Advanced Synthesis & Catalysis
10.1002/adsc.201901035
(
-
5aS,10bR)-9-methoxy-6H-5a,10b-butanobenzofuro[2,3
b]indol-2-ol (3i): White solid, 45.1 mg, yield: 73%; mp. =
r 2
t (minor) = 5.93 min. HRMS (ESI+) calcd for C18H16FNO
+
(M+H) , m/z 298.1238, found 298.1229.
(5aS,10bR)-9-chloro-6H-5a,10b-butanobenzofuro[2,3-
b]indol-2-ol (3m): White solid, 59.5 mg, yield: 95%; mp.
2
5
1
1
82-183 °C; [α]
) δ 6.84 (d, J = 2.1 Hz, 1H), 6.70 (d, J = 4.3
Hz, 1H), 6.65 (d, J = 2.4 Hz, 1H), 6.62 (dd, J = 7.3, 5.0 Hz,
D
3
= 1.04 (c 0.25, CHCl ); H NMR (500
MHz, CDCl
3
25
1
= 207-208 °C; [α]
D 3
= 2.68 (c 0.25, CHCl ); H NMR (500
2
3
1
H), 6.54 (d, J = 2.5 Hz, 1H), 4.68 (d, J = 5.0 Hz, 2H),
.71 (s, 3H), 2.39-2.34 (m, 1H), 2.21-2.16 (m, 1H), 1.89-
MHz, CDCl ) δ 7.00 (dd, J = 6.5, 2.2 Hz, 2H), 6.84 (d, J =
3
2.2 Hz, 1H), 6.62-6.54 (m, 3H), 4.73 (s, 1H), 4.62 (s, 1H),
2.36 (dt, J = 14.0, 4.0 Hz, 1H), 2.18 (dt, J = 14.0, 4.4 Hz,
1H), 1.88 (ddd, J = 14.1, 11.5, 4.8 Hz, 1H), 1.69-1.58 (m,
3H), 1.55-1.48 (m, 1H), 1.42-1.35 (m, 1H). 13C{ H} NMR
.85 (m, 1H), 1.68-1.59 (m, 4H), 1.53-1.48 (m, 1H).
1
3
1
C{ H} NMR (125 MHz, CDCl
3
) δ 153.3, 151.9, 148.9,
1
1
1
39.4, 134.7, 132.0, 115.2, 113.3, 111.6, 109.3, 109.2,
08.9, 55.7, 54.9, 31.3, 31.0, 19.9, 19.1. 86% ee as
3
(125 MHz, CDCl ) δ 152.9, 150.1, 145.2, 136.0, 132.5,
determined by HPLC (Chiralcel IA, 80:20 hexanes/i-PrOH, 127.7, 125.0, 123.2, 114.6, 110.5, 110.3, 110.0, 109.7, 56.5,
mL/min), t (major) = 14.14 min, t (minor) = 10.67 min. 32.2, 31.8, 20.6, 19.9. 87% ee as determined by HPLC
(M+H) , m/z 310.1438, (Chiralcel IA, 80:20 hexanes/i-PrOH, 1 mL/min), t
(major) = 6.14 min, t (minor) = 10.36 min. HRMS (ESI+)
1
r
r
+
HRMS (ESI+) calcd for C19
H
19NO
3
r
found 310.1435.
r
+
(
5aS,10bR)-7-ethyl-6H-5a,10b-butanobenzofuro[2,3-
calcd for C18
314.0937.
2
H16ClNO (M+H) , m/z 314.0942, found
b]indol-2-ol (3j): White solid, 43.6 mg, yield: 71%; mp. =
2
5
1
1
71-172 °C; [α]
MHz, DMSO) δ 8.85 (s, 1H), 6.95-6.83 (m, 4H), 6.63 (t, J
7.5 Hz, 1H), 6.48 (s, 2H), 2.55-2.51 (m, 2H), 2.43-2.34
D
= -0.1 (c 0.25, CHCl
3
); H NMR (500
(5aS,10bR)-7-chloro-6H-5a,10b-butanobenzofuro[2,3-
b]indol-2-ol (3n): White solid, 38.2 mg, yield: 61%; mp. =
25
1
=
153-154 °C; [α]
D
3
= 8.88 (c 0.25, CHCl ); H NMR (500
(
(
(
m, 1H), 2.34-2.24 (m, 1H), 1.82-1.72 (m, 1H), 1.62-1.50
MHz, DMSO) δ 8.91 (s, 1H), 7.41 (s, 1H), 7.08 (dd, J =
7.5, 3.4 Hz, 2H), 6.92 (d, J = 1.9 Hz, 1H), 6.68 (t, J = 7.7
m, 2H), 1.48-1.40 (m, 1H), 1.36-1.30 (m, 1H), 1.20-1.10
m, 4H). 13C{ H} NMR (125 MHz, DMSO) δ 151.9, 151.7, Hz, 1H), 6.60-6.44 (m, 2H), 2.43-2.29 (m, 2H), 1.81-1.72
1
1
1
9
46.0, 134.1, 133.6, 126.9, 124.2, 120.4, 118.9, 113.9,
10.7, 109.6, 109.3, 56.3, 32.5, 31.6, 23.9, 20.7, 20.0, 14.2.
0% ee as determined by HPLC (Chiralcel IA, 80:20
(m, 1H), 1.65-1.54 (m, 2H), 1.48-1.39 (m, 1H), 1.32 (d, J =
13
1
23.6 Hz, 1H), 1.16 (d, J = 7.2 Hz, 1H). C{ H} NMR (125
MHz, DMSO) δ 152.0, 151.7, 145.1, 136.6, 132.7, 127.8,
121.8, 119.9, 114.4, 113.3, 110.8, 109.6, 109.0, 57.2, 32.1,
31.1, 20.3, 19.7. 95% ee as determined by HPLC
hexanes/i-PrOH, 1 mL/min), t
r
(major) = 6.48 min, t
r
(
(
(
minor) = 5.22 min. HRMS (ESI+) calcd for C20H21NO
M+H) , m/z 308.1645, found 308.1638.
5aS,10bR)-9-fluoro-6H-5a,10b-butanobenzofuro[2,3-
2
+
(Chiralcel IA, 80:20 hexanes/i-PrOH, 1 mL/min), t
(major) = 8.59 min, t (minor) = 5.55 min.HRMS (ESI+)
r
r
+
b]indol-2-ol (3k): White solid, 36.2 mg, yield: 61%; mp. =
calcd for C18
314.094.
2
H16ClNO (M+H) , m/z 314.0942, found
2
5
1
8
5-86 °C; [α]
MHz, DMSO) δ 8.86 (d, J = 15.9 Hz, 1H), 7.06 (s, 1H),
.99-6.92 (m, 2H), 6.82 (td, J = 9.4, 2.7 Hz, 1H), 6.59 (dd,
J = 8.4, 4.3 Hz, 1H), 6.49 (dd, J = 10.2, 1.6 Hz, 2H), 2.43-
.36 (m, 1H), 2.18 (dt, J = 13.6, 4.2 Hz, 1H), 1.73 (ddd, J
13.8, 11.7, 4.8 Hz, 1H), 1.61-1.53 (m, 2H), 1.47-1.41 (m,
D
3
= 2.96 (c 0.25, CHCl ); H NMR (500
(5aS,10bR)-9-bromo-6H-5a,10b-butanobenzofuro[2,3-
b]indol-2-ol (3o): White solid, 66.4 mg, yield: 93%; mp. =
6
25
1
252-253 °C; [α]
D
3
= 2.42 (c 0.25, CHCl ); H NMR (500
2
=
MHz, CDCl ) δ 7.16-7.11 (m, 2H), 6.84 (d, J = 2.2 Hz,
3
1H), 6.57 (dd, J = 4.3, 3.8 Hz, 3H), 4.70 (d, J = 43.7 Hz,
2H), 2.36 (dt, J = 13.7, 4.1 Hz, 1H), 2.18 (dt, J = 14.0, 4.4
Hz, 1H), 1.88 (ddd, J = 14.1, 11.5, 4.8 Hz, 1H), 1.69-1.60
(m, 3H), 1.53-1.49 (m, 1H), 1.42-1.36 (m, 1H). 13C{ H}
H), 1.28 (s, 1H), 1.18-1.10 (m, 1H). 1 C{ H} NMR (125
3
1
1
MHz, DMSO) δ 156.5 (d, J = 233.1 Hz), 151.9, 144.4,
1
1
1
7
36.2 (d, J = 7.6 Hz), 132.7, 114.3, 113.8 (d, J = 22.7 Hz),
10.9, 110.6 (d, J = 23.9 Hz), 110.2, 109.4, 109.2 (d, J =
.6 Hz), 56.5, 32.1, 31.7, 20.7, 19.9. 1 F NMR (471 MHz,
3
NMR (125 MHz, CDCl ) δ 152.9, 150.1, 145.7, 136.5,
9
132.5, 130.6, 126.0, 114.6, 111.6, 111.1, 110.4, 110.0,
109.5, 56.5, 32.2, 31.8, 20.6, 19.8. 87% ee as determined
by HPLC (Chiralcel IA, 80:20 hexanes/i-PrOH, 1 mL/min),
CDCl
3
) δ -114.8. 91% ee as determined by HPLC
(
(
Chiralcel IA, 80:20 hexanes/i-PrOH, 1 mL/min), t
major) = 19.80 min, t
r
r
(minor) = 21.27 min. HRMS (ESI+)
(M+H) , m/z 298.1238, found
r r
t (major) = 6.15 min, t (minor) = 8.18 min. HRMS (ESI+)
+
+
calcd forC18
98.1228.
5aS,10bR)-7-fluoro-6H-5a,10b-butanobenzofuro[2,3-
b]indol-2-ol (3l): White solid, 33.8 mg, yield: 57%; mp. =
H
16FNO
2
calcd for C18
358.0434.
2
H16BrNO (M+H) , m/z 358.0437, found
2
(
(5aS,10bR)-7-bromo-6H-5a,10b-butanobenzofuro[2,3-
b]indol-2-ol (3p): White solid, 56.4 mg, yield: 79%; mp. =
2
5
1
25
1
1
93-194 °C; [α]
D
= 0.06 (c 0.25, CHCl
3
); H NMR (500
101-102 °C; [α]
D
3
= 0.32 (c 0.25, CHCl ); H NMR (500
MHz, CDCl
3
) δ 6.84 (dd, J = 12.7, 4.9 Hz, 3H), 6.70 (dt, J
MHz, DMSO) δ 8.80 (s, 1H), 7.17 (s, 1H), 7.10 (d, J = 8.0
Hz, 1H), 6.99 (d, J = 7.2 Hz, 1H), 6.80 (d, J = 2.2 Hz, 1H),
6.51 (t, J = 7.6 Hz, 1H), 6.44-6.33 (m, 2H), 2.30-2.18 (m,
2H), 1.64 (ddd, J = 13.9, 11.5, 4.8 Hz, 1H), 1.47 (ddd, J =
12.0, 11.4, 4.5 Hz, 2H), 1.36-1.28 (m, 1H), 1.25-1.17 (m,
1H), 1.03 (d, J = 8.0 Hz, 1H). C{ H} NMR (125 MHz,
DMSO) δ 152.0, 151.7, 146.6, 136.4, 132.8, 130.6, 122.3,
120.3, 114.4, 110.8, 109.5, 108.7, 101.7, 57.4, 32.2, 31.0,
20.3, 19.7. >99% ee as determined by HPLC (Chiralcel IA,
=
12.2, 6.3 Hz, 1H), 6.64-6.50 (m, 2H), 4.83 (s, 1H), 4.61
(
(
s, 1H), 2.37 (d, J = 14.0 Hz, 1H), 2.27-2.18 (m, 1H), 1.92
dd, J = 18.2, 7.1 Hz, 1H), 1.66 (ddd, J = 16.9, 13.6, 5.4
Hz, 3H), 1.55-1.47 (m, 1H), 1.41 (d, J = 11.3 Hz, 1H).
13
1
13
1
C{ H} NMR (125 MHz, CDCl
3
) δ 151.5 (d, J = 362.9
Hz), 137.53 (d, J = 6.0 Hz), 133.9, 132.8, 120.6 (d, J = 8.0
Hz), 118.3, 114.7, 114.6, 114.5, 110.3, 110.0, 109.7, 57.0,
1
9
3
1
8
2.2, 31.9, 20.6, 19.9. F NMR (471 MHz, CDCl
13.6. 85% ee as determined by HPLC (Chiralcel IA,
0:20 hexanes/i-PrOH, 1 mL/min), t (major) = 11.02 min,
3
) δ -
80:20 hexanes/i-PrOH, 1 mL/min), t
r
(major) = 7.475 min,
r
t (minor) = 5.124 min. HRMS (ESI+) calcd for
r
+
18 2
C H16BrNO (M+H) , m/z 358.0437, found 358.0431.
6
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