HETEROCYCLES, Vol. 66, 2005
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2
3
1
amorphous solid: [α]D +2.6° (c 1.030, CHCl ); H NMR (300 MHz, CDCl ) δ 8.73 (d, J = 4.5 Hz, 1H),
3
3
8
6
.10 (d, J = 2.4 Hz, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.39 (dd, J = 2.7, 9.3 Hz, 1H), 7.29 (d, J = 4.5 Hz, 1H),
.93 (d, J = 2.1 Hz, 1H), 4.38 (ddd, J = 2.4, 6.6, 11.4 Hz, 1H), 4.29 (dd, J = 4.2, 10.5 Hz, 1H), 4.24-4.15
(
m, 2H), 4.12-4.06 (m, 2H), 4.10 (s, 3H), 3.98 (dd, J = 7.4, 13.8 Hz, 1H), 3.17 (ddd, J = 6.6, 11.4, 14.1 Hz,
1
H), 2.96 (s, 3H), 2.87 (s, 3H), 2.26 (s, 3H), 2.08-1.94 (m, 1H), 1.87-1.56 (m, 3H), 1.48 (s, 9H), 1.42-1.33
13
(
m, 1H), 1.26-1.20 (m, 1H); C NMR (75 MHz, CDCl ) δ 169.6, 158.5, 155.3, 147.1, 144.4, 141.8, 131.2,
3
1
2
26.5, 122.8, 117.4, 102.3, 80.5, 73.0, 66.7, 66.4, 56.2, 55.4, 42.9, 38.5, 37.4, 37.3, 29.5, 28.4, 26.7, 23.2,
-1
1.2; FT-IR (neat) 2974, 1745, 1678, 1624, 1412, 1354, 1236, 1169 cm ; HRMS (EI) calcd for
+
C H N O S (M ): 644.2073, found 644.2070.
2
8
40
2
11
2
(
2S,4R)-2-[(R)-Acetoxy(6-methoxyquinolin-4-yl)methyl]-5-methylenequinuclidine (22). To an
ice-cooled solution of 20 (42.3 mg, 0.066 mmol) in MeCN (1.3 mL) were added NaI (29.7 mg, 0.198
mmol) and chlorotrimethylsilane (0.03 mL, 0.198 mmol). After being stirred at rt for 1 h, the reaction
mixture was diluted with CHCl , washed with 10% Na CO and brine, dried, and concentrated to give the
3
2
3
1
corresponding amine (38.9 mg) as a yellow amorphous solid: H NMR (300 MHz, CDCl ) δ 8.75 (d, J =
3
4
3
5
.2 Hz, 1H), 8.04 (d, J = 9.0 Hz, 1H), 7.47-7.37 (m, 3H), 6.33 (d, J = 6.0 Hz, 1H), 4.41-4.20 (m, 4H),
.99 (s, 3H), 3.23-3.09 (m, 2H), 3.03 (s, 3H), 3.01 (s, 3H), 2.65-2.53 (m, 1H), 2.19 (s, 3H), 2.05-1.58 (m,
H), 1.39-1.16 (m, 2H).
A solution of the crude amine (38.9 mg) in MeCN (5.0 mL) was refluxed for 6 h. After cooling, the
reaction mixture was diluted with CHCl , washed with 10% Na CO and brine, dried, concentrated to give
3
2
3
1
2
4
0
3
1 (32.0 mg), a yellow viscous oil, as a 7:3 epimeric mixture: H NMR (300 MHz, CDCl ) δ 8.73 (d, J =
3
.5 Hz, 1H), 8.03 (d, J = 7.2 Hz, 1H), 7.42-7.27 (m, 3H), 6.55 (d, J = 6.3 Hz, 0.3H), 6.52 (d, J = 6.3 Hz,
.7H), 4.34 (dd, J = 3.9, 8.1 Hz, 0.6H), 4.19 (dd, J = 6.0, 7.8 Hz, 1.4H), 3.96 (s, 3H), 3.45-3.25 (m, 2H),
.07 (s, 0.9H), 3.03 (s, 2.1H), 3.01-2.49 (m, 3H), 2.36-1.12 (m, 6H), 2.18 (s, 0.9H), 2.16 (s, 2.1H).
A mixture of crude 21 (32.0 mg), tetra-n-butylammonium iodide (27.0 mg, 0.073 mmol) and DBU (0.04
mL, 0.264 mmol) in xylene (6.0 mL) was refluxed for 9 h. The reaction mixture was concentrated and
purified with preparative TLC (CHCl /MeOH = 10/1) to give 22 (13.4 mg, 58% from 20) as a colorless
3
2
4
1
viscous oil: [α]D –12.8° (c 0.670, CHCl ); H NMR (300 MHz, CDCl ) δ 8.74 (d, J = 4.5 Hz, 1H), 8.02
3
3
(
(
d, J = 9.3 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.38 (dd, J = 2.4, 9.3 Hz, 1H), 7.34 (d, J = 4.8 Hz, 1H), 6.51
d, J = 6.9 Hz, 1H), 4.83 (s, 1H), 4.70 (s, 1H), 3.97 (s, 3H), 3.77 (br dd, J = 1.8, 16.8 Hz, 1H), 3.43 (ddd,
J = 8.1, 8.1, 8.1 Hz, 1H), 3.30 (br d, J = 17.7 Hz, 1H), 2.87-2.71 (m, 2H), 3.51 (br t, J = 3.0 Hz, 1H), 2.12
13
(
s, 3H), 1.84 (br dd, J = 3.0, 8.7 Hz, 2H), 1.69-1.63 (m, 2H); C NMR (75 MHz, CDCl ) δ 170.0, 158.0,
3
1
2
51.4, 147.5, 144.8, 143.7, 131.9, 127.0, 121.9, 118.8, 103.9, 101.5, 73.8, 58.8, 55.7, 51.2, 50.7, 33.1,
-
1
9.8, 27.2, 21.1; FT-IR (neat) 2940, 1741, 1622, 1508, 1466, 1367, 1230, 1078, 1028 cm ; HRMS (EI)
+
calcd for C H N O (M ): 352.1787, found 352.1784.
21
24
2
3