pad of Celite, washing the solids with EtOAc (3 × 30 cm3).
The combined organic phases were washed with brine (30 cm3),
dried (Na2SO4 anhydrous), filtered, and concentrated under
reduced pressure (20–30 mmHg). The residue was purified by
flash chromatography to afford, after concentration, the desired
1,4-addition product (76–99% yield).
chromatography (hexanes : EtOAc, 9 : 1), 5d (80 mg, 99%) as
the only diastereomer (colorless oil). Rf 0.50 (hexanes : EtOAc,
7 : 3); [a]2D1 +43.0 (c 0.1 in CHCl3); mmax (film)/cm−1 2872–2958
=
=
(CH), 1792, 1723 (C O), 1482, 1457 (C C), 1197; dH (200 MHz,
CDCl3) 0.97 (9 H, s, Me3C), 1.52–2.05 (6 H, m, 3 × CH2), 2.28
(2 H, dd, J 7.3 and 6.8, CH2CO2), 3.67 (3 H, s, OCH3), 4.26
(1 H, dd, J 7.3 and 6.8, NCHCO), 5.18 (2 H, s, CH2Ar), 5.56
(1 H, s, NCHO), 7.37 (5 H, s, ArH); dC (50 MHz, CDCl3) 24.4
(CH2), 24.9 (3 × CH3), 25.8 (CH2), 33.0 (CH2), 33.7 (CH2), 36.9
(C), 51.5 (CH), 56.9 (CH3), 68.3 (CH2), 96.3 (CH), 128.5 (2 ×
CH), 128.6 (CH), 128.7 (2 × CH), 135.2 (C), 156.0 (C), 172.6
(C), 173.7 (C); m/z (EI) 391 (3%, M+), 334 (16, M+ − C4H9), 91
(100).
(2S,4S)-2-(1,1-Dimethylethyl)-4-hexyl-5-oxo-3-oxazolidinecarb-
oxylic acid phenylmethyl ester (5a)
Following the general experimental procedure, a mixture of
oxazolidinone 3 (100 mg, 0.345 mmol) and 1-iodopentane
(0.090 cm3, 0.69 mmol) was treated with CuI (131 mg,
0.69 mmol) and Zn (135 mg, 2.07 mmol) to give, after column
chromatography (hexanes : EtOAc, 9 : 1), 5a (120 mg, 96%) as the
only diastereomer (colorless oil). Rf 0.57 (hexanes : EtOAc, 7 : 3);
[a]D20 +31.6 (c 0.1 in CHCl3); mmax (film)/cm−1 2859–2958 (CH),
(2S,4S)-2-(1,1-Dimethylethyl)-4-(4-hydroxybutyl)-5-oxo-3-oxa-
zolidinecarboxylic acid phenylmethyl ester (5e)
=
1794 (CO), 1721, 1482 (C C), 1466; dH (200 MHz, CDCl3) 0.88
Following the general experimental procedure, a mixture of
oxazolidinone 3 (56 mg, 0.193 mmol) and 3-iodopropanol
(0.040 cm3, 0.415 mmol) was treated with CuI (79 mg,
0.415 mmol) and Zn (81 mg, 1.244 mmol) to give, after column
chromatography (hexanes : EtOAc, 9 : 1), 5e (40 mg, 60%) as the
only diastereomer (colorless oil). Rf 0.1 (hexanes : EtOAc, 7 : 3);
(3 H, t, J 6.8, CH3), 0.97 (9 H, s, Me3C), 1.23–1.95 (10 H, m, 5 ×
CH2), 4.26 (1 H, t, J 7.3, NCHCO), 5.18 (2 H, s, CH2Ar), 5.56
(1 H, s, NCHO), 7.37 (5 H, s, ArH); dC (50 MHz, CDCl3) 14.0
(CH3), 22.5 (CH2), 24.9 (3 × CH3), 26.3 (CH2), 28.9 (CH2), 31.5
(CH2), 33.4 (CH2), 36.9 (C), 57.2 (CH), 68.2 (CH2), 96.3 (CH),
128.4 (2 × CH), 128.59 (CH), 128.64 (2 × CH), 135.3 (C), 156.0
(C), 172.8 (C); m/z (EI) 361 (1%, M+), 304 (23 M+ − C4H9), 91
(100).
mmax (film)/cm−1 3441 (OH), 2872–2959 (CH), 1719, 1790 (C O),
=
=
1457, 1482 (C C), 1326, 1198, 1040; dH (200 MHz, CDCl3) 0.96
(9 H, s, Me3C), 1.55–1.98 (6 H, m, 3 × CH2), 3.59 (2 H, dd, J 6.3
and 5.8, CH2OH), 4.28 (1 H, dd, J 7.3 and 6.8, NCHCO), 5.17
(2 H, s, CH2Ar), 5.55 (1 H, s, NCHO), 7.37 (5 H, s, ArH); dC
(50 MHz, CDCl3) 22.6 (CH2), 24.9 (3 × CH3), 32.1 (CH2), 33.0
(CH2), 36.9 (C), 57.0 (CH), 62.4 (CH2), 68.4 (CH2), 96.4 (CH),
128.5 (2 × CH), 128.7 (3 × CH), 135.2 (C), 156.0 (C), 172.7 (C).
(2S,4S)-2-(1,1-Dimethylethyl)-4-(2-methylpropyl)-5-oxo-3-oxa-
zolidinecarboxylic acid phenylmethyl ester (5b)
Following the general experimental procedure, a mixture of oxa-
zolidinone 3 (100 mg, 0.345 mmol) and 2-iodopropane (0.07 cm3,
0.691 mmol) was treated with CuI (131 mg, 0.69 mmol) and
Zn (135 mg, 2.07 mmol) to give, after column chromatography
(hexanes : EtOAc, 9 : 1), 5b (87 mg, 76%) as the only diastereomer
(colorless oil). Rf 0.56 (hexanes : EtOAc, 7 : 3); [a]2D2 +53.0 (c 0.1
in CHCl3); mmax (film)/cm−1 2872–959 (CH), 1793 (CO), 1721,
(2S,4S)-2-(1,1-Dimethylethyl)-4-(4-hydroxytridecyl)-5-oxo-3-
oxazolidinecarboxylic acid phenylmethyl ester (5f)
Following the general experimental procedure, a mixture of
oxazolidinone 3 (60 mg, 0.207 mmol) and 12-iodododecanol
(129 mg, 0.415 mmol) was treated with CuI (79 mg, 0.415 mmol)
and Zn (81 mg, 1.244 mmol) to give, after column chromatog-
raphy (hexanes : EtOAc, 9 : 1), 5f (95 mg, 96%) as the only
diastereomer (colorless oil). Rf 0.35 (hexanes : EtOAc, 7 : 3);
[a]D25 +26.4 (c 0.1 in CHCl3); mmax (film)/cm−1 3440 (OH), 2854–
=
1497 (C C), 1467; dH (200 MHz, CDCl3) 0.92 (6 H, d, J 6.3,
2 × CH3), 0.97 (9 H, s, Me3C), 1.58–2.07 (3 H, m, CHCH2), 4.33
(1 H, dd, J 7.8 and 6.3, NCHCO), 5.17 (2 H, s, CH2Ar), 5.56
(1 H, s, NCHO), 7.37 (5 H, s, ArH); dC (50 MHz, CDCl3) 21.9
(CH3), 22.7 (CH3), 24.9 (3 × CH3), 36.9 (C), 42.4 (CH2), 55.5
(CH), 68.3 (CH2), 96.3 (CH), 128.6 (5 × CH), 135. 2 (C), 156.0
(C), 173.0 (C), 198.5 (C); m/z (EI) 333 (1%, M+), 276 (49, M+ −
C4H9), 91 (100).
=
=
2925 (CH), 1721, 1794 (C O), 1482 (C C), 1465, 1325, 1198,
1041; dH (200 MHz, CDCl3) 0.97 (9 H, s, Me3C), 1.26–1.98 (24
H, m, 12 × CH2), 3.64 (2 H, m, CH2OH), 4.26 (1 H, t, J 7.3,
NCHCO), 5.18 (2 H, s, CH2Ar), 5.55 (1 H, s, NCHO), 7.37 (5
H, s, ArH); dC (50 MHz, CDCl3) 24.9 (3 × CH3), 25.7 (CH2),
26.4 (CH2), 29.2 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 29.6
(CH2), 32.8 (CH2), 33.4 (CH2), 36.9 (C), 57.2 (CH), 63.1 (CH2),
63.1 (CH2), 68.2 (CH2), 96.3 (CH), 128.4 (2 × CH), 128.6 (CH),
128.6 (2 × CH), 135.3 (C), 156.0 (C), 172.8 (C); m/z (FAB) 476
(10%, M+ + H).
(2S,4S)-4-(Cyclohexylmethyl)-2-(1,1-dimethylethyl)-5-oxo-3-
oxazolidinecarboxylic acid phenylmethyl ester (5c)
Following the general experimental procedure, a mixture of
oxazolidinone 3 (60 mg, 0.207 mmol) and iodocyclohexane
(0.054 cm3, 0.415 mmol) was treated with CuI (79 mg,
0.415 mmol) and Zn (81 mg, 1.244 mmol) to give, after column
chromatography (hexanes : EtOAc, 9 : 1), 5c (75 mg, 98%) as the
only diastereomer (colorless oil). Rf 0.57 (hexanes : EtOAc, 7 : 3);
[a]D23 +54.9 (c 0.07 in CH3Cl); mmax (film)/cm−1 2851–2924 (CH),
(aR,2S,4S)-a-{[(1,1-Dimethylethoxy)carbonyl]amino}-2-(1,1-
dimethylethyl)-5-oxo-3-[(phenylmethoxy)carbonyl]-4-
oxazolidinebutanoic acid methyl ester (9)
=
=
1793 (C O), 1721, 1481 (C C), 1448; dH (200 MHz, CDCl3)
0.97 (9 H, s, Me3C), 0.89–1.82 (13 H, m, cC6H11CH2), 4.37 (1
H, dd, J 7.8 and 5.4, NCHCO), 5.17 (2 H, dd, J 12.2 and 15.6,
CH2Ar), 5.56 (1 H, s, NCHO), 7.37 (5 H, s, ArH); dC (50 MHz,
CDCl3) 24.9 (3 × CH3), 25.9 (2 × CH2), 26.4 (2 × CH2), 32.8
(CH2), 33.4 (CH2), 34.2 (CH), 36.9 (C), 41.1 (CH2), 54.9 (CH),
96.3 (CH), 128.6 (5 × CH), 135.2 (C), 156.0 (C), 173.1 (C); m/z
(EI) 316 (5%, M+ − C4H9), 91 (100).
Following the general experimental procedure, a mixture of
oxazolidinone 3 (100 mg, 0.346 mmol) and iodide 8 (220 mg,
0.691 mmol) was treated with CuI (132 mg, 0.691 mmol) and
Zn (135 mg, 2.074 mmol) to give, after column chromatography
(hexanes : EtOAc, 8 : 2), 9 (132 mg, 78%) as the only diastereomer
(colorless oil). Rf 0.23 (hexanes : EtOAc, 7 : 3); mmax (film)/cm−1
=
3372 (NH), 2974–2875 (CH), 1791, 1719 (C O), 1500, 1455
=
(C C), 1319, 1170, 1040; dH (200 MHz, CDCl3) 0.95 (9 H, s,
(2S,4S)-2-(1,1-Dimethylethyl)-4-(methoxycarbonylbutyl)-5-oxo-
3-oxazolidinecarboxylic acid phenylmethyl ester (5d)
Me3CC), 1.44 (9 H, s, Me3CO), 1.97 (4 H, m, 2 × CH2), 3.74 (3
H, s, OCH3), 4.24–4.31 (2 H, m, 2 × NCHCO), 5.06 (1 H, br
m, NH), 5.18 (2 H, s, CH2Ar), 5.55 (1 H, s, O2CH), 7.33–7.41
(5 H, m, ArH); dC (50 MHz, CDCl3) 24.9 (3 × CH3), 28.3 (3 ×
CH3), 29.2 (CH2), 29.6 (CH2), 36.8 (C), 52.4 (CH), 53.1 (CH),
56.7 (CH3), 68.5 (CH2), 80.0 (C), 96.5 (CH), 128.5 (2 × CH),
Following the general experimental procedure, a mixture of
oxazolidinone 3 (60 mg, 0.207 mmol) and methyl 4-iodobutyrate
(0.056 cm3, 0.415 mmol) was treated with CuI (79 mg,
0.415 mmol) and Zn (81 mg, 1.244 mmol) to give, after column
3 5 8 6
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 5 8 4 – 3 5 8 7