New Homoalanine Carbanion Equivalent
J . Org. Chem., Vol. 64, No. 3, 1999 939
J ) 4.5, 6.2 Hz), 4.10 (ddd, 1 H, J ) 2.3, 4.5, 6.5 Hz), 3.96 (dd,
1 H, J ) 6.5, 9.8 Hz), 3.87 (dd, 1 H, J ) 2.3, 9.8 Hz), 3.49 (q,
1 H, J ) 0.7 Hz), 1.52 and 1.44 (2 s, 6 H), 1.46 (s, 9 H), 1.22
4.80 and 4.56 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.49 and 4.44 (2
d, 2 H, J ) 12.1 Hz, PhCH2), 4.47 (dd, 1 H, J 1a,2 ) 7.8, J 1b,2
)
3.8 Hz, H-2), 4.07 (dd, 1 H, J 7,8 ) 2.8, J 8,9 ) ∼0.5 Hz, H-8),
1
(d, 1 H, J ) 6.2 Hz). H NMR (DMSO-d6, 120 °C) for a n ti-7
4.05 (dd, 1 H, J 1a,1b ) 9.0 Hz, H-1a), 3.81 (dd, 1 H, H-1b), 3.76
Mosh er ester : δ 7.54-7.40 (m, 5 H, Ph), 5.42 (dq, 1 H, J )
3.8, 6.2 Hz), 3.99-3.91 (m, 2 H), 3.83-3.75 (m, 1 H), 3.53 (q,
1 H, J ) 1.8 Hz), 1.42 (s, 9 H), 1.40 and 1.22 (2 s, 6 H), 1.29
(d, 1 H, J ) 6.2 Hz).
(dd, 1 H, J 6,7 ) 9.1 Hz, H-7), 3.74 (ddd, 1 H, J 4a,5 ) 2.5, J 4b,5 )
8.8, J 5,6 ) 9.2 Hz, H-5), 3.69 (ddd, 1 H, J 9,10a ) 6.0, J 9,10b ) 6.5
Hz, H-9), 3.60 (t, 1 H, H-6), 3.57 (dd, 1 H, J 10a,10b ) 10.0 Hz,
H-10a), 3.51 (dd, 1 H, H-10b), 2.82 (dd, 1 H, J 4a,4b ) 16.1 Hz,
H-4a), 2.63 (dd, 1 H, H-4b), 1.52 and 1.44 (2 s, 6 H, 2 Me),
1.32 (s, 9 H, t-Bu). MALDI-TOF MS: 788.5 (M+ + Na), 804.4
(M+ + K). Anal. Calcd for C46H55NO9: C, 72.13; H, 7.24; N,
1.83. Found: C, 72.21; H, 7.25; N, 1.83. Eluted fifth was the
R-linked C-glycoside 11 (465 mg, 30%) as a syrup: [R]D ) +53.3
(4R )-2,2-Dim e t h yl-N -(t er t -b u t oxyca r b on yl)-4-(1-t r i-
m eth ylsilyloxyvin yl)-1,3-oxa zolid in e (1a ). A mixture of
ketone 8 (500 mg, 2.06 mmol), activated 4-Å powdered molec-
ular sieves (700 mg), and anhydrous CH2Cl2 (6 mL) was stirred
at room temperature for 15 min, then cooled to -15 °C. Freshly
distilled triethylamine (460 µL, 3.29 mmol) and TMSOTf (520
µL, 2.88 mmol) were added in three portions every 15 min.
After an additional 30 min at -15 °C, the mixture was diluted
with Et2O (80 mL), filtered through a pad of Celite, and
washed with cold saturated aqueous NH4Cl (2 × 10 mL). The
organic phase was dried (MgSO4), concentrated (bath temper-
ature not exceeding 40 °C), and eluted from a short column of
silica gel (4 × 2 cm, d × h) with 4:1 cyclohexane-AcOEt (100
mL) to give the trimethylsilyl enol ether 1a (531 mg, 82%) as
a low-melting solid: mp 45-48 °C; [R]D ) +23.4 (c 0.6). 1H
NMR (C2D2Cl4, 120 °C): δ 4.26 (d, 1 H, J ) 1.5 Hz), 4.24 (dd,
1 H, J ) 3.5, 7.0 Hz), 4.21 (d, 1 H, J ) 1.5 Hz), 4.04 (dd, 1 H,
J ) 7.0, 8.5 Hz), 3.95 (dd, 1 H, J ) 3.5, 8.5 Hz), 1.63 and 1.58
1
(c 0.9). H NMR (DMSO-d6, 120 °C): δ 7.35-7.20 (m, 20 H, 4
Ph), 4.74-4.41 (m, 10 H, 4 PhCH2, H-2, H-5), 4.09 (dd, 1 H,
J 1a,1b ) 9.0, J 1a,2 ) 7.2 Hz, H-1a), 4.04-3.97 (m, 2 H), 3.86
(dd, 1 H, J 1b,2 ) 3.2 Hz, H-1b), 3.85-3.62 (m, 4 H), 2.91 (dd, 1
H, J 4a,4b ) 17.0, J 4a,5 ) 8.2 Hz, H-4a), 2.68 (dd, 1 H, J 4b,5 ) 4.5
Hz, H-4b), 1.55 and 1.46 (2 s, 6 H, 2 Me), 1.38 (s, 9 H, t-Bu).
MALDI-TOF MS: 788.6 (M+ + Na), 804.7 (M+ + K). Anal.
Calcd for C46H55NO9: C, 72.13; H, 7.24; N, 1.83. Found: C,
72.15; H, 7.30; N, 1.63. Eluted sixth was (4R)-4-acetyl-2,2-
dimethyl-N-[(2,3,4,6-tetra-O-benzyl-R-D-galactopyranosyl)oxy-
carbonyl]-1,3-oxazolidine (17, 57 mg, 4%) as a syrup: [R]D
)
1
+72.2 (c 0.9). H NMR (C2D2Cl4, 120 °C): δ 7.44-7.22 (m, 20
H, 4 Ph), 6.37 (d, 1 H, J 1′,2′ ) 3.4 Hz, H-1′), 4.98 and 4.63 (2 d,
2 H, J ) 11.6 Hz, PhCH2), 4.84 and 4.78 (2 d, 2 H, J ) 11.7
Hz, PhCH2), 4.77 and 4.72 (2 d, 2 H, J ) 11.8 Hz, PhCH2),
4.55 and 4.49 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.35 (dd, 1 H,
J 4,5b ) 3.1, J 4,5a ) 7.2 Hz, H-4), 4.20 (dd, 1 H, J 2′,3′ ) 9.2 Hz,
H-2′), 4.15 (dd, 1 H, J 5a,5b ) 9.0 Hz, H-5a), 4.04 (dd, 1 H, J 3′,4′
) 2.5, J 4′,5′ ) ∼0.5 Hz, H-4′), 3.98 (dd, 1 H, H-5b), 3.86 (ddd,
1 H, J 5′,6′a ) J 5′,6′b ) 6.0 Hz, H-5′), 3.80 (dd, 1 H, H-3′), 3.68
(dd, 1 H, J 6′a,6′b ) 9.1 Hz, H-6′a), 3.61 (dd, 1 H, H-6′b), 2.16 (s,
3 H, COMe), 1.72 and 1.50 (2 s, 6 H, 2 Me). MALDI-TOF MS:
733.0 (M+ + Na), 749.0 (M+ + K). Anal. Calcd for C42H47NO9:
C, 71.07; H, 6.67; N, 1.97. Found: C, 71.00; H, 6.74; N, 1.80.
The reaction of 1a (631 mg, 2.00 mmol) with trichloroace-
timidate 9 (2.73 g, 4.00 mmol) in anhydrous CH2Cl2 (-15 °C,
addition in 4.5 h, total reaction time 5 h) using freshly
sublimed ZnBr2 (1.35 g, 6.00 mmol) instead of BF3‚Et2O,
afforded the â-linked C-glycoside 13 (92 mg, 6%) and the
R-linked C-glycoside 11 (367 mg, 24%).
(2 s, 6 H), 1.46 (s, 9 H), 0.30 (s, 9 H). Anal. Calcd for C15H29
-
NO4Si: C, 57.11; H, 9.26; N, 4.44. Found: C, 56.99; H, 9.28;
N, 4.44.
(4R)-2,2-Dim et h yl-N-(ter t-b u t oxyca r b on yl)-4-(1-ter t-
bu tyld im eth ylsilyloxyvin yl)-1,3-oxa zolid in e (1b). A mix-
ture of ketone 8 (100 mg, 0.41 mmol), activated 4-Å powdered
molecular sieves (200 mg), and anhydrous CH2Cl2 (2 mL) was
stirred at room temperature for 15 min, then cooled to 0 °C.
Freshly distilled triethylamine (91 µL, 0.66 mmol) and tert-
butyldimethylsilyl triflate (132 µL, 0.58 mmol) were added in
three portions every 15 min. After an additional 30 min at 0
°C, the mixture was diluted with Et2O (20 mL), filtered
through a pad of Celite, and washed with cold saturated
aqueous NH4Cl (2 × 4 mL). The organic phase was dried
(MgSO4), concentrated, and eluted from a column of silica gel
with 20:1 cyclohexane-AcOEt to give the tert-butyldimethyl-
silyl enol ether 1b (132 mg, 90%) as an oil: [R]D ) +22.5 (c
1
0.8). H NMR (C2D2Cl4, 120 °C): δ 4.26 (d, 1 H, J ) 1.4 Hz),
Con ver sion of th e Tetr a -O-ben zyl-r-C-glycosid e 11
in to th e Tetr a -O-a cetyl Der iva tive. To prove the R-D-
configuration the C-glycoside 11 was debenzylated (H2, 20%
Pd(OH)2/C, 1:1 MeOH-AcOEt, 1 bar, room temperature) and
peracetylated (Ac2O, Py, room temperature, 2 h). 1H NMR
(DMSO-d6, 120 °C): δ 5.31 (dd, 1 H, J 7,8 ) 3.2, J 8,9 ) 2.8 Hz,
4.23 (dd, 1 H, J ) 3.6, 6.6 Hz), 4.22 (d, 1 H, J ) 1.4 Hz), 4.03
(dd, 1 H, J ) 6.6, 8.7 Hz), 3.97 (dd, 1 H, J ) 3.6, 8.7 Hz), 1.65
and 1.58 (2 s, 6 H), 1.48 (s, 9 H), 1.00 (s, 9H), 0.22 (s, 6 H).
Anal. Calcd for C18H35NO4Si: C, 60.46; H, 9.87; N, 3.92.
Found: C, 60.48; H, 9.68; N, 3.81.
H-8), 5.21 (dd, 1 H, J 6,7 ) 8.7 Hz, H-7), 5.14 (dd, 1 H, J 5,6
)
5,9-An h yd r o-6,7,8,10-t et r a -O-b en zyl-2,4-d id eoxy-1,2-
N,O-isopr opyliden e-2-(ter t-bu toxycar bon ylam in o)-D-th r eo-
L-gu lo-3-d ecu lose (11) a n d 5,9-An h yd r o-6,7,8,10-tetr a -O-
b e n zy l-2,4-d id e o x y -1,2-N ,O -is o p r o p y lid e n e -2-(t er t -
bu toxyca r bon yla m in o)-D-th r eo-L-ga la cto-3-d ecu lose (13).
A mixture of silyl enol ether 1a (631 mg, 2.00 mmol),
trichloroacetimidate 9 (1.37 g, 2.00 mmol), activated 4-Å
powdered molecular sieves (600 mg), and anhydrous Et2O (10
mL) was stirred at room temperature for 15 min, then cooled
to -15 °C. To the mixture were added freshly distilled BF3‚
Et2O (250 µL, 2.00 mmol) and then, after 10 min at -15 °C, a
solution of trichloroacetimidate 9 (1.37 g, 2.00 mmol) in
anhydrous Et2O (2 mL) by a syringe-pump apparatus during
1.5 h. The mixture was stirred at -15 °C for an additional 20
min, diluted with 1 M phosphate buffer at pH ) 7 (0.5 mL)
and Et2O (200 mL), filtered through a pad of Celite, and
washed with 1 M phosphate buffer at pH ) 7 (2 × 20 mL).
The organic phase was dried (MgSO4) and concentrated. The
residue was purified by MPLC (8:1 cyclohexane-AcOEt) to
afford first silyl enol ether 1a (252 mg, 40%). Eluted second
was a ∼1:1 mixture of anomeric galactosyl trichloroacetamides
15 (1.96 g, 72%). Eluted third was the ketone 8 (72 mg, 15%).
Eluted forth was the â-linked C-glycoside 13 (25 mg, 2%) as a
syrup: [R]D ) +22.4 (c 0.4). 1H NMR (DMSO-d6, 120 °C): δ
7.42-7.21 (m, 20 H, 4 Ph), 4.85 and 4.67 (2 d, 2 H, J ) 11.7
Hz, PhCH2), 4.83 and 4.63 (2 d, 2 H, J ) 11.9 Hz, PhCH2),
4.7 Hz, H-6), 4.66 (ddd, 1 H, J 4a,5 ) 8.0, J 4b,5 ) 4.6 Hz, H-5),
4.50 (dd, 1 H, J 1a,2 ) 7.6, J 1b,2 ) 3.2 Hz, H-2), 4.23 (ddd, 1 H,
J 9,10a ) 9.8, J 9,10b ) 4.6 Hz, H-9), 4.16 (dd, 1 H, J 10a,10b ) 11.2
Hz, H-10a), 4.16 (dd, 1 H, J 1a,1b ) 9.4 Hz, H-1a), 4.06 (dd, 1 H,
H-10b), 3.90 (dd, 1 H, H-1b), 3.07 (dd, 1 H, J 4a,4b ) 17.6 Hz,
H-4a), 2.70 (dd, 1 H, H-4b), 2.08, 2.01, 1.99, and 1.98 (4 s, 12
H, 4 Ac), 1.58 and 1.48 (2 s, 6 H, 2 Me), 1.42 (s, 9 H, t-Bu).
Con ver sion of th e Tetr a -O-ben zyl-â-C-glycosid e 13
in to th e Tetr a -O-a cetyl Der iva tive. To prove the â-D-
configuration the C-glycoside 13 was debenzylated (H2, 20%
Pd(OH)2/C, 1:1 MeOH-AcOEt, 1 bar, room temperature) and
peracetylated (Ac2O, Py, room temperature, 2 h). 1H NMR
(DMSO-d6, 120 °C): δ 5.34 (dd, 1 H, J 7,8 ) 3.5, J 8,9 ) ∼0.8 Hz,
H-8), 5.18 (dd, 1 H, J 6,7 ) 10.0 Hz, H-7), 4.94 (dd, 1 H, J 5,6
)
9.8 Hz, H-6), 4.48 (dd, 1 H, J 1a,2 ) 7.6, J 1b,2 ) 3.6 Hz, H-2),
4.16-4.05 (m, 3 H, H-1a, H-5, H-9), 4.00 (d, 2 H, J 9,10 ) 6.0
Hz, 2 H-10), 3.88 (dd, 1 H, J 1a,1b ) 9.3 Hz, H-1b), 2.73 (dd, 1
H, J 4a,5 ) 8.6, J 4a,4b ) 17.0 Hz, H-4a), 2.61 (dd, 1 H, J 4b,5 ) 3.2
Hz, H-4b), 2.10, 2.00, 1.99, and 1.96 (4 s, 12 H, 4 Ac), 1.58,
1.46 (2 s, 6 H, 2 Me), 1.40 (s, 9 H, t-Bu).
5,9-An h yd r o-6,7,8,10-t et r a -O-b en zyl-2,4-d id eoxy-1,2-
N,O-isopr opyliden e-2-(ter t-bu toxycar bon ylam in o)-D-er yth -
r o-L-gu lo-3-d ecu lose (12) a n d 5,9-An h yd r o-6,7,8,10-tetr a -
O-b e n zyl-2,4-d id e oxy-1,2-N ,O-isop r op ylid e n e -2-(t er t -
b u t oxyca r b on yla m in o)-D-er yth r o-L-ga la cto-3-d ecu lose