16
A. Dondoni, A. Marra / Tetrahedron Letters 44 (2003) 13–16
,
19. A mixture of 14 (3.29 g, 5.00 mmol), activated 4-A
powdered molecular sieves (2.5 g), anhydrous CH2Cl2 (25
mL), and anhydrous CH3CN (25 mL) was stirred at rt
for 10 min, then methyl triflate (0.85 mL, 7.50 mmol) was
added. The suspension was stirred at rt for 30 min and
then concentrated to dryness without filtering off the
molecular sieves. To a cooled (0°C), stirred suspension of
the crude N-methylbenzothiazolium salt in CH3OH (50
mL) was added NaBH4 (190 mg, 5.00 mmol). The mix-
ture was stirred at rt for an additional 10 min, diluted
with acetone, filtered through a pad of Celite, and con-
centrated. A solution of the residue in CH2Cl2 (200 mL)
was washed with H2O (40 mL), dried (Na2SO4), and
concentrated to afford a pale yellow syrup (2.95 g). To a
vigorously stirred solution of the diastereomeric benzoth-
iazolines in CH3CN (50 mL) was added dropwise H2O (5
mL) and then AgNO3 in one portion (1.70 g, 10.00
mmol). The mixture was stirred at rt for 15 min, then
diluted with 1 M phosphate buffer at pH 7 (5 mL).
Stirring was continued for an additional 15 min, then the
reaction mixture was diluted with 1 M phosphate buffer
at pH 7 (50 mL) and partially concentrated to remove
CH3CN (bath temperature not exceeding 40°C). The
suspension was extracted with CH2Cl2 (200+50 mL), the
combined organic phases were dried (Na2SO4), filtered
through a pad of Celite (1×6 cm, h×d), and concentrated
to give a yellow syrup (2.47 g). A solution of the residue
in Et2O (ca. 100 mL) was filtered through another pad of
Celite (1×4 cm, h×d), and concentrated to afford 11
together with the gem-diol 15 (2.26 g, 82%) as a colorless
syrup. High temperature 1H NMR experiments showed
that this mixture was transformed into at least 95% pure
collect the ketose 12 which crystallized during the extrac-
tion. The white solid was washed with H2O and Et2O (10
mL) and dried to give pure 12 (9.87 g, 58%). The
combined organic layers were dried (Na2SO4) and con-
centrated. The residue was eluted from a column of silica
gel with cyclohexane–AcOEt (from 4:1 to 3:1) to give 12
(3.40 g, 20%) as a white solid; mp 115–117°C (Et2O);
1
[h]D=−20 (c 0.4, CHCl3). H NMR (CDCl3, 400 MHz):
l 8.08–8.05, 7.88–7.85, 7.53–7.49, and 7.44–7.40 (4 m, 4
H, BTh), 7.36–7.20 and 7.09–6.92 (2 m, 20 H, 4 Ph), 4.92
(s, 2 H, PhCH2), 4.87 and 4.66 (2 d, 2 H, J=10.8 Hz,
PhCH2), 4.70 (s, 1 H, OH), 4.65 and 4.54 (2 d, 2 H,
J=12.1 Hz, PhCH2), 4.60 and 4.31 (2 d, 2 H, J=11.0 Hz,
PhCH2), 4.22 (ddd, 1 H, J4,5=10.2, J5,6a=4.0, J5,6b=1.8
Hz, H-5), 4.13 (dd, 1 H, J2,3=J3,4=9.2 Hz, H-3), 4.05 (d,
1 H, H-2), 3.90 (dd, 1 H, H-4), 3.85 (dd, 1 H, J6a,6b=11.4
Hz, H-6a), 3.72 (dd, 1 H, H-6b).
17. To a solution of 12 (5.60 g, 8.31 mmol) in anhydrous
CH2Cl2 (50 mL) were added at rt distilled triethylamine
(15 mL) and acetic anhydride (15 mL). The solution was
kept at rt for 24 h and then concentrated. The residue
was triturated with Et2O (2×20 mL) to give pure 13 (5.23
g, 88%); mp 136–137°C (cyclohexane); [h]D=+27 (c 1.1,
CHCl3). 1H NMR (CDCl3, 400 MHz): l 8.06–8.03 and
7.87–7.84 (2 m, 2 H, BTh), 7.49–7.01 (m, 22 H, 4 Ph,
BTh), 4.98 and 4.91 (2 d, 2 H, J=11.0 Hz, PhCH2), 4.88
and 4.67 (2 d, 2 H, J=10.5 Hz, PhCH2), 4.77 and 4.64 (2
d, 2 H, J=12.0 Hz, PhCH2), 4.50 and 4.26 (2 d, 2 H,
J=10.8 Hz, PhCH2), 4.22 (dd, 1 H, J2,3=9.4, J3,4=9.1
Hz, H-3), 3.99 (dd, 1 H, J4,5=10.2 Hz, H-4), 3.92 (dd, 1
H, J5,6a=3.2, J6a,6b=11.6 Hz, H-6a), 3.84–3.80 (m, 2 H,
H-5, H-6b), 3.67 (d, 1 H, H-2), 2.24 (s, 3 H, Ac).
1
aldehyde 11. Compound 11. H NMR (CDCl3, 25°C, 400
MHz): l 9.65 (d, 1 H, J1,2=1.6 Hz, H-1), 7.39–7.24 and
7.18–7.12 (2 m, 20 H, 4 Ph), 4.89 (s, 2 H, PhCH2), 4.80
and 4.54 (2 d, 2 H, J=10.7 Hz, PhCH2), 4.78 and 4.64 (2
d, 2 H, J=10.5 Hz, PhCH2), 4.61 and 4.55 (2 d, 2 H,
J=12.3 Hz, PhCH2), 3.82 (dd, 1 H, J2,3=9.8 Hz, H-2),
3.76 (dd, 1 H, J3,4=J4,5=8.7 Hz, H-4), 3.75 (dd, 1 H,
18. To a stirred mixture of 13 (5.73 g, 8.00 mmol), activated
,
4-A powdered molecular sieves (8.0 g), and triethylsilane
(12.8 mL, 80.0 mmol) in anhydrous CH2Cl2 (65 mL) was
added TMSOTf (2.17 mL, 12.00 mmol). The mixture was
stirred at rt for 1.5 h, then diluted with triethylamine (3
mL) and CH2Cl2 (100 mL), and filtered through Celite.
The solution was washed with H2O (30 mL), dried
(Na2SO4), and concentrated to afford a ca. 1.5:1 mixture
of 14 and 16. The residue was triturated with cyclohexane
(2×20 mL) to give pure 14 (3.16 g, 60%) as a white solid.
The mother liquor was concentrated, and the residue was
treated with a 0.2 M solution of CH3ONa in CH3OH (50
mL). After 24 h at rt the reaction mixture was neutralized
with acetic acid, concentrated, diluted with CH2Cl2 (100
mL), washed with H2O (20 mL), dried (Na2SO4), and
concentrated. The residue was triturated with cyclohex-
ane (2×10 mL) to give 14 (1.05 g, 20%) as a white solid;
mp 137–139°C; [h]D=−11 (c 0.8, CHCl3). 1H NMR
(CDCl3, 400 MHz): l 8.06–8.03 and 7.98–7.95 (2 m, 2 H,
BTh), 7.58–7.00 (m, 22 H, 4 Ph, BTh), 4.96 and 4.91 (2 d,
2 H, J=11.0 Hz, PhCH2), 4.87 and 4.64 (2 d, 2 H,
J=10.8 Hz, PhCH2), 4.78 (d, 1 H, J1,2=9.0 Hz, H-1),
4.65 and 4.57 (2 d, 2 H, J=12.2 Hz, PhCH2), 4.55 and
4.25 (2 d, 2 H, J=10.6 Hz, PhCH2), 3.88 (dd, 1 H,
J
6,7a=2.1, J7a,7b=11.0 Hz, H-7a), 3.70 (dd, 1 H, J6,7b
4.3 Hz, H-7b), 3.67 (dd, 1 H, H-3), 3.63 (dd, 1 H,
5,6=9.6 Hz, H-5), 3.52 (ddd, 1 H, H-6). 1H NMR
=
J
(DMSO-d6, 160°C, 300 MHz): l 9.63 (d, 1 H, J1,2=1.6
Hz, H-1), 7.40–7.19 (m, 20 H, 4 Ph), 4.80 (s, 2 H,
PhCH2), 4.75 and 4.62 (2 d, 2 H, J=11.5 Hz, PhCH2),
4.73 and 4.64 (2 d, 2 H, J=11.5 Hz, PhCH2), 4.58 and
4.54 (2 d, 2 H, J=11.5 Hz, PhCH2), 3.98 (dd, 1 H,
J2,3=8.6 Hz, H-2), 3.87 (dd, 1 H, J3,4=J4,5=7.7 Hz,
H-4), 3.78 (dd, 1 H, H-3), 3.76–3.68 (m, 3 H, H-6, 2 H-7),
3.59 (dd, 1 H, J5,6=8.3 Hz, H-5). Compound 15. 1H
NMR (CDCl3, 25°C, 400 MHz): l 7.38–7.23 and 7.18–
7.13 (2 m, 20 H, 4 Ph), 5.16 (ddd, 1 H, J1,2=1.6,
J1,OH=9.8, J1,OH=8.4 Hz, H-1), 4.92 (s, 2 H, PhCH2),
4.90 and 4.71 (2 d, 2 H, J=10.8 Hz, PhCH2), 4.82 and
4.56 (2 d, 2 H, J=10.8 Hz, PhCH2), 4.56 and 4.51 (2 d,
2 H, J=12.0 Hz, PhCH2), 3.74 (dd, 1 H, J3,4=9.2,
J4,5=8.8 Hz, H-4), 3.73 (dd, 1 H, J6,7a=2.3, J7a,7b=10.8
Hz, H-7a), 3.70 (dd, 1 H, J2,3=9.4 Hz, H-3), 3.69 (dd, 1
H, J6,7b=4.3 Hz, H-7b), 3.62 (dd, 1 H, J5,6=9.7 Hz,
H-5), 3.51 (ddd, 1 H, H-6), 3.39 (dd, 1 H, H-2), 3.28 (d,
1 H, OH), 3.26 (d, 1 H, OH).
J2,3=8.6, J3,4=8.7 Hz, H-3), 3.82 (dd, 1 H, H-2), 3.79
(dd, 1 H, J4,5=9.5 Hz, H-4), 3.78 (d, 2 H, J5,6=3.2 Hz,
2 H-6), 3.70 (ddd, 1 H, H-5).