Synthesis of 2-oxazolidinones by direct palladium-catalyzed oxidative carbonylation of 2-amino-1-alkanols

Article abstract of DOI:10.1021/ol9913789

(equation presented) 2-Oxazolidinones 2 are obtained in excellent yields (up to 100%) and with unprecedented catalytic efficiencies (up to 2000 mol of product/mol of catalyst used) by direct Pdl₂/Kl-catalyzed oxidative carbonylation of the readily available 2-amino-1-alkanols 1. Reactions are carried out in MeOH as the solvent at 100 °C using a 1/6/5 CO/O₂/air mixture (60 atm total pressure at 25 °C).

Full text of DOI:10.1021/ol9913789

ORGANIC
LETTERS
2
000
Vol. 2, No. 5
25-627
Synthesis of 2-Oxazolidinones by Direct
Palladium-Catalyzed Oxidative
6
Carbonylation of 2-Amino-1-alkanols
,
†
,†,‡
†
§
Bartolo Gabriele,* Giuseppe Salerno,* Donatella Brindisi, Mirco Costa, and
§
Gian Paolo Chiusoli
Dipartimento di Chimica, UniVersit a` della Calabria, 87030 ArcaVacata di Rende,
Cosenza, Italy, and Dipartimento di Chimica Organica e Industriale, UniVersit a` di
Parma, Parco Area delle Scienze, 43100 Parma, Italy
b.gabriele@unical.it
Received December 21, 1999
ABSTRACT
2
-Oxazolidinones 2 are obtained in excellent yields (up to 100%) and with unprecedented catalytic efficiencies (up to 2000 mol of product/mol
of catalyst used) by direct PdI /KI-catalyzed oxidative carbonylation of the readily available 2-amino-1-alkanols 1. Reactions are carried out in
MeOH as the solvent at 100 °C using a 1/6/5 CO/O /air mixture (60 atm total pressure at 25 °C).
2
2
2
-Oxazolidinones 2 are a very important class of heterocyclic
2-Oxazolidinones are usually prepared by reaction of
2-amino-1-alkanols 1 with diethyl carbonate. We wish to
report herein the preparation of 2 by direct palladium-
catalyzed oxidative carbonylation of 1 according to eq 1.6
5
compounds. Chiral 2-oxazolidinones are widely used as
chiral auxiliaries in many important asymmetric syntheses,
and some molecules containing the 2-oxazolidinone moiety
have shown antibacterial activity. Recently, they have also
1
2
found application as intermediates in the synthesis of
3
4
aldehydes and chiral amines.
†
Universit a` della Calabria.
E-mail: g.salerno@unical.it.
Universit a` di Parma.
‡
§
(1) For reviews on chiral 2-oxazolidinones in asymmetric synthesis,
see: (a) Evans, D. A. Aldrichim. Acta 1982, 15, 23-32. (b) Ager, D. J.;
Prakash, I.; Schaad, D. R. Chem. ReV. 1996, 96, 835-875. (c) Ager, D. J.;
Prakash, I.; Schaad, D. R. Aldrichim. Acta 1997, 30, 3-12. For a recent
review on stoichiometric asymmetric syntheses, see: (d) Regan, A. C. J.
Chem. Soc., Perkin Trans. 1 1999, 357-373. For some recent examples of
application of 2 as chiral auxiliaries, see: (e) K o¨ ll, P.; L u¨ tzen, A.
Tetrahedron: Asymmetry 1996, 7, 637-640. (f) L u¨ tzen, A.; K o¨ ll, P.
Tetrahedron: Asymmetry 1997, 8, 29-32. (g) L u¨ tzen, A.; K o¨ ll, P.
Tetrahedron: Asymmetry 1997, 8, 1193-1206. (h) Fonquerna, S.; Moyano,
A.; Peric a` s, M. A.; Riera, A. Tetrahedron: Asymmetry 1997, 8, 1685-
Our method consists of the reaction of 1 at 100 °C with
2
carbon monoxide and oxygen (CO/O /air ) 1/6/5, 60 atm
total at 25 °C) in MeOH as the solvent in the presence of
PdI
PdI
2
2
in conjunction with an excess of KI (200 mol/mol of
). The use of pure oxygen rather than oxygen diluted
with air invariably led to lower yields of 2, probably due to
competitive oxidation processes.
Table 1 reports the results obtained with different â-amino
alcohols. 2-Oxazolidinones 2 were consistently obtained in
excellent yields (86-100%) and with unprecedented catalytic
efficiencies for this kind of reaction (860-2000 mol of
1
6
1
691. (i) Gibson, C. L.; Gillon, K.; Cook, S. Tetrahedron Lett. 1998, 39,
733-6736. (j) Reddy, G. V.; Rao, G. V.; Iyengar, D. S. Chem. Commun.
999, 317-318. (k) Davies, S. G.; Sanganee, H. J.; Szolcsanyi, P.
Tetrahedron 1999, 55, 3337-3354. (l) Bull, S. D.; Davies, S. G.; Jones,
S.; Sanganee, H. J. J. Chem. Soc., Perkin Trans. 1 1999, 387-398. (m)
Bravo, P.; Fustero, S.; Guidetti, M.; Volonterio, A.; Zanda, M. J. Org. Chem.
1
999, 64, 8731-8735.
1
0.1021/ol9913789 CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/12/2000

a substrate/catalyst ratio of 1000 ensured faster kinetics and
higher yields of the corresponding 2-oxazolidinones (compare
entries 7 and 9 with entries 8 and 10, respectively). The lower
yield of 2 obtained with a lower amount of catalyst in such
cases suggests the occurrence of a competitive uncatalyzed
decomposition pathway of the substrates.
A large excess of both oxygen and iodide anions is
essential for the process. In fact, by employing the conditions
we previously used for the oxidative carbonylation of
Table 1. Synthesis of 2-Oxazolidinones 2 by PdI
KI-Catalyzed Oxidative Carbonylation of 2-Amino-1-alkanols 1
2
/
a
conversn of
1 (%)b
yield of
entry
1
R1
R2
1/PdI2
2 (%)c
1
2
3e
4
5
6
7
8
9
1a
H
H
H
H
H
Me
Ph
Me2CH
Me2CH
PhCH2
PhCH2
2000
2000
2000
2000
2000
2000
2000
1000
2000
1000
96
100
69
99
97
100
79
100
84
90 (85)
100 (92)
53
87 (79)
93 (85)
98 (89)
57
100 (91)
65
86 (78)
1bd
1bd
1cd
Me
Me
Ph
H
H
H
H
H
H
1d d
1ef
1fg
1fg
1gg
1gg
2
1-alkynes, i.e. KI/PdI molar ratio ) 10 under 20 atm total
7
pressure of a 3:1 mixture of CO/air, no reaction at all
occurred. Very poor results were also obtained when the
reaction was carried out with KI/PdI
partial pressure was only 1-2 atm (as in the mixture CO/air
3:1 at 20 or 40 atm of total pressure) or using KI/PdI
10 under an oxygen partial pressure of 35 atm (as in the
mixture CO/O /air ) 1/6/5 at 60 atm of total pressure). On
the other hand, the use of a KI/PdI molar ratio of 100 rather
than 200 with CO/O /air ) 1/6/5 (60 atm total pressure) led
to less satisfactory results with respect to KI/PdI ) 200
compare entries 2 and 3). We believe that a large excess of
2
) 200 when the oxygen
1
0
100
)
2
)
a
Unless otherwise noted, all reactions were carried out in MeOH (0.5
mmol of 1/mL of MeOH, 10-15 mmol scale based on 1) at 100 °C for 15
2
h under 60 atm of a 1/6/5 mixture of CO/O2/air in the presence of PdI2 in
b
c
2
conjunction with 200 equiv of KI. Determined by GLC. GLC yield
e
(
isolated yield) based on 1. d Racemic. The reaction was carried out using
2
f
g
a KI/PdI2 molar ratio of 100 rather than 200. R enantiomer. S enantiomer.
2
(
iodide anions and oxygen are primarily required to ensure a
fast reoxidation of Pd(0) according to Scheme 1 (anionic
product/mol of catalyst used). Although a substrate/catalyst
ratio as high as 2000 could be used successfully with most
substrates (entries 1, 2, and 4-6), for less reactive 2-amino-
1-alkanols such as L-valinol (1f) and L-phenylalaninol (1g)
Scheme 1
(2) For representative examples, see: 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,
3
2, 1673-1681. 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, 2569-2578. 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-
1
165. Seneci, P.; Caspani, M.; Ripamonti, F.; Ciabatti, R. J. Chem. Soc.,
Perkin Trans. 1 1994, 2345-2351. Grega, K. C.; Barbachyn, M. R.;
Brickner, S. J.; Mizsak, S. A. J. Org. Chem. 1995, 60, 5255-5261. 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, 673-679. 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, 680-685. Lohray,
B. B.; Baskaran, S.; Rao, B. S.; Reddy, B. Y.; Rao, I. N. Tetrahedron Lett.
iodide ligands are omitted for simplicity). As we already
suggested, the most likely mechanism of reoxidation of Pd-
7
(0) ensuing from the oxidative carbonylation process in our
reactions involves the oxidation of HI by oxygen to give
iodine, which then oxidatively adds to Pd(0). In the presence
of an amino group, HI is almost completely “blocked” as
ammonium salt, and the reoxidation process becomes more
1
999, 40, 4855-4856.
3) Bach, J.; Bull, S. D.; Davies, S. G.; Nicholson, R. L.; Sanganee, H.
J. Smith, A. D. Tetrahedron Lett. 1999, 40, 6677-6680.
4) O’Hagan, D.; Tavasli, M.; Tetrahedron: Asymmetry 1999, 10, 1189-
192.
5) Gage, J. R.; Evans, D. A. Org. Synth. 1990, 68, 77-82. For a review
on the synthesis of 2, see ref 1b. For some recent developments in
-oxazolidinone synthesis, see: Tingoli, M.; Testaferri, L.; Temperini, A.;
(
8
(
difficult. However, a large excess of iodide ions may
1
effectively shift the acid-base equilibrium to the left, and a
(
2
Inesi, A.; Mucciante, V.; Rossi, L. Tetrahedron Lett. 1999, 40, 6059-6060.
Sugiyama, S.; Watanabe, S.; Ishii, K. Tetrahedron Lett. 1999, 40, 7489-
7492. Chiusoli, G. P.; Costa, M.; Gabriele, B.; Salerno, G. J. Mol. Catal.
A 1999, 143, 297-310.
Tiecco, M. J. Org. Chem. 1996, 61, 7085-7091. Sep u´ lveda-Arques, J.;
Armero-Alarte, T.; Acero-Alarc o´ n, A.; Zaballos-Garcia, E.; Solesio, B. Y.;
Carrera, J. E. Tetrahedron 1996, 52, 2097-2102. Misiti, D.; Zappia, G.;
Delle Monache, G. Liebigs Ann. 1996, 235-238. Bacchi, A.; Chiusoli, G.
P.; Costa, M.; Gabriele, B.; Righi, C.; Salerno, G. Chem. Commun. 1997,
(6) Oxidative carbonylation of 1 to give 2 was previously reported to
occur at 80 °C and under an atmospheric pressure of CO in DME as the
solvent using a stoichiometric amount of PdCl2 in the presence of 2 equiv
of NaOAc: Tam, W. J. Org. Chem. 1986, 51, 2977-2981. More recently,
complex PdCl2(MeCN)2 in conjunction with CuI (5-20 equiv) in acetonitrile
(under an atmospheric pressure of a 1:1 mixture of CO and O2 at 50 °C or
under 85 atm of a 94:6 mixture of CO and O2 at room temperature) were
shown to catalyze the reaction with catalytic efficiencies not higher than
19 mol of 2/mol of palladium used: Imada, Y.; Mitsue, Y.; Ike, K.;
Washizuka, K.; Murahashi, S.-I. Bull. Chem. Soc. Jpn. 1996, 69, 2079-
2090.
1
209-1210. Sudharshan, M.; Hultin, P. G. Synlett 1997, 171-172. Tamaru,
Y.; Kimura, M. Synlett 1997, 749-757 and references therein. Arcadi, A.
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1
997, 944-946. Tiecco, M.; Testaferri, L.; Marini, F.; Temperini, A.;
Bagnoli, L.; Santi, C. Synth. Commun. 1997, 27, 4131-4140. Inesi, A.;
Mucciante, V.; Rossi, L. J. Org. Chem. 1998, 63, 1337-1338. Le Gendre,
P.; Thominot, P.; Bruneau, C.; Dixneuf, P. H. J. Org. Chem. 1998, 63,
1
806-1809. Takacs, J. M.; Jaber, M. R.; Vellekoop, A. S. J. Org. Chem.
1998, 63, 2742-2748. Tenholte, P.; Thijs, L.; Zwanenburg, B. Tetrahedron
Lett. 1998, 39, 7407-7410. Sitzmann, M. E.; Kenar, J. A.; Trivedi, N. J.
Tetrahedron Lett. 1998, 39, 8211-8212. Knolker, H. J.; Braxmeier, T.
Tetrahedron Lett. 1998, 39, 9407-9410. Li, G.; Lenington, R.; Willis, S.;
Kim, S. H. J. Chem. Soc., Perkin Trans. 1 1998, 1753-1754. Feroci, M.;
(7) Gabriele, B.; Costa, M.; Salerno, G.; Chiusoli, G. P. J. Chem. Soc.,
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(8) Bonardi, A.; Costa, M.; Gabriele, B.; Salerno, G.; Chiusoli, G. P.
Tetrahedron Lett. 1995, 36, 7495-7498.
626
Org. Lett., Vol. 2, No. 5, 2000

high O
HI to iodine, thus allowing fast and effective regeneration
of the catalytically active species PdI
2
partial pressure may further favor the oxidation of
Supporting Information Available: Experimental pro-
cedures and characterization data for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
2
.
Acknowledgment. Financial support from the Ministero
dell’Universit a` e della Ricerca Scientifica e Tecnologica is
gratefully acknowledged.
OL9913789
Org. Lett., Vol. 2, No. 5, 2000
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