3152
S. Sugiyama et al. / Tetrahedron: Asymmetry 15 (2004) 3149–3153
mixture was used in the next reaction without further
separation. Characteristic signals of H NMR spectrum
4.3. Removal of the 1-(1-naphthyl)ethyl groups
1
(300MHz, CDCl3) d (major): 1.52 (3H, d, J = 6.6Hz,
Me), d (minor): 1.43 (3H, d, J = 6.6Hz, Me).
Methanesulfonic acid (257mg, 2.30mmol) and anisole
(129mg, 1.15mmol) were added to a stirred solution
of 5a (86.2mg, 0.23mmol) in nitromethane (2.3mL),
and the mixture stirred for 6h at 50ꢁC. The reaction
mixture was poured into saturated aqueous sodium
hydrogen carbonate and extracted twice with dichloro-
methane. The organic extracts were combined, dried
over magnesium sulfate, and concentrated in vacuo.
The residue (139mg) was purified with silica gel column
chromatography (chloroform) to give a pure (ꢀ)-1
(46.0mg, 90%, >98% ee) as colorless needles.
4.2. One-pot silylation, cyclization and desilylation giving
5a and 6a from 8 and 9
tert-Butyldimethylchlorosilane (115mg, 0.76mmol) was
added to a mixture of 8 and 9 (223mg, 0.64mmol), tri-
ethylamine (96mg, 0.95mmol) and DMAP (7.3mg,
60lmol) in dichloromethane (6.4mL). After the mixture
was stirred at room temperature for 30h, 1,1-carbonyl
bis-1H-imidazole (CDI) (208mg, 1.28mmol) was added
portionwise to the mixture. After being stirred for four
days at room temperature, dichloromethane (15mL)
and 6M hydrochloric acid (20mL) were added to the
mixture, and the resulting mixture stirred for 23h at
room temperature. The reaction mixture was then ex-
tracted three times with dichloromethane. The extracts
were combined, dried over magnesium sulfate and con-
centrated in vacuo. The residue (257mg) was chromato-
graphed on silica gel (hexane/ethyl acetate, 4:1) to give
5a (70.0mg, 29%) and 6a (38.5mg, 16%).
4.3.1. (ꢀ)-Cytoxazone, (4R,5R)-hydroxymethyl-(4-methoxy-
phenyl)oxazolidin-2-one
(ꢀ)-1. Mp
115–116ꢁC.
D
26
D
23
½aꢁ ¼ ꢀ70:9 (c 0.87, MeOH) {Ref. 1 ½aꢁ ¼ ꢀ71 (c
1
0.100, MeOH)}. H NMR (DMSO-d6) d: 8.00 (1H, s,
NH), 7.14 (2H, d, J = 8.4Hz, Ar), 6.92 (2H, d,
J = 8.8Hz, Ar), 4.89 (1H, d, J = 8.4Hz, NCHAr), 4.80
(1H, t, J = 3.2Hz, OH), 4.66–4.71 (1H, m, OCHCH2OH),
3.74 (3H, s, OMe), 2.94–2.97 (2H, m, COCH2). 13C NMR
(DMSO-d6) d: 158.7 (C@O), 158.4 (Ar, C), 129.0 (Ar, C),
127.7 (Ar, CH · 2), 113.4 (Ar, CH · 2), 79.9 (OCH),
61.0 (CH2), 56.1 (NHCH), 55.0 (OMe). MS (FAB) (gly-
cerol) m/z: 224 [(M+1)+]. HRMS (FAB) (glycerol)
calcd for C11H14NO4 (M+1): 224.0923. Found: 224.0915.
4.2.1. (4R,5R)-5-Hydroxymethyl-4-(4-methoxyphenyl)-3-
[(R)-1-(1-naphthyl)ethyl]oxazolidin-2-one 5a. Rf = 0.20
(hexane/ethyl acetate, 1:1). Colorless needles, mp 169–
30
170ꢁC. ½aꢁ ¼ ꢀ104:9 (c 1.7, CHCl3). 1H NMR (CDCl3)
4.3.2. (+)-Cytoxazone, (4S,5S)-hydroxymethyl-(4-meth-
oxyphenyl)oxazolidin-2-one (+)-1. According to the
method described above, (+)-1 (35.4mg, 86%, >98%
ee) was synthesized from 6a (69.4mg, 0.18mmol).
D
d: 8.00 (1H, d, J = 8.1Hz, Ar), 7.88 (1H, d, J = 7.8Hz,
Ar), 7.84 (1H, d, J = 8.1Hz, Ar), 7.49–7.57 (2H, m,
Ar), 7.38 (1H, t, J = 7.6Hz, Ar), 7.30 (1H, br s, Ar),
7.14 (1H, d, J = 6.8Hz, Ar), 6.65–7.00 (2H, br m, Ar),
6.40–6.65 (1H, br s, Ar), 5.88 (1H, q, J = 6.8Hz, ArCH),
4.27–4.32 (1H, m, OCHCH2OH), 3.81 (3H, s, OMe),
3.77 (1H, d, J = 8.4Hz, CHAr), 3.36 (1H, dd, J = 11.9,
8.0Hz, HOCHH), 3.00 (1H, dd, J = 11.9, 4.4Hz,
HOCHH), 1.34 (3H, d, J = 6.8Hz, Me). 13C NMR
(CDCl3) d: 159.7, 157.1, 133.7, 133.6, 131.3, 128.9,
128.8, 127.7, 127.0, 125.9, 124.5, 124.4, 122,6, 113.9,
82.4, 78.7, 61.5, 59.0, 55.2, 49.2, 18.4. IR (CHCl3)
cmꢀ1: 1770, 1610, 1550, 1400, 1250, 1030. MS (FAB)
(glycerol) m/z: 378 [(M+1)+]. HRMS (FAB) (glycerol)
calcd for C23H24NO4 (M+1): 378.1705. Found:
378.1702.
26
D
1
½aꢁ ¼ þ70:9 (c 0.7, CH3OH). H NMR spectrum was
in good agreement with that of (ꢀ)-1.
Acknowledgements
The authors wish to thank the staff of the Analysis Cen-
ter of Meiji Pharmaceutical University for performing
the mass spectra (Ms. T. Koseki).
References
1. (a) Kakeya, H.; Morishita, M.; Kobinata, K.; Osono, M.;
Ishizuka, M.; Osada, H. J. Antibiot. 1998, 51, 1126–1128;
(b) Kakeya, H.; Morishita, M.; Koshino, H.; Morita, T.-i;
Kobayashi, K.; Osada, H. J. Org. Chem. 1999, 64, 1052–
1053.
2. (a) Miyata, O.; Asai, H.; Naito, T. Synlett 1999, 1915–
1916; (b) Miyata, O.; Koizumi, T.; Asai, H.; Iba, R.;
Naito, T. Tetrahedron 2004, 60, 3893–3914.
4.2.2. (4S,5S)-5-Hydroxymethyl-4-(4-methoxyphenyl)-3-
[(R)-1-(1-naphthyl)ethyl]oxazolidin-2-one 6a. Rf = 0.12
(hexane/ethyl acetate, 1:1). Colorless amorphous solid.
31
1
½aꢁ ¼ þ7:6 (c 1.4, CHCl3). H NMR (CDCl3) d: 8.07
D
(1H, d, J = 8.4Hz, Ar), 7.67 (1H, d, J = 8.0Hz, Ar),
7.54 (1H, d, J = 8.4Hz, Ar), 7.36–7.48 (3H, m, Ar),
7.17–7.21 (1H, m, Ar), 6.54 (2H, br d, J = 7.2Hz, Ar),
6.30 (2H, br s, Ar), 5.68 (1H, q, J = 6.8Hz, ArCH),
4.66 (2H, m, OCHCH2OH and NCHAr), 3.62 (3H, s,
OMe), 3.32–3.37 (1H, m, HOCHH), 3.05–3.09 (1H, m,
HOCHH), 1.86 (3H, d, J = 7.2Hz, Me). 13C NMR
(CDCl3) d: 158.8, 157.3, 134.8, 133.3, 131.3, 128.3,
126.2, 125.7, 125.4, 124.6, 124.1, 123.1, 112.9, 78.2,
61.9, 59.4, 55.1, 49.0, 17.9. IR (CHCl3) cmꢀ1: 1740,
1610, 1260, 1030. MS (FAB) (glycerol) m/z: 378
[(M+1)+]. HRMS (FAB) (glycerol) calcd for
C23H24NO4 (M+1): 378.1705. Found: 378.1708.
3. Hamersak, Z.; Ljubovic, E.; Mercep, M.; Mesic, M.;
Sunjic, V. Synthesis 2001, 1989–1992.
4. (a) Sakamoto, Y.; Shiraishi, A.; Seonhee, J.; Nakata, T.
Tetrahedron Lett. 1999, 40, 4203–4206; (b) Seki, M.; Mori,
K. Eur. J. Org. Chem. 1999, 2965–2967; (c) Park, J. N.;
Ko, S. Y.; Koh, H. Y. Tetrahedron Lett. 2000, 41, 5553–
5556; (d) Madhan, A.; Kumar, A. R.; Rao, B. V.
Tetrahedron: Asymmetry 2001, 12, 2009–2011; (e) Carda,
M.; Gonzalez, F.; Sanchez, R.; Marco, J. A. Tetrahedron:
Asymmetry 2002, 13, 1005–1010; (f) Carter, P. H.;
LaPorte, J. R.; Scherle, P. A.; Decicco, C. P. Bioorg.
Med. Chem. Lett. 2003, 13, 1237–1239; (g) Kumar, A. R.;