M. Anwar et al. / Tetrahedron: Asymmetry 21 (2010) 1758–1770
1765
chromatography (EtOAc/petrol, 1:3) to give the cis-oxazolidine 4
(1.3 g, 84% yield) as a light brown oil.
tered, dried over MgSO4 and evaporated in vacuo. Recrystallisation
from ethyl acetate gave oxazolidine 6a (334 mg, 49%) as colourless
crystals.
Rf = 0.21 (EtOAc/petrol, 1:3); ½a D22
ꢂ
¼ ꢁ71:1 (c 1.6, CHCl3); mmax
/
cmꢁ1 (KBr) 2980 (m), 2960 (m), 2875 (w), 1745 (s), 1675 (s),
1390, 1370 and 1240; dH (400 MHz, CDCl3) (1.5:1 mixture of con-
formers) Major: 0.88 (9H, s, C(CH3)3), 1.23–1.27 (3H, m, CH2CH3),
1.32 (3H, d, J 3.8 Hz, CHCH3), 3.41 (1H, d, J 15.4 Hz, COCHHCO),
3.55 (1H, d, J 15.4 Hz, COCHHCO), 3.78 (3H, s, CO2CH3), 4.12–4.20
(2H, m, CH2CH3), 4.29 (1H, d, J 3.8 Hz, C(4)H), 4.72–4.76 (1H, m,
C(5)H), 5.40 (1H, s, C(2)H); dC (100.6 MHz) 14.0 (CH2CH3), 20.1
(CHCH3), 25.8 (C(CH3)3), 37.8 (C(CH3)3), 42.8 (C(7)), 52.8 (CO2CH3),
61.6 (COCH2CO), 65.4 (C(4)), 76.1 (C(5)), 96.1 (C(2)), 166.6, 167.2,
167.3 and 170.0 (amide and ester carbonyls); m/z (ES+) 338
(M+Na+, 100%), 316 (M+H+, 70%); (M+H+) Found 316.1764,
Compound 6a: mp 130–132 °C; Rf = 0.34 (EtOAc/petrol, 1:3);
½
a 2D2
ꢂ
¼ ꢁ43:4 (c 2.0, CHCl3);
m
max/cmꢁ1 (KBr) 2990 (m), 2960 (m),
2922 (w), 2875 (w), 1745 (s), 1675 (s), 1390, 1370 and 1170; dH
(400 MHz, CDCl3) 0.79 (3H, d, J 6.3 Hz, CHCH3), 0.93 (9H, s,
C(CH3)3), 1.27 (3H, t, J 7.1 Hz, CO2CH2CH3), 3.89 (3H, s, CO2CH3),
4.05 (1H, d, J 3.0 Hz, C(4)H), 4.16–4.22 (2H, q, J 7.1 Hz, CH2CH3),
4.65–4.70 (1H, m, C(5)H), 4.90 (1H, s, CHPh), 5.40 (1H, s, C(2)H),
7.30–7.37 (5H, m, ArH); dC (100.6 MHz, CDCl3) 14.0 (CO2CH2CH3),
19.2 (CHCH3), 25.7 (C(CH3)3), 37.7 (CMe3), 52.9 (CO2CH3), 58.2
(CHPh), 61.7 (COCH2CH3), 64.4 (C(4)), 75.3 (C(5)), 95.9 (C(2)),
127.9, 128.2, 128.5, 129.2 and 132.1 (ArC), 168.3, 169.0, 170.0
(amide and ester carbonyls); m/z (ES+) 392 (M+H+, 100%), (M+H+)
Found 392.2069, C21H30NO6 requires 392.2073. The crystal struc-
ture was determined from X-ray diffraction data.
C15H26NO6 requires 316.1760.
The racemic form ( )-4 was similarly prepared from ( )-3 in
77% yield and exhibited similar spectroscopic data.
Purification of the residue from the above-mentioned crystalli-
sation with flash column chromatography (EtOAc/petrol) gave oxa-
zolidine 6a (29 mg, 4.2%), mixture of oxazolidines 6a and 6b (1:1)
(40 mg, 5.8%) and oxazolidine 6b (75 mg, 11%) as a colourless oil.
3.2.2. (2R,4S,5R)-2-(tert-Butyl)-3-(3-ethoxy-2-methyl-3-oxo
propanoyl)-4-methoxycarbonyl-5-methyloxazolidine 5a and
(2S,4S,5R,20S)-2-(tert-butyl)-3-(3-ethoxy-2-methyl-3-oxoprop-
anoyl)-4-methoxycarbonyl-5-methyl-oxazolidine 5b
Compound 6b: Rf = 0.31 (EtOAc/petrol, 1:3); ½a D22
¼ þ87 (c 2.0,
ꢂ
According to Section 3.1, oxazolidine 3 (0.30 g, 1.5 mmol) was
CHCl3); m
max/cmꢁ1 (KBr) 2990 (m), 2958 (m), 2920 (w), 2870 (w),
reacted with pyridine (0.25 ml, 3.15 mmol) and ethyl-
a
-methyl-
1745 (s), 1677 (s), 1390, 1375 and 1170; dH (400 MHz, CDCl3)
0.82 (9H, s, C(CH3)3), 1.27 (3H, t, J 7.1 Hz, CO2CH2CH3), 1.39 (3H,
d, J 6.2 Hz, CHCH3), 3.75 (3H, s, CO2CH3), 4.23 (2H, q, J 7.1 Hz,
CO2CH2CH3), 4.49 (1H, d, J 3.2 Hz, C(4)H), 4.83–4.85 (1H, m,
C(5)H), 4.92 (1H, s, CHPh), 5.51 (1H, s, C(2)H), 7.33–7.39 (3H, m,
ArH), 7.43–7.48 (2H, m, ArH); dC (100.6 MHz, CDCl3) 14.1
(CO2CH2CH3), 19.9 (CHCH3), 25.7 (C(CH3)3), 37.7 (CMe3), 52.7
(CO2CH3), 57.3 (CHPh), 62.0 (COCH2CH3), 65.6 (C(4)), 76.0 (C(5)),
96.0 (C(2)), 128.0, 128.3, 128.6, 129.3, 129.7 and 133.6 (ArC),
168.4, 169.5, 170.0 (amide and ester carbonyls); m/z (ES+) 392
(M+H+, 100%), HRMS (M+H+) Found 392.2065, C21H30NO6 requires
392.2073.
malonyl chloride (0.49 g, 3.0 mmol) in DCM (15 ml). Purification
by flash column chromatography (EtOAc/petrol, 1:4) gave oxazoli-
dine 5a (0.31 g, 63% yield) as a viscous oil and oxazolidine 5b
(0.11 g, 23%) as a colourless crystalline solid.
Compound 5a: Rf = 0.33 (EtOAc/petrol, 1:4); ½a D22
¼ þ95:2 (c 2.2,
ꢂ
CHCl3); m
max/cmꢁ1 (CHCl3) 2980 (m), 2960 (m), 2875 (w), 1744 (s),
1675 (s), 1395, 1370 and 1240; dH (400 MHz, CDCl3) 0.88 (9H, s,
C(CH3)3), 1.24 (3H, t, J 7.1 Hz, CH2CH3), 1.34 (3H, d, J 6.2 Hz,
CHCH3), 1.44 (3H, d, J 6.8 Hz, COCHCH3), 3.63 (1H, q, J 6.8 Hz,
COCHCH3), 3.86 (3H, s, CO2CH3), 4.12 (2H, q, J 7.1 Hz, CH2CH3),
4.52 (1H, d, J 3.5 Hz, C(4)H), 4.78–4.83 (1H, m, C(5)H), 5.47 (1H,
s, C(2)H); dC (100.6 MHz, CDCl3) 14.1 (CH2CH3), 14.5 (COCHCH3),
20.2 (CHCH3), 25.7 (C(CH3)3), 37.7 (C(CH3)3), 45.5 (COCHCH3),
52.8 (CO2CH3), 61.6 (CH2CH3), 65.2 (C(4)), 75.8 (C(5)), 95.7 (C(2)),
169.9, 170.3 and 171.7 (amide and ester carbonyls); m/z (ES+)
388 (M+H2OꢁCH3CN+, 100%), 330 (M+H+, 10%), (M+H+) Found
330.1845, C16H28NO6 requires 330.1838.
3.2.4. (2R,4S,5R)-2-(tert-Butyl)-3-(2-phenylacetyl)-5-methyl-4-
methoxycarbonyl-oxazolidine 7
According to Section 3.1, oxazolidine 3 (1.0 g, 4.98 mmol) and
pyridine (0.59 g, 7.46 mmol) in DCM (15 ml) were reacted with
phenylacetyl chloride (0.93 g, 5.97 mmol) in DCM (8 ml). Purifica-
tion by flash column chromatography on silica gel (DCM/petrol, 1:1
gradually increasing polarity to DCM) gave the title compound 7
(1.22 g, 77%) as a white crystalline solid.
Compound 5b: Rf = 0.21 (EtOAc/petrol, 1:4); mp 92–93 °C;
½
a 2D2
ꢂ
¼ þ87:2 (c 2.2, CHCl3);
m
max/cmꢁ1 (CHCl3) 2980 (m), 2960
(m), 2875 (w), 1744 (s), 1675 (s), 1395, 1370 and 1240; dH
(400 MHz, CDCl3) 1.03 (9H, s, C(CH3)3), 1.27 (3H, t, J 7.2 Hz,
CH2CH3), 1.34 (3H, d, J 6.1 Hz, CHCH3), 1.42 (3H, d, J 7.2 Hz,
COCHCH3), 3.47 (1H, q, J 6.7 Hz, COCHCH3), 3.76 (3H, s, CO2CH3),
3.85 (1H, d, J 8.8 Hz, C(4)H), 4.06–4.22 (3H, m, C(5)H and CH2CH3),
5.10 (1H, s, C(2)H); dC (100.6 MHz, CDCl3) 14.1 (CH2CH3), 15.2
(COCHCH3), 20.2 (CHCH3), 25.8 (C(CH3)3), 38.8 (C(CH3)3), 45.8
(COCHCH3), 52.8 (CO2CH3), 61.6 (CH2CH3), 65.8 (C(4)), 75.8 (C(5)),
96.6 (C(2)), 169.7, 170.0 and 171.4 (amide and ester carbonyls);
m/z (ES+) 330 (M+H+, 100%), (M+H+) Found 330.1834, C16H28NO6
requires 330.1838. The crystal structure was determined from X-
ray diffraction data.
Rf = 0.34 (DCM); ½a D22
ꢂ
¼ ꢁ4:9 (c 1.56, CHCl3)
m
max/cmꢁ1 (KBr)
2956 (s), 2870 (m), 1746 (s), 1436 (s), 1208 (s), 1173 (s); dH
(400 MHz, CDCl3) 0.93 (9H, s, C(CH3)3), 1.12 (3H, d, J 5.9 MHz,
CHCH3), 3.68 (1H, d, J 15.0 Hz, CHHPh), 3.78 (1H, d, J 15.0 Hz,
CHHPh), 3.81 (3H, s, CO2CH3), 4.20 (1H, d, J 3.5 Hz, C(4)H), 4.67–
4.70 (1H, m, C(5)H), 5.43 (1H, s, C(2)H), 7.21–7.37 (5H, m, ArH);
dC (100.6 MHz, CDCl3) 20.0 (CHCH3), 25.9 (C(CH3)3), 37.9 (CMe3),
42.3 (CH2Ph), 52.7 (CO2CH3), 65.2 (C(4)), 76.0 (C(5)), 96.4 (C(2)),
127.1, 128.8, 129.0, 129.2 and 134.1 (ArC), 170.3 and 172.0 (amide
t
and ester carbonyls); m/z (ES+) 320 (M+H+, 100%), 264 (M+H+ꢁ Bu),
(M+H+) Found 320.1871, C18H26NO4 requires 320.1862.
The racemic form ( )-7 was similarly prepared from ( )-3 in
77% yield and exhibited similar spectroscopic data.
The racemic forms ( )-5a,b were similarly prepared from ( )-3
in 77% yield and exhibited similar spectroscopic data.
3.2.3. (2R,4S,5R,20R)-2-(tert-Butyl)-3-(3-ethoxy-2-phenyl-3-oxo-
propanoyl)-4-methoxycarbonyl-5-methyl-oxazolidine 6a and
(2R,4S,5R,20S)-2-(tert-butyl)-3-(3-ethoxy-2-phenyl-3-oxoprop-
anoyl-4-methoxycarbonyl-5-methyl-oxazolidine 6b
According to Section 3.2, oxazolidine 3 (350 mg, 1.74 mmol),
DCCI (392 mg, 1.91 mmol) and DMAP (16 mg, 0.13 mmol) in
3.2.5. (2R,4S,5R)-2-(tert-Butyl)-3-(2-cyanoacetyl)-4-methoxycar
bonyl-5-methyl-oxazolidine 8
According to Section 3.2, a solution of oxazolidine 3 (0.6 g,
3.0 mmol), DMAP (0.04 mg, 0.3 mmol) and DCCI (0.62 g, 3.0 mmol)
in DCM (10 ml) at 0 °C were reacted with cyanoacetic acid
(0.26 mg, 3.0 mmol) in CH3CN (2 ml). The reaction mixture was
stirred at room temperature for 4 h and then filtered, the residue
was washed with DCM (3 ꢀ 15 ml) and combined filtrates were
DCM (10 ml) were reacted with ethyl
a-phenylmalonic acid
(252 mg, 1.91 mmol) in DCM (4 ml). The reaction mixture was fil-