Preparation of Variously Protected Glycals Using TiIII
J . Org. Chem., Vol. 64, No. 11, 1999 3989
ice. The acetylated sugar was then precipitated and collected
by filtration.53
Meth yl 2,3,4,6-Tetr a-O-acetyl-r-D-glu copyr an oside (2d).
The title compound52 was prepared (88% yield) from methyl
R-D-glucopyranoside (Aldrich, 5.07 g, 26.13 mmol).
for 2 h with exclusion of atmospheric moisture. The mixture
was poured into cold saturated NaHCO3, extracted (CHCl3),
washed (H2O), and dried (MgSO4). Concentration gave 1.40 g
of crude product as a white solid; this was recrystallized from
ethanol to give 1.06 g (82%) of the title compound as white
crystals: 1H NMR (270 MHz, CDCl3) δ 8.1 (d, 2 H), 7.5 (t, 1
H), 7.4 (t, 2 H), 5.77 (d, J ) 8.24, H1), 5.31 (t, J ) 8.9, H3),
5.25 (dd, J ) 8.9, 9.4 H4), 5.18 (dd, J ) 8.24, 8.9 H2), 4.50 (dd,
J ) 12.45, 2.3 H6) 4.39 (dd, J ) 12.45, 4.28 H6′), 3.99 (ddd, J
) 2.39. 4.28, 9.40 H5), 2.16 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H),
2.07 (s, 3H).
3,4,6-Tr i-O-ben zylglu cop yr a n ose (48). The title com-
pound61,62 was prepared in 85% yield from 3,4,6-tri-O-benzyl-
glucal.
2,3:4,6-Di-O-isop r op ylid en em a n n op yr a n ose (49). The
title compound was prepared from mannose according to the
literature.56,57
Gen er a l Meth od for th e Syn th esis of P er a cetyla ted
Glycosyl Br om id es. Glycosyl bromides were prepared either
by reaction with bromotrimethylsilane (method A)63 or by
reaction with bromine and triphenyl phosphite (method B).64
Meth od A. The peracetylated sugar was dissolved in CH2-
Cl2 or CHCl3 and cooled to -40 °C under N2. Bromotrimeth-
ylsilane (TMS-Br) was added, and the mixture was stirred and
allowed to warm to room temperature. Reactions were moni-
tored by NMR, and additional TMS-Br was added as needed.
When the reaction was complete, the solvent, any excess TMS-
Br, and TMS-OAc were removed in vacuo to give the glycosyl
bromide as a thick syrup.
Meth od B. A solution of the peracetylated sugar in THF
(4 mL/g) was stirred for 2 h with piperidine (2 mL/g). The
mixture was poured into ice-water, extracted (CHCl3), washed
(ice-cold 1 M HCl; then NaHCO3), and dried. Concentration
gave a syrup that was chromatographed on silica gel (3:2 ethyl
acetate/hexanes) to give the lactol. A solution of bromine (1.4
equiv) and triphenyl phosphite (1.4 equiv) in CH2Cl2 at 0 °C
was allowed to warm to room temperature over 0.5 h. To this
was added a solution of the lactol and pyridine (1.3 equiv) in
CH2Cl2; the mixture was stirred for 15 min and then quenched
by the addition of a saturated NaHCO3 solution, extracted,
washed, and dried.
2,3,4,6-Tetr a -O-a cetyl-r-D-m a n n op yr a n osyl Br om id e
(4a ). The title compound65 (93% yield) was prepared according
to method A from 1,2,3,4,6-penta-O-acetyl-R-D-mannopyranose
(Aldrich, 200 mg, 0.51 mmol) and TMS-Br (720 mg, 4.71 mmol)
by reaction over a period of 3 days.
2,3,4-Tr i-O-a cetyl-r-D-xylop yr a n osyl Br om id e (5). The
title compound66 was prepared (88% yield) according to method
A from 1,2,3,4-tetra-O-acetyl-â-D-xylopyranose (500 mg, 1.57
mmol) and TMS-Br (910 mg, 5.94 mmol) after stirring for 3
days.
1,2,3-Tr i-O-a cetyl-4,6-O-eth ylid en eglu cop yr a n ose (39).
The title compound was prepared in 95% yield as primarily
the R-anomer from 4,6-O-ethylideneglucose (1.1 g, 5.33
mmol): 1H NMR (300 MHz, CDCl3) δ 6.26 (d, J ) 4.03 Hz,
H1), 5.48 (dd, J ) 9.89, 10.25 Hz, H3), 5.05 (dd, J ) 4.03, 9.89
Hz, H2), 4.70 (q, J ) 5.13, 1H), 4.14 (dd, J ) 5.12, 10.25 Hz,
H4), 3.88 (dt, J ) 5.13, 9.89 Hz, H5), 3.53 (d, J ) 9.89 Hz, H6),
3.47 (d, J ) 9.89 Hz, H6′), 2.18 (s, 3H), 2.08 (s, 3H), 2.02 (s,
3H), 1.36 (d, J ) 4.9 Hz, 3H).
1-O-Acetyl-2,3,4,6-tetr a -O-ben zylglu cop yr a n ose (40).
The title compound54,55 was prepared from 2,3,4,6-tetra-O-
benzylglucopyranose (93% yield) according to method A.
1-O-Acet yl-2,3,4,6-t et r a -O-m et h ylglu cop yr a n ose (41).
The title compound was prepared (72% yield) as a mixture of
anomers (65% R and 35% â) from 2,3,4,6-tetra-O-methylglu-
copyranose (Sigma, 200 mg, 0.84 mmol): 1H NMR (300 MHz,
CDCl3) δ 6.32 (d, J ) 3.66 Hz, H1R), 5.45 (d, J ) 7.69 Hz, H1â),
3.8-3.2 (m, 18 H), 2.12 (s, 3 H).
1-O-Ace t yl-2,3:4,6-d i-O-isop r op ylid e n e m a n n ofu r a -
n ose (42). The title compound56,57 was prepared in 83% yield
from 2,3;4,6-di-O-isopropylidene mannofuranose (Aldrich, 1.00
g, 3.84 mmol) according to method A.
1-O-Ace t yl-2,3:4,6-d i-O-isop r op ylid e n e m a n n op yr a -
n ose (43). The title compound56,57 was prepared from 2,3;4,6-
di-O-isopropylidenemannopyranose.
1,3,4-T r i-O -a c e t y l-2-d e o x y -r-D -er yt h r o-p e n t o p y r a -
n ose (44). The title compound58 was prepared (27% yield) from
2-deoxyribose according to method A.
1,2,3,4-Tetr a -O-a cetyl-6-O-ben zylglu cose (45). The ace-
tal of 4,6-O-benzylideneglucose (Aldrich) was reductively
opened according to the literature.59,60 To an ice-cooled solution
of 590 mg (1.5 mmol) of 4,6-O-benzylidene glucose in 10 mL
of THF under N2 was added 15 mL of NaCNBH3 (1 M in THF).
A solution of HCl (1 M in ether) was added until gas
effervescence ceased. The mixture was stirred for 10 min and
then poured into CH2Cl2 and washed (H2O, NaHCO3). Con-
centration gave a yellow syrup that was acetylated by method
A to give 485 mg (74%) of the title compound as a white powder
(60:40 mixture of R/â anomers): 1H NMR (300 MHz, CDCl3) δ
7.2-7.5 (m, 5 H), 6.30 (d, J ) 2.93 Hz, H1R, 0.6 H), 5.66 (d, J
) 8.06 Hz, H1â, 0.4 H), 5.41 (t, J ) 9.89 Hz, 0.6 H), 5.20-5.03
(m, 2.2 H), 4.55-4.38 (m, 2 H), 4.04-4.00 (m, 0.6 H), 3.74-
3.72 (m, 0.4 H), 3.54-3.44 (m, 2 H), 2.20-1.81 (m, 12 H).
1,2,3,4-Tet r a -O-a cet yl-6-O-ter t-b u t yld ip h en ylsilylglu -
cop yr a n ose (46). A solution of 1,2,3,4-tetra-O-acetylglucopy-
ranose (Sigma, 1.0 g, 2.87 mmol), imidazole (215 mg, 3.15
mmol, 1.1 equiv), and tert-butyldiphenylchlorosilane (0.8 mL,
3.08 mmol, 1.07 equiv) in 10 mL of CH2Cl2 was stirred
overnight under N2. The mixture was poured into water,
extracted (CHCl3), washed (H2O), and dried (Na2SO4). Con-
centration gave 1.65 g (98%) of the title compound as a white
solid: 1H NMR (300 MHz, CDCl3) δ 7.82-7.61 (m, 10 H), 5.73
(d, J ) 3.6, 1 H), 5.43-5.22 (m, 3 H), 3.84-3.64 (m, 3 H), 2.22
(s, 3 H), 2.02 (s, 6 H), 1.91 (s, 3 H), 1.15 (s, 3 H), 1.05 (s, 6 H).
1,2,3,4-Tetr a -O-a cetyl-6-O-ben zoylglu cop yr a n ose (47).
A solution of 1,2,3,4-tetra-O-acetylglucopyranose (Sigma, 1.0
g, 2.87 mmol) and benzoyl chloride (0.5 mL, 4.30 mmol, 1.5
equiv) in 5 mL of pyridine was stirred at room temperature
2,3,4-Tr i-O-a cetyl-D-r ibop yr a n osyl Br om id e (6). The
title compound63 was prepared (85% yield) according to method
A from 1,2,3,4-tetra-O-acetyl-R-D-ribopyranose (300 mg, 0.94
mmol) and TMS-Br (7.4 g, 48.37 mmol).
2,3,4,6-Tetr a -O-ben zylglu cop yr a n osyl Br om id e (12).
The title compound67 was prepared in quantitative yield from
1-O-acetyl-2,3,4,6-tetra-O-benzylglucopyranose (20) according
to method A.
2,3,4,6-Tetr a -O-m eth ylglu cop yr a n osyl Br om id e (13).68
The title compound was prepared from 1-O-acetyl-2,3,4,6-tetra-
O-methylglucopyranose according to method A: 1H NMR (300
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