Allylation of 1-phenyl-1-propyne with N- and O-pronucleophiles using polymer supported triphenylphosphine palladium complex as a heterogeneous and recyclable catalyst

Article abstract of DOI:10.1016/j.tetlet.2011.08.099

Simple methodology for the allylation of various N- and O-pronucleophiles with 1-phenyl-1-propyne as an allylating agent, using PS-TPP-Pd (polymer supported triphenylphosphine palladium) as a highly active heterogeneous recyclable catalyst has been developed. The protocol is applicable for a wide variety of hindered and functionalized aromatic amines, alcohols, and carboxylic acids. The catalyst exhibited remarkable catalytic activity for five consecutive recycles.

Full text of DOI:10.1016/j.tetlet.2011.08.099

Tetrahedron Letters 52 (2011) 5676–5679
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Tetrahedron Letters
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Allylation of 1-phenyl-1-propyne with N- and O-pronucleophiles using
polymer supported triphenylphosphine palladium complex as a
heterogeneous and recyclable catalyst
⇑
Yogesh S. Wagh, Dinesh N. Sawant, Kishor P. Dhake, Krishna M. Deshmukh, Bhalchandra M. Bhanage
Department of Chemistry, Institute of Chemical Technology, N. Parekh Marg, Matunga, Mumbai 400 019, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 July 2011
Revised 16 August 2011
Accepted 18 August 2011
Available online 27 August 2011
Simple methodology for the allylation of various N- and O-pronucleophiles with 1-phenyl-1-propyne as
an allylating agent, using PS-TPP-Pd (polymer supported triphenylphosphine palladium) as a highly
active heterogeneous recyclable catalyst has been developed. The protocol is applicable for a wide variety
of hindered and functionalized aromatic amines, alcohols, and carboxylic acids. The catalyst exhibited
remarkable catalytic activity for five consecutive recycles.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Allylation
Pronucleophiles
Alkynes
Palladium
Heterogeneous catalyst
Allyl amines, allyl ethers, and allyl esters have wide applica-
tions in organic synthesis,1,2 synthesis of biologically active
compounds,3,4 natural products synthesis,3b and perfumery indus-
tries.5 These allylated products can be obtained via palladium cat-
alyzed allylation of respective amines, alcohols, and carboxylic
acids with various allylating agents such as allyl alcohols, deriva-
tives of allyl alcohols (e.g., allyl acetate, allyl carbonates, allyl tri-
flates, etc.), allenes, or internal alkynes.6–10 The use of allylating
agents like allylic alcohols and their derivatives is not advanta-
geous as it produces stoichiometric amount of side products in
the reaction. However, the use of allenes and internal alkynes as
an allylating agent is more advantageous, as the allylated products
are formed by simple addition reaction of N- and O-pronucleo-
philes with allenes and alkynes. Among the allenes and alkynes, al-
kynes are easily available and are also cost-effective. Yamamoto
and coworkers11 reported various homogeneous palladium cata-
lyst such as Pd(PPh3)4, Pd2(dba)3ꢀCHCl3 with 2-(dicyclohexylphos-
phanyl)-20-(dimethylamino)biphenyl as a ligand, for the allylation
of pronucleophiles. Recently, we have reported allylation of vari-
ous N- and O-pronucleophiles using homogeneous Pd(OAc)2/dppf
as catalyst.12 Homogeneous catalytic systems have several
drawbacks like the presence of palladium based impurities in
synthesized products, catalyst-product separation, and lack of
catalyst reusability. It is noteworthy to mention that such toxic
palladium based impurities creates considerable problems in case
of pharmaceutical products as the purity of the product is of enor-
mous importance.
Hence, suitable efforts to anchor such homogeneous complex
catalyst which can overcome such limitation of catalyst-product
separation and recycle are necessary. In this context, we recently
reported an effective heterogeneous catalytic methodology for
allylic amination of internal alkynes using polymer supported pal-
ladium catalyst.13 The exploration of developed methodology for
the allylation of weaker pronucleophiles such as hindered amines,
alcohols, and carboxylic acids still remains the scope of further re-
search. We herein report allylic amination of alkynes using poly-
mer supported palladium catalyst for the allylation of weaker N-
and O-pronucleophiles using polymer supported triphenylphos-
phine palladium complex (PS-TPP-Pd) as a heterogeneous and
recyclable catalyst (Scheme 1).
In this work the allylation of 2-methylaniline with 1-phenyl-
1-propyne (1) as a model reaction using Pd(OAc)2 as a catalyst pre-
cursor using polymer supported triphenylphosphine as a ligand
and benzoic acid as a co-catalyst was studied. Various reaction
parameters such as molar ratio, solvent, temperature, time, and
catalyst loading were studied to obtain the best optimized reaction
conditions (Table 1).
Molar ratio has always shown a profound effect on the yield of
the desired product. Hence, we have studied the effect of different
molar ratios of 1-phenyl-1-propyne/2-methylaniline and found
that the molar ratio 1:1.2 revealed excellent yields (90%) within
5 h (Table 1, entry 2). Various non-polar organic solvents like tolu-
⇑
Corresponding author. Tel.: +91 22 33612601; fax: +91 22 33611020.
E-mail addresses: bhalchandra_bhanage@yahoo.com, bm.bhanage@gmail.com
(B.M. Bhanage).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.099

Y. S. Wagh et al. / Tetrahedron Letters 52 (2011) 5676–5679
5677
R
HN
R
R'
Ph
N
R'
Pd(OAc)2/PS-TPP,
PhCOOH
HO
R
R
O
Ph
CH3
Ph
Ph
O
Toluene, 110 °C
(1)
O
R
HO
R = Alkyl, aryl; R' = H, alkyl, aryl
O
R
Scheme 1. PS-TPP-Pd catalyzed allylation of N- and O-pronucleophiles with 1-phenyl-1-propyne.
Table 1
Effect of reaction parameters on the allylation of 2-methyl aniline with 1-phenyl-1-propyne (1)a
Entry
Molar ratio
Solvent
Temperature (°C)
Time (h)
Catalyst loading (mol %)
Pd:P ratio
Yieldb (%)
Influence of molar ratio
1
2
3
1:1
1:1.2
1.2:1
Toluene
Toluene
Toluene
110
110
110
5
5
5
10
10
10
1:4
1:4
1:4
88
90
86
Influence of solvent
4
5
6
1:1.2
1:1.2
1:1.2
Xylene
n-Hexane
Cyclohexane
110
70
80
5
5
5
10
10
10
1:4
1:4
1:4
60
05
—
Influence of temperature
7
1:1.2
1:1.2
1:1.2
Toluene
Toluene
Toluene
100
80
120
5
5
5
10
10
10
1:4
1:4
1:4
78
60
90
8
9c
Influence of time
10
11
12
1:1.2
1:1.2
1:1.2
Toluene
Toluene
Toluene
110
110
110
2
4
6
10
10
10
1:4
1:4
1:4
31
76
92
Influence of catalyst loading
13
14
1:1.2
1:1.2
Toluene
Toluene
110
110
5
5
5
15
1:4
1:4
76
90
Influence of Pd:P ratio
15
16
17
18
1:1.2
1:1.2
1:1.2
1:1.2
Toluene
Toluene
Toluene
Toluene
110
110
110
110
5
5
5
5
10
10
10
10
1 : 1
1:2
1:3
40
73
76
94
1:5
a
b
c
Reaction condition: 1 1-phenyl-1-propyne (5 mmol), 2 2-methylaniline, Pd(OAc)2 , PS-TPP, benzoic acid (10 mol %), solvent (20 mL).
GC yield.
The reaction was performed in sealed vial.
ene, xylene, cyclohexane, and n-hexane were screened and toluene
was found to be the best solvent, furnishing excellent yield (90%)
(Table 1, entry 2). It was observed that with increase in the reaction
temperature from 80 °C to 110 °C, the yield was increased, while
further increase in temperature to 120 °C had no significant effect
on the yield of the reaction (Table 1, entries 2, 7–9). We further
investigated the effect of reaction time and observed that 5 h
was sufficient for the reaction (Table 1, entries 2, 10–12). The cat-
alyst loading of 10 mol % was adequate to catalyze the allylation
reaction at the palladium: phosphine ratio of 1:5 (Table 1, entries
2, 13–18). We observed that excess amount of phosphine ligand
was necessary to stabilize palladium complex for the allylation
reaction. Hence, the final optimized reaction conditions are: 1-phe-
nyl-1-propyne (1 equiv), 2-methylaniline (1.2 equiv), toluene at
110 °C, Pd(OAc)2/PS-TPP (10 mol %), ratio of Pd:P (1:5) for 5 h.
Furthermore, the efficiency of developed methodology for the
allylation of various N- and O-pronucleophiles was studied (Table
2). Several weaker N-pronucleophiles such as different aniline
derivatives containing sterically hindered N-substituted com-
pound (N-benzylaniline) as well as electron deficient anilines were
subjected for the allylation reaction. We observed that (2-cyanoan-
iline) and N-sulphonated aniline (N-tosylaniline) were well toler-
ated offering good to excellent yield (82–94%) of the desired allyl
amines (Table 2, entries 1–4). Encouraged with the results, we ex-
tended our protocol to much weaker pronucleophiles like alcohols
and carboxylic acids (Table 2, entries 5–12). Among the O-pronu-
cleophiles screened, the carboxylic acids were found to be much
more effective for allylation reaction as compared with alcohols.
Benzylalcohol and its derivatives reacted smoothly with 1 provid-
ing good yield of the desired product while the reaction of cin-
namyl alcohol with 1 offered excellent yield of dicinnamyl ether
(90%) as a product (Table 2, entries 5–8). Furthermore, we em-
ployed some less nucleophilic O-pronucleophiles, that is, various
carboxylic acids such as acetic acid, benzoic acid, ortho-toluic acid,
and cinnamic acid for the developed methodology. To our delight,
all these substrates reacted smoothly to endow excellent yield of
their respective allyl esters (Table 2, entries 9–12). In order to
avoid the formation of cinnamyl benzoate as a side product in
the reaction medium, the reaction of acetic acid and ortho-toluic
acid with 1 were performed in the absence of benzoic acid (co-cat-

5678
Y. S. Wagh et al. / Tetrahedron Letters 52 (2011) 5676–5679
Table 2
Allylation of N- and O-pronucleophiles with 1-phenyl-1-propynea
Entry
Pronucleophile (2)
Product (3)
Time (h)
6
Yieldb (%)
94
NH2
HN
Ph
OCH3
OCH3
1
Ph
NH
Ph
N
Ph
2
3
12
12
84
82
NH2
HN
Ts
Ph
CN
CN
Ts
NH
N
Ph
4
18
85
OH
O
5
6
18
18
82
88
Ph
OH
O
H3CO
H3CO
Ph
OH
O
7
18
80
Ph
OH
O
8
18
18
90
85
Ph
O
O
9c
OH
O
Ph
O
O
10
12
12
12
92
93
95
OH
O
O
Ph
Ph
CH3
O
CH3 O
11c
12
OH
O
O
OH
O
Ph
a
Reaction condition: 1 1-phenyl-1-propyne (5 mmol), 2 N- or O-pronucleophiles (6 mmol), Pd(OAc)2 (10 mol %), PS-TPP (5 equiv to Pd(OAc)2), benzoic acid (10 mol %),
toluene (20 mL), temperature (110 °C).
b
Isolated yields.
Reaction without PhCOOH.
c
Figure 1. Recyclability study for allylation reaction.

Y. S. Wagh et al. / Tetrahedron Letters 52 (2011) 5676–5679
5679
6. (a) Al-Masumb, M.; Megurob, M.; Yamamoto, Y. Tetrahedron Lett. 1997, 38,
6071–6074; (b) Meguro, M.; Yamamoto, Y. Tetrahedron Lett. 1998, 39, 5421–
5424.
7. (a) Yang, S. C.; Hung, C. W. J. Org. Chem. 1999, 64, 5000–5001; (b) Yang, S. C.;
Hsu, Y. C.; Gan, K. H. Tetrahedron 2006, 62, 3949–3958.
8. Nishikata, T.; Lipshutz, B. H. Chem. Commun. 2009, 6472–6474.
9. (a) Adak, L.; Chattopadhyay, K.; Ranu, B. C. J. Org. Chem. 2009, 74, 3982–3985;
(b) Feuerstein, M.; Laurenti, D.; Doucet, H.; Santelli, M. Chem. Commun. 2001, 1,
43–44.
10. Moreno, -M. M.; Morral, L.; Pleixats, R. J. Org. Chem. 1998, 63, 6160–6166.
11. (a) Kadota, I.; Shibuya, A.; Lutete, M. L.; Yamamoto, Y. J. Org. Chem. 1999, 64,
4570–4571; (b) Lutete, M. L.; Kadota, I.; Shibuya, A.; Yamamoto, Y. Heterocycles
2002, 58, 347–357; (c) Lutete, M. L.; Kadota, I.; Yamamoto, Y. J. Am. Chem. 2004,
26, 1622–1623; (d) Patil, N. T.; Wu, H.; Kadota, I.; Yamamoto, Y. J. Org. Chem.
2004, 69, 8745–8750; (e) Bajracharya, G. B.; Huo, Z.; Yamamoto, Y. J. Org. Chem.
2005, 70, 4883–4886; (f) Patil, N. T.; Song, D.; Yamamoto, Y. Eur. J. Org. Chem.
2006, 4211–4213.
alyst) to provide the desired allyl esters with excellent yield. How-
ever, the use of benzoic acid as a co-catalyst was essential for the
allylation of cinnamic acid as it provided excellent yield of cinnam-
ylcinnamate in the presence of co-catalyst, while reacted slug-
gishly in the absence of co-catalyst providing only 58% yield.
Though, the hydroxyl group of alcohol is more nucleophilic
than the hydroxyl of carboxylic acid, they react sluggishly with
alkyne. This observed controversy may be due to the dual role
of carboxylic acid as a substrate as well as co-catalyst. Hence,
present methodology sounds to be general and economical for
the allylation of various structurally and electronically different
pronucleophiles such as amines, alcohols, and carboxylic acids
with 1 providing good to excellent yields of the desired allylated
products.
12. Wagh, Y. S.; Sawant, D. N.; Tambade, P. J.; Dhake, K. P.; Bhanage, B. M.
Tetrahedron 2011, 67, 2414–2421.
In addition to make the protocol more economically feasible,
the catalytic activity of PS-TPP-Pd was investigated for five consec-
utive recycles under optimized reaction conditions (Fig. 1). The cat-
alyst was effectively recycled with marginal decline in the catalytic
activity for the fifth recycle. The marginal decline in the yield
might be due to the handling loss of Pd catalyst. In relation, we per-
formed the ICP-AES analysis of the reaction mixture and observed
leaching of the Pd below the detectable level.
In conclusion, we have developed a facile, highly efficient, and
common protocol for the allylation of different weak nucleophilic
O- and N-pronucleophiles using PS-TPP-Pd complex as a heteroge-
neous and recyclable catalyst. The present methodology facilitates
allylation of weaker nucleophilic amines, alcohols, and carboxylic
acids providing good to excellent yield of the desired products.
Also, the PS-TPP-Pd complex was recycled for five consecutive cy-
cles without any significant loss in catalytic activity.
13. Wagh, Y. S.; Sawant, D. N.; Tambade, P. J.; Bhanage, B. M. Eur. J. Org. Chem. 2010,
5071–5076.
General procedure for allylation reaction: In a typical experimental procedure,
50 mL round-bottomed flask was charged with Pd(OAc)2 (112 mg, 10 mol %),
polymer supported triphenylphosphane (PS-TPP; 831 mg, 5 equiv to Pd(OAc)2)
and toluene (20 mL) and was stirred for 20 min at 110 °C. The reaction mixture
was cooled to rt followed by the addition of 1-phenyl-1-propyne (580 mg,
5 mmol), pronucleophile (6 mmol), and benzoic acid (60 mg, 10 mol %). The
resulting mixture was stirred for 5–18 h at 110 °C and was then cooled to room
temperature. On completion of reaction, the catalyst was separated by
filtration, washed with an excess amount of toluene and dried under vacuum
(The dried catalyst can be used as it is for further recycles). The reaction
mixture was analyzed using a gas chromatography (Perkin Elmer, Clarus 400)
equipped with a flame ionization detector (FID) and capillary column (Elite-1,
30 m ꢁ 0.32 mm ꢁ 0.25
lm). The crude product was purified by column
chromatography (silica gel, 60–120 mesh; petroleum ether/ethyl acetate,
95:05) to afford pure products. All the prepared compounds were confirmed
by comparing with their authentic samples and were characterized by GC–MS
(Shimadzu QP 2010) , 1H NMR (Varian 300 MHz) or (Varian 400 MHz), 13C NMR
(Varian 75 MHz), and HRMS (Bruker daltonics, ESI micrOTOF-Q) analysis.
Spectral data of selected compounds:
N-Cinnamyl-2-methoxyaniline (Table 2, entry 1). Yield: 94% (1048 mg). 1H
NMR (400 MHz, CDCl3, 25 °C): d = 7.22–7.39 (m, 5H, Ar), 6.6–6.89 (m, 5H, (4H,
Ar and 1H, CH@CH-Ph)), 6.35 (td, J = 15.76, 5.86 Hz, 1H, CH2–CH@CH), 4.42 (br
Acknowledgments
s, 1H, NH), 3.95 (dd, J = 5.5, 1.46 Hz, 2H, HN–CH2–CH), 3.85 (s, 3H, –OCH3). 13
C
The author (YSW) is greatly thankful to the Council of Scientific
and Industrial Research (CSIR), India for providing fellowship.
NMR (75 MHz, CDCl3, 25 °C): d = 146.92 (Cq, Ar), 138.02 (N-Cq, Ar), 136.99 (Cq,
Ar), 131.35 (CH2–CH@CH), 128.56 (2CH, Ar), 127.46 (CH, Ar), 127.27 (CH@CH-
Ph), 126.36 (2CH, Ar), 121.34 (CH, Ar), 116.71 (CH, Ar), 110.24 (CH, Ar), 109.45
(CH, Ar), 55.41 (–OCH3), 45.94 (HN–CH2–CH) ppm. GC–MS (EI, 70 eV): m/z
(%) = 239 (43) [M+], 117 (100), 115 (41), 91 (31), 77 (10), 45 (46), 44 (38). HRMS
(ESI+) calcd for (MH+): 240.1388, found (MH+): 240.1387.
References and notes
Cinnamyl acetate: (Table 2, entry 9). Yield: 85% (748 mg). 1H NMR (300 MHz,
CDCl3, 25 °C): d = 7.2–7.4 (m, 5H, Ph), 6.65 (d, J = 15.76 Hz, 1H, CH@CH-Ph),
6.28 (td, J = 15.76, 6.23 Hz, 1H, CH2–CH@CH), 4.72 (dd, J = 6.23, 1.1 Hz, 2H, O–
CH2–CH), 2.1 (s, CH3–CO–O, 3H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): d = 170
(CH3–CO–OCH2), 136.26 (Cq, Ar), 134.25 (CH@CH-Ph), 128.65 (2CH, Ar), 128.11
(CH, Ar), 126.66 (2CH, Ar), 123.23 (CH2–CH@CH), 65.11 (O–CH2), 21 (CH3) ppm.
GC–MS (EI, 70 eV): m/z (%) = 176 (28) [M+], 134 (40), 133 (39), 117 (29), 115
(86), 92 (35), 43 (100).
1. For a review on allylic amination, see: (a) Johannsen, M.; Jorgensen, A. Chem.
Rev. 1998, 98, 1689–1708; (b) Yamamoto, Y.; Radhakrishnan, U. Chem. Soc. Rev.
1999, 28, 199–207; (c) Muller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada,
M. Chem. Rev. 2008, 108, 3795–3892.
2. Cheikh, R. B.; Chaabouni, R.; Laurent, A.; Mison, P.; Nafti, A. Synthesis 1983,
685–699.
3. (a) Walsh, C. Tetrahedron 1982, 38, 871–909; (b) Stutz, A. Angew. Chem., Int. Ed.
Engl. 1987, 26, 320–328; (c) Prashad, M. J. Med. Chem. 1993, 36, 631–632; (d)
Michalson, E. T.; Szmuszkovicz J. Prog. Drug. Res. 1989, 22, 135–149.
4. (a) Reina, M.; Mericli, A. H.; Cabrera, R.; Gonzales-Coloma, C. Phytochemistry
1995, 38, 355–358; (b) Bergdahl, M.; Hett, R.; Friebe, T. L.; Gangloff, A. R.; Iqbal,
J.; Wu, Y.; Helquist, P. Tetrahedron Lett. 1993, 34, 7371–7374; (c) Genisson, Y.;
Mehmandoust, M.; Marazano, C.; Das, B. C. Heterocycles 1994, 39, 811–818; (d)
Jain, P.; Garraffo, H. M.; Spande, T. F.; Yeh, H. J. C.; Daly, J. W. J. Nat. Prod. 1995,
58, 100–104.
Cinnamyl benzoate (Table 2, entry 10). Yield: 92% (1094 mg). 1H NMR
(300 MHz, CDCl3, 25 °C): d = 8.1 (d, J = 8.43 Hz, 2H, Ar), 7.2–5.9 (m, 8H, Ar),
6.75 (d, J = 15.76, 1H, CH@CH-Ph), 6.4 (td, J = 15.76, 6.23 Hz, 1H, CH2–CH@CH),
5.0 (dd, J = 6.23, 1.1 Hz, 2H, O–CH2–CH) ppm. 13C NMR (75 MHz, CDCl3, 25 °C):
d = 166.37 (CO), 136.25 (Cq, Ar), 134.27 (Cq-CO, Ar), 133 (CH, Ar), 129.67 (2CH,
Ar), 128.63 (2CH, Ar), 128.39 (2CH, Ar), 128.1 (CH@CH-Ph, Ar), 126.67 (2CH,
Ar), 123.29 (CH2-CH@CH), 65.23 (O–CH2–CH) ppm. GC–MS (EI, 70 eV): m/z
(%) = 238 (4) [M+], 133 (11), 117 (12), 115 (28), 105 (100), 45 (27).
5. Wessermel, K.; Arpe, H. J. Industrial Organic Chemistry, 3rd ed.; VCH: New York,
NY, 1997.