May 1998
SYNTHESIS
769
2), 63.3 (C-3), 71.7, 73.5, 74.4 (CMe3), 76.1 (C-5), 127.7, 127.8,
128.4, 137.7, 170.4 (C-1).
Anal. Calcd for C17H24O4: C 69.84; H 8.27; Found: C 69.92; H 8.28.
MS (CI): m/z (%) = 293 (MH+, 3), 237 (4), 219 (9), 157 (3), 129 (8),
91 (100).
Tetrahydropyranyl Dibenzyl Ether (–)-(2S,4R,6R,1¢R)-(9):
To a suspension of NaH (prewashed from mineral oil with hexane,
0.87 g, 36 mmol) in DMF (30 mL) was successively added dropwise
at 0°C a solution of unpurified diol (-)-8 (4.62 g, 14 mmol) in DMF
(60 mL) and benzyl bromide (4.1 mL, 34 mmol). After stirring over a
24–48 h period at r.t. (meanwhile gas evolution had ceased and medi-
um had become nearly clear yellow), quenching with H2O (150 mL),
extraction with Et2O (200 mL), and drying (MgSO4), the evaporated
product was chromatographed (Et2O/petroleum ether 1:1), giving
dibenzyl ether (–)-9 (6.42 g, 93%, 85% from diester (+)-6) as a thick
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D-2,4-dideoxygluconolactone (+)-12; [a]D +19.5 (c = 2.4, MeOH)
was obtained from adduct (–)-(2R,4R,1¢S)-4cb by the same five-step
procedure.
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white oil; Rf 0.60 (Et2O/petroleum ether 1:1); [a]D –4.8 (c = 4.3,
O-6-Benzyl-L-2,4-dideoxygluconolactone [(+)-13]:
MeOH).
To a solution oflactone (+)-12 (0.292 g, 1.0 mmol) in CH2Cl2 (2 mL) was
added trifluoroacetic acid (1 mL) at r.t. After stirring for 24 h, the mixture
was diluted with CH2Cl2 (50 mL), washed with sat. aq NaHCO3, dried
andtheconcentratedoilyresiduewasextractedwithboilingEt2O.After
evaporation, thecrudeproductwaschromatographed(EtOAc/cyclohex-
ane4:6),givinglactone(+)-13;(0.175g,75%,)asanoil;Rf0.10(EtOAc/
cyclohexane 4:6); [a]D20 +19.4 (c = 1.03, MeOH).
1H NMR (400 MHz, CDCl3): d = 1.19 (s, 9H, Me3C), 1.23 (í q, 1H,
J í 12 Hz), 1.51 (ddd, 1H, J = 11, 13 Hz), 1.82 (m, 1H), 2.12 (m, 1H),
3.38–3.56 (m, 3H), 3.57–3.74 (m, 3H), 4.39 (d, 1H, J = 12.1 Hz, ben-
zyl), 4.44 (d, 1H, J = 12.1 Hz, benzyl), 4.54 (d, 1H, J = 12.1 Hz, ben-
zyl), 4.59 (d, 1H, J = 12.1 Hz, benzyl), 4.77 (dd, 1H, J = 9.8 and 1.8
Hz), 4.95 (dd, 1H, J = 8.0 and 3.7 Hz), 7.3–7.5 (m, 15H).
13C NMR (100 MHz, CDCl3): d = 28.4, 37.0, 40.9, 66.4, 72.1, 73.0,
73.3, 73.4, 73.7, 75.1, 79.3, 100.8, 126.8, 127.4, 127.5, 127.6, 128.1,
128.3, 128.4, 138.3, 138.5, 139.8.
IR (neat): n = 3430 (OH), 1735 cm–1 (C=O).
1H NMR (400 MHz, CDCl3): d = 1.76 (ddd, 1H, J = 8.0, 9.8 and 14.0
Hz, 4-Hax), 2.22 (dddd, 1H, 4-Heq), 2.47 (dd, 1H, J = 7.4 and 17.2 Hz,
2-Hax), 2.80 (ddd, 1H, J = 1.5, 5.4 and 17.2 Hz, 2-Heq), 3.30 (br s, 1H,
OH), 3.62 (m, 2H, 6-H), 4.18 (m, 1H), 4.39 (m, 1H), 4.58 (s, 2H, ben-
zyl), 7.32 (m, 5H, Ar-H).
MS(EI): m/z (%) = 341 (M+-CH2OH – CH2=CMe2, 1), 277 (1), 251
(2), 235 (2), 219 (5), 203 (5), 157 (14), 107 (27), 91 (100), 57 (43).
13C NMR (100 MHz, CDCl3): d = 33.8 (C-4), 39.4 (C-2), 62.6 (C-3),
71.0, 73.0, 75.7 (C-5), 127.8, 128.0, 128.5, 137.4, 170.6 (C-1).
HRMS for C13H17O4 (CI), (M+H)+ Calcd: 237.1127. Found:
237.1127.
6-O-Benzyl-3-O-tert-butyl-L-2,4-dideoxyglucopyranose (10):
To a solution of (–)-9 (6.06 g, 12 mmol) in THF (120 mL) was added
3 N aq HCl (80 mL) at r.t. After stirring for 48 h (meanwhile clearness
of the medium was maintained by THF dilution), the mixture was
poured into sat. aq NaHCO3 (350 mL) and extensively extracted with
hot EtOAc (10 ´ 80 mL). The combined organic layers were washed
with sat. brine (20 mL), dried (MgSO4) and the concentrated product
was chromatographed (EtOAc/cyclohexane 4:6), giving benzyloxy-
phenylethanol (–)-11 (Rf 0.44, 2.58 g) and then lactol L-10 (Rf 0.26,
3.37 g, 91%) as clear oily mixture of anomers (a/b 70:30) which
slowly crystallized; mp 50–54°C.
(4R,6S)-6-Benzyloxymethyl-4-tert-butoxytetrahydro-2H-pyran-
2-one [(+)-15]:
A solution of lactone (–)-12 (0.59 g, 2 mmol) in THF (30 mL) was
treated with 1 M aq NaOH (10 mL) for 1 h at 4°C. The mixture was
next treated with excess sat. aq NH4Cl (5 mL) then solid NH4Cl (1 g),
and diluted with CH2Cl2 (50 mL). After rapid extraction with cold
CH2Cl2 (5 ´ 50 mL), the dried solution (MgSO4) was concentrated
(´ 10) at 4 °C. To the resulting solution (ca. 30 mL) were added PPh3
(0.50 g) and then, at 4°C, dropwise diisopropyl azodicarboxylate
(420 mL). After stirring for 60 h, the concentrated product was chro-
matographed (Et2O/petroleum ether 4:6), giving trans-lactone (+)-15
(0.25 g, 42%,) as a solid; needles; mp 79–80°C); Rf 0.30 (Et2O/petro-
leum ether 4:1); [a]D20 +10.5 (c = 1.03, MeOH).
IR (neat): n = 3400 cm–1 (OH).
1H NMR (400 MHz, CDCl3): d = a anomer: 1.20 (s, 9H, Me3C), 1.32
(í q, 1H, J í 12 Hz), 1.55 (m, 1H), 1.75 (m, 1H), 1.92 (m, 1H), 3.10
(m, 1H), 3.41 (dd, 1H, J = 10.0 and 3.5 Hz), 3.47 (dd, 1H, J = 10.0
and 6.7 Hz), 4.01 (m, 1H), 4.23 (m, 1H), 4.53 (d, 1H, J = 12.0 Hz,
benzyl), 4.57 (d, 1H, J = 12.0 Hz, benzyl), 5.41 (m, 1H), 7.3–7.5 (m,
5H). b anomer: 1.19 (s, 9H, Me3C), 1.35 (í q, 1H, J í 12 Hz), 1.75
(m, 2H), 2.06 (m, 1H), 3.43 (m, 1H), 3.60 (m, 3H), 3.73 (m, 1H), 4.53
(d, 1H, J = 12.2 Hz, benzyl), 4.59 (d, 1H, J = 12.2 Hz, benzyl), 4.72
(m, 1H), 7.3–7.5 (m, 5H).
IR (neat): n = 1740 cm–1 (C=O).
1H NMR (400 MHz, CDCl3): d = 1.17 (s, 9H, Me3C), 1.82 (ddt, 1H,
4-Hax), 2.12 (dddd, 1H, J = 1.5, 4.7, 8.2 and 8.2 Hz, 4-Heq), 2.53 (ddd,
1H, J = 1.3, 4.5 and 17.2 Hz, 2-Heq), 2.62 (dd, 1H, J = 4.9 and
17.2 Hz, 2-Hax), 3.62 (dd, 1H, J = 4.3 and 10.6 Hz, 6-H), 3.68 (dd, 1H,
J = 4.0 and 10.6 Hz, 6-H), 4.13 (m, 1H, 3-H), 4.58 (d, 2H, benzyl),
4.80 (m, 1H, 5-H), 7.32 (m, 5H, Ar-H).
13C NMR (100 MHz, CDCl3): d = a anomer: 28.4, 37.3, 39.1, 62.7,
67.2, 73.4, 73.4, 73.9, 93.1, 127.7, 127.8, 128.4, 138.1. b anomer:
28.4, 36.5, 42.1, 60.4, 66.1, 71.8, 72.9, 74.0, 94.8, 127.7, 127.8,
128.4, 138.1.
13C NMR (100 MHz, CDCl3): d = 28.2 (Me3C), 32.9 (C-4), 38.9 (C-
2), 62.0 (C-3), 71.8, 73.6, 74.4 (CMe3), 75.6 (C-5), 127.7, 127.8,
128.4, 137.8, 170.6 (C-1).
Anal. Calcd for C17H24O4: C 69.84; H 8.27; Found: C 69.54; H 8.13
MS (CI): m/z (%) = 293 (M+H+, 8), 237 (4), 219 (19), 157 (4), 129
(9), 91 (100).
Anal. Calcd for C17H26O4: C 69.36; H 8.90; Found: C 69.01; H 8.71.
O-6-Benzyl-O-3-tert-butyl-L-2,4-dideoxygluconolactone [(–)-12]:
To a solution of lactol L-10 (3.23 g, 11 mmol) in CH2Cl2 (80 mL)
were successively added PCC (7.76 g, 36 mmol) and 3A powdered
molecular sieves. After stirring for 15 h at r.t., the mixture was diluted
with Et2O (150 mL) and filtered. The filtrate was dried (MgSO4) and
evaporated, and the crude residue was chromatographed (Et2O/petro-
leum ether from 1:1 to 2:1), giving lactone (–)-12 (2.86 g, 89%,) as an
oil; Rf 0.44 (Et2O/petroleum ether 2:1); [a]D20 –19.5 (c = 2.4, MeOH).
IR (neat): n = 1741 cm–1 (C=O).
(4R,6S)-6-Benzyloxymethyl-4-hydroxytetrahydro-2H-pyran-2-
one [(+)-16]:
To a solution of lactone (+)-15 (0.292 g, 1 mmol) in CH2Cl2 (2 mL)
was added trifluoroacetic acid (1 mL) at r.t. After stirring for 24 h, the
mixture was diluted with CH2Cl2 (50 mL), washed with sat. aq
NaHCO3, dried and the concentrated oily residue was extracted with
boiling Et2O. After evaporation, the crude product was chromato-
1H NMR (400 MHz, CDCl3): d = 1.20 (s, 9H, Me3C), 1.74 (ddd, 1H,
J = 10.0, 11.7 and 13.7 Hz, 4-Hax), 2.12 (dddd, 1H, J = 1.5, 3.3, 4.9
and 13.7 Hz, 4-Heq), 2.43 (dd, 1H, J = 8.4 and 17.4 Hz, 2-Hax), 2.80
(ddd, 1H, J = 1.5, 6.0 and 17.4 Hz, 2-Heq), 3.61 (dd, 1H, J = 4.8 and
10.3 Hz, 6-H), 3.65 (dd, 1H, J = 4.9 and 10.3 Hz, 6-H), 3.97 (dddd,
1H, 3-H), 4.38 (m, 1H, 5-H), 4.58 (s, 2H, benzyl), 7.32 (m, 5H, Ar-H).
13C NMR (100 MHz, CDCl3): d – 28.2 (Me3C), 34.5 (C-4), 39.7 (C-
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graphed, giving lactone (+)-16 (0.17 g, 72%); [a]D + 6.5 (c = 1.0,
CHCl3); Rf 0.15 (Et2O); as an oily product whose physiochemical
properties were in good agreement with reported data, (Lit.19 [a]D
6.59 (c = 1.032, CHCl3).
+
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