M.B. Fusaro et al. / Tetrahedron 69 (2013) 542e550
547
crude product was purified by silica gel chromatography (cyclo-
hexane/EtOAc gradient) to provide 7-b (217 mg, 96%) as a colorless
1073 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
7.34e7.2 (m, 20H, Ar), 5.64
(dddd, J¼16.9, 10.5, 7.8, 6.7 Hz, 1H, H-7), 4.99 (m, 2H, H-8), 4.83 (d,
J¼11.4 Hz, 1H, OeCH2ePh), 4.78 (d, J¼11.4 Hz, 1H, OeCH2ePh), 4.69
(d, J¼11.4 Hz, 1H, OeCH2ePh), 4.56 (d, J¼11.4 Hz, 1H, OeCH2ePh),
4.56 (d, J¼11.6 Hz, 1H, OeCH2ePh), 4.39 (d, J¼11.6 Hz, 1H,
OeCH2ePh), 4.08 (dd, J¼7.1, 4.2 Hz, 1H, H-3), 3.88 (d, J¼12.9 Hz, 1H,
NeCH2ePh), 3.78 (dd, J¼7.0, 2.4 Hz, 1H, H-2), 3.74 (dd, J¼11.6,
5.2 Hz, 1H, H-5a), 3.63 (dd, J¼11.6, 4.3 Hz, 1H, H-5b), 3.59 (d,
J¼12.9 Hz, 1H, NeCH2ePh), 3.38 (dd, J¼9.3, 4.4 Hz, 1H, H-4), 2.63
(ddd, J¼7.8, 5.1, 2.5 Hz, 1H, H-1), 2.43 (m, 1H, H-6a), 2.26 (m, 1H, H-
oil; 1H NMR (300 MHz, CDCl3)
d 7.31e7.11 (m, 15H, Ar), 6.66 (t,
J¼5.8 Hz, 1H, NH), 5.64 (ddt, J¼17.1, 10.2, 5.8 Hz, 1H, H-7), 5.05 (ddd,
J¼16.4, 2.6, 1.2 Hz, 1H, H-8), 4.99 (dq, J¼10.2, 1.4 Hz, 1H, H-8),
4.68e4.37 (m, 6H, CH2Bn), 4.05 (d, J¼2.5 Hz, 1H, H-2), 3.99 (dd,
J¼6.9, 2.5 Hz, 1H, H-3), 3.89e3.77 (m, 1H, H-6), 3.73e3.63 (m, 2H,
H-6, H-4), 3.60 (dd, J¼12.0, 4.0 Hz, 1H, H-5), 3.41 (dd, J¼11.9, 5.4 Hz,
1H, H-5); 13C NMR (75 MHz, CDCl3)
d 170.7 (CONH), 138.2 (CqeAr),
137.9 (CqeAr), 136.5 (CqeAr), 133.7 (C-7), 129.0e127.6 (CHeAr),
117.0 (C-8), 79.9 (C-3), 79.7 (C-4, C-2), 75.3 (CH2Ph), 73.9 (CH2Ph),
73.3 (CH2Ph), 61.8 (C-5), 41.7 (C-6). Analytical data were in agree-
ment with the literature but NMR data have been added.20
6b); 13C NMR (CDCl3, 300 MHz)
d 140.7 (CqeAr), 138.8 (CqeAr),
138.4 (CqeAr), 138.3 (CqeAr), 136.1 (C-7), 128.6e127.0 (CHeAr),
117.2 (C-8), 80.1 (C-2, C-3), 78.4 (C-4), 74.7 (OeCH2ePh), 74.3
(OeCH2ePh), 72.1 (OeCH2ePh), 61.7 (C-5), 56.5 (C-1), 51.1
(NeCH2ePh), 35.3 (C-6); HRMS calcd for C36H42NO4 552.3114,
found m/z 552.3110 [MþH]þ.
3.11. N-(n-Nonyl)-2,3,4-tri-O-benzyl-D-xylonamide (7-c)
Aldose 6 (200 mg, 0.476 mmol) was treated as described in the
general procedure A using n-nonylamine (0.18 mL, 0.952 mmol),
K2CO3 (197 mg, 1.430 mmol), and I2 (242 mg, 0.952 mmol). The
resulting crude product was purified by silica gel chromatography
3.14. 1-C-Allyl-2,3,4-tri-O-benzyl-1-deoxy-1-(n-nonylamino)-
D-xylitol (11-b)
(cyclohexane/EtOAc gradient) to provide 7-c (262 mg, 98%) as
Aldose 6 (200 mg, 0.476 mmol) was treated as described in the
general procedure B, using n-nonylamine (174 mL, 0.952 mmol),
20
a white solid: mp 49e50 ꢀC; [
a
]
þ13.0 (c 0.12, CH2Cl2); IR (ATR)
D
1663 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
7.34e7.07 (m,15H, Ar), 6.57
imidazole (65 mg, 0.952 mmol), and I2 (242 mg, 0.951 mmol) for
the first step, and allylmagnesium bromide (4.76 mL, 1 M in Et2O,
4.756 mmol) for the second step. The resulting crude product was
purified by silica gel chromatography (cyclohexane/EtOAc gradient)
to provide 11-b (237 mg of mixture of diastereoisomers, 85%) as
(t, J¼5.8 Hz, 1H, NH), 4.71e4.32 (m, 6H, CH2Ph), 4.03 (d, J¼2.5 Hz,
1H, H-2), 3.99 (dd, J¼6.9, 2.5 Hz, 1H, H-3), 3.68 (ddd, J¼6.8, 5.4,
4.0 Hz, 1H, H-4), 3.60 (dd, J¼11.9, 4.0 Hz, 1H, H-5), 3.43 (dd, J¼11.9,
5.4 Hz, 1H, H-5), 3.22 (td, J¼13.5, 7.1 Hz, 1H, H-6), 3.03 (ddd, J¼13.2,
7.0, 5.4 Hz, 1H, H-6), 1.39e1.26 (m, 2H, H-7), 1.25e1.07 (m, 12H, H-8,
H-9, H-10, H-11, H-12, and H-13), 0.83e0.77 (m, 3H, H-14); 13C NMR
yellow oil. Analytical data of the major diastereoisomer after pu-
20
rification; [
a]
ꢁ2 (c 0.2, CHCl3); IR (ATR) 3421, 2925, 2854, 1454,
D
(75 MHz, CDCl3)
d
170.7 (CONH), 138.6e135.6 (CqeAr), 129.1e127.6
1074 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 7.27e7.16 (m, 15H, Ar), 5.58
(CHeAr), 80.3e79.4 (C-2, C-3, C-4), 75.7e72.7 (3ꢂCH2Ph), 61.8 (C-
5), 39.4 (C-6), 31.9 (C-12), 30.0e29.1 (C-7, C-9, C-10, C-11), 27.1 (C-
8), 22.8 (C-13), 14.2 (C-14); HRMS calcd for C35H48NO5 562.3532,
found m/z 562.3539 [MþH]þ.
(ddt, J¼17.0,10.2, 7.1 Hz,1H, H-7), 4.91 (dd, J¼10.2, 2.0 Hz,1H, H-8a),
4.85 (dd, J¼17.0, 2.0 Hz, 1H, H-8b), 4.71 (d, J¼11.4 Hz, 1H, CH2Ph),
4.66 (d, J¼11.4 Hz, 1H, CH2Ph), 4.61 (d, J¼11.4 Hz, 1H, CH2Ph), 4.59
(d, J¼11.6 Hz, 1H, CH2Ph), 4.52 (d, J¼11.6 Hz, 1H, CH2Ph), 4.46 (d,
J¼11.4 Hz, 1H, CH2Ph), 3.93 (dd, J¼6.4, 5.0 Hz, 1H, H-3), 3.75 (dd,
J¼11.5, 5.1 Hz, 1H, H-5a), 3.66e3.54 (m, 3H, H-2, H-4, H-5b), 2.57
(m, 2H, H-1, H-9a), 2.30e2.10 (m, 3H, H-6, H-9b), 1.17 (m, 14H, H-10,
3.12. N-3-Hydroxypropyl-2,3,4-tri-O-benzyl-D-xylonamide (7-
d)
H-11, H-12, H-13, H-14, H-15, H-16), 0.80 (t, J¼6.7 Hz, 3H, H-17); 13
C
Aldose 6 (200 mg, 0.476 mmol) was treated as described in the
general procedure using 3-aminopropan-1-ol (73 L,
NMR (CDCl3, 300 MHz) d 138.8 (CqeAr), 138.5 (CqeAr), 138.3
A
m
(CqeAr), 136.2 (C-7), 128.5e127.6 (CHeAr), 117.1 (C-8), 79.9e79.3
(C-3, C-4, C-5), 74.6 (CH2Ph), 74.0 (CH2Ph), 72.2 (CH2Ph), 61.8 (C-5),
57.5 (C-1), 47.6 (C-9), 35.5 (C-6), 32.0e22.8 (C-10, C-11, C-12, C-13,
C-14, C-15, C-16), 14.2 (C-17); HRMS calcd for C38H54NO4 588.4053,
found m/z 588.4045 [MþH]þ.
0.952 mmol), K2CO3 (197 mg, 1.430 mmol), and I2 (242 mg,
0.952 mmol). The resulting crude product was purified by silica gel
chromatography (cyclohexane/EtOAc gradient) to provide 7-
20
d (230 mg, 98%) as a white solid: mp 77e78 ꢀC; [
a
]
D
þ10.2 (c 1.2,
CH2Cl2); IR (ATR) 1654 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 7.42e7.23
(m, 15H, Ar), 6.99 (t, J¼6.2 Hz, 1H, NH), 4.78e4.53 (m, 6H, CH2Ph),
4.18 (d, J¼2.6 Hz, 1H, H-2), 4.12 (dd, J¼6.8, 2.6 Hz, 1H, H-3),
3.85e3.71 (m, 2H, H-4 and H-5), 3.63e3.39 (m, 4H, H-5, H-8 and H-
6), 3.37e3.23 (m, 1H, H-6), 1.74e1.50 (m, 2H, H-7); 13C NMR
3.15. 1-C-Allyl-2,3,4-tri-O-benzyl-1-allylamino-1-deoxy-D-xy-
litol (11-c)
Aldose 6 (200 mg, 0.476 mmol) was treated as described in the
general procedure B, using allylamine (71 L, 0.952 mmol), imid-
(75 MHz, CDCl3)
d
172.0 (CONH), 138.3e136.4 (CqeAr), 129.1e127.6
m
(CHeAr), 80.2e79.3 (C-3, C-4, C-2), 75.3 (CH2Ph), 74.1 (CH2Ph), 73.3
(CH2Ph), 61.8 (C-5), 59.5 (C-8), 36.2 (C-6), 32.2 (C-7); HRMS calcd
for C29H35NO6Na 516.2362, found m/z 516.2380 [MþNa]þ.
azole (65 mg, 0.952 mmol), and I2 (242 mg, 0.952 mmol) for the
first step, and allylmagnesium bromide (4.76 mL, 1 M in Et2O,
4.756 mmol) for the second step. The resulting crude product was
purified by silica gel chromatography (cyclohexane/EtOAc gradient)
to provide 11-c (189 mg of mixture of diastereoisomers, 79%) as
yellow oil. Analytical data of the major diastereoisomer after pu-
3.13. 1-C-Allyl-2,3,4-tri-O-benzyl-1-benzylamino-1-deoxy-D-
xylitol (11-a)
rification; [
a
]
20 ꢁ8 (c 0.2, CHCl3); IR (ATR) 3438, 2972, 2900, 1454,
D
Aldose 6 (200 mg, 0.476 mmol) was treated as described in the
general procedure B, using benzylamine (104 L, 0.952 mmol),
1074 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
7.28e7.19 (m, 15H, Ar), 5.74
m
(ddt, J¼17.1,10.1, 6.0 Hz,1H, H-10), 5.57 (m,1H, H-7), 4.96 (m, 4H, H-
8, H-11), 4.74 (d, J¼11.4 Hz, 1H, CH2Ph), 4.68 (d, J¼11.3 Hz, 1H,
CH2Ph), 4.62 (d, J¼11.3 Hz, 1H, CH2Ph), 4.59 (d, J¼11.6 Hz, 1H,
CH2Ph), 4.49 (d, J¼11.4 Hz, 1H, CH2Ph), 4.49 (d, J¼11.6 Hz, 1H,
CH2Ph), 3.97 (dd, J¼6.7, 4.5 Hz, 1H, H-3), 3.75 (dd, J¼11.3, 4.9 Hz, 1H,
H-5a), 3.68 (dd, J¼6.7, 2.7 Hz, 1H, H-2) 3.66e3.54 (m, 2H, H-4, H-
5b), 3.26 (ddt, J¼13.9, 5.9, 1.4 Hz, 1H, H-9a), 3.00 (ddt, J¼13.9, 6.0,
1.4 Hz, 1H, H-9b), 2.63 (ddd, J¼7.9, 5.3, 2.7 Hz, 1H, H-1), 2.30e2.11
imidazole (65 mg, 0.952 mmol), and I2 (242 mg, 0.952 mmol) for
the first step, and allylmagnesium bromide (4.76 mL, 1 M in Et2O,
4.756 mmol) for the second step. The resulting crude product was
purified by silica gel chromatography (cyclohexane/EtOAc gradient)
to provide 11-a (251.7 mg of mixture of diastereoisomers, 96%) as
yellow oil. Analytical data of the major diastereoisomer after pu-
rification; [
a]
20 ꢁ12 (c 0.2, CHCl3); IR (ATR) 3445, 2925, 2855, 1453,
D