Palladium(II)-catalyzed tandem reaction of intramolecular aminopalladation of allenyl N-tosylcarbamates and conjugate addition

Article abstract of DOI:10.1021/ol016727p

equation presented A divalent palladium-catalyzed tandem cyclization-coupling reaction of allenyl N-tosylcarbamates and acrolein was developed. The reaction gave aldehyde-functionalized 2-oxazolidinones in one step with high regioselectivity. A mechanism

Full text of DOI:10.1021/ol016727p

ORGANIC
LETTERS
2
001
Vol. 3, No. 24
879-3882
Palladium(II)-Catalyzed Tandem Reaction
of Intramolecular Aminopalladation of
Allenyl N-Tosylcarbamates and
Conjugate Addition
3
Guosheng Liu and Xiyan Lu*
State Key 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 September 7, 2001
ABSTRACT
A divalent palladium-catalyzed tandem cyclization−coupling reaction of allenyl N-tosylcarbamates and acrolein was developed. The reaction
gave aldehyde-functionalized 2-oxazolidinones in one step with high regioselectivity. A mechanism involving intramolecular aminopalladation
of allene, followed by insertion of alkene and C−Pd bond protonolysis, is proposed.
The vinylic palladium species is a versatile reactive inter-
mediate in palladium-catalyzed coupling reactions. Besides
nucleophile attacks the â-carbon atom to form a π-allylic
palladium species (â-adduct) (Scheme 1).
1
3
the well-studied oxidative addition of vinylic halides or
triflates to Pd(0), which generates the vinylic palladium
1
species, it can be also obtained from the addition of a
Scheme 1
1,2
nucleophile to the divalent palladium-coordinated alkynes
1
a,3
or allenes.
There are two kinds of pathways for the
reaction of Pd(II)-coordinated allenes with nucleophiles: (1)
the nucleophile attacks the R- or γ-carbon atom to form a
vinylic palladium species (R-adduct or γ-adduct); (2) the
(
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) Maitlis, P. M. The Oragnic Chemistry of Palladium; Academic
Press: New York, 1971; Vol. 1, p 79. (b) Maitlis, P. M. Acc. Chem. Res.
976, 9, 93-99. (c) Kaneda, K.; Uchiyama, T.; Fujiwarka, Y.; Teranishi,
1
S. J. Org. Chem. 1979, 44, 55. (d) Yanagihara, N.; Lambert, C.; Iritani, K.;
Utimoto, K.; Nozaki, H. J. Am. Chem. Soc. 1986, 108, 2753. (e) Lu, X.;
Zhu, G.; Wang, Z. Synlett. 1998, 115. (f) Lu, X.; Ma, S. New Age of
Divalent Palladium Catalysis. In Transition Metal Catalyzed Reaction;
Murahashi, S.-I., Davies, S. G., Eds.; Blackwell Science, Oxford, 1999;
Chapter 6, p 133. (g) Zhang, Q.; Lu, X. J. Am. Chem. Soc. 2000, 122,
A number of Pd(II)-catalyzed reactions of allenes with
nucleophiles have been reported in the literature. However,
in most of these reactions, some oxidant (e.g., Cu(II) salts
or quinones) must be used to regenerate Pd(II) from Pd(0)
in order to achieve a catalytic reaction. To our knowledge,
nucleophilic addition reactions of allenes catalyzed by
7
604.
3) (a) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem.
(
ReV. 2000, 100, 3067. (b) Hiemstra, H.; Hengouwen, W. G. B. V. Current
Trends in Organic Synthesis; Scolastico, C., Nicotra, F., Eds.; Kluwer
Academic/Plenum Publishers: New York, 1999; pp 267-274.
4
1
0.1021/ol016727p CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/31/2001

divalent palladium without additional oxidants have not been
widely reported. In our previous work, we studied the
and 3, Table 1). In the absence of halide ions, no coupling
reaction occurred, but a Pd black precipitate appeared within
a few minutes (entry 4, Table 1). Addition of HOAc did not
improve the yield of the reaction (entry 5, Table 1), and
surprisingly, no reaction occurred when neat HOAc was used
as the solvent (entry 6, Table 1). The yield of 2c can be
improved by using a higher concentration of acrolein and
slow addition of 1 (entries 7-9, Table 1). Further, in a
control experiment with only 1c as the substrate and no
acrolein, the reaction finished within 1 h at room temperature
and gave 3c as the main product in good yield (79%),7
confirming that 3c is the self-coupling product of 1c. Finally,
the standard procedure was carried out by adding a THF
solution of allenyl N-tosylcarbamate 1 dropwise to a mixture
5
protonolysis reaction of the carbon-palladium bond in the
presence of excess halide ions and found it to be an effective
method to quench the carbon-palladium bond and regenerate
6
Pd(II) species. These results prompted us to explore the
possibility of a Pd(II)-catalyzed nucleophilic addition reaction
of allenes using C-Pd bond protonolysis as the Pd(II)
regeneration step. Herein, we report the development of a
novel Pd(II)-catalyzed tandem cyclization-conjugate addi-
tion reaction of allenyl N-tosylcarbamates to acrolein by
applying this principle.
We first investigated the reaction of allenyl N-tosyl-
1
2
3
carbamate 1c (R ) R ) H, R ) i-Pr, 0.5 mmol) with
acrolein (2.5 mmol) in the presence of Pd(OAc) (5 mol %)
2
of Pd(OAc)
2
, LiBr, and acrolein in THF over 3 h and then
and NaI (2 mmol) in THF (5 mL) (Scheme 2). The reaction
stirring the mixture for an additional 2 h. A series of allenyl
1
2
3
N-tosylcarbamates with different R , R , and R substituents
was coupled with acrolein using the standard procedure. The
results are shown in Table 2.
Scheme 2
Table 2. Reactions of Allenyl N-Tosylcarbamates 1 with
Acrolein Catalyzed by Pd(II)a
yield of product (%)b
was complete within 12 h and gave the expected cyclization-
conjugate addition product 2c (yield: 46%), as well as
another product, 3c, formed from cyclization and coupling
with another molecule of 1 (yield: 47%) (entry 1, Table 1).
When LiCl or LiBr was used in place of NaI, the reaction
also proceeded smoothly, giving similar results (entries 2
R1
R2
R3
2 (trans:cis)c
entry
1
3
1
2
3
4
5
1a
1b
1c
1d
1e
1f
H
H
H
H
H
H
H
H
H
H
H
H
H
Et
2a
74
3a , 17
3b, 10
2b
2c
2d
2e
2f
67 (2.8:1)
Pri
Prn
n-C5H11
Ph
86 (>97:3) trace
60 (2.4:1)
3d , 17
73 (4.4:1)
trace
6d
84 (>97:3) trace
Table 1. Reactions of 1c with Acrolein Catalyzed by Pd(II)
Speciesa
7
8
1g
1h
Me Me
Me Me Et
H
2g
2h
85
trace
trace
71 (1.7:1)
a
All reaction were carried out using 1 (0.5 mmol) at room temperature.
A solution of 1 in THF (3 mL) was added to a mixture of Pd(OAc)2 (0.025
mmol), LiBr (2 mmol). and acrolein (7.5 mmol) in THF (5 mL) over 3 h,
and the mixture was stirred for another 2 h. Isolated yield. c The cis:trans
b
1
yield (%)b
ratio was determined by the H NMR spectra of the product mixture.
acrolein:1c
d
Compound 1f is unstable, was synthesized from allenyl alcohol with
entry (molar ratio) additive
solvent
THF
THF
THF
THF
THF/HOAc
time (h) 2c
3c
46 47
41 47
TsNCO, and was used in situ without purification.
1
5
5
5
5
5
NaI
12
2
2
3
4c
5
LiCl
LiBr
none
LiBr
2
55 35
The cyclization is highly regioselective, giving five-
4
4
no reaction
47 26
membered ring products (oxazolidinones). For the substrate
3
1
with a bulky R group, only trans-2 was obtained, showing
(v/v: 4/1)
6
7
8
9
5
20
15
15
LiBr
LiBr
LiBr
LiBr
HOAc
THF
THF
THF
12
2
3d
5e
no reaction
66 23
79 13
(
4) (a) Alper, H.; Hartstock, F. H.; Despeyrous, B. J. Chem. Soc., Chem.
Commun. 1984, 905. (b) Hegedus, L. S.; Kambe, N.; Ishii, Y.; Mori, A. J.
Org. Chem. 1985, 50, 2240. (c) Walkup, R. D.; Mosher, M. D. Tetrahedron
Lett. 1987, 28, 1023. (d) Walkup, R. D.; Mosher, M. D. Tetrahedron. 1993,
86 trace
4
9, 9285. (e) Gallagher, T.; Davis, I.W.; Jones, S. W.; Lathbury, D.; Mahon,
a
All reactions were carried out using 1c (0.5 mmol), Pd(OAc)2 (0.025
M. F.; Molly, K. F.; Shaw, R. W.; Vernon, P. J. Chem. Soc., Perkin Trans.
1 1992, 433. (f) Kimura, M.; Saeki, N.; Uchida, S.; Harayama, H.; Tanaka,
S.; Fugami, K.; Tamaru, Y. Tetrahedron Lett. 1993, 34, 7611. (g) B a¨ ckvall,
J.-E.; Jonasson, C. Tetrahedron Lett. 1997, 38, 291. (h) Jonasson, C.;
Howath, A.; B a¨ ckvall, J.-E. J. Am. Chem. Soc. 2000, 122, 9600.
(5) (a) Prasad, J. S.; Liebeskind, L. S. Tetrahedron Lett. 1988, 29, 4257.
(b) Kimura, M.; Fugami, K.; Tanaka, S.; Tamaru, Y. J. Org. Chem. 1992,
57, 6377. (c) Kimura, M.; Tanaka, S.; Tamaru, Y. J. Org. Chem. 1995, 60,
mmol), additive (2 mmol), and acrolein in the specified solvent (5 mL) at
room temperature. Isolated yield. A black precipitate appeared within
several minutes. A solution of 1c in THF was added dropwise into a
solution of Pd(OAc)2, LiBr, and acrolein in THF in 1 h, and then the mixture
was stirred for another 2 h. A solution of 1c in THF was added dropwise
into a solution of Pd(OAc)2, LiBr, and acrolein in THF in 3 h, and then the
mixture was stirred for another 2 h.
b
c
d
e
3764. (d) Ma, S.; Gao, W. Tetrahedron Lett. 2000, 41, 8933.
3880
Org. Lett., Vol. 3, No. 24, 2001

that the reaction is stereoselective (entries 3 and 6, Table
2 2
to give product 3, CO , and TsNH and regenerate the
Pd(II) species (Scheme 4, path B). Here, the halide ion plays
3
2). The stereoselectivity decreases with less bulky R groups
(
2
entries 2, 3, 4, and 8, Table 2). The coupled products 2a-
h were characterized by H NMR, IR, MS, and elemental
a very important role in inhibiting the â-H elimination of
both 5 and 6, making the reaction proceed with high catalytic
1
8
analyses or HRMS. The stereoconfigurations were deter-
mined by NOESY spectra and compared with the literature
data. For substrates with a substituent at the allene carbon
where the cyclization occurs (e.g., compound 1i), the reaction
gave a complex mixture (Scheme 3).
efficiency and good selectivity. In this reaction, the proton
needed for protonolysis may come from the dissociation of
the acidic N-H in 1. A related observation is that the reaction
is completely shut down in neat HOAc (entry 6, Table 1).
This is possibly due to suppression of the N-H dissociation,
which is imperative for aminopalladation to occur.
5
c
To examine the generality of the present reaction, as well
as to develop synthetic methods for other nitrogen-containing
heterocyclic compounds, e.g., functionalized lactams, we
prepared 7 and tested its reaction with acrolein under the
standard conditions. To our delight, product 8 was obtained
as the single product in very high yield (95%) (Scheme 5).
Scheme 3
Scheme 5
The following mechanism was proposed: First, the nu-
cleophile intramolecularly attacks the Pd(II)-coordinated
allene 1 to form the vinylic palladium intermediate 4. This
is followed by the insertion of the acrolein into the vinylic
palladium bond to yield intermediate 5 and then the newly
formed carbon-palladium bond is protonized in the presence
of halide ions to give 2 (Scheme 4, path A). However,
Scheme 4
It is not clear why 7 gives a higher yield and selectivity than
1
. A possible explanation is that the relative rate for the
insertion of acrolein versus insertion of allene (path A versus
path B, Scheme 4) is higher for the vinylic palladium
intermediate 9 formed from 7 than that for 4. Another
possibility is that the insertion of allene to the vinylic
palladium is reversible, so when â-heteroatom elimination
becomes impossible for the allyl palladium intermediate 11,
the reaction will solely give acrolein-coupled product 8 via
path A.
In summary, we have developed a divalent palladium
catalyzed coupling reaction of allenyl N-tosylcarbamates or
N-tosyl allenamide with acrolein. Functionalized 2-oxazo-
lidinones and lactams can be synthesized with high regio-
selectivity in one step. The reaction mechanism involves
3
because allenes are more reactive than alkenes, 1 can
compete favorably to insert into the vinylic palladium bond
of 4 to yield 6, which undergoes â-heteroatom elimination
(
6) (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.
997, 38, 5213. (d) Wang, Z.; Lu, X.; Lei, A.; Zhang, Z. J. Org. Chem.
998, 63, 3806. (e) Xie, X.; Lu, X. Synlett 2000, 707. (f) Lu, X.; Wang, Z.
(8) In the Pd(II)-mediated conjugate addition reaction, the halide ion can
block the â-H elimination of a (2-oxoalkyl)palladium species, giving
preferentially the protonolysis product, see: Wang, Z.; Zhang, Z.; Lu, X.
Organometallics 2000, 19, 775. Zhang, Z.; Lu, X.; Xu, Z.; Zhang, Q.; Han,
X. Organometallics 2001, 20, 3724.
1
1
Polyhedron 2000, 19, 577. (g) Lei. A.; Lu, X. Org. Lett. 2000, 2, 2699.
7) Toluenesulfonamide, TsNH2, was isolated as a byproduct.
(
Org. Lett., Vol. 3, No. 24, 2001
3881

intramolecular aminopalladation of allene, acrolein insertion,
and halide-assisted protonolysis to regenerate Pd(II) species
without using oxidants.
also thank the National Natural Sciences Foundation of China
and the Chinese Academy of Sciences for financial support.
Supporting Information Available: Spectroscopic data
for new compounds 2a-2h, 7, and 8. This material is
available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. This work was funded by the Major
State Basic Research Program (Grant G2000077502-A). We
OL016727P
3882
Org. Lett., Vol. 3, No. 24, 2001