Job/Unit: O20489
/KAP1
Date: 19-06-12 15:24:07
Pages: 7
G. R. Dong, S. Hong, S. I. Kim, I. S. Kim, Y. H. Jung
FULL PAPER
3031, 2965, 2932, 2876, 1496, 1456, 1366, 1216, 1103, 1029, 772,
1 H), 7.21–7.40 (m, 15 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
1
739, 698, 609 cm–1. H NMR (500 MHz, CDCl3): δ = 0.94 (t, J = 10.1, 10.2, 23.9, 51.1, 66.7, 72.3, 72.5, 82.9, 83.0, 126.8, 127.4,
281
8.0 Hz, 1 H), 1.64–1.70 (m, 2 H), 2.27 (t, J = 6.5 Hz, 1 H), 3.51 (d,
127.9, 128.0, 128.1, 128.2, 128.3, 128.6, 128.7, 132.9, 133.0, 136.8,
J = 5.0 Hz, 1 H), 3.60 (d, J = 5.5 Hz, 1 H), 4.59–4.70 (m, 4 H), 138.7, 155.8 ppm. HRMS (CI): calcd. for C27H30NO3 [M + H]+
7.25–7.38 (m, 10 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 9.8, 416.2221; found 416.2226.
24.0, 61.8, 72.4, 73.0, 80.6, 80.8, 127.2, 127.9, 128.0, 128.1, 128.2,
221
(3R,4S,Z)-4-(Benzyloxy)-1-phenylhex-1-en-3-amine (8): To a stirred
solution of carbamate 7 (2 g, 4.8 mmol, 100 mol-%) in DMSO
(22.5 mL) was added a solution of KOH (2.2 g, 38.4 mmol,
128.6, 128.7, 128.8, 138.4, 138.6 ppm. HRMS (CI): calcd. for
286
291
296
301
C19H25O3 [M + H]+ 301.1800; found 301.1804.
(3R,4S)-1-Phenylhex-1-ene-3,4-diyl-bis(oxy)bis(methylene)dibenzene
(6): To a stirred solution of alcohol 5 (4.5 g, 15 mmol, 100 mol-
%) in CH2Cl2 (150 mL) was added DMSO (34 mL), triethylamine
(12.5 mL, 90 mmol, 600 mol-%), and SO3·Pyr (7.2 g, 45 mmol,
300 mol-%). The reaction mixture was then stirred at room tem-
perature for 3 h. At this point, CH2Cl2 was concentrated in vacuo,
and the resulting syrup was taken up in Et2O (600 mL). The or-
ganic layer was then washed with a saturated CuSO4 solution
(3ϫ150 mL) followed by H2O (150 mL). The organic layers were
then dried with MgSO4 and concentrated in vacuo. The residue
was used without further purification in the next step. To a stirred
solution of BnPPh3Cl (11.7 g, 30 mmol, 200 mol-%) in THF
(125 mL) was added a solution of NaHMDS (1.0 m in THF, 30 mL,
30 mmol, 200 mol-%) at 0 °C. The reaction mixture was stirred for
1 h at 0 °C. The crude lactol (4.38 g) suspended in THF (25 mL)
was added dropwise to the reaction mixture at 0 °C. The resulting
mixture was stirred for 12 h at room temperature. The reaction mix-
ture was quenched with H2O and extracted with EtOAc (100 mL).
The organic layer was washed with H2O and brine, dried with
MgSO4, and concentrated in vacuo. The residue was purified by
800 mol-%) in H2O (2.5 mL) at 0 °C. The reaction mixture was
stirred at 80 °C for 48 h and then cooled to room temperature. The
resulting solution was extracted with CH2Cl2 (2ϫ20 mL). The or-
ganic layer was washed with H2O and brine, dried with MgSO4,
and concentrated in vacuo. The residue was purified by column
chromatography (n-hexane/EtOAc, 1:2) to afford 8 (1 g, 75%) as a
bright yellow syrup. Rf = 0.23 (n-hexane/EtOAc, 1:2). [α]2D2 = +6.8
226
231
236
241
246
251
256
(c = 1, CHCl ). IR (neat): ν = 3259, 3026, 2963, 2928, 2873, 1601,
˜
3
1494, 1454, 1372, 1071, 805, 773, 739, 700, 611 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 0.86 (t, J = 7.5 Hz, 3 H), 1.48–1.69 (m, 2
H), 3.34–3.38 (br., 1 H), 4.03–4.05 (br., 1 H), 4.55–4.60 (m, 2 H),
5.72 (dd, J = 11.5, 10.0 Hz, 1 H), 6.56 (d, J = 11.5 Hz, 1 H), 7.22–
7.34 (m, 10 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 10.4, 23.6,
50.7, 72.4, 84.4, 127.2, 127.8, 127.9, 128.5, 128.6, 128.8, 129.2,
130.7, 133.4, 137.4, 139.1 ppm. HRMS (CI): calcd. for C19H24NO
[M + H]+ 282.1860; found 282.1858.
(3R,4S)-4-(Benzyloxy)-N-(but-3-enyl)-1-phenylhex-1-en-3-amine (9):
To a stirred solution of amine 8 (0.2 g, 0.71 mmol, 100 mol-%) in
anhydrous DMF (4.0 mL) was added 4-bromo-1-butene (0.1 mL,
0.92 mmol, 130 mol-%) and K2CO3 (0.4 g, 2.84 mmol, 400 mol-%)
at room temperature. The reaction mixture was stirred at 60 °C for
3 h. DMF was removed under reduced pressure, and the residue
was diluted with EtOAc. The resulting solution was washed with
H2O and brine, dried with MgSO4, and concentrated in vacuo. The
residue was purified by column chromatography (n-hexane/EtOAc,
8:1) to afford 9 (167 mg, 70%) as a colorless oil. Rf = 0.23 (n-
306
311
column chromatography (n-hexane/EtOAc, 10:1) to afford
6
(4.75 g, 85%) as a colorless syrup. Rf = 0.37 (n-hexane/EtOAc,
10:1). [α]2D2 = –86.8 (c = 3, CHCl ). IR (neat): ν = 3259, 3061, 3029,
˜
3
2925, 2857, 1738, 1495, 1455, 1366, 1217, 1072, 773, 738, 699,
611 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.94 (t, J = 7.5 Hz, 2.6
H), 0.98 (t, J = 7.5 Hz, 0.4 H), 1.60–1.77 (m, 2 H), 3.53–3.59 (m,
0.86 H), 4.02–4.04 (m, 0.14 H), 4.25 (d, J = 12.0 Hz, 1 H), 4.44–
4.49 (m, 1 H), 4.55–4.74 (m, 3 H), 4.76 (d, J = 12.0 Hz, 1 H), 5.81
(dd, J = 12.0, 9.5 Hz, 0.86 H), 6.31 (dd, J = 16.0, 8.0 Hz, 0.14 H),
6.64 (d, J = 16.0 Hz, 0.14 H), 6.91 (d, J = 12.0 Hz, 0.86 H), 7.15–
7.47 (m, 15 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 10.0, 10.3,
24.3, 24.4, 70.3, 70.6, 73.1, 73.2, 75.6, 82.4, 82.7, 83.2, 126.9, 127.4,
127.5, 127.6, 127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4,
128.5 (2 C), 128.6 (2 C), 128.8, 129.1, 130.9, 134.2, 134.3, 137.1,
138.7, 139.2 ppm. HRMS (CI): calcd. for C26H27O2 [M – H]+
371.2012; found 371.2011.
hexane/EtOAc, 8:1). [α]2D2 = –6.6 (c = 3, CHCl ). IR (neat): ν =
˜
3
3062, 3026, 2966, 2931, 2873, 1723, 1640, 1601, 1494, 1453, 1363,
1208, 1070, 1029, 994, 915 cm–1. 1H NMR (500 MHz, CDCl3): δ = 316
0.86 (t, J = 7.5 Hz, 3 H), 1.53–1.76 (m, 2 H), 1.81 (s, 1 H), 2.13
(dd, J = 13.5, 7.0 Hz, 2 H), 2.39–2.44 (m, 1 H), 2.66–2.71 (m, 1
H), 3.41–3.44 (m, 1 H), 3.84–3.87 (m, 1 H), 4.55 (s, 2 H), 5.00 (dd,
J = 11.0, 3.5 Hz, 2 H), 5.58 (dd, J = 12.0, 10.0 Hz, 1 H), 5.67–5.75
(m, 1 H), 6.68 (d, J = 12.0 Hz, 1 H), 7.22–7.36 (m, 10 H) ppm. 13
C
321
NMR (125 MHz, CDCl3): δ = 10.8, 23.9, 34.6, 46.7, 57.0, 72.4,
83.8, 116.4, 127.1, 127.8, 128.0, 128.4, 128.5, 128.7, 129.6, 132.4,
132.8, 136.8, 137.7, 139.1 ppm. HRMS (CI): calcd. for C23H30NO
[M + H]+ 336.2327; found 336.2327.
261
266
271
276
Benzyl (3R,4S)-4-(Benzyloxy)-1-phenylhex-1-en-3-ylcarbamate (7):
To a stirred solution of 6 (2.87 g, 7.71 mmol, 100 mol-%) in anhy-
drous toluene (26 mL) was added Na2CO3 (3.7 g, 34.71 mmol,
450 mol-%) and CSI (2.0 mL, 23.14 mmol, 300 mol-%) at 0 °C un- (R)-6-[(S)-1-(Benzyloxy)propyl]-1,2,3,6-tetrahydropyridine (10): To 326
der an atmosphere of N2. The reaction mixture was stirred for 16 h
at 0 °C and quenched with H2O (13 mL). The aqueous layer was
extracted with EtOAc (2ϫ20 mL). The organic layer was added to
a solution of aqueous 25% Na2SO3 (10 mL), and the reaction mix-
ture was stirred for 6 h at room temperature. The organic layer was
washed with H2O and brine, dried with MgSO4, and concentrated
in vacuo. The residue was purified by column chromatography (n-
hexane/EtOAc, 8:1) to afford 7 (2.85 g, 89%, anti/syn = 37:1) as a
white solid. Rf = 0.28 (n-hexane/EtOAc, 8:1). [α]2D2 = +88.2 (c = 2,
a solution of 9 (118 mg, 0.35 mmol, 100 mol-%) in anhydrous
CH2Cl2 (2 mL) was added second generation Grubbs catalyst
(24 mg, 0.028 mmol, 8 mol-%) and anhydrous pTsOH (66 mg,
0.35 mmol, 100 mol-%) under an atmosphere of N2. The reaction
mixture was heated at reflux for 6 h. The resulting mixture was
filtered through a Celite pad and concentrated in vacuo. The resi-
due was purified by column chromatography (CHCl3/MeOH =
15:1) to afford 10 (60 mg, 72%) as a brownish oil. Rf = 0.30 (n-
331
hexane/EtOAc, 5:1). [α]2D2 = +1.3 (c = 0.2, MeOH). IR (neat): ν =
˜
CHCl ). IR (neat): ν = 3327, 3029, 2965, 2875, 1718, 1498, 1454,
3259, 1219, 1077, 772 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.94 336
(t, J = 7.2 Hz, 3 H), 1.53–1.81 (m, 2 H), 2.14–2.20 (br., 1 H), 3.02–
˜
3
1344, 1215, 1070, 776, 699, 610 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 0.67 (t, J = 7.5 Hz, 2.3 H), 0.97 (t, J = 7.5 Hz, 0.7 H), 1.33– 3.10 (m, 1 H), 3.50–3.53 (br., 1 H), 3.61–3.67 (m, 1 H), 3.97 (br. s,
1.71 (m, 2 H), 3.43 (br., 0.8 H), 3.50–3.51 (br., 0.2 H), 4.47–4.67
(m, 3 H), 4.84–4.87 (br., 1 H), 5.05–5.14 (br., 3 H), 5.67 (dd, J =
11.5, 10.0 Hz, 0.8 H), 6.16–6.21 (m, 0.2 H), 6.65 (d, J = 11.5 Hz,
1 H), 4.58 (d, J = 11.4 Hz, 2 H), 5.66–5.70 (br., 1 H), 5.98–6.01
(br., 1 H), 7.22–7.36 (m, 5 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 10.0, 22.0, 23.1, 40.8, 54.6, 72.5, 80.2, 121.1, 127.7, 128.1, 128.2,
341
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