1610
A. Nguyen Van Nhien et al. / Carbohydrate Research 344 (2009) 1605–1611
1369, 1244, 1209, 1157, 1107, 1060 cmꢀ1
;
1H NMR (CDCl3,
26.4, 26.1, 25.4 (4 ꢃ CH3). HRMS: C21H27O9NSNa calcd 492.1304,
300 MHz) d 5.77 (s, 1H, H-5), 4.85 (t, J3a,4 = 5.5 Hz, J3a,6a = 5.5 Hz,
found 492.1296.
1H, H-3a), 4.66 (m, 3H, H-4, H-6a, H-40), 4.22 (dd, J4 ,5 A = 6.1 Hz,
0
0
J5 A,5 B = 8.1 Hz, 1H, H-50A), 3.81 (t, J4 ,5 B = 8.1 Hz, 1H, H-50B), 1.45,
1.42, 1.40, 1.37 (s, 12H, 4 ꢃ CH3), 0.93 [SiC(CH3)], 0.14 (SiCH3),
0.13 (SiCH3); 13C NMR (CDCl3, 75 MHz) d 142.9 (C-6), 130.4 (C-5),
112.6 [OC(CH3)2], 109.3 [OC(CH3)2], 83.5 (C-3a), 79.0, 74.8, 73.8
(C-4, C-6a, C-40), 69.6 (C-50), 27.8, 27.0, 26.8, 26.3 (4 ꢃ CH3), 26.3
[SiC(CH3)3], 18.9 [SiC(CH3)3], ꢀ3.9 (SiCH3), ꢀ4.3 (SiCH3). HRMS:
0
0
0
0
5
O
4
6
O
OBz
OBz
O
6a
O
3a
3
O
O
1
2
O
O
C19H34O5Si calcd 393.2073, found 393.2089. Compound 8a: ½a 2D0
ꢄ
7b
8b
+73.0 (c 0.32, CHCl3); IR (ATR)
m 2985, 2929, 2856, 1471, 1464,
1369, 1249, 1209, 1155, 1058 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d
5.75 (s, 1H, H-5), 5.16 (d, J3a,6a = 5.7 Hz, 1H, H-3a), 4.72 (s, 1H, H-
4), 4.63 (m, 1H, H-40), 4.50 (d, 1H, H-6a), 4.21 (dd, J4 ,5 A = 6.3 Hz,
0
0
J5 A,5 B = 8.3 Hz, 1H, H-50A), 3.74 (t, J4 ,5 B = 8.3 Hz, 1H, H-50B), 1.44,
1.42, 1.38, 1.33 (s, 12H, 4 ꢃ CH3), 0.91 [SiC(CH3)], 0.13 (SiCH3),
0.11 (SiCH3); 13C NMR (CDCl3, 75 MHz) d 145.9 (C-6), 128.8 (C-5),
112.2 [OC(CH3)2], 109.3 [OC(CH3)2], 87.5 (C-6a), 84.2 (C-3a), 81.2
(C-4), 74.2 (C-40), 69.5 (C-50), 27.3, 26.7, 26.3, 26.2 (4 ꢃ CH3), 26.1
[SiC(CH3)3], 18.5 [SiC(CH3)3], ꢀ4.2 (SiCH3), ꢀ4.3 (SiCH3). HRMS:
C19H34O5Si calcd 393.2073, found 393.2075.
5.4.7. (3aR,4R,6aS)-6-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-
dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl
benzoate (7b), and (3aR,4S,6aS)-6-((S)-2,2-dimethyl-1,3-
dioxolan-4-yl)-2,2-dimethyl-4,6a-dihydro-3aH-
0
0
0
0
cyclopenta[d][1,3]dioxol-4-yl benzoate (8b)
Following the general method C, compound 6b (924 mg,
1.97 mmol), Bu2SnO (490 mg, 1.97 mmol), and TMSN3 (0.52 mL,
3.94 mmol) in toluene (19.7 mL) for 22 h at 100 °C gave after flash
chromatography (EtOAc/cyclohexane, 15/85), compounds 7b
(39 mg, 5%) and 8b (258 mg, 36%). Compound 7b: ½a 2D0
ꢄ
+28.0 (c
5.4.5. 1-O-Benzoyl-2,3:5,6-di-O-isopropylidene-D-mannitol (5b)
To a solution of compound 4 (1.96 g, 7.48 mmol) in pyridine
(10 mL) and CH2Cl2 (50 mL) was added benzoyl chloride
(0.95 mL, 8.23 mmol) at 0 °C. After stirring for 19 h at room tem-
perature, water and diethyl ether were added. The organic layer
was washed with HCl 1 M, dried over Na2SO4, filtered, and evapo-
rated under vacuo. The residue was purified by flash chromatogra-
phy (EtOAc/cyclohexane, 25/75) to give product 5b (1.94 g, 70%) as
0.29, CHCl3); IR (ATR):
m 2985, 2935, 1718, 1452, 1371, 1269,
1209, 1155, 1109, 1062, 1026 cmꢀ1 1H NMR (CDCl3, 300 MHz)
;
d 8.11–7.42 (m, 5H, C6H5), 5.97 (t, J4,5 = J5,6a = 1.7 Hz, 1H, H-5),
5.61 (ddd, J4,6a = 1.7 Hz, J4,3a = 5.5 Hz, 1H, H-4), 5.09 (t,
J6a,3a = 5.5 Hz, 1H, H-3a), 5.00 (d, 1H, H-6a), 4.71 (m, 1H, H-40),
4.28 (dd, J4 ,5 A = 6.3 Hz, J5 A,5 B = 8.3 Hz, 1H, H-50A), 3.88 (t,
0
0
0
0
J4 ,5 B = 8.3 Hz, 1H, H-50B), 1.49, 1.43, 1.38, 1.35 (s, 12H,
4 ꢃ CH3); 13C NMR (CDCl3, 75 MHz) d 166.3 (CO), 147.2 (C-6),
133.4-128.7 (C6H5), 126.0 (C-5), 113.5 [OC(CH3)2], 109.6
[OC(CH3)2], 83.7 (C-6a), 77.6 (C-3a), 75.8 (C-4), 73.9 (C-40), 69.5
(C-50), 27.8, 27.1, 26.8, 26.2 (4 ꢃ CH3). HRMS: C20H24O6Na calcd
0
0
a white solid [mp 98–99 °C; ½a 2D0
ꢄ
+19.0 (c 0.3, H2O)], showing spec-
troscopic data {IR (ATR)
m
3466, 2989, 2939, 2885, 1691, 1456,
1365, 1286, 1215, 1128, 1068, 1051 cmꢀ1
;
1H NMR (CDCl3,
300 MHz) d 8.07, 7.56–7.28 (m, 5H, C6H5), 4.68–4.48 (m, 5H, OH,
2H-1, H-2, H-3), 4.13–4.02 (m, 3H, H-5, H-6A, H-6B), 3.67 (dd,
J4,OH = 7.5 Hz, J4,5 = 1.5 Hz, 1H, H-4), 1.54 (s, 3H, CH3), 1.42 (s, 6H,
2 ꢃ CH3), 1.36 (s, 3H, CH3); 13C NMR (CDCl3, 75 MHz) d 166.6
(CO), 133.5–128.7 (C6H5), 109.9, 109.2 [2 ꢃ OC(CH3)2], 76.6, 75.8,
75.4 (C-2, C-3, C-4), 70.6 (C-5), 67.6 (C-6), 64.6 (C-1), 27.2 (CH3),
27.1 (CH3), 25.6 (CH3), 25.0 (CH3). HRMS: C19H26O7Na calcd
389.1576, found 389.1578}, in good agreement with those re-
ported in the literature.13
383.1471, found 383.1483. Compound 8b: ½a 2D0
ꢄ
+133.0 (c 0.63,
m 2985, 2935, 1716, 1452, 1371, 1247, 1207,
CHCl3); IR (ATR):
; d
1153, 1109, 1062, 1026 cmꢀ1 1H NMR (CDCl3, 300 MHz)
8.01–7.46 (m, 5H, C6H5), 5.98 (s, 1H, H-5), 5.79 (d, J4,3a = 0.7 Hz,
1H, H-4), 5.21 (dd, J6a,3a = 5.8 Hz, 1H, H-3a), 4.80 (d, 1H, H-6a),
4.67 (m, 1H, H-40), 4.25 (dd, J4 ,5 A = 6.3 Hz, J5 A,5 B = 8.3 Hz, 1H,
0
0
0
0
H-50A), 3.78 (dd, J4 ,5 B = 8.3 Hz, 1H, H-50B), 1.45, 1.43, 1.42, 1.31
(s, 12H, 4 ꢃ CH3); 13C NMR (CDCl3, 75 MHz) d 166.3 (CO), 149.8
(C-6), 133.5–128.7 (C6H5), 124.9 (C-5), 113.0 [OC(CH3)2], 109.5
[OC(CH3)2], 84.3 (C-6a), 84.0 (C-3a), 83.1 (C-4), 74.1 (C-40), 69.5
(C-50), 27.6, 26.7, 26.2, 26.1 (4 ꢃ CH3). HRMS: C20H24O6Na calcd
383.1471, found 383.1483.
0
0
5.4.6. 1-O-Benzoyl-4-C-cyano-4-O-mesyl-2,3:5,6-di-O-
isopropylidene-D-mann(tall)itol (6b)
Following general method A, compound 5b (1.94 g, 5.30 mmol),
Ac2O (1.74 mL, 18.55 mmol), and PDC (1.39 g, 3.71 mmol) for 22 h
gave crude ulose. Following the general method B, to a solution of
this crude ulose in CH2Cl2 (50 mL) were added NaHCO3 (890 mg,
10.6 mmol) in water (12.33 mL) and KCN (737 mg, 11.34 mmol).
After stirring for 19 h, the crude cyanohydrins were dissolved in
CH2Cl2 (50 mL) followed by addition of Et3N (5.95 mL, 42.4 mmol)
and MsCl (2.25 mL, 29.15 mmol). After 22 h and extraction, the res-
idue was purified by flash chromatography (EtOAc/cyclohexane,
30/70) to give product 6b (1.8 g, 72%) as an inseparable mixture
of diastereoisomers in 86/14 ratio, as a slight yellow syrup: IR
5.5. Computational methods
All calculations were carried out with the GAUSSIAN 03 program.18
The optimizations were carried out using hybrid density functional
B3LYP19 with the 6-31G(d,p) basis set. This polarized basis set adds
p functions to hydrogen atoms in addition to the d functions on
heavy atoms. Single-point energy calculations with the triple split
valence basis set 6-311+G(d,p) were later performed on the opti-
mized geometries. Basis sets with diffuse functions are recom-
mended for molecules with lone pairs, for anions, and for
systems with significant negative charge. Vibrational frequency
analyses were carried out in order to assess the nature of the sta-
tionary points and to obtain the zeropoint vibrational energies
(ZPVEs) and thermodynamic parameters. From the transition
structures, the intrinsic reaction coordinate (IRC) was obtained
using the IRC routine in Gaussian. Natural bond orbital (NBO) anal-
yses20 have been performed by the module NBO v.3.1 implemented
in GAUSSIAN 03 at the optimization level.
(ATR)
m
2993, 2983, 1724, 1454, 1384, 1363, 1271, 1249, 1215,
1182, 1118, 1070 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 8.07, 7.55–
7.40 (m, 5H, C6H5), 5.09 (m, 1H, H-1A), 4.83–4.75 (m, 3H, H-1B,
H-2, H-5), 4.63 (d, J2,3 = 4.8 Hz, 1H, H-3), 4.26 (dd, J5,6A = 6.9 Hz,
J6A,6B = 10.1 Hz, 1H, H-6A), 4.20 (dd, J5,6B = 7.4 Hz, 1H, H-6B), 3.32
(s, 3H, OSO2CH3), 1.62, 1.54, 1.42, 1.38 (s, 12H, 4 ꢃ CH3); 13C
NMR (CDCl3, 75 MHz) d 166.5 (CO), 133.5–128.7 (C6H5), 114.1
(CN), 111.5, 111.1 (2 ꢃ [OC(CH3)2]), 82.8 (C-4), 77.7 (C-5), 77.0
(C-3), 76.4, (C-2), 67.3 (C-6), 62.6 (C-1), 41.0 (OSO2CH3), 27.0,