Isoprene hydroamination catalyzed by palladium xantphos complexes

Article abstract of DOI:10.1016/j.apcata.2012.05.018

Pd(II) Xantphos or Xantphos chalcogenide complexes with general folmula [PdCl₂(X∩X)] (where X = P, O, S or Se) were synthesized by the addition of corresponding ligands to [PdCl₂(COD)] (COD = 1,5-cyclooctadiene). Prepared Complexes [

Full text of DOI:10.1016/j.apcata.2012.05.018

Applied Catalysis A: General 433–434 (2012) 188–196
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Applied Catalysis A: General
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Isoprene hydroamination catalyzed by palladium xantphos complexes
Bahareh Tamaddoni Jahromia, Ali Nemati Kharata,∗, Sara Zamaniana, Abolghasem Bakhodab,
Kobra Mashayekha, Sadegh Khazaelib
a School of Chemistry, University College of Science, University of Tehran, Tehran, Iran
b Department of Chemistry, Southern Illinois University, Edwardsville, IL 62026, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Pd(II) Xantphos or Xantphos chalcogenide complexes with general folmula [PdCl2(X∩X)] (where X = P,
O, S or Se) were synthesized by the addition of corresponding ligands to [PdCl2(COD)] (COD = 1,5-
cyclooctadiene). Prepared Complexes [PdCl2(Xantphos)] and [PdCl2(Xantphos = S)] showed distorted
square planar geometries, from X-ray crystallographic analysis. All of the prepared complexes showed
activity toward intermolecular hydroamination of isoprene with a variety of secondary amines. Com-
plete conversion (∼100%) of pyrrolidine was observed using Pd–Xantphos as catalysts. Hydroamination
reactions exhibited regioselectivity when crowded secondary amines were used.
Received 26 February 2012
Received in revised form 11 May 2012
Accepted 14 May 2012
Available online 22 May 2012
Keywords:
Isoprene
Secondary amines
Hydroamination
Palladium complexes
Xantphos
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
and benzylic amines to acrylic type alkenes [20]. Although the iso-
lated yields were remarkable in most cases, drastic conditions were
Intermolecular hydroamination, the addition of N H bond
across C C multiple bonds has recently received great deal of atten-
tion because being a 100% atom-economy process. The reaction
allows direct access to a large variety of amines which are impor-
tant target products or intermediates in organic and medicinal
chemistry. A number of papers were published [1–10], report-
ing the hydroamination of alkenes or alkynes and the difference
between hydroamination and related oxidative amination reac-
tions. Hydroamination is known to be catalyzed by complexes
of early/late transition metals (especially groups IX and X) and
some lanthanide complexes [11–15]. The big step in hydroami-
nation of C C bonds took place at the start of the 21st century
when Hartwig and his co-workers published intermolecular reac-
tions of vinylarenes with −arylamines using palladium–phosphine
necessary for the reaction.
Hydroamination of 1,3-dienes with ammonia underlie the
promising preparation procedures for higher amines. The most
interesting product of butadiene hydroamination with NH3 is
tris(2,7-octadienyl)amine that can be easily hydrogenated to obtain
trioctylamine, a valuable extractant extensively applied in isola-
tion processes of a large number of noble and rare metals. In the
earlier studies, butadiene hydroamination was performed in the
presence of palladium catalyst with triarylphosphine or dialky-
larylphosphine oxide ligands, with anhydrous ammonia under
high pressure. The product distribution depends on the ratio of
butadiene to ammonia and on the character of the solvent, as
well as the concentration of NH3. Hydroamination of isoprene
catalyzed by Pd and Ni complexes provides a convenient syn-
thetic method to aminoterpenes [21,22]. Since the isoprene could
be coupled in four fashion (head-to-tail, tail-to-head, head-to-
head, and tail-to-tail), the composition of the 2:1 adducts of
isoprene and amines are usually complex. From the synthetic
point of view, the importance of the procedure for the prepara-
tion of amino-substituted hemiterpenes and monoterpenes is its
selectivity to prenolamine, buteneamines and 3,7-dimethylocta-
2,7-dien-1-amine. These compounds are structural elements of a
diverse natural isoprenoids [23] (see Scheme 1).
systems either with OTf
or in the presence of triflic or triflu-
oroacetic acids as co-catalysts [16]. The addition took place in
anti-Markovnikov fashion and strong evidence (computational [17]
and experimental [18]) supported the presence of ␩3-phenethyl
palladium complex as the intermediate. Pd complexes bearing ster-
ically hindered PXP ligands (where X = C or N) were discovered to
catalyzethe hydroaminationofprimary and secondary amines with
activated alkenes [19]. Palladium diphosphine complexes were also
found to catalyze the hydroamination of secondary alkyl, cycloalkyl
The main factors determining the regioselectivity in the reac-
tions of isoprene with amines are (a) the nature of initial amine,
(b) the structure of activating ligand in the catalyst, and (c) the
presence of acid co-catalyst (HOTf or BF3·Et2O) [24]. The nature
∗
Corresponding author. Tel.: +98 21 61112499; fax: +98 21 66495291.
E-mail address: alnema@khayam.ut.ac.ir (A. Nemati Kharat).
0926-860X/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.apcata.2012.05.018

B. Tamaddoni Jahromi et al. / Applied Catalysis A: General 433–434 (2012) 188–196
189
Table 1
Analytical and physical data for Xantphos derivatives and their Pd complexes.
Compound
Color (% yield)
Melting point (◦C)
R'RN
Xantphos = O
Xantphos = S
Xantphos = Se
Complex II
Complex III
Complex IV
White powder (91)
167–171
221–224
264–269 (December)
201–206 (December)
240–244 (December)
289–291 (December)
Pale yellow crystals (88)
Pale yellow powder (83)
Orange powder (96)
Red crystals (94)
NRR'
Deep red powder (93)
Catal.
+
RNHR'
Δ
R'RN
was observed at 42.5 ppm for the sulfide analog III. Likewise, com-
plex IV (Se derivative) exhibited a singlet at 31.4 ppm and selenium
satellites at 33.3 and 29.6 ppm with 1JP-Se = 749 Hz (Table 2).
The IR spectra of the complexes II, III and IV exhibit higher fre-
quencies for the P X (X = O, S and Se) bands than the free ligands
(1175, 641 and 549 compared to 1169, 625 and 535 cm−1), respec-
tively.
NRR'
2.2. X-ray crystallographic analyses
Scheme 1. Catalytic hydroamination of isoprene with secondary amines.
Crystallographic data and selected bond lengths (Å) and angles
(◦) are listed in Tables 3 and 4, respectively. C40H33Cl3OP2S2 (Xant-
phos = S·CHCl3; Structure 1) crystallizes as colorless blocks in the
monoclinic space group C2/c (No. 15) with four molecules in the
unit cell (see Fig. 1).
Structure 1 consists of [Xantphos = S] ligand with one chloro-
form solvated molecule (Fig. 1). The P S bond distance is 1.944(9)
Å, consistent with the range observed for similar phosphine sulfide
compounds [27,28]. The unit cell-packing diagram of the ligand
is presented in Fig. S1. Some weak hydrogen bonds exist in the
structure which may stabilize the crystal packing. One of these
hydrogen bonds exists between the H atom of the C H bond of the
solvated chloroform and the S atom of the phosphine sulfide moi-
of the solvents and reaction conditions are also important. Iso-
prene and N-methylaniline were reacted in 1:1 stoichiometry with
95% selectivity in MeOH using PdCl2–PPh3 as catalyst (the overall
yield was ca. 60%) [25]. Isoprene reacted with diethylamine in the
presence of Pd complex of tris(2,4,6-trimethoxyphenyl) phosphine
(cone angle 185◦) to give the 2:1 head-to-head adduct in almost
quantitative yield [21]. Furthermore, the presence of a strong Lewis
acid (HOTf or BF3·Et2O) enhanced the selectivity up to 82% in some
cases [24]. Hydroamination of isoprene with secondary amines cat-
alyzed by Pd(acac)2–P(OBu)3 system gave the tail-to-tail as the
main products [26]. In most cases, high selectivity was not obtained
in the mild reaction conditions. Also, longer reaction times were
needed to obtain remarkable conversion. The above information
encouraged us to synthesize and develop highly selective palla-
dium complexes for the synthesis of practically important alicyclic
isoprenoid amines via hydroamination using mild reaction condi-
tions. These compounds are important intermediates in fragrance,
medicine, and agricultural industries.
◦
˚
ety (C21–H21···S1 = 2.942 A and C21–H21–S1 angle of 134.4 ) and
another one exists between the C H bond of a phenyl ring and the
˚
Cl atom of the free chloroform molecule (C8–H8···Cl1 = 2.878 A and
C21–H21–S1 angle of 140.6◦). Notably, the chloroform molecule is
disordered as can be seen in Fig. 1.
Complex I ([Pd(Xantphos)Cl2]·CH2Cl2; Structure 2) consists of
one bidentate chelating Xantphos ligand and crystallizes as orange
blocks in the triclinic space group P¯ı (No. 2) with two molecules in
the unit cell. The molecular structure containing atom numbering
scheme is shown in Fig. 2. The complex has a distorted square planar
geometry. The wide bite angle of the ligand can be the main factor
accounting for this geometry. The average Pd P and Pd Cl bond
2. Results and discussion
2.1. Synthesis and characterization of ligands and metal
complexes
A
set of Pd(II) complexes containing the ligand 4,5-
˚
distances for complex I (structure 2) are 2.3(2) and 2.33 A, respec-
bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) were
synthesized. To determine the effect of ␲-acidity of the ligands
on the activity and selectivity of the hydroamination reaction,
we prepared chalcogenide derivatives of this ligand. The neutral
Pd(II) complexes, [Pd(Xantphos)Cl2] (I), [Pd(Xantphos = O)Cl2]
(II), [Pd(Xantphos = S)Cl2] (III) and [Pd(Xantphos = Se)Cl2] (IV),
synthesized from [PdCl2(COD)] (COD 1,5-cyclooctadiene) and
corresponding xantphos or xantphos chalcogenide were isolated
as air stable complexes in quantitative yields, 98%, 96%, 94% and
93%, respectively (see Scheme 2). Mixture of dichloromethane and
tetrahydrofuran was chosen as the solvent. Analytical date can be
found in Table 1.
tively, and are in agreement with the values reported for similar
structures [29].
There are also a number of hydrogen bonds in complex I (struc-
ture 2), which are between the THF and dichloromethane free
molecules, coordinated chloride atom of the complex, and C
bonds of phenyl rings, C45–H45A ··Cl1 = 2.81 A and C44–H45A–Cl1
H
i
i
˚
Table 2
31P NMR chemical shifts (ı ppm)a of ligand molecules, Xantphos chalcogenides, and
their Pd(II) complexes.
Compound
ı (ppm)
Compound
ı (ppm)
Xantphos = O
Xantphos = S
Xantphos = Se
Complex I
56.5
39.7
31.4b
22.4c
Complex II
Complex III
Complex IV
60.2d
42.5
The palladium complexes I, II, III and IV all exhibit a singlet in
1
the 31P{ H} NMR spectra in the range 22.4–48.6 ppm, which are in
36.2e
a similar range to the chemical shifts reported for the palladium
complexes containing bidentate phosphines (see Table 2).
Upon substitution of the chalcogenide Xantphos, the resonances
a
Referred to 85% H3PO4 as external standard in CDCl3 solution.
b
c
1JP–Se = 749 Hz.
Ref. [29].
1
due to the phosphorus atom in the 31P{ H} NMR spectra shifted
significantly to the highfield. The 31P{1H} NMR spectrum for II
d
e
In DMF-d7 solution.
1JP–Se = 790 Hz.
(oxide derivative) exhibited a singlet at 48.6 ppm while the singlet

190
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H2O2, Elemental S or Se
O
O
PPh2
PPh2
Ph2P
PPh2
X
X
X = O, S or Se
O
Ph2P
PPh2
X
X
Pd
Cl
Cl
Scheme 2. Synthetic procedures for preparation of palladium: Xantphos chalcogenide catalysts.
Table 3
Crystallographic and structure refinements data of Xantphos = S, complexes (I) and (III).a
Compound
Xantphos = S
40H33Cl5OP2PdS2
Complex I
Complex III
Formula
Formula weight
C
C44H42Cl4O2P2Pd
912.94
C40H34Cl4OP2PdS2
904.95
762.09
Crystal system
Space Group
Monoclinic
C2/c
Triclinic
P¯ı
Triclinic
P¯ı
a/Å
b/Å
12.919(3)
17.840(4)
16.546(3)
90
103.86(3)
90
3702.4(15)
4
1.367
2.1–29.2
1576
0.479
−17 ≤ h ≤ 17
−24 ≤ k ≤ 24
−22 ≤ l ≤ 20
14524
10.564 (2)
11.985 (2)
16.401 (3)
76.77 (3)
89.56 (3)
87.31 (3)
2019.2 (7)
2
11.9136 (3)
12.2522 (2)
16.1724 (4)
94.0480 (14)
110.0800 (11)
116.3920 (12)
1914.90 (7)
2
1.569
2.7–27.5
916
0.99
c/Å
␣/◦
␤/◦
␥/◦
Volume/Å3
Z
Density (calc.)/g cm−1
ꢀ ranges for data collection
F(0 0 0)
1.502
2.6–17.6
932
Absorption coefficient/mm−1
Index ranges
0.84
−13 ≤ h ≤ 13
−15 ≤ k ≤ 15
−18 ≤ l ≤ 21
18899
−15 ≤ h ≤ 15
−15 ≤ k ≤ 15
−20 ≤ l ≤ 21
30920
Data collected
Unique data (Rint
)
3413, (0.038)
234, 1
0.085, 0.1404
0.0535, 0.1273
1.02
0.53, −0.38
w(Fo2)2]1/2
.
4884, (0.077)
480, 0
0.1654, 0.2642
0.0846, 0.2126
1.05
7263, (0.044)
453, 0
0.0481, 0.0837
0.0350, 0.0773
1.03
Parameters, restrains
a
Final R1, wR2 (Obs. data)
a
Final R1, wR2 (All data)
Goodness of fit on F2 (S)
Largest diff peak and hole/e Å3
1.68, −1.49
0.86, −0.59
ꢀ
ꢀ
ꢀ
ꢀ
a
2
R1
=
||Fo| − |Fc||/
|Fo|, wR2 = [
(w(Fo − Fc2)2)/
Table 4
Selected bond distances (Å) and angles (◦) for Xantphos = S, complexes (I) and (III).
Xantphos = S
Complex(I)
Complex(III)
S1–P1
P1–C7
P1–C14
P1–C1
Cl1–C21
Cl2–C21
1.9444 (9)
1.815 (2)
1.815 (2)
1.825 (2)
1.901 (3)
1.635 (4)
Cl1–Pd1
Cl2–Pd1
Pd1–P1
Pd1–P2
C1–P1
C8–P1
C35–P2
C29–P2
P1–Pd1–P2
P1–Pd1–Cl2
P2–Pd1–Cl2
P1–Pd1–Cl1
P2–Pd1–Cl1
Cl2–Pd1–Cl1
2.3341(19)
2.330(2)
2.293(2)
Pd1–S2
Pd1–Cl2
Pd1–S1
Pd1–Cl1
Cl3–C1S
Cl4–C1S
S1–P1
S2–P2
S2–Pd1–Cl
S2–Pd1–S1
Cl2–Pd1–S1
S2–Pd1–Cl1
Cl2–Pd1–Cl1
S1–Pd1–Cl1
P1–S1–Pd1
P2–S2–Pd1
2.0074(9)
2.0074(9)
2.0074(9)
2.0074(9)
2.0074(9)
2.0074(9)
2.0074(9)
2.0074(9)
87.23 (3)
86.37 (2)
172.07 (3)
174.33 (2)
89.39 (3)
96.60 (2)
109.99 (3)
108.09 (3)
2.307(2)
1.816 (7)
1.838 (8)
1.830 (7)
1.826 (7)
100.92 (7)
167.91 (7)
84.80 (7)
85.46 (7)
168.37 (7)
87.20 (7)
C7–P1–S1
C14–P1–S1
C1–P1–S1
114.27 (8)
116.72 (8)
111.99 (8)

B. Tamaddoni Jahromi et al. / Applied Catalysis A: General 433–434 (2012) 188–196
191
Fig. 1. ORTEP drawings of ligand Xantphos = S with atomic numbering scheme. The thermal ellipsoids are drawn at the 50% probability level at 298 K and disordered
chloroform solvated molecule was omitted for more clarity.
◦
◦
ii
˚
analogous to structure 2 with xantphos sulfide instead of xantphos,
and a distorted square planar configuration around the palla-
dium center. The average Pd S, Pd Cl and P S bond distances
for 3 are 2.303(7), 2.308(7) and 2.008(9) Å, respectively, and are
in agreement with the values reported previously for palladium
phosphine sulfide complexes [30]. Longer P S bond distance can
be attributed to the coordination of the S atoms to the Pd metal
core.
with an angle of 160 , C25–H25···Cl2 = 2.74 A with an angle of
ii
˚
C25–H25–Cl2 = 167.0 and C16–H16···Cl1 = 2.72 A with an angle of
C16–H16–Cl1i = 164.0◦ (symmetry codes: i = −x, −y + 1, −z + 1 and
ii = −x, −y + 1, −z). Packing diagram of complex I can be found in
Fig. S2 in supplemental material of this paper.
Complex III, ([Pd(Xantphos = S)Cl2]·CH2Cl2; structure 3) crys-
tallizes as red plates in the triclinic space group P¯ı (No. 2)
with two molecules in the unit cell (see Fig. 3). Structure 3 is
Fig. 2. The molecular structure of complex I, showing atom numbering scheme of complex [PdCl2(Xantphos)]. The thermal ellipsoids are drawn at the 40% probability level
at 293 K. Hydrogen atoms were omitted for clarity.

192
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Table 5
Hydroamination of isoprene with morpholine in various solvents using complex I as the catalyst.
Catalyst
Solventa
Time (h)
Conversion (%)b
Total selectivity of
butylamine (%)c
Selectivity of
octylamines (%)
MeOH
EtOH
MeCN
DMF
DMSO
Benzene
Toluene
12
12
12
12
12
12
12
91%
94%
96%
82%
74%
67%
73%
79%
81%
90%
68%
56%
58%
62%
12%
13%
6%
14%
18%
9%
[PdCl2(Xantphos)]
11%
a
All reactions were performed at reflux temperature of the corresponding solvent.
Conversion of morpholine based on GC analyses.
Total selectivity of butylamines.
b
c
Similarly, there are
a
number of hydrogen bonds in
et al. [26] was not sufficiently effective even at high temperature
(140–146 ◦C) and long reaction time. Another competitive reaction
was happened simultaneously to produce 4-(3-methylbut-2-
enyl)morpholine in low yield of 16% before reduction with LiAlH4.
We succeeded to hydroaminate isoprene with secondary
amines in the presence of Pd catalysts consisting of Xant-
phos/Xantphos chalcogenide ligands with improved conversion
up to 69% and with high regioselectivity up to 93% for hin-
dered secondary amines. In order to find the optimum conditions
for hydroamination reactions, some attempts were made to
investigate the effects of solvent and catalyst loading. At first,
hydroamination of isoprene with morpholine in the presence of
complex I, [Pd(Xantphos)Cl2], as a model substrate was carried
out in various solvents such as alcohols, acetonitrile, DMF and
DMSO. The reactions were run with molar ratio of 1–2:100:200 for
catalyst:amine:isoprene. This ratio was found to be the optimum
condition. The reaction was followed by reduction of the produced
2-buteneamine to the corresponding aliphatic amines as described
in experimental section.
complex III (structure 3), which are between the solvated
dichloromethane molecules, coordinated chloride atom of the
complex, and C H bonds of phenyl rings. Hydrogen bonds of
◦
˚
C1S–H1SB Cl1 = 2.57 A and C1S–H1SB–Cl1with an angle of 156 ◦,
˚
C44–H44A ··Cl2 = 2.61 A with an angle of C44–H44A–Cl2 = 149.0
◦
˚
and C34–H34A ··Cl2 = 2.79 A with angle of C34–H34A–Cl2 = 141.0
(symmetry codes: A = x, y, z) are found in the packing of Structure
3 which may stabilize the unit cells (See Fig. S3). Besides, crystal
structure packing dominates by C H···␲ interactions between
˚
neighboring molecules (C23–H23A ··Cg1 = 2.827 A, Cg1 being
the ring C54/C53/C52/C51/C56/C55, with A = x, y, z, see Fig. S3,
Supplemental Materials).
2.3. Catalytic hydroamination of isoprene
The isoprene hydroamination with
a wide range of sec-
ondary amines in the presence of the catalytic system,
Pd(Xantphos/Xantphos chalcogenide)Cl2, occurred homoge-
neously in acetonitrile as reaction solvent. Even though the excess
amount of isoprene complicated the processing and characteriza-
tion of the products, it resulted in the enhancement of conversion,
and selectively produces monooctadienyl amines (see Scheme 1),
so we performed the reaction with two equivalents of isoprene.
Palladium catalyzed hydroamination of isoprene with mor-
pholine to give 4-(2-methylbut-2-enyl)morpholine by Takahashi
The hydroamination reaction proceeded at 82 ◦C (boiling point
of MeCN) within 8–12 h and led to the formation of 4-(2-methylbut-
2-enyl)morpholine in 78% selectivity and ∼95–100% amine
conversion (prior to reduction with LiAlH4). The molar ratio of cat-
alyst and reagents was 1.5–2:100:200 for catalyst:amine:isoprene,
respectively. The yield of unsaturated octadienylamines was neg-
ligible and essentially depended on the solvent character. The
Fig. 3. The molecular structure of complex III, showing atom numbering scheme of complex [PdCl2(Xantphos = S)]. The thermal ellipsoids are drawn at the 50% probability
level at 150 K. Hydrogen atoms and dichloromethane solvated molecule were omitted for clarity.

B. Tamaddoni Jahromi et al. / Applied Catalysis A: General 433–434 (2012) 188–196
193
Table 6
Oxidation of a wide range of alcohols using Pd(II) complexes of Xantphos/Xantphos chalcogenides as catalyst in water at room temperature.a,b,c
Entry
Amine
PdCl2(COD)
Complex I
Complex II
Complex III
Complex IV
Conv. (%)
Sel. (%)
72:17
79:11
Conv. (%)
Sel. (%)
79:18
81:16
Conv. (%)
Sel. (%)
68:19
79:11
Conv. (%)
Sel. (%)
72:16
80:12
Conv. (%)
Sel. (%)
1
2
96
94
∼100
∼100
96
94
97
95
99
97
76:17
82:14
3
4
94
91
81:10
71:12
94
96
73:17
78:12
93
95
70:14
71:15
91
91
70:12
73:15
93
93
75:10
75:14
5
6
83
79
68:10
41:29
92
91
80:8
93
76
73:11
17:53
88
89
76:7
90
90
79:9
21:67
16:66
13:73
7
89
87
14:67
16:63
92
90
13:76
15:71
78
75
14:61
20:49
92
88
15:77
18:66
94
92
9:81
8
10:80
9
72
73
17:52
11:56
88
80
15:70
17:54
76
71
15:53
15:49
77
72
16:53
13:54
84
82
13:65
14:62
10
11
12
79
80
11:63
18:51
82
85
13:62
12:69
74
81
14:52
13:61
71
76
13:52
12:61
79
84
13:61
14:64
13
75
12:56
76
9:59
73
10:57
71
11:57
79
10:63
a
Isoprene:Amine:Catalyst (200:100:2) were stirred in a N2-filled 10 mL stainless steel thermo-regulated (electric oven) autoclave with a glass liner and a magnetic bar.
The conversion was calculated based on amine substrate, by using GC and with comparison of authentic samples.
Selectivity (%) [2-methyl-N,N-dialkyl/arylbutan-1-amine]:[N,N-dialkyl/aryl-3-methylbutan-2-amine].
b
c
hydroamination with secondary amines was clean and effective in
alcoholic solvents (MeOH and EtOH) or acetonitrile. However, the
conversion of the amines was not quantitative in alcohols.
Under same conditions, the higher yield of the unsaturated
octadienylamine (14–18%) in hot DMF or DMSO may be due to coor-
dination of the solvent to Pd center and deactivation of the catalyst
(see Table 5). At such temperatures, dimerization of the isoprene
can occur conveniently and hydroamination reaction becomes
unfavorable. In aromatic solvents such as benzene or toluene, the
yield of octadienylamines was lower (9–11%) than aprotic polar
solvents (DMF or DMSO), however the amine conversion was not
quantitative (67–73%). Moreover, the reaction time was strongly
influenced by the reaction temperature. When reaction temper-
ature was maintained at reflux, the reaction completed in 8 h.
At lower temperature (40–50 ◦C) the reaction rate decreased five
times (∼36–40 h), and concurrently the selectivity of the process

194
B. Tamaddoni Jahromi et al. / Applied Catalysis A: General 433–434 (2012) 188–196
Electron withdrawing substituents (Cl and Br) on N-methyl-aniline
R
moiety had lower activities might be owing to the electron with-
drawing effect on the N atom. On the contrary, electron donating
group OMe had more reactivity toward isoprene. All of the sec-
ondary aromatic amines preferred position 4 in isoprene which has
lower steric hindrance.
PdLn
X
R
R
R
H
LnPd
LnPd
LnPd-
3. Conclusion
+
NR1R2
NR1R2
Anti-Markovnikov regioselective hydroamination of isoprene
by Pd–Xantphos/Xantphos chalcogenide system, especially for
pyrrolidine and piperidine, were observed in mild conditions
(80 ◦C, 8 h) with high yields. A regular correlation was observed
between the reactivity of the amine and its basicity as well as
its steric hindrance. After reduction of the initial buteneamines
by LiAlH4, total yield of hydroamination products with secondary
amines were increased. We investigated the PdCl2(COD) complex
as catalyst. The complex showed lower activity than all of the
four complexes tested in this research. So, the catalytic property
depends on presence of phosphine/phosphine Chalcogenides sys-
tem. PdCl2(COD) complex was efficient only for pyrolidine and
piperidine amines which have the highest basicity among the tried
amines. Catalytic activity of Pd complexes with chalcogenides of
Xantphos decreased with increasing electronegativity of the sub-
stituent on the phosphorus atom. Notably, electron withdrawing
groups on aromatic amines as well as steric hindrance of them can
affect reactivity of the amine substrates. It should be mentioned
that in the course of isoprene hydroamination experiments some
dimerization/oligomerization reactions compete with hydroami-
nation, which is extremely dependent on the reaction time and
the temperature as well as the solvent type and the catalyst
selectivity.
R
R
HNR1R2
LnPd
NR1R2
Scheme 3. Proposed reaction pathways for hydroamination of isoprene via
intramolecular or intermolecular attack.
was reduced by the formation of a mixture of adducts. The yield of
target butylamines decreased to 24–59%.
To study the applicability of the prepared catalysts, hydroam-
ination of isoprene with a wide range of secondary amines were
carried out to obtain the saturated butylamines (see Table 6). The
reactivity and conversion were dependent on the nature of the
amines as well as the catalyst substitute. In the case of stronger
bases (lower pKb of the base), higher conversion of the amine
was observed (see Table 6, Entries 1, 2, 4 and 5). Also, amines
with higher steric hindrance could be converted to the corre-
sponding 1-isopentylamines with high selectivity. In these cases,
1-isopentylamines were obtained in higher percentages compared
to the reactions with lower steric hindrance amines, which were
led to 2-methyl-buteneamines before reduction with LiAlH4 (1-(2-
methylbutyl) amines after reduction). As we used LiAlH4 in our
reduction step, we could not recover our Pd complexes, compe-
tently. Most of the Pd in complexes precipitated as Pd black. To
resolve this economic problem, we are testing direct reduction of
our alkenylamine products by hydrogenation in the presence of Pd
catalysts.
4. Experimental
4.1. Instrumentation, methods and materials
Complex I ([Pd(Xantphos)Cl2]·CH2Cl2, Pd(COD)Cl2 and 4,5-
Concerning the influence of amine reactants on the reaction,
amines with higher basicity react more efficiently. Pyrrolidine and
piperidine with pKa = 11.26 and 11.22 respectively [31], showed
higher activity and quantitative conversion under our hydroami-
nation conditions. Diethylamine and dimethylamine showed more
reactivity while dibutylamine and diisopropylamine had mini-
mum conversion amongst selected secondary amines despite their
higher basic character. This may be due to the higher steric hin-
drance of their alkyl/aryl chains (iso-propyl and butyl). On the other
hand, such bases produced 1-isopentylamine as the major product
in high selectivity. Remarkably, amines with less steric hindrance
yield 1-isopentylamines.
Correspondingly, the ligand type has remarkable effect on the
catalyst efficiency. As can be seen in Tables 5 and 6, the best con-
version as well as the most selectivity was obtained from complex I
([Pd(Xantphos)Cl2]). According to the proposed catalytic cycle (see
Scheme 3), Xantphos P-donor ligand may leave the palladium cen-
ter easier at the first stage rather than leaving its chalcogenides.
Higher activity of selenide derivative could be ascribed to the
same reason, as well. It is clear that oxygenated phosphine species
have least efficiency and selenide phosphine species were more
capable toward hydroamination of isoprene. It should be noted
that selenide derivative has lower activity compared to complex
I ([Pd(Xantphos)Cl2]). Moreover, we run sets of reactions with N-
methyl-aniline, its chloro, bromo and methoxide derivatives as well
as diphenylamine. These amines react slightly lower than aliphatic
secondary amines, may be due to the aromatic system of the phenyl
ring and participating of the unpaired electrons on the N atom.
bis(diphenylphosphino)-9,9-dimethylxanthene
(Xantphos)
were prepared according to the previously published meth-
ods [29,32,33]. PPh2Cl, butyl lithium (15% solution in hexane),
elemental S and red Se, H2O2 (35% aqueous solution) and the
solvents were purchased from Merck and Fluka. The solvents were
analytical grade, and were purified and deoxygenated prior to use
based on standard methods. Isoprene was dried over CaH2, distilled
under N2 at atmospheric pressure, and the fraction distilled at
32 ◦C was collected and stored under N2 at −15 ◦C. Melting points
are uncalibrated and were measured with an Electrothermal 9200
melting point apparatus. IR spectra from 250 to 4000 cm−1 of
solid samples were taken from 1% dispersions in CsI pellets using
a Shimadzu-470 spectrometer. 1H and 31P NMR spectra were
recorded at room temperature on a Bruker AVANCE 500 MHz spec-
trometer. The NMR spectra are referenced to TMS (1H NMR) and
85% H3PO4 (
31P NMR). Elemental analyses were performed using
a Heraeus CHN–O Rapid analyzer. The course of the reactions was
monitored by gas chromatography (Agilent Technologies 7890A
Instrument), equipped with a capillary column (DB–5, 5% phenyl
methyl siloxane, capillary 60 m × 0.25 mm I.D. × 0.25 ␮m). The
samples were collected periodically for analyses with an off-line
GC equipped with a mass selective detector (MSD, Agilent 5975C).
Peaks were identified on the basis of the mass spectra by matching
to a library of NIST spectra. GC/FID was used to determine the
concentrations of products in the samples. Catalytic experiments
were conducted in an N2-filled 10 mL flask with a magnetic stirring
bar.

B. Tamaddoni Jahromi et al. / Applied Catalysis A: General 433–434 (2012) 188–196
195
4.2. Preparation of xantphos = O
of the ligand. After stirring for 30 min at 50 ◦C, the volume of the
reaction mixture was reduced to ca. 5 mL by rotary evaporator and
then freshly distilled Et2O (25 mL) was added. The resulting precipi-
tate was filtered off and washed with cold diethyl ether (10 mL) and
finally dried over P2O5. Recrystallization from mixture of THF: EtOH
afforded the analytically pure complex (94% yield). mp = 240–244 ◦C
(December). Anal. calcd. for: C40H33Cl5OP2PdS2: C, 51.14; H, 3.54;
found: C, 51.2; H, 3.6. NMR (CDCl3): 1H (500 MHz): ı (ppm) = 1.70
(s, 6H); 6.57 (m, 2H); 6.89 (d, 2H); 7.40 (m, 12H); 7.45 (d, 2H); 7.57
(m 8H). 31P: ı (ppm) = 42.5 (s). IR (CsI)/cm−1: 611 (ꢁ P S).
Xantphos (1.15, 2 mmol) was dissolved in THF (50 mL) and
excess amount of 3% H2O2 was added gently with cooling in an ice
bath. The mixture was stirred for an additional 1 h at RT and then
the reaction mixture was filtered through Büchner funnel to sep-
arate the white precipitate. Crystallization from hot ethanol:THF
(5:1) afforded pure Xantphos oxide as a white powder (91% yield).
mp = 164–171 ◦C. Anal. calcd. for: C39H32O3P2: C, 76.71; H, 5.28;
found: C, 76.9; H, 5.4. NMR (CDCl3): 1H (500 MHz): ı (ppm) = 1.76
(s, 6H); 6.95 (m, 2H); 7.16 (d, 2H); 7.39 (m, 6H); 7.46 (m, 6H); 7.61
(d, 2H); 7.77 (m 8H). 31P: ı (ppm) = 56.5 (s). IR (CsI)/cm−1: 1173 (ꢁ
4.7. Preparation of [PdCl2(Xantphos = Se)]·CHCl3; complex IV
P
O).
In darkness and under N2atmosphere, a solution of Xant-
phos = Se ligand, (0.1 g, 0.14 mmol) in hot chloroform (15 mL) was
added to a solution of PdCl2(COD) (0.039 g, 0.14 mmol) in same
solvent (15 mL). The color of the reaction mixture changed immedi-
ately from yellow to deep red. After stirring for 30 min at 50 ◦C, the
volume of the reaction mixture was reduced to ca. 5 mL by rotary
evaporator and then freshly distilled Et2O (25 mL) was added. The
resulting red precipitate was filtered off and washed twice with
cold diethyl ether (2 × 15 mL) and finally dried over silica gel in
darkness. Recrystallization from mixture of THF: EtOH afforded the
analytically pure complex (93% yield). mp = 289–291 ◦C (Dec.). Anal.
calcd. for: C40H33Cl5OP2PdS2: C, 51.14; H, 3.54; found: C, 51.2; H,
3.6. NMR (CDCl3): 1H (500 MHz): ı (ppm) = 1.63 (s, 6H); 6.77 (m,
2H); 6.84 (d, 2H); 7.19 (m, 12H); 7.26 (s, 1H); 7.41 (d, 2H); 7.48
(m 8H). 31P: ı (ppm) = 36.2 (s); satellites were observed at 38.4 and
34.5 ppm (1JP–Se = 790 Hz). IR (CsI)/cm−1: 529 (ꢁ P Se).
4.3. Preparation of xantphos = S
Xantphos (1.15 g, 2 mmol) was dissolved in toluene (50 mL) and
was mixed with elemental sulfur (0.13 g, 4.05 mmol) and refluxed
overnight under dried N2. Evaporation of the solvent under vac-
uum afforded crude sulfide derivative. Crystallization from hot
chloroform yielded pure Xantphos sulfide as colorless block crys-
tals suitable for X-ray crystallography (88% yield). mp = 221–224 ◦C.
Anal. calcd. for: C40H33Cl3OP2S2: C, 63.04; H, 4.36; found: C, 63.2;
H, 4.4. NMR (CDCl3): 1H (500 MHz): ı (ppm) = 1.71 (s, 6H); 6.88 (m,
2H); 7.12 (d, 2H); 7.43 (m, 12H); 7.59 (d, 2H); 7.78 (m 8H). 31P: ı
(ppm) = 39.7 (s). IR (CsI)/cm−1: 619 (ꢁ P S).
4.4. Preparation of xantphos = Se
Xantphos (1.15 g, 2 mmol) was dissolved in toluene (50 mL)
and was mixed with elemental red selenium (0.32 g, 4.05 mmol)
and refluxed overnight under dried N2. Filtration of the reaction
mixture and evaporation of toluene by rotary evaporator afforded
crude selenide derivative. Crystallization from hot benzene yielded
pure Xantphos selenide as a pale yellow powder (83% yield).
mp = 264–269 ◦C (December). Anal. calcd. for: C39H32OP2Se2: C,
63.60; H, 4.38; found: C, 63.9; H, 4.5. NMR (CDCl3): 1H (500 MHz):
ı (ppm) = 1.69 (s, 6H); 6.89 (m, 2H); 7.04 (d, 2H); 7.36 (m, 6H); 7.41
(m, 6H); 7.61 (d, 2H); 7.77 (m 8H). 31P: ı (ppm) = 31.4 (s). Satel-
lites were observed for 77Se (Natural abundance = 7.63%) at 33.3
and 29.6 ppm (1JP–Se = 749 Hz). IR (CsI)/cm−1: 533 (ꢁ P Se).
4.8. General procedure for the hydroamination of isoprene
All hydroamination reactions were performed in an N2-filled
10 mL flask with a magnetic stirring bar. A solution of the cata-
lyst (0.02 mmol, 0.02 equiv.), isoprene (2.0 mmol, 2.0 equiv.), and
the secondary amine (1 mmol, 1 equiv.) dissolved in MeCN (5 mL)
were charged by cannulation techniques. After refluxing the mix-
ture for required time, the reaction mixture was allowed to cool
to room temperature. For reduction of prepared alkene amines a
slurry of LiAlH4 (1.5 mmol, 1.5 equiv.) in dry Et2O (5–10 mL) was
added. This mixture was stirred at room temperature overnight
under an atmosphere of N2. Quenching of reaction mixture per-
formed by slow addition of water (0.1 mL), then 1 M NaOH (0.1 mL),
and a further aliquot of water (0.3 mL). After filtration, the solvents
were removed under reduced pressure. Column chromatography
(hexane: Et2O, SiO2) afforded the purified amine products either as
single compound or as a mixture of regioisomers. Characterization
of the products was done by NMR.
4.5. Preparation of [PdCl2(Xantphos = O)].THF; complex II
To a solution of Xantphos = O ligand, (0.1 g, 0.16 mmol) in THF
(20 mL), PdCl2(COD) (0.038 g, 0.16 mmol) in chloroform (15 mL)
was added under an atmosphere of N2. The color of the reaction
mixture changed from pale yellow to light orange. After stirring for
30 min at 50 ◦C, the volume of the reaction mixture was reduced to
ca. 5 mL by rotary evaporator and then freshly distilled Et2O (20 mL)
was added. The resulting precipitate was filtered off and washed
with cold diethyl ether (10 mL) and finally dried over P2O5. Recrys-
tallization from mixture of THF: EtOH afforded the analytically pure
complex (96% yield). mp = 201–206 ◦C (December). Anal. calcd. for:
Supplementary data
Supplementary data associated with this article can be found
in the online version of the article. CCDC numbers 856776-856778
contains the supplementary crystallographic data for xantphos = S
and complex I and complex III. These data can be obtained free
of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or
from the Cambridge Crystallographic Data Center, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336 033; or e mail:
deposit@ccdc.cam.ac.uk.
C
43H40Cl2O4P2Pd: C, 60.05; H, 4.69; found: C, 60.2; H, 4.7. NMR
(DMF d7): 1H (500 MHz): ı (ppm) = 1.73 (s, 6H); 1.95 (m, 4H); 3.69
(dd, 4H); 7.03 (m, 2H); 7.22 (d, 2H); 7.48 (m, 6H); 7.52 (m, 6H); 7.67
(d, 2H); 7.78 (m 8H). 31P: ı (ppm) = 60.2 (s). IR (CsI)/cm−1: 1165 (ꢁ
P
O).
4.6. Preparation of [PdCl2(Xantphos = S)]·CHCl3; complex III
Acknowledgements
To a solution of Xantphos = S ligand, (0.1 g, 0.15 mmol) in chlo-
roform (10 mL), PdCl2(COD) (0.043 g, 0.15 mmol) was added in
chloroform (15 mL) under N2 atmosphere. The color of the reaction
mixture changed from light yellow to deep orange upon addition
The authors gratefully acknowledge the financial support from
the University of Tehran. Also, we are thankful to Dr. Alan J. Lough
from the University of Toronto for crystal structure determinations.

196
B. Tamaddoni Jahromi et al. / Applied Catalysis A: General 433–434 (2012) 188–196
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