Job/Unit: O50209
/KAP1
Date: 20-04-15 15:23:30
Pages: 10
W. Fan, S. Ma
leum ether/ethyl acetate, from 15:1 to 10:1) to afford 3ad (151.3 mg,
FULL PAPER
1.2 mmol) in dioxane (1.0 mL), and 2a (102.5 mg, 1.2 mmol) in di-
1
oxane (1.0 mL) were added sequentially under Ar. The resulting
mixture was then stirred at 40 °C until the reaction reached comple-
tion, as monitored by TLC (14 h). The crude reaction mixture was
filtered through a short pad of silica gel [diethyl ether (30 mL)].
After evaporation of the filtrate, the residue was purified by
chromatography on silica gel (petroleum ether/ethyl acetate, 20:1)
to afford 3aa (161.5 mg, 64%) as a liquid. 1H NMR (300 MHz,
57%) as a liquid. H NMR (300 MHz, CDCl
5.4 Hz, 1 H, =CH), 5.66 (d, J = 5.7 Hz, 1 H, =CH), 4.33–4.14 (m,
2 H, OCH ), 2.70–2.32 (m, 6 H, 2 NCH and CH ), 2.25–2.08 (m,
2 H, CH ), 1.81–1.38 (m, 8 H, 4 CH ), 1.27 (t, J = 6.9 Hz, 3 H,
CH ): δ = 170.6, 136.6, 125.7,
) ppm. 13C NMR (75 MHz, CDCl
3
): δ = 6.25 (d, J =
2
2
2
2
2
3
3
106.6, 89.8, 61.3, 47.1, 35.3, 35.2, 25.6, 24.2, 14.0, 11.4 ppm. MS
+
(ESI): m/z = 266 [M + H] . IR (neat): ν˜ = 2981, 2934, 2852, 2820,
CDCl
1
2
3
): δ = 5.96 (d, J = 5.7 Hz, 1 H, =CH), 5.64 (d, J = 5.7 Hz,
H, =CH), 4.37–4.16 (m, 2 H, OCH ), 2.72–2.61 (m, 2 H, NCH
.50–2.40 (m, 2 H, NCH ), 1.70–1.54 (m, 4 H, 2 CH ), 1.50–1.35 H] 266.1751; found 266.1753.
and 2 CH ), 1.29 (t, J = 7.1 Hz, 3 H, CH
NMR (75 MHz, CDCl ): δ = 171.2, 139.6, 125.6, 106.4, 87.7, 61.2,
7.4, 27.5, 26.9, 25.8, 24.2, 14.0 ppm. MS (ESI): m/z = 254 [M +
1748, 1620, 1468, 1453, 1344, 1312, 1249, 1221, 1186, 1153, 1118,
–
1
2
2 3
), 1092, 1075, 1031 cm . HRMS (ESI): calcd. for C15H24NO [M +
+
2
2
1
3
(
m, 8 H, CH
2
3
3
) ppm.
C
2
(
-(Ethoxycarbonyl)-2-(piperidin-1-yl)-1-oxaspiro[4.4]non-3-ene
3ae): By following the same procedure as that described for 3aa,
the reaction of CuBr (98% purity, 29.5 mg, 0.2 mmol), MS (4 Å,
00.0 mg), 1e (98 % purity, 112.9 mg, 1.0 mmol) in dioxane
3
4
+
+
H] , 276 [M + Na] . IR (neat): ν˜ = 2975, 2934, 2854, 2820, 1747,
3
1
1
2
467, 1454, 1444, 1361, 1336, 1311, 1248, 1216, 1172, 1120, 1093,
081, 1032 cm . HRMS (ESI): calcd. for C14
54.1751; found 254.1754.
–1
[M + H]+
H24NO
3
(1.0 mL), ethyl glyoxalate (50% in toluene, 245.7 mg, 1.2 mmol) in
dioxane (1.0 mL), and 2a (102.5 mg, 1.2 mmol) in dioxane (1.0 mL)
gave the crude product, which was purified by column chromatog-
2
-(Ethoxycarbonyl)-5,5-diethyl-2-(piperidin-1-yl)-2,5-dihydrofuran
raphy (petroleum ether/ethyl acetate, 20:1) to afford 3ae (176.6 mg,
1
(
3ab): By following the same procedure as that described for 3aa,
the reaction of CuBr (98% purity, 29.2 mg, 0.2 mmol), MS (4 Å,
00.2 mg), 1b (98 % purity, 115.3 mg, 1.0 mmol) in dioxane
1.0 mL), ethyl glyoxalate (50% in toluene, 245.7 mg, 1.2 mmol) in NCH
dioxane (1.0 mL), and 2a (102.0 mg, 1.2 mmol) in dioxane (1.0 mL) H, 4 CH
63%) as a liquid. H NMR (300 MHz, CDCl
3
): δ = 5.94 (d, J =
5.7 Hz, 1 H, =CH), 5.64 (d, J = 5.7 Hz, 1 H, =CH), 4.37–4.11 (m,
2 H, OCH ), 2.68–2.57 (m, 2 H, NCH ), 2.47–2.36 (m, 2 H,
), 2.14–2.00 (m, 1 H), 1.96–1.80 (m, 3 H), 1.78–1.51 (m, 8
), 1.49–1.37 (m, 2 H, CH ), 1.28 (t, J = 7.1 Hz, 3 H,
) ppm. C NMR (75 MHz, CDCl ): δ = 171.2, 138.1, 125.6,
106.2, 97.8, 61.2, 47.4, 38.5, 38.1, 25.7, 24.7, 24.6, 24.3, 14.0 ppm.
3
(
2
2
2
2
2
1
3
gave the crude product, which was purified by column chromatog-
raphy (petroleum ether/ethyl acetate, 20:1) to afford 3ab (163.7 mg,
CH
3
3
1
+
5
6
2
8%) as a liquid. H NMR (300 MHz, CDCl
3
): δ = 6.01 (d, J = MS (ESI): m/z = 302 [M + Na] . IR (neat): ν˜ = 2934, 2852, 2819,
1747, 1625, 1469, 1444, 1345, 1256, 1233, 1214, 1173, 1121, 1101,
.0 Hz, 1 H, =CH), 5.73 (d, J = 6.0 Hz, 1 H, =CH), 4.33–4.16 (m,
H, OCH ), 2.73–2.61 (m, 2 H, NCH ), 2.52–2.40 (m, 2 H, 1077, 1034, 1006 cm . HRMS (ESI): calcd. for C16
), 1.80–1.50 (m, 8 H, 4 CH ), 1.50–1.38 (m, 2 H, CH
t, J = 7.1 Hz, 3 H, CH ), 0.96 (t, J = 7.5 Hz, 3 H, CH ), 0.85 (t,
) ppm. 1 C NMR (75 MHz, CDCl
J = 7.7 Hz, 3 H, CH ): δ =
–
1
2
2
3
H26NO [M +
+
NCH
(
2
2
2
), 1.28 H] 280.1907; found 280.1912.
3
3
3
2-(Ethoxycarbonyl)-2-(piperidin-1-yl)-1-oxaspiro[4.5]dec-3-ene (3af):
By following the same procedure as that described for 3aa, the
reaction of CuBr (98 % purity, 29.3 mg, 0.2 mmol), MS (4 Å,
3
3
1
1
71.1, 137.7, 126.3, 105.7, 93.5, 61.1, 47.6, 29.9, 29.5, 26.0, 24.4,
4.1, 8.7, 8.4 ppm. MS (ESI): m/z = 304 [M + Na] . IR (neat): ν˜
+
3
00.1 mg), 1f (97 % purity, 127.3 mg, 1.0 mmol) in dioxane
=
1
2964, 2935, 2879, 2853, 2819, 1748, 1456, 1445, 1383, 1311, 1274,
–1
(1.0 mL), ethyl glyoxalate (50% in toluene, 244.9 mg, 1.2 mmol) in
dioxane (1.0 mL), and 2a (102.1 mg, 1.2 mmol) in dioxane (1.0 mL)
gave the crude product, which was purified by column chromatog-
256, 1226, 1206, 1164, 1119, 1085, 1061, 1034 cm . HRMS (ESI):
+
calcd. for C16
3
H28NO [M + H] 282.2064; found 282.2070.
2
-(Ethoxycarbonyl)-5-ethyl-5-methyl-2-(piperidin-1-yl)-2,5-dihydro-
raphy (petroleum ether/ethyl acetate, 20:1) to afford 3af (182.5 mg,
1
furan (3ac): By following the same procedure as that described for
aa, the reaction of CuBr (98% purity, 29.2 mg, 0.2 mmol), MS
62%) as a liquid. H NMR (300 MHz, CDCl
3
): δ = 6.13 (d, J =
3
6.0 Hz, 1 H, =CH), 5.68 (d, J = 6.0 Hz, 1 H, =CH), 4.34–4.13 (m,
2 H, OCH ), 2.70–2.59 (m, 2 H, NCH ), 2.49–2.39 (m, 2 H,
NCH ), 1.87–1.35 (m, 16 H, 8 CH ), 1.28 (t, J = 7.2 Hz, 3 H,
) ppm. C NMR (75 MHz, CDCl ): δ = 171.5, 138.0, 126.1,
(4 Å, 300.1 mg), 1c (98% purity, 101.0 mg, 1.0 mmol) in dioxane
2
2
(1.0 mL), ethyl glyoxalate (50% in toluene, 245.7 mg, 1.2 mmol) in
2
2
1
3
dioxane (1.0 mL), and 2a (102.3 mg, 1.2 mmol) in dioxane (1.0 mL) CH
3
3
gave the crude product, which was purified by column chromatog-
105.7, 89.7, 61.2, 47.5, 37.2, 36.4, 25.8, 25.3, 24.3, 23.3, 23.2,
14.0 ppm. MS (ESI): m/z = 294 [M + H] . IR (neat): ν˜ = 2964,
+
raphy (petroleum ether/ethyl acetate, 10:1) to afford 3ac (159.3 mg,
1
5
9%; mixture of two diastereomers, 1.26:1 dr) as a liquid. H NMR 2935, 2879, 2853, 2819, 1748, 1627, 1455, 1445, 1383, 1311, 1256,
–
1
(
300 MHz, CDCl
H, =CH), 4.39–4.15 (m, 2 H, OCH
.52–2.38 (m, 2 H, NCH ), 1.76–1.51 (m, 6 H, 3 CH
m, 2 H, CH ), 1.37–1.23 (m, 6 H, 2 CH ), [0.99 (t, J = 7.5 Hz,
.33 H, minor isomer), 0.90 (t, J = 7.4 Hz, 1.67 H, major isomer),
3
): δ = 6.03–5.93 (m, 1 H, =CH), 5.73–5.64 (m, 1
), 2.73–2.59 (m, 2 H, NCH ), calcd. for C17
), 1.50–1.38
1226, 1206, 1164, 1119, 1094, 1085, 1062, 1035 cm . HRMS (ESI):
H28NO
3
[M + H]+ 294.2064; found 294.2069.
2
2
2
(
1
3
2
2
2
(
-(Ethoxycarbonyl)-5-methyl-2-(piperidin-1-yl)-2,5-dihydrofuran
3ag): By following the same procedure as that described for 3aa,
the reaction of CuBr (98% purity, 29.2 mg, 0.2 mmol), MS (4 Å,
00.1 mg), 1g (69.2 mg, 1.0 mmol) in dioxane (1.0 mL), ethyl gly-
2
3
+
+
3
H, CH ] ppm. MS (ESI): m/z = 268 [M + H] , 290 [M + Na] .
3
IR (neat): ν˜ = 2934, 2853, 2819, 1748, 1627, 1454, 1369, 1256, 1231,
–
1
oxalate (50% in toluene, 245.1 mg, 1.2 mmol) in dioxane (1.0 mL),
and 2a (102.3 mg, 1.2 mmol) in dioxane (1.0 mL) gave the crude
product, which was purified by column chromatography [petroleum
1
211, 1168, 1119, 1093, 1083, 1033, 1011 cm . HRMS (ESI): calcd.
+
for C15
3
H26NO [M + H] 268.1907; found 268.1911.
6-(Ethoxycarbonyl)-6-(piperidin-1-yl)-5-oxaspiro[3.4]oct-7-ene (3ad):
ether (400 mL)/ethyl acetate (40 mL)/Et
3
N (0.3 mL)] to afford 3ag
By following the same procedure as that described for 3aa, the
reaction of CuBr (98 % purity, 29.1 mg, 0.2 mmol), MS (4 Å,
(133.0 mg, 56%; mixture of two diastereomers, 1.5:1 dr) as a liquid.
1
H NMR (300 MHz, CDCl
1.5 Hz, 0.40 H, minor isomer), 5.98 (dd, J
0.60 H, major isomer), 1 H, =CH], 5.75–5.69 (m, 1 H, =CH), 5.07–
4.95 (m, 1 H, CH), 4.36–4.15 (m, 2 H, OCH ), 2.76–2.60 (m, 2 H,
NCH ), 2.51–2.39 (m, 2 H, NCH ), 1.70–1.51 (m, 4 H, 2 CH ),
3
): δ = [6.06 (dd, J
1
2
= 6.0 Hz, J =
300.1 mg), 1d (95.7 mg, 1.0 mmol) in dioxane (1.0 mL), ethyl gly-
1
= 5.9 Hz, J
2
= 1.4 Hz,
oxalate (50% in toluene, 245.4 mg, 1.2 mmol) in dioxane (1.0 mL),
and 2a (102.1 mg, 1.2 mmol) in dioxane (1.0 mL) gave the crude
product, which was purified by column chromatography (petro-
2
2
2
2
4
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