Dawid and Warkentin
605
(dd, J = 8.6, 7.5 Hz, 1H), 2.68 (br s 1H), 2.50 (m 1H), 1.32–
1.93 (m, 8H). 13C NMR (50 MHz, CDCl3) δ: 179.1, 73.2,
69.2, 41.0, 31.6, 23.6, 21.8, 21.0. EI-MS m/z (%): molecular
ion not observed, 154 (13), 112 (42), 97 (57), 83 (78), 55
(100). CI-MS (NH3) m/z: 174 ([M + NH4]+, 100). The con-
nectivity and stereochemistry of 9 were established by
means of single crystal X-ray diffraction.
was evaporated. Chromatography of the residue gave pure
oxadiazoline 3c (60%) as a colorless oil. IR (neat) (cm–1):
1
2959, 2888, 1742, 1458, 1211, 1140, 1104, 917. H NMR
(300 MHz, CDCl3, mixture of two diastereoisomers) δ:
3.81–4.02 (overlapping multiplets, 4H), 3.43 (s, 3H), 3.42 (s,
3H), 1.60–2.42 (m, 14H), 1.54 (s, 6H), 1.53 (s, 3H), 1.52 (s,
3H). 13C NMR (75 MHz, CDCl3) δ: 218.5, 136.9, 119.5,
63.6, 63.5, 52.0, 48.8, 38.7, 27.0, 24,3, 24.1, 20.9. EI-MS
m/z (%): molecular ion not observed, 211 ([M – OMe]+, 9),
173 (38), 139 (11), 129 (10), 97 (100), 84 (26), 69 (100). CI-
MS (NH3) m/z: 260 ([M + NH4]+, 58).
Synthesis of 3b
A
solution in CH2Cl2 of 2-acetoxy-2-methoxy-5,5-
dimethyl-∆3-1,3,4-oxadiazoline (1), containing about 40% of
an acyclic isomer (19), was treated with hydroxy ketone 2b
and trifluoroacetic acid in dichloromethane. After washing
with dilute base, the organic layer was dried and the solvent
was evaporated. Chromatography of the residue gave pure
oxadiazoline 3b (57%) as a colorless oil. IR (neat) (cm–1):
Thermolysis of 3c
A solution of 3c (0.51 g, 2 mmol) in benzene (20 mL) in a
sealed tube was heated at 110°C for 20 h. Evaporation of the
solvent left a residue that was chromatographed on silica
(hexane:ethyl acetate, 90:10) to afford bicyclic ketone 28
(28%), 25 (10% isolated, unstable compound, hydrolysing,
in part, to hydroxylactone 26 during the separation proce-
dure), product 22 (2% isolated, undergoes hydrolyses to α-
hydroxylactone 26), hydroxylactone 26, product 27, some of
which could have hydrolysed to 26 during TLC separation
(5% isolated), and dimers 29 and 30 (about 3% each).
1
2961, 2885, 1744, 1449, 1212, 1136, 1125, 1108, 921. H
NMR (300 MHz, CDCl3, 1:1 mixture of two diastereomers)
δ: 3.70–3.85 (m, 4H, -OCH2), 3.43 (s, 3H, -OCH3), 3.42 (s,
3H, -OCH3), 2.43–1.50 (m, 18H), 1.53 (s, 12H). 13C NMR
(75 MHz, CDCl3) δ: 220.7, 137.1, 119.2, 63.1, 52.0, 46.4,
38.0, 29.8, 29.6, 24.3, 24.2, 20.9. EI-MS m/z (%): molecular
ion not observed, 181, 153 (100), 129, 112, 111, 83 (100).
CI-MS (NH3) m/z: 274 ([M + NH4]+).
Product 22
Colourless oil. 1H NMR (200 MHz, C6D6) δ: 4.09 (dd, J =
9.0 Hz, J = 6.4 Hz, 1H), 3.62 (s, 3H), 3.47 (dd, J = 9.0, J =
2.9 Hz, 1H), 2.57 (m, 1H), 2.32 (m, 1H), 2.0–1.55 (m, 4H),
1.54 (s, 3H), 1.50 (s, 3H), 1.27 (m, 1H). 13C NMR (50 MHz,
C6 D6) δ: 124.8, 109.4, 98.1, 70.9, 51.1, 50.1, 34.2, 31.3,
28.1, 27.7, 25.5. Product 22 hydrolysed easily to 26.
Thermolysis of 3b
A solution of 3b (0.51 g, 2 mmol) in benzene (20 mL) in
a sealed tube was heated at 110°C for 20 h. Evaporation of
the solvent left a residue that was chromatographed on silica
(hexane:ethyl acetate, 90:10) to afford bicyclic ketone 17
(33%), hydroxyorthoester 18 (~10% after thermolysis), and
dimer 19 (ca. 4%).
Product 25
Colourless oil. IR (neat) (cm–1): 3510 (br), 2954, 2881,
1449, 1365, 1168, 1135, 1113, 1045, 982. 1H NMR
(500 MHz, CDCl3) δ: 3.92 (t, J = 10.1 Hz, 1H), 3.37 (dd, J =
10.2, J = 5.6 Hz, 1H), 3.34 (s, 3H), 3.31 (s, 3H), 2.88 (br. s,
1H), 2.34 (m, 1H), 1.98–2.10 (m, 2H), 1.72–1.80 (m, 3H),
1.45 (m, 1H). 13C NMR (125 MHz, CDCl3) δ: 118.2, 90.6,
69.6, 51.5, 50.7, 47.9, 35.1, 32.6, 26.1. EI-MS m/z (%): 189
([M + 1]+, 5), 157 ([M – OMe]+, 100), 98 (10), 75 (8).
Product 17
Yield: 33%, colourless oil. IR (neat) (cm–1): 2946, 2861,
1
1740, 1464, 1452, 1164, 1064, 1044. H NMR (300 MHz,
CDCl3) δ: 4.09 (dd, J = 11.8, 6.1 Hz, 1H), 3.60 (d, J = 12.2,
J = 4.4, Hz, 1H), 3.39 (s 3H), 2.86 (m, 1H), 1.51–2.26 (m,
8H). 13C NMR (75 MHz, CDCl3) δ: 212.8, 102.5, 65.0, 50.4,
45.4, 40.5, 35.9, 32.0, 17.9. HR-MS m/z calcd. for C9H14O3:
170.0943; found: 170.0969.
Product 18
Product 26
Colourless oil. IR (neat) (cm–1): 3425 (br), 2962, 2876,
1765, 1446, 1383, 1211, 1156, 1008, 978. 1H NMR
(200 MHz, C6D6) δ: 3.74 (t, J = 9.3 Hz, 1H), 3.04 (dd, J =
9.4, J = 5.8 Hz, 1H), 2.91 (br s, 1H), 2.29 (m, 1H), 2.00–
0.85 (m, 6H). 13C NMR (50 MHz, C6D6) δ: 179.5, 83.6,
71.1, 46.4, 39.0, 31.3, 24.8. EI-MS m/z (%): 143 ([M + 1]+,
41), 112 (10), 98 (94), 97 (100), 83 (19). CI-MS (NH3) m/z:
160 ([M + NH4]+, 100).
Only a few colourless crystals could be obtained for X-ray
diffraction. The compound hydrolysed spontaneously to the
corresponding hydroxylactone.
Product 19
1
Colourless crystals, yield ca. 3%. H NMR (200 MHz,
CDCl3) δ: 3.77 (m, 4H), 3.28 (s, 6H, -OCH3), 2.73 (m, 2H),
2.18–1.32 (m, 16H). 13C NMR (75 MHz, CDCl3) δ: 108.9,
84.9, 61.4, 47.9, 42.6, 33.5, 27.8, 27.2, 20.9. The structure
and stereochemistry were confirmed by means of single
crystal X-ray diffraction.
Product 27
Colourless oil. IR (neat) (cm–1): 3051, 2954, 2875, 1754,
1642, 1441, 1364, 1202, 1074, 1018, 929. 1H NMR
(200 MHz, C6D6) δ: 5.69 (m, 1H), 4.97 (m, 2H), 4.04 (dd,
J = 9.1, J = 6.2 Hz, 1H), 3.69 (s, 3H), 3.43 (dd, J = 9.1, J =
1.6 Hz, 1H), 3.37 (s, 3H), 2.47 (m, 1H), 1.50–2.25 (m, 12H).
13C NMR (125 MHz, C6D6) δ: 171.1, 138.4, 127.1, 115.2,
106.8, 98.7, 71.7, 51.7, 50.1, 36.0, 33.8, 32.7, 31.6, 25.9,
22.1. EI-MS m/z (%): 264 (9), 254 (100), 253 ([M – CO-
Synthesis of 3c
A
solution in CH2Cl2 of 2-acetoxy-2-methoxy-5,5-
dimethyl-∆3-1,3,4-oxadiazoline (1), containing about 40% of
an acyclic isomer (19), was treated with hydroxy ketone 2c
and trifluoroacetic acid in dichloromethane. After washing
with dilute base, the organic layer was dried and the solvent
© 2003 NRC Canada