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[4.6 × 250 mm Daicel IF column, 98.8:0.2 hexanes:iPrOH, 2 mL/min,
J = 2.9 Hz, 1 H), 2.15 (dd, J = 19.3, 2.6 Hz, 1 H), 1.90–2.00 (m, 1 H),
2
54 nm, retention times 18.3 min (major) and 36.8 min (minor)]: 1.72–1.86 (m, 2 H), 1.54–1.61 (m, 1 H), 1.50 (s, 9 H), 1.18 (s, 3 H)
2
3
13
[
α] = + 23 (c = 1.0, CHCl ). IR (neat): ν˜ = 3375, 2949, 2833, 1721, ppm. C NMR (100 MHz, CDCl ): δ = 215.2, 176.1, 152.3, 141.9,
D
3
3
–1 1
1
6
2
2
1
515, 761 cm . H NMR (400 MHz, CDCl ): δ = 6.70–6.78 (m, 2 H),
115.0, 114.7, 81.2, 56.5, 55.9, 49.83, 49.75, 40.5, 38.1, 28.1, 22.2, 20.9,
19.0 ppm. HRMS (ES ) Calcd for C H NO (M ), 360.2175 found
3
+
+
.59–6.64 (m, 2 H) 4.68 (d, J = 2.6 Hz, 1 H), 4.25 (qd, J = 7.0, 1.3 Hz,
H), 3.72 (s, 3 H), 3.19 (br. s, 1 H), 2.57 (dt, J = 19.3, 3.1 Hz, 1 H),
.43 (q, J = 2.8 Hz, 1 H), 2.39 (quin, J = 2.6 Hz, 1 H), 2.17 (dd, J =
9.3, 2.6 Hz, 1 H), 1.90–2.00 (m, 1 H), 1.80–1.87 (m, 1 H), 1.51–1.75
21 29 4
360.2175.
Bicyclic Amine 6g: (100 mg, 0.22 mmol, 83 %, 90.3: 9.7 er, 12:1 dr),
as a colorless oil, enantiomeric ratio was determined by chiral HPLC
(
(
m, 3 H), 1.30 (t, J = 7.0 Hz, 3 H), 1.23 (s, 3 H) ppm. 13C NMR
[
9
4.6 × 250 mm Phenomenex Lux 5u Cellulose-3 column, 99:1 to
100 MHz, CDCl ): δ = 215.0, 177.2, 152.3, 141.8, 115.1, 114.7, 61.4,
3
0:10 hexanes:iPrOH, 1 mL/min, 254 nm, retention times 7.1 min
+
5
6.7, 55.9, 49.8, 49.4, 40.4, 38.0, 22.3, 20.8, 14.4 ppm. HRMS (ES )
23
(minor) and 9.6 min (major)]: [α]D = + 15.1 (c = 1, CHCl ). IR (neat):
3
+
Calcd for C H NO (M ), 332.1862 found 332.1852.
–1 1
19
25
4
ν˜ = 3357, 2980, 2954, 2881, 1730, 1625 cm . H NMR (700 Mz,
Bicyclic Amine 6c: (61 mg, 0.14 mmol, 53 %, 88.2:12.8 er, 11:1 dr)
CDCl ): δ = 7.78 (s, 2 H), 7.74 (s, 1 H), 4.00 (d, J = 14.4 Hz, 1 H), 3.83
3
as a colorless oil, enantiomeric ratio was determined by chiral HPLC (d, J = 2.7 Hz, 1 H), 3.81 (d, J = 14.2 Hz, 1 H), 2.53 (dt, J = 19.0,
4.6 × 250 mm Phenomenex Lux 5u Cellulose-2 column, 99:1 to 3.1 Hz, 1 H), 2.48 (q, J = 2.9 Hz, 1 H), 2.37 (quin, J = 3.0 Hz, 1 H),
0:10 hexanes:iPrOH, 1 mL/min, 254 nm, retention times 11.4 min 2.12 (dd, J = 19.0, 2.6 Hz, 1 H), 1.77–1.85 (m, 2 H), 1.66–1.71 (m, 1
[
9
2
3
13
(minor) and 12.1 min (major)]: [α]D = –8.1 (c = 1, CHCl ). IR (neat): H), 1.54–1.59 (m, 1 H), 1.46 (s, 9 H), 1.28 (s, 3 H) ppm. C NMR
3
–
1 1
ν˜ = 3350, 2958, 2879, 1731, 1624 cm . H NMR (700 MHz, CDCl ): (176 MHz, CDCl ): δ = 215.2, 176.1, 143.2, 131.7, 131.5, 128.27,
3
3
δ = 7.78 (s, 2 H), 7.75 (s, 1 H), 4.19 (qd, J = 7.1, 0.7 Hz, 2 H), 4.01 (d,
128.25, 125.9, 124.4, 122.8, 121.3, 121.13, 121.11, 81.2, 60.2, 51.3,
+
J = 14.4 Hz, 1 H), 3.85 (d, J = 2.7 Hz, 1 H), 3.82 (d, J = 14.4 Hz, 1 H),
49.6, 48.2, 40.2, 37.7, 28.0, 22.2, 21.0, 19.2 ppm. HRMS (ES ) Calcd
+
2
.55 (dt, J = 19.0, 3.2 Hz, 1 H), 2.49 (q, J = 2.8 Hz, 1 H), 2.42 (quin,
for C H F NO (M ), 480.1973 found 480.1954.
23
27
6
3
J = 2.9 Hz, 1 H), 2.14 (dd, J = 19.1, 2.7 Hz, 1 H), 1.78–1.83 (m, 2 H),
Bicyclic Amine 6h: (30 mg, 0.09 mmol, 34 %, 83.6:16.4 er, 20:1 dr),
as a colorless oil, enantiomeric ratio was determined by chiral HPLC
1
7
1
1
2
4
.62–1.69 (m, 1 H), 1.55–1.61 (m, 1 H), 1.31 (s, 3 H), 1.26 (t, J =
.1 Hz, 3 H) ppm. 13C NMR (176 MHz, CDCl ): δ = 214.9, 177.1, 143.1,
3
[4.6 × 250 mm Daicel IF column, 98.8:0.2 hexanes:iPrOH, 2 mL/min,
31.9, 131.7, 131.5, 131.3, 128.3, 125.9, 124.3, 122.8, 121.23, 121.20,
21.17, 121.15, 121.13, 121.11, 61.4, 60.3, 51.3, 49.1, 48.2, 40.2, 37.6,
2
54 nm, retention times 16.6 min (major) and 34.5 min (minor)]:
23
[α] = + 27.5 (c = 1.0, CHCl ). IR (neat): ν˜ = 3368, 2932, 2876, 1720,
D
3
+
+
2.2, 21.0, 19.0, 14.3 ppm. HRMS (ES ) Calcd for C H F NO (M ),
–1 1
2
1
23
6
3
1
670, 1513, 1238, 762 cm . H NMR (400 MHz, CDCl ): δ = 6.74 (d,
3
52.1660 found 452.1643.
J = 9.2 Hz, 2 H), 6.53 (d, J = 8.8 Hz, 2 H), 4.67 (br. s, 1 H), 3.72 (s, 3
H), 2.90–3.02 (m, 3 H), 2.60 (dt, J = 19.0, 3.2 Hz, 1 H), 2.38–2.47 (m,
Bicyclic Amine 6d: (57 mg, 22 mmol, 85 %, 6:1 dr), as a colorless
2
3
oil: [α] = + 9.2 (c = 1, CHCl ). IR (neat): ν˜ = 3429, 2949, 2876, 1734, 2 H), 2.21 (dd, J = 19.3, 2.6 Hz, 1 H), 1.92–1.98 (m, 1 H), 1.70–1.82
D
3
1
–
1
1
672, 1647, 1465, 1453 cm . H NMR (700 MHz, CDCl ): δ = 5.80– (m, 1 H), 1.49–1.60 (m, 1 H), 1.29 (t, J = 7.5 Hz, 3 H), 1.29 (s, 3 H)
3
5
.86 (m, 1 H), 5.14 (dd, J = 17.2, 1.8 Hz, 1 H), 5.05 (d, J = 10.1 Hz, 1
ppm. 13C NMR (100 MHz, CDCl ): δ = 214.8, 205.8, 117.2, 115.1,
3
H), 4.18 (q, J = 7.0 Hz, 2 H), 3.81 (d, J = 3.1 Hz, 1 H), 3.30 (dd, J = 114.9, 56.6, 56.2, 55.9, 49.8, 40.9, 39.2, 23.7, 21.7, 20.8, 19.6, 14.8
+
+
1
3
2
4.1, 5.7 Hz, 1 H), 3.14 (dd, J = 14.1, 6.2 Hz, 1 H), 2.51 (dt, J = 18.9, ppm. HRMS (ES ) Calcd for C H NO S (M ), 348.1633 found
19 25 3
.1 Hz, 1 H), 2.43 (q, J = 2.6 Hz, 1 H), 2.36 (quin, J = 2.6 Hz, 1 H),
.08 (dd, J = 18.9, 2.6 Hz, 1 H), 1.71–1.83 (m, 2 H), 1.60–1.69 (m, 1
348.1624.
Bicyclic Amine 6i: (41 mg, 0.13 mmol, 57 %, 83.2:16.8 er, 6:1 dr), as
a colorless oil, enantiomeric ratio was determined by chiral HPLC
4.6 × 250 mm Phenomenex Lux 5u Cellulose-3 column, 99:1 to
0:10 hexanes:iPrOH, 1 mL/min, 254 nm, retention times 27.8 min
H), 1.52 (dddd, J = 14.0, 11.4, 5.0, 3.1 Hz, 1 H), 1.25–1.28 (m, 6 H)
ppm. 13C NMR (176 MHz, CDCl ): δ = 215.1, 177.3, 136.8, 116.0, 61.1,
3
[
+
5
9.7, 50.8, 48.0, 40.2, 37.7, 22.3, 21.0, 18.9, 14.3 ppm. HRMS (ES )
9
(
+
Calcd for C H NO (M ), 266.1756 found 266.1753.
23
15
24
3
minor) and 29.4 min (major)]: [α]D = + 8.0 (c = 1, CHCl ). IR (neat):
3
–
1 1
Bicyclic Amine 6e: (26 mg, 0.08 mmol, 30 %, 95.7:4.3er, 20:1 dr), as ν˜ = 3346, 2951, 2878, 1724, 1642 cm . H NMR (700 MHz, CDCl ):
3
a colorless oil, enantiomeric ratio was determined by chiral HPLC
4.6 × 250 mm Daicel IF column, 98.8:0.2 hexanes:iPrOH, 2 mL/min,
54 nm, retention times 5.2 min (major) and 7.8 min (minor)]:
δ = 7.32–7.38 (m, 5 H), 5.79–5.85 (m, 1 H), 5.18 (d, J = 1.5 Hz, 2 H),
5.11–5.16 (m, 1 H), 5.05 (dq, J = 10.2, 1.4 Hz, 1 H), 3.85 (d, J = 2.7 Hz,
1 H), 3.30 (ddt, J = 14.1, 5.7, 1.5, 1.5 Hz, 1 H), 3.13 (ddt, J = 14.0,
[
2
[
2
3
α] = + 7.5 (c = 1.0, CHCl ). IR (neat): ν˜ = 3353, 2957, 1710, 1601, 6.2, 1.4, 1.4 Hz, 1 H), 2.52 (dt, J = 19.0, 3. 2 Hz, 1 H), 2.44 (q, J =
D
3
–1 1
1
6
8
1
1
255, 694 cm . H NMR (400 MHz, CDCl ): δ = 7.09–7.18 (m, 2 H),
.58–6.71 (m, 3 H), 4.74 (dd, J = 8.33, 3.07 Hz, 1 H), 3.45 (d, J =
2.9 Hz, 1 H), 2.39 (quin, J = 3.0 Hz, 1 H), 2.08 (dd, J = 19.0, 2.7 Hz,
1 H), 1.76–1.82 (m, 1 H), 1.70–1.76 (m, 1 H), 1.60 (dddt, J = 13.9,
3
1
3
.33 Hz, 1 H), 2.56 (dt, J = 19.29, 3.07 Hz, 1 H), 2.43 (q, J = 3.07 Hz, 11.2, 5.3, 2.8, 2.8 Hz, 1 H), 1.30 (s, 3 H) 1.47–1.53 (m, 1 H) ppm.
C
H), 2.35 (quin, J = 3.10 Hz, 1 H), 2.17 (dd, J = 19.29, 2.63 Hz, 1 H),
NMR (176 MHz, CDCl ): δ = 215.1, 177.1, 136.7, 136.0, 128.7, 128.5,
3
.94–2.03 (m, 1 H), 1.73–1.88 (m, 2 H), 1.54–1.63 (m, 2 H), 1.51 (s, 9
128.2, 116.1, 67.0, 59.8, 50.8, 49.0, 47.9, 40.1, 37.8, 22.3, 20.9, 18.9
1
3
+
+
H), 1.18 (s, 3 H) ppm. C NMR (100 MHz, CDCl ): δ = 215.1, 176.0,
ppm. HRMS (ES ) Calcd for C H NO (M ), 328.1913 found
3
20 25 3
1
1
3
47.7, 129.4, 117.6, 113.2 81.3, 55.32, 50.0, 40.6, 38.1, 28.1, 22.3, 20.9, 328.1905.
+
+
8.9 ppm. HRMS (ES ) Calcd for C H NO (M ), 330.2069 found
2
0
27
3
Bicyclic Amine 8a: (70 mg, 0.20 mmol, 80 %, 86.7:13.3 er, 9:1 dr),
as a colorless solid, enantiomeric ratio was determined by chiral
HPLC [4.6 × 250 mm Daicel IF column, 98.8:0.2 hexanes:iPrOH, 2 mL/
30.2071.
Bicyclic Amine 6f: (59 mg, 0.16 mmol, 66 %, 89.3:10.7 er, 20:1 dr),
as a colorless oil, enantiomeric ratio was determined by chiral HPLC min, 254 nm, retention times 79.2 min (major) and 83.4 min (mi-
2
3
[
2
[
1
6
2
4.6 × 250 mm Daicel IF column, 98.8:0.2 hexanes:iPrOH, 2 mL/min, nor)]: m.p. 71–73 °C [α] = + 10.2 (c = 1.0, CHCl ). IR (neat): ν˜ =
D
3
–
1 1
54 nm, retention times 9.3 min (major) and 32.1 min (minor)]:
3430, 3337, 2977, 2951, 2878, 1724, 1454 cm . H NMR (700 MHz,
2
3
α] = + 14.6 (c = 1.0, CHCl ). IR (neat): ν˜ = 3387, 2977, 2949, 1723, CDCl ): δ = 7.27–7.32 (m, 4 H), 7.21–7.24 (m, 1 H), 3.83–3.88 (m, 2
D
3
3
–1 1
515 cm . H NMR (400 MHz, CDCl ): δ = 6.69–6.78 (m, 2 H), 6.56–
H), 3.66 (d, J = 12.9 Hz, 1 H), 2.53 (dt, J = 18.9, 2.9 Hz, 1 H), 2.50 (q,
3
.65 (m, 2 H), 4.64 (br. s, 1 H), 3.72 (s, 3 H), 3.18 (d, J = 4.0 Hz, 1 H),
.55 (dt, J = 19.3, 3.1 Hz, 1 H), 2.42 (q, J = 2.8 Hz, 1 H), 2.34 (quin,
J = 2.9 Hz, 1 H), 2.33 (t, J = 2.9 Hz, 1 H), 2.08 (dd, J = 19.0, 2.8 Hz,
1 H), 1.71–1.84 (m, 3 H), 1.50–1.56 (m, 1 H), 1.45–1.48 (m, 9 H), 1.28
Eur. J. Org. Chem. 2016, 150–157
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim