Palladium(II)-catalyzed tandem intramolecular aminopalladation of alkynes and conjugate addition. Synthesis of oxazolidinones, imidazolidinones, and lactams

Article abstract of DOI:10.1021/ol006266s

(equation presented) Under the catalysis of a divalent palladium species, oxazolidinones, imidazolidinones, or lactams were conveniently obtained with high chemo-and stereoselectivity from the tandem intramolecular aminopalladation of alkynes, and protono

Full text of DOI:10.1021/ol006266s

ORGANIC
LETTERS
2000
Vol. 2, No. 17
2699-2702
Palladium(II)-Catalyzed Tandem
Intramolecular Aminopalladation of
Alkynes and Conjugate Addition.
Synthesis of Oxazolidinones,
Imidazolidinones, and Lactams
Aiwen Lei and Xiyan Lu*
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai, 200032, China
xylu@pub.sioc.ac.cn.
Received June 27, 2000
ABSTRACT
Under the catalysis of a divalent palladium species, oxazolidinones, imidazolidinones, or lactams were conveniently obtained with high chemo-
and stereoselectivity from the tandem intramolecular aminopalladation of alkynes, followed by insertion of alkenes, and protonolysis of the
newly formed carbon−palladium bond.
The reactions of vinylpalladium intermediates formed from
the oxidative addition of Pd(0) with RX have been exten-
sively studied (Scheme 1).1 However, the reactions of
regenerate the divalent palladium species are rarely
reported,2c-g and the carbon-palladium bond is easily
quenched by â-hydride elimination or reductive elimination
which in general generates the Pd(0) species, making the
catalytic cycle impossible. Thus, a large excess of oxidizing
reagents is necessary to recycle the divalent palladium
catalyst.1a In our previous work, we explored the protonolysis
reaction of the carbon-palladium bond in the presence of
halide ions, which is an effective method to quench the
carbon-palladium bond and regenerate the divalent pal-
ladium species (Scheme 1).3 Palladium(II)-catalyzed tandem
Scheme 1
(1) (a) Tsuji, J. Palladium Reagents and Catalysis: InnoVations in
Organic Synthesis; John Wiley: Chichester, 1995. (b) Soderberg, B. C. In
ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G.
A., Wilkinson, G., Eds.; Pergamon: 1995; Vol. 12, Chapter 3.5, p 241.
(2) (a) Mailtis, P. M. The Organic Chemistry of Palladium; Academic
Press: New York, 1971; Vol. 1, p 79. (b) Maitlis, P. M. Acc. Chem. Res.
1976, 9, 93-99. (c) Kaneda, K.; Uchiyama, T.; Fujiwarka, Y.; Teranishi,
S. J. Org. Chem. 1979, 44, 55. (d) Lambert, C.; Utimoto, K.; Nozaki, H.
Tetrahedron Lett. 1984, 25, 5323. (e) Yanagihara, N.; Lambert, C.; Iritani,
K.; Utimoto, K.; Nozaki, H. J. Am. Chem. Soc. 1986, 108, 2753. (f) Lu,
X.; Zhu, G.; Wang, Z. Synlett. 1998, 115. (g) Lu, X.; Ma, S. New Age of
Divalent Palladium Catalysis. In Transition Metal Catalyzed Reaction;
Murahashi, S.-I., Davies, S. G., Eds.; 1999; Chapter 6, p 133.
vinylpalladium intermediates which can also easily be
obtained from nucleopalladation of alkynes have received
only limited attention (Scheme 1).2 The main reason is that
methods of quenching the carbon-palladium bond to
10.1021/ol006266s CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/02/2000

reactions of nucleopalladation (Nu ) halogen,3a,c,d and
oxygen3b) of alkynes and conjugate addition have been
reported. Here, we wish to report our recent result in the
Pd(II)-catalyzed synthesis of oxazolidinones and their ana-
logues via tandem aminopalladation of alkynes and conjugate
addition.
However, the reaction of compounds 3a (1.0 mmol) and
acrolein (15 mmol) in the presence of LiBr (4 mmol) and
Pd(OAc)2 (0.05 mmol) in HOAc still produced the halo-
palladation-insertion-protonolysis product 4 rather than the
expected aminopalladation-insertion-protonolysis product
5a (Scheme 4).
In the literature, the aminopalladation was reported using
amines substituted with electron-withdrawing groups as
observed in the catalytic cyclization of o-allylanilines,
carbamates, and sulfonamides.1a,4,5 Thus, we initiated our
studies with N-tosyl-protected 4-pentynylamine 1. The reac-
tion of compound 1 (1 mmol) and acrolein (15 mmol) in
the presence of LiBr (4 mmol) and Pd(OAc)2 (0.05 mmol)
in HOAc afforded the product 2 initiated by halopalladation
instead of the expected product initiated by intramolecular
aminopalladation (Scheme 2), indicating that the halopalla-
Scheme 4
No reaction occurred when the bromide ion was changed
Scheme 2
to iodide ion in HOAc as solvent (Table 1, entries 2-4).
Table 1. Reaction of 3a with Acrolein under Different
Conditionsa
dation reaction is competitive with the expected aminopal-
ladation reaction.
product (yield)b
entry
solvent
additive
4
5a
With the aim of exploring the divalent palladium-catalyzed
reaction utilizing protonolysis of the carbon-palladium bond
as the key step in regenerating the divalent palladium species,
halide ions and acidic conditions for protonolysis are
necessary.3 Therefore, the nucleophile should be still able
to work properly even under acidic conditions. From our
previous work on the intramolecular oxypalladation of
alkynoic acids,3a,b,e it was known that carboxylic acids can
serve as effective nucleophiles in acetic acid. On comparing
the pKa values of carboxylic acid and different kinds of
amides (Scheme 3), we learned that the pKa values of N-tosyl
1
2
3
4
5
6
7
8
9
HOAc
HOAc
HOAc
HOAc
THF
THF
THF
THF
THF
LiBr
Bu4NI
LiI
LiI/LiOAc
LiI/LiOAc
LiI
NaI
LiBr
LiCl
59
70
70
70
68
61
a Reaction conditions: 3a (1.0 mmol), acrolein (15 mmol), Pd(OAc)2
(0.05 mmol), and LiX (2.0 mmol) in solvent (5 mL) at room temperature.
b Isolated yields.
Scheme 3
However, the aminopalladation-insertion-protonolysis prod-
uct 5a did form when THF was used instead of HOAc as
the solvent (Table 1, entries 5-7). Use of either bromide or
chloride ions gave similar results (Table 1, entries 8 and 9).
A wide range of substituted carbamates 3 were examined
under similar conditions (Scheme 5 and Table 2), and they
(4) (a) Utimoto, K.; Miwa, H.; Nozaki, H.; Tetrahdron, Lett. 1981, 22,
4277. (b) Pugin, B.; Venanzi, L. M. J. Am. Chem. Soc. 1983, 105, 6877.
(5) Tamaru, Y.; Hojo, M.; Higashimura, H.; Yoshida, Z. J. Am. Chem.
Soc. 1988, 110, 3994, and references therein.
carbamates and N-tosylamides6 are comparable with that of
carboxylic acids. Thus, we chose N-tosyl carbamate 3a to
examine the possibility of the aminopalladation reaction.7
(6) Schaaf, T. K.; Hess, H. J. J. Med. Chem. 1979, 22, 1340.
(7) N-Tosyl carbamates could be used as the efficient nucleophiles in
the aminopalladation reaction of alkenes or alkynes. (a) Trost, B. M.;
Vranken, D. L.-V. Angew. Chem., Int. Ed. Engl. 1992, 31, 228. (b) Tamaru,
Y.; Kimura, M. Synlett 1997, 749. (c) Bando, T.; Harayama, H.; Fukazawa,
Y.; Shiro, M.; Fugami, K.; Tanaka, S.; Tamaru, Y. J. Org. Chem. 1994,
59, 1465. (d) Kimura, M.; Wakamiya, Y.; Horino, Y.; Tamaru, Y.
Tetrahedron Lett. 1997, 38, 3963. (e) Arcadi, A. Synlett 1997, 941.
(3) (a) Wang, Z.; Lu, X. Chem. Commun. 1996, 535. (b) Wang, Z.; Lu,
X. J. Org. Chem. 1996, 61, 2254. (c) Wang, Z.; Lu, X. Tetrahedron, Lett.
1997, 38, 5213. (d) Wang, Z.; Lu, X.; Lei, A.; Zhang, Z. J. Org. Chem.
1998, 63, 3806. (e) Wang, Z.; Zhang, Z.; Lu, X. Organometallics 2000,
19, 775.
2700
Org. Lett., Vol. 2, No. 17, 2000

In addition, the reaction can be carried out in a one-pot
manner via in situ formation of N-tosyl carbamates from the
corresponding alkynols,9a followed by a Pd(II)-catalyzed
reaction, as exemplified by the preparation of aldehyde 5a
from propargyl alcohol in 82% overall yield with the in situ
formation of N-tosyl carbamate 3a (Scheme 6).
Scheme 5
Scheme 6
all gave exclusively the products initiated by aminopallada-
tion.8 It was found that the substituents in 3 played an
important role in the reaction. With the disubstituted 3f or
3h, oxazolidinone 6 was also formed as a byproduct together
with the expected product 5 (Table 2, entries 6-9).
A similar reaction could also occur in an analogous way,
e.g., the oxygen atom in carbamate 3 could be replaced by
a nitrogen atom or a methylene group. Imidazolidinone 8b
could be obtained in 58% yield from urea 7b, but no expected
product was obtained with urea 7a under the same conditions.
In addition, lactam 10 could be obtained from amide 9 in
88% yield (Scheme 7).
Table 2. Reaction of Substituted 3 with Alkenes under Pd(II)
Catalysisa
Scheme 7
3
product (%)b
entry
3
R1
R2
R3
R4
5
6
1
2
3
4
5
6
7
8
9
3a
3a
3c
3c
3e
3f
3f
3h
3h
3j
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
Me
Me
H
Me
H
85 (5a )
50 (5b)
61 (5c)
72 (5d )
83 (5e)
68 (5f)
54 (5g)
31 (5h )
39 (5i)
72 (5j)
63 (5k )
Et
Et
Ph
Me
Me
n-C5H11
n-C5H11
H
H
H
Me
Me
Me
Me
H
32 (6f)
46 (6f)
22 (6h )
33 (6h )
The following mechanism was proposed: First, the Pd-
(II) species coordinated with the triple bond of carbamate 3.
Trans attack of the tosyl amide anion to the coordinated triple
bond afforded (E)-vinylpalladium intermediate 12 (amino-
H
Me
Me
Me
H
Me
10
11
3j
H
a Reaction conditions: 3 (1.0 mmol), electron-deficient alkenes (15
mmol), Pd(OAc)2 (0.05 mmol), and LiBr (2.0 mmol) at room temperature.
b Isolated yields.
Scheme 8
The structures of oxazolidinones 5 were characterized
using NMR, IR, MS, and elementary analysis. The stereo-
chemistry of exocyclic double bonds in oxazolidinones 5 was
in the (E)-configuration as determined by comparing the
chemical shifts of the vinylic protons with literature values9
or by NOESY spectra (for 5j10).
(8) Typical procedure: 3a (1.0 mmol) was reacted with acrolein (15
mmol) in THF (5 mL) in the presence of Pd(OAc)2 (0.05 mmol) and NaI
(2.0 mmol) at room temperature. After the reaction was complete as
monitored by TLC, the reaction mixture was concentrated under reduced
pressure and the residue was purified by column chromatography on silica
gel (eluent: petroleum ether/ethyl acetate ) 4/1-2/1) to give product 5a
1
in 85% yield: oil; H NMR (300 MHz, CDCl3) δ 9.73 (s, 1H), 7.84 (d, J
) 8.5 Hz, 2H), 7.28 (d, J ) 8.1 Hz, 2H), 5.79 (tt, J ) 2.6, 7.9 Hz, 1H),
4.82 (t, J ) 2.6 Hz, 2H), 2.59 (t, J ) 6.8 Hz, 2H), 2.38 (s, 3H), 2.13 (dt,
J ) 8.3, 6.8 Hz, 2H); IR (neat) ν 2852, 2747, 1792, 1725, 1692, 1391,
1160, 1089, 1060 cm-1; MS m/e 310 (M+ + 1), 309 (M+), 253, 228, 155,
138, 91 (100), 65. Anal. Calcd for C14H15NO5S: C, 54.36; H, 4.89; N,
4.53. Found: C, 54.33; H, 5.02; N, 4.73.
Org. Lett., Vol. 2, No. 17, 2000
2701

palladation),5,7e followed by insertion of alkenes and proto-
nolysis of the newly formed carbon-palladium bond in
palladium enolate 13 in the presence of halide ions to yield
aldehyde or ketone 5 and regenerate the divalent palladium
species to complete the catalytic cycle (Scheme 8).3 The key
point is that the â-hydride elimination reaction is inhibited
in the presence of excess halide ions.3e In this reaction, the
source of proton for protonolysis may be the ionization of
tosyl amide in 3. The possible depression of the ionization
of tosylamide in HOAc may result in the preference of THF
as solvent for the reaction. The direct protonolysis of
intermediate 12 yielded the byproduct 6.
In summary, we developed an efficient method for the
synthesis of oxazolidinones, imidazolidinones, or lactams
with high chemo- and stereoselectivity from alkynol car-
bamates and R,â-unsaturated carbonyls. This Pd(II)-catalyzed
reaction involves tandem intramolecular aminopalladation,
olefin insertion, and protonolysis of the carbon-palladium
bond.
Acknowledgment. We thank the National Natural Sci-
ences Foundation of China and the Chinese Academy of
Sciences for financial support.
(9) (a) Tamaru, Y.; Kimura, M.; Tanaka, S.; Kure, S.; Yoshida, Z. Bull.
Chem. Soc. Jpn. 1994, 67, 2838. (b) Gaudemer, A. Determination of
Configuration by NMR Spectroscopy. In Stereochemistry, Fundamentals
and Methods; Kagan, H. B., Ed.; Georg Thieme: Stuggart, 1977; Vol. 1,
p 44.
(10) There is strong NOE between two allylic protons in the NOESY
spectra of compound 5j.
Supporting Information Available: Spectral and ana-
lytical data for new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL006266S
2702
Org. Lett., Vol. 2, No. 17, 2000