See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/238130655

DCC/DMAP-Mediated Coupling of Carboxylic Acids with Oxazolidinones and

Thiazolidinethiones

Article in Synlett · December 2003

DOI: 10.1055/s-2003-42117

CITATIONS READS

37 7,718

5 authors, including:

Carlos Kleber Z Andrade Otilie Vercillo

University of Brasília University of Brasília
106 PUBLICATIONS 1,767 CITATIONS 18 PUBLICATIONS 665 CITATIONS

SEE PROFILE SEE PROFILE

Wender A Silva Ricardo Matos

University of Brasília Universidade Federal de Jataí
56 PUBLICATIONS 899 CITATIONS 10 PUBLICATIONS 92 CITATIONS

SEE PROFILE SEE PROFILE

All content following this page was uploaded by Wender A Silva on 05 September 2014.

The user has requested enhancement of the downloaded file.

LETTER 2351

DCC/DMAP-Mediated Coupling of Carboxylic Acids with Oxazolidinones

and Thiazolidinethiones
DC /DMAP-MediatedCouplingofCarboxylicAcids Kleber Z. Andrade,* Rafael O. Rocha, Otilie E. Vercillo, Wender A. Silva, Ricardo Alexandre F. Matos
Carlos
Laboratório de Química Metodológica e Orgânica Sintética (LaQMOS), Instituto de Química, Universidade de Brasília, C.P. 4478,
70910-970, Brasília, DF, Brazil
Fax +55(61)2734149; E-mail: ckleber@unb.br
Received 10 September 2003

Table 1 Results of the DCC/DMAP-Mediated Acylations of

Abstract: Dicyclohexylcarbodiimide and catalytic dimethylami- Oxazolidinones and Thiazolidinethiones8,9
nopyridine were successfully used in the coupling of carboxylic
acids with oxazolidinones and thiazolidinethiones. The acylated
products were obtained in good yields.
Key words: oxazolidinones, thiazolidinethiones, acylation

Oxazolidinones1 and more recently thiazolidinethiones2

Downloaded by: Angelo Machado, Dot. Lib Information. Copyrighted material.

have reached widespread use in stereoselective organic
synthesis as chiral auxiliaries due to their high chiral in- Entry Substrate R¢CO2H R¢ = Yield (%)a Time (h)
duction abilities.
1 1 Me 81 2.5
The most common method of coupling these compounds
b
to the substrates is the nucleophilic attack of their lithium 2 1 Et 72 3
salts (generated by reaction with BuLi in dry THF) to acid 3 1 Et 100 3
chlorides or anhydrides.3 Although the yields of the acy-
c
lated products are generally very good, there are some dis- 4 1 CH2=CH 90 16
advantages associated with this methodology: the reaction 5 1 PhCH=CH 85 3.5
is run at –78 °C, using a very strong base in a dry ethereal
solvent and in some cases it may require an additional step 6 1 EtO2CCH=CH 44 16
for the preparation of the activated acylating agent.
7 2 Et 82 24
To circumvent these problems, other methods have been
reported in which mild reaction conditions were proposed 8 2 Et 100c 6
but still using acid chlorides or anhydrides.4 Recently two 9 2 CH3CH2CH2 89 16
methods of in situ generation of mixed anhydrides were
reported. The first one employs pivaloyl chloride and tri- 10 2 PhCH=CH 100 6
ethylamine in toluene, at 80–110 °C, and is especially 11 2 PhCH2 65 24
good for arylacetic acids whereas aliphatic and conjugat-
ed acids gave only modest yields.5 The second one em- 12 3 Et 82 1
ploys diisopropylcarbodiimide (DIC) and stoichiometric 13 3 PhCH=CH 100 2
DMAP.6 This method is also good for arylacetic acids but
suffers from the fact that the acids must be added over 14 3 PhCH2 85 16
long periods of time in order to maintain the reported
15 4 Et 88 2
yields. Besides, DIC is a relatively expensive reagent.
In this paper we describe the acylation of oxazolidinones 16 4 PhCH=CH 100 2.5
and thiazolidinethiones with DCC and catalytic (10 a
Isolated yields of the chromatographically pure products.
mol%) DMAP, in CH2Cl2, at room temperature. DCC is b
1.0 Equiv of the acid and DCC was used.
c
far less expensive than DIC and is widely used along with 2.0 Equiv of the acid and DCC were used.
DMAP in ester formation.7
The results are shown in Table 1.8,9 Several acids were re-
acted with oxazolidinones 1 and 2 and thiazolidinethiones excellent yields in all cases except for fumaric acid mono-
3 and 4 and the N-acylated products were obtained in ethyl ester (entry 6). There is a significant improvement in
the yield when an excess (1.3 equiv) of the acid and DCC
is used (entries 2 and 3). Noteworthy is that acylation of 1
SYNLETT 2003, No. 15, pp 2351–235201.2 03 with BuLi and propionyl chloride gave only 50% of the
Advanced online publication: 07.11.2003 product due to the low solubility of 1 in THF (compare
DOI: 10.1055/s-2003-42117; Art ID: S09103ST with entry 3).
© Georg Thieme Verlag Stuttgart · New York
2352 C. K. Z. Andrade et al.
The order of reactivity turned out to be 3>4>1>2. In some
cases, the reaction was over within a couple of hours and
in others cases it required stirring overnight. Arylacetic
acetic and conjugated acids also gave very good results.
The acylations of less reactive 2 were faster when 2.0
equivalents of the acid and DCC were added (compare
entries 7 and 8); this is particularly advantageous when
the acid is inexpensive. The order in which the reagents
are added did not have influence on the results and the
reagents can be all mixed together.
In summary the DCC/DMAP-mediated acylation of
oxazolidinones and thiazolidinethiones proved to be very
efficient and should be of general interest. The main
advantages are the mild reaction conditions avoiding
the very strong base BuLi, cryogenic temperatures and
ethereal solvents. It is a general methodology which can
be used with a variety of acids and besides there is no need
for preparation and isolation of acid chlorides or mixed
anhydrides, thus complementing the previous methods.5,6
Acknowledgment
The authors thank the Instituto de Química, Universidade de
Brasília and FINATEC for financial support, FINEP-CT INFRA nº
0970/01 and CNPq and CAPES for fellowships. We also thank
Prof. Edson L. S. Lima (UFRJ) for helpful suggestions.
Synlett 2003, No. 15, 2351–2352 © Thieme Stuttgart · New York
View publication stats
LETTER
References
(1) Ager, D. J.; Prakash, I.; Schaad, D. R. Aldrichimica Acta
1997, 30, 3.
(2) (a) Crimmins, M. T.; King, B. W.; Tabet, E. A.; Chaudhary,
K. J. Org. Chem. 2001, 66, 894. (b) Velazquez, F.; Olivo,
H. F. Curr. Org. Chem. 2002, 6, 303.
(3) Evans, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1989, 111,
1063.
(4) (a) Ho, G. J.; Mathre, D. J. J. Org. Chem. 1995, 60, 2271.
(b) Ager, D. J.; Allen, D. R.; Schaad, D. R. Synthesis 1996,
1283. (c) Lee, J. Y.; Chung, Y. J.; Kim, B. H. Synlett 1994,
197. (d) Thom, C.; Kocienski, P. Synthesis 1992, 582.
(e) Evans, D. A.; Chapman, K. T.; Bisaho, J. J. Am. Chem.
Soc. 1988, 110, 1238. (f) Feroci, M.; Inesi, A.; Palombi, L.;
Rossi, L.; Sotgiu, G. J. Org. Chem. 2001, 66, 6185.
(5) Prashad, M.; Kim, H.-Y.; Har, D.; Repic, O.; Blacklock, T.
J. Tetrahedron Lett. 1998, 39, 9369.
(6) Graham, J. M.; Shireman, B. T.; Maddux, T. M.; Brandstedt,
C. M.; Zeller, W. E. Synth. Commun. 2000, 30, 1221.
(7) (a) Neises, B.; Steglish, W. Angew. Chem., Int. Ed. Engl.
1978, 17, 522. (b) Hassner, A.; Alexanian, V. Tetrahedron
Lett. 1978, 19, 4475.
Downloaded by: Angelo Machado, Dot. Lib Information. Copyrighted material.
(8) Typical Experimental Procedure: To a suspension of
oxazolidinone 1 (1.13 mmol), DMAP (0.15 mmol) and
cinnamic acid (1.47 mmol) in CH2Cl2 (1.5 mL) at 0 °C,
under an argon atmosphere, was added DCC in one portion
(1.47 mmol). After 10 min the temperature was raised to r.t.
and stirring was continued until no starting material has left
as confirmed by TLC. The dicyclohexylurea formed was
filtered and the precipitate washed with CH2Cl2 (10 mL).
The filtrate was washed with sat. NaHCO3 (10 mL), dried
with Na2SO4 and concentrated at reduced pressure to furnish
the crude product, which was purified by silica gel
chromatography (30% EtOAc in hexanes).
(9) All the compounds gave satisfactory spectral data.