630
I. Atodiresei et al. / Tetrahedron: Asymmetry 17 (2006) 620–633
(400 MHz, CD3OD): d = 0.74 (s, 9H), 1.75–1.92 (m,
4H), 1.99–2.07 (m, 1H), 2.11–2.18 (m, 1H), 2.96–3.05
(m, 2H), 3.36–3.43 (m, 1H), 3.69 (dd, J = 7.4, 11.3 Hz,
1H), 3.74 (dd, J = 5.5, 11.3 Hz, 1H), 3.69/3.74 (AB part
of an ABX-system), 3.68–3.74 (m, 2H), 4.99 (dd,
J = 5.5, 7.4 Hz, 1H), 7.22–7.32 (m, 5H); 13C NMR
(100 MHz, CD3OD): d = 25.2, 26.0, 30.6, 31.8, 33.3,
48.7, 49.6, 55.8, 59.4, 61.0, 64.9, 126.8, 126.9, 128.0,
139.8, 175.6, 176.1; IR (KBr): 3317, 2961, 2872, 1623,
1540, 1368, 1253, 1086, 1049 cmꢀ1; EI-MS: m/z = 377
(M++1, 4), 345 (M+ꢀ31, 100), 327 (9), 319 (14), 260
(29), 240 (54), 194 (4), 157 (6), 140 (35), 121 (16), 106
(25), 95 (10), 86 (12). Anal. Calcd for C21H32N2O4
(376.49): C, 66.99; H, 8.57; N, 7.44. Found: C, 66.79;
H, 8.83; N, 7.48.
31.2, 42.6, 69.6, 75.1, 126.6, 127.5, 128.7, 142.5, 170.5;
IR (in CHCl3): 2964, 2900, 1660, 1494, 1453, 1359,
1176, 1026 cmꢀ1; EI-MS: m/z = 360 (M+, 96), 242
(48), 214 (100), 199 (16), 187 (24), 174 (55), 120 (54),
104 (51), 95 (21), 91 (26), 67 (17). HRMS for
C23H24N2O2: calcd 360.1838; found: 360.1838.
4.7.3. (1R,2R)-Bis-[40-(S)-tert-butyloxazolin-20-yl]-cyclo-
pentane 18. The product was synthesized from 14
(0.891 g, 2.5 mmol) according to GP-7. Purification by
column chromatography (pentane–EtOAc, 1:2) yielded
0.742 g (2.31 mmol, 92% yield) of the title com-
rt
pound as a white solid: mp 53.5–54.5 ꢁC; ½aꢁD ¼
1
ꢀ186:9 ðc 1:08; CHCl3Þ; H NMR (400 MHz, CDCl3):
d = 0.86 (s, 18H), 1.72–1.89 (m, 4H), 2.02–2.10 (m,
2H), 3.13 (t, J = 5.8 Hz, 2H), 3.79 (dd, J = 7.4, 9.9 Hz,
2H), 4.04 (dd, J = 7.4, 8.5 Hz, 2H), 4.12 (dd, J = 8.5,
9.9 Hz, 2H); 13C NMR (100 MHz, CDCl3): d = 25.4,
25.7, 31.3, 33.7, 42.0, 68.5, 75.3, 168.7; IR (KBr):
2959, 2905, 2869, 1670, 1480, 1359, 1258, 1229,
1019 cmꢀ1; EI-MS: m/z = 320 (M+, 14), 305 (6), 263
(100), 205 (6), 194 (15), 163 (24), 136 (21), 95 (2), 67
(3). Anal. Calcd for C19H32N2O2 (320.47): C, 71.21; H,
10.06; N, 8.74. Found: C, 70.81; H, 9.74; N, 8.68.
4.7. General procedure for the preparation of various
C2- and C1-symmetric bisoxazolines with cyclopentane
as backbone GP-7
Diethylaminosulfur trifluoride (0.67 mL, 5.50 mmol,
2.2 equiv) was added dropwise to a cooled (ꢀ78 ꢁC) sus-
pension of the corresponding bis-hydroxyamide
(2.50 mmol) in dry CH2Cl2 (25.0 mL). After stirring
for 3–5 h at the indicated temperature, anhydrous
K2CO3 (1.04 g, 7.50 mmol, 3.0 equiv) was added and
the reaction mixture was allowed to warm to rt. A satu-
rated aq NaHCO3 solution was added and after phase
separation the aqueous layer was extracted with
CH2Cl2. The combined organic layers were dried over
MgSO4, filtered, and concentrated in vacuum to yield
the crude product, which was purified by column
chromatography.
4.7.4. (1S,2S)-Bis-[40-(S)-tert-butyloxazolin-20-yl]-cyclo-
pentane ent-19. The product was synthesized from
ent-15 (0.891 g, 2.50 mmol) according to GP-7. Purifica-
tion by column chromatography (pentane–EtOAc, 1:2)
yielded 0.663 g (2.07 mmol, 83%) of the title comp-
rt
ound as
a
white solid: mp 51 ꢁC; ½aꢁD ¼
þ2:5 ðc 0:69; CHCl3Þ; 1H NMR (400 MHz, CDCl3):
d = 0.87 (s, 18H), 1.70–1.77 (m, 2H), 1.81–1.89 (m,
2H), 2.00–2.08 (m, 2H), 3.09–3.16 (m, 2H), 3.80 (dd,
J = 7.4, 10.2 Hz, 2H), 4.03 (dd, J = 7.4, 8.5 Hz, 2H),
4.12 (dd, J = 8.5, 10.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d = 25.4, 25.7, 31.2, 33.6, 42.1, 68.5, 75.3,
168.5; IR (KBr): 2956, 2902, 2873, 1670, 1476, 1360,
1249, 1188 cmꢀ1; EI-MS: m/z = 320 (M+, 15), 305 (5),
263 (100), 205 (4), 194 (9), 163 (15), 136 (18). HRMS
for C19H32N2O2: calcd 320.2464; found: 320.2464.
4.7.1. (1R,2R)-Bis-[40-(R)-phenyloxazolin-20-0yl]-cyclo-
pentane 16. The product was synthesized from 12
(0.991 g, 2.50 mmol) according to GP-7. Purification
by column chromatography (pentane–EtOAc, 1:2)
yielded 0.818 g (2.27 mmol, 90%) of the title compound
rt
as a colorless oil: ½aꢁ ¼ ꢀ20:8 ðc 0:65; CHCl3Þ; 1H
D
NMR (300 MHz, CDCl3): d = 1.72–1.82 (m, 2H),
1.86–1.98 (m, 2H), 2.06–2.17 (m, 2H), 3.20–3.30 (m,
2H), 4.02 (t, J = 8.2 Hz, 2H), 4.54 (dd, J = 8.2,
10.1 Hz, 2H), 5.10 (dd, J = 7.9, 10.1 Hz, 2H), 7.13–
7.26 (m, 10H); 13C NMR (75 MHz, CDCl3): d = 25.5,
31.3, 42.6, 69.6, 75.0, 126.7, 127.5, 128.7, 142.7, 170.3;
IR (capillary): 3061, 3029, 2962, 2899, 1660, 1493,
1453, 1360, 1177, 1079 cmꢀ1; EI-MS: m/z = 360 (M+,
96), 242 (59), 214 (100), 199 (15), 187 (20), 174 (45),
120 (12), 104 (48), 95 (21), 91 (27), 67 (17). HRMS for
C23H24N2O2: calcd 360.1838; found: 360.1838.
4.7.5.
(1S,2S)-[40-(S)-tert-Butyloxazolin-20-yl]-[400-(S)-
phenyloxazolin-200-yl]-cyclopentane 24. The product
was synthesized from 21 (0.941 g, 2.50 mmol) according
to GP-7. Purification by column chromatography (pen-
tane–EtOAc, 1:2) yielded 0.705 g (2.07 mmol, 83% yield)
rt
of the title compound as a colorless oil: ½aꢁD ¼
þ9:6 ðc 1:56; CHCl3Þ; 1H NMR (400 MHz, CDCl3):
d = 0.88 (s, 9H), 1.77–1.98 (m, 4H), 2.04–2.15 (m, 2H),
3.17–3.28 (m, 2H), 3.83 (ddd, J = 0.8, 7.7, 10.2 Hz,
1H), 4.06 (dd, J = 7.7, 8.8 Hz, 1H), 4.07 (dd, J = 8.0,
8.2 Hz, 1H), 4.16 (dd, J = 8.8, 10.2 Hz, 1H), 4.59 (dd,
J = 8.2, 9.9 Hz, 1H), 5.14 (dd, J = 8.0, 9.9 Hz, 1H),
7.21–7.28 (m, 3H), 7.30–7.35 (m, 2H); 13C NMR
(100 MHz, CDCl3): d = 25.4, 25.7, 31.1, 31.2, 33.6,
42.1, 42.2, 68.5, 69.4, 74.8, 75.3, 126.4, 127.2, 128.4,
142.4, 168.4, 170.3; IR (capillary): 2957, 2902, 2872,
1664, 1477, 1454, 1361, 1180, 1025 cmꢀ1; EI-MS:
m/z = 340 (M+, 39), 325 (4), 283 (100), 242 (11), 214
(29), 163 (55), 136 (34), 120 (13), 103 (7), 95 (8), 67
(8). HRMS for C21H28N2O2: calcd 340.2151; found:
340.2151.
4.7.2.
(1R,2R)-Bis-[40-(R)-phenyloxazolin-20-yl]-cyclo-
pentane 17. The product was synthesized from 13
(0.991 g, 2.50 mmol) according to GP-7. Purification
by column chromatography (pentane–EtOAc, 1:2)
yielded 0.721 g (2.00 mmol, 80%) of the title compound
rt
as a colorless oil: ½aꢁ ¼ ꢀ189:6 ðc 3:00; CHCl3Þ; 1H
D
NMR (400 MHz, CDCl3): d = 1.80–1.89 (m, 2H),
1.95–2.04 (m, 2H), 2.15–2.23 (m, 2H), 3.28–3.35 (m,
2H), 4.09 (t, J = 8.2 Hz, 2H), 4.63 (dd, J = 8.5,
10.2 Hz, 2H), 5.18 (dd, J = 8.0, 10.2 Hz, 2H), 7.22–
7.33 (m, 10H); 13C NMR (100 MHz, CDCl3): d = 25.5,