The Journal of Organic Chemistry
Article
chromatography of 36 allowed separation of three fractions 36a,b
(containing two diastereomers), 36c, and 36d for characterization.
The regioisomeric fraction 37 contained substantially one diaster-
eomer of unknown configuration.
flash chromatography (EtOAc/PE = 1/2) to give compound 40 (18
mg, yield: 34%) and alcohol 41 (18 mg, yield: 34%).
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Compound 40: Pale yellow oil. [α]D −133.4 (c 1.0, CHCl3). IR
(film) vmax 3436, 2921, 1768, 1651, 1453, 1377, 1286, 1205, 1025,
1
36a,b: White solid. IR (film) vmax 3345, 2953, 2914, 1743, 1737,
1442, 1159, 1109, 1098, 833, 779 cm−1. 1H NMR (400 MHz, CDCl3,
data read from the diastereomeric mixture) δ 7.37−7.23 (m, 5H),
5.92−5.66 (m, 1H), 5.20−4.90 (m, 2H), 4.60−4.50 (m, 1H), 4.44−
4.26 (m, 1H), 3.92−3.66 (m, 6H), 3.52−3.34 (m, 1H), 3.06−2.80
(m, 1H), 2.80−2.54 (m, 3H), 2.50−2.04 (m, 3H), 1.43−1.34 (m,
1H), 1.32 (s, 3H), 0.91 (s, 9H), 0.09 (s, 6H). 13C{1H} NMR (100
MHz, CDCl3, data read from the diastereomeric mixture) δ 207.6,
175.7, 138.4, 137.9, 132.9, 132.1, 128.4 (2C), 128.2, 127.7, 127.4
(2C), 127.3, 119.4, 118.0, 83.4, 80.8, 76.9, 73.4, 72.7, 71.2, 68.5, 67.9,
63.1, 61.7, 61.1, 60.9, 57.0, 53.5, 52.8, 52.3, 49.7, 48.3, 45.0, 44.0,
39.8, 39.0, 34.5, 32.2, 26.0 (3C), 25.9 (3C), 24.9, 23.7, 18.5, 18.2,
−5.25, −5.29, −5.36, −5.42. HRMS (ESI-TOF) m/z [M + H]+ calcd
for C29H46NO6Si 532.3089, found 532.3087.
871, 698 cm−1. H NMR (400 MHz, CDCl3) δ 7.39−7.26 (m, 5H),
5.86−5.72 (m, 1H), 5.44 (s, 1H), 5.13 (br d, J = 10.2 Hz, 1H), 5.06
(br d, J = 17.1 Hz, 1H), 4.55 (d, J = 12.0 Hz, 1H), 4.42 (d, J = 12.0
Hz, 1H), 4.30 (d, J = 7.7 Hz, 1H), 4.17 (dd, J = 8.8, 3.8 Hz, 1H),
3.63−3.53 (m, 2H), 2.74 (ddd, J = 13.6, 8.7, 5.5 Hz, 1H), 2.65−2.54
(m, 2H), 2.45 (dd, J = 14.7, 6.2 Hz, 1H), 2.38 (td, J = 13.3, 3.6 Hz,
1H), 1.92 (s, 3H), 1.47 (dd, J = 13.1, 3.8 Hz, 1H). 13C{1H} NMR
(100 MHz, CDCl3) δ 171.1, 149.6, 147.9, 137.8, 131.8, 128.4 (2C),
127.79, 127.77 (2C), 119.8, 119.2, 107.7, 82.7, 71.9, 66.4, 59.4, 54.3,
45.5, 38.6, 35.0, 8.2. HRMS (ESI-TOF) m/z [M + H]+ calcd for
C22H26NO4 368.1856, found 368.1864.
Compound 41: White solid. Mp 159−167 °C. [α]D20 −25.7 (c 1.0,
CHCl3). IR (film) vmax 2919, 1767, 1330, 1303, 1254, 1213, 1165,
1
1102, 1074, 1011, 974, 931, 752, 701 cm−1. H NMR (400 MHz,
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CDCl3) δ 7.37−7.20 (m, 5H), 5.79−5.65 (m, 1H), 5.06 (br d, J =
10.1 Hz, 1H), 5.00 (br d, J = 17.1 Hz, 1H), 4.50 (d, J = 12.0 Hz, 1H),
4.41 (d, J = 12.0 Hz, 1H), 4.14 (d, J = 7.5 Hz, 1H), 3.95−3.82 (m,
2H), 3.82−3.73 (m, 1H), 3.29−3.17 (m, 1H), 3.00 (td, J = 15.3, 4.3
Hz, 1H), 2.78 (d, J = 14.8 Hz, 1H), 2.54−2.36 (m, 3H), 2.25 (d, J =
14.8 Hz, 1H), 1.81 (s, 3H), 1.38 (dd, J = 12.7, 2.8 Hz, 1H). 13C{1H}
NMR (100 MHz, CDCl3) δ 172.4, 164.0, 137.9, 132.6, 128.4 (2C),
127.8, 127.6 (2C), 121.0, 118.4, 103.2, 79.9, 71.7, 63.0, 62.3, 56.9,
47.1, 41.9, 37.1, 37.0, 8.5. HRMS (ESI-TOF) m/z [M + H]+ calcd for
C22H26NO4 368.1856, found 368.1869.
Methyl (Z)-2-{(1S,5S,6S)-5-allyl-6-(benzyloxy)-8-[2-(tert-
butyldimethylsilyloxy)ethyl]-3-oxo-8-azabicyclo[3.2.1]octan-2-
ylidene}propanoate [(Z)-38] and Methyl (E)-2-{(1S,5S,6S)-5-allyl-6-
(benzyloxy)-8-[2-(tert-butyldimethylsilyloxy)ethyl]-3-oxo-8-
azabicyclo[3.2.1]octan-2-ylidene}propanoate [(E)-38]. To a cooled
solution (0 °C) of the diastereoisomeric mixture 36 (1743 mg, 3.28
mmol) in anhydrous pyridine (16.4 mL) was slowly added
phosphorus oxychloride (1.53 mL, 16.4 mmol). The mixture was
warmed to room temperature and stirred overnight. The reaction was
quenched with a saturated aqueous NH4Cl (20 mL). The organic
layer was separated and the aqueous layer was extracted with EtOAc
(3 × 30 mL). The combined organic layers were washed with brine,
dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. The residue was purified by flash chromatography
(EtOAc/PE = 1/15) to give compound (E)-38 (280 mg, yield: 17%)
and compound (Z)-38 (1000 mg, yield: 59%).
36c: Colorless oil. [α]D +65.7 (c 1.0, CHCl3). IR (film) vmax
3339, 2952, 2928, 2883, 2856, 1757, 1731, 1712, 1462, 1454, 1256,
1
1189, 1156, 1098, 836, 778 cm−1. H NMR (400 MHz, CDCl3) δ
7.37−7.22 (m, 5H), 6.36 (br s, 1H), 5.87−5.74 (m, 1H), 5.16−5.06
(m, 2H), 4.55 (d, J = 12.1 Hz, 1H), 4.39 (d, J = 12.1 Hz, 1H), 4.09
(br d, J = 8.3 Hz, 1H), 3.87 (dd, J = 9.7, 4.7 Hz, 1H), 3.80 (t, J = 5.8
Hz, 2H), 3.72 (s, 3H), 2.98 (dt, J = 12.9, 5.8 Hz, 1H), 2.76 (d, J =
17.0 Hz, 1H), 2.72−2.58 (m, 2H), 2.54 (s, 1H), 2.45−2.36 (m, 2H),
2.31 (dd, J = 15.0, 7.9 Hz, 1H), 1.56 (s, 3H), 1.40 (ddd, J = 14.3, 4.7,
0.9 Hz, 1H), 0.91 (s, 9H), 0.08 (s, 6H). 13C{1H} NMR (100 MHz,
CDCl3) δ 208.7, 174.5, 138.0, 132.3, 128.4 (2C), 127.6, 127.3 (2C),
119.3, 83.6, 72.7, 68.1, 62.9, 62.6, 57.9, 52.3, 49.5, 47.5, 39.1, 34.6,
26.0, 25.9 (3C), 18.3, −5.4 (2C). HRMS (ESI-TOF) m/z [M + H]+
calcd for C29H46NO6Si 532.3089, found 532.3083.
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36d: Colorless oil. [α]D −25.5 (c 1.0, CHCl3). IR (film) vmax
3441, 2953, 2928, 2856, 1729, 1712, 1462, 1454, 1384, 1361, 1253,
1
1164, 1099, 836, 777 cm−1. H NMR (400 MHz, CDCl3) δ 7.35−
7.24 (m, 5H), 5.80−5.66 (m, 1H), 5.01 (br d, J = 10.3 Hz, 1H), 4.95
(dd, J = 17.1, 1.4 Hz, 1H), 4.53 (d, J = 12.0 Hz, 1H), 4.30 (d, J = 12.0
Hz, 1H), 3.83 (s, 1H), 3.80−3.65 (m, 6H), 3.46 (dd, J = 7.4, 3.1 Hz,
1H), 3.11 (br s, 1H), 2.90−2.77 (m, 2H), 2.60 (d, J = 14.6 Hz, 1H),
2.24 (d, J = 7.2 Hz, 2H), 2.18−2.05 (m, 2H), 1.89 (dd, J = 14.0, 3.8
Hz, 1H), 1.63 (s, 3H), 0.91 (s, 9H), 0.08 (s, 6H). 13C{1H} NMR
(100 MHz, CDCl3) δ 207.9, 174.5, 138.4, 132.8, 128.2 (2C), 127.4
(3C), 118.1, 80.5, 75.5, 71.3, 68.7, 62.0, 59.1, 54.3, 52.4, 45.2, 45.0,
39.4, 32.2, 26.8, 25.9 (3C), 18.4, −5.27, −5.29. HRMS (ESI-TOF)
m/z [M + H]+ calcd for C29H46NO6Si 532.3089, found 532.3090.
(Z)-38: Pale yellow oil. [α]D20 −33.7 (c 1.0, CHCl3). IR (film) vmax
2926, 2855, 1731, 1693, 1625, 1462, 1433, 1383, 1241, 1189, 1153,
1102, 918, 835, 777, 738 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.35−
7.22 (m, 5H), 5.85−5.70 (m, 1H), 5.01 (dd, J = 10.2, 1.0 Hz, 1H),
4.93 (dd, J = 17.1, 1.0 Hz, 1H), 4.53 (d, J = 12.0 Hz, 1H), 4.33 (d, J =
12.0 Hz, 1H), 4.26 (d, J = 7.6 Hz, 1H), 3.91 (dd, J = 9.4, 3.1 Hz, 1H),
3.76 (s, 3H), 3.68 (t, J = 6.4 Hz, 2H), 2.84−2.70 (m, 2H), 2.68−2.57
(m, 1H), 2.45−2.32 (m, 1H), 2.28−2.22 (m, 2H), 2.19 (d, J = 17.6
Hz, 1H), 1.94 (s, 3H), 1.48 (dd, J = 13.4, 3.1 Hz, 1H), 0.90 (s, 9H),
0.06 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ 198.0, 171.5,
138.2, 137.3, 135.8, 133.0, 128.3 (2C), 127.5, 127.4 (2C), 118.0, 80.1,
71.5, 66.3, 63.1, 57.5, 52.3, 45.5, 43.0, 40.1, 35.4, 26.0 (3C), 18.5,
15.8, −5.3 (2C). HRMS (ESI-TOF) m/z [M + H]+ calcd for
C29H44NO5Si 514.2983, found 514.2979.
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37: Colorless oil. [α]D +2.0 (c 0.9, CHCl3). IR (film) vmax 3406,
2952, 2928, 2883, 2856, 1747, 1721, 1462, 1454, 1251, 1178, 1145,
1103, 835, 778 cm−1. 1H NMR (400 MHz, CDCl3) δ 9.07 (br s, 1H),
7.37−7.22 (m, 5H), 5.82−5.66 (m, 1H), 5.08−4.95 (m, 2H), 4.43 (d,
J = 11.9 Hz, 1H), 4.32 (d, J = 11.9 Hz, 1H), 3.93−3.82 (m, 2H),
3.82−3.74 (m, 2H), 3.70 (s, 3H), 3.43 (br s, 1H), 2.97 (dt, J = 12.7,
5.5 Hz, 1H), 2.86 (dd, J = 15.3, 3.4 Hz, 1H), 2.66−2.55 (m, 1H),
2.50−2.28 (m, 4H), 1.57 (br d, J = 14.0 Hz, 1H), 1.26 (s, 3H), 0.89
(s, 9H), 0.07 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ 205.9,
177.1, 137.8, 132.7, 128.3 (2C), 127.49, 127.46 (2C), 118.0, 84.4,
74.6, 72.6, 72.3, 62.9, 58.3, 57.0, 52.4, 50.1, 49.3, 37.4, 34.1, 28.5, 25.9
(3C), 18.2, −5.4, −5.5. HRMS (ESI-TOF) m/z [M + H]+ calcd for
C29H46NO6Si 532.3089, found 532.3085.
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(E)-38: Pale yellow oil. [α]D +2.8 (c 1.0, CHCl3). IR (film) vmax
(4S,6S,7S)-7-Allyl-6-(benzyloxy)-9-(2-hydroxyethyl)-3-methyl-
4,5,6,7-tetrahydro-2H-4,7-epiminocyclohepta[b]furan-2-one (40)
and (9S,10aS)-8-Allyl-9-(benzyloxy)-1-methyl-5,6,8,9,10,10a-hexa-
hydro-2H-3a,8-methanofuro[3,2-f ]pyrrolo[1,2-d][1,4]oxazepin-2-
one (41). A solution of the diastereoisomeric mixture 36 (74 mg, 0.14
mmol) and PTSA (p-toluenesulfonic acid monohydrate) (106 mg,
0.56 mmol) in toluene (7.0 mL) was refluxed for 3 h. After being
cooled to room temperature, a saturated aqueous NaHCO3 was added
until pH = 8. The organic layer was separated and the aqueous layer
was extracted with EtOAc (3 × 10 mL). The combined organic layers
were washed with brine, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by
2952, 2926, 2854, 1721, 1691, 1462, 1383, 1229, 1186, 1149, 1099,
1
916, 835, 777 cm−1. H NMR (400 MHz, CDCl3) δ 7.35−7.24 (m,
5H), 5.87−5.72 (m, 1H), 5.01 (dd, J = 10.1, 1.0 Hz, 1H), 4.92 (dd, J
= 17.1, 1.0 Hz, 1H), 4.54 (d, J = 12.0 Hz, 1H), 4.34 (d, J = 12.0 Hz,
1H), 4.30 (d, J = 7.7 Hz, 1H), 3.87 (dd, J = 9.6, 3.5 Hz, 1H), 3.77 (s,
3H), 3.71−3.56 (m, 2H), 2.86−2.71 (m, 2H), 2.61 (ddd, J = 12.5,
7.2, 5.2 Hz, 1H), 2.44−2.32 (m, 1H), 2.28−2.18 (m, 3H), 2.17 (s,
3H), 1.49 (dd, J = 13.8, 3.5 Hz, 1H), 0.89 (s, 9H), 0.05 (s, 6H).
13C{1H} NMR (100 MHz, CDCl3) δ 200.9, 169.5, 147.5, 140.3,
138.3, 135.0, 133.1, 128.3 (2C), 127.5, 127.4 (2C), 117.9, 80.1, 71.4,
66.8, 61.8, 59.7, 52.0, 45.6, 39.8, 35.4, 26.0 (3C), 18.4, 16.9, −5.31,
L
J. Org. Chem. XXXX, XXX, XXX−XXX