Microwave-enhanced Pd(0)/acetic acid catalyzed allylation reactions of C, N, and O-pronucleophiles with alkynes

Article abstract of DOI:10.1016/j.tetlet.2004.09.099

An efficient method for the allylation of C, N, and O-nucleophiles with alkynes under solvent-free conditions and by microwave activation is established. The process can be termed as a real eco-chemical process since no waste elements are produced in the

Full text of DOI:10.1016/j.tetlet.2004.09.099

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8497–8499
Microwave-enhanced Pd(0)/acetic acid catalyzed allylation
reactions of C, N, and O-pronucleophiles with alkynes
Nitin T. Patil, F. Nawaz Khan and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Received 4 August 2004; revised 7 September 2004; accepted 13 September 2004
Available online 1 October 2004
Abstract—An efficient method for the allylation of C, N, and O-nucleophiles with alkynes under solvent-free conditions and by
microwave activation is established. The process can be termed as a real eco-chemical process since no waste elements are produced
in the reaction, moreover it is solvent free. This technique can also be used for the allylation of dimethyl methylmalonate, which
proves inert under the previously reported reaction conditions (refluxing in 1,4-dioxane).
Ó 2004 Elsevier Ltd. All rights reserved.
The palladium catalyzed allylation of C, N, and O-
nucleophiles is well recognized as one of the most
powerful synthetic tools for the construction of C–C
and C–X bonds (Eq. 1).1 However, from the eco-chemical
point of view, the method suffers some problems; for in-
stance a stoichiometric amount of base is needed to gen-
erate the nucleophiles (Nuꢀ) and a stoichiometric
amount of a leaving group (Xꢀ) is liberated. To solve
these problems, we recently reported a novel procedure
for the allylation of C,2 N,3 and O4-pronucleophiles with
alkynes, which serves as an alternative to the existing
methods, by using a Pd(PPh3)4/carboxylic acid catalytic
system in an organic solvent such as 1,4-dioxane (Eq.
2).2 Since the products formed in these reactions are
via formal addition of pronucleophiles to alkynes, no
waste elements are produced. Although the yields and
regioselectivities of the reactions were satisfactory, we
were not satisfied because a high temperature and long
reaction time were drawbacks of the process. Moreover,
the use of an organic solvent was unavoidable.
significantly reduced reaction times, enhanced conver-
sions, and sometimes, higher selectivity, with several
advantages for the eco-friendly approach, termed green
chemistry.6 Herein, we report an efficient method for the
allylation of C, N, and O-pronucleophiles with alkynes,
using solvent-free conditions under microwave activa-
tion (Eq. 2).
Nu
X
-Nu/Pd
-X
R1
ð1Þ
R
R1
R
X = OH, OAc, OCO2R, OTs, OTf, Br/Cl/I, OP(O)Ph2, NR2
Nu
Pd(0)-R'COOH
R
R
R1
R1
ð2Þ
H-Nu
H-Nu: HCR2(EWG)2, H2C(EWG)2, HNR32, HOR3
Nowadays, microwave (MW) activation has emerged as
a powerful technique as a nonconventional energy
source to promote a variety of chemical reactions and
has become a very popular and useful technique in or-
ganic chemistry.5 The combination of solvent-free reac-
tion conditions and microwave irradiation leads to
As a starting point, we studied the microwave assisted
reaction of diethyl malonate with 1-phenyl-1-propyne
[Eq. 2, R = Ph, R1 = H, H–Nu = H2C(COOEt)2]. Thus
a mixture of 1-phenyl-1-propyne 1a and diethyl malo-
nate 2a was irradiated in a microwave oven at 500W
for 15min in the presence of Pd(PPh3)4 (5mol%)/acetic
acid (20mol%). TLC analysis indicated the presence of
the desired product along with unreacted diethyl
malonate and 1-phenyl-1-propyne. However, when
700W was used for the above reaction, the yield
dramatically increased and 3a was isolated in 88% yield
(Table 1, entry 1). In our earlier observation the same
Keywords: Palladium catalyst; Microwave; Allylation; Pronucleophile;
Alkyne; Acetic acid.
*
Corresponding author. Tel.: +81 22 217 6581; fax: +81 22 217
6784; e-mail addresses: yoshi@yamamoto1.chem.tohoku.ac.jp; tl@
yamamoto1.chem.tohoku.ac.jp
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.099

8498
N. T. Patil et al. / Tetrahedron Letters 45 (2004) 8497–8499
Table 1. Pd(0)/acetic acid catalyzed allylation of C-, N-, and O-nucleophiles with alkynes under MW irradiationa
Entry
1
Alkyne (1)
Ph CH3
1a
H–Nu (2)
MW power (W)
700
Time (min)
15
Product (3)
Yield (%)b
88
COOEt
COOEt
3a
COOEt
COOEt
Ph
2a
COPh
COPh
Ph
Ph
2
3
4
500
700
500
6
15
7
92
76
69
COOEt
COOEt
2b
3b
COOCH3
COOCH3
COOCH3
COOCH3
2c
3c
O
O
O
O
OEt
OEt
Ph
2d
3d
COOEt
COOEt
COOEt
COOEt
2a
EtOOC
5
6
500
500
10
5
81
78
EtOOC
1b
CH3
3e
O
O
O
O
OEt
OEt
COOEt
2d
3f
7
Ph
CH3
HNBn2
2e
500
500
500
500
10
10
8
72
78
88
82
Ph
Ph
NBn2
1a
3g
N
8
H N
O
O
3h
3i
2f
9
BnOH
2g
Ph
Ph
OBn
10
8
HO
O
3j
2h
a All reactions mixtures were irradiated for the time and power specified in the table.
b Isolated yield.
reaction when carried out under reflux in 1,4-dioxane,
afforded the product in 92% yield but after a long reac-
tion time (12h). Intrigued with this preliminary result we
planned to study the generality of these findings and the
results are shown in Table 1.
established procedure.2a However, under the present
reaction conditions, the notorious substrate 2c gave a
good yield of the allylation product. All additional at-
tempts to increase the yield in this reaction, however,
proved to be futile. The allylation of cyclic b-keto ester
2d with 1a also proceeded giving the product 3d in 69%
yield (entry 4). The alkyne 1b reacted with 2a and 2d giv-
ing the corresponding allylation products 3e and 3f in
good yields (entries 5 and 6). Next, we studied the allyl-
ation of N- and O-nucleophiles with alkynes under these
conditions. Thus, 1-phenyl-1-propyne 1a when treated
with amines 2e and 2f gave N-allyl amines 3g and 3h
in 72% and 78% yields, respectively (entries 7 and 8).
Microwave assisted addition of alcohols 2g and 2h to
1-phenyl-1-propyne 1a gave the allyl ethers 3i and 3j
in 88% and 82% yields, respectively (entries 9 and 10).
Treatment of 2b with 1-phenyl-1-propyne 1a in the pres-
ence of Pd(PPh3)4 and acetic acid at a power of 500W
gave the desired product in 92% yield. Similarly, the
reaction of dimethyl methylmalonate 2c gave the corre-
sponding allylation product 3c, when treated with 1a
upon microwave irradiation for 15min (entry 3). It
should be noted that the reaction of dimethyl methyl-
malonate 2c with alkynes gave only a trace amount of
the adducts even after heating at 100°C in 1,4-dioxane
for a prolonged reaction time under our previously

N. T. Patil et al. / Tetrahedron Letters 45 (2004) 8497–8499
8499
It should be noted that the hydroalkoxylation of alky-
References and notes
nes is a slow process and heating for three days was
needed in order to obtain good yields of the products
under our previously established procedure,4a that is
heating at 100°C in 1,4-dioxane. However, significant
rate enhancement of the reaction was observed under
microwave conditions.
1. (a) Godleski, S. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: New York,
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G. A., Abel, E. W., Eds.; Pergamon: Oxford, UK, 1995;
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In summary, we have succeeded in developing an effi-
cient method for the allylation of C-, N-, and O-pronu-
cleophiles with alkynes under solvent-free conditions
and by microwave activation. Since the process does
not need any organic solvents and nothing is liberated
from the starting material, the reaction may lead to a
method, which solves some environmental problems.
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In a typical experiment, diethyl malonate 2a (0.100g,
0.624mmol) was mixed with 1-phenyl-1-propyne 1a
(0.073g, 0.624mmol), Pd(PPh3)4 (0.036g, 0.031mmol),
and CH3COOH (0.007g, 0.125mmol). The mixture
was added to a 5mL conical flask and was placed in a
microwave oven (cooking type, Hitachi MRO-EX3)
and irradiated for the time and power as specified in
Table 1. On completion of the reaction, the flask was al-
lowed to cool, diluted with diethyl ether and passed
through a short silica gel column using diethyl ether as
eluent. The solvent was evaporated under reduced pres-
sure and the residue was purified by column chromatog-
raphy (hexane/ethyl acetate: 9/1) to give product 3a as a
dense liquid (0.152g, 88%).
Acknowledgements
N.T.P. thanks the Japan Society for the Promotion of
Science (JSPS) for a post-doctoral research fellowship.
6. Varma, R. S. Green Chem. 1999, 1, 43–55.