Palladium nanoparticle-catalyzed C-N bond formation. A highly regio- and stereoselective allylic amination by allyl acetates

Article abstract of DOI:10.1021/jo9003037

(Chemical Equation Presented) Palladium nanoparticles, generated in situ from the reaction of palladium(II) chloride, have been demonstrated to be an efficient catalyst for C-N bond formation. A variety of aliphatic and aromatic amines have been allylated by substituted and unsubstituted allyl acetates in high yields by using palladium nanoparticles in the presence of a base without any ligand. The allylations are highly regio- and stereoselective.

Full text of DOI:10.1021/jo9003037

SCHEME 1. Palladium Nanoparticle-Catalyzed Allylic
Animation with Allyl Acetates
Palladium Nanoparticle-Catalyzed C-N Bond
Formation. A Highly Regio- and Stereoselective
Allylic Amination by Allyl Acetates
Laksmikanta Adak, Kalicharan Chattopadhyay, and
Brindaban C. Ranu*
catalysts are found to be the most powerful. Usually, palladium
complexes in combination with ligands are employed for allylic
amination reactions.10 Recently, metal nanoparticles have at-
tracted considerable interest in the catalysis of organic reac-
tions.11 As a part of our continued activities to explore the
potential of Pd nanoparticles as catalysts for organic transforma-
tions,12 we discovered that allylic amination was very efficiently
catalyzed by Pd nanoparticles in the presence of a base (Scheme
1). Our literature survey found only one example of allylic
amination using Pd nanoparticles supported on mesoporous
silica in the presence of a ligand.13
Department of Organic Chemistry, Indian Association for the
CultiVation of Science, JadaVpur, Kolkata-700 032, India
ocbcr@iacs.res.in
ReceiVed February 11, 2009
To standardize the reaction conditions a series of experiments
were performed in different solvents with various palladium
salts, bases, and stabilizers for a representative reaction of aniline
and allyl acetate. The results are summarized in Table 1. It was
found that the reaction proceeds best in toluene by using PdCl2
and tetrabutylammonium bromide (TBAB) as a stabilizer11d in
the presence of K2CO3 (Table 1, entry 6). The amount of PdCl2
was also optimized to 4.5 mol %. The reaction also proceeds
well in the presence of Cs2CO3; however, Cs2CO3 being more
expensive K2CO3 was used in all these reactions.
In a typical experimental procedure, a mixture of amine, allyl
acetate, palladium(II) chloride, TBAB, and K2CO3 in toluene
was heated at 85 °C for a period of time as required for
completion (TLC). The usual workup and purification by column
chromatography provided the product.
Palladium nanoparticles, generated in situ from the reaction
of palladium(II) chloride, have been demonstrated to be an
efficient catalyst for C-N bond formation. A variety of
aliphatic and aromatic amines have been allylated by
substituted and unsubstituted allyl acetates in high yields by
using palladium nanoparticles in the presence of a base
without any ligand. The allylations are highly regio- and
stereoselective.
TABLE 1. Standardization of Reaction Conditionsa
The allylamines are of great importance in organic synthesis.
They are found in a wide variety of bioactive natural products,1
and are useful intermediates to a range of products such as
alkaloids,2 R- and ꢀ-amino acids, etc.3 Thus, their synthesis is
of high interest. The transition metal-catalyzed allylic amination
of allyl alcohols or their derivatives is one of the most effective
protocols for C-N bond formation.4 Although several metals
such as Rh,5 Ir,6 Fe,7 Ru,8 Ni,9 and Pd10 have been used, Pd
entry
solvent
Pd salt
stabilizer
base
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
dioxan
DMF
CH3CN
H2O
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Na2PdCl4
Pd(OAc)2
PdNPsb
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DBU
0
0
0
15
35
80
0
THF
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
(1) (a) Trost, B. M.; Crawley, M. L. Chem. ReV. 2003, 103, 2921–2944. (b)
Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1–14.
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Magnus, P.; Lacour, J.; Coldham, I.; Murgrage, B.; Banta, W. B. Tetrahedron
1995, 51, 11087–11110.
(3) (a) Burgess, K.; Liu, L. T.; Pal, B. J. Org. Chem. 1993, 58, 4758–4763.
(b) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.; Yanagi, K.
J. Am. Chem. Soc. 1989, 111, 6301–6311. (c) Bower, J. F.; Jumnah, R.; Williams,
A. C.; Williams, J. M. J. J. Chem. Soc., Perkin Trans. 1 1997, 1411–1420.
(4) Trost, B. M.; Vanvranken, D. L. Chem. ReV. 1996, 96, 395–422.
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121, 6761–6762.
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K. Chem.sEur. J. 2006, 12, 3596–3609. (b) Welter, C.; Koch, O.; Lipowsky,
G.; Helmchen, G. Chem. Commun. 2004, 896–897.
SDS
PEG-6000
TBAI
0
20
55
0
0
38
0
10
15
60
65
82
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
KF
K3PO4
Na2CO3
Et3N
Cs2CO3
a Reaction conditions: aniline (1 mmol), allyl acetate (3 mmol), Pd
salt (4.5 mol %), stabilizer (1 mmol), solvent (3 mL), and base (2
mmol) were heated at 85 °C. b Pd nanoparticles were prepared
separately.
(7) Plietker, B. Angew. Chem., Int. Ed. 2006, 45, 6053–6056.
(8) Kawatsura, M.; Ata, F.; Hirakawa, T.; Hayase, S.; Itoh, T. Tetrahedron
Lett. 2008, 49, 4873–4875.
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1084.
3982 J. Org. Chem. 2009, 74, 3982–3985
10.1021/jo9003037 CCC: $40.75 2009 American Chemical Society
Published on Web 04/21/2009

TABLE 2. Pd Nanoparticle-Catalyzed Allylation of Amines in the
Presence of K2CO3
TABLE 3. Allylation of Anilines in the Presence of K2CO3
a Yields refer to those of purified isolated products characterized by
1
spectroscopic data (IR, H NMR, 13C NMR).
3. The cyclic amines such as piperidine, pyrrolidine, morpholine,
and piperazine participated in this reaction. Very interestingly,
both trans- and cis-cinnamyl acetates on reaction with piperidine
(Table 2, entries 1 and 2) or piperazine (Table 2, entries 8 and
9) provided the trans-allylated amines as sole products. No cis-
isomer was detected in the crude. The branched cinnamyl
acetates (Table 2, entries 3, 10, 13, and 14) provided the same
linear trans-products. The branched allyl acetates (Table 2,
entries 5 and 12) also provided the corresponding products
without any hydride elimination.14 The F, Cl, Br, and I
functionalities (Table 2, entries 4, 7-11, and 14) in the aromatic
ring remained inert during this allylic amination reaction without
undergoing Buchwald-Hartwig amination.15 The open chain
amines (Table 2, entries 12-14) produced the corresponding
trans-products without any difficulty. The aliphatic primary
amines (Table 2, entries 15-17) led to bis-allylated products
in all three reactions. No monoallylation was detected at any
stage of the reaction. The anilines (Table 3, entries 18-22)
underwent allylations by allyl acetate and 2-carboxyallyl acetates
giving the corresponding allylated anilines with a terminal
double bond. However, aniline and N-substituted anilines failed
to react with cinnamyl acetate under this condition. We
rationalized that possibly -NH2 of aniline binds strongly to Pd
nanoparticles16a thus reducing its nucleophilicity. Hence, we
investigated this reaction in the presence of a stronger base than
K2CO3. After a series of experiments with different bases, we
found Cs2CO3 as the only one to perform this reaction efficiently.
Although the reaction of aniline itself was not good, several
N-substituted anilines underwent allylations by a variety of
cinnamyl acetates efficiently. The results are reported in Table
4. The tetrahydroquinolines (Table 4, entries 7-9) and brached
cinnamyl acetates (Table 4, entries 4 and 9) also participated
in this reaction. In this allylation too, cis- and trans-cinnamyl
acetates led to the same trans products (Table 4, entries 2, 3, 7,
and 8). The monoallylated anilines which failed to undergo a
second allylation in the presence of K2CO3 were allylated
without any difficulty under this condition (Table 4, entries 5
a Yields refer to those of purified isolated products characterized by
1
spectroscopic data (IR, H NMR, 13C NMR).
To check the formation of Pd nanoparticles in situ in the
reaction mixture, an extract of aniline and allyl acetate taken
after 4 h from the start of the reaction showed the formation of
3-5 nm nanoparticles by a TEM (Transmission Electron
Microscope) image. The identity of these particles as palladium
was confirmed by EDS (Energy Dispersive Spectroscopy). The
residual powder left after extraction of product also showed the
presence of Pd metal by XRD (X-ray Diffraction).
A wide variety of substituted cyclic and open chain amines,
aniline, and ring-substituted anilines underwent allylations by
allyl acetates with varied substituents to produce the corre-
sponding allylated amines by this procedure catalyzed by Pd
nanoparticles. The results of allylations of amines are sum-
marized in Table 2 and those of anilines are reported in Table
J. Org. Chem. Vol. 74, No. 10, 2009 3983

TABLE 4. Pd Nanoparticle-Catalyzed Allylation of Anilines by
Allyl Acetates in the Presence of Cs2CO3
SCHEME 3. Proposed Reaction Pathway
SCHEME 4
a Yields refer to those of purified isolated products characterized by
1
spectroscopic data (IR, H NMR, 13C NMR).
SCHEME 2
cinnamyl acetate, probably via a π-σ-π process,16b and 100%
in the case of a branched cinnamyl acetate. This supports our
proposed pathway (Scheme 4).
and 6). These bis-allylated products are useful precursors to
N-aryl dihydropyrroles (Scheme 2).
In general, the reactions are very clean and high yielding.
No additional step is required for the preparation of palladium
nanoparticles in our procedure in contrast to the tedious
preparation of mesoporous silica-supported Pd nanoparticles
used for allylic amination reported earlier.13 Several function-
alities such as F, Cl, Br, I, OMe, and NO2 are compatible with
this procedure. The remaining Pd nanoparticles, after extraction
of product, were recycled for three runs with gradual loss of
efficiency possibly due to agglomerization of Pd nanoparticles
on each exposure. It may be mentioned that the TEM image of
the Pd catalyst, left after the first cycle, showed particle sizes
in the range of 10-12 nm compared to 3-5 nm before the first
cycle. Usually, the reactivity and efficiency of nanoparticles
decrease with an increase of size.17
In conclusion, we have developed an efficient procedure for
C-N bond formation leading to allylic amination by allyl
acetates using in situ generated Pd nanoparticles in the absence
of any ligand. Most significantly, a wide range of amines (cyclic,
open chain, aromatic) and allyl acetates have been addressed
making it a general methodology and to the best of our
knowledge no other existing procedure demonstrated such a
In view of these observations that both cis and trans and
branched substituted allyl acetates led to the same trans-products,
we proposed the reaction pathway outlined in Scheme 3. An
allyl acetate undergoes complexation and oxidative addition with
Pd nanoparticles to form the corresponding η1-σ-allyl palladium
acetate complex 1, which then leads to a common η3-π-complex
2. This undergoes nucleophilic addition of an amine at the less
hindered terminal position to provide an intermediate 3, which
on decomplexation with a base produces the trans-allylated
amine and gives back Pd nanoparticles which take part in the
next cycle. This process is applicable straightway in case of
trans-allyl acetates. In the case of cis-allyl acetates η3-π-complex
1a was formed after initial complexation, oxidative addition,
and ionization, which then changes its heptacity with the loss
of its stereochemistry to give rise to 1b.12d,16b This intermediate
then isomerizes to the more stable intermediate 2. Similarly,
the branched allyl acetate also proceeds to lead to the same
intermediate 2 via 1c. To check the feasibility of isomerization
of η3-π-complex 1a and η1-σ-complex 1c to 2, we carried out
two blank experiments with cis and branched acetates in the
absence of amine and we observed 53% isomerization in cis-
3984 J. Org. Chem. Vol. 74, No. 10, 2009

wide scope. The allylations are highly regio- and stereoselective
providing only one product in each reaction. Nevertheless, this
demonstrates the potential of Pd nanoparticles for C-N bond
formation.
Experimental Section
Representative Experimental Procedure for Allylation of
Amine (Table 3, Entry 18). A mixture of aniline (93 mg, 1 mmol),
allyl acetate (300 mg, 3 mmol), PdCl2 (8 mg, 0.045 mmol),
tetrabutylammonium bromide (323 mg, 1 mmol), and K2CO3 (276
mg, 2 mmol) in toluene (3 mL) was heated with stirring at 85 °C
for 10 h (TLC). The reaction mixture was extracted with Et2O (3
× 10 mL). The extract was washed with water and brine then dried
(Na2SO4). Evaporation of solvent left the crude product, which was
purified by column chromatography over neutral alumina (hexane/
ether 95:5) to provide allylphenylamine as a colorless oil (106 mg,
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80%). The spectroscopic data (IR, H NMR, 13C NMR) of this
1
compound are in good agreement with those reported.10g The
remaining black Pd nanoparticles, after extraction with ether, were
further washed with ether, dried, and reused for subsequent runs.
Several of these products are known compounds (see the
references in Tables 2 and 3) and were easily characterized by
comparison of their spectroscopic data with those reported. The
1
unknown compounds were properly characterized by their IR, H
NMR, 13C NMR, and HRMS data (see the SI).
This procedure was followed for all the reactions listed in Tables
2-4. Although the representative procedure is based on a 1 mmol
scale reaction, it has been scaled up to 10 mmol with reproducible
results.
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Acknowledgment. We are pleased to acknowledge financial
support from DST, New Delhi under a J.C. Bose National
Fellowship (Grant No. SR/S2/JCB-11/2008). L.A. and K.C. are
thankful to CSIR for their fellowships.
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Supporting Information Available: TEM (Figure 1), EDS
(Figure 2), XRD (Figure 3), and recyclability chart (Figure 4);
characterization data (IR, 1H and 13C NMR spectroscopic data,
HRMS, or elemental analysis report) of the products in entries
4 and 7-14 in Table 2 and entries 19, 21, 23-25 in Table 3
1
and entries 3, 4, and 7-9 in Table 4; copies of H and 13C
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NMR spectra of all products listed in Tables 2-4. This material
is available free of charge via the Internet at http://pubs.acs.org.
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JO9003037
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