Page 11 of 17
The Journal of Organic Chemistry
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5
5
EtOAc/hexane); H NMR (CDCl ) δ major diastereoisomer 7.79
1H, H ), 3.20 (dd, J = 11.4, 8.1 Hz, 1H, H ), 2.79 (br s, 1H, OH),
3
2
1
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3
4
5
6
7
8
9
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1
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(d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 6.83ꢀ6.77 (m, 4H),
3.91ꢀ3.85 (m, 1H, H ), 3.77 (s, 3H, OMe), 3.54 (dq, J = 9.2,
.2 Hz, 1H, H ), 3.40ꢀ3.31 (m, 2H, H , H ), 3.18 (dd, J = 11.4, 7.6
Hz, 1H, H ), 2.60 (dd, J = 11.7, 9.2 Hz, 1H, H ), 2.48 (s, 3H),
.03ꢀ1.95 (m, 1H, H ), 1.35 (d, J = 6.2 Hz, 3H, H ); minor
diastereoisomer 7.82 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H),
.63 (d, J = 8.9 Hz, 2H), 6.57 (d, J = 8.9 Hz, 2H), 3.91ꢀ3.85 (m,
H, H ), 3.74ꢀ3.70 (m, 1H, H ), 3.74 (s, 3H, OMe), 3.27 (dd,
J = 10.2, 8.0 Hz, 1H, H ’), 3.10 (dd, J = 7.1, 4.4 Hz, 1H, H ),
2.92 (dd, J = 10.8, 5.9 Hz, 1H, H ), 2.85ꢀ2.74 (m, 1H, H ), 2.60
(dd, J = 11.7, 9.6 Hz, 1H, H ), 2.49 (s, 3H), 1.46 (d, J = 6.2 Hz,
H, H ); C NMR (CDCl ) δ major diastereoisomer 159.1,
43.7, 135.1, 129.8, 129.4, 128.7, 127.5, 114.4, 63.9 (C ), 56.3
C ), 55.3 (OMe), 52.2 (C ), 46.6 (C ), 43.7 (C ), 21.6, 20.5 (C );
minor diastereoisomer 158.6, 143.6, 135.1, 129.9, 129.6, 128.9,
27.5, 113.9, 61.4 (C ), 55.2 (OMe), 53.9 (C ), 51.1 (C ), 44.1
2.98 (dd, J = 11.4, 9.0 Hz, 1H, H ), 2.52 (s, 3H), 2.03ꢀ1.96 (m,
4
3
1H, H ); minor diastereoisomer 7.85 (d, J = 7.8 Hz, 2H), 7.44 (t,
1
4
5
6
J = 6.9 Hz, 2H), 7.17 (t, J = 7.4 Hz, 1H), 7.05 (t, J = 7.4 Hz, 2H),
6.58 (d, J = 7.6 Hz, 2H), 3.94 (d, J = 9.8 Hz, 1H, H ), 3.84ꢀ3.75
(m, 3H, H , H , H ), 3.50 (dd, J = 7.2, 5.1 Hz, 1H, H ), 3.36ꢀ
3.31 (m, 1H, H ), 2.90 (dd, J = 10.6, 5.6 Hz, 1H, H ), 2.70 (br s,
1H, OH), 2.87ꢀ2.81 (m, 1H, H ), 2.52 (s, 3H), 2.44 (t,
J = 10.6 Hz, 1H, H ); C NMR (CDCl ) δ major diastereoisomer
144.3, 135.5, 134.2, 130.1, 129.1, 127.8, 127.8, 127.7, 69.7 (C ),
63.1 (C ), 53.6 (C ), 50.7 (C ), 46.9 (C ), 43.4 (C ), 21.6; minor
diastereoisomer 144.4, 135.4, 133.8, 130.1, 128.7, 127.9, 127.8,
127.4, 66.9 (C ), 65.4 (C ), 52.3 (C ), 50.0 (C ), 44.4 (C ), 42.9
(C ), 21.6; FTIR (ν
(sp CꢀH), 1335 (sulfone), 1154 (sulfone); HRMS (ESI+)
calculated for C H ClNO S [M+H] 380.1082, found 380.1074.
5
2
6’
3
6
1’
4’
6’
2’
2
4’
5’
3’
6
1
1’
4’
5’ 13
3
4
2’
1
5
’
3’
6
4
2
3
5
5
’
0
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9
0
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0
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0
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8
9
0
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7
8
9
0
6
’
13
1’
6’
4’
2’
3’
3
1
(
3
1
5’
ꢀ1
3
cm ) 3487 (OH), 2926 (sp CꢀH), 2871
max
2
4
3
5
6
3
+
19
23
3
1’
2’
4’
1
(
3’
5’
6’
ꢀ1
3
C ), 43.1 (C ), 23.0 (C ), 21.6; FTIR (ν cm ) 2964 (sp Cꢀ
H), 2929 (sp CꢀH), 1343 (sulfone), 1247 (ether CꢀO), 1141
(sulfone); HRMS (ESI+) calculated for C H ClNO SNa
max
3
2
0
24
3
+
[M+Na] 416.1058, found 416.1049.
3-(chloromethyl)-1-tosyl-1,2,3,3a,8,8a-hexahydroindeno[2,1-
b]pyrrole (4p). According to general procedure C1, isolated as a
yellow oil (51.5 mg, 0.142 mmol, 71%) of a mixture of non
separable diastereoisomers (dr = 60:40). With general procedure
C2 (56.2 mg, 0.155 mmol, 78%). R 0.44 (30% EtOAc/hexane);
f
1
H NMR (CDCl ) δ major diastereoisomer 7.79ꢀ7.74 (m, 2H),
4
-(chloromethyl)-2-methyl-3-(5-phenylthiophen-2-yl)-1-
3
7
5
.36 (d, J = 7.9 Hz, 2H), 7.24ꢀ7.15 (m, 4H), 4.45 (dt, J = 8.0,
tosylpyrrolidine (4n). According to general procedure C1,
isolated as an orange oil (62.1 mg, 0.139 mmol, 70%) of a
mixture of non separable diastereoisomers (dr = 65:35). With
general procedure C2 (50.1 mg, 0.112 mmol, 56%). R 0.43 (30%
EtOAc/hexane); H NMR (CDCl ) δ major diastereoisomer 7.80
(d, J = 8.0 Hz, 2H), 7.50 (d, J = 7.6 Hz, 2H), 7.42ꢀ7.33 (m, 3H),
7.30ꢀ7.25 (m, 2H), 7.10 (d, J = 3.6 Hz, 1H), 6.71 (d, J = 3.6 Hz,
1
1
2
.4 Hz, 1H, H ), 3.89 (t, J = 7.7 Hz, 1H, H ), 3.52ꢀ3.46 (m, 1H,
4
5
6
H ), 3.36ꢀ3.29 (m, 4H, 2H , 2H ), 3.20 (dd, J = 10.9, 7.7 Hz, 1H,
H ), 2.46 (s, 3H), 2.44ꢀ2.39 (m, 1H, H ); minor diastereoisomer
7.79ꢀ7.74 (m, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.24ꢀ7.15 (m, 4H),
4
3
f
1
3
1’
4
.37 (dt, J = 6.9, 2.3 Hz, 1H, H ), 3.57 (dd, J = 7.2, 3.5 Hz, 1H,
2’
4’
6’
6’
H ), 3.45ꢀ3.37 (m, 2H, H , H ), 3.36ꢀ3.29 (m, 1H, H ), 3.29ꢀ
3
2
4
’
5’
5’
4
1
.24 (m, 2H, H , H ), 2.97 (dd, J = 11.1, 8.4 Hz, H, H ), 2.64ꢀ
H), 3.89ꢀ3.8 (m, 1H, H ), 3.65 (dq, J = 9.0, 6.2 Hz, 1H, H ), 3.51
3
’
13
5
4
.59 (m, 1H, H ), 2.45 (s, 3H); C NMR (CDCl ) δ major
(dd, J = 11.5, 3.5 Hz, 1H, H ), 3.46ꢀ3.39 (m, 1H, H ), 3.34 (dd,
3
5
2
diastereoisomer 143.7, 143.3, 137.9, 134.6, 129.8, 128.0, 127.5,
J = 11.5, 7.2 Hz, 1H, H ), 3.01 (dd, J = 11.1, 9.0 Hz, 1H, H ),
1
2
4
3
3
6
1
4
26.9, 125.3, 123.5, 64.0 (C ), 52.3 (C ), 52.2 (C ), 44.8 (C ),
2
.48 (s, 3H), 2.07ꢀ1.99 (m, 1H, H ), 1.48 (d, J = 6.2 Hz, 3H, H );
minor diastereoisomer 7.83 (d, J = 8.0 Hz, 2H), 7.42ꢀ7.33 (m,
H), 7.30ꢀ7.25 (m, 1H), 7.01 (d, J = 3.6 Hz, 1H), 6.50 (d,
6
5
3.2 (C ), 40.9 (C ), 21.6; minor diastereoisomer 143.7, 141.7,
1
’
141.4, 134.7, 129.8, 127.9, 127.4, 127.0, 125.3, 123.5, 63.3 (C ),
6
2’
4’
3’
5’
6’
1
’
53.7 (C ), 51.8 (C ), 47.1 (C ), 45.1 (C ), 40.7 (C ), 21.6; FTIR
J = 3.6 Hz, 1H), 3.89ꢀ3.82 (m, 1H, H ), 3.80 (dd, J = 9.9, 5.8 Hz,
1H, H ), 3.32ꢀ3.28 (m, 1H, H ), 3.46ꢀ3.39 (m, 1H, H ),3.14ꢀ3.09
ꢀ
1
3
3
4’
4’
2’
(
(
[
νmax cm ) 2912 (sp CꢀH), 2853 (sp CꢀH), 1338 (sulfone), 1154
sulfone); HRMS (ESI+) calculated for C H ClNO SNa
M+Na] 384.0795, found 384.0791.
5’
3’
5’
(m, 1H, H ), 2.90ꢀ2.85 (m, 2H, H , H ), 2.45 (s, 3H), 1.54 (d,
19 20
2
+
6
’
13
J = 6.2 Hz, 3H, H ); C NMR (CDCl ) δ major diastereoisomer
3
1
1
4
1
1
43.8, 143.6, 140.5, 134.8, 133.9, 129.9, 128.9, 127.8, 127.6,
1
2
4
3
26.8, 125.6, 122.9, 64.2 (C ), 52.0 (C ), 51.9 (C ), 47.4 (C ),
5
6
3.5 (C ), 21.6, 20.8 (C ); minor diastereoisomer 143.7, 143.6,
39.7, 134.8, 133.8, 129.8, 128.9, 127.7, 127.1, 126.4, 125.5,
1’
2’
4’
2’
4’
3’
22.5, 62.7 (C ), 50.5 (C or C ), 50.4 (C or C ), 43.8 (C ),
5’
6’
ꢀ1
3
42.6 (C ), 23.2 (C ), 21.6; FTIR (ν
2924 (sp CꢀH), 2851 (sp CꢀH), 1341 (sulfone), 1161 (sulfone);
HRMS (ESI+) calculated for C H ClNO S [M+H] 446.1010,
found 446.0999.
cm ) 2962 (sp CꢀH),
max
1-(chloromethyl)-3-tosyl-2,3,3a,4,5,9b-hexahydro-1H-
benzo[e]indole (4q). According to general procedure C1, isolated
as a clear yellow oil (27.6 mg, 0.073 mmol, 37%) of a mixture of
3
3
+
23 25
2
2
non separable diastereoisomers (dr = 81:19). R 0.46 (30%
f
1
EtOAc/hexane); H (CDCl ) δ for major diastereoisomer 7.78 (d,
3
J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.18ꢀ7.10 (m, 3H), 6.99
1
(
d, J = 6.9 Hz, 1H), 3.99 (td, J = 7.9, 4.5 Hz, 1H, H ), 3.62 (dd,
4
5
J = 10.0, 6.9 Hz, 1H, H ), 3.57 (dd, J = 11.5, 3.9 Hz, 1H, H ),
.43 (dd, J = 11.5, 6.3 Hz, 1H, H ), 3.19 (t, J = 9.4 Hz, 1H, H ),
.91 (t, J = 8.2 Hz, 1H, H ), 2.89ꢀ2.83 (m, 1H, H ), 2.76ꢀ2.70 (m,
1H, H ), 2.50ꢀ2.46 (m, 1H, H ), 2.45 (s, 3H), 2.21ꢀ2.14 (m, 1H,
5
4
3
2
2
7
4
-(chloromethyl)-3-phenyl-1-tosylpyrrolidin-2-yl)methanol
7
3
(4o). According to general procedure C1, isolated as an colorless
6
6
H ), 2.06ꢀ1.99 (m, 1H, H ); minor diastereoisomer 7.78 (d,
oil (37.2 mg, 0.098 mmol, 49%) of a mixture of non separable
diastereoisomers (dr = 53:47). With general procedure C2 (41 mg,
0
(CDCl ) δ major diastereoisomer 7.83 (d, J = 7.8 Hz, 2H), 7.44
(t, J = 6.9 Hz, 2H), 7.25ꢀ7.21 (m, 3H), 6.80 (dd, J = 6.0, 2.7 Hz,
2H), 4.04ꢀ3.98 (m, 1H, H ), 3.63ꢀ3.55 (m, 2H, H , H ), 3.87 (d,
J = 11.4 Hz, 1H, H ), 3.40 (t, J = 11.5 Hz, 1H, H ), 3.36ꢀ3.31 (m,
J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.18ꢀ7.10 (m, 3H), 7.05
1’
(
(
d, J = 6.9 Hz, 1H), 3.86 (td, J = 9.7, 4.5 Hz, 1H, H ), 3.67ꢀ3.63
1
.108 mmol, 54%). R 0.27 (30% EtOAc/hexane); H NMR
4’
2’
3’
f
m, 1H, H ), 3.35 (t, J = 8.3 Hz, 1H, H ), 3.32ꢀ3.24 (m, 2H, H ,
H ), 2.83ꢀ2.77 (m, 1H, H ), 2.69ꢀ2.64 (m, 1H, H ), 2.45 (s, 3H),
2.40ꢀ2.35 (m, 1H, H ), 1.75ꢀ1.67 (m, 1H, H ); C NMR (CDCl
3
4’
7’
7’
6’
6’ 13
4
1
6
3
)
δ major diastereoisomer 143.7, 137.1, 134.6, 133.9, 129.8, 128.9,
6
4
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