104
G. S. Coumbarides et al.
LETTER
MeO
+
O
O
O
O
O
1. n-BuLi
THF, –78 °C
N
O
N
O
HN
R
O
2. (R)-12
(S)-17
Me
syn-
Adducts
H
H
Me
R
R
(rac)-
(2 equiv)
syn-
Adducts
derived from (S)-17
Entry
1
Oxazolidinones
derived from (R)-12
(rac)-1; R = Ph
syn-:anti-13; 95:5 (65%)
syn-:anti-21; 95:5 (61%)
syn-:anti-22; 95:5 (59%)
syn-:anti-23; 95:5 (59%)
2
3
(rac)-14; R= i-Pr
syn-:anti-15; 95:5 (57%)
syn-:anti-20; 95:5 (55%)
(rac)-16; R = CO2Et
Scheme 8 Parallel kinetic resolution of racemic oxazolidinones 1, 14 and 16 using quasi-enantiomeric active esters (R)-12 and (S)-17
O
O
DCC
OC6F5
OH
+
C6F5OH
CH2Cl2
Me
H
Me
H
(R)-25; 79%
(R)-24
MeO
O
O
O
O
O
1. n-BuLi
THF, –78 °C
N
O
HN
Ph
O
N
O
+
Me
H
2. (S)-17
(R)-25
H
Me
Ph
Ph
syn-21
syn-:anti-; 95:5 (49%)
syn-26
syn-:anti-; >95:<5 (52%)
(rac)-1
(2 equiv)
Scheme 9 Parallel kinetic resolution of racemic oxazolidinone 1 using quasi-enantiomeric active esters (S)-17 and (R)-25
(6) Davies, S. G.; Diez, D.; El Hammouni, M. M.; Garner, A. C.;
Acknowledgment
Garrido, N. M.; Long, M. J. C.; Morrison, R. M.; Smith, A.
D.; Sweet, M. J.; Withey, J. M. Chem. Commun. 2003, 2410.
(7) Coumbarides, G. S.; Dingjan, M.; Eames, J.; Flinn, A.;
Northen, J.; Yohannes, Y. Tetrahedron Lett. 2005, 46, 2897.
(8) (a) Coumbarides, G. S.; Eames, J.; Flinn, A.; Northen, J.;
Yohannes, Y. Tetrahedron Lett. 2005, 46, 849; and
references therein. (b) Yohannes, Y. PhD Thesis; University
of London: UK, 2004. (c) Fukuzawa, S.-I.; Chino, Y.;
Yokoyama, T. Tetrahedron: Asymmetry 2002, 13, 1645.
(9) Experimental Section: Representative Procedure for the
Parallel Kinetic Resolution of Oxazolidinone (rac)-1
Using quasi-Enantiomeric Profen Esters (S)-17 and (R)-
25.
We are grateful to the EPSRC, Onyx Scientific Limited and Queen
Mary, University of London for studentships (to M.D. and Y.Y.),
The Royal Society and The University of London Central Research
Fund for their financial support (to J.E.), and the EPSRC National
Mass Spectrometry Service (Swansea) for accurate mass determina-
tions.
References and Notes
(1) New address: Department of Chemistry, University of Hull,
Kingston upon Hull, HU6 7RX, UK.
(2) (a) Eames, J. Angew. Chem. Int. Ed. 2000, 39, 885; and
references therein. (b) Dehli, J.; Gotor, V. Chem. Soc. Rev.
2002, 31, 365. (c) Vedejs, E.; Jure, M. Angew. Chem. Int.
Ed. 2005, 44, 3974. (d) For a review into the separation of
enantiomers, see: Fogassy, E.; Nogradi, M.; Palovicsc, E.;
Schindlerc, J. Synthesis 2005, 20, 1555.
(3) (a) Brandt, J.; Jochum, C.; Ugi, I.; Jochum, P. Tetrahedron
1997, 33, 1353. (b) Vedejs, E.; Rozners, E. J. Am. Chem.
Soc. 2001, 123, 2428. (c) Vedejs, E.; Daugulis, O.; Mackay,
J. A.; Rozners, E. Synlett 2001, 1499. (d) Davies, S. G.;
Garner, A. C.; Long, M. J. C.; Smith, A. D.; Sweet, M. J.;
Withey, J. M. Org. Biomol. Chem. 2004, 2, 3355.
n-BuLi (0.61 mL, 2.5 M in hexane, 1.52 mmol) was added
to a stirred solution of oxazolidinone (rac)-1 (0.18 g, 1.08
mmol) in THF (2 mL) at –78 °C. After stirring for 1 h, a
solution of active esters (S)-17 (0.22 g, 0.55 mmol) and (R)-
25 (0.20 g, 0.55 mmol) in THF (2 mL) were slowly added.
The resulting solution was stirred for a further 2 h at –78 °C.
The reaction was quenched with H2O (10 mL) and extracted
with Et2O (2 × 20 mL). The combined organic layers were
dried (over MgSO4) and evaporated under reduced pressure.
The residue was purified by flash column chromatography
eluting with light PE (40–60 °C)–Et2O (1:1) to give
oxazolidinone syn-21 (101 mg, 49%) as a white solid and
oxazolidinone syn-26 (99 mg, 52%) as a white solid.
Oxazolidinone syn-21: mp 168–170 °C; Rf = 0.19 [light PE
(40–60 °C)–Et2O (1:1)]; [a]D24 +166.2 (c 1.5, CHCl3). IR
(CHCl3): nmax = 1780 and 1706 (CO), 1632, 1605 and 1500
(e) Zhang, Q. S.; Curran, D. P. Chem.–Eur. J. 2005, 4866.
(4) Liao, L.; Zhang, F.; Dmitrenko, O.; Bach, R. D.; Fox, J. M.
J. Am. Chem. Soc. 2004, 126, 4490.
(5) Vedejs, E.; Chen, X. J. Am. Chem. Soc. 1997, 119, 2584.
Synlett 2006, No. 1, 101–105 © Thieme Stuttgart · New York