Lewis Acid Catalysed [4ϩ2]-Heterocycloadditions
FULL PAPER
H, Me), 0.07 (s, 3 H, Me), 0.72 (s, 9 H, tBu), 1.40Ϫ2.35 (m, 7 H), 0.05 (s, 3 H, Me), 0.20 (s, 3 H, Me), 0.80 (s, 9 H, tBu), 3.82 (s, 3
3.35 (dd, J ϭ 3.6, J ϭ 4.0 Hz, 1 H, 4-H), 3.82 (s, 3 H, CO2Me), H, CO2Me), 6.35 (d, J ϭ 4.1 Hz, 1 H, 3-H), 7.10Ϫ7.35 (m, 5 H,
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6.29 (dd, J ϭ 4.0, J ϭ 0.7 Hz, 1 H, 3-H), 7.15Ϫ7.35 (m, 5 H, Ph). Ph). (4S*,4aS*,14aR*)-4l: H NMR (400 MHz, CDCl3): δ ϭ 0.02
13C NMR (100 MHz, CDCl3): δ ϭ Ϫ3.6, Ϫ3.5, 17.5, 18.7, 25.5,
(s, 3 H, Me), 0.14 (m, 1 H), 0.23 (s, 3 H, Me), 0.52 (m, 1 H), 0.90
28.9, 37.8, 40.4, 48.2, 52.0, 106.9, 112.9, 126.1, 127.7, 128.1, 141.0, (s, 9 H, tBu), 0.75Ϫ1.7 (m, 17 H), 1.97 (dd, J ϭ 5.2, J ϭ 6.9 Hz,
143.3, 163.3. Rf ϭ 0.52 (cyclohexane/EtOAc, 8:2). (4S*,4aR*,7aR*)- 1 H, 4a-H), 2.25 (ddd, 1 H, J ϭ 14.7, J ϭ 12.3, J ϭ 2.9, 14-H),
4j: 1H NMR (400 MHz, CDCl3): δ ϭ 0.07 (s, 3 H, Me), 0.23 (s, 3.83 (s, 3 H, CO2Me), 4.23 (dd, J ϭ 5.2, J ϭ 1.7 Hz, 1 H, 4-H),
1 H, Me), 0.89 (s, 9 H, tBu), 1.20Ϫ2.30 (m, 7 H), 3.45 (dd, J ϭ 6.35 (dd, J ϭ 1.7, J ϭ 1.7 Hz, 1 H, 3-H), 7.15Ϫ7.35 (m, 5 H, Ph).
11.5, J ϭ 2.1, 4-H), 3.81 (s, 3 H, CO2Me), 6.22 (d, J ϭ 2.1 Hz, 1
13C NMR (100 MHz, CDCl3): δ ϭ Ϫ3.87, Ϫ2.85, 18.3, 20.0, 21.3,
H, 3-H), 7.15Ϫ7.35 (m, 5 H, Ph). 13C NMR (100 MHz, CDCl3): 22.0, 22.5, 24.0, 24.4, 25.4, 26.2, 26.0, 26.9, 35.7, 39.5, 42.3, 52.1,
δ ϭ Ϫ4.0, Ϫ3.6, 17.9, 18.7, 25.1, 25.4, 35.2, 41.4, 49.8, 51.9, 105.4, 104.6, 113.7, 126.4, 128.4, 128.6, 141.9, 142.2, 163.3. Rf ϭ 0.59
116.4, 126.5, 128.0, 128.4, 142.3, 142.4, 163.3. Rf ϭ 0.55 (cyclohex-
(cyclohexane/EtOAc, 8:2). (4R*,4aS*,14aS*) -5l: 1H NMR
(400 MHz, CDCl3): δ ϭ 0.06 (s, 3 H, Me), 0.21 (s, 3 H, Me), 0.42
ane/EtOAc, 8:2). (4S*,4aS*,7aR*)-5j: 1H NMR (400 MHz,
CDCl3): δ ϭ 0.11 (s, 3 H, Me), 0.21 (s, 3 H, Me), 0.89 (s, 9 H, (m, 1 H), 0.90 (s, 9 H, tBu), 0.75Ϫ2.1 (m, 20 H), 3.33 (dd, J ϭ
tBu), 1.00Ϫ2.30 (m, 7 H), 3.81 (s, 3 H, CO2Me), 3.83 (dd, J ϭ 6.3, 10.8, J ϭ 2.3 Hz, 1 H, 4-H), 3.76 (s, 3 H, CO2Me), 6.00 (d, J ϭ
J ϭ 2.4 Hz, 1 H, 4-H), 6.22 (d, J ϭ 2.4 Hz, 1 H, J ϭ 1.4 Hz, 3-
H), 7.15Ϫ7.35 (m, 5 H, Ph). Rf ϭ 0.55 (cyclohexane/EtOAc, 8:2). CDCl3): δ ϭ Ϫ3.77, Ϫ2.53, 18.2, 20.3, 22.9, 23.0, 23.4, 24.0, 25.3,
13C NMR (100 MHz, CDCl3): δ ϭ Ϫ4.0, Ϫ3.6, 17.9, 18.7, 25.1,
25.4, 26.6, 27.4, 25.8, 38.0, 41.7, 44.6, 52.1, 104.0, 116.1, 126.8,
25.4, 35.2, 41.4, 49.8, 51.9, 105.4, 116.4, 126.5, 128.0, 128.4, 142.3, 128.4, 128.6, 140.4, 143.3, 163.5. Rf ϭ 0.65 (cyclohexane/EtOAc,
2.3 Hz, 1 H, 3-H), 7.15Ϫ7.35 (m, 5 H, Ph). 13C NMR (100 MHz,
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142.4, 163.3.
8:2). (4S*,4aS*,14aS*)-6l: H NMR (400 MHz, CDCl3); (selected
signals): δ ϭ 0.09 (s, 3 H, Me), 0.23 (s, 3 H, Me), 0.80 (s, 9 H, tBu),
3.66 (dd, J ϭ 8.2, J ϭ 4.8 Hz, 1 H, 4-H), 3.79 (s, 3 H, CO2Me), 6.22
(t, J ϭ 4.1 Hz, 1 H, 3-H), 7.10Ϫ7.35 (m, 5 H, Ph).
Methyl 10a-tert-Butyldimethylsiloxy-4-phenyl-4a,5,6,7,8,9,10,10a-
octahydro-4H-cycloocta[b]pyran-2-carboxylate (3؊5k): A mixture
of diastereomers 3k/4k/5k (53:16:31, 450 mg, 98%) was obtained as
a viscous colourless oil by Procedure 1B (eluent: cyclohexane/
EtOAc, 98:2), from heterodiene 1a (205 mg, 1.07 mmol) and dien-
ophile 2k (324 mg, 1.25 equiv.). The diastereomers 4k/5k (11:89,
Methyl 4-Benzyloxy-8a-tert-butyldimethylsiloxy-4a,5,6,7,8,8a-hexa-
hydro-4H-chromene-2-carboxylate (3nϪ5n): A mixture of diastereo-
mers 3n/4n (87:13, 93 mg, 19%) was obtained by Procedure 1A,
395 mg, 81%) were obtained as a viscous colourless oil by Proced- from heterodiene 1b (246 mg, 1.12 mmol) and dienophile 2h
ure 2A (eluent: cyclohexane/EtOAc, 98:2), from heterodiene 1a (297 mg, 1.25 equiv.). A mixture of diastereomers 4n/5n (11:89,
(217 mg, 1.14 mmol) and dienophile 2k (300 mg, 1.1 equiv.). IR 112 mg, 35%) was obtained by Procedure 2A (SnCl4: 5%), from
(film): ν ϭ 1741 (CϭO, ester) cm
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Ϫ1, 1655 (CϭC, conjugated al-
heterodiene 1b (160 mg, 0.73 mmol) and dienophile 2h (169 mg, 1.1
kene). HRMS (C25H38O4Si): calcd. 430.25392; found 430.2543. equiv.). IR (film): ν˜ ϭ 1741 (CϭO, ester), 1654 (CϭC, conjugated
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(4R*,4aS*,10aR*)-3k: H NMR (400 MHz, CDCl3): δ ϭ 0.11 (s, 3
alkene). HRMS (C24H36O5Si): calcd. 432.23318; found 432.2319.
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H, Me), 0.25 (s, 3 H, Me), 0.84 (s, 9 H, tBu), 1.25Ϫ2.25 (m, 13 H), (4R*,4aS*,8aR*)-3n: H NMR (400 MHz, CDCl3): δ ϭ 0.11 (s, 3
3.54 (dd, J ϭ 9.7, J ϭ 3.0 Hz, 1 H, 4-H), 3.78 (s, 3 H, CO2Me), H), 0.19 (s, 3 H), 0.8’ (s, 9 H), 0.80Ϫ2.10 (m, 9 H), 3.78 (dd, J ϭ
6.04 (d, J ϭ 3.0 Hz, 1 H, 3-H), 7.18Ϫ7.35 (m, 5 H, Ph). 13C NMR 3.9, J ϭ 3.5 Hz, 1 H, 4-H), 3.88 (s, 3 H), 4.53 (d, J ϭ 11.8 Hz, 1
(100 MHz, CDCl3): δ ϭ Ϫ3.0, Ϫ2.9, 18.1, 23.1, 23.2, 25.9, 28.2, H), 4.64 (d, J ϭ 11.8 Hz, 1 H), 6.33 (d, J ϭ 3.9 Hz, 1 H, 3-H),
35.7, 42.1, 47.3, 51.7, 104.8, 113.6, 126.5, 127.8, 128.4, 141.0, 142.3, 7.25Ϫ7.40 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ ϭ Ϫ3.2,
163.1. Rf ϭ 0.59 (cyclohexane/EtOAc, 8:2). (4S*,4aS*,10aR*)-4k:
Ϫ2.7, 18.0, 23.0, 25.7, 29.7, 33.9, 44.9, 52.5, 70.3, 72.2, 101.0, 109.1,
1H NMR (400 MHz, CDCl3): δ ϭ 0.05 (s, 3 H, Me), 0.21 (s, 3 H, 127.5, 127.9, 128.2, 138.3, 141.8, 163.7. (4R*,4aS*,8aS*)-5n: 1H
Me), 0.90 (s, 9 H, tBu), 1.00Ϫ2.10 (m, 13 H), 3.25 (dd, J ϭ 11.2,
J ϭ 2.3 Hz, 1 H, 4-H), 3.76 (s, 3 H, CO2Me), 6.02 (d, J ϭ 2.3 Hz,
NMR (400 MHz, CDCl3): δ ϭ 0.07 (s, 3 H), 0.16 (s, 3 H), 0.83 (s,
9 H), 1.20Ϫ1.70 (m, 7 H), 2.00 (m, 2 H, 4a-H and 8-H), 3.70 (m,
1 H, 3-H), 7.15Ϫ7.35 (m, 5 H, Ph). Rf ϭ 0.55 (cyclohexane/EtOAc, 1 H, 4-H), 3.81 (s, 3 H), 4.52 (d, J ϭ 11.8 Hz, 1 H), 4.63 (d, J ϭ
8:2). (4R*,4aS*,10aS*)-5k: 1H NMR (400 MHz, CDCl3): δ ϭ 0.05 11.8 Hz, 1 H), 6.24 (d, J ϭ 3.8 Hz, 1 H, 3-H), 7.25Ϫ7.40 (m, 5 H).
(s, 3 H, Me), 0.22 (s, 3 H, Me), 0.91 (s, 9 H, tBu), 1.0Ϫ2.3 (m, 13 13C NMR (100 MHz, CDCl3): δ ϭ Ϫ2.7, Ϫ3.4, 18.0, 23.2, 23.0,
H), 3.82 (s, 3 H, CO2Me), 4.18 (dd, J ϭ 5.6, J ϭ 2.5 Hz, 1 H, 4- 25.6, 27.0, 37.0, 43.9, 52.0, 70.3, 72.0.100.5 (8a-C), 108.6 (3-C);
H), 6.36 (dd, J ϭ 2.5, J ϭ 1.6 Hz, 1 H, 3-H), 7.15Ϫ7.35 (m, 5 H, 127.9, 128.2, 128.3, 138.3, 141.5, 163.4. (4S*,4aS*,8aR*)-4n: 1H
Ph). 13C NMR (100 MHz, CDCl3): δ ϭ Ϫ4.0, Ϫ2.7, 18.2, 22.0, NMR (400 MHz, CDCl3): δ ϭ 0.01 (s, 3 H), 0.14 (s, 3 H), 0.77 (s,
24.5, 25.7, 26.9, 27.2, 28.1, 38.1, 42.6, 43.6, 51.7, 103.2, 116.1, 9 H), 1.10Ϫ1.90 (m, 9 H), 3.78 (s, 3 H), 4.56 (m, 2 H), 4.68 (d, 1
126.6, 128.4, 128.7, 140.4, 142.6, 163.4. Rf ϭ 0.53 (cyclohexane/ H), 6.08 (dd, J ϭ 2.1, J ϭ 1.4, 1 H), 7.25Ϫ7.40 (m, 5 H). IR (neat):
EtOAc, 8:2).
ν ϭ 1728 (CϭO) cmϪ1, 1643 (CϭC, conjugated alkene).
˜
Methyl
14a-tert-Butyldimethylsiloxy-4-phenyl-4a,5,6,7,8,9,10,11,
Methyl 4-(1,3-Benzodioxol-5-ylmethoxy)-8a-tert-butyldimethylsi-
12,13,14,14a-dodecahydro-4H-cyclododeca[b]pyran-2-carboxylate
(3؊6l): A mixture of diastereomers 3l/5l/6l (13:11:76, 438 mg, 83%)
loxy-4a,5,6,7,8,8a-hexahydro-4H-chromene-2-carboxylate (3؊5o):
A mixture of diastereomers 3o/4o (86:14, 46 mg, 38%) was obtained
was obtained by Procedure 1B (eluent: cyclohexane/EtOAc, 98:2), by Procedure 1B, from heterodiene 1c (67 mg, 0.254 mmol) and
from heterodiene 1a (207 mg, 1.09 mmol) and dienophile 2l dienophile 2h (68 mg, 1.25 equiv.). The diastereomers 3o/4o/5o
(404 mg, 1.25 equiv.). The diastereomers 4l/5l (46:54, 479 mg, 94%) (32:18:50, 150 mg, 51%) were obtained by Procedure 2A (SnCl4:
were obtained by Procedure 2A (SnCl4: 5%; eluent: cyclohexane/ 5%), from heterodiene 1c (164 mg, 0.62 mmol) and dienophile 2h
EtOAc, 98:2), from heterodiene 1a (200 mg, 1.05 mmol) and dien- (145 mg, 1.1 equiv.). IR (film): ν˜ ϭ 1741 (CϭO, ester) cmϪ1, 1654
˜
ophile 2l (343 mg, 1.1 equiv.). IR (film): ν ϭ 1741 (CϭO, ester)
cmϪ1, 1655 (CϭC, conjugated alkene). C29H46O4Si (486.8): calcd. found 476.2217. (4R*,4aS*,8aR*)-3o: 1H NMR (400 MHz,
C 71.56, H 9.53, Si 5.77; found C 71.52, H 9.69, Si 6.90. (4R*,4aS* CDCl3): δ ϭ 0.10 (s, 3 H, SiMe2), 0.19 (s, 3 H), 0.86 (s, 9 H, tBu),
,14aR*)-3l: 1H NMR (400 MHz, CDCl3) (selected signals): δ ϭ 1.00Ϫ2.40 (m, 9 H), 3.77 (dd, J ϭ 3.8, J ϭ 3.4, 1 H), 3.83 (s, 3 H,
(CϭC, conjugated alkene). HRMS (C25H38O4Si): calcd. 476.22301;
Eur. J. Org. Chem. 2002, 514Ϫ525
523