A short and efficient methodology for the synthesis of novel 3-aryloxazolidin-2-one derivatives

Article abstract of DOI:10.1002/adsc.200303232

An efficient synthesis of novel oxazolidinone derivatives is disclosed. Novel oxazolidinone derivatives were synthesized by a copper-catalyzed N-arylation reaction with control of the substituents on both the sides of the phenyl ring.

Full text of DOI:10.1002/adsc.200303232

FULL PAPERS
A Short and Efficient Methodology for the Synthesis of Novel
3-Aryloxazolidin-2-one Derivatives
Mecheril V. Nandakumar
Organic Chemistry Division, Regional Research Laboratory (CSIR), Thiruvananthapuram 695019, India
Fax: (þ91)-471-2491712, e-mail: nandakumarmv@yahoo.com
Received: December 13, 2003; Revised: May 27, 2004; Accepted: June 5, 2004
Abstract: An efficient synthesis of novel oxazolidi- Keywords: amination; copper; diiodobenzene; ethyl-
none derivatives is disclosed. Novel oxazolidinone de- enediamine; N-arylation; oxazolidinone
rivatives were synthesized by a copper-catalyzed N-ar-
ylation reaction with control of the substituents on
both the sides of the phenyl ring.
Introduction
to the synthesis of Linezolid-type antibacterial agents.
The results of our investigation on the controlled cou-
Recently there has been an upsurge of interest in the pling of diiodobenzene with oxazolidinone leading to
synthesis and development of antimicrobial agents mono and bis-coupled products are presented here.
against multi-drug resistant pathogens.[1] This is evident
from the array of reports on the synthesis of novel com-
pounds effective against Gram-positive bacterial patho- Results and Discussion
gens.[2] Among them, Linezolid, an oxazolidinone deriv-
ative, represents a novel and important class of antimi- Our studiescommenced with the reaction of4-methyl-5-
crobial agent that possesses excellent activity against an- phenyl-2-oxazolidinone with diiodobenzene in the pres-
tibiotic-sensitive and MIC90 Gram-positive bacteria.[3] ence of CuI/ethylenediamine at 808C in dioxane. The re-
As a part of a program to synthesize novel antimicrobial action afforded both the mono- and bis-coupled prod-
agents of the oxazolidinone class, we have carried out ucts in 72% yield (Scheme 1).
the synthesis of the key oxazolidinone pharmacophore
present in Linezolid, Eperezolid etc. by a copper-cata- found to be 59:13 and 26:40 at 808C for reaction times
lyzed N-arylation reaction. of 5 h and 24 h, respectively. It is clear that the higher
The ratios (mono:bis) of the coupled products were
À
The palladium- and copper-catalyzed C N bond for- yields of mono-coupled product were obtained by con-
mation using aryl iodides has been an area of intense re- trolling the reaction time and the results are given in Ta-
search in the last few years. The pioneering work by ble 1.
Buchwald,[4] Hartwig[5] and others[6] on the palladium-
In most cases both mono- and bis-coupled products
catalyzed N-arylation of different nitrogen-containing were formed. This controlled coupling was found to be
compounds is an excellent alternative to the classical general with all other oxazolidinones tried. The prod-
Ullmann coupling. Recently, a report by Buchwald ucts of the coupling were characterized on the basis of
À
et al. on the operationally simple C N bond forming
protocol using copper has generated lot of interest in
heterocyclic chemistry.[7] Except for the scant informa-
tion available,[8] there is no report on the copper-cata-
lyzed N-arylation of oxazolidinones and its application
Figure 1. Linezolid.
Scheme 1.
954
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/adsc.200303232
Adv. Synth. Catal. 2004, 346, 954 958

Synthesis of 3-Aryloxazolidin-2-one Derivatives
FULL PAPERS
Table 1. CuI-mediated N-arylation of oxazolidinones with
Table 2. CuI-mediated N-arylation of mono-coupled prod-
diiodobenzene.[a]
ucts.[a]
[a]
Reaction conditions: 1 equiv. of oxazolidinone, 1 equiv. of
diiodobenzene, 10 mol % CuI, 10 mol % ethylenediamine,
3 mL dioxane, 808C.
Yield of isolated product.
[b]
spectral data. The high-resolution mass spectra of both
the mono- and bis-coupled products further confirmed
the proposed structures.
The mono-coupled products A (entries 1 4) can ef-
fectively couple with a suitable substrate to yield a novel
class of oxazolidinone derivatives. An important com-
pound of this class is Linezolid. The special architecture
[a]
Reaction conditions: 1 equiv. of oxazolidinone, 1 equiv. of
diiodobenzene, 10 mol % CuI, 10 mol % ethylenediamine,
K3PO4, 3 mL dioxane, 808C, 24 h.
Yield of isolated product.
À
of Linezolid with two C N bonds at the para-positions
[b]
of the phenyl ring can be synthesized using the copper-
catalyzed coupling reaction with control of substituents
and the synthetic route is given in Scheme 2.
[c]
Coupling of mono-coupled product with morpholine.
In order to confirm the validity of this methodology,
we have carried out the CuI/ethylenediamine-mediated
coupling of the mono-coupled product with different ox-
azolidinones and the results are summarized in Table 2.
A one-pot synthesis of bis-coupled product with same
substituent was achieved by conducting the reaction
with 2 equivalents of oxazolidinone as depicted in
Scheme 3.
It is clear from the above results that both the substitu-
ents on the phenyl ring were controllable and can be
used for the synthesis of novel oxazolidinone derivatives
Scheme 3.
including the Linezolid- and Eperezolid-type com- core was introduced either by a series of reactions or in a
pounds in an efficient way. In most of the reported pro- few cases by the palladium-catalyzed N-arylation of ox-
cedures for the synthesis of Linezolid, the oxazolidinone azolidinones with properly substituted aryl halides. In
Scheme 2.
Adv. Synth. Catal. 2004, 346, 954 958
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
955

Mecheril V. Nandakumar
FULL PAPERS
4.69 (d, J¼7.64 Hz, 1H, N-CH), 0.84 (d, J¼6.45 Hz, 3H,
both these methods, one of the substituents on one side
of the phenyl ring is fixed. But the above-mentioned
methodology offers the freedom to select the substitu-
ents on both sides of the benzene ring.
13
¼
CH3); C-NMR: d¼154.4 (C O), 138.1, 137.4, 136.8, 134.3,
130.1, 128.6, 125.9, 122.8, 78.0, 56.5, 14.3; HR-MS: calcd. for
Mþ: 379.0070; found: 379.0071.
Bis-coupled product B: mp 224 2268C; 1H NMR: d¼7.59
7.55 (m, Ar, 4H), 7.41 7.25 (m, Ar, 10H), 5.79 (d, J¼7.7, 2H),
4.73 4.64 (m, 2H, N-CH), 0.84 0.83 (m, 6H, 2CH3); 13C NMR:
d¼154.87, 134.5, 133.9, 128.6, 128.0, 122.24, 78.2, 56.8, 14.61;
HR-MS: calcd. for Mþ: 428.1736; found: 428.1743.
Conclusions
In summary, we have reported here the first efficient
mono- and bis-coupling reactions of diiodobenzene
with oxazolidinones in the presence CuI/ethylenedia-
mine catalyst system. The route is flexible and one can
control the mono-coupling reaction by means of the re-
action time. This procedure gives an easy and efficient
methodology for the synthesis of novel oxazolidinone
derivatives, which are important cores of antimicrobial
agents like Linezolids, Eperezolid, etc.
3-(4’-Iodophenyl)-4-methylphenyl-2-oxazolidinone A
and Bis-Coupled Product B (Table 1, entry 2)
Following the general procedure, the oxazolidinone (177 mg,
1 mmol), diiodobenzene (330 mg, 1 mmol), CuI(19 mg,
10 mol %), ethylenediamine (6 mg, 10 mol %), K3PO4
(424 mg, 2 mmol) and 3 mL of dry dioxane at 808C for 5 h.
gave mono- (yield: 231 mg, 61%) and bis-coupled (yield:
72.7 mg, 17%) products. Total yield: 78%.
1
Mono-coupled product A: H NMR: d¼7.73 7.70 (d, J¼
Experimental Section
8.6 Hz, 2H, Ar,), 7.3 7.2 (5H, Ar), 7.1 7.08 (m, 2H, Ar),
4.63 4.57 (m, 1H, CH-N), 4.36 (t, J¼8.8 Hz, 1H, O-CH3),
4.21 4.17(dd, J¼4.5, 8.8 Hz,1H, O-CH2), 3.14 3.08 (dd, J¼
3.2, 13.7 Hz, 1H, Ph-CH2), 2.79 2.72 (dd, J¼9.7, 13.7 Hz,
1H, Ph-CH2); 13C NMR: d¼154.8 (CO), 138.3, 129.1, 129.0,
127.4, 122.9, 65.8, 56.9, 37.6; HR-MS: calcd. for Mþ: 379.0069;
found: 379.0073.
General Considerations
All reactions were performed under an atmosphere of argon in
oven-dried glass ware. Solvents used for the experiments were
distilled or dried as specified. Copper(I) iodide was used with-
out recrystallization. 1H- and 13C-NMR spectra were recorded
on a Bruker 300 MHz NMR spectrometer. NMR spectra were
obtained using CDCl3 as solvent. Chemical shifts are given as d
(ppm) with tetramethylsilane as internal standard. Mass spec-
tra were recorded on a JEOL-JMX-600 H mass spectrometer.
Bis-coupled product B: mp 160 1628C; 1H NMR: d¼7.63
7.60 (m, Ar, 3H), 7.30 7.24 (m, Ar, 7H), 7.16 7.11 (m, Ar,
4H), 4.66 4.61 (m, 2H, N-CH), 4.44 4.32 (m, 2H, O-CH2),
4.2 4.03 (m, 2H, O-CH2), 3.17 3.12 (dd, J¼3.24, 13.7 Hz,
2H, CH2), 2.85 2.73 (m, 2H, CH2); 13C NMR: d¼155.3
(CO), 135.06, 133.70, 129.12, 128.97, 127.71, 127.34, 127.24,
122.20, 121.71, 66.03, 53.76, 37.89; HR-MS: calcd. for Mþ:
428.1736; found: 428.1741.
General Procedure for the Coupling of
Oxazolidinones with Diiodobenzene
CuI(10 mol %) and K 3PO4 (2 mmol) were added to a Schlenk
tube with a Teflon cap. The tube was evacuated and back-filled
with argon three times. The respective oxazolidinone
(1 mmol), diiodobenzene (1 mmol), ethylenediamine
(10 mol %) and 3 mL dry dioxane were added. The tube was
sealed and heated at 808C. The reaction mixture was cooled
to room temperature after heating for the specified time. The
reaction mixture was filtered and the filtrate was concentrated
under vacuum. The crude product was purified by column
chromatography using EtOAc and hexane (1:2) as eluants to
afford the coupled products.
3-(4’-Iodophenyl)-4-isopropyl-2-oxazolidinone
(Table 1, entry 3)
Following the general procedure, the oxazolidinone (129 mg,
1 mmol), diiodobenzene (330 mg, 1 mmol), CuI(19 mg,
10 mol %), ethylenediamine (6 mg, 10 mol %), K3PO4
(424 mg, 2 mmol) and 3 mL of dry dioxane at 808C for 5 h.
gave only the mono-coupled product; yield: 149 mg (45%);
mp 70 728C; 1H NMR: d¼7.6 7.58 (m, J¼8.79 Hz, 2H,
Ar), 7.27 (m, Ar, 2H), 4.35 4.27 (m, 2H, O-CH2), 4.19 4.11
(m, 1H, N-CH), 2.08 1.96 (m, 1H, CH), 0.85 0.83 (m, 3H,
13
¼
CH3), 0.77 0.75 (m, 3H, CH3); C NMR: d¼155.9 (C O),
138.1, 136.7, 123.5, 62.3, 60.1, 27.5, 17.7, 14.2; HR-MS: calcd.
for Mþ: 331.0069; found: 331.0075.
3-(4’-Iodophenyl)-4-methyl-5-phenyl-2-oxazolidinone
A and the Bis-Coupled Product B (Table 1, entry 1)
Following the general procedure, the oxazolidinone (177 mg,
1 mmol), diiodobenzene (330 mg, 1 mmol), CuI(19 mg,
10 mol %), ethylenediamine (6 mg, 10 mol %), K3PO4
(424 mg, 2 mmol) and 3 mL of dry dioxane at 808C for 5 h
gave the mono- (yield: 223 mg, 59%) and bis-coupled (yield:
55.6 mg, 13%) products. Total yield: 72%.
3-(4’-Iodophenyl)-4-(2-methylpropyl)-2-oxazolidinone
A and Bis-Coupled Product B (Table 1, entry 4)
Following the general procedure, the oxazolidinone (143 mg,
1 mmol), diiodobenzene (330 mg, 1 mmol), CuI(19 mg,
10 mol %), ethylenediamine (6 mg, 10 mol %), K3PO4
(424 mg, 2 mmol) and 3 mL of dry dioxane at 808C for 5 h.
Mono-coupled product A: 1H NMR: d¼7.69 7.66 (m, 2H,
Ar), 7.41 7.25 (m, 7H, Ar), 5.77 (d, J¼7.64 Hz, 1H, O-CH),
956
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Adv. Synth. Catal. 2004, 346, 954 958

Synthesis of 3-Aryloxazolidin-2-one Derivatives
FULL PAPERS
gave the mono- (yield: 196.6 mg, 54%) and bis-coupled (yield:
86.4 mg, 24%) products. Total yield: 78%.
Bis-Coupled Product (Table 2, entry 4)
1
Following the general procedure, 3-(4’-iodophenyl)-4-methyl-
5-phenyl-2-oxazolidinone (379 mg, 1 mmol), the oxazolidi-
none (161 mg, 1 mmol), CuI(19 mg, 10 mol %), ethylenedia-
mine (6 mg, 10 mol %), K3PO4 (424 mg, 2 mmol) and 3 mL of
dry dioxane at 808C for 24 h gave the bis-coupled product;
Mono-coupled product A: H NMR: d¼7.60 7.58 (d, J¼
8.79 Hz, 2H, Ar), 7.12 7.09 (d, J¼8.8 Hz, 2H, Ar), 4.47
4.25 (t, J¼8.2 Hz, 1H, -N-CH), 4.34 4.26 (m, 1H, O-CH2),
4.04 4.00 (dd, J¼5.0, 8.32 Hz, 1H, O-CH2), 1.59 1.54 (m,
2H, CH2), 1.40 1.34 (m, 1H, CH), 0.88 0.84 (m, 6H, 2CH3);
13C NMR: d¼155.03, 138.0, 136.6, 123.0, 67.39, 54.5, 40.8,
29.6, 24.6, 23.5; HR-MS: calcd. for Mþ: 345.0226; found:
345.0227.
1
yield: 383 mg (93%); mp 140 1428C; H NMR (CDCl3): d¼
7.51 7.20 (m, 9H, Ar), 5.7 (d, J¼7.7 Hz, O-CH-Ph), 4.68
4.59 (m, 1H, N-CH-CH3), 4.51 4.46 (m, 2H, O-CH2), 4.13
4.09 (m, 1H, N-CH-), 2.52 2.39 (m, 2H, CH2-S-), 1.97 (s, 3H,
-S-CH3), 1.81 1.75 (m, 2H, -S-CH2-CH2-), 0.76 (d, J¼6.4 Hz,
CH3); 13C NMR: d¼155.3, 154.8, 134.4, 133.9, 133.3, 128.5,
125.9, 122.28, 122.25, 78.1, 69.8, 56.7, 55.2, 34.1, 29.2, 15.6, 14.4.
Bis coupled product B: 1H NMR (CDCl3): d¼7.36 (m, 4H,
Ar), 4.50 4.41 (t, J¼8 Hz, 2H), 4.35 4.33 (m, 2H), 4.07
4.02 (dd, J¼5.3, 8.08 Hz, 2H), 1.64 1.53 (m, 4H), 1.36 1.0
(m, 2H), 0.89 0.85 (12H, 4CH3); 13C NMR: d¼155.5, 133.7,
122.2, 67.5, 54.9, 41.1, 24.7, 23.5, 21.6; HR-MS: calcd. for Mþ:
360.2049; found: 360.2045.
Bis-Coupled Product (Table 2, entry 5)
Bis-Coupled Product (Table 2, entry 1)
Following the general procedure, 3-(4’-iodophenyl)-4-methyl-
phenyl-2-oxazolidinone (379 mg, 1 mmol), the oxazolidinone
(177 mg, 1 mmol), CuI(19 mg, 10 mol %), ethylenediamine
(6 mg, 10 mol %), K3PO4 (424 mg, 2 mmol) and 3 mL of dry di-
oxane at 808C for 24 h gave the bis-coupled product; yield:
325 mg (76%); data same as for Table 1, entry 2B above.
Following the general procedure, 3-(4’-iodophenyl)-4-methyl-
5-phenyl-2-oxazolidinone (379 mg, 1 mmol), the respective ox-
azolidinone (177 mg, 1 mmol), CuI(19 mg, 10 mol %), ethyle-
nediamine (6 mg, 10 mol %), K3PO4 (424 mg, 2 mmol) and
3 mL of dry dioxane at808C for 24 hgave the bis-coupled prod-
uct; yield: 278 mg (65%); data same as for Table 1, entry 1B
above.
Bis-Coupled Product (Table 2, entry 6)
Following the general procedure, 3-(4’-iodophenyl)-4-methyl-
phenyl-2-oxazolidinone (379 mg, 1 mmol), oxazolidinone
(129 mg, 1 mmol), CuI(19 mg, 10 mol %), ethylenediamine
(6 mg, 10 mol %), K3PO4 (424 mg, 2 mmol) and 3 mL of dry di-
oxane at 808C for 24 h gave the bis-coupled product; yield:
Bis-Coupled Product (Table 2, entry 2)
Following the general procedure, 3-(4’-iodophenyl)-4-methyl-
5-phenyl 2-oxazolidinone (379 mg, 1 mmol), the oxazolidinone
(177 mg, 1 mmol), CuI(19 mg, 10 mol %), ethylenediamine
(6 mg, 10 mol %), K3PO4 (424 mg, 2 mmol) and 3 mL of dry di-
oxane at 808C for 24 h gave the bis-coupled product; yield:
282.4 mg (66%); mp 188 1908C; 1H NMR (CDCl3): d¼
7.51 7.41 (m, 3H, Ar), 7.3 7.29 (m, 6H, Ar), 7.2 7.1 (m,
3H, Ar), 7.06 7.03 (m, 2H, Ar), 5.75 (d, J¼7.7 Hz, CH-Ph),
4.71 4.60 (m, 2H, O-CH2), 4.31 (t, J¼8.5 Hz, N-CH), 4.14
1
254 mg (67%); mp 268 2708C; H NMR (CDCl3): d¼7.52
7.43 (m, 3H, Ar), 7.26 7.22 (m, 2H,Ar), 7.18 (m, 2H, Ar),
7.11 7.04 (m, 2H, Ar), 4.56 4.52 (dd, J¼4.2, 8.7 Hz, 1H,
-CH-CH2-Ph), 4.39 4.35 (m, 2H, O-CH2-), 4.31 4.25 (m,
1H, -CH-N-), 4.19 4.11 (m,2H, O-CH2-), 3.12 (dd, J¼3.5,
13.7 Hz, 1H, Ph-CH2- ), 2.7 (dd, J¼9.4, 13.7 Hz, 1H, C6H5-
CH-), 2.11 (m, -CH-), 0.88 0.80 (m, 6H, 2CH3);13C NMR:
¼
(dd, J 4.7, 8.7 Hz, 1H, N-CH), 3.0 (dd, J¼3.24, 13.7 Hz, 1H,
Ph-CH2), 2.75 (dd, J¼9.1, 13.7 Hz, 1H, Ph-CH2), 0.79 (t, J¼
6.4 Hz, 3H, CH3); 13C NMR: d¼155.0, 154.6, 134.7, 134.3,
133.7, 133.3, 128.9, 128.4, 127.0, 125.7, 122.1, 122.0, 77.9, 66.7,
65.7, 56.9, 37.5, 14.3; HR-MS: calcd. for Mþ: 428.1736; found:
428.1739.
¼
¼
d¼155.8 (C O), 154.7 (C O), 134.5, 133.8, 133.2, 128.8,
126.2, 123.5, 122.7, 78.4, 57.1, 56.2, 27.6, 14.7, 14.3; HR-MS:
calcd. for Mþ: 380.1736; found: 380.1740.
Bis-Coupled Product (Table 2, entry 7)
Bis-Coupled Product (Table 2, entry 3)
Following the general procedure, 3-(4’-iodophenyl)-4-methyl-
phenyl-2-oxazolidinone (379 mg, 1 mmol), the oxazolidinone
(143 mg, 1 mmol), CuI(19 mg, 10 mol %), ethylenediamine
(6 mg, 10 mol %), K3PO4 (424 mg, 2 mmol) and 3 mL of dry di-
oxane at 808C for 24 h gave the bis-coupled product; yield:
Following the general procedure, 3-(4’-iodophenyl)-4-methyl-
5-phenyl 2-oxazolidinone (379 mg, 1 mmol), the oxazolidinone
(129 mg, 1 mmol), CuI(19 mg, 10 mol %), ethylenediamine
(6 mg, 10 mol %), K3PO4 (424 mg, 2 mmol) and 3 mL of dry di-
oxane at 808C for 5 h gave the bis-coupled product; yield:
1
263 mg (67%); H NMR (CDCl3): d¼7.59 7.46 (m, 4H, Ar),
1
300 mg (79%); H NMR (CDCl3): d¼7.5 7.1 (m, 9H, Ar),
7.29 7.25 (m, 3H, Ar), 7.13 7.11 (m, 2H, Ar), 4.63 4.34 (m,
4H, OCH2), 4.23 4.16 (m, 2H, -N-CH), 3.19 (dd, J¼3.3 Hz,
13.6 Hz, 1H, Ph-CH2), 2.8 (dd, J¼13.7, 9.5 Hz, 1H, Ph-CH2),
5.72 (d, J¼7.7 Hz, 1H, O-CH-Ph), 4.6 4.58 (m, 1H, CH3-
CH-N), 4.37 4.30 (m, 2H, O-CH2-), 4.19 4.12 (m, 1H, N-
CH), 2.09 2.06 (m, 1H, CH), 0.85 (d, J¼7.10 Hz, 3H, CH3),
0.78 0.75 (m, 6H, 2CH3); 13C NMR: d¼155.83, 154.92,
134.59, 133.93, 133.67, 128.66, 126.03, 122.83, 122.38, 122.29,
121.68, 78.18, 62.40, 60.51, 56.96, 27.52, 17.7, 14.5, 14.2; HR-
MS: calcd. for Mþ: 380.1736; found: 380.1743.
1.6 1.2 (m, 3H, Ph-CH2-CH-), 0.98 0.86 (m, 6H, 2CH3);
13
¼
¼
C NMR: d¼155.46 (C O), 155.3 (C O), 135.2, 134.0, 133.8,
129.1, 129.0, 127.3, 122.5, 122.2, 121.8, 77.4, 70.6, 51.6, 44.6,
41.3, 38.0, 25.1, 22.9, 22.2; HR-MS: calcd. for Mþ: 394.1893;
found: 394.1890.
Adv. Synth. Catal. 2004, 346, 954 958
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¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
957

Mecheril V. Nandakumar
FULL PAPERS
Bis-Coupled Product (Table 2, entry 8)
Acknowledgements
Following the general procedure, 3-(4’-iodophenyl)-4-methyl-
isopropyl-2-oxazolidinone (345 mg, 1 mmol), the oxazolidi-
none (143 mg, 1 mmol), CuI(19 mg, 10 mol %), ethylenedia-
mine (6 mg, 10 mol %), K3PO4 (424 mg, 2 mmol) and 3 mL of
dry dioxane at 808C for 24 h gave the bis-coupled product;
yield: 311 mg (90%); 1H NMR (CDCl3): d¼7.49 7.40 (m,
4H, Ar), 4.57 (m, 2H, OCH2), 4.53 4.39 (m, 2H, OCH2),
MVN thank the Council of Scientific and Industrial Research,
New Delhi,for research funding (Task force project CMM
005.3 on speciality chemicals).
References
4.14 4.05 (m, 2H), 1.7 1.6 (m, 3H), 1.47 (m, 1H), 0.97 0.85
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13
¼
¼
(m, 12H, 4CH3); C NMR: d¼155.7 (C O), 155.4 (C O),
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21.6, 17.7, 14.5; HR-MS: calcd. for Mþ: 346.1893; found:
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Bis-Coupled Product (Table 2, entry 9)
Following the general procedure, 3-(4’-iodophenyl)-4-methyl-
phenyl-2-oxazolidinone (379 mg, 1 mmol), morpholine
(130 mg, 1.5 mmol), CuI(19 mg, 10 mol %), ethylenediamine
(6 mg, 10 mol %), K3PO4 (424 mg, 2 mmol) and 3 mL of dry di-
oxane at 808 C for 24 h gave the bis-coupled product; yield:
1
196 mg, (58%); H NMR (CDCl3): d¼7.71 7.6 (m, 2H, Ar),
7.35 7.25 (m, 5H, Ar), 7.20 7.16 (m, 2H, Ar), 4.31 4.22 (m,
2H, OCH2), 4.15 4.00 (m, 1H), 3.79 3.6 (m, 4H, morph),
[8] S. K. Kang, D. H. Kim, J. N. Park, Synlett 2002, 427 430;
b) B. Mallesham, B. M. Rajesh, P. Rajmohan Reddy, D.
Srinivas, S. Trehan, Org. Lett. 2003, 5, 963 965.
3.10 3.07 (m, 5H, morph. and CH2Ph), 2.80 2.71 (m, 1H,
13
¼
CH2Ph); C NMR: d¼155.1 (C O), 135.1, 133.7, 129.4,
126.4, 121.6, 120.3, 67.4, 65.1, 54.3, 49.6, 36.1.
958
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 954 958