Helvetica Chimica Acta Vol. 85 (2002)
1067
Experimental Part
General. Cyclohexanone, acetone, butanone, and pentan-3-one were purchased and used directly without
special treatment. M.p.: VEB Wagetechnik Rapio PHMK05; uncorrected. [a]D: WZZ-1S (Shanghai, China)
polarimeter. IR Spectra: Testscan Shimadzu FTIR 8000 and Nicolet 170 SX FT-IR spectrophotometers; in KBr;
1
n in cmÀ1. H- and 13C-NMR Spectra: Varian Mercury VS-300 and JEOL FX-90Q spectrometers; d in (ppm)
relative to Me4Si. EI-MS: VG ZAB-HF-3F spectrometer (70 eV); m/z (rel. %). Elemental analysis: Perkin-
Elmer 240 B analyzer.
threo-(1S,2S)-2-ANP was supplied by the Wuhan Pharmaceutical Factory and was purified by recrystal-
lization: prior to use: m.p. 1638; [a]D 31.2( c 1, 6n HCl).
Preparation of 2,2,4,5-Tetrasubstituted Oxazolidines. Method A: threo-(4S,5S)-4-(Hydroxymethyl)-2,2-
dimethyl-5-(4-nitrophenyl)-1,3-oxazolidine (1b). To a 250 ml round-bottom flask, threo-(1S,2S)-2-ANP (4.24 g,
20 mmol) and acetone (4 ml) in toluene (35 ml) were added, and then fitted successively with an oil-water
separator, a reflux condenser, and an oil bubbler with a stopcock. Under Ar, the mixture was refluxed with
stirring for 3 h to form a homogeneous yellow soln. The soln. was cooled to r.t. to give 5.0 g of a solvate of the
condensate 1b with toluene as colorless needles (m.p. 40 428 (dec.)). The product was desolvated by treatment
with Et2O, crystallized, and dried under reduced pressure to give 4.7 g 1b. Yield 93%. M.p. 76 788 (dec.).
[a]1D5 45.02( c 2, EtOH). IR: (3404m, 3261m, 3209 (sh, NH, OH); 2980m, 2920m, 2880m, 2860m (CÀH);
1603m (CCÀC); 1522vs, 1350vs (NO2), 1047s (asym. CÀOÀC), 854s (ArÀH). 1H-NMR ((D6)DMSO,
90 MHz): 8.15 (d, J 8.7, HÀC(3'), HÀC(5')); 7.57 (d, J 8.7, HÀC(2'), HÀC(6')); 4.96 (t, J 5.4, CH2OH);
4.65 (d, J(5,4) 8.1, HÀC(5)); 3.59 (br. s, CH2OH; after adding D2O: d, J 3.6); 3.32(br. s, NH; disappeared
after adding D2O); 3.00 (br. s, HÀC(4); after adding D2O: m); 1.42( s, Me); 1.38 (s, Me). 1H-NMR ((D6)-
DMSO, 300 MHz): 8.18 (d, J 9.0, HÀC(3'), HÀC(5')); 7.61 (d, J 8.7, HÀC(2'), HÀC(6')); 4.85 (t, J 5.4,
CH2OH); 4.67 (d, J(5,4) 7.8, HÀC(5)); 3.60 (m, CH2OH); 3.21 (s, NH); 3.04 (m, HÀC(4)); 1.42( s, Me); 1.38
(s, Me). MS: 237 (14, [M À Me] ), 221 (15, [M À CH2OH] ), 195 (11), 177 (5), 165 (15), 146 (8), 136 (7), 131
(9), 117 (26), 101 (100), 100 (95), 89 (11), 84 (32), 83 (45), 77 (13), 68 (18), 59 (18), 58 (37), 51 (5), 43 (34).
Anal. calc. for C12H16N2O4 (252.27): C 57.13, H 6.39, N 11.11; found: C 57.02, H 6.26, N 11.00.
threo-(2S,3S)-3-(Hydroxymethyl)-2-(4-nitrophenyl)-1-oxa-4-azaspiro[4.5]decane (1a). Similar to the
above procedure: Condensation of threo-(1S,2S)-2-ANP (8.48 g, 40 mmol) and cyclohexanone (4.2 ml, ca.
3.98 g, 40.5 mmol) in xylene (70 ml) gave 13.8 g of the xylene solvate of 1a as yellowish needles. Yield 92.5%.
M.p. 54 568 (dec.). IR: 3404m, 3276m (sh, NH, OH); 2996s, 2858ms (CÀH); 1601m (CCÀC); 1520vs, 1348vs
(NO2); 1056s (asym. CÀOÀC); 848s (ArÀH). MS: 292 (M ), 263 ([M À C2H5] ), 249 ([M À C3H7] ), 195
([M À C6H11N] ), 177 ([M À C6H13NO] ), 141 ([M À C7H5NO3] ), 140 ([M À C7H6NO3] ), 123 ([M À
.
C8H13N] ), 109 ([M À C8H9NO4] ), 106 (M (xylene)), 91 ([M(xylene) À Me] ), 77 (C6H5 ), 55 (C4H7 ).
Anal. calc. for C15H20N2O4 ¥ 0.5 C6H4(CH3)2 (345.41): C 66.06, H 7.30, N 8.11; found: C 65.62, H 7.26, N 7.81.
The 1aÀxylene solvate was treated with Et2O, crystallized, to give pure 1a (data reported under Method B).
Method B: Under Ar, a mixture of threo-(1S,2S)-2-ANP (16.96 g, 80 mmol) and cyclohexanone (8.4 ml, ca.
7.95 g, 81.0 mmol) in toluene (70 ml) was refluxed azeotropically for 3 h in a 250 ml round-bottomed flask to
offer a homogeneous yellow soln. The soln. was evaporated to dryness. The residue was extracted with hot Et2O
(30 ml), and the extract was cooled to r.t., from which 19.30 g of yellowish crystals of 1a were isolated. The
mother liquor was concentrated to yield a further 2.3 g of crystals. Overall yield 92.5%. M.p. 78 808 (dec.).
[a]1D5 51.50 (c 2, EtOH). IR: 3429s, 3288s, 3248 (sh, NH, OH); 1601m (CCÀC); 1516vs, 1350vs (NO2);
1057vs (asym. CÀOÀC); 843s (ArÀH). 1H-NMR ((D6)DMSO, 300 MHz): 8.19 (d, J 8.7, HÀC(3'),
HÀC(5')); 7.59 (d, J 9.0, HÀC(2'), HÀC(6')); 5.00 (t, J 4.8, CH2OH); 4.62( d, J(5,4) 6.6 HÀC(2)); 3.50
(m, CH2OH); 2.92 (m, 2H, H ÀC(3), NH); 1.80 1.20 (m, C6H10). 13C-NMR ((D6)DMSO, 300 MHz): 150.807;
147.503; 127.804; 123.974; 97.323; 79.386; 68.133; 59.999; 41.315; 41.040; 40.765; 40.483; 40.208; 39.934; 39.651;
.
38.133; 37.874; 25.781; 24.247. MS: 292 (14, M ), 263 (8), 261 (6, [M À CH2OH] ), 250 (16), 249 (100), 236 (4),
219 (4), 205 (3), 195 (9), 177 (9), 165 (4), 141 (30), 140 (42), 124 (10), 123 (10), 117 (8), 110 (9), 81 (8), 55 (24),
41 (15). Anal. calc. for C15H20N2O4 (292.33): C 61.63, H 6.90, N 9.59; found: C 61.67, H 7.98, N 9.66.
threo-(2RS,4S,5S)-2-Ethyl-4-(hydroxymethyl)-2-methyl-5-(4-nitrophenyl)-1,3-oxazolidine (1c). As descri-
bed for 1a under Method B. Mixture of epimers: yield, 88%. M.p. 62 64 8 (dec.). [a]1D5 52.56 (c 2, EtOH).
IR: 3400s, 3291m, 3205m (NH, OH); 1603m (CCÀC); 1525vs, 1351vs (NO2); 1052s (asym. CÀOÀC); 852s
(ArÀH). 1H-NMR ((D6)DMSO, 300 MHz): 8.18 (d, J 8.7, HÀC(3'), HÀC(5'), both epimers); 7.61 (d, J 8.4,
HÀC(2'), HÀC(6'), both epimers); 4.87 (t, J 5.4, CH2OH, (2R,4S,5S)); 4.84 (t, J 5.7, CH2OH, (2S,4S,5S));
4.68 (d, J(5.4) 8.1, HÀC(5), (2R,4S,5S)); 4.64 (d, J(5,4) 8.1, HÀC(5), (2S,4S,5S)); 3.61 (m, CH2OH,
(2R,4S,5S)); 3.58 (m, CH2OH, (2S,4S,5S)); 3.01 (m, HÀC(4), NH, (2R,4S,5S)); 2.96 (m, HÀC(4), NH,