by silica gel column chromatography (AcOEt–hexane, 10:90)
afforded 1 (0.643 g, 70%) as white crystals, mp 63–64 ЊC
(Found: C, 72.67; H, 6.48; N, 4.73. C18H19NO3 requires C,
72.70; H, 6.44; N, 4.71%); νmax (Nujol)/cm–1 3320, 1725, 1690,
1540, 1310, 1260, 1205, 1150, 1065, 1005; δH (CDCl3) 2.15 (3H,
s), 3.03, 3.07 (each 1H, dd, J 6.5 and 12.3 Hz), 4.63 (1H, q, J 6.5
Hz), 5.08, 5.09 (each 1H, d, J 12.1 Hz), 5.38 (1H, d, J 6.5 Hz),
7.09–7.39 (10H, m); δC (CDCl3) 27.9, 37.5, 61.1, 66.9, 127.1,
128.0, 128.2, 128.5, 128.7, 129.2, 135.7, 136.3, 155.7, 206.2;
m/z (EI) 297 (Mϩ), 254 (Mϩ Ϫ Ac).
requires C, 71.91; H, 6.86; N, 3.81%); νmax (neat)/cmϪ1 3290,
1775, 1705, 1530, 1255, 1135, 1080, 1030, 975; δH (CDCl3) 1.10
(3H, d, J 7.0 Hz), 1.36 (3H, s), 2.31 (1H, dd, J 11.9 and 17.1 Hz),
2.58 (1H, dd, J 7.2 and 17.1 Hz), 2.67 (2H, m), 3.21 (1H, dd,
J 4.1 and 14.0 Hz), 4.08 (1H, dt, J 4.1 and 9.9 Hz), 4.68 (1H, d,
J 9.9 Hz), 4.70, 4.82 (each 1H, d, J 12.2 Hz), 7.06–7.32 (10H,
m); m/z (EI) 367 (Mϩ), 276 (Mϩ Ϫ CH2Ph).
(4S*,5R*,1ЈR*)-5-[1-(Benzyloxycarbonyl)amino-3-methyl-
butyl]tetrahydro-4,5-dimethylfuran-2-one (syn-trans-ꢁ-lactone)
4. White solid, mp 104–105 ЊC (Found: C, 68.46; H, 8.12; N,
4.11. C19H27NO4 requires C, 68.44; H, 8.16; N, 4.20%); νmax
(Nujol)/cmϪ1 3290, 1780, 1695, 1545, 1270, 1140, 1080, 1040,
950; δH (CDCl3) 0.91, 0.93 (each 3H, d, J 6.8 Hz), 1.17 (3H, d,
J 7.0 Hz), 1.29 (1H, ddd, J 3.2, 10.4, and 14.1 Hz), 1.36 (3H, s),
1.39 (1H, ddd, J 2.7, 11.2, and 14.1 Hz), 1.58 (1H, m), 2.32 (1H,
dd, J 7.0 and 17.1 Hz), 2.41 (1H, dquintet, J 8.2 and 7.0 Hz),
2.65 (1H, dd, J 8.2 and 17.1 Hz), 4.02 (1H, dt, J 2.7 and 10.4
Hz), 4.54 (1H, d, J 10.4 Hz), 5.09, 5.11 (each 1H, d, J 12.0 Hz),
7.28–7.38 (5H, m); δC (CDCl3) 13.0, 21.4, 23.4, 23.9, 24.4, 37.7,
40.3, 40.8, 52.4, 67.0, 89.5, 128.1, 128.2, 128.5, 136.4, 156.0,
176.0; m/z (EI) 333 (Mϩ).
( )-3-[(Benzyloxycarbonyl)amino]-5-methylhexan-2-one 3
Swern oxidation of ( )-N-Z-leucinol, addition of MeMgBr,
and PDC oxidation in accord with the procedure previously
described furnished 3 in 69% yield as white crystals, mp 107–
108 ЊC (Found: C, 68.31; H, 8.10; N, 5.37. C15H21NO3 requires
C, 68.41; H, 8.04; N, 5.32%); νmax (Nujol)/cmϪ1 3310, 1725,
1680, 1545, 1350, 1315, 1270, 1225, 1190, 1120, 980; δH (CDCl3)
0.93, 0.98 (each 3H, d, J 6.7 Hz), 1.38 (1H, ddd, J 4.8, 9.9, and
13.5 Hz), 1.59 (1H, ddd, J 3.8, 8.6, and 13.5 Hz), 1.72 (1H, m),
2.21 (3H, s), 4.41 (1H, dt, J 4.8 and 8.6 Hz), 5.10 (2H, s), 5.26
(1H, d, J 8.6 Hz), 7.29–7.39 (5H, m); δC (CDCl3) 21.7, 23.3,
24.9, 27.0, 40.6, 58.9, 67.0, 128.0, 128.2, 128.5, 136.3, 156.1,
207.4; m/z (EI) 263 (Mϩ), 220 (Mϩ Ϫ Ac).
(4R*,5R*,1ЈR*)-5-[1-(Benzyloxycarbonyl)amino-3-methyl-
butyl]tetrahydro-4,5-dimethylfuran-2-one (syn-cis-ꢁ-lactone) 8.
Colorless oil (Found: C, 68.55; H, 8.09; N, 4.25. C19H27NO4
requires C, 68.44; H, 8.16; N, 4.20%); νmax (neat)/cmϪ1 3290,
1780, 1695, 1545, 1270, 1140, 1080, 1040, 950; δH (CDCl3) 0.90,
0.92 (each 3H, d, J 6.8 Hz), 1.06 (3H, d, J 7.0 Hz), 1.22 (3H, s),
1.45 (2H, m), 1.63 (1H, m), 2.26 (1H, m), 2.55 (2H, m), 3.81
(1H, dt, J 3.6 and 10.3 Hz), 4.65 (1H, d, J 10.3 Hz), 5.09, 5.13
(each 1H, d, J 12.5 Hz), 7.29–7.39 (5H, m); m/z (EI) 333 (Mϩ).
Preparation of THF solution of SmI2
To a slurry of Sm metal powder (2.00 g, 13.3 mmol) in THF
(100 mL) was added CH2I2 (0.900 mL, 11.2 mmol). The mixture
was stirred at room temperature for 3 h. The resulting blue
solution was used directly to effect the following reductive
couplings.
General procedure for reductive coupling of ꢀ-(benzyloxy-
carbonyl)amino ketone with crotonic acid ester
(4R*,5R*,1ЈS*)-4-Benzyl-5-(3-acetoxy-1-methylpropyl)-5-
To a solution of 1 or 3 (0.067 mmol) and methyl, ethyl, iso-
propyl, or tert-butyl crotonate (0.101 mmol) in a mixture of
THF (0.70 mL) and MeOH (0.35 mL) was added 0.10 M THF
solution of SmI2 (1.68 mL, 0.168 mmol). After stirring for 5
min, TLC analysis of the reaction mixture showed complete
consumption of the starting ketone. The reaction mixture was
quenched with saturated aqueous NaHCO3 and extracted with
ether. The combined ethereal extracts were washed with H2O
and brine, dried over Na2SO4, and concentrated in vacuo. The
residue was dissolved in CH2Cl2 (1.0 mL), and CSA (5.00 mg,
0.022 mmol) was added. The mixture was stirred at room tem-
perature for 12 h and diluted with ether. The ethereal solution
was washed with saturated aqueous NaHCO3 and brine, dried
over Na2SO4, and concentrated in vacuo. The diastereoisomeric
ratios (trans:cis) were determined from the 400 MHz 1H-NMR
spectra of the crude product. Purification by preparative silica
gel TLC (AcOEt–PhMe, 30:70) gave the syn-cis- and syn-trans-
lactones.
methyl-1,3-oxazolidin-2-one 5
The following describes the general procedure for the synthesis
of the 1,3-oxazolidin-2-ones from the syn-γ-lactones (tetra-
hydrofuran-2-ones). To a solution of the syn-trans-γ-lactone 2
(35.0 mg, 0.095 mmol) in THF (1.0 mL) cooled at 0 ЊC was
added LiAlH4 (20.0 mg, 0.527 mmol). The reaction was stirred
at 0 ЊC for 5 min and quenched with AcOEt. The mixture
was treated with successive additions of H2O (0.02 mL), 15%
aqueous NaOH (0.02 mL), and H2O (0.06 mL). The resultant
white precipitate was filtered off and the filtrate was concen-
trated in vacuo. The residue was diluted with a 1.0 M MeOH
solution of NaOH (0.30 mL). Stirring was continued at
ambient temperature for 5 h and AcOEt was added. The
resulting solution was washed with brine, dried over Na2SO4,
and concentrated in vacuo to afford a crude product containing
4-benzyl-5-(3-hydroxy-1-methylpropyl)-5-methyl-1,3-oxazol-
idin-2-one. The crude product was dissolved in pyridine
(0.50 mL) and treated with DMAP (1.00 mg, 8.19 µmol) and
Ac2O (90.0 µL, 0.954 mmol). After stirring at room tem-
perature for 30 min, the mixture was diluted with ether. The
ethereal solution was washed with saturated aqueous CuSO4,
H2O, saturated aqueous NaHCO3, and brine, and dried over
Na2SO4. Concentration in vacuo and purification by silica gel
column chromatography (AcOEt–PhMe, 20:80) furnished 7
(20.5 mg, 70%) as a colorless oil (Found: C, 66.56; H, 7.52;
N, 4.61. C17H23NO4 requires C, 66.86; H, 7.59; N, 4.59%); νmax
(neat)/cmϪ1 3280, 2950, 1755, 1495, 1455, 1390, 1370, 1245,
1090, 1035, 990; δH (CDCl3) 1.09 (3H, d, J 7.0 Hz), 1.41 (3H, s),
1.42 (1H, m), 1.93 (2H, m), 2.06 (3H, s), 2.70 (1H, dd, J 11.0
and 13.5 Hz), 2.85 (1H, dd, J 3.1 and 13.5 Hz), 3.77 (1H, dd,
J 3.1 and 11.0 Hz), 4.09 (1H, ddd, J 6.4, 8.3, and 10.9 Hz), 4.22
(1H, ddd, J 4.5, 7.4, and 10.9 Hz), 4.79 (1H, br s), 7.18 (2H, d,
J 8.1 Hz), 7.28 (1H, t, J 8.1 Hz), 7.35 (2H, t, J 8.1 Hz); m/z (EI)
246 (Mϩ Ϫ OAc), 214 (Mϩ Ϫ CH2Ph).
(4S*,5R*,1ЈR*)-5-[1-(Benzyloxycarbonyl)amino-2-phenyl-
ethyl]tetrahydro-4,5-dimethylfuran-2-one (syn-trans-ꢁ-lactone)
2. Colorless oil (Found: C, 71.96; H, 6.89; N, 3.68. C22H25NO4
requires C, 71.91; H, 6.86; N, 3.81%); νmax (neat)/cmϪ1 3290,
1775, 1705, 1530, 1255, 1135, 1080, 1030, 975; δH (CDCl3) 1.21
(3H, d, J 7.0 Hz), 1.51 (3H, s), 2.39 (1H, dd, J 10.4 and 16.5
Hz), 2.49 (1H, m), 2.63 (2H, m), 3.11 (1H, dd, J 3.5 and 13.6
Hz), 4.22 (1H, dt, J 3.5 and 10.9 Hz), 4.57 (1H, d, J 10.9 Hz),
4.77, 4.81 (each 1H, d, J 12.3 Hz), 7.07–7.32 (10H, m);
δC (CDCl3) 13.0, 23.8, 24.8, 37.0, 37.7, 40.3, 60.5, 88.3, 127.1,
128.0, 128.2, 128.5, 128.7, 129.1, 135.7, 136.3, 155.8, 175.9;
m/z (EI) 367 (Mϩ), 276 (Mϩ Ϫ CH2Ph).
(4R*,5R*,1ЈR*)-5-[1-(Benzyloxycarbonyl)amino-2-phenyl-
ethyl]tetrahydro-4,5-dimethylfuran-2-one (syn-cis-ꢁ-lactone) 7.
Colorless oil (Found: C, 72.01; H, 6.77; N, 3.72. C22H25NO4
2374
J. Chem. Soc., Perkin Trans. 1, 1999, 2371–2375