39, 159.38,
153.9 (d, J ) 245.7 Hz), 142.9 (d, J ) 12.2 Hz), 137.9, 137.8,
135.6, 132.8, 132.4 (d, J ) 5.0 Hz), 130.3, 130.2, 129.9, 129.7,
129.6, 129.0, 128.6, 128.5, 128.4, 128.0, 126.4, 126.3, 123.0 (d, J
) 2.8 Hz), 121.0, 115.8 (d, J ) 19.6 Hz), 113.84, 113.80, 102.0,
101.6, 99.8 (1JCH ) 169.5 Hz), 95.0 (1JCH ) 155.4 Hz), 79.2, 79.1,
78.2, 75.8, 75.7, 75.0, 74.6, 72.3, 72.0, 69.1, 69.0, 67.2, 64.9, 55.4,
B) from 14 with a yield of 45.3 mg (77%): colorless oil; [R]24
D
1
-65.8 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 7.51-7.31
(m, 7H), 6.91 (s, 1H), 6.89 (s, 1H), 5.53 (s, 1H), 5.08 (d, J ) 11.5
Hz, 1H), 4.89 (s, 1H), 4.61 (d, J ) 12.0 Hz, 1H), 4.29-4.26 (dd,
J ) 5.0, 10.5 Hz, 1H), 3.87 (t, J ) 10.5 Hz, 1H), 3.82 (s, 3H),
3.82-3.73 (m, 3H), 3.36-3.31 (dt, J ) 5.0, 9.5 Hz, 1H), 2.39 (d,
J ) 8.5 Hz, 1H), 2.20 (s, 3H), 1.90 (d, J ) 11.0 Hz, 3H), 1.83 (d,
J ) 11.5 Hz, 3H), 1.69 (d, J ) 12.5 Hz, 3H), 1.64 (d, J ) 12.0
Hz, 3H); 13C NMR (125.6 MHz, CDCl3) δ 159.7, 153.9 (d, J )
245.6 Hz), 143.0 (d, J ) 12.0 Hz), 137.7, 135.7, 134.1, 132.8, 132.2
(d, J ) 6.5 Hz), 131.9, 130.3, 130.1, 129.8, 129.4, 129.1, 128.4,
128.0, 127.9, 126.3, 123.3 (d, J ) 3.8 Hz), 121.2 (d, J ) 1.9 Hz),
116.0 (d, J ) 18.6 Hz), 114.1, 101.7, 87.3, 79.2, 77.5, 76.1, 72.7,
72.4, 68.7, 65.7, 55.5, 26.7, 19.9; HRESIMS calcd for C31H38O7Na
[M + Na]+ 545.2515, found 545.2515.
4,6-O-Benzylidene-2-O-(4-methoxybenzyl)-ꢀ-D-mannopyranosyl-
(1f3)-1,2:5,6-diisopropylidene-r-D-glucofuranose (23). Prepared by
the general procedure for the removal of 4-(tert-butyldiphenylsi-
lyloxy)-3-fluorobenzyl group using a microwave reactor (method
A) from 15 with a yield of 19.7 mg (76%): colorless oil; [R]23
D
1
-53.0 (c 0.4, CHCl3); H NMR (500 MHz, CDCl3) δ 7.49-7.47
(m, 2H), 7.37-7.27 (m, 5H), 6.92 (s, 1H), 6.90 (s, 1H), 5.94 (d, J
) 3.5 Hz, 1H), 5.55 (s, 1H), 4.90 (d, J ) 11.5 Hz, 1H), 4.71 (s,
1H), 4.56 (d, J ) 12.0 Hz, 1H), 4.51 (d, J ) 3.5 Hz, 1H), 4.44 (d,
J ) 11.0 Hz, 1H), 4.42 (d, J ) 11.0 Hz, 1H), 4.36 (d, J ) 3.5 Hz,
1H), 4.33-4.28 (m, 2H), 4.18-4.15 (dd, J ) 6.5, 8.5 Hz, 1H),
4.10-4.10 (dd, J ) 5.5, 8.5 Hz, 1H), 3.89-3.79 (m, 3H), 3.82 (s,
3H), 3.38-3.33 (dt, J ) 5.0, 10.0 Hz, 1H), 2.52 (s, 1H), 1.53 (s,
3H), 1.46 (s, 3H), 1.38 (s, 3H), 1.35 (s, 3H); 13C NMR (125.6 MHz,
CDCl3) δ 159.6, 137.4, 130.2, 130.1, 129.4, 128.5, 126.5, 114.3,
112.3, 109.1, 105.2, 102.2, 100.3, 83.0, 81.0, 80.7, 79.5, 77.9, 75.3,
2492 J. Org. Chem. Vol. 74, No. 6, 2009

4-(tert-Butyldiphenylsiloxy)-3-fluorobenzyl Group
55.1, 42.6, 36.4, 30.8, 26.7, 19.9; HRESIMS calcd for
7.75-7.71 (m, 8H), 7.48-7.34 (m, 22H), 7.26-7.22 (dd, J ) 2.0,
12.0 Hz, 1H), 6.91-6.89 (dd, J ) 1.5, 12.0 Hz, 1H), 6.84 (s, 1H),
6.82 (s, 1H), 6.63 (d, J ) 8.5 Hz, 1H), 6.76 (t, J ) 8.0 Hz, 1H),
6.58-6.51 (m, 3H), 5.59 (s, 1H), 5.47 (s, 1H), 4.97 (d, J ) 12.0
Hz, 1H), 4.93 (d, J ) 12.0 Hz, 1H), 4.87 (s, 1H), 4.80 (s, 1H),
4.65 (d, J ) 12.0 Hz, 1H), 4.62 (d, J ) 12.0 Hz, 1H), 4.31-4.22
(m, 5H), 4.15 (t, J ) 9.5 Hz, 1H), 4.04 (t, J ) 9.5 Hz, 1H), 4.01
(d, J ) 3.5 Hz, 1H), 3.90 (t, J ) 10.0 Hz, 1H), 3.76 (t, J ) 9.5 Hz,
1H), 3.74 (s, 3H), 3.60-3.58 (dd, J ) 3.0, 10.0 Hz, 1H), 3.43-3.41
(dd, J ) 3.0, 10.0 Hz, 1H), 3.37-3.32 (dt, J ) 5.0, 9.5 Hz, 1H),
3.29-3.25 (dt, J ) 5.0,10.0 Hz, 1H), 2.18 (s, 3H), 1.76 (d, J )
10.0 Hz, 3H), 1.70 (d, J ) 11.0 Hz, 3H), 1.67 (d, J ) 11.5 Hz,
3H), 1.60 (d, J ) 12.0 Hz, 3H), 1.14 (s, 9H); 13C NMR (125.6
MHz, CDCl3) δ 159.3, 153.88 (d, J ) 245.0 Hz), 153.85 (d, J )
246.1 Hz), 142.83 (d, J ) 12.1 Hz), 142.79 (d, J ) 12.1 Hz), 137.9,
137.7, 135.7, 132.91, 132.88, 132.87, 132.7 (d, J ) 5.7 Hz), 132.3
(d, J ) 6.0 Hz), 131.2, 131.0, 130.2, 129.1, 129.0, 128.5, 128.4,
128.0, 126.30, 126.26, 123.1 (d, J ) 2.8 Hz), 121.0, 120.9, 116.0
C75H83O14FSiNa [M + Na]+ 1277.5434, found 1277.5403. 26ꢀ:
1
colorless oil; [R]24 -54.2 (c 1.0, CHCl3); H NMR (500 MHz,
D
CDCl3) δ 7.73-7.72 (m, 4H), 7.49-7.17 (m, 21H), 6.70-6.65 (m,
5H), 6.57 (t, J ) 8.5 Hz, 1H), 5.61 (s, 1H), 5.49 (s, 1H), 4.93 (d,
J ) 12.5 Hz, 1H), 4.871 (s, 1H), 4.87 (d, J ) 12.0 Hz, 1H), 4.82
(d, J ) 12.0 Hz, 1H), 4.64 (d, J ) 12.0 Hz, 1H), 4.44 (d, J ) 12.5
Hz, 1H), 4.36 (d, J ) 12.0 Hz, 1H), 4.32-4.29 (dd, J ) 5.0, 10.5
Hz, 1H), 4.18-4.15 (dd, J ) 5.0, 10.5 Hz, 1H), 4.10 (t, J ) 9.5
Hz, 1H), 4.06-4.03 (dd, J ) 3.0, 10.5 Hz, 1H), 4.00 (t, J ) 10.0
Hz, 1H), 3.96 (t, J ) 10.0 Hz, 1H), 3.88 (s, 1H), 3.83 (t, J ) 10.5
Hz, 1H), 3.80 (d, J ) 3.0 Hz, 1H), 3.73 (s, 3H), 3.60 (s, 3H),
3.60-3.59 (m, 1H), 3.42-3.38 (dt, J ) 5.0, 9.5 Hz, 1H), 3.16-3.13
(dd, J ) 3.0, 9.5 Hz, 1H), 2.85-2.80 (dt, J ) 4.5, 9.5 Hz, 1H),
2.22 (s, 3H), 1.94 (d, J ) 11.0 Hz, 3H), 1.86 (d, J ) 11.0 Hz, 3H),
1.70 (d, J ) 12.0 Hz, 3H), 1.66 (d, J ) 12.5 Hz, 3H), 1.13 (s, 9H);
13C NMR (125.6 MHz, CDCl3) δ 159.6, 159.2, 153.9 (d, J ) 245.7
Hz), 142.9 (d, J ) 11.2 Hz), 137.8, 135.7, 132.8, 132.5 (d, J ) 5.5
Hz), 131.0, 130.8, 130.4, 130.24, 130.21, 129.1, 129.0, 128.41,
128.37, 128.0, 126.5, 126.2, 122.8 (d, J ) 3.7 Hz), 121.1, 115.7
(d, J ) 19.6 Hz), 113.9, 113.7, 102.0, 101.5, 97.4 (1JCH ) 156.5
Hz), 95.8 (1JCH ) 154.0 Hz), 78.4, 77.8, 77.2, 75.9, 75.0, 74.3,
73.76, 73.74, 73.6, 71.2, 69.1, 68.7, 67.9, 67.7, 55.45, 55.42, 42.8,
36.4, 30.9, 26.8, 19.0; HRESIMS calcd for C75H83O14FSiNa [M +
Na]+ 1277.5434, found 1277.5483.
(d, J ) 18.5 Hz), 115.7 (d, J ) 19.6 Hz), 113.7, 104.4 (1JCH
)
154.0 Hz), 101.8, 101.5, 94.6 (1JCH ) 154.0 Hz), 79.1, 78.5, 78.3,
76.6, 75.7, 74.0, 73.9, 70.7, 70.6, 69.2, 68.9, 68.0, 67.5, 55.4, 42.8,
36.4, 30.8, 26.8; HRESIMS calcd for C90H98O14F2Si2Na [M + Na]+
1519.6361, found 1519.6327.
Acknowledgment. We thank the NIH (GM57335 and
GM62160) for financial support.
1-Adamantanyl 4,6-O-Benzylidene-3-O-[4-(tert-butyldiphenyl-
siloxy)-3-fluorobenzyl]-2-O-(4-methoxybenzyl)-ꢀ-D-mannopyrano-
syl-(1f2)-4,6-O-benzylidene-3-O-[4-(tert-butyldiphenylsiloxy)-3-
fluorobenzyl]-ꢀ-D-mannopyranoside (27). Prepared by the general
1
Supporting Information Available: Copies of H and 13C
NMR spectra of all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
glycosylation procedure with a yield of 98.4 mg (62%). 27: colorless
1
oil; [R]23 -29.7 (c 2.0, CHCl3); H NMR (500 MHz, CDCl3) δ
JO900026E
D
J. Org. Chem. Vol. 74, No. 6, 2009 2493