G. S. Coumbarides et al. / Tetrahedron Letters 46 (2005) 2897–2902
2901
and 18.6 (CH3), found MH+, 296.1286; C18H18NO3 re-
quires 296.1287. Evaporation of the resulting organic
solution gave the (R,S)-oxazolidinone syn-215 (49 mg,
60%) as an oil; Rf [light petroleum (40–60 ꢁC):ether
22
(1:1)] 0.50; ½aꢁ ꢀ24.7 (c 0.73, CHCl3); mmax(CHCl3)/
D
cmꢀ1 1774 (CO), 1703 (CO), 1601 (Ph), 1559 (Ph) and
1489 (Ph); dH(250 MHz; CDCl3) 7.39–7.19 (5H, m,
5 · CH; Ph), 5.14 (1H, q, J 7.0, CHCO), 4.92–4.46
(1H, m, CHN), 4.24 (1H, t, J 8.8, CHAHBO), 4.10
(1H, dd, J 8.8 and 3.5, CHAHBO), 2.24–2.12 (1H, m,
CH(CH3)2), 1.47 (3H, d, J 6.9, CH3CHCO), 0.79 (3H,
d, J 7.0, CH3CHCH3) and 0.46 (3H, d, J 6.9,
CH3CHCH3); dC (62.9 MHz; CDCl3) 174.5 (C@O),
153.5 (C@O), 140.5 (i-CH; Ph), 128.6, 128.1 and 127.2
(3 · CH; Ph), 62.9 (CHN), 58.1 (CH2O), 43.3 (CHCO),
27.9 (CH(CH3)2), 18.7, 17.8 and 14.1 (3 · CH3), found
MH+, 262.1432; C15H20NO3 requires 262.1443.
Figure 1. ORTEP diagram of oxazolidinone adduct syn-23.
Acknowledgements
We are grateful to the EPSRC for a studentship (to
Y.Y.), The Royal Society and The University of London
Central Research Fund for their financial support
(to J.E.), Pfizer for a summer studentship and the
EPSRC National Mass Spectrometry Service (Swansea)
for accurate mass determinations.
References and notes
1. (a) Noyori, R.; Nagai, K.; Kitamura, M. J. J. Org. Chem.
1987, 52, 3176; (b) Stille, J. K.; Parinello, G. J. J. Mol.
Catal. 1983, 21, 203; (c) Alper, H.; Nathalie, H. J. Am.
Chem. Soc. 1990, 112, 2803; (d) Hiyami, T.; Wasake, N.
Tetrahedron Lett. 1985, 26, 3259; (e) Larson, R. D.;
Corely, E. G.; Davis, P.; Reider, P. J.; Grabowski, E. J. J.
J. Am. Chem. Soc. 1989, 111, 7650; (f) Kumar, A.;
Salunke, R. V.; Rane, R. A.; Dike, S. Y. J. Chem. Soc.,
Chem. Commun. 1991, 485.
Figure 2. ORTEP diagram of oxazolidinone adduct syn-24.
Representative experimental procedure. Parallel kinetic
resolution of active ester (rac)- 21 using oxazolidinones
syn- 2 and syn- 23: n-BuLi (0.25 mL, 2.5 M in hexane,
0.62 mmol) was added to a stirred solution of oxazolid-
inones (S)-4 (40 mg, 0.31 mmol) and (R)-14 (51 mg,
0.31 mmol) in THF (2 mL) at ꢀ78 ꢁC. After stirring
for 1 h, a solution of pentafluorophenyl 2-phenylpropio-
nate (rac)-21 (0.2 g, 0.62 mmol) in THF (2 mL) was
slowly added. The resulting solution was stirred for a
further 2 h at ꢀ78 ꢁC. The reaction was quenched with
water (10 mL) and extracted with ether (2 · 20 mL).
The combined organic layers were dried (over MgSO4)
and evaporated under reduced pressure. The residue
was purified by trituration using light petroleum (40–
60 ꢁC):diethyl ether (1:1), which gave, after filtration,
the (S,R)-oxazolidinone syn-2315 (55 mg, 60%) as a
2. (a) Evans, D. A.; Ennis, M. D.; Mathrp, D. J. J. Am.
Chem. Soc. 1982, 104, 1737; (b) Evans, D. A. Aldrichim.
Acta 1982, 15, 23.
3. Yohannes, Y. Ph.D. Thesis, University of London, 2004.
4. Coumbarides, G. S.; Eames, J.; Flinn, A.; Northen, J.;
Yohannes, Y. Tetrahedron Lett. 2005, 46, 849.
5. For a comprehensive study into the conformational effects
of oxazolidinones see: Bull, S. D.; Davies, S. G.; Key,
M.-S.; Nicholson, R. L.; Savory, E. D. Chem. Commun.
2000, 1721. It appears this diastereoselectivity is lowered
to 92:8 (anti-2:syn-2) by quenching the resulting lithium
enolate with MeI at 0 ꢁC.
6. (a) Davies, S. G.; Sanganee, H. Tetrahedron: Asymmetry
1995, 6, 671; (b) Bull, S. D.; Davies, S. G.; Jones, S.;
Polywka, M. E. C.; Prasad, R. S.; Sanganee, H. Synlett
1988, 519; (c) Bull, S. D.; Davies, S. G.; Jones, S.;
Sanganee, H. J. Chem. Soc., Perkin. Trans. 1 1999, 387.
7. Seebach, D.; Hintermann, T. Helv. Chim. Acta 1998, 81,
2093.
8. For a related kinetic resolution see: Fukuzawa, S.-I.;
Chion, Y.; Yokoyama, T. Tetrahedron: Asymmetry 2002,
13, 1645.
9. Bew, S. P.; Davies, S. G.; Fukuzawa, S.-I. Chirality 2000,
12, 483.
10. For recent reviews see: (a) Eames, J. Angew. Chem., Int.
Ed 2000, 39, 885; (b) Eames, J. In Parallel Kinetic
Resolutions In Organic Synthesis Highlights; VCH-Wiley:
white solid; mp = 140–142 ꢁC; Rf [light petroleum (40–
27
60 ꢁC):ether (1:1)] 0.42; ½aꢁ 88.5 (c 4.0, CHCl3); mmax
D
(CHCl3)/cmꢀ1 1778 (CO), 1701 (CO) and 1601 (Ph);
dH (270 MHz; CDCl3) 7.29–7.21 (10H, m, 10 · CH;
2 · Ph), 5.45 (1H, dd, J 9.0 and 5.1, CHN), 5.09 (1H,
q, J 6.9, CHCH3), 4.63 (1H, t, J 9.0, CHAHBCH),
4.08 (1H, dd, J 9.0 and 5.1, CHAHBCH) and 1.39 (3H,
d, J 6.9, CH3CH); dC (62.9 MHz; CDCl3) 173.7
(C@O), 153.2 (C@O), 139.9 (i-CH; Ph), 138.3 (i-CH;
Ph), 128.9, 128.7, 128.5, 128.2, 127.1 and 125.9
(6 · CH; Ph), 69.6 (NCH), 57.9 (CH2O), 43.9 (CHCO)