1526 Bull. Chem. Soc. Jpn. Vol. 82, No. 12 (2009)
Asymmetric Synthesis of Hydroisoquinolines
¹4.7, 18.2, 25.9, 28.3, 46.2, 47.7, 91.8, 106.9, 114.1, 116.1, 128.7,
132.4, 152.6; IR (neat): ¯ 3384, 3115, 2957, 2930, 2858, 1715,
9H), 1.51 (brs, 1H), 1.78-1.84 (overlapped, 2H), 2.25 (d, J =
12.0 Hz, 1H), 2.36 (brs, 1H), 2.87 (brs, 2H), 3.10 (brs, 1H), 3.48
(brs, 1H), 3.66 (s, 3H), 3.81 (br, 2H), 4.66 (br, 1H), 4.72 (br, 1H),
5.27 (m, 2H), 5.73 (broad, 1H), 7.4-7.5 (m, 3H), 7.77-7.79 (m,
2H), 9.69 (s, 1H); 13C NMR (CDCl3, 100 MHz, 55 °C): ¤ ¹4.5,
¹4.4, 14.2, 17.9, 21.0, 29.7, 47.1, 52.9, 55.0, 60.4, 63.7, 116.1,
127.8, 129.2, 133.1, 135.0, 135.3, 171.2, 201.9; IR (neat): ¯ 2954,
2927, 2858, 1693, 1446, 1257, 1171 cm¹1; LRMS (FAB) m/z 549
[M + H]+; HRMS (FAB) calcd for C27H41N2O6SSi [M + H]+
549.2455, found 549.2448.
1648, 1590, 1472, 1462, 1391, 1368, 1299, 1252, 1216, 1163,
¹1
1025, 1005, 942, 879, 828, 781 cm
.
N-Allyl-N-[(E)-3-(t-butyldimethylsiloxy)-1,3-butadienyl]acet-
amide (20c). To a solution of enamine 22c (2.9 g, 17 mmol) in
DCM (43 mL) was added Et3N (3.6 mL, 19 mmol). The reaction
mixture was cooled to 0 °C, and TBSOTf (4.3 mL, 19 mmol) was
added dropwise. After being stirred for 0.5 h, the reaction was
quenched by addition of cold sat. NaHCO3. The organic layer was
separated and the aqueous layer was extracted with DCM twice.
Combined organic layers were dried over MgSO4 and concentrated
in vacuo. The residue was purified by alumina column chroma-
tography (0% to 20% EtOAc in n-hexane) to afford 20c as a
yellow oil (3.4 g, 71%): 1H NMR (CDCl3, 400 MHz, 55 °C): ¤ 0.20
(s, 6H), 0.98 (s, 9H), 2.22 (s, 3H), 4.19 (overlapped d (J = 6.8 Hz)
and brs, 2.5H), 4.27 (brs, 1.5H), 5.10-5.17 (m, 2H), 5.49 (d,
J = 14.0 Hz, 1H), 5.75 (m, 1H), 7.13 (brs, 1H); 13C NMR (CDCl3,
100 MHz, 55 °C): ¤ ¹4.7, 21.9, 25.8, 45.1, 53.3, 93.2, 109.6,
Its structure was further determined after conversion to
methyl
(4aS,8S,8aS)-allyl(2-benzenesulfonyl-8a-formyl-6-oxo-
by
1,2,3,4,4a,4,5,6,7,8,8a-decahydroisoquinolin-8-yl)carbamate
cleavage of silylether. To a solution of 24a (28 mg, 51 mmol) in
DCM (1.5 mL) was added CSA (5.9 mg, 25 mmol). After being
stirred at rt for 4 h, the reaction was quenched by addition of sat.
NaHCO3. The organic layer was separated and the aqueous layer
was extracted with DCM twice. Combined organic layers were
washed with brine, dried over MgSO4 and concentrated in vacuo.
The residue was purified by flash column chromatography (silica
gel, 20% EtOAc in n-hexane) to afford methyl (4aS,8S,8aS)-
allyl(2-benzenesulfonyl-8a-formyl-6-oxo-1,2,3,4,4a,4,5,6,7,8,8a-
decahydroisoquinolin-8-yl)carbamate as a colorless oil (20 mg,
90%): 1H NMR (CDCl3, 400 MHz, 55 °C): ¤ 1.61-1.67 (over-
lapped, 2H), 2.00 (br, 1H), 2.12-2.19 (overlapped br and d
(J = 15.7 Hz), 2H), 2.39 (br, 1H), 2.49 (dd, J = 15.0, 3.3 Hz, 1H),
3.07 (dd, J = 15.0, 5.5 Hz, 1H), 3.70 (s, 5H), 3.82 (dd, J = 15.7,
8.1 Hz, 1H), 4.01 (br, 2H), 4.48 (br, 1H), 5.23 (d, J = 10.3 Hz,
1H), 5.30 (d, J = 17.2 Hz, 1H), 5.74-5.84 (m, 1H), 7.57-7.60
(m, 2H), 7.64-7.68 (m, 1H), 7.77-7.80 (m, 2H), 9.97 (s, 1H);
13C NMR (CDCl3, 100 MHz, 55 °C): ¤ 27.9, 35.3, 42.8, 43.4, 46.1,
47.6, 51.3, 52.8, 53.9, 55.7, 118.7, 128.0, 129.3, 133.3, 133.4,
135.1, 156.6, 198.7, 206.1; IR (neat): ¯ 3067, 2928, 2852,
2852, 1684, 1658, 1629 cm¹1; LRMS (FAB) m/z 435 [M + H]+;
HRMS (FAB) calcd for C21H27N2O6S [M + H]+ 435.1590, found
435.1578.
116.5, 128.7, 132.3, 154.1, 169.1; IR (neat): ¯ 3450, 2956, 2930,
¹1
2858, 1682, 1644, 1400, 1300, 1216, 1024, 828 cm
.
N-Allyl-N-[(E)-3-(t-butyldimethylsiloxy)-1,3-butadienyl]chlo-
roacetamide (20d). To a solution of enamine 22d (19 g,
95 mmol) in DCM (240 mL) was added Et3N (17 mL, 123 mmol).
The reaction mixture was cooled to 0 °C, and TBSOTf (25 g,
95 mmol) was added dropwise. After being stirred for 2 h, the
reaction was quenched by addition of cold sat. NaHCO3. The
organic layer was separated, and the aqueous layer was extracted
with DCM twice. Combined organic layers were dried over
MgSO4 and concentrated in vacuo. The residue was purified by
alumina column chromatography (0% to 20% EtOAc in n-hexane)
1
to afford aminodiene 20d as a yellow oil (23.7 g, 79%): H NMR
(CDCl3, 400 MHz, 55 °C): ¤ 0.23 (s, 6H), 1.00 (s, 9H), 4.15-4.32
(overlapped, 6H), 5.16 (d, J = 17.6 Hz, 1H), 5.20 (d, J = 12.0 Hz,
1H), 5.62 (d, J = 13.6 Hz, 1H), 5.78 (ddd, J = 17.6, 12.0, 4.8 Hz,
1H), 7.13 (d, J = 13.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz,
55 °C): ¤ ¹4.7, 18.2, 25.8, 40.9, 46.1, 94.3, 111.8, 117.0, 127.2,
131.3, 153.5, 165.2; IR (neat): ¯ 3448, 3087, 2955, 2930, 2886,
2858, 1678, 1644, 1589, 1471, 1463, 1440, 1408, 1362, 1306,
1255, 1218, 1194, 1134, 1021, 1005, 941, 924, 840, 809, 782, 738,
690, 570, 543 cm¹1; LRMS (FAB) m/z 316 [M + H]+; HRMS
(FAB) calcd for C15H27ClNO2Si [M + H]+ 316.1500, found
316.1487.
General Procedure for the Asymmetric Diels-Alder Reac-
tion (1 mmol Scale Experiments). After a mixture of Cr-salen
complex (25-29, 50 mol %, based on dienophile) and oven-dried
powdered 4A MS (0.8 g) was dried under vacuum for 20 min, a
solution of dienophile 10b (1 mmol) in PhCF3 (5 mL) was added
and the mixture was stirred for 1 h at rt. To this mixture, was added
aminodiene 20 (2 mmol) and the resulting mixture was stirred at rt.
The reaction mixture was then filtered through a pad of Celite and
the pad was washed with DCM. The filtrate was concentrated in
vacuo and residue was purified by flash column chromatography
(20 to 50% EtOAc in n-hexane) to afford 24 as a colorless foam.
Methyl (4aS,8S,8aS)-Allyl[2-benzenesulfonyl-6-(t-butyldi-
methylsiloxy)-8a-formyl-1,2,3,4,4a,5,8,8a-octahydroisoquinolin-
8-yl]carbamate (24a) and Methyl (4aS,8S,8aS)-Allyl(2-ben-
zenesulfonyl-8a-formyl-6-oxo-1,2,3,4,4a,5,6,7,8,8a-decahydro-
isoquinolin-8-yl)carbamate: Because of instability, the structure
analysis of 24a was limited. NMR spectra showed that 24a was a
mixture of rotational isomers due to the carbamate group. 1H NMR
(CDCl3, 400 MHz, 55 °C): ¤ 0.06 (s, 3H), 0.09 (s, 3H), 0.88 (s,
t-Butyl
(4aS,8S,8aS)-Allyl[2-benzenesulfonyl-6-(t-butyldi-
methylsiloxy)-8a-formyl-1,2,3,4,4a,5,8,8a-octahydroisoquinolin-
8-yl]carbamate (24b): 1H NMR (C6D6, 400 MHz, 75 °C): ¤ 0.03
(s, 3H), 0.07 (s, 3H), 0.90 (s, 9H), 1.12 (br, 1H), 1.25-1.31 (br,
1H), 1.34 (s, 9H), 1.55-1.67 (m, 1H), 2.03 (br, 2H), 2.74 (br, 2H),
3.12 (br, 1H), 3.34 (br, 1H), 3.97 (br, 2H), 4.73 (s, 1H), 4.76 (s,
1H), 5.01 (d, J = 10.3 Hz, 1H), 5.16 (d, J = 17.3 Hz, 1H), 5.78-
5.88 (m, 1H), 6.95-7.03 (m, 3H), 7.61-7.64 (m, 2H), 9.95 (s, 1H);
13C NMR (C6D6, 100 MHz, 75 °C): ¤ ¹4.32, ¹4.27, 18.1, 25.8,
27.2, 28.4, 30.0, 30.8, 43.3, 47.9, 49.9, 52.5, 55.4, 59.9, 103.2,
115.8, 129.0, 132.6, 136.2, 137.0, 150.9, 155.6, 169.8, 200.8; IR
(neat): ¯ 3418, 3060, 2956, 2931, 2858, 1732, 1682, 1471, 1463,
1446, 1393, 1367, 1335, 1266, 1254, 1210, 1170, 1092, 978, 931,
889, 837, 781, 740, 692 cm¹1; LRMS (FAB) m/z 592 [M + H]+;
HRMS (FAB) calcd for C30H47N2O6SSi [M + H]+ 591.2917,
found 591.2892.
(4aS,8S,8aS)-N-Allyl-N-[2-benzenesulfonyl-6-(t-butyldimeth-
ylsiloxy)-8a-formyl-1,2,3,4,4a,5,8,8a-octahydroisoquinolin-8-yl]-
acetamide (24c): 1H NMR (CDCl3, 400 MHz, 55 °C): ¤ 0.03 (s,
3H), 0.06 (s, 3H), 0.86 (s, 9H), 1.26-1.27 (m, 1H), 1.37-1.40 (m,
1H), 1.79-1.88 (overlapped, 2H), 1.98 (s, 3H), 2.11-2.14 (m, 1H),
2.45 (m, 1H), 2.63 (m, 1H), 3.27-3.32 (m, 1H), 3.80 (m, 1H),
3.86 (s, 2H), 4.62 (d, J = 4.8 Hz, 1H), 4.96 (s, 1H), 5.08 (d,
J = 17.2 Hz, 1H), 5.16 (d, J = 10.8 Hz, 1H), 5.67-5.77 (m, 1H),
7.51-7.61 (m, 3H), 7.76-7.78 (m, 2H), 9.58 (s, 1H); 13C NMR
(CDCl3, 100 MHz, 55 °C): ¤ ¹4.5, ¹4.4, 14.1, 17.9, 20.9, 22.5,