Caputo et al.
the solvents were evaporated under reduced pressure. Chro-
matography of the crude residue on silica gel (hexane/EtOAc
) 8/2) afforded the pure dihydropyran 5, beside a small
amount of its epimer at C-1 (0.83 g, 90% overall yield;
diastereomeric ratio 85:15).
tion of D and L fully hydroxylated hexoses, by replacing
benzyl glycidyl ether with D- and L-glyceraldehyde,
respectively. Work is also in progress in our lab to
prepare D- and L-iminosugars starting with the coupling
of 1 with the enantiomeric Garner aldehydes.
Da ta for d ih yd r op yr a n 5: lower Rf compound, 0.71 g, oily;
[R]25 +39.0 (c 1.4, CHCl3); 1H NMR (400 MHz) δ 1.95 (dd,
D
Exp er im en ta l Section
1H, J ) 3.4, 16.5 Hz), 2.41 (dd, 1H, J ) 11.6, 16.5 Hz), 3.08-
3.18 (m, 2H), 3.21-3.31 (m, 2H), 3.43 (s, 3H), 3.55 (dd, 2H, J
) 4.6), 4.28-4.34 (m, 1H), 4.57 (d, 1H, J ) 12.1 Hz), 4.61 (d,
1H, J ) 12.1 Hz), 4.76 (s, 1H), 7.25-7.38 (m, 5H); 13C NMR
(50 MHz) δ 27.3, 28.5, 32.8, 55.2, 66.3, 71.6, 73.1, 98.2, 118.3,
123.5, 127.3, 128.1, 137.8. Anal. Calcd for C16H20O3S2: C,
59.23; H, 6.21. Found: C, 59.39; H 6.23.
(2R)-1-(Ben zyloxy)-3-(3-{[(4-m eth oxyben zyl)oxy]m eth yl}-
5,6-dih ydr o-1,4-dith iin -2-yl)pr opan -2-ol (2a). Typical Cou -
p lin g P r oced u r e of 1. To a stirred solution of 1 (1.0 g; 3.6
mmol) [prepared in situ according to ref 18] in anhydrous THF
(5 mL), at -78 °C and under argon atmosphere, was added
dropwise over 10 min a solution of (R)-(-)-benzyl glycidyl ether
(0.7 mL; 4.4 mmol) and Ti(OPri)4 (0.2 mL; 0.9 mmol) in the
same solvent (2 mL). The reaction mixture was stirred 1 h at
-78 °C and 3 h at -40 °C and then quenched carefully with
10% aqueous NH4Cl. Usual workup18 and chromatography on
silica gel (hexane/acetone ) 8/2) of the crude residue finally
Da ta for th e C-1 ep im er of 5: higher Rf compound, 0.12
g, oily; [R]25 +18.2 (c 0.9, CHCl3); 1H NMR (200 MHz) δ 1.95
D
(dd, 1H, J ) 3.3, 16.6 Hz), 2.40 (dd, 1H, J ) 11.4, 16.6 Hz),
3.00-3.30 (m, 4H), 3.54 (dd, 1H, J ) 4.5, 10.4 Hz), 3.57 (dd,
1H, J ) 5.3, 10.3 Hz), 3.83 (s, 3H), 4.30-4.37 (m, 1H), 4.57 (d,
1H, J ) 12.1 Hz), 4.61 (d, 1H, J ) 12.1 Hz), 4.85 (s, 1H), 7.20-
7.40 (m, 5H); 13C NMR (75 MHz) δ 27.6, 29.7, 33.1, 63.7, 66.6,
71.9, 73.4, 97.4, 118.8, 124.0, 127.6, 128.1, 128.4, 138.1. Anal.
Calcd for C16H20O3S2: C, 59.23; H, 6.21. Found: C, 59.32; H,
6.19.
afforded pure 2a (1.4 g; 90%, oily): [R]25 +8.0 (c 2.0, CHCl3);
D
IR (film) 3430 cm-1; H NMR (400 MHz) δ 2.39 (dd, 1H, J )
1
4.5, 15.0 Hz), 2.65 (dd, 1H, J ) 8.4, 15.0 Hz), 3.12-3.22 (m,
4H), 3.44 (dd, 1H, J ) 5.8, 10.0 Hz), 3.48 (dd, 1H, J ) 4.6,
10.0 Hz), 3.78 (s, 3H), 3.90 (d, 1H, J ) 11.5 Hz), 3.96-4.06
(m, 1H), 4.14 (d, 1H, J ) 11.5 Hz), 4.46 (s, 2H), 4.57 (s, 2H),
6.83 (d, 2H, J ) 8.0 Hz), 7.25 (d, 2H, J ) 8.0 Hz), 7.28-7.38
(m, 5H); 13C NMR (75 MHz) δ 29.6 (2xC), 39.2, 55.2, 69.2, 69.8,
72.0, 73.3, 73.8, 113.7, 122.1, 126.4, 127.6, 128.3, 129.6, 138.1,
159.2. Anal. Calcd for C23H28O4S2: C, 63.68; H, 6.54. Found:
C, 63.75; H, 6.55.
(2R,6R)-2-[(Ben zyloxy)m eth yl]-6-m eth oxy 3,6-d ih yd r o-
2H-p yr a n (6). A solution of dihydropyran 5 (0.6 g; 1.85 mmol)
in THF (10 mL) was added in one portion to a stirred
suspension of Raney-Ni (W2) (5.5 g, wet) in the same solvent
(5 mL) at room temperature and under an argon stream. The
suspension was stirred for 5 min (TLC monitoring), and then
the solid was filtered off and washed with THF. The filtrate
was evaporated under reduced pressure to afford a crude
residue whose chromatography on silica gel (hexane/acetone
Under the same conditions, the enantiomer 3a was obtained
from the coupling of 1 with (S)-(+)-benzyl glycidyl ether (89%
yield): [R]25 -8.0 (c 2.0, CHCl3). Anal. Calcd for C23H28O4S2:
D
) 8/2) gave pure 6 (0.32 g, 75% yield): [R]25 +23.7 (c 1.5,
C, 63.86; H, 6.52. Found: C, 63.75; H, 6.55. H NMR and 13C
1
D
CHCl3); 1H NMR (500 MHz) δ 1.94 (dddd, 1H, J ) 1.5, 3.4,
5.6, 17.6 Hz), 2.17 (dddd, 1H, J ) 2.0, 4.4, 11.3, 17.6 Hz), 3.44
(s, 3H), 3.58 (d, 2H, J ) 4.88 Hz), 4.08-4.16 (m, 1H), 4.58 (d,
1H, J ) 12.2 Hz), 4.63 (d, 1H, J ) 12.2 Hz), 4.91 (s, 1H), 5.72-
5.80 (m, 1H), 6.00-6.05 (m, 1H), 7.25-7.40 (m, 5H); 13C NMR
(50 MHz) δ 29.7, 55.1, 65.6, 72.4, 73.2, 95.7, 125.3, 127.5, 128.3,
128.6, 138.3. Anal. Calcd for C14H18O3: C, 71.77; H, 7.74.
Found: C, 71.56; H, 7.77.
NMR spectra superimposable on those of 2a .
Da ta for Com p ou n d 2b: oily, [R]25 +9.0 (c 2.5, CHCl3);
D
IR (KBr) 1740 cm-1; H NMR (400 MHz) δ 2.05 (s, 3H), 2.48
1
(dd, 1H, J ) 5.8, 14.8 Hz), 2.75 (dd, 1H, J ) 7.8, 14.8 Hz),
3.07-3.19 (m, 4H), 3.50-3.62 (m, 2H), 3.82 (s, 3H), 4.05 (d,
1H, J ) 11.9 Hz), 4.21 (d, 1H, J ) 11.9 Hz), 4.44 (s, 2H), 4.48
(d, 1H, J ) 12.0 Hz), 4.52 (d, 1H, J ) 12.0 Hz), 5.21-5.30 (m,
1H), 6.80 (d, 2H, J ) 8.0 Hz), 7.25-7.40 (m, 7H); 13C NMR
(75 MHz) δ 21.1, 28.5, 29.2, 36.3, 55.2, 69.7, 70.4, 71.7, 71.9,
73.1, 73.3, 113.8, 123.8, 124.6, 127.6, 128.4, 129.5, 130.1, 138.1,
159.3, 170.3. Anal. Calcd for C25H30O5S2: C, 63.26; H, 6.37.
Found: C, 63.18; H, 6.39.
Ca r ba ld eh yd e 4. Oxid a tive Clea va ge of th e MP M
P r otectin g Gr ou p . To a stirred CH2Cl2/H2O (9:1) emulsion
(50 mL) containing the MPM ether 2b (0.5 g; 1.0 mmol) was
added DDQ (0.3 g; 1.3 mmol) in one portion at room temper-
ature. After 1 h, the suspension was filtered, and the solid was
washed with CH2Cl2. The organic layer was separated and
dried (Na2SO4), and the solvents were evaporated under
reduced pressure. Chromatography of the crude product on
silica gel (hexane/acetone ) 8/2) gave the pure carbaldehyde
4 (0.32 g; 90%, oily): [R]25D -22.1 (c 3.0, CHCl3); IR (film) 2880,
1705, 1738, 1235 cm-1; 1H NMR (300 MHz) δ 2.06 (s, 3H), 2.86
(dd, 1H, J ) 4.4, 14.8 Hz), 3.08-3.18 (m, 2H), 3.26-3.34 (m,
2H), 3.40 (dd, 1H, J ) 8.8, 14.8 Hz), 3.62 (d, 2H, J ) 4.6 Hz),
4.58 (s, 2H), 5.24-5.35 (m, 1H), 7.24-7.50 (m, 5H), 9.82 (s,
1H); 13C NMR (75 MHz) δ 20.9, 30.3, 30.8, 35.8, 69.8, 71.5,
73.2, 122.0, 124.2, 127.6, 128.3, 128.7, 137.3, 170.1, 183.2.
Anal. Calcd for C17H20O4S2: C, 57.93; H, 5.72. Found: C, 58.05;
H 5.74.
Met h yl 6-O-Ben zyl-4-d eoxy-r-L-lyxo-h exop ir a n osid e
(7a ). To a solution of 6 (0.12 g; 0.52 mmol) in 1:1 tert-butyl
alcohol/acetone (4.8 mL) cooled in ice bath was added an excess
of a chilled 1:1 (w/w) solution of 4-methylmorpholine-N-oxide
(0.14 g; 1.04 mmol) in water in one portion. After some
minutes, a catalytic amount (2% mol) of OsO4 was added to
the reaction mixture, and stirring was continued for 28 h at
room temperature. The reaction was quenched with saturated
aqueous Na2SO3, and the mixture was extracted with Et2O
and washed with brine. The combined organic layers were
dried (Na2SO4) and filtered, the solvent was evaporated, and
the crude residue was purified on silica gel (hexane/acetone
) 1/1) to give the diol 7a (0.13 g) in 96% yield: mp 79-81 °C
(from diethyl ether); [R]25D -20.9 (c 1.6, CHCl3); IR (film) 1230,
1
1738, 1750 cm-1, H NMR (500 MHz) δ 1.64 (apparent q, 1H,
J 4ax,3 ) J 4ax,4eq ) J 4ax,5 ) 12.0 Hz, H-4ax), 1.71-1.76 (m, 1H,
H-4eq), 2.20-2.70 (m, 2 x OH), 3.38 (s, 3H, OCH3), 3.53 (dd,
1H, J 6a,5 ) 4.4, J 6a,6b ) 10.2 Hz, H-6a), 3.56 (dd, 1H, J 6b,5
)
5.4, J 6b,6a )10.2 Hz, H-6b), 3.73 (brs, 1H, H-2), 3.88-3.93 (m,
1H, H-5), 3.94-4.00 (m, 1H, H-3), 4.58 (d, 1H, J a,b ) 12.2 Hz,
Bn-Ha), 4.62 (d, 1H, J b,a ) 12.2 Hz, Bn-Hb), 4.79 (s, 1H, H-1),
7.27-7.39 (m, 5H, H-arom); 13C NMR (50 MHz) δ 30.7 (C-4),
54.8 (OCH3), 65.5, 67.3 and 68.8 (C-2, C-3 and C-5), 72.4 and
73.3 (C-6 and C-Bn), 101.3 (C-1), 127.5, 128.2 (C-arom), 137.8
(C-arom). Anal. Calcd for C14H20O5: C, 62.67; H, 7.51. Found:
C, 62.72; H, 7.52.
(5R,7R)-7-[(Ben zyloxy)m et h yl]-5-m et h oxy-2,3,7,8-t et -
r a h yd r o-5H-[1,4]d ith iin o[2,3-c]p yr a n (5). To a stirred solu-
tion of carbaldehyde 4 (1.0 g; 2.8 mmol) in methanol (5 mL)
at room temperature were added TEA (1.95 mL; 14.0 mmol)
and then TMSOTf (2.2 mL; 14.0 mmol) portionwise over 1 h.
After 2 h, most of the solvent was evaporated under reduced
pressure and replaced by EtOAc. The organic phase was
washed with brine until neutral and then dried (Na2SO4), and
Da ta for d ia ceta te 7b: oily (98% yield); [R]25 -29.7 (c
D
0.4, CHCl3); 1H NMR (400 MHz) δ 1.77-1.96 (m, 2H), 2.03 (s,
3H), 2.16 (s, 3H), 3.41 (s, 3H), 3.55 (dd, 1H, J ) 4.2, 10.3 Hz),
3.62 (dd, 1H, J ) 5.7, 10.3 Hz), 4.03-4.12 (m, 1H), 4.58 (d,
7036 J . Org. Chem., Vol. 69, No. 21, 2004