The Journal of Organic Chemistry
Article
138.9 (Car), 139.1 (Car), 140.0 (Car); HRMS calculated for
C36H42NO5: 568.3063 [M + H]+. Found: 568.3069.
4.93 (m, 6H, 3 × PhCH2O), 7.28−7.38 (m, 15H, Ph); 13C NMR (δ,
100 MHz, CDCl3): 14.1 (CH3), 20.5 (CH2), 29.8 (CH2), 41.6 (C6),
48.4 (NCH2), 60.3 (C2), 63.5 (C7), 72.3 (C1), 72.5 (PhCH2O), 74.7
(PhCH2O), 75.4 (PhCH2O), 75.8 (C5), 79.8 (C3), 83.7 (C4), 127.6−
128.7 (CHar), 138.6 (Car), 138.8 (Car), 139.1 (Car); HRMS
calculated for C32H42NO5: 520.3063 [M + H]+. Found: 520.3061.
Data for 25c: Pale yellow oil; [α]2D5 +12.4 (c 0.84, CHCl3); IR
(film): υ = 3309, 3078, 3051, 3028, 2851, 1493, 1458, 1090, 1065,
Data for 25a: Pale yellow oil; [α]2D5 +6.8 (c 1.00, CHCl3); IR (film):
υ = 3389, 3063, 3030, 2924, 2854, 1666, 1496, 1454, 1360, 1066, 1028,
1
750, 698 cm−1; H NMR (δ, 500 MHz, CDCl3): 1.84−1.90 (m, 1H,
H-5), 2.64 (t, 1H, J = 10.9 Hz, H-6), 2.72−2.89 (m, 2H, PhCH2),
2.95−3.08 (m, 2H, NCH2), 3.24 (t, 1H, J = 9.9 Hz, H-4), 3.30 (t, 1H, J
= 9.3 Hz, H-2), 3.54−3.62 (m, 2H, H-1, H-3), 3.66 (dd, 1H, J = 10.6,
7.8 Hz, H-7), 3.99 (dd, 1H, J = 10.6, 3.0 Hz, H-7′), 4.55−4.98 (m, 6H,
3 × PhCH2O), 7.20−7.38 (m, 20H, Ph); 13C NMR (δ, 100 MHz,
CDCl3): 36.3 (PhCH2), 42.6 (C5), 45.6 (NCH2), 60.5 (C6), 63.9
(C7), 72.4 (C1), 75.5 (PhCH2O), 75.6 (PhCH2O), 75.7 (PhCH2O),
79.5 (C4), 83.8 (C2), 85.6 (C3), 126.6−128.8 (CHar), 138.0 (Car),
138.36 (Car), 138.42 (Car), 138.9 (Car); HRMS calculated for
C36H42NO5: 568.3063 [M + H]+. Found: 568.3045.
1
1025, 668 cm−1; H NMR (δ, 500 MHz, CDCl3): 0.83−1.54 (m, 7H,
CH3, 2 × CH2), 2.12−2.18 (m, 1H, H-5), 2.95−3.15 (m, 3H, CH2, H-
6), 3.27 (t, 1H, J = 9.7 Hz, H-4), 3.39 (t, 1H, J = 9.2 Hz, H-2), 3.61 (t,
1H, J = 9.2 Hz, H-3), 3.74 (dd, 1H, J = 10.6, 8.9 Hz, H-7), 3.80 (t, 1H,
J = 9.8 Hz, H-1), 4.16 (dd, 1H, J = 10.8, 2.9 Hz, H-7′), 4.53−4.96 (m,
6H, 3 × PhCH2O), 7.26−7.40 (m, 15H, Ph); 13C NMR (δ, 100 MHz,
CDCl3): 13.6 (CH3), 19.7 (CH2), 29.8 (CH2), 40.7 (C5), 45.8
(NCH2), 61.8 (C6), 63.3 (C7), 71.3 (C1), 75.5 (PhCH2O), 75.7
(PhCH2O), 75.8 (PhCH2O), 78.3 (C4), 82.7 (C2), 84.7 (C3), 127.8−
128.8 (CHar), 137.6 (Car), 138.0 (Car), 138.1 (Car); HRMS
calculated for C32H42NO5: 520.3063 [M + H]+. Found: 520.3080.
(1R,2S,3S,4S,5R,6S)-2-Azido-3,4,5-tris(benzyloxy)-6-(hydroxy-
methyl)cyclohexanol (24e) and (1R,2S,3S,4R,5R,6S)-6-Azido-2,3,4-
tris(benzyloxy)-5-(hydroxymethyl)cyclohexanol (25e). According to
the general method A, the ring-opening of epoxide 5 (171 mg, 0.38
mmol) with NaN3 (0.25 g, 3.8 mmol) afforded a mixture of
regioisomers 25e and 24e in a ratio of 75:25. Chromatography on
silica gel (hexane/EtOAc, 2:1) provided 25e (115 mg, 0.23 mmol,
61%), followed by 24e (39 mg, 0.08 mmol, 21%).
(1R,2S,3S,4S,5R,6S)-3,4,5-Tris(benzyloxy)-6-(hydroxymethyl)-2-
(octylamino)cyclohexanol (24b) and (1R,2S,3S,4R,5R,6S)-2,3,4-Tris-
(benzyloxy)-5-(hydroxymethyl)-6-(octylamino)cyclohexanol (25b).
According to the general method A, the ring-opening of epoxide 5
(131 mg, 0.29 mmol) with octylamine (0.48 mL, 2.9 mmol) afforded a
mixture of regioisomers 25b and 24b in a ratio of 83:17.
Chromatography on silica gel (hexane/EtOAc, 1:2) provided 24b
(22 mg, 0.04 mmol, 13%), followed by 25b (117 mg, 0.20 mmol,
69%).
Data for 24b: Pale yellow oil; [α]2D5 +38.7 (c 0.64, CHCl3); IR
(film): υ = 3389, 3081, 3061, 3021, 2954, 2926, 2855, 1471, 1451,
1060, 1023, 661 cm−1; 1H NMR (δ, 500 MHz, CDCl3): 0.88 (t, 3H, J
= 6.9 Hz, CH3), 1.18−1.42 (m, 12H, 6 × CH2), 2.12−2.20 (m, 1H, H-
6), 2.39−2.54 (m, 2H, NCH2), 3.04 (t, 1H, J = 3.8 Hz, H-2), 3.75 (dd,
1H, J = 10.9, 2.1 Hz, H-7), 3.87 (t, 1H, J = 8.5 Hz, H-5), 3.90 (t, 1H, J
= 8.5 Hz, H-4), 3.98 (dd, 1H, J = 8.5, 4.1 Hz, H-3), 4.06 (dd, 1H, J =
10.9, 3.2 Hz, H-7′), 4.15−4.18 (m, 1H, H-1), 4.59−4.91 (m, 6H, 3 ×
PhCH2O), 7.26−7.38 (m, 15H, Ph); 13C NMR (δ, 100 MHz, CDCl3):
14.3 (CH3), 22.8 (CH2), 27.4 (CH2), 29.4 (CH2), 29.6 (CH2), 29.8
(CH2), 32.0 (CH2), 41.6 (C6), 48.7 (NCH2), 60.3 (C2), 63.5 (C7),
72.4 (C1), 72.5 (PhCH2O), 74.7 (PhCH2O), 75.4 (PhCH2O), 75.8
(C5), 80.3 (C3), 83.8 (C4), 127.7−128.7 (CHar), 138.6 (Car), 138.8
(Car), 139.1 (Car); HRMS calculated for C36H50NO5: 576.3689 [M +
H]+. Found: 576.3693.
Data for 24e: Colorless oil; [α]2D5 +22 (c 1.00, CHCl3); IR (film): υ
= 3440, 3049, 3022, 2909, 2104, 1714, 1496, 1452 cm−1; 1H NMR (δ,
500 MHz, CDCl3): 1.71−1.76 (m, 1H, H-6), 3.70−3.74 (m, 1H, H-7),
3.82−3.92 (m, 3H, H-2, H-4, H-5), 4.00 (dd, 1H, J = 10.9, 2.3 Hz, H-
7′), 4.06−4.08 (m, 2H, H-1, H-3), 4.70−5.00 (m, 6H, 3 × PhCH2O),
7.29−7.40 (m, 15H, Ph); 13C NMR (δ, 100 MHz, CDCl3): 41.6 (C6),
62.8 (C2), 63.0 (C7), 73.1 (C1), 73.5 (PhCH2O), 74.7 (C5), 75.0
(PhCH2O), 76.0 (PhCH2O), 80.3 (C3), 84.3 (C4), 127.7−128.8
(CHar), 138.2 (Car), 138.6 (Car), 138.8 (Car); HRMS calculated for
C28H31N3O5Na: 512.2161 [M + Na]+. Found: 512.2159.
Data for 25e: Colorless oil; [α]2D5 −8.8 (c 1.00, CHCl3); IR (film): υ
1
= 3439, 3054, 3026, 2903, 2106, 1953, 1721, 1493, 1455 cm−1; H
Data for 25b: Pale yellow oil; [α]2D5 +5.1 (c 1.00, CHCl3); IR (film):
υ = 3389, 3084, 3056, 3026, 2958, 2927, 2852, 1478, 1458, 1081, 1024,
NMR (δ, 500 MHz, CDCl3): 1.41−1.47 (m, 1H, H-5), 2.57−2.75
(brs, 1H, OH), 3.38−3.45 (m, 2H, H-2, H-6), 3.56−3.62 (m, 3H, H-1,
H-3, H-4), 3.79 (dd, 1H, J = 10.8, 2.4 Hz, H-7), 3.85 (dd, 1H, J = 10.8,
1.6 Hz, H-7′), 4.72−5.02 (m, 6H, 3 × PhCH2O), 7.28−7.40 (m, 15H,
Ph); 13C NMR (δ, 100 MHz, CDCl3): 45.2 (C5), 58.3 (C7), 60.9
(C6), 75.3 (PhCH2O), 75.7 (PhCH2O), 75.9 (PhCH2O), 76.3, 76.8,
83.2 (C2), 85.7 (C3), 127.9−128.8 (CHar), 138.1 (Car), 138.27
(Car), 138.35 (Car); HRMS calculated for C28H31N3O5Na: 512.2161
[M + Na]+. Found: 512.2153.
(1S,2R,3S,4S,5R,6S)-3,4,5-Tris(benzyloxy)-6-(benzyloxymethyl)-2-
(phenethylamino)cyclohexanol (27a). According to the general
method A, the ring-opening of epoxide 6 (56 mg, 0.10 mmol) with
2-phenylethylamine (0.13 mL, 1.0 mmol) afforded 51 mg (0.08 mmol,
74%) of 27a after chromatography on silica gel (hexane/EtOAc, 2:1 to
1:1).
1
893, 651 cm−1; H NMR (δ, 500 MHz, CDCl3): 0.87 (t, 3H, J = 7.1
Hz, CH3), 1.15−1.55 (m, 12H, 6 × CH2), 1.95−2.01 (m, 1H, H-5),
2.74−2.88 (m, 3H, H-6, NCH2), 3.24 (t, 1H, J = 9.8 Hz, H-4), 3.33 (t,
1H, J = 9.3 Hz, H-2), 3.58 (t, 1H, J = 9.3 Hz, H-3), 3.65 (t, 1H, J = 9.8
Hz, H-1), 3.70 (dd, 1H, J = 10.7, 8.2 Hz, H-7), 4.07 (dd, 1H, J = 10.5,
2.7 Hz, H-7′), 4.54−4.97 (m, 6H, 3 × PhCH2O), 7.26−7.36 (m, 15H,
Ph); 13C NMR (δ, 100 MHz, CDCl3): 14.2 (CH3), 22.8 (CH2), 27.0
(CH2), 29.3 (CH2), 29.4 (CH2), 29.9 (CH2), 31.9 (CH2), 41.8 (C5),
45.0 (NCH2), 61.0 (C6), 63.7 (C7), 71.8 (C1), 75.6 (PhCH2O), 75.70
(PhCH2O), 75.73 (PhCH2O), 79.0 (C4), 83.4 (C2), 85.3 (C3),
127.9−128.8 (CHar), 137.8 (Car), 138.2 (Car), 138.3 (Car); HRMS
calculated for C36H50NO5: 576.3689 [M + H]+. Found: 576.3702.
(1R,2S,3S,4S,5R,6S)-3,4,5-Tris(benzyloxy)-2-(butylamino)-6-
(hydroxymethyl)cyclohexanol (24c) and (1R,2S,3S,4R,5R,6S)-2,3,4-
tris(benzyloxy)-6-(butylamino)-5-(hydroxymethyl)cyclohexanol
(25c). According to the general method A, the ring-opening of epoxide
5 (141 mg, 0.32 mmol) with butylamine (0.32 mL, 3.2 mmol) afforded
a mixture of regioisomers 25c and 24c in a ratio of 87:13.
Chromatography on silica gel (hexane/EtOAc, 1:2) provided 24c
(19 mg, 0.04 mmol, 11%), followed by 25c (121 mg, 0.23 mmol,
74%).
Data for 27a: Pale yellow oil; [α]2D5 +11.6 (c 0.43, CHCl3); IR
(film): υ = 3331, 3062, 3028, 2923, 2853, 1658, 1495, 1453, 1069,
1028, 876, 750 cm−1; 1H NMR (δ, 500 MHz, CDCl3): 1.68 (t, 1H, J =
10.2 Hz, H-6), 2.49 (t, 1H, J = 10.2 Hz, H-2), 2.68−2.77 (m, 2H,
PhCH2), 2.91 (dt, 1H, J = 11.2, 7.1 Hz, NCH2), 3.13 (dt, 1H, J = 11.3,
7.1 Hz, NCH2), 3.43 (t, 1H, J = 9.2 Hz, H-3), 3.49 (t, 1H, J = 10.3 Hz,
H-1), 3.60−3.67 (m, 2H, H-4, H-5), 3.80 (dd, 1H, J = 8.9, 3.0 Hz, H-
7), 3.88 (dd, 1H, J = 8.9, 1.9 Hz, H-7′), 4.54−4.99 (m, 8H, 4 ×
PhCH2O), 7.14−7.34 (m, 25H, Ph); 13C NMR (δ, 100 MHz, CDCl3):
37.1 (PhCH2), 47.2 (C6), 47.9 (NCH2), 65.2 (C2), 65.9 (C7), 66.9
(C1), 73.4 (PhCH2O), 75.3 (PhCH2O), 75.60 (PhCH2O), 75.62
(PhCH2O), 77.9, 80.7 (C3), 88.0, 126.3−128.9 (CHar), 138.4 (Car),
138.51 (Car), 138.53 (Car), 138.7 (Car), 139.8 (Car); HRMS
calculated for C43H48NO5: 658.3532 [M + H]+. Found: 658.3545.
(1S,2R,3S,4S,5R,6S)-3,4,5-Tris(benzyloxy)-6-(benzyloxymethyl)-2-
(octylamino)cyclohexanol (27b). According to the general method A,
Data for 24c: Pale yellow oil; [α]2D5 +41.4 (c 0.88, CHCl3); IR
(film): υ = 3389, 3088, 3063, 3030, 2956, 2924, 2854, 1496, 1454,
1
1360, 1094, 1067, 1028, 733, 697, 665 cm−1; H NMR (δ, 500 MHz,
CDCl3): 0.90 (t, 3H, J = 7.3 Hz, CH3), 1.23−1.54 (m, 4H, 2 × CH2),
2.14−2.19 (m, 1H, H-6), 2.44−2.57 (m, 2H, CH2), 3.07 (t, 1H, J = 3.6
Hz, H-2), 3.77 (dd, 1H, J = 11.0, 2.5 Hz, H-7), 3.89 (t, 1H, J = 8.5 Hz,
H-5), 3.92 (t, 1H, J = 8.4 Hz, H-4), 4.00 (dd, 1H, J = 8.6, 4.1 Hz, H-3),
4.07 (dd, 1H, J = 11.0, 4.1 Hz, H-7′), 4.17−4.21 (m, 1H, H-1), 4.62−
L
J. Org. Chem. XXXX, XXX, XXX−XXX