Novel stereoselective synthesis of functionalized oxazolidinones from chiral aziridines

Article abstract of DOI:10.1021/jo025545l

Enantiomerically pure N-(R)-α-methylbenzyl-4(R)-(chloromethyl)oxazolidinones (4R)-5a-k were synthesized in one step and high yields from various aziridine-2-methanols (S)-2a-k by intramolecular cyclization with phosgene. The α-methylbenzyl substituent on the nitrogen was easily cleaved to give both enanatiomers of 4-(chloromethyl)oxazolidinones (R)-7a and (S)-7a. (R)-7a was used for the efficient syntheses of (L)-homophenylalaninol analogues (S)-12a-j. We also applied the same methodology to prepare oxazolidinones 9a-c containing a heteroatom-substituted alkyl group at C-4 in high yields.

Full text of DOI:10.1021/jo025545l

Novel Ster eoselective Syn th esis of F u n ction a lized Oxa zolid in on es
fr om Ch ir a l Azir id in es†
Chan Sun Park, Min Sung Kim, Tae Bo Sim, Do Kyu Pyun,‡ Cheol Hae Lee,‡
Daeock Choi,§ and Won Koo Lee*
Department of Chemistry, Sogang University, Seoul 121-742, Korea
J ae-Won Chang and Hyun-J oon Ha*
ChemBioNex, HUFS BI, Wangsan, Yongin, Kyunggi 449-791, Korea
Received J anuary 22, 2002
Enantiomerically pure N-(R)-R-methylbenzyl-4(R)-(chloromethyl)oxazolidinones (4R)-5a -k were
synthesized in one step and high yields from various aziridine-2-methanols (S)-2a -k by intramo-
lecular cyclization with phosgene. The R-methylbenzyl substituent on the nitrogen was easily cleaved
to give both enanatiomers of 4-(chloromethyl)oxazolidinones (R)-7a and (S)-7a . (R)-7a was used
for the efficient syntheses of (L)-homophenylalaninol analogues (S)-12a -j. We also applied the same
methodology to prepare oxazolidinones 9a -c containing a heteroatom-substituted alkyl group at
C-4 in high yields.
I. In tr od u ction
many important asymmetric syntheses4 and as biologi-
cally active compounds themselves.5 Especially, an enan-
tiomerically pure 4-(halomethyl)oxazolidin-2-one has
played a key role as an alanine or alaninol synthon in
the synthesis of (-)-Slaframine,6 nonprotein R-amino acid
derivatives such as E- or Z-â,γ-unsaturated amino alco-
hols,7 silicon-containing alanines,8 and chiral â-amido
alkylzinc iodides.9 Also, chiral oxazolidinones function-
alized at the 4- and 5-position are very useful and
generally applicable in organic and medicinal chemistry
R-Amino acids and their derivatives continue to attract
much attention because of the biological and biochemical
properties, prompting many organic chemists to develop
useful and enantioselective methods for the synthesis of
various structurally modified R-amino acids.1,2 Chiral
oxazolidinones are prepared from R-amino acids, and
functionalized chiral oxazolidin-2-ones have been used
as versatile chiral synthons in asymmetric syntheses of
biologically active compounds or their synthetic inter-
mediates.3 They are also used as chiral auxiliaries in
(4) (a) Friestad, G. K.; Qin, J . J . Am. Chem. Soc. 2000, 122, 8329.
(b) Bull, S. D.; Davies, S. G.; Nicholson, R. L.; Sanganee, H. J .; Smith
A. D. Tetrahedron: Asymmetry 2000, 11, 3475. (c) Bravo, P.; Fustero,
S.; Guidetti, M.; Volonterio, A.; Zanda, M. J . Org. Chem. 1999, 64,
8731-8735. (d) Bull, S. D.; Davies, S. G.; J ones, S.; Sanganee, H. J . J .
† In memory of the late Professor Henry Rapoport.
‡ Korea Research Institute of Chemical Technology.
§ Sunchon National University.
Chem. Soc., Perkin Trans. 1 1999, 387-398. (e) Davies, S. G.;
(1) (a) Williams, R. M. Synthesis of Optically Active R-Amino Acids;
Pergamon Press: Oxford, 1989. (b) Duthaler, R. O. Tetrahedron 1994,
50, 1539.
(2) (a) Wagner, I.; Musso, H. Angew. Chem., Int. Ed. Engl. 1983,
22, 816. (b) Izumi, Y.; Chibata, I.; Itoh, T. Angew. Chem., Int. Ed. Engl.
1978, 17, 176.
Sanganee, H. J .; Szolcsanyi, P. Tetrahedron 1999, 55, 3337-3354. (f)
Reddy, G. V.; Rao, G. V.; Iyengar, D. S. Chem. Commun. 1999, 317.
(g) Regan, A. C. J . Chem. Soc., Perkin Trans. 1 1999, 357. (h) Gibson,
C. L.; Gillon, K.; Cook, S. Tetrahedron Lett. 1998, 39, 6733. (i)
Fonquerna, S.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron:
Asymmetry 1997, 8, 1685. (j) Lu¨tzen, A.; Ko¨ll, P. Tetrahedron: Asym-
metry 1997, 8, 1193. (k) Lu¨tzen, A.; Ko¨ll, P. Tetrahedron: Asymmetry
1997, 8, 29. (l) Ager, D. J .; Prakash, I.; Schaad, D. R. Aldrichim. Acta
1997, 30, 3. (m) Ager, D. J .; Prakash, I.; Schaad, D. R. Chem. Rev.
1996, 96, 835. (n) Ko¨ll, P.; Lu¨tzen, A. Tetrahedron: Asymmetry 1996,
7, 637. (o) Evans, D. A. Aldrichim. Acta 1982, 15, 23.
(3) (a) Bach, J .; Bull, S. D.; Davies, S. G.; Nicholson, R. L.; Sanganee,
H. J .; Smith, A. D. Tetrahedron Lett. 1999, 40, 6677. (b) O’Hagan, D.;
Tavasli, M. Tetrahedron: Asymmetry 1999, 10, 1189. (c) Lohray, B.
B.; Baskaran, S.; Rao, B. S.; Reddy, B. Y.; Rao, I. N. Tetrahedron Lett.
1999, 40, 4855. (d) Barbachyn, M. R.; Hutchinson, D. K.; Brickner, S.
J .; Cynamon, M. H.; Kilburn, J . O.; Klemens, S. P.; Glickman, S. E.;
Grega, K. C.; Hendges, S. K.; Toops, D. S.; Ford, C. W.; Zurenko, G. E.
J . Med. Chem. 1996, 39, 680. (e) Brickner, S. J .; Hutchinson, D. K.;
Barbachyn, M. R.; Manninen, P. R.; Ulanowicz, D. A.; Garmon, S. A.;
Grega, K. C.; Hendges, S. K.; Toops, D. S.; Ford, C. W.; Zurenko, G. E.
J . Med. Chem. 1996, 39, 673. (f) Grega, K. C.; Barbachyn, M. R.;
Brickner, S. J .; Mizsak, S. A. J . Org. Chem. 1995, 60, 5255. (g) Seneci,
P.; Caspani, M.; Ripamonti, F.; Ciabatti, R. J . Chem. Soc., Perkin
Trans. 1 1994, 2345. (h) Park, C.-H.; Brittelli, D. R.; Wang, C. L.-J .;
Marsh, F. D.; Gregory, W. A.; Wuonola, M. A.; McRipley, R. J .; Eberly,
V. S.; Slee, A. M.; Forbes, M. J . Med. Chem. 1992, 35, 1156. (i) Gregory,
W. A.; Brittelli, D. R.; Wang, C. L.-J .; Kezar, H. S.; Carlson, R. K.;
Park, C.-H.; Corless, P. F.; Miller, S. J .; Rajagopalan, P.; Wuonola, M.
A.; McRipley, R. J .; Eberly, V. S.; Slee, A. M.; Forbes, M. J . Med. Chem.
1990, 33, 2569. (j) Gregory, W. A.; Brittelli, D. R.; Wang, C. L.-J .;
Wuonola, M. A.; McRipley, R. J .; Eustice, D. C.; Eberly, V. S.;
Bartholomew, P. T.; Slee, A. M.; Forbes, M. J . Med. Chem. 1989, 32,
1673.
(5) (a) J andu, K. S.; Barrett V.; Brockwell, M.; Cambridge, D.;
Farrant, D. R.; Foster, C.; Giles, H.; Glen, R. C.; Hill, A. P.; Hobbs, H.;
Honey, A.; Martin, G. R.; Salmon, J .; Smith, D.; Woollard, P.; Selwood,
D. L. J . Med. Chem. 2001, 44, 681. (b) Iwama, S.; Segawa, M.; Fujii,
S.; Ikeda, K.; Katsumura, S. Bioorg. Med. Chem. Lett. 1998, 8, 3495
(c) Brickner, S. J .; Hutchinson, D. K.; Barbachyn, M. R.; Manninen,
P. R.; Ulanowicz, D. A.; Garmon, S. A.; Grega, K. C.; Hendges, S. K.;
Toops, D. S.; Ford, C. W.; Zurenko, G. E. J . Med. Chem. 1996, 39, 673.
(d) Barbachyn, M. R.; Hutchinson, D. K.; Brickner, S. J .; Cynamon,
M. H.; Klemens, S. P.; Glickman S. E.; Grega, K. C.; Hendges, S. K.;
Toops, D. S.; Ford, C. W.; Zurenko, G. E. J . Med. Chem. 1996, 39, 680.
(6) Sibi, M. P.; Christensen, J . W.; Li, B.; Renhowe, P. A. J . Org.
Chem. 1992, 57, 4329.
(7) Sibi, M. P.; Renhowe, P. A. Tetrahedron Lett. 1990, 35, 7407.
(8) Sibi, M. P.; Harris, B. J .; Shay J . J .; Hajra, S. Tetrahedron 1998,
54, 7221.
(9) Duddu, R.; Eckhardt, M.; Furlong, M.; Knoess, H. P.; Berger,
S.; Knochel, P. Tetrahedron 1994, 50, 2415.
10.1021/jo025545l CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/16/2002
J . Org. Chem. 2003, 68, 43-49
43

Park et al.
SCHEME 2
F IGURE 1.
SCHEME 1
SCHEME 3
(Figure 1). Despite their various usefulness and general
applicability, there are only a few preparative methods
available from L- and D-serine,6-8,10 N-sulfonylated allylic
carbamates,11 amino alcohols,12 a chiral aziridine,13 and
allylic amine.14 The requirement of a more efficient
preparative pathway to enantiomerically pure function-
alized oxazolidinones prompted us to develop a new
efficient synthetic route.
In this report we describe a novel efficient preparative
pathway to enantiomerically pure functionalized oxazo-
lidinones from aziridine-2(S)- and 2(R)-methanols.
II. Resu lts a n d Discu ssion
Recently, we reported the preparation and elaboration
of enantiomerically pure aziridine-2(S)- and 2(R)-car-
boxylates obtained from the reaction of optically pure
R-methylbenzylamine and ethyl 2,3-dibromopropionate.15
However, if we use the commercially available aziridine-
2(R)-carboxylate (R)-1 various aziridine-2(R)-methanols
(R)-2a -k are readily available from organometallic ad-
dition to the corresponding aziridine-2(R)-carboxaldehyde
(R)-3 and directly to the aziridine-2(R)-carboxylate (R)-1
(Scheme 1).16
Since we observed highly regioselective nucleophilic
ring opening of aziridine-2-methanols in the presence of
proton or Lewis acid, we selected phosgene as the
intramolecular cyclizing agent of the amino alcohol
moiety to form a cyclic carbamate with regioselective ring
opening of the aziridine by the chloride ion. However, the
reaction of phosgene with the enantiomerically pure
aziridine 2(R)-methanol (R)-2a provided a mixture of the
oxazolidinone (S)-5 through the bicyclic intermediate
(R)-4 and the recovered starting material (R)-2a . The
recovered starting material (R)-2a might have been
formed from base workup of the quaternary ammonium
salt (S)-6 which originated from ring opening of the
aziridine-2(R)-methanol (R)-2a by in situ generated HCl.
We varied equivalents of phosgene, bases, reaction
solvents, and reaction temperatures to obtain the opti-
mum condition for the 4(S)-chloromethyloxazolidin-2-one
(S)-5. We found that the elimination of HCl generated
in situ by treating (R)-2a with NaH and 2 equiv of
phosgene in THF at - 78 to 0 °C (entry 6) provided the
best result in terms of selectivity and yield (Scheme 2).
We applied the optimized reaction condition to various
aziridine-2(S)-methanols (S)-2a -k , which were prepared
from nucleophilic additions to the corresponding aziri-
dine-2(S)-carboxaldehyde, to prepare 4(R)-(chloromethyl)-
5-substituted-2-oxazolidinones (4R)-5a -k in good yields
in one step (Scheme 3). Even with a bulky tertiary alcohol
containing diphenyl group, we obtained the correspond-
ing oxazolidinone (4R)-5c in 83% yield (entry c). The
absolute configuration at C-4 of 4,5-disubstituted 2-ox-
azolidinones was indirectly established by measuring the
coupling constants of the two vicinal protons at C-4 and
C-5. It is well-known that the coupling constant of cis-
4,5-disubstituted 2-oxazolidinone is ∼7.5 Hz, whereas
that of the trans-isomer is ∼4.5 Hz.14 The coupling
(10) Sibi, M. P.; Li, B. Tetrahedron Lett. 1992, 29, 4115.
(11) Hirama, M.; Iwashita, M.; Yamazaki, Y.; Itoˆ, S. Tetrahedron
Lett. 1984, 25, 4963.
(12) Gabriele, B.; Salerno, G.; Brindisi, D.; Costa, M.; Chiusoli, G.
P. Org. Lett. 2000, 2, 625
(13) Lucarini, S.; Tomasini, C. J . Org. Chem. 2001, 66, 727.
(14) Cardillo, G.; Orena, M.; Sandri, S. J . Org. Chem. 1986, 51, 713.
(15) Lim, Y.; Lee, W. K. Tetrahedron Lett. 1995, 36, 8431.
(16) Hwang, G.; Chung, J .; Lee, W. K. J . Org. Chem. 1996, 61, 6183.
Both 2(R)- and 2(S)-aziridinecarboxylic acid menthol esters are avail-
able from ChemBioNex.
44 J . Org. Chem., Vol. 68, No. 1, 2003

Synthesis of Functionalized Oxazolidinones
SCHEME 4
SCHEME 6
SCHEME 7
SCHEME 5
the easily accessible 4(R)-(chloromethyl)-2-oxazolidinone
(R)-7a for the synthesis of various aryl-substituted ho-
mophenylalaninols.
The 4(R)-(chloromethyl)-2-oxazolidinone (R)-7a was
converted to the corresponding phosphonium salt (R)-10
in 95% yield by stirring with NaI and PPh3 in DMF at
100 °C for 24 h.7 Treatment of the phosphonium salt with
LiHMDS at -78 °C generated the ylide which was then
reacted with benzaldehyde to provide the E alkene (S)-
11a exclusively (E:Z ) 99:1) in 88% yield.7,26 The alkene
(S)-11a was reduced by catalytic hydrogenation (5% Pd/
C, H2, EtOH, rt, 12 h, 99%) to give the 4(S)-phenylethyl-
substituted oxazolidin-2-one (S)-12a which was hydro-
lyzed in aqueous EtOH by LiOH to provide the corres-
ponding (L)-homophenylalaninol (S)-13a in 92% yield
(Scheme 7).27
constants of (4R)-5g (3.0 Hz), (4R)-5h (3.1 Hz), and (4R)-
5i (3.2 Hz) for the J 4,5 were consistent with the assigned
trans configuration. Comparison of the coupling constants
of (4R)-5j (3.5 Hz) and (4R)-5k (8.0 Hz) clearly indicates
the difference between cis- and trans-4,5-disubstituted
oxazolidinones (Scheme 4).
The benzyl group on the nitrogen was successfully
removed by refluxing N-benzyl compounds [(R)-5a and
(S)-5] in the presence of anisole and CH3SO3H in hexane
to provide the free 4-(chloromethyl)oxazolidin-2-ones (R)-
7a and (S)-7 in almost quantitative yields (Scheme 5).17
We recently reported the introduction of various het-
eroatom nucleophiles at C-3 of the aziridine-2(R)-
methanol (R)-2a by highly regioselective ring opening
reaction with HOAc,18 HSPh,19 and TMSN3.20 We applied
the same protocol to prepare oxazolidinones containing
heteroatoms such as 4-acetyloxymethyl [(R)-9a ], phe-
nylthiomethyl [(S)-9b], and azidomethyl [(R)-9c] in high
yields (Scheme 6).
Once we had enantiomerically pure 4(R)-(chlorom-
ethyl)-2-oxazolidinone (R)-7a in hand we utilized it for
the synthesis of homophenylalanine and its analogues.
The preparation of enantiomerically pure homophenyla-
lanine has been accomplished by using alkenyl boronic
acid,21 organozinc,22 allylic amination,23 Rh-catalyzed
asymmetric hydrogenation,24 and Friedel-Crafts acyla-
tion.25 Since each of the methods has room for improve-
ment in terms of yield and stereoselectivity, we applied
We prepared various homophenylalaninol precursors
(S)-12a -j using this protocol with substituted benzalde-
hydes under the same reaction condition, and the results
are summarized in Scheme 8.
IV. Con clu sion
In summary, we have developed a novel methodology
to prepare functionalized oxazolidin-2-ones from a com-
(22) J ackson, R. F. W.; Moore, R. J .; Dexter, C. S. J . Org. Chem.
1998, 63, 7875. (b) Dunn, M. J .; J ackson, R. F. W.; Pietruszka, J .;
Turner, D. J . J . Org. Chem. 1995, 60, 2210. (c) J ackson, R. F. W.;
Wishart, N.; Wood, A.; J ames, K.; Wythes, M. J . J . Org. Chem. 1992,
57, 3397.
(23) Evans, P. A.; Robinson, J . E.; Nelson, J . D. J . Am. Chem. Soc.
1999, 121, 6761.
(24) (a) RajanBabu, T. V.; Ayers, T. A.; Halliday, G. A.; You, K. K.;
Calabrese, J . C. J . Org. Chem. 1997, 62, 6012. (b) Li, X.; Yeung, C.;
Chan, A. S. C.; Lee, D.; Yang, T. Tetrahedron: Asymmetry 1999, 10,
3863.
(25) Xu, Q.; Wang, G.; Wang, X.; Wu, T.; Pan, X.; Chan, A. S. C.;
Yang, T. Tetrahedron: Asymmetry 2000, 11, 2309.
(26) Sibi, M. P.; Renhowe, P. A. Tetrahedron Lett. 1990, 31, 7407.
(27) (a) Bertozzi, C. R.; Hoeprich, P. D.; Bednarski, M. D. J . Org.
Chem. 1992, 57, 6092. (b) Sibi, M. P.; Li, B. Tetrahedron Lett. 1992,
33, 4115.
(17) Sugiyama, S.; Morishita, K.; Ishii, K. Heterocycles 2001, 55, 353.
(18) Choi, S.; Lee, J .; Kim, J .; Lee, W. K. J . Org. Chem. 1997, 62,
743.
(19) Bae, J .; Shin, S.; Park, C. S.; Lee, W. K. Tetrahedron 1999, 55,
10041.
(20) Shin, S.; Han, E. Y.; Park, C. S.; Lee, W. K.; Ha, H. Tetrahe-
dron: Asymmetry 2000, 11, 3293.
(21) Petasis, N. A.; Zavialov, I. A. J . Am. Chem. Soc. 1997, 119, 445.
(b) Petasis, N. A.; Zavialov, I. A. J . Am. Chem. Soc. 1998, 120, 11798.
(28) Combret, Y.; Duflos, J .; Dupas, G.; Bourguignon, J .; Queguiner,
G. Tetrahedron: Asymmetry 1993, 4, 1635.
J . Org. Chem, Vol. 68, No. 1, 2003 45

Park et al.
was extracted with CH2Cl2 (5 × 5 mL). The combined extract
was dried over MgSO4, and the solvent was evaporated to give
the crude product as a white solid which was purified by silica
gel flash chromatography with 15% EtOAc/hexane to give 119
SCHEME 8
mg (88%) of (S)-5 as a white solid. mp ) 83-84 °C; [R]28
)
D
-13.0° (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.42-7.32
(m, 5H), 5.21 (q, J ) 7.3 Hz, 1H), 4.36-4.19 (m, 2H), 3.68-
3.64 (m, 1H), 3.52 (dd, J ) 3.5, 11.7 Hz, 1H), 3.48 (dd, J )
6.8, 11.2 Hz, 1H), 1.68 (d, J ) 7.3 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 157.8, 138.4, 128.9, 128.2, 127.2, 65.6, 54.5, 52.6, 45.1,
18.5. Anal. Calcd for C12H14ClNO2: C, 60.13; H, 5.89; N, 5.84.
Found: C, 60.14; H, 5.88; N, 5.89.
(4R)-5a . [R]29D ) +104.4° (c 1.0, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 7.43-7.30 (m, 5H), 5.17 (q, J ) 7.1 Hz, 1H), 4.35 (t,
J ) 8.7 Hz, 1H), 4.20 (dd, J ) 4.4, 9.1 Hz, 1H), 4.09-4.04 (m,
1H), 2.97 (dd, J ) 3.4, 11.3 Hz, 1H), 2.93 (dd, J ) 8.1, 11.3
Hz, 1H), 1.70 (d, J ) 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3)
δ 157.8, 140.4, 128.7, 128.1, 126.9, 65.9, 54.0, 51.5, 44.2, 16.1.
Anal. Calcd for C12H14ClNO2: C, 60.13; H, 5.89; N, 5.84.
Found: C, 60.08; H, 5.92; N, 5.83.
(4R)-5b. mp ) 72-74 °C; [R]28D ) +46.1° (c 1.0, CHCl3); 1H
NMR (500 MHz, CDCl3) δ 7.34-7.21 (m, 5H), 5.08 (q, J ) 7.1
Hz, 1H), 3.55 (dd, J ) 2.8, 8.7 Hz, 1H), 3.01 (dd, J ) 2.8, 12.0
Hz, 1H), 2.89 (dd, J ) 8.7, 12.0 Hz, 1H), 1.62 (d, J ) 7.2 Hz,
3H), 1.39 (s, 3H), 1.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
156.6, 140.6, 128.6, 127.9, 126.8, 79.9, 63.0, 51.6, 40.7, 28.8,
21.0, 16.3. Anal. Calcd for C14H18ClNO2: C, 62.80; H, 6.78; N,
5.23. Found: C, 62.82; H, 6.82; N, 5.30.
(4R)-5c. mp ) 209-210 °C; [R]26D ) -171.4° (c 1.0, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.47-7.14 (m, 15H), 4.98 (q, J )
6.8 Hz, 1H), 4.50 (dd, J ) 4.4, 4.9 Hz, 1H), 2.92 (m, 2H), 1.51
(d, J ) 7.3 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 156.0, 142.5,
140.3, 137.5, 128.7, 128.6, 128.6, 128.4, 128.13, 128.12, 128.0,
127.1, 126.6, 125.7, 86.9, 63.4, 53.6, 42.8, 17.8. Anal. Calcd
for C24H22ClNO2: C, 73.56; H, 5.66; N, 3.57. Found: C, 73.59;
H, 5.76; N, 3.44.
mercially available enantiomerically pure aziridine-2-
carboxylate and aziridine-2-carboxaldehyde through or-
ganometallic addition followed by intramolecular cycliza-
tion of the amino alcohol moiety with regiospecific ring
opening of the aziridine with phosgene. We have also
developed an efficient pathway for the preparation of
enantiomerically pure (L)-homophenylalaninol and its
analogues using a Wittig reaction and catalytic hydro-
genation from 4(R)-(chloromethyl)-2-oxazolidinone. Using
the same protocol the (D)-homophenylalaninol analogues
can be also available starting from the 4(S)-(chlorom-
ethyl)-2-oxazolidinone.
(4R)-5d . mp ) 75-76 °C; [R]26D ) -34.3° (c 1.0, CHCl3); 1H
NMR (500 MHz, CDCl3) δ 7.47-7.14 (m, 5H), 5.24 (q, J ) 7.1
Hz, 1H), 4.39 (qd, J ) 3.5, 6.3 Hz, 1H), 3.45 (m, J ) 3.6 Hz,
1H), 2.83 (dd, J ) 8.4, 11.2 Hz, 1H), 2.79 (dd, J ) 3.7, 11.2
Hz, 1H), 1.61 (d, J ) 7.1 Hz, 3H), 1.32 (d, J ) 6.3 Hz, 3H); 13
C
NMR (125 MHz, CDCl3) δ 157.1, 140.6, 128.8, 128.2, 127.0,
74.3, 60.6, 51.4, 43.9, 21.3, 16.2. Anal. Calcd for C13H16ClNO2:
C, 61.54; H, 6.36; N, 5.52. Found: C, 61.56; H, 6.43; N, 5.54.
(4R)-5e. mp ) 93 °C; [R]26D ) +28.2° (c 1.0, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.38-7.21 (m, 5H), 5.12 (q, J ) 7.2 Hz,
1H), 4.26 (m, 1H), 3.49 (m, 1H), 2.83 (dd, J ) 8.5, 11.2 Hz,
1H), 2.78 (dd, J ) 3.4, 11.3 Hz, 1H), 1.60 (d, J ) 7.1 Hz, 3H),
1.64-1.50 (m, 3H), 1.42-1.25 (m, 3H), 0.84 (t, J ) 7.0, 3H);
13C NMR (125 MHz, CDCl3) δ 157.3, 140.6, 128.8, 128.2, 127.0,
77.8, 59.0, 51.5, 44.2, 35.1, 26.3, 22.3, 16.2, 13.8; HRMS Calcd
for C16H22ClNO2 295.133907, found 295.133095.
V. Exer im en ta l Section
Gen er a l. Flash chromatography was performed with 230-
400 mesh silica gel. Melting points were determined on a
capillary melting point apparatus and are uncorrected. 1H
NMR spectra were obtained on 200, 300, and 500 MHz
spectrometers. NMR spectra were recorded in ppm (δ) related
to tetramethylsilane (δ ) 0.00) as an internal standard unless
stated otherwise and are reported as follows; chemical shift,
multiplicity (br ) broad, s ) singlet, t ) triplet, q )quartet,
m ) multiplet), coupling constant, and integration. Elemental
analyses were performed by an elemental analyzer. Optical
rotations were obtained on a digital polarimeter. Data are
(4R)-5f. mp ) 120-121 °C; [R]27 ) +18.4° (c 1.0, CHCl3);
D
1H NMR (500 MHz, CDCl3) δ 7.38-7.23 (m, 5H), 5.10 (q, J )
7.1 Hz, 1H), 3.90 (d, J ) 3.4 Hz, 1H), 3.69 (m, 1H), 2.85-2.84
(m, 2H), 1.62 (d, J ) 7.1 Hz, 3H), 0.86 (s, 9H); 13C NMR (125
MHz, CDCl3) δ 157.5, 140.6, 128.7, 128.2, 127.2, 84.3, 55.0,
51.8, 45.1, 34.4, 24.5, 16.3; HRMS Calcd for C16H22ClNO2:
295.133194, found: 295.133907.
reported as follow: [R]25 (concentration g/100 mL, solvent).
D
Solvents and liquid reagents were transferred using hypoder-
mic syringes. All other reagents and solvents used were
reagent grade. All glassware was dried in an oven at 150 °C
prior to use. Methylene chloride and triethylamine were dried
over calcium hydride prior to use. Small and medium scale
purifications were performed by flash chromatography.
P r ep a r a tion of 4(S)-(Ch lor om eth yl)-3-(1′(R)-r-m eth -
ylben zyl)oxa zolid in -2-on e (S)-5. To a solution of [1-(1′(R)-
R-methylbenzyl)aziridin-2(R)-yl]methanol (R)-2a (100 mg, 0.564
mmol) in 2.82 mL of THF under nitrogen atmosphere was
added a 60% oil dispersion of NaH (68 mg, 1.693 mmol) at 0
°C. The mixture was stirred for 1 h at 0 °C and then cooled to
-78 °C. To the mixture was slowly added phosgene solution
(0.60 mL, 1.13 mmol, 1.89 M in toluene) at -78 °C. The
mixture was stirred for 2 h at -78 °C then quenched with
water and warmed to room temperature. The aqueous layer
(4R)-5g. mp ) 92 °C; [R]26D ) -33.2° (c 1.0, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.36-7.18 (m, 10H), 5.28 (d, J ) 3.0 Hz,
1H), 5.16 (q, J ) 7.1 Hz, 1H), 3.70 (m, 1H), 2.98 (dd, J ) 8.6,
11.4 Hz,1H), 2.85 (dd, J ) 3.0, 11.4 Hz, 3H), 1.48 (d, J ) 7.1
Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 157.3, 140.2, 138.9,
129.0, 128.9, 128.8, 128.4, 127.2, 125.0, 78.0, 62.2, 51.7, 44.0,
16.3. Anal. Calcd for C18H18ClNO2: C, 68.46; H, 5.75; N, 4.44.
Found: C, 68.44; H, 5.78; N, 4.43.
(4R)-5h . mp ) 81-82 °C; [R]26D ) -29.1° (c 1.0, CHCl3); 1H
NMR (500 MHz, CDCl3) δ 7.36-7.00 (m, 9H), 5.26 (d, J ) 3.1
Hz, 1H), 5.16 (q, J ) 7.1 Hz, 1H), 3.66 (m, 1H), 2.88 (dd, J )
8.9, 11.5 Hz, 1H), 2.84 (dd, J ) 3.1, 11.4 Hz, 1H), 1.49 (d, J )
7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 163.8, 161.9, 157.1,
46 J . Org. Chem., Vol. 68, No. 1, 2003

Synthesis of Functionalized Oxazolidinones
140.1, 134.8, 128.9, 128.5, 127.1, 127.0, 126.9, 116.1, 115.9,
77.4, 62.2, 51.8, 43.8, 16.3. Anal. Calcd for C18H17ClFNO2: C,
64.77; H, 5.13; N, 4.20. Found: C, 64.75; H, 5.20; N, 4.21.
and warmed to room temperature. The aqueous layer was
extracted with CH2Cl2 (5 × 5 mL). The combined extract was
dried over MgSO4, and the solvent was evaporated to give the
crude product as a white solid which was purified by silica
gel flash chromatography with 15% EtOAc/hexane to give 321
(4R)-5i. mp ) 67-68 °C; [R]26 ) -36.2° (c 1.0, CHCl3); 1H
D
NMR (500 MHz, CDCl3) δ 7.36-7.02 (m, 9H), 5.24 (d, J ) 3.2
Hz, 1H), 5.14 (q, J ) 7.1 Hz, 1H), 3.71 (m, 1H), 2.99 (dd, J )
8.5, 11.4 Hz, 1H), 2.87 (dd, J ) 3.0, 11.4 Hz, 1H), 2.29 (s, 3H),
1.50 (J ) 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 157.4,
149.6, 140.2, 138.9, 138.8, 129.5, 128.8, 128.4, 127.2, 125.6,
mg (90%) of (R)-9a as a white solid. mp ) 64-66 °C; [R]25
)
D
+25.3° (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.31-7.21
(m, 5H), 5.10 (q, J ) 7.2 Hz, 1H), 4.14 (t, J ) 8.9 Hz, 1H),
4.03-3.99 (m, 2H), 3.93 (dd, J ) 5.5, 11.7 Hz, 1H), 3.55 (m,
1H), 1.96 (s, 3H), 1.57 (d, J ) 7.2 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 170.3, 157.8, 138.6, 128.7, 127.9, 127.1, 65.0, 63.7,
52.54, 52.52, 20.4, 18.1. Anal. Calcd for C14H17NO4: C, 63.87;
H, 6.51; N, 5.32. Found: C, 63.84; H, 6.63; N, 5.33.
122.1, 78.0, 62.2, 51.8, 44.0, 21.4, 16.3. Anal. Calcd for C19H20
-
ClNO2: C, 69.19; H, 6.11; N, 4.25. Found: C, 69.18; H, 6.17;
N, 4.25.
(4R)-5j. mp ) 81-82 °C; [R]26 ) +17.8° (c 1.0, CHCl3); 1H
D
P r ep a r a tion of 3-[1′(R)-r-m eth ylben zyl]-4(S)-(p h en yl-
su lfa n ylm et h yl)oxa zolid in -2-on e (S)-9b. To a solution
1-[(1′(R)-R-methylbenzyl)aziridin-2(R)-yl]methanol (R)-2a (150
mg, 0.846 mmol) in 4.20 mL of methylene chloride was added
thiophenol (0.26 mL, 2.54 mmol). The mixture was stirred
under a nitrogen atmosphere for 2 h at room temperature and
then was quenched by 5 mL of saturated aqueous NaOH
solution. The organic layer was separated, and the aqueous
layer was extracted with CH2Cl2 (5 × 10 mL). The combined
extracts were dried over MgSO4, and the solvent was evapo-
rated to give the crude product as a yellow oil. To the solution
of crude product in 4.2 mL of THF was slowly added phosgene
solution (0.90 mL, 1.69 mmol, 1.89 M in toluene) at -78 °C.
The mixture was stirred under a nitrogen atmosphere for 2 h
at -78 °C then quenched with water and warmed to room
temperature. The aqueous layer was extracted with CH2Cl2
(5 × 5 mL). The combined extract was dried over MgSO4, and
the solvent was evaporated to give the crude product as a white
solid which was purified by silica gel flash chromatography
with 15% EtOAc/hexane to give 247 mg (93%) of (S)-9b as a
NMR (500 MHz, CDCl3) δ 7.35-7.23 (m, 5H), 5.80-5.74 (m,
1H), 5.39 (ddd, J ) 0.8, 1.4, 16.5 Hz, 1H), 5.25 (dt, J ) 0.9,
10.5 Hz,1H), 5.11 (q, J ) 7.1 Hz, 1H), 4.73-4.71 (m, 1H), 3.57
(dt, J ) 3.3, 8.5 Hz, 1H), 2.89 (dd, J ) 8.5, 11.4 Hz, 1H), 2.8
(dd, J ) 3.2, 11.4 Hz, 1H), 1.57 (d, J ) 7.1 Hz, 3H); 13C NMR
(125 MHz, CDCl3) δ 157.1, 140.3, 134.3, 128.8, 128.3, 127.1,
118.1, 77.5, 59.5, 51.6, 43.7, 16.2. Anal. Calcd for C14H16
-
ClNO2: C, 63.28; H, 6.07; N, 5.27. Found: C, 63.26; H, 6.14;
N, 5.16.
(4R)-5k . mp ) 96 °C; [R]27D ) +66.8° (c 1.0, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.35-7.23 (m, 5H), 5.99-5.92 (m, 1H),
5.47 (dt, J ) 1.2, 17.2 Hz,1H), 5.37 (dt, J ) 1.1, 10.6 Hz, 1H),
5.07 (q, J ) 7.1 Hz, 1H), 4.92 (m, 1H), 3.97 (td, J ) 2.6, 7.8
Hz, 1H), 2.99 (dd, J ) 2.6, 11.8, 1H), 2.87 (dd, J ) 7.8, 11.8
Hz, 1H), 1.66 (d, J ) 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3)
δ 157.3, 140.5, 129.7, 128.8, 128.2, 127.0, 121.2, 77.4, 58.1, 52.3,
40.8, 16.9; HRMS Calcd for C14H16ClNO2: 265.086234, found:
265.086970.
P r ep a r a tion of 4(R)-(Ch lor om eth yl)oxa zolid in -2-on e
(R)-7a . To a solution 4(R)-(Chloromethyl)-3-[1′(R)-R-methyl-
benzyl]oxazolidin-2-one (4R)-5a (70 mg, 0.29 mmol) in 1.5 mL
of hexane under nitrogen atmosphere were added methane-
sulfonic acid (95 µL, 1.48 mmol) and anisole (79 µL, 0.73
mmol). The mixture was refluxed for 4 h and then cooled to
room temperature. The reaction was quenched by 4 mL of
saturated NaHCO3 solution. The aqueous layer was extracted
with CH2Cl2 (5 × 5 mL). The combined extract was dried over
MgSO4, and the solvent was evaporated to give the crude
product which was purified by silica gel flash chromatography
with 15% EtOAc/hexane to give 39 mg (99%) of (R)-7a as a
white solid. mp ) 58-59 °C; [R]24 ) -65.4° (c 1.0, CHCl3);
D
1H NMR (500 MHz, CDCl3) δ 7.21-6.88 (m, 10H), 5.08 (q, J )
7.1 Hz, 1H), 4.12 (t, J ) 8.7 Hz, 1H), 4.05 (dd, J ) 5.1, 9.0 Hz,
1H), 3.46-3.41 (m, 1H), 3.13 (dd, J ) 3.1, 13.6 Hz, 1H), 2.64
(dd, J ) 10.5, 13.6 Hz, 1H), 1.57 (d, J ) 7.2 Hz, 3H); 13C NMR
(125 MHz, CDCl3) δ 157.8, 138.1, 133.6, 129.2, 129.0, 128.7,
127.9, 127.2, 126.5, 66.7, 53.0, 52.3, 37.0, 18.7; HRMS Calcd
for C18H19NO2S: 313.113651, found: 313.113780.
P r ep a r a t ion of 4(R)-Azid om et h yl-3-[1′(R)-r-m et h yl-
ben zyl]oxa zolid in -2-on e (R)-9c. To a solution 1-[(1′(R)-R-
methylbenzyl)aziridin-2(R)-yl]methanol (R)-2a (150 mg, 0.846
mmol) in 4.20 mL of methylene chloride was added azidotri-
methylsilane (0.34 mL, 2.54 mmol). The mixture was stirred
under a nitrogen atmosphere for 3 h at room temperature and
then was quenched by 2 mL of 1 N H2SO4 solution. The organic
layer was separated, and the aqueous layer was extracted with
CH2Cl2 (5 × 10 mL). The combined extract was dried over
MgSO4, and the solvent was evaporated to give the crude
product as a yellow oil. To the solution of the crude product in
4.20 mL of THF was slowly added phosgene solution (0.90 mL,
1.69 mmol, 1.89 M in toluene) at -78 °C. The mixture was
stirred under a nitrogen atmosphere for 2 h at -78 °C. The
reaction was quenched with water and warmed to room
temperature. The aqueous layer was extracted with CH2Cl2
(5 × 5 mL). The combined extract was dried over MgSO4, and
the solvent was evaporated to give the crude product as a white
solid which was purified by silica gel flash chromatography
with 15% EtOAc/hexane to give 200 mg (96%) of (R)-9c as a
colorless oil. [R]26D ) -52.0° (c 1.0, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 7.30-7.19 (m, 15H), 5.13 (q, J ) 7.2 Hz, 1H), 4.08 (t,
J ) 8.9 Hz, 1H), 3.96 (dd, J ) 4.5, 9.0 Hz, 1H), 3.46 (m, 1H),
3.34 (dd, J ) 5.3, 12.8 Hz, 1H), 3.31 (dd, J ) 3.8, 12.7 Hz,
1H), 1.58 (d, J ) 7.3 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
157.5, 138.5, 128.5, 127.7, 126.8, 65.0, 53.0, 52.7, 52.5, 18.2.
Anal. Calcd for C12H14N4O2: C, 58.53; H, 5.73; N, 22.75.
Found: C, 58.55; H, 5.81; N, 22.74.
white solid. mp ) 44-45 °C; [R]25 ) +18.3° (c 10.0, CHCl3);
D
1H NMR (500 MHz, CDCl3) δ 6.85 (s, HNCO), 4.53 (t, J ) 8.7
Hz, 1H), 4.27 (dd, J ) 4.6, 9.2 Hz, 1H), 4.19-4.14 (m, 1H),
3.60 (dd, J ) 5.3, 11.3 Hz, 1H), 3.57 (dd, J ) 6.2, 11.2 Hz,
1H); 13C NMR (125 MHz, CDCl3) δ 159.6, 67.9, 53.2, 45.6. Anal.
Calcd for C4H6ClNO2: C, 35.44; H, 4.46; N, 10.33. Found: C,
35.45; H, 4.53; N, 10.28.
1
(S)-7. mp ) 44-45 °C; [R]25 ) -18.2° (c 10.0, CHCl3); H
D
NMR (500 MHz, CDCl3) δ 6.85 (s, HNCO), 4.53 (t, J ) 8.7 Hz,
1H), 4.27 (dd, J ) 4.6, 9.2 Hz, 1H), 4.19-4.14 (m, 1H), 3.60
(dd, J ) 5.3, 11.3 Hz, 1H), 3.57 (dd, J ) 6.2, 11.2 Hz, 1H); 13
C
NMR (125 MHz, CDCl3) δ 159.6, 67.9, 53.2, 45.6. Anal. Calcd
for C4H6ClNO2: C, 35.44; H, 4.46; N, 10.33. Found: C, 35.48;
H, 4.53; N, 10.29.
P r ep a r a tion of Acetic Acid 2-Oxo-3-[1′(R)-r-m eth yl-
ben zyl]oxa zolid in -4(R)-yl Meth yl Ester (R)-9a . To a solu-
tion 1-[(1′(R)-R-methylbenzyl)-aziridin-2(R)-yl]-methanol (R)-
2a (240 mg, 1.35 mmol) in 6.77 mL of methylene chloride was
added acetic acid (0.40 mL, 6.77 mmol). The mixture was
stirred under a nitrogen atmosphere for 14 h at room tem-
perature and then was quenched with 10 mL of saturated
aqueous NaHCO3 solution. The organic layer was separated,
and the aqueous layer was extracted with CH2Cl2 (5 × 10 mL).
The combined extract was dried over MgSO4, and the solvent
was evaporated to give the crude product as a yellow oil. To
the solution of crude product in 6.80 mL of THF was slowly
added phosgene solution (1.43 mL, 2.71 mmol, 1.89 M in
toluene) at -78 °C. The mixture was stirred under a nitrogen
atmosphere for 2 h at -78 °C and then quenched with water
P r ep a r a tion of [(4R)-2-Oxo-1,3-oxa zolid in -4-yl]tr ip h -
en ylp h osp h on iu m Iod id e (R)-10. To a solution of (R)-7a (56
mg, 0.41 mmol) in 2 mL of DMF was added NaI (93 mg, 0.61
J . Org. Chem, Vol. 68, No. 1, 2003 47

Park et al.
mmol) and PPh3 (1.0 g, 4.13 mmol). The reaction mixture was
heated at 100 °C for 24 h and then cooled to room temperature.
To the mixture was added ethyl ether to remove excess
triphenylphosphine followed by washing with THF to afford
127.1, 70.0, 54.9; HRMS(EI) calcd for C11H10NO2Cl: 223.0400,
found 223.0395.
1
(S)-11h . 75% yield, [R]25 -21.5° (c 1.0, CHCl3); H NMR
D
(CDCl3, 200 MHz) δ 7.43-7.31 (m, 1H), 6.88-6.71 (m,2H), 6.65
(d, J ) 16.0 Hz, 1H), 6.14 (dd, J ) 7.5, 16.0 Hz, 1H), 6.02 (br,
1H), 4.64-4.47 (m, 2H), 4.12 (dt, J ) 8.3, 11.6 Hz, 1H); 13C
NMR (CDCl3, 50 MHz) δ 159.6, 128.7, 125.3, 111.8, 111.4,
104.5, 104.1, 103.8, 70.0, 55.2; HRMS(EI) calcd for C11H9-
NO2F2: 225.0601, found: 225.0599.
a white solid (190 mg, 95%). mp 88-89 °C; [R]25 -11.4° (c
D
1
1.0, CHCl3); H NMR (D2O, 200 MHz) δ 7.91-7.70 (m, 15H),
4.54-5.44 (m, 1H), 4.38 (t, J ) 9.0 Hz, 1H), 4.03 (dd, J ) 4.7,
9.0 Hz, 1H), 3.92 (dd, J ) 6.1, 13.3 Hz, 1H), 3.81 (d, J ) 6.1,
13.8 Hz, 1H); 13C NMR (D2O, 50 MHz) δ 157.6, 135.1, 133.4-
(d), 130.3(d), 116.5(d), 68.9, 47.2, 27.8; HRMS(EI) calcd for
(S)-11i. 79% yield, mp 125-126 °C; [R]25 +0.9° (c 1.0,
D
C
22H21NO2P: 362.1309, found: 362.1310.
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 8.20-8.10 (m, 1H), 7.73-
7.40 (m, 3H), 6.67 (d, J ) 16.0 Hz, 1H), 6.30 (dd, J ) 7.1, 16.0
Hz, 1H), 6.07 (br, 1H), 4.67-4.54 (m, 2H), 4.17 (dt, J ) 10.3,
11.3 Hz, 1H); 13C NMR (CDCl3, 50 MHz) δ 159.3, 137.2, 133.3,
132.3, 131.2, 130.7, 129.5, 128.2, 122.6, 69.6, 54.4; HRMS(EI)
calcd for C11H10N2O4: 234.0640, found: 234.0642.
(4S)-4-[(E)-2-P h en yleth en yl]-1,3-oxa zolid in -2-on e (S)-
11a . To a suspension of (R)-10 (120 mg, 0.24 mmol) in 2 mL
of dry THF was added LiHMDS (1.0 M in THF, 0.52 mL) at
-78 °C. The reaction mixture was stirred for 1 h at the same
temperature and quenched with benzaldehyde (20.8 µL, 0.20
mmol). The resulting mixture was stirred for 2 h at room
temperature and then quenched with 1 mL of sat. aqueous
NH4Cl. The mixture was extracted with EtOAc (3 × 3 mL).
The combined organic extract was washed with brine, dried
over MgSO4, filtered, and concentrated under reduced pres-
sure. Purification by silica gel flash chromatography (EtOAc/
n-hexane ) 1/1) provided 34 mg (88%) of (S)-11a as white
crystals. mp 139-140 °C; [R]25D -17.6° (c 1.0, CHCl3); 1H NMR
(CDCl3, 200 MHz) δ 7.37-7.28 (m, 5H), 6.60 (d, J ) 15.9 Hz,
1H), 6.12 (dd, J ) 7.5, 15.9 Hz, 1H), 5.95 (br, 1H), 4.59 (dd, J
) 1.8, 4.2 Hz, 2H), 4.13 (dt, J ) 10.5, 11.8 Hz, 1H); 13C NMR
(CDCl3, 50 MHz) δ 159.7, 135.3, 133.6, 128.6, 128.3, 126.6,
126.4, 70.1, 55.0; HRMS(EI) calcd for C11H11NO2: 189.0789,
found: 189.0785.
(S)-11j. 81% yield, mp 199-200 °C; [R]25 -12.1° (c 1.0,
D
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.19 (d, J ) 9.5 Hz, 2H),
6.60 (d, J ) 8.7 Hz, 2H), 6.43 (d, J ) 15.8 Hz, 1H), 5.98 (br,
1H), 5.82 (dd, J ) 7.5, 15.6 Hz, 1H), 4.55-4.38 (m, 2H), 4.08-
4.05 (m, 1H), 2.90 (s, 6H); 13C NMR (CDCl3, 50 MHz) δ 159.7,
150.8, 133.2, 128.1, 127.9, 124.1, 114.0, 72.2, 55.2, 28.8; HRMS-
(EI) calcd for C12H13NO3: 219.0895, found: 219.0892.
(4S)-4-(2-P h en yleth yl)-1,3-oxa zolid in -2-on e (S)-12a . To
a solution of (S)-11a (30 mg, 0.15 mmol) in 3 mL of EtOH was
added 15 mg of 5% Pd/C. The mixture was stirred under a
balloon pressure of hydrogen for 10 h at room temperature.
The reaction mixture was filtered and concentrated under
reduced pressure. Purification by silica gel flash chromatog-
raphy (EtOAc/n-hexane ) 1/1) provided 30 mg (99%) of (S)-
(S)-11b. 86% yield, mp 82-83 °C; [R]25 -19.6° (c 1.0,
D
12a as white crystals. mp 96-97 °C; [R]25 -32.8° (c 1.0,
D
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.43-7.37 (m, 1H), 7.25-
7.11 (m, 3H), 6.82 (d, J ) 15.6 Hz, 1H), 6.12 (br, 1H), 6.02
(dd, J ) 7.1, 15.6 Hz, 1H), 4.64-4.51 (m, 2H), 4.13 (dt, J )
8.7, 11.5 Hz, 1H), 2.33 (s, 3H); 13C NMR (CDCl3, 50 MHz) δ
159.7, 135.6, 134.4, 131.4, 130.3, 128.2, 127.7, 126.1, 125.7,
70.1, 55.2, 19.6; HRMS(EI) calcd for C12H13NO2: 203.0946,
found: 203.0947.
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.35-7.15 (m, 5H), 6.12
(br, 1H), 4.45 (t, J ) 8.3 Hz, 1H), 4.01 (dd, J ) 6.2, 8.3 Hz,
1H), 3.86 (quintet, J ) 6.5 Hz, 1H), 2.68 (dt, J ) 2.9, 7.9 Hz,
2H), 1.98-1.85 (m, 2H); 13C NMR (CDCl3, 50 MHz) δ 160.3,
140.2, 128.3, 128.1, 126.0, 70.0, 51.8, 36.7, 31.3; HRMS(EI)
calcd for C11H13NO2: 191.0946, found: 191.0948.
(S)-12b. 98% yield, [R]25 -19.9° (c 1.0, CHCl3); 1H NMR
(S)-11c. 80% yield, mp 117-118 °C; [R]25 -12.5° (c 1.0,
D
D
(CDCl3, 200 MHz) δ 7.14-7.07 (m, 4H), 6.43 (br, 1H), 4.46 (t,
J ) 8.1 Hz, 1H), 4.00 (dd, J ) 6.3, 8.1 Hz, 1H), 3.89 (m, 1H),
2.64 (dt, J ) 4.5, 7.3 Hz, 2H), 2.28 (s, 3H), 1.85 (m, 2H); 13C
NMR (CDCl3, 50 MHz) δ 160.1, 138.4, 135.6, 130.4, 128.7,
126.4, 126.1, 70.1,52.3, 35.6, 29.0, 19.1; HRMS(EI) calcd for
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.68-7.39 (m, 4H), 6.62
(d, J ) 15.6 Hz, 1H), 6.21 (dd, J ) 7.1, 15.7 Hz, 1H), 6.01 (br,
1H), 4.63-4.50 (m, 2H), 4.13 (dt, J ) 9.5, 11.2 Hz, 1H); 13C
NMR (CDCl3, 50 MHz) δ 159.6, 138.9, 132.0, 131.9, 129.2,
128.5, 128.2, 126.8, 125.6, 69.9, 54.7, 28.8; HRMS(EI) calcd
for C12H10NO2F3: 257.0663, found: 257.0661.
C
12H15NO2: 205.1102, found: 205.1096.
(S)-12c. 99% yield, mp 70-71 °C; [R]25 -23.3° (c 1.0,
(S)-11d . 78% yield, mp 121-122 °C; [R]25 -14.1° (c 1.0,
D
D
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.54 (d, J ) 8.1 Hz, 2H),
7.29 (d, J ) 7.7 Hz, 2H), 6.94 (br, 1H), 4.48 (t, J ) 8.5 Hz,
1H), 4.03 (dd, J ) 6.1, 8.5 Hz, 1H), 3.87 (m, 1H), 2.75 (q, J )
7.7 Hz, 2H), 1.87 (m, 2H); 13C NMR (CDCl3, 50 MHz) δ 160.3,
144.4, 131.9, 128.6, 128.2, 125.4, 70.0, 51.8, 36.6, 31.3; HRMS-
(EI) calcd for C12H12NO2F3: 259.0820, found: 259.0821.
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.30 (d, J ) 8.7 Hz, 2H),
6.86 (d, J ) 6.9 Hz, 2H), 6.54 (d, J ) 15.6 Hz, 1H), 5.98 (dd,
J ) 7.7, 15.6 Hz, 1H), 5.63 (br, 1H), 4.62-4.51 (m, 2H), 4.12-
(dt, J ) 6.3, 12.4 Hz, 1H), 3.81 (s, 3H); 13C NMR (CDCl3, 50
MHz) δ 159.7, 150.8, 133.2, 128.1, 127.9, 124.1, 114.0, 72.2,
55.2, 28.8; HRMS(EI) calcd for C12H13NO3: 219.0895, found:
219.0892.
(S)-12d . 98% yield, mp 77-78 °C; [R]25 -32.8° (c 1.0,
D
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.06 (d, J ) 8.7 Hz, 2H),
6.81 (d, J ) 8.7 Hz, 2H), 6.37 (br, 1H), 4.41 (t, J ) 8.3 Hz,
1H), 3.97 (dd, J ) 6.3, 8.3 Hz, 1H), 3.82 (m, 1H), 3.76 (s, 3H),
2.60 (dt, J ) 3.3, 6.9 Hz, 2H), 1.82 (m, 2H); 13C NMR (CDCl3,
50 MHz) δ 160.1, 158.0, 132.1, 129.1, 114.0, 70.1, 55.2, 52.0,
37.0, 30.7; HRMS(EI) calcd for C12H15NO3: 221.1051, found:
221.1054.
(S)-11e. 82% yield, [R]25 -14.1° (c 1.0, CHCl3); 1H NMR
D
(CDCl3, 200 MHz) δ 7.53-7.40 (m, 2H), 6.51 (d, J ) 16.0 Hz,
1H), 6.05 (dd, J ) 7.5, 16.0 Hz, 1H), 5.87 (br, 1H), 4.63-4.47
(m, 2H), 4.14 (dt, J ) 6.2, 10.0 Hz, 1H), 3.86 (s, 6H), 3.85 (s,
3H); 13C NMR (CDCl3, 50 MHz) δ 159.4, 153.1, 133.1, 131.7,
131.1, 128.4, 126.1, 69.9, 60.7, 55.9, 54.8; HRMS(EI) calcd for
C
14H17NO5: 279.1106, found: 279.1106.
(S)-12e. 96% yield, [R]25 -15.6° (c 1.0, CHCl3); 1H NMR
(S)-11f. 81% yield, mp 147-148 °C; [R]25 -1.6° (c 1.0,
D
D
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.58-7.26 (m, 4H), 6.63
(br, 1H), 6.48 (d, J ) 15.8 Hz, 1H), 6.13 (dd, J ) 6.5, 15.7 Hz,
1H), 4.46-4.43 (m, 2H), 4.05-3.93 (m, 1H); 13C NMR (CDCl3,
50 MHz) δ 159.3, 139.9, 132.2, 131.7, 131.1, 128.4, 127.0, 118.5,
69.5, 54.4; HRMS(EI) calcd for C12H10N2O2: 214.0742, found:
214.0745.
(CDCl3, 200 MHz) δ 7.67-7.40 (m, 2H), 6.56 (br, 1H), 4.44 (t,
J ) 8.3 Hz, 1H), 4.00 (dd, J ) 6.1, 8.3 Hz, 1H), 3.87 (m, 1H),
3.81 (s, 6H), 3.79 (s, 3H), 2.58 (dt, J ) 6.3, 10.9 Hz, 2H), 1.94-
1.81 (m, 2H); 13C NMR (CDCl3, 50 MHz) δ 160.1, 153.1, 136.0,
131.8, 128.5, 70.0, 60.7, 55.9, 36.9, 31.8; HRMS (EI) calcd for
C
14H19NO5: 281.1263, found: 281.1268.
(S)-11g. 87% yield, mp 96-97 °C; [R]25D -22.7 (c 1.0, CHCl3);
1H NMR (CDCl3, 200 MHz) δ 7.35-7.26 (m, 4H), 6.56 (d, J )
15.8 Hz, 1H), 6.25 (br, 1H), 6.10 (dd, J ) 7.1, 15.7 Hz, 1H),
4.63-4.49 (m, 2H), 4.12 (dt, J ) 9.7, 11.6 Hz, 1H); 13C NMR
(CDCl3, 50 MHz) δ 159.7, 133.9, 132.3, 128.8, 128.2, 127.8,
(S)-12f. 99% yield, mp 86-87 °C; [R]25 -32.8° (c 1.0,
D
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.43 (d, J ) 8.6 Hz, 2H),
7.27 (d, J ) 8.6 Hz, 2H), 7.04 (br, 1H), 4.47 (t, J ) 8.5 Hz,
1H), 4.02 (dd, J ) 6.1, 8.5 Hz, 1H), 3.85 (m, 1H), 2.72 (m, 2H),
1.89 (m, 2H); 13C NMR (CDCl3, 50 MHz) δ 159.8, 146.1, 131.8,
48 J . Org. Chem., Vol. 68, No. 1, 2003

Synthesis of Functionalized Oxazolidinones
129.0, 118.7, 109.9, 69.7, 51.6, 36.3, 31.4; HRMS (EI) calcd for
2.58 (t, J ) 7.3 Hz, 2H), 1.88 (m, 2H); 13C NMR (CDCl3, 50
MHz) δ 159.9, 149.2, 128.8, 127.9, 112.9, 70.2, 52.1, 40.6, 37.1,
30.6; HRMS (EI) calcd for C13H18N2O2: 234.1368, found:
234.1367.
C
12H12N2O2: 216.0898, found: 216.0892.
(S)-12g. 99% yield, mp 76-77 °C; [R]25D -22.1 (c1.0, CHCl3);
1H NMR (CDCl3, 200 MHz) δ 7.26 (d, J ) 8.5 Hz, 2H), 7.10 (d,
J ) 8.2 Hz, 2H), 6.78 (br, 1H), 4.45 (dt, J ) 2.4, 8.5 Hz, 1H),
4.01 (dd, J ) 6.1, 8.5 Hz, 1H), 3.86 (m, 1H), 2.61 (dt, J ) 7.0,
13.6 Hz, 2H), 1.87 (m, 2H); 13C NMR (CDCl3, 50 MHz) δ 160.2,
138.7, 132.0, 129.6, 128.2, 70.0, 51.8, 36.8, 30.8; HRMS (EI)
(2S)-2-Am in o-4-p h en yl-1-bu ta n ol (S)-13a . To a solution
of (S)-12a (30 mg, 0.16 mmol) in 4 mL of 30% aqueous EtOH
was added LiOH (200 mg, 4.81 mmol). The mixture was
refluxed for 2 h and cooled to room temperature. The reaction
mixture was concentrated to 2 mL and then extracted with
EtOAc (5 ×5 mL). The combined extracts were dried over
MgSO4, filtered, and concentrated under reduced pressure.
Purification by silica gel flash chromatography (EtOAc/MeOH
) 2/3) provided 24 mg (92%) of (S)-13a as white crystals. mp
calcd for C11H12NO2Cl: 225.0556, found: 225.0554.
1
(S)-12h . 99% yield, [R]25 -32.9° (c 1.0, CHCl3); H NMR
D
(CDCl3, 200 MHz) δ 7.13 (m, 1H), 6.80 (m, 2H), 6.56 (br, 1H),
4.49 (t, J ) 8.5 Hz, 1H), 4.04 (dd, J ) 6.1, 8.5 Hz, 1H), 3.85
(m, 1H), 2.66 (m, 2H), 1.87 (dq, J ) 2.9, 6.9 Hz, 2H); 13C NMR
(CDCl3, 50 MHz) δ 160.1, 150.9, 131.0, 128.3, 122.7, 111.4,
78-79 °C; [R]25 -4.5° (c 0.8, CH3OH); 1H NMR (CD3OD, 200
D
103.8, 70.0, 51.5, 35.6, 24.5; HRMS (EI) calcd for C11H11
NO2F2: 227.0757, found: 227.0757.
-
MHz) δ 7.31-7.12 (m, 5H), 3.59 (dd, J ) 7.0, 9.9 Hz, 1H), 3.37
(dd, J ) 7.0, 10.9 Hz, 1H), 2.80 (m, 1H), 2.71 (dt, J ) 6.4, 9.3
Hz, 2H), 1.86-1.55 (m, 2H); 13C NMR (CD3OD, 50 MHz) δ
144.2, 130.2, 127.7, 68.1, 54.3, 37.2, 34.2; HRMS (EI) calcd for
(S)-12i. 85% yield, [R]25 -16.5° (c 1.0, CHCl3); 1H NMR
D
(CDCl3, 200 MHz) δ 7.08 (t, J ) 7.8 Hz, 1H), 6.57-6.50 (m,
3H), 5.87 (br, 1H), 4.44 (t, J ) 8.3 Hz, 1H), 3.99 (dd, J ) 6.3,
8.3 Hz, 1H), 3.84 (m, 1H), 3.69 (br, 2H), 2.58 (t, J ) 8.2 Hz,
2H), 1.94-1.82 (m, 2H). 13C NMR (CDCl3, 50 MHz) δ 159.6,
146.7, 141.3, 129.6, 118.4, 114.9, 113.2, 70.1, 52.0, 36.6, 31.8.
HRMS (EI) calcd for C11H14N2O2: 206.1055, found: 206.1059.
C
10H15NO: 165.1153, found: 165.1149.
Ack n ow led gm en t. W.K.L. is grateful to Korea
Research Foundation for financial support (2000-015-
DP0260) and ChemBioNex for providing enantiomeri-
cally pure chiral aziridines.
(S)-12j. 99% yield, mp 163-164 °C; [R]25 -12.7° (c 1.0,
D
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.03 (d, J ) 8.5 Hz, 2H),
6.68 (d, J ) 8.5 Hz, 2H), 6.05 (br, 1H), 4.42 (t, J ) 8.1 Hz,
1H), 3.98 (dd, J ) 6.5, 8.1 Hz, 1H), 3.84 (m, 1H), 2.91 (s, 6H),
J O025545L
J . Org. Chem, Vol. 68, No. 1, 2003 49