Ring Opening of Oxetanes
4512±4521
addition, the solution was stirred for another 18 h. The solvents were
removed in vacuo and the crude product was purified by flash chromatog-
raphy (TBME/P 3/2). The ester rac-15 was obtained as a white solid.
Yield: 85 mg (0.26 mmol, 53%); Rf 0.39 (EtOAc); m.p. 49 ± 518C;
1H NMR (500 MHz): d 7.60 (virt.dt, 3J 7.5 Hz, 4J 1.3 Hz, 1H; HAr),
7.54 (virt.t, 4J 1.9 Hz, 1H; HAr), 7.42 (virt.t, 3J 7.7 Hz, 1H; HAr), 7.33
(ddd, 3J 7.9 Hz, 4J 2.3 Hz, 4J 1.3 Hz, 1H; HAr), 5.63 (brs, 1H; NH),
3.06 (virt.dt, 2J 11.7 Hz, 4J 2.3 Hz, 1H; NCHH), 2.93 (d, 2J 11.7 Hz,
1H; NCHH), 2.69 (virt.dt, 2J 14.2 Hz, 4J 2.2 Hz, 1H; CHH), 9.86 (s,
1H; CHO), 2.45 (virt.dt, 2J 14.2 Hz, 4J 2.2 Hz, 1H; CHH), 1.67 (virt.dt,
2J 13.0 Hz, 4J 2.2 Hz, 1H; CHH), 1.28 (s, 3H; CH3), 1.20 (dd, 2J
7.4 Hz, 1H; HAr), 7.65 (s, 1H; HAr), 7.50 ± 7.42 (m, 2H; HAr), 4.49 (virt.dt,
3J 10.9 Hz, 3J 4.3 Hz, 1H; COOCH), 3.70 (dd, 2J 12.6 Hz, 4J 2.1 Hz,
1H; CONCHH), 3.30 (dd, 2J 12.6 Hz, 4J 1.5 Hz, 1H; CONHCHH),
2.87 (d, 2J 14.3 Hz, 1H; CHH), 2.62 (d, 2J 14.3 Hz, 1H; CHH), 1.92 ±
1.80 (m, 2H; (CH3)2CH, CHH), 1.42 (s, 3H; CH3), 1.28 (s, 3H; CH3), 1.09 (s,
3H; CH3), 0.79 (d, 3J 7.2 Hz, 3H; CH3-Menthyl), 0.76 (d, 3J 6.4 Hz, 3H;
CH3-Menthyl), 1.75 ± 0.50 (m, 11H; 6 Â CHH-Menthyl, 4 Â CH-Menthyl,
3
3 Â CHH), 0.42 (d, J 6.9 Hz, 3H; CH3-Menthyl); 13C NMR (125 MHz):
d 191.5 (s; CHO), 174.2 (s; CO), 174.0 (s; CO), 153.0 (s; CAr), 151.6 (s;
NCOO), 137.4 (s; CAr), 129.8 (d; CArH), 128.1 (d; CArH), 126.0 (d; CArH),
123.3 (d; CArH), 76.7 (d; COOCH), 58.1 (t; CONCH2), 46.5 (d; CH-
Menthyl), 46.1 (t; CH2), 45.7 (t; CH2), 44.4 (t; CH2), 42.7 (s; C), 41.4 (s; C),
40.2 (t; CH2-Menthyl), 34.0 (t; CH2-Menthyl), 31.5 (d; CH-Menthyl), 31.2
(q; CH3), 30.5 (s; C), 29.4 (q; CH3), 26.0 (q; CH3), 25.4 (d; CH-Menthyl),
4
2
13.0 Hz, J 2.1 Hz, 1H; CHH), 1.12 (d, J 14.2 Hz, 1H; CHH), 1.11 (s,
3H; CH3), 1.06 (dd, 2J 14.2 Hz, 4J 2.1 Hz, 1H; CHH), 0.89 (s, 3H; CH3);
13C NMR (125 MHz): d 191.9 (s; CHO), 176.0 (s; CO), 175.2 (s; CO),
152.0 (s; CAr), 138.0 (s; CAr), 130.5 (d; CArH), 128.5 (d; CArH), 127.2 (d;
22.8 (t; CH2-Menthyl), 21.9 (q; CH3-Menthyl), 20.9 (q; CH3-Menthyl), 15.5
CArH), 123.4 (d; CArH), 53.6 (t; NCH2), 46.4 (t; CH2), 45.5 (t; 2C; CH2),
(q; CH3-Menthyl); MS (70 eV, EI): m/z (%): 390 (2) [M
OArCHO], 330
43.3 (s; C), 38.9 (s; C), 31.5 (q; CH3), 31.0 (s; C), 29.2 (q; CH3), 25.3
(q; CH3); IR (film): nÄ 3198 (m, NH), 3060 (m), 2956 (m, CH), 2924
(m, CH), 1750 (s, C O), 1699 (s), 1660 (m), 1446 (m), 1458 (m), 1230 (m),
(1), 208 (100) [MH
COOC10H19], 180 (58) [208 CO], 139 (5)
[C10H19 ], 135 (8), 121 (12), 95 (34), 83 (69), 77 (2) [C6H5 ], 69 (33), 65
(2) [C5H5 ], 57 (53), 55 (38).
1
1150 (s), 1074 cm (s); MS (70 eV, EI): m/z (%): 208 (100) [M
The corresponding N-menthoxycarbonyl amide was treated with neat
trifluoroacetic acid (TFA; 1 mL) under argon (see below for detailed
conditions) and stirred for 15 h at room termperature. Upon complete
conversion water was added to the solution and the aqueous layer was
thoroughly extracted with CH2Cl2. The combined organic layers were
successively washed with a saturated NaHCO3 solution (10 mL) and with
brine (10 mL). After the solution had been dried over MgSO4 and filtered,
the solvent was removed in vacuo.
OArCHO], 180 (92) [208 CO], 135 (65), 121 (23), 107 (29), 93 (23),
81 (22), 77 (12) [C6H5 ], 70 (22), 67 (12); elemental analysis calcd (%
for C19H23NO4 (329.39): C 69.28, H 7.04, N 4.25; found: C 69.30, H 7.03,
N 4.13.
Resolution of compound 15: N,N-Diisopropylamine (160 mL, 1.14 mmol)
was dissolved in THF (20 mL) and the solution was cooled 788C. n-
Butyllithium (0.60 mL of a 1.53 m solution in n-hexane, 0.92 mmol) was
added dropwise to this solution and the mixture subsequently stirred for
another 1.5 h at 788C. A solution of the bicyclic amide rac-15 (250 mg,
0.76 mmol) in THF (15 mL) was added dropwise to the lithium diisopro-
pylamide (LDA) solution within 45 min. After an additional 1 h at 788C
()-(1R,5S,7S)-15: According to the procedure outlined above, the
more polar diastereoisomer (60 mg, 0.12 mmol) was hydrolyzed. The
crude product was purified by flash chromatography (TBME/P 1/1).
Yield of ()-15 (23 mg, 0.07 mmol; 60%). [a]2D0 51.8 (c 1.13 in
CH2Cl2).
(
)-menthyl chloroformate (0.81 mL, 0.835 g, 3.80 mmol) was added
slowly over 45 min. The solution was stirred for another 1 h at 788C,
for 1 h at 08C and finally for 15 h at room temperature. It was quenched
with a saturated NH4Cl-solution (12 mL) and the mixture was reduced in
vacuo. The residue was partioned between a saturated NaHCO3 solution
(10 mL) and CH2Cl2 (20 mL). The organic layer was removed and the
aqueous layer extracted with CH2Cl2 (4 Â 20 mL). The combined organic
(
)-(1S,5R,7R)-15: According to the procedure outlined above, the more
polar diastereoisomer (40 mg, 0.08 mmol) was hydrolyzed. The crude
product was purified by flash chromatography (TBME/P 1/1). Yield of
(
)-15 (10 mg, 0.03 mmol; 36%). [a]D20
52.8 (c 0.86 in CH2Cl2).
(1RS,5SR,7SR,1ꢀSR,6ꢀRS,8ꢀRS)-3-Aza-2-oxo-1,5,7-trimethylbicyclo-
[3.3.1]-7-nonanoic acid 3-(2'-aza-7'-oxa-3'-oxobicyclo[4.2.0]oct-8ꢀ-yl)phen-
yl ester (16): According to the general irradiation procedure, the aldehyde
rac-15 (80 mg, 0.24 mmol) and 3,4-dihydropyridone 6a[9] (48 mg,
0.49 mmol) were irradiated in toluene (20 mL) at l 300 nm and V
108C for 4 h. The solvent was removed in vacuo and the residue purified
by flash chromatography (EtOAc). Yield: 58 mg (0.14 mmol, 56%); Rf
0.32 (EtOAc/EtOH 5/1); m.p. 194 ± 1968C; 1H NMR (500 MHz): d 8.61
(brs, 1H; NH), 8.00 (brs, 1H; NH), 7.37 ± 7.10 (m, 3H; HAr), 6.90 (s, 1H;
layers were successively washed with
a saturated NaHCO3 solution
(10 mL) and with brine (10 mL). After drying over MgSO4 and filtration,
the solvent was removed in vacuo. The two diastereoisomers were
separated by flash chromatography (TBME/P 1/6 !1/2).
More polar diastereoisomer (89 mg, 0.17 mmol, 23%): Rf 0.38 (P/
TBME 5/1); [a]2D0
46.3 (c 0.99 in CH2Cl2); 1H NMR (500 MHz):
d 10.00 (s, 1H; CHO), 7.73 ± 7.64 (m, 2H; HAr), 7.52 ± 7.42 (m, 2H; HAr),
4.49 (virt.dt, 3J 10.9 Hz, 3J 4.3 Hz, 1H; COOCH), 3.79 (dd, 2J
12.5 Hz, 4J 2.3 Hz, 1H; CONCHH), 3.21 (dd, 2J 12.5 Hz, 4J 1.7 Hz,
H
Ar), 5.95 (d, 3J 6.6 Hz, 1H; ArCH), 5.49 ± 5.46 (m, 1H; ArCHOCH),
4.80 (virt.dt, 3J 7.0 Hz, 3J 4.3 Hz, 1H; ArCHCH), 3.16 (d, 2J 12.3 Hz,
1H; NCHH), 2.95 (d, 2J 12.3 Hz, 1H; NCHH), 2.82 (d, 2J 14.1 Hz, 1H;
CHH), 2.54 (d, 2J 14.0 Hz, 1H; CHH), 2.31 ± 2.26 (m, 1H;
NHCOCHHCH2), 2.11 ± 2.00 (m, 2H; NHCOCHHCHH), 1.74 (d, 2J
12.8 Hz, 1H; CHH), 1.66 ± 1.63 (m, 1H; NHCOCH2CHH), 1.36 (s, 3H;
2
2
1H; CONHCHH), 2.87 (d, J 14.2 Hz, 1H; CHH), 2.60 (d, J 14.2 Hz,
1H; CHH), 1.85 (d, 2J 13.0 Hz, 1H; CHH), 1.78 (dsep, 3J 7.0 Hz, 3J
2.8 Hz, 1H; (CH3)2CH), 1.72 ± 1.62 (m, 1H; CH-Menthyl), 1.61 ± 1.53 (m,
2H; CHH-Menthyl, CHH-Menthyl), 1.52 ± 1.47 (m, 1H; CHH-Menthyl),
1.42 (s, 3H; CH3), 1.35 (dd, 2J 13.0 Hz, 4J 2.4 Hz, 1H; CHH), 1.29 (d,
2J 14.4 Hz, 1H; CHH), 1.28 (s, 3H; CH3), 1.28 ± 1.21 (m, 1H; CHH-
Menthyl), 1.21 (dd, 2J 14.2 Hz, 4J 1.7 Hz, 1H; CHH), 1.07 (s, 3H; CH3),
2
CH3), 1.26 ± 1.20 (m, 2H; CHH), 1.19 (s, 3H; CH3), 1.07 (dd, J 14.1 Hz,
4J 1.6 Hz, 1H; CHH), 0.96 (s, 3H; CH3); 13C NMR (125 MHz): d 176.8
(s; CO), 175.4 (s; CO), 173.9 (s; CO), 149.8 (s; CAr), 138.7 (s; CAr), 128.6 (d;
CArH), 121.7 (d; CArH), 121.3 (d; CArH), 118.6 (d; CArH), 84.0 (d; ArCHO),
75.7 (d; ArCHOCH), 52.5 (t; NHCH2), 52.0 (d; ArCHCH), 45.9 (t; CH2),
45.4 (t; CH2), 45.1 (t; CH2), 42.5 (s; C), 38.1 (s; C), 30.7 (q; CH3), 30.2 (s; C),
29.0 (q; CH3), 27.5 (t; NHCOCH2CH2), 25.1 (t; NHCOCH2CH2), 25.0 (q;
CH3); IR (film): nÄ 3217 (s, NH), 2962 (s, CH), 2927 (s, CH), 1754 (s, C
O), 1669 (vs, b), 1489 (m), 1261 (s), 1096 (s), 801 cm 1 (m); MS (70 eV, EI):
3
0.95 ± 0.90 (m, 1H; CH-Menthyl), 0.78 (d, J 7.0 Hz, 3H; CH3-Menthyl),
0.76 ± 0.70 (m, 2H; CHH-Menthyl, CHH-Menthyl), 0.69 (d, 3J 6.6 Hz,
3H; CH3-Menthyl), 0.64 (d, 3J 6.9 Hz, 3H; CH3-Menthyl); 13C NMR
(125 MHz): d 191.6 (s; CHO), 174.4 (s; CO), 174.3 (s; CO), 152.2 (s; Car),
151.5 (s; NCOO), 137.4 (s; CAr), 129.8 (d; CArH), 128.3 (d; CArH), 126.1 (d;
CArH), 123.6 (d; CArH), 77.0 (d; COOCH), 57.6 (t; CONCH2), 46.5 (d; CH-
Menthyl), 46.0 (t; CH2), 45.8 (t; CH2), 44.2 (t; CH2), 42.7 (s; C), 41.3 (s; C),
40.2 (t; CH2-Menthyl), 34.0 (t; CH2-Menthyl), 31.5 (d; CH-Menthyl), 31.2
(q; CH3), 30.5 (s; C), 29.4 (q; CH3), 26.0 (q; CH3), 25.9 (d; CH-Menthyl),
23.1 (t; CH2-Menthyl), 21.8 (q; CH3-Menthyl), 20.8 (q; CH3-Menthyl), 16.1
m/z (%): 426 (<1) [M ], 330 (85) [M
[M
(70), 121 (36), 107 (33), 97 (95) [NHCOC4H6 ], 81 (27), 69 (73), 55 (34);
HRMS calcd (u) for C24H30N2O5: 426.2155; found 426.2163.
NHCOC4H5], 288 (3), 208 (95)
OArC6H8NO2], 180 (100) [M
COOArC6H8NO2], 152 (19), 135
(q; CH3-Menthyl); IR (film): nÄ 2924 (s, CH), 1749 (brs, C O), 1699 (brs),
1
1450 (s), 1148 cm (m); MS (EI, 70eV): m/z (%): 390 (4) [M
( )-(1R,5S,7S,1'S,6'R,8'R)-(16): In an analogous fashion, the enantio-
OArCHO], 330 (3), 208 (100) [MH
COOC10H19], 180 (59) [208 CO],
139 (4) [C10H19 ], 135 (8), 121 (13) [OArCHO ], 95 (23), 83 (41), 77 (2)
merically pure compound ()-15 was converted into the oxetane ( )-16,
the optical purity of which was proven by HPLC (column: Chiracel OD;
[C6H5 ], 69 (18), 65 (3) [C5H5 ], 57 (17), 55 (25).
eluent: hexane/isopropanol). [a]D20
25.5 (c 0.55, CH2Cl2).
Less polar diastereoisomer (40 mg, 0.08 mmol, 10%): Rf 0.48 (P/
2-aza-8,8-diphenyl-5-methyl-7-oxabicyclo[4.2.0]octan-3-one (8b/8b'): Ac-
cording to the general irradiation procedure, benzophenone (248 mg,
1
3
TBME 5/1); H NMR (500 MHz): d 10.00 (s, 1H; CHO), 7.71 (d, J
Chem. Eur. J. 2001, 7, No. 20
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0720-4519 $ 17.50+.50/0
4519