Copper-catalyzed N-arylation of 2-oxazolidinones. An expeditious route to toloxatone

Article abstract of DOI:10.3987/COM-03-S7

3-Aryl-2-oxazolidinones are obtained in excellent yields through the copper-catalyzed N-arylation of 2-oxazolidinones with a variety of aryl iodides. With aryl halides containing both iodo and bromo substituents, a high C-I/C-Br selectivity can be achieved. The procedure has been successfully applied to the preparation of a key intermediate in the synthesis of linezolid and to develop an expeditious route to toloxatone.

Full text of DOI:10.3987/COM-03-S7

HETEROCYCLES, Vol. 61, 2003
505
HETEROCYCLES, Vol. 61, 2003, pp. 505 - 512
Received, 1st April, 2003, Accepted, 15th May, 2003, Published online 19th May, 2003
COPPER-CATALYZED N-ARYLATION OF 2-OXAZOLIDINONES. AN
EXPEDITIOUS ROUTE TO TOLOXATONE
Sandro Cacchi,* Giancarlo Fabrizi, and Antonella Goggiamani
Department of Chemistry and Technology of Biologically Active Substances,
University of Rome “La Sapienza”, P.le A. Moro 5, 00185 Rome, Italy
sandro.cacchi@uniroma1.it.
Abstract – 3-Aryl-2-oxazolidinones are obtained in excellent yields through the
copper-catalyzed N-arylation of 2-oxazolidinones with a variety of aryl iodides.
With aryl halides containing both iodo and bromo substituents, a high C-I/C-Br
selectivity can be achieved. The procedure has been successfully applied to the
preparation of a key intermediate in the synthesis of linezolid and to develop an
expeditious route to toloxatone.
3-Aryl- and heteroaryl-2-oxazolidinones are important pharmacologically active compounds and because
of this they have attracted much attention of late. For example, 5-acetamidomethyl-3-aryl-
2-oxazolidinones have been shown to exhibit a potent antibacterial activity,1 3-(1H-pyrrol-1-yl)-
2-oxazolidinones are reversible, highly potent, and selective inhibitors of monoamine oxidase type A,2
and 5-hydroxymethyl-3-(3-methylphenyl)-2-oxazolidinone is a drug used as antidepressant.3
Recently, we reported a simple and versatile synthesis of this class of compounds4 that compares well
with known procedures.1e,5 Indeed, 3-aryl-2-oxazolidinones are prepared, usually in good to high yields,
through the palladium-catalyzed reaction of a variety of neutral, electron-poor and electron-rich aryl
bromides with 2-oxazolidinones.
The reaction, however, appears to be influenced by steric effects. For example, low yields or trace
amounts of the desired products were obtained with aryl bromides containing substituents close to the
oxidative addition site. To remove this drawback and widen the scope of our procedure, we decided to
explore new reaction conditions. In particular, encouraged by the recent renewed interest in
copper-catalyzed reactions6 and by the work of Buchwald using amine ligands to facilitate the N-arylation
of amides,6l we investigated the copper-catalyzed coupling of 2-oxazolidinone with aryl halides (Scheme
1). We report here the results of this study.

506
HETEROCYCLES, Vol. 61, 2003
O
O
Cu cat
Ar
ArX
HN
O
N
O
1
2
3
Scheme 1
Initial attempts were made by using m-bromoanisole and 1.2 equiv of 2-oxazolidinone (2) as the model
system in the presence of commercially available CuI and (±)-trans-cyclohexanediamine with a variety of
carbonate bases and K3PO4 in dioxane at 110 °C. However, unsatisfactory results were always obtained.
Only after switching to m-iodoanisole did the reaction produced the desired product in 94 % isolated yield
in 2 h [CuI (5 mol %), (±)-trans- cyclohexanediamine (10 mol %), K3PO4 (2 equiv), dioxane, 110 °C].
Therefore, these conditions were subsequently applied to a variety of aryl iodides.
As shown in Table 1, 3-aryl-2-oxazolidinones were isolated in excellent yields with neutral, electron-rich
and electron-poor aryl iodides. The presence of substituents close to the carbon-iodo bond does not
hamper the reaction (our original task) (Table 1, entries 3, 4, 5, 11, 15). With aryl iodides containing
bromo substituents, competitive N-arylation involving the C-Br bond may be observed. For example,
1-bromo-4-iodobenzene produced 9 % of 3-(p-iodophenyl)-2-oxazolidinone (Table 1, entry 6). Lowering
the reaction temperature to 80 °C, however, led to a high C-I/C-Br selectivity and, though longer reaction
times were observed, none of this product was observed (Table 1, entry 7).
Table 1. Copper-Catalyzed N-Arylation of 2-Oxazolidinone (2).a
entry
aryl iodide (1)
p-MeO-C6H4-I
m-MeO-C6H4-I
o-MeO-C6H4-I
t (h) yield% of (3)
entry
aryl iodide (1)
p-Cl-C6H4-I
p-F-C6H4-I
t (h) yield% of 3
1
2
3
4
2.5
2
97 3a
94 3b
93 3c
86 3d
8
9
5
4
6
96 3g
90 3h
89 3i
10
48
10 m-F-C6H4-I
o-Me-C6H4-Ib
11 o-F-C6H4-I
3.5 91 3j
4.5 92 3k
I
12 m-CF3-C6H4-I
13 p-MeOC-C6H4-I
14 p-EtOOC-C6H4-I
15 o-MeOOC-C6H4-I
16 p-NO2-C6H4-I
5
24
90 3e
67c 3f
5
3
92 3l
95 3m
6
7
p-Br-C6H4-I
p-Br-C6H4-Id
8
4.5 70 3n
93 3o
120 88 3f
5
a Unless otherwise stated, reactions were carried out by using 1 equiv. of aryl iodide, 1.2 equivb. of 2-oxazolidinone, 5 mol %
c
of CuI, 10 mol % of (±)-trans-cyclohexanediamine, 2 equiv. of K3PO4 in dioxane at 110 °C. 10 mol % of CuI, 120 °C.
3-(p-iodophenyl)oxazolidinone was isolated in 9% yield. d 80 °C.

HETEROCYCLES, Vol. 61, 2003
507
The high C-I/C-Br selectivity achieved with 1-bromo-4-iodobenzene prompted us to develop an
expeditious approach to the synthesis of the N-aryl derivative (4), a strategic intermediate in the synthesis
of linezolid (a member of a new class of antibiotics),7 from racemic 5-hydroxymethyl-2-oxazolidinone8
and commercially available 1-bromo-2-fluoro-4-iodobenzene (Scheme 2). The alcohol was not protected
and compound (4) was isolated in good yield under unoptimized conditions.
F
F
O
O
O
O
N
Br
F
NH
N
N
O
O
OH
NHCOMe
Linezolid
O
Br
HN
O
I
OH
F
Br
O
F
O
O
CuI, K3PO4
Br
F
(±)-trans-cyclohexanediamine
dioxane, 80 °C, 120 h
OH
O
HN
OH
O
HN
N
O
Br
I
O
4 (60%)
(5%)
Scheme 2. Synthesis of a Linezolid Intermediate.
This protocol was also applied to the synthesis of toloxatone (Scheme 3).
Me
O
O
Me
O
CuI, K3PO4
Me
(±)-trans-cyclohexanediamine
O
HN
N
O
I
O
HN
dioxane, 110 °C, 24 h
O
OH
OH
Toloxatone (82%)
(16%)
Scheme 3
While this manuscript was in preparation, a similar synthesis of 3-aryl-2-oxazolidinones appeared that
uses recrystallized CuI.9 Under these conditions, aryl bromides can be used as aryl donors. However, the
syntheses of toloxatone and linezolid require a protection/deprotection protocol for the alcohol that may
lead to lower yields. For example, toloxatone was isolated in 40% overall yield in two 2 steps from
m-bromotoluene and the tetrahydropyran derivative of 5-hydroxymethyl-2-oxazolidinone.

508
HETEROCYCLES, Vol. 61, 2003
To sum up, we have developed a convenient and straightforward procedure for the preparation of
3-aryl-2-oxazolidinones. The method shows a high substrate generality: excellent yields are obtained with
neutral, electron-rich and electron-poor aryl iodides and the presence of substituents close to the
carbon-iodo bond does not hamper the reaction. A high C-I/C-Br selectivity can be achieved with aryl
halides containing both iodo and bromo substituents. The preparation of a key intermediate in the
synthesis of linezolid and the synthesis of toloxatone from 5-hydroxymethyl-2-oxazolidinone according
to the procedure developed do not require the protection and deprotection of the alcohol.
EXPERIMENTAL
Melting points are uncorrected. Aryl iodides, dioxane, CuI, K3PO4, and (±)-trans-cyclohexanediamine
are commercially available and were used as purchased, without further purification. Racemic
5-hydroxymethyl-2-oxazolidinone was prepared according to ref. 8. Reaction products were purified on
axially compressed columns, packed with SiO2 25-40 µm, connected to a solvent delivery system and to a
1
refractive index detector, and eluting with n-hexane/ethyl acetate mixtures. H NMR spectra were
13
recorded at 400 MHz and C NMR spectra were recorded at 100.6 MHz (in CDCl3, unless otherwise
stated).
Typical Procedure for the Preparation of 3-Aryl-2-oxazolidinones (3): In a Carousel Tube Reaction
(Radley Discovery), to a solution of 2-iodoanisole (175.5 mg, 0.750 mmol) and 2-oxazolidinone (78.4
mg, 0.9 mmol) in 2 mL of 1,4-dioxane, CuI (7.1 mg, 0.038 mmol), (±)-trans-cyclohexanediamine (9 µL,
0.075 mmol), K3PO4 (318.4 mg, 0.15 mmol) were added. The mixture was warmed under argon at 110 °C
and stirred for 10 h. After cooling, the reaction mixture was diluted with ethyl acetate, washed with
water, dried over Na2SO4 and concentrated under reduced pressure. The reaction mixture was purified by
chromatography (silica gel, 35 g; n-hexane/ethylacetate 60/40 v/v) to give 135.7 mg (93 %) of 3c: oil; IR
(neat) 1734 cm-1; 1H NMR δ 7.38 (dd, J1 = 7.7 Hz, J2 = 1.6 Hz, 1 H), 7.31-7.27 (m, 1 H), 7.03-6.96 (m, 2
13
H), 4.52-4.47 (m, 2 H), 4.02-3.97(m, 2 H), 3.9 (s, 3 H); C NMR δ 157.5, 155.0, 129.0, 128.5, 126.1,
121.1, 112.1, 62.5, 55.7, 47.1; Anal. Calcd for C10H11NO3: C, 62.17; H, 5.74; N, 7,25. Found: C, 62.3; H,
5.8; N, 7.3.
3a: mp 107-108 °C (methanol); IR (KBr) 1721 cm-1; 1H NMR δ 7.43 (d, J = 9.1 Hz, 2 H), 6.91 (d J = 9.1
13
Hz, 2 H), 4.48-4.42 (m, 2 H), 4.03-3.99 (m, 2 H), 3.80 (s, 3 H); C NMR δ 156. 8, 156.0, 131.9, 120.7,
114.7, 61.7, 55.9, 46.1; Anal. Calcd for C10H11NO3: C, 62.17; H, 5.74; N, 7.25. Found: C, 62.2; H, 5.8; N,
7.1.
3b: mp 73-74 °C (n-hexane/dichloromethane); lit.,4 mp 73-74°C.
1
3c: oil; IR (neat) 1734 cm-1; H NMR δ 7.38 (dd, J1 = 7.7 Hz, J2 = 1.6 Hz, 1 H), 7.31-7.27 (m, 1 H),

HETEROCYCLES, Vol. 61, 2003
509
7.03-6.96 (m, 2 H), 4.52-4.47 (m, 2 H), 4.02-3.97(m, 2 H), 3.9 (s, 3 H); 13C NMR δ 157.5, 155.0, 129.0,
128.5, 126.1, 121.1, 112.1, 62.5, 55.7, 47.1; Anal. Calcd for C10H11NO3: C, 62.17; H, 5.74; N, 7.25.
Found: C, 62.3; H, 5.8; N, 7.3.
3d: oil; IR (neat) 1728 cm-1; 1H NMR δ 7.30-7.23 (m, 4 H), 4.55-4.48 (m, 2 H), 3.97-3.91 (m, 2 H), 2.33
(s, 3 H); 13C NMR δ 156.9, 136.1, 131.5, 128.3, 127.1, 126.6, 62.4, 48.0, 18.0; Anal. Calcd for
C10H11NO2: C, 67.78; H, 6.26; N, 7.90. Found: C, 67.9; H, 6.3 ; N, 7.8.
3e: 233-234 °C (methanol); lit.,4 mp 233-234 °C.
3f: mp 132-133 °C (methanol); IR (KBr) 1741 cm-1; 1H NMR δ 7.50-7.27 (m, 4 H), 4.51-4.46 (m, 2 H),
4.05-4.00 (m, 2 H); 13C NMR δ 155.1, 137.5, 132.1, 119.7, 116.9, 61.3, 45.1; Anal. Calcd for
C9H8NO2Br: C, 44.66; H, 3.33; N, 5.79. Found: C, 44.7; H, 5.6; N, 7.3.
3g: mp 117-118 °C (methanol); IR (KBr) 1744 cm-1; 1H NMR δ 7.50 (d, J = 9.1 Hz, 2 H), 7.34 (d, J =
9.1 Hz, 2 H), 4.52-4.46 (m, 2 H), 4.06-4.00 (m, 2 H); 13C NMR δ 155.2, 137.0, 129.3, 129.1, 119.4, 61.4,
45.2; Anal. Calcd for C9H8NO2Cl: C, 54.70; H, 4.08; N, 7.09. Found: C, 54.6; H, 4.2; N, 7.0.
3h: mp 71-72 °C (n-hexane/dichloromethane); lit.,4 mp 71-72 °C.
3i: mp 87-88 °C (n-hexane/dichloromethane); lit.,4 mp 87-88 °C.
1
3j: mp 84-85 °C (n-hexane/dichloromethane); IR (KBr) 1746 cm-1; H NMR (DMSO-d6) δ 7.53 (dt, J =
7.5 Hz, J2 = 1.6 Hz, 1 H), 7.29-7.11 (m, 3 H), 4.52-4.48 (m, 2 H), 4.09-4.04 (m, 2 H); 13C NMR
(DMSO-d6) δ 157.0 (d, J =250.5 Hz), 156.6, 128.4 (d, J = 8 Hz), 127.2 (d, J = 1.4 Hz), 125.5 (d, J = 11.0),
124.8 (d, J = 3.6 Hz), 116.7 (d, J = 19.9 Hz), 62.6, 47.1; 19F NMR {H}(DMSO-d6) δ -121.43; Anal. Calcd
for C9H8NO2F: C, 59.67; H, 4.45; N, 7.73. Found: C, 59.5; H, 4.5; N, 7.6.
3k: mp 52-53 °C (n-hexane/dichloromethane); lit.,4 mp 52-53 °C.
3l: mp 146-147 °C (methanol); lit.,4 mp 146-147 °C.
3m: mp114-115 °C (ethanol); IR (KBr) 1743, 1697 cm-1; 1H NMR δ 8.06 (d, J = 9.4 Hz, 2 H), 7.63 (d, J
= 9.4 Hz, 2 H),4.6-4.49 (m, 2 H), 4.38 (q, J = 7.1 Hz, 2 H9, 4.13-4.07 (m, 2 H), 1.40 (t, J = 7.1 Hz, 3 H);
13C NMR δ 166.1, 155.3, 142.2, 130.8, 125.8, 117.2, 61.4, 61.0, 45.0, 14.4; Anal. Calcd for C12H13NO4:
C, 61.27; H, 5.57; N, 5.95. Found: C, 61.3; H, 5.6; N, 6.0.
1
3n: oil; IR (neat) 1753, cm-1; H NMR δ 7.96-7.92 (m, 1 H) 7.56-7.52 (m, 1 H), 7.39-7.36 (m, 1 H),
7.32-7.29 (m, 1 H), 4.53-4.48 (m, 2 H) 4.05-4.00 (m, 2 H), 3.88 (s, 3 H); 13C NMR δ 166.2, 157.2, 137.5,
133.1, 131.5, 127.9, 127.6, 127.5, 62.6, 52.4, 48.1; Anal. Calcd for C11H11NO4: C, 59.73; H, 5.01; N, 6.33.
Found C, 59.8; H, 5.0; N, 6.4.
3o: mp 153-154 °C (ethanol); lit.,4 mp 153-154 °C.
4: mp 108-109 °C (ethanol); IR (KBr) 3394, 1724 cm-1; 1H NMR (DMSO-d6) δ 7.82-7.65 (m, 2 H), 7.36
(dd, Ji = 8.9 Hz, J2 = 2.6 Hz, 1 H), 5.22 (t, J = 5.59 Hz, 1 H), 4.74-4.70 (m, 1 H), 3.86-3.81 (m, 1 H),

510
HETEROCYCLES, Vol. 61, 2003
3.72-3.65 (m, 1 H), 3.60-3.53 (m, 1 H); 13C NMR (DMSO-d6) δ 158.8 (d, J = 242.5), 154.8, 140.3 (d, J =
10.0 Hz), 134.0, 115.6 (d, J = 3.0 Hz), 106.6 (d, J = 27.9 Hz), 101.6 (d, J = 21.0 Hz), 74.0, 62.1, 46.5; 19F
NMR {H} (DMSO-d6) δ -107.3. Anal Calcd for C10H9NO3BrF: C, 41.40; H, 3.13; N, 4.83. Found C,
41.3; H, 3.0; N, 4.7.
Toloxatone: mp 75-76 °C (methanol); lit.,3a mp 76 °C.
ACKNOWLEDGEMENTS
Work carried out in the framework of the National Project "Stereoselezione in Sintesi Organica.
Metodologie ed Applicazioni" supported by MURST, Rome. Financial support of this research by the
University “La Sapienza” is also gratefully acknowledged.
REFERENCES
1. For some leading works in this area, see: (a) M. Selvakumar, D. Srinivas, M. K. Khera, M. S. Kumar,
N. V. S. R. Mamidi, H. Sarnaik, C. Chandrasekar, B. S. Rao, M. A. Raheem, J. Das, J. Iqbal, and R.
Rajagopalan, J. Med. Chem., 2002, 45, 3953; (b) J. A. Tucker, D. A. Allwine, K. C. Grega, M. R.
Barbachyn, J. L. Klock, J. L. Adamski, S. J. Brickener, D. K. Hutchinson, C. W. Ford, G. E.
Zurenko, R. A. Conradi, P. S. Burton, and R. M. Jensen, J. Med. Chem., 1998, 41, 3727; (c) M. J.
Genin, D. K. Hutchinson, D. A. Allwine, J. B. Hester, D. E. Hemmert, S. A. Garmon, C. W. Ford, G.
E. Zurenko, J. C. Hamel, R. D. Schaadt, D. Stapert, B. H. Yagi, J. M. Friis, E. M. Shobe, and W. J.
Adams, J. Med. Chem., 1998, 41, 5144; (d) D. M. Gleave, S. J. Brickner, P. R. Manninen, D. A.
Allwine, K. D. Lovasz, D. C. Rohrer, J. A. Tucker, G. E. Zurenko, and C. W. Ford, Bioorg. Med.
Chem. Lett., 1998, 8, 1231; (e) S. J. Brickner, D. K. Hutchinson, M. R. Barbachyn, P. R. Manninen,
D. A. Ulanowicz, S. A. Garmon, K. C. Grega, S. K. Hendges, D. S. Toops, C. W. Ford, and G. E.
Zurenko, J. Med. Chem., 1996, 39, 673; (f) S. J. Brickner, Curr. Pharm. Des., 1996, 2, 175; (g) D. M.
Gleave and S. J. Brickner, J. Org. Chem., 1996, 61, 6470; f) J. Gante, H. Juraszyk, P. Raddatz, H.
Wurzziger, S. Bernotat-Danielowski, G. Melzer, and F. Rippmann, Bioorg. Med. Chem. Lett., 1996,
6, 2425; (h) M. R. Barbachyn, D. K. Hutchinson, S. J. Brickner, M. H. Cynamon, J. O. Kilburn, S. P.
Klemens, S. E. Glickman, K.C. Grega, S. K. Hendges, D. S. Toops, C. W. Ford, and G. E. Zurenko,
J. Med. Chem., 1996, 39, 680; (i) C. Z. Ding and R. B. Silverman, J. Med. Chem., 1993, 36, 3606; (j)
C.-O. Park, D. R. Brittelli, C. L.-J. Wang, F. D. Marsh, W. A. Gregory, M. A. Wuonola, R. J.
McRipley, V. S. Eberly, A. M. Slee, and M. Forbes, J. Med. Chem., 1992, 35, 1156; (k) W. A.
Gregory, D. R. Brittell, C.-L. J. Wang, III H. S. Kezar, R. K. Carlson, C.-H. Park, P. F. Corless, S. J.
Miller, P. Rajagopalan, M. A. Wuonola, R. J. McRipley, V. S. Eberly, A. M. Slee, and M. Forbes, J.

HETEROCYCLES, Vol. 61, 2003
511
Med. Chem., 1990, 33, 2569; (l) W.A. Gregory, D. R. Brittell, C.-L. J. Wang, M. A. Wuonola, R. J.
McRipley, D. C. Eustice, V. S. Eberly, P. T. Bartholomew, A. M. Slee, and M. Forbes, J. Med.
Chem., 1989, 32, 1673.
2. A. Mai, M. Artico, M. Esposito, G. Sbardella, S. Massa, O. Befani, P. Turini, V. Giovannini, and B.
Mondovi, J. Med. Chem., 2002. 45, 1180.
3. (a) The Merck Index, Monograph number 9659, 12th Edition on CD-ROM, Version 12:3a 2000,
Chapman & Hall/CRCnetBase; (b) F. Moureau, J. Wouters, D. P. Vercauteren, S. Collin, G. Evrard,
F. Durant, F. Ducrey, J. J. Koenig, and F. X. Jarreau, Eur. J. Med. Chem., 1994, 29, 269; (c) F.
Moureau, J. Wouters, D. P. Vercauteren, S. Collin, G. Evrard, F. Durant, F. Ducrey, J. J. Koenig,
and F. X. Jarreau, Eur. J. Med. Chem., 1992, 27, 939; (d) P. E. Keane, J. P. Kan, N. Sontag, and M.
S. Benedetti, J. Pharm. Pharmacol., 1979, 31, 752.
4. S. Cacchi, G. Fabrizi. A. Goggiamani, and G. Zappia, Org. Lett., 2001, 3, 2539.
5. K.C. Nicolaou, Y-L. Zhong, and P.S. Baran, Angew. Chem. Int. Ed., 2000, 39, 625; S., Jegham, A.
Nedelec, Ph. Burnier, Y. Guminski, F. Puech, J. J. Koenig, and P. George, Tetrahedron Lett., 1998,
39, 4453; S. E. Schaus and E. N. Jacobsen, Tetrahedron Lett., 1996, 37, 7937. For Pd-catalyzed
reactions, see: M. Moreno-Manas, L. Morral, R. Pleixats, and S. Villarroya, Eur. J. Org. Chem.,
1999, 181; C. Larksarp and H. Alper, J. Am. Chem. Soc., 1997, 119, 3709; B. Trost and A.R.
Sudhakar, J. Am. Chem. Soc., 1988, 110, 7933; T. Hayashi, A. Yamamoto, and Y. Ito, Tetrahedron
Lett., 1988, 29, 99.
6. For recent references, see: (a) M. O. Frederick, J. A. Mulder, M. R. Tracey, R. P. Hsung, J. Huang,
K. C. M. Kurtz, L. Shen, and C. J. Douglas, J. Am. Chem. Soc., 2003, 125, 2368; (b) G. Evindar and
R. A. Batey, Org. Lett., 2003, 5, 133; (c) M. Wolter, G. Nordmann, G. E. Job, and S. L. Buchwald,
Org. Lett., 2002, 4, 973; (d) F. V. Kwang, A. Klapars, and S. L. Buchwald, Org. Lett., 2002, 4, 581;
(e) J. M. Baskin and Z. Wang, Org. Lett., 2002, 4, 4423; (f) J. C. Antilla, A. Klapars, and S. L.
Buchwald, J. Am. Chem. Soc., 2002, 124, 11684; (g) C. G. Bates, P. Saejueng, J. M. Murphy, and
D.Venkataraman, Org. Lett., 2002, 4, 4727; (h) C. G. Bates, R. K. Gujadhur, and D.Venkataraman,
Org. Lett., 2002, 4, 2803; (i) G. E. Job and S. L. Buchwald, Org. Lett., 2002, 4, 3703; (j) E. J.
Hennessy and S. L. Buchwals, Org. Lett., 2002, 4, 269; (k) M. Wolter, G. Nordmann, G. E. Job, and
S. L. Buchwald, Org. Lett., 2002, 4, 973; (l) A. Klapars, J. C. Antilla, X. Huang, and S. L. Buchwald,
J. Am. Chem. Soc., 2001, 123, 7727; (m) R. K. Gujadhur, C. G. Bates, and D. Venkataraman, Org.
Lett., 2001, 3, 4315; (n) R. Gujadhur, D. Venkataraman, and J. T. Kintigh, Tetrahedron Lett., 2001,
42, 4791; (o) F. Lang, D. Zewge, I. N. Houpis, and R. P. Volante, Tetrahedron Lett., 2001, 42, 3251;
(p) J. C. Antilla and S. L. Buchwald, Org. Lett., 2001, 3, 2077; (q) M. Wolter, A. Klapars, and S. L.
Buchwald, Org. Lett., 2001, 3, 3803;(r) P. J. Fagan, E. Hauptman, R. Shapiro. And A. Casalnuovo, J.

512
HETEROCYCLES, Vol. 61, 2003
Am. Chem. Soc., 2000, 122, 5043; (s) Y. Moritani, D. H. Appella, V. Jurkauskas, and S. L.
Buchwald, J. Am. Che. Soc., 2000, 122, 6797; (t) D. H. Appella, Y. Moritanni, R. Shintani, E. M.
Ferriera, and S. L. Buchwald, J. Am. Chem. Soc., 1999, 121, 9473; (u) S. Iyer, C. Ramesh, A. Sarkar,
and P. P. Wadgaonkar, Tetrahedron Lett., 1997, 38, 8113.
7. Chem. Eng. News 2000, March 6, 43.
8. Racemic 5-hydroxymethyl-2-oxazolidinone was prepared according to: P. Seneci, M. Caspani, F.
Ripamonti, and R. Ciabatti, J. Chem. Soc., Perkin Trans., 1, 1994, 2345.
9. B. Mallesham, B. M. Rajesh, P. R. Reddy, D. Srinivas, and S. Trehan, Org. Lett., 2003, 5, 963.