2
316 J . Org. Chem., Vol. 66, No. 7, 2001
Ghavami et al.
The cyclic sulfite (12) (3.5 g, 14 mmol) was dissolved in a
mixture of MeCN (50 mL) and CCl (50 mL), and NaIO (4.1
g, 1.5 equiv) and RuCl ‚H O (50 mg) were added followed by
O (50 mL). The mixture was stirred vigorously at room
temperature until TLC (hexanes/EtOAc, 4:1) showed complete
disappearance of the starting material. The mixture was
MeOH, 10:1 + 0.1% Et
amorphous solid (40%). [R]
for C37 : C, 64.14; H, 5.82. Found: C, 64.13; H, 5.74.
2,3,5-Tr i-O-b e n zyl-1,4-d id e oxy-1,4-[[(2R ,3R )-2,4-O-
ben zylid en e-3-(su lfooxy)bu tyl]-ep isu lfon iu m ylid en e]-D-
3
N] of the crude product gave an
4
4
D
2 2
+14.3° (c 1.4, CH Cl ). Anal. Calcd
3
2
40 9 2
H O S
H
2
a r a bin itol In n er Sa lt (16). Column chromatography [CHCl
MeOH, 10:1 + 0.1% Et N] of the crude product gave an
amorphous solid (79%). [R]
(CD Cl ): δ 7.43-7.10 (20H, m, Ar), 5.49 (1H, s, CHPh), 4.59
and 4.51 (2H, 2d, J A,B ) 11.8 Hz, CH Ph), 4.54 and 4.42 (2H,
2d, J A,B ) 11.7 Hz, CH Ph), 4.56 (1H, ddd, J 2′,3′ ) J 3′,4′ax ) 9.7,
3′,4′eq ) 4.2 Hz H-3′), 4.50 (1H, dd, H-4′eq), 4.45 (1H, m, H-2),
4.44 (1H, dd, H-1′a), 4.41 (1H, m, H-3), 4.40 and 4.36 (2H, 2d,
A,B ) 11.7 Hz, CH Ph), 4.27 (1H, ddd, J 1′a,2′ ) J 1′b,2′ ) 3.5 Hz,
H-2′), 4.24 (1H, br dd, H-4), 3.96 (1H, dd, J 5a,5b ) 9.7, J 4,5a
3
/
diluted with Et
and brine (200 mL). The organic solution was dried (Na
2
O (200 mL) and washed with H
2
O (200 mL)
SO
3
1
2
4
)
D
2 2
-46.9° (c 0.65, CH Cl ); H NMR
and concentrated on a rotary evaporator. The product was
2
2
purified by flash chromatography [hexanes/EtOAc, 4:1 + 0.1%
2
Et
3
N] to yield a white solid (3.5 g, 95%). A portion of the
2
product was recrystallized from EtOAc/hexanes. Mp 115-125
J
1
°
7
J
C (dec); [R]
D
+4° (c 1.0, CHCl
3 2 2
); H NMR (CD Cl ): δ 7.48-
.37 (5H, m, Ar), 5.65 (1H, s, CHPh), 4.86 (1H, ddd, J 2,3
)
J
2
3,4ax ) 10.0, J 3,4eq ) 5.0 Hz, H-3), 4.76 (1H, dd, J 1ax,2 ) 10.7,
1ax,1eq ) 10.5 Hz, H-1ax), 4.65 (1H, dd, J 1eq,2 ) 5.0 Hz, H-1eq),
.44 (1H, dd, J 4eq,4ax ) 10.5 Hz, H-4eq), 4.25 (1H, ddd, H-2),
.97 (1H, dd, H-4ax); C NMR (CD Cl ): δ 136.32 (Cipso),
2 2
30.03 (Cpara), 128.74 (2C) and 126.52 (2C) (Cortho and Cmeta),
)
J
6.2 Hz, H-5a), 3.90 (1H, dd, J 1′b,1′a ) 13.3 Hz, H-1′b), 3.82 (1H,
dd, J 4,5b ) 9.7 Hz, H-5b), 3.76 (1H, dd, J 4′ax,4′eq ) 10.2 Hz,
H-4′ax), 3.73 (1H, br d, H-1a), 3.51 (1H, dd, J 1b,1a ) 13.2, J 1b,2
4
3
1
1
4
1
3
1
3
) 3.9 Hz, H-1b); C NMR (CD
136.29 (4Cipso), 129.80-126.56 (20CAr), 102.16 (CHPh), 84.25
(C-3), 82.56 (C-2), 77.07 (C-2′), 74.02, 72.74 (3CH Ph), 69.75
2 2
Cl ): δ 137.62, 137.27, 136.48,
02.98 (CHPh), 75.74 (C-3), 73.19 (C-1), 71.68 (C-2), 67.64 (C-
+
); MALDI-TOF MS: m/e 273 (M + H), Anal. Calcd for
2
C
11
H
12
O
6
S: C, 48.53; H, 4.44. Found: C, 48.43; H, 4.39.
(C-4′), 67.19 (C-5), 66.82 (C-3′), 65.76 (C-4), 50.41 (C-1′), 49.60
+
1
,4-An h yd r o-2,3,5-tr i-O-ben zyl-4-th io-D-a r a bin itol (8).
(C-1); MALDI-TOF MS: m/e 693 (M + H). Anal. Calcd for
1
4
A mixture of 1,4-anhydro-3-O-benzyl-4-thio-D-arabinitol (17)
1.0 g, 4.2 mmol) and 60% NaH (0.85 g, 5 equiv) in DMF (20
37 40 9 2
C H O S : C, 64.14; H, 5.82. Found: C, 64.16; H, 5.73.
(
3-O-Ben zyl-1,4-dideoxy-1,4-[[(2S,3S)-2,4-O-ben zyliden e-
3-(su lfooxy)bu tyl]-ep isu lfon iu m ylid en e]-D-a r a bin itol In -
n er Sa lt (18). Column chromatography [CHCl /MeOH, 10:1
+ 0.1% Et N] of the crude product gave an amorphous solid
(32%); H NMR (CD Cl ): δ 7.49-7.26 (10H, m, Ar), 6.22 (1H,
d, J 2,OH ) 4.4 Hz, 2-OH), 5.54 (1H, s, CHPh), 4.96 (1H, br s,
H-2), 4.65 and 4.56 (2H, 2d, J A,B ) 11.6 Hz, CH Ph), 4.64 (1H,
br m, 5-OH), 4.52 (1H, ddd, J 2′,3′ ) 9.6 Hz, H-3′), 4.46 (1H, dd,
4′eq,4′ax ) 10.6, J 3′,4′eq ) 5.4 Hz, H-4′eq), 4.32 (1H, br s, H-3),
4.30 (1H, br d, H-1a), 4.28 (1H, ddd, H-2′), 4.12 (1H, dd, J 1′a,2′
) 2.6 Hz, H-1′a), 4.10 (1H, dd, H-4), 4.01 (1H, dd, J 1′b,1′a
13.5, J 1′b,2′ ) 3.5 Hz, H-1′b), 3.92-3.78 (2H, m, H-5a, H-5b),
3.78 (1H, dd, J 3′,4′ax ) 10.1 Hz, H-4′ax), 3.67 (1H, dd, J 1b,1a
13.4, J 1b,2 ) 3.9 Hz, H-1b); 13C NMR (CD
Cl ): δ 136.92, 136.73
(2Cipso), 129.97-126.61 (10CAr), 102.32 (CHPh), 88.45 (C-3),
76.61 (C-2′), 76.22 (C-2), 72.96 (CH Ph), 71.24 (C-4), 69.27 (C-
4′), 66.96 (C-3′), 60.51 (C-5), 52.43 (C-1), 48.30 (C-1′); MALDI-
mL) was stirred in an ice-bath for 1 h. A solution of benzyl
bromide (1.9 mL, 3.8 equiv) in DMF (5 mL) was added, and
the solution was stirred at room temperature for 3 h. The
mixture was added to ice-water (150 mL) and extracted with
3
3
1
2
2
Et
concentrated. The product was purified by flash chromatog-
raphy [hexanes/EtOAc, 4:1] to give a syrup (1.6 g, 90%). [R]
2 2 4
O (150 mL). The organic solution was dried (Na SO ) and
2
D
1
+
5° (c 1.6, CHCl
Ar), 4.61 (2H, s, CH
Hz, CH
3
); H NMR (CDCl
Ph), 4.53 and 4.48 (2H, 2d, J A,B ) 12.1
Ph), 4.51 and 4.47 (2H, 2d, J A,B ) 11.9 Hz, CH Ph),
.19 (1H, ddd, J 1b,2 ) 4.6 Hz, H-2), 4.11 (1H, dd, J 2,3 ) 3.8,
3,4 ) 3.6 Hz, H-3), 3.69 (1H, dd, J 5a,5b ) 8.8, J 4,5a ) 7.6 Hz,
3
): δ 7.38-7.23 (15H, m,
J
2
2
2
)
4
J
)
H-5a), 3.57 (1H, ddd, J 4,5b ) 6.3 Hz, H-4), 3.50 (1H, dd, H-5b),
.08 (1H, dd, J 1a,1b ) 11.4, J 1a,2 ) 5.1 Hz, H-1a), 2.90 (1H, dd,
H-1b). 13C NMR (CDCl
): δ 138.16, 138.06, 137.88 (3Cipso),
28.40-127.59 (15CAr), 85.08 (C-3), 85.04 (C-2), 73.01 (CH
Ph), 72.34 (C-5), 71.85, 71.50 (2CH Ph), 48.99 (C-4), 33.10 (C-
S: C, 74.25; H, 6.71. Found: C,
2
2
3
3
2
1
2
-
+
2
28 9 2
TOF MS: m/e 513 (M + H). Anal. Calcd for C23H O S : C,
1
7
). Anal. Calcd for C26
4.18; H, 6.53.
H
28
O
3
53.89; H, 5.51. Found: C, 53.64; H, 5.34.
Gen er a l P r oced u r e for th e Dep r otection of th e P r o-
Gen er a l P r oced u r e for th e Syn th esis of th e P r otected
tected Su lfon iu m Su lfa tes. The protected compound (120
Su lfon iu m Su lfa tes (14, 15, 16). The thiosugar (3 mmol) and
mg, 0.17 mmol) was dissolved in AcOH/H
2
O, 4:1 (3 mL) and
the cyclic sulfate (1.2 equiv) were dissolved in dry acetone (0.5
stirred with Pd-C (80 mg) under H (52 psi). After 60 h the
2
mL), and anhydrous K
2
CO
3
(7 mg) was added. The mixture
reaction mixture was filtered through a pad of Celite, which
was subsequently washed with MeOH. The combined filtrates
were concentrated, and the residue was purified by column
chromatography.
was stirred in a sealed tube in an oil-bath (75 °C) overnight.
The solvent was removed under reduced pressure, and the
product was purified by column chromatography.
2
,3,5-T r i-O -b e n zy l-1,4-d id e o x y -1,4-[[(2S ,3S )-2,4-O -
ben zylid en e-3-(su lfooxy)bu tyl]-ep isu lfon iu m ylid en e]-D-
a r a bin itol In n er Sa lt (14). Column chromatography [CHCl
MeOH, 10:1 + 0.1% Et N] of the crude product gave an
amorphous solid (33%). [R]
1,4-Did eoxy-1,4-[[(2S,3S)-2,4-d ih yd r oxy-3-(su lfooxy)-
bu tyl]-ep isu lfon iu m ylid en e]-D-a r a bin itol In n er Sa lt (4).
3
/
Column chromatography [CHCl
crude product gave an amorphous solid (67%). [R]
1
3
/MeOH/H
2
O, 7:3:1] of the
3
D
+2.1° (c
1
10
28
D
-11.9° (c 1.7, CH
): δ 7.49-7.12 (20H, m, Ar), 5.54 (1H, s, CHPh), 4.59
1H, ddd, J 2′,3′ ) 9.6, J 3′,4′ax ) 10.7, J 3′,4′eq ) 5.4 Hz, H-3′), 4.54
2H, s, CH Ph), 4.51 (1H, br d, H-2), 4.50 (1H, dd, J 4′eq,4′ax
0.7 Hz, H-4′eq), 4.48 and 4.37 (2H, 2d, J A,B ) 11.7 Hz, CH
Ph), 4.38 (1H, dd, J 1′a,1′b ) 13.6, J 1′a,2′ ) 2.7 Hz, H-1′a), 4.35
2
Cl
2
); H NMR
0.48, MeOH) (lit. [R]
D
+4.9° (c 0.35, MeOH)); H NMR
(
(
(
CD
2
Cl
2
(pyridine-d ): δ 5.25 (1H, ddd, J 2′,3′ ) 7.4, J 3′,4′b ) 3.8, J 3′,4′a )
5
3.6 Hz, H-3′), 5.14-5.09 (2H, m, H-3, H-2), 5.00 (1H, m, H-2′),
4.78 (1H, dd, J 1′a,1′b ) 13.0, J 1′a,2′ ) 4.9 Hz, H-1′a), 4.70 (1H,
m, H-4), 4.63 (1H, dd, J 1′b,2′ ) 4.0 Hz, H-1′b), 4.61 (1H, dd,
2
)
2
-
1
J
4′a,4′b ) 11.8 Hz, H-4′a), 4.54 (1H, dd, J 5a,5b ) 11.6, J 4,5a ) 6.5
Hz, H-5a), 4.51 (1H, dd, J 4,5b ) 7.5 Hz, H-5b), 4.37 (1H, dd,
H-4′b), 4.32 (2H, br-s, H-1a, H-1b); 13C NMR (pyridine-d
): δ
(
1H, br s, H-3), 4.29 (1H, ddd, J 1a′,2′ ) 3.4 Hz, H-2′), 4.25 and
4
1
.15 (2H, 2d, J A,B ) 11.9 Hz, CH
2
Ph), 4.06 (1H, br-d, J 1a,1b
)
5
3.3, H-1a), 4.00 (1H, dd, H-1′b), 3.98 (1H, br dd, H-4), 3.77
79.14 (C-3′), 79.06 (C-3), 78.18 (C-2), 72.30 (C-4), 67.44 (C-2′),
62.05 (C-4′), 59.98 (C-5), 52.46 (C-1′), 50.35 (C-1). HRMS Calcd
for C H O S (M + H): 335.0471. Found: 335.0481.
9 18 9 2
1,4-Did eoxy-1,4-[[(2R,3R)-2,4-d ih yd r oxy-3-(su lfooxy)-
bu tyl]-ep isu lfon iu m ylid en e]-L-a r a bin itol In n er Sa lt (5).
(
1H, dd, H-4′ax), 3.74 (1H, dd, J 1b,2 ) 3.8 Hz, H-1b), 3.62 (1H,
dd, J 5a,5b ) 9.9, J 4,5a ) 8.7 Hz, H-5a), 3.53 (1H, dd, J 4,5b ) 7.2
1
3
Hz, H-5b); C NMR (CD
2
Cl
2
): δ 137.34, 137.24, 136.56, 136.39
(
4Cipso), 129.73-126.62 (20CAr), 101.95 (CHPh), 83.75 (C-3),
2.82 (C-2), 76.80 (C-2′), 73.73, 72.84, 72.52 (3CH
C-4′), 67.01 (C-5), 66.48 (C-3′), 65.27 (C-4), 49.67 (C-1′), 48.28
C-1); MALDI-TOF MS: m/e 693 (M + H). Anal. Calcd for
37 40 9 2
C H O S : C, 64.14; H, 5.82. Found: C, 63.88; H, 5.83.
8
2
Ph), 69.54
Column chromatography [CHCl
3
/MeOH/H
2
O, 7:3:1] of the
-1.6° (c
9 18 9 2
H O S (M + H): 335.0471.
(
(
crude product gave an amorphous solid (80%). [R]
0.6, MeOH); HRMS Calcd for C
Found: 335.0466.
D
+
2
,3,5-Tr i-O-b e n zyl-1,4-d id e oxy-1,4-[[(2R ,3R )-2,4-O-
ben zylid en e-3-(su lfooxy)bu tyl]-ep isu lfon iu m ylid en e]-L-
a r a bin itol In n er Sa lt (15). Column chromatography [CHCl
1,4-Did eoxy-1,4-[[(2R,3R)-2,4-d ih yd r oxy-3-(su lfooxy)-
bu tyl]-ep isu lfon iu m ylid en e]-D-a r a bin itol In n er Sa lt (7).
Column chromatography [CHCl :MeOH:H O, 7:3:1] of the
3 2
3
/