Air- and moisture-stable cationic (diphosphine)palladium(II) complexes as hydroamination catalysts X-ray crystal structures of two complexes

Article abstract of DOI:10.1016/S0022-328X(02)02138-1

A series of cationic (diphosphine)palladium(II) complexes have been prepared and fully characterized, including two crystal structures. These complexes were evaluated as catalysts for the hydroamination of acyclic alkenes. The reactivity of the catalysts is dependent on the nature of the diphosphine ligand and the substituents on the amine and alkene substrates.

Full text of DOI:10.1016/S0022-328X(02)02138-1

Journal of Organometallic Chemistry 665 (2003) 250ꢃ257
/
www.elsevier.com/locate/jorganchem
Air- and moisture-stable cationic (diphosphine)palladium(II)
complexes as hydroamination catalysts
X-ray crystal structures of two
[(diphosphine)Pd(NCMe)(OH2)]2ꢀ[OTf]2ꢁ complexes
Kelin Li a, Peter N. Horton b, Michael B. Hursthouse b, King Kuok (Mimi) Hii a,*
a Department of Chemistry, King’s College London, Strand, London WC2R 2LS, UK
b EPSRC X-ray Crystallography Service, Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK
Received 29 September 2002; received in revised form 12 November 2002; accepted 12 November 2002
Abstract
A series of cationic (diphosphine)palladium(II) complexes have been prepared and fully characterized, including two crystal
structures. These complexes were evaluated as catalysts for the hydroamination of acyclic alkenes. The reactivity of the catalysts is
dependent on the nature of the diphosphine ligand and the substituents on the amine and alkene substrates.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Palladium; Diphosphine; Hydroamination
1. Introduction
pyran rings [2]. In this paper, we report a class of
dicationic palladium catalysts for the hydroamination of
acyclic olefins under pH neutral conditions. Being well-
defined, highly active, as well as relatively stable to air
and moisture, we believe they offer significant advan-
tages over other catalysts that have been reported
recently in this area [3].
Generating no waste products, the addition of amine
NÃ/H bond across an olefin (hydroamination) is argu-
ably one of the most efficient ways of accessing
nitrogen-containing molecules from cheap, readily avail-
able starting materials (Scheme 1). Despite extensive
studies over the last four decades, it remained a
challenge in synthetic chemistry [1]. Uncatalysed reac-
tions with unactivated olefins often require harsh
reaction conditions. In addition, there is also the
challenge of stereochemical control when the reaction
involves unsymmetrical olefins. With conventional Mi-
2. Result and discussion
Five diphosphine ligands were chosen in this study for
their different steric and electronic characteristics. The
chael acceptors (where Rꢂelectron-withdrawing
/
(diphosphine)palladium(II) chlorides 1aꢃ1e were pre-
/
group), the reaction tends to favour the anti-Markovni-
kov product, whereas the opposite regiomer, containing
a stereogenic center, offers the more valuable product.
Previously, we reported the use of palladium catalysts
for the hydroamination of cyclic olefins and applied
them in the synthesis of a-amino-tetrahydrofuran and
pared simply by the reaction of the appropriate diphos-
phine ligands with PdCl2(NCMe)2 or PdCl2(cod) in
dichloromethane. The dichloride complexes 1aꢃ1e were
/
subsequently subjected to ligand exchange with silver
trifluoromethanesulfonate in acetonitrile, furnishing
dicationic (diphosphine)palladium(II) complexes 2aꢃ
2e, in moderate to high yields [dppfꢂ1,1?-bis(diphenyl-
phosphino)ferrocene (a); dpprꢂ1,1?-bis(diphenylphos-
phino)ruthenocene (b); dippfꢂ1,1?-bis(diisopropyl-
phosphino)ferrocene (c); dpppꢂ1,3-bis(diphenylphos-
/
/
/
* Corresponding author. Tel.: ꢀ
7848-2810.
E-mail address: mimi.hii@kcl.ac.uk (K.K.M. Hii).
/
44-20-7848-1183; fax: ꢀ44-20-
/
/
/
0022-328X/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 3 2 8 X ( 0 2 ) 0 2 1 3 8 - 1

K. Li et al. / Journal of Organometallic Chemistry 665 (2003) 250ꢃ
/257
251
100 8C (entries 1ꢃ3), the catalytic loading can be
/
reduced to as low as 0.25 mol% without any observable
lost in catalytic activity or yield (entries 4 and 5). An
increase in bite angle (2b) and electronic donating nature
(2c) of the phosphine ligand led to the termination and
decrease in reactivity, respectively (entries 6 and 7). The
reaction catalysed by the less rigid diphosphine ligand
(2d) is less efficient, leading to the formation of
unidentifiable side products and a corresponding drop
in yield (entry 8).
In comparison, the chiral complex (2e) offers moder-
ate activity. Lowering the reaction temperature ensured
a better yield at the expense of reactivity (entries 9 and
10). Interestingly, the ee of the product (70% S) is not
dependent on the reaction temperature. We believe this
compares favourably to a similar system previously
reported [4]. Overall, the rate of the reaction decreases in
Scheme 1. Hydroamination of an olefin.
phino)propane (d); BINAPꢂ
/
1,1?-bis(diphenylphos-
phino)naphthalene (e)] (Scheme 2).
Freshly prepared samples of complexes 2aꢃ2e contain
/
two coordinated acetonitrile solvent molecules in solu-
tion (integration of 1H-NMR resonances). Once iso-
lated, these triflate salts are somewhat hygroscopic, but
may be stored indefinitely under nitrogen and handled
briskly in air. Upon standing, one of the acetonitrile
ligands is labile and is susceptible to displacement by a
water molecule (through contact with atmospheric
moisture), giving rise to crystalline monoꢃaqua com-
/
plexes of the type [(P2)Pd(NCMe)(H2O)]2ꢀ[TfO]2ꢁ. The
molecular composition of the isolated crystals is sup-
ported by elemental analysis, and the requisite molecu-
the order: dppfꢀ
/
BINAPꢀ
/
dippfꢀ
/
dppeꢀdppr.
/
The system is also sensitive to changes in the steric
and electronic character of the substrates. Substitution
of aniline with electron-donating and -withdrawing
groups led to retardation of the reaction, suggesting
subtle counter-effects (entries 11 and 12). N-methyl
aniline also reacted slower (entry 13). Vinyl naphthalene
undergoes similar reactions (entries 14 and 15).
lar weight is also observed in the ESꢃMS. Further
/
evidence was provided by the crystal structures obtained
of compounds 2c and 2e (Fig. 1). Each molecule
contains water molecules in the asymmetric unit cell.
Palladium catalysts enabling the addition of nBuNH2,
piperidine and aniline to activated olefins (acrylic acid
derivatives) have been described by Kawatsura and
Hartwig [5], generated in situ from a mixture of
Pd(OAc)2 or Pd(TFA)2 with PCP and PNP ligands. In
comparison, the (diphosphine)palladium(II) complexes
3. Catalytic studies
The hydroamination reaction between substituted
anilines and styrenes were subsequently performed in
the presence of these catalysts (Scheme 3) and the results
are summarized in Table 1.
2aꢃ2d can also catalyse these reactions in comparable
/
The reactions were carried out in thick-walled sealed
Young tubes for convenience. In all cases, the addition
activity. More interestingly, complex 2a is also able to
catalyse the addition of piperidine to the less activated
methyl cinnamate (Table 2).
The addition of the amine is regiospecific, occurring
at the b-position exclusively. Once again, the dppf-
ligated complex 2a appears to be the most active catalyst
in the addition of piperidine to methylmethacrylate at
was regiospecific * the branched product N-phenyl-N-
/
(1-phenylethyl)amine was the only observed isomer.
Unsurprisingly, the rate and turnover of the reactions
are dependent on the diphosphine ligand employed. The
most active complex is the complex 2a, derived from the
dppf ligand. At the optimal reaction temperature of
Scheme 2. Preparation of (diphosphine)palladium(II) complexes.
Scheme 3.

252
K. Li et al. / Journal of Organometallic Chemistry 665 (2003) 250ꢃ257
/
Fig. 1. ORTEP views of complexes 2c×
/
2H2O (left) and 2e×0.5H2O (right) drawn with 50% thermal ellipsoids. Hydrogen atoms, solvent molecules and
/
counterions are omitted for the sake of clarity.
room temperature (entries 1ꢃ
/
4), where the loading can
are reported in d (ppm) referenced to residual protons
and 13C signals of deuterated chloroform or deuterated
actonitrile as internal standard. 31P-NMR spectra were
referenced to H3PO4. The coupling constants are in
Hertz (J Hz). Infrared spectra were recorded on a
be reduced to 0.2 mol% (giving a yield of 76%).
Decreasing the nucleophilicity of amine requires
higher reaction temperature, with a corresponding
decrease in the reaction yield (entries 5ꢃ7). Methyl
/
crotonate undergoes reaction with piperidine and pyr-
rolidine under ambient conditions to yield the Michael
products (entries 8 and 10). Here, a more pronounced
dependence of the yield on the ring size of the cyclic
amine was observed (compared with entries 1 and 7).
The addition of piperidine to the less activated cinna-
mate is comparatively slow (entry 9). Aniline can be
similarly induced to undergo reaction with the methyl
acrylate and acrylonitrile to give fairly good yields
(entries 10 and 11).
In summary, we demonstrated that cationic dipho-
sphinepalladium(II) complexes can catalyse hydroami-
nation of different olefin substrates, including styrenes,
acrylates, crotonates and methyl cinnamate (reported
for the first time). Reactivity is found to be dependent
on the diphosphine ligands, the nucleophilicity of the
amine and the nature of the olefin.
PerkinꢃElmer 1600 FTIR spectrometer, either as Nujol
/
mull between NaCl plates, or as KBr discs. Elemental
analyses were carried out by Elemental Analysis Service,
University of North London. Mass spectra (MS) were
recorded using ES techniques by the EPSRC MS
Services, Swansea, Wales. (P2)PdCl2 complexes were
synthesized from bidentate ligand P2 and PdCl2(cod) or
PdCl2(NCMe)2. All other compounds were used as
received, unless otherwise specified.
Suitable crystals were selected and data collected on a
Bruker Nonius KappaCCD Area Detector at the
window of a Bruker Nonius FR591 rotating anode
˚
(lMo–K ꢂ0:71073 A) driven by COLLECT [7] and
DENZO [8] software at 120 K. Structures were deter-
a
mined in SHELX-97 [9] and refined using SHELXL-97 [10]
(Table 3).
Improvement in this and other combinations of
olefins, amines and catalysts are currently under exam-
ination and will be reported in due course.
4.1. Typical procedure for the synthesis of
[(diphosphine)Pd(NCMe)(H2O)](OTf)2 complexes
4.1.1. [(dppf)Pd(NCMe)(H2O)](OTf)2 (2a)
A solution of AgOTf (0.17 g, 0.68 mmol) in 10 ml
CH3CN was added to a solution of (dppf)PdCl2 (0.20 g,
0.27 mmol) in 20 ml CH2Cl2. The orange solution
turned purple immediately followed the white precipi-
tate of AgCl. The mixture was stirred at room tempera-
ture for at most 5 min, then it was filtered and
evaporated to give a purple residue, which was recrys-
4. Experimental
All manipulations were performed using standard
Schlenk techniques. Dichloromethane and acetonitrile
were dried over CaH2, distilled and stored under a
nitrogen atmosphere. NMR spectra were recorded on a
Bruker AVANCE 360 instrument (1H at 360 MHz, 31P
at 145.8 MHz and 13C at 90.6 MHz). The chemical shifts
tallized from CH2Cl2 to give 0.17 g purple solid. Yieldꢂ
/
61%. Anal. Calc. for C38H32F6NO7P2S2FePd×4CH2Cl2:
/

K. Li et al. / Journal of Organometallic Chemistry 665 (2003) 250ꢃ
/257
253
Table 1
Hydroamination between vinylarenes and substituted anilines
a
Substrate/catalyst ratio.
b
Isolated yields, reproducible to within 9
70% ee (S), enantiopurity determined by chiral HPLC (Chiralcel OD-H column).
/3%.
c
C, 37.15; H, 2.97; N, 1.03. Found: C, 37.87; H, 2.31; N,
130.4, 130.3, 79.6, 79.5, 79.4, 77.4, 77.3, 77.2. IR (Nujol,
cmꢁ1): 2326, 2298.
1
1.48%. ESꢃ
NMR (CD3CN): dꢂ
2JHH 8.2 Hz, Ph); 7.58 (t, 8H, 2JHH
(s, 4H, Cp); 4.59 (s, 4H, Cp); 1.96 (s, 3H, NCCH3).
31P{1H}-NMR (CD3CN): dꢂ43.8. 13C{1H}-NMR
(CD3CN): dꢂ134.8, 134.8, 134.7, 134.4, 134.4, 130.5,
/MS (MeOH, 20 V): 725.1, 677.3, 661.1. H-
/
7.72ꢃ
/
7.83 (m, 8H, Ph); 7.74 (t, 4H,
8.2 Hz, Ph); 4.75
ꢂ
/
ꢂ
/
4.1.2. [(dppr)Pd(NCMe)(H2O)](OTf)2 (2b)
Yellow solid, yieldꢂ
C38H32F6NO7P2S2PdRu×2CH2Cl2: C, 40.63; H, 3.07;
N, 1.18. Found: C, 39.92; H, 2.97; N, 1.12%. ESꢃMS
/99%. Anal. Calc. for
/
/
/
/

254
K. Li et al. / Journal of Organometallic Chemistry 665 (2003) 250ꢃ257
/
Table 2
Addition of amines to substituted acrylate, crotonate and cinnamatea
a
Reactions were performed with 2 mol% catalyst for 18 h (unoptimized). Uncatalysed reactions performed under the same reaction gave
negligible yields [6].
b
After 48 h.
(MeOH, 20 V): 764.1, 723.0, 706.7. 1H-NMR (CD3CN):
(CD3CN): dꢂ
/
39.9. 13C{1H}-NMR (CD3CN): dꢂ
/
2
dꢂ
Ph); 7.57 (t, 8H, JHH
4.90 (s, 4H, Cp); 1.96 (s, 3H, NCCH3). 31P{1H}-NMR
/
7.78ꢃ
/
7.84 (m, 8H, Ph); 7.73 (t, 4H, JHH
ꢂ
/
7.7 Hz,
134.6, 134.5, 134.4, 134.4, 134.3, 130.5, 130.4, 130.3,
81.6, 81.5, 81.4, 79.6, 79.5, 79.4. IR (Nujol, cmꢁ1): 2320,
2295.
2
ꢂ7.7 Hz, Ph); 5.13 (s, 4H, Cp);
/

K. Li et al. / Journal of Organometallic Chemistry 665 (2003) 250ꢃ
/257
255
Table 3
Crystallographic data for the 2c and 2e
2.15ꢃ
/
2.34 (m, 2H, PCH2CH2); 1.96 (s, 3H, NCCH3).
31P{1H}-NMR (CD3CN): dꢂ
/
12.3. 13C{1H}-NMR
(CD3CN): dꢂ134.1, 134.0, 134.0, 130.6, 130.5, 130.4,
/
Identification 2c
code
2e
126.1, 125.4, 21.8, 21.6, 21.3, 18.9. IR (Nujol, cmꢁ1):
2324, 2297.
Formula
[(C22H36FeP2Pd)(NCMe) [(C44H32P2Pd)(NCMe)
(H2O)][CF3SO3]2ꢁ
×
/
2H2O (H2O)][CF3SO3]2ꢁ
Monoclinic
11.2625(4)
17.4583(9)
12.6295(7)
109.85
×0.5H2O
/
4.1.5. [(R-BINAP)Pd(NCMe)(H2O)](OTf)2 (2e)
Crystal system Monoclinic
Yellow crystal from recrystallization from CH2Cl2ꢃ
Et2O, yieldꢂ97%. Anal. Calc. for C48H36F6NO7-
P2S2Pd×0.5H2O×2CH2Cl2: C, 47.47; H, 3.27; N, 1.11.
Found: C, 47.05; H, 3.02; N, 1.10%. ESꢃMS (MeOH, 20
V): 789.3, 746.3, 729.2. H-NMR (CD3CN): dꢂ7.77ꢃ
7.87 (m, 7H); 7.74 (d, 4H, Jꢂ8.2 Hz); 7.65ꢃ7.70 (m,
6H); 7.52ꢃ7.62 (m, 5H); 7.21 (t, 2H, Jꢂ8.6 Hz); 7.10 (t,
2H, Jꢂ7.2 Hz); 6.91 (s, br, 4H); 6.67 (d, 2H, Jꢂ8.6
Hz); 1.96 (s, 3H). 31P{1H}-NMR (CD3CN): dꢂ
31.0
ppm. 13C{1H}-NMR (CD3CN): dꢂ
141.0, 136.0, 135.8,
/
˚
a (A)
39.1915(9)
11.9660(3)
17.0622(5)
111.748(2)
7432.0(3)
8
˚
/
b (A)
˚
c (A)
/
/
b (8)
/
3
V (A )
˚
2335.7(2)
2
Block; Yellow
1
/
/
Z
Crystal
/
/
Block; Red
/
/
Crystal size
(mm)
0.06ꢄ
/
0.05ꢄ
/
0.03
0.10ꢄ
/
0.08ꢄ0.05
/
/
/
Absolute
structure
parameter
u range (8);
completeness
(%)
ꢁ/
0.04(2)
/
/
135.7, 135.6, 135.5, 134.2, 133.9, 131.4, 131.3, 130.4,
130.3, 130.2, 129.8, 129.2, 128.8, 128.5, 128.4, 128.0,
127.4, 123.9, 120.3, 119.5, 118.8. IR (Nujol, cmꢁ1):
2318, 2291.
2.96ꢃ
/
25.03; 99.6
2.98ꢃ25.03; 99.8
/
Reflections
collected
Independent
reflections
Data/
26 663
30 673
6548 [Rint
ꢂ/
0.1221]
8129 [Rint
ꢂ0.0963]
/
4.2. Typical reaction procedure for hydroamination
6548/0/458
8129/7/630
0.999
restraints/
parameters
Goodness-of- 0.952
fit on F2
0.021 g (0.020 mmol) of complex 2a was suspended in
0.5 ml of toluene in a thick-walled Young’s tube.
Freshly distilled styrene (0.17 ml, 1.50 mmol) and aniline
(0.09 ml, 1.00 mmol) were added via syringe. The tube
was sealed via a PTFE tap and the reaction mixture was
stirred and heated in a thermostatic oil bath. After the
appropriate reaction time (typically 18 h), the homo-
geneous red solution was subjected to column chroma-
Final R
indices
R1ꢂ
0.1488
/
0.0772, wR2ꢂ
/
R1ꢂ
wR2ꢂ
/
0.0536,
0.0773
/
[I2ꢀ2s(I2)]
/
R indices (all R1ꢂ
data) 0.1807
/
0.1633, wR2ꢂ
/
R1ꢂ
wR2ꢂ
/
0.0948,
0.0866
/
tography (silica gel: CH2Cl2ꢃhexane, 2:1) to furnish the
/
1
product, which was subsequently characterized by H-
and 13C-NMR spectroscopy. Yield was calculated with
respect to aniline (the limiting reagent).
4.1.3. [(dippf)Pd(NCMe)(H2O)](OTf)2 (2c)
Purple solid, which was recrystallized from CH2Cl2ꢃ
/
ether to give purplish-red crystals suitable for X-ray
analysis.
Yieldꢂ
C26H41F6NO7P2S2FePd×
/
60%.
Anal.
2CH2Cl2: C, 30.92; H,
Calc.
for
4.2.1. N-Phenyl-N-(1-phenylethyl)amine (3) [11]
2
7.38 (d, 2H, Ph, JHH
/
2H2O×
/
1H-NMR (CDCl3): dꢂ
Hz); 7.33 (t, 2H, Ph, JHH
/
ꢂ6.8
/
4.54; N, 1.29. Found: C, 31.63; H, 4.29; N, 0.90%. ESꢃ
/
2
MS (MeOH, 20 V): 585.2, 541.2, 525.1. 1H-NMR
(CD3CN): 4.96 (s, 4H, Cp); 4.72 (s, 4H, Cp); 2.69 (m,
ꢂ7.3 Hz); 7.25 (t, 1H, Ph,
/
2
7.3 Hz); 7.10 (t, 2H, Ph, JHH
2JHH
1H, Ph, 2JHH
ꢂ
/
ꢂ7.3 Hz); 6.65 (t,
/
7.3 Hz); 6.52 (d, 2H, Ph, 2JHH
ꢂ7.3 Hz);
/
i
4H, Pr); 1.96 (s, 3H, NCCH3); 1.55 (dd, 12H, JHH
2
ꢂ
/
ꢂ
/
2
4.40 (q, 1H, CHCH3, JHH
3
i
2
ꢂ6.8 Hz); 3.94 (s, br, 1H,
/
7.0 Hz, JPH
Hz, 3JPH 17.3 Hz, iPr). 31P{1H}-NMR (CD3CN): dꢂ
91.4. 13C{1H}-NMR (CD3CN): dꢂ
77.4, 77.3, 77.2,
ꢂ/18.4 Hz, Pr); 1.31 (dd, 12H, JHH
ꢂ6.8
/
2
NH); 1.43 (d, 3H, CHCH3, JHH
ꢂ
6.8 Hz). 13C{1H}-
/
ꢂ
/
/
NMR (CDCl3): dꢂ147.7, 145.6, 129.5, 129.0, 127.3,
/
/
126.2, 117.6, 113.7, 53.9, 25.5.
75.5, 75.4, 75.3, 30.6, 30.4, 30.3, 30.2, 20.5, 20.3. IR
(Nujol, cmꢁ1): 2316, 2289.
4.2.2. N-(4-Methoxyphenyl)-N-(1-phenylethyl)amine
(4) [12]
4.1.4. [(dppp)Pd(NCMe)(H2O)](OTf)2 (2d)
1H-NMR (CDCl3): dꢂ
/
7.32ꢃ
/
7.40 (m, 4H, Ph); 7.24
2
(t, 1H, Ph, JHH
2
Light-yellow solid, yieldꢂ/51%. Anal. Calc. for
ꢂ
/
7.3 Hz); 6.71 (d, 2H, Ph, JHH
ꢂ
/
9.1
9.1 Hz); 4.45 (q, 1H,
6.8 Hz); 3.91 (s, br, 1H, NH); 3.72 (s,
2
C31H30F6NO7P2S2Pd×4CH2Cl2: C, 34.58; H, 3.15; N,
/
Hz); 6.49 (d, 2H, Ph, JHH
ꢂ
/
2
1.15. Found: C, 34.11; H, 2.78; N, 1.33%. ESꢃ
/
MS
(MeOH, 20 V): 577.1, 535.3, 518.2. 1H-NMR (CD3CN):
CHCH3, JHH
3H, OCH3); 1.52 (d, 3H, CHCH3, JHH
13C{1H}-NMR (CDCl3): dꢂ
152.3, 145.9, 142.0, 129.0,
127.2, 126.3, 115.1, 114.9, 56.1, 54.6, 25.5.
ꢂ
/
2
ꢂ6.8 Hz).
/
2
7.67 (m, 12H, Ph); 7.49 (t, 8H, JHH
dꢂ
/
7.57ꢃ
/
ꢂ
/
7.2 Hz,
/
Ph); 2.86 (td, 4H, 2JHH
ꢂ
/
6.4 Hz, 2JPH
ꢂ1.8 Hz, PCH2);
/

256
K. Li et al. / Journal of Organometallic Chemistry 665 (2003) 250ꢃ257
/
4.2.3. N-(4-Chlorophenyl)-N-(1-phenylethyl)amine (5)
[13]
4.2.8. Methyl-3-(dibutylamino)-2-methylpropionate
(10) [17]
1H-NMR (CDCl3): dꢂ
/
7.28ꢃ
/
7.30 (m, 4H, Ph); 7.21
1H-NMR (CDCl3): dꢂ
/
3.66 (s, 3H, COOCH3); 2.58ꢃ
2.72 (m, 2H, NCH2CH (1H) and NCH2CH (1H)); 2.28ꢃ
2.42 (m, 5H, CH2CH2NCH2CH2 (4H) and NCH2CH
(1H)); 1.31ꢃ1.40 (m, 4H, CH2CH2NCH2CH2); 1.21ꢃ
1.31 (m, 4H, CH2CH3); 1.11 (d, 3H, CHCH3, JHH
6.8 Hz); 0.89 (t, 6H, CH2CH3, 2JHH 7.0 Hz). 13C{1H}-
NMR (CDCl3): dꢂ177.2, 58.6, 54.6, 51.8, 39.4, 29.7,
20.9, 15.9, 14.5.
/
2
2
(t, 1H, Ph, JHH
ꢂ
/
6.8 Hz); 6.99 (d, 2H, Ph, JHH
ꢂ
/
8.6
8.6 Hz); 4.40 (q, 1H,
6.8 Hz); 4.08 (s, br, 1H, NH); 1.54 (d,
3H, CHCH3, JHH
6.8 Hz). 13C{1H}-NMR (CDCl3):
/
2
Hz); 6.38 (d, 2H, Ph, JHH
ꢂ
/
2
CHCH3, JHH
ꢂ
/
/
/
2
2
ꢂ
/
ꢂ
/
144.9, 143.8, 128.1, 127.9, 126.2, 124.9, 120.9, 113.5,
52.7, 24.2.
ꢂ
/
/
4.2.4. N-Methyl-N-phenyl-N-(1-phenylethyl)amine (6)
[14]
4.2.9. Methyl 3-(benzylamino)-2-methylpropanoate
(11) [18]
1H-NMR (CDCl3): dꢂ
/
7.35ꢃ
/
7.38 (m, 3H, Ph); 7.26ꢃ
/
2
1H-NMR (CDCl3): dꢂ
/
7.23ꢃ
(s, 2H, PhCH2); 3.69 (s, 3H, COOCH3); 2.85ꢃ
1H, PhCH2NCH2); 2.63ꢃ2.73 (m, 2H, PhCH2NCH2
(1H), PhCH2NCH2CH (1H)); 1.16 (d, 3H, CHCH3,
2JHH 6.8 Hz). 13C{1H}-NMR (CDCl3): dꢂ
176.4,
/
7.35 (m, 5H, Ph); 3.79
7.30 (m, 4H, Ph); 6.88 (d, 2H, Ph, JHH
ꢂ
/
8.6 Hz); 6.77
7.3 Hz); 5.17 (q, 1H, CHCH3,
6.8 Hz); 2.73 (s, 3H, NCH3); 1.59 (d, 3H,
2
(t, 1H, Ph, JHH
2JHH
CHCH3, JHH
ꢂ
/
/2.92 (m,
ꢂ
/
/
2
ꢂ
/
6.8 Hz). 13C{1H}-NMR (CDCl3): dꢂ
/
150.6, 143.2, 129.6, 128.8, 127.3, 127.2, 117.0, 113.5,
56.9, 32.3, 16.7.
ꢂ
/
/
140.4, 128.5, 128.1, 127.0, 53.8, 52.2, 51.7, 40.2, 15.4.
4.2.5. N-[1-(2-Naphthyl)ethyl]-N-phenylamine (7)
[15]
4.2.10. 2-Methyl-3-pyrrolindin-1-yl-propionic acid
methyl ester (12) [19]
1H-NMR (CDCl3): dꢂ
7.54 (d, 1H, naphthyl, JHH
/
7.82ꢃ7.86 (m, 4H, naphthyl);
/
1H-NMR (CDCl3): dꢂ
3.66 (s, 3H, COOCH3); 2.76
/
2
ꢂ
/
8.6 Hz); 7.46ꢃ
/
7.51 (m,
1
2
(dd, 1H, NCH2CH, JHH
2.59ꢃ2.70 (m, 1H, NCH2CH); 2.43ꢃ
pyrrolindinyl); 2.42 (dd, 1H, NCH2CH, JHH
2JHH
11.4 Hz); 1.71ꢃ1.75 (m, 4H, pyrrolindinyl); 1.16
(d, 3H, CHCH3, JHH
(CDCl3): dꢂ177.0, 60.0, 54.6, 52.0, 40.0, 23.9, 16.2.
ꢂ
/
8.2 Hz, JHH
ꢂ11.4 Hz);
/
2
2H, naphthyl); 7.12 (t, 2H, Ph, JHH
ꢂ/7.7 Hz); 6.70 (t,
/
/2.52 (m, 4H,
1H, Ph, 2JHH
4.68 (q, 1H, CHCH3, JHH
ꢂ
/
7.7 Hz); 6.58 (d, 2H, Ph, 2JHH
ꢂ7.7 Hz);
/
1
ꢂ6.2 Hz,
/
2
ꢂ6.5 Hz); 4.16 (s, br, 1H,
/
ꢂ
/
/
2
NH); 1.62 (d, 3H, CHCH3, JHH
ꢂ
6.5 Hz). 13C{1H}-
/
2
ꢂ
7.3 Hz). 13C{1H}-NMR
/
NMR (CDCl3): dꢂ147.7, 143.2, 134.0, 133.2, 129.5,
/
/
128.9, 128.3, 128.1, 126.4, 125.9, 124.8, 124.7, 117.7,
113.8, 54.1, 25.5.
4.2.11. 3-Piperidin-1-yl-butyric acid methyl ester (13)
[20]
4.2.6. N-Methyl-N-[1-(2-naphthyl)ethyl]-N-
phenylamine (8)
1H-NMR (CDCl3): dꢂ
/
3.65 (s, 3H, COOCH3); 3.05ꢃ
3.15 (m, 1H, NCH); 2.57 (dd, 1H, NCHCH2, 1JHH
5.6
14.1 Hz); 2.43 (t, 2H, pyrrolindinyl, JHH
/
1H-NMR (CDCl3): dꢂ
/
7.78ꢃ
/
7.86 (m, 4H, naphthyl);
7.3
8.6 Hz); 6.79 (t, 1H, Ph,
ꢂ
/
2
2
7.47ꢃ
Hz); 6.93 (d, 2H, Ph, JHH
2JHH
7.3 Hz); 5.31 (q, 1H, CHCH3, JHH
2.72 (s, 3H, NCH3); 1.68 (d, 2H, CHCH3, JHH
Hz). 13C{1H}-NMR (CDCl3): dꢂ
150.6, 140.9, 133.8,
/
7.53 (m, 3H, naphthyl); 7.31 (t, 2H, Ph, 2JHH
ꢂ
/
Hz, JHH
5.5 Hz); 2.21 (dd, 1H, NCHCH2, JHH
2JHH
14.1 Hz); 1.50ꢃ1.56 (m, 4H, pyrrolindinyl);
1.36ꢃ1.42 (m, 4H, pyrrolindinyl); 1.03 (d, 3H,
CHCH3, JHH
173.8, 57.4, 54.6, 51.9, 49.8, 38.2, 26.8, 25.2, 15.6.
ꢂ
/
ꢂ
/
1
2
ꢂ8.6 Hz,
/
ꢂ
/
2
ꢂ
/
/
ꢂ
/
ꢂ6.8 Hz);
/
2
/
ꢂ6.8
/
2
ꢂ
/
6.8 Hz). 13C{1H}-NMR (CDCl3): dꢂ
/
/
133.0, 129.7, 128.5, 128.4, 128.0, 126.5, 126.1, 125.3,
117.2, 113.5, 57.0, 32.3, 16.4.
4.2.12. 3-Phenyl-3-piperidino-propionic acid methyl ester
(14) [21]
4.2.7. 2-Methyl-3-piperidin-1-yl-propionic acid methyl
ester (9) [16]
1H-NMR (CDCl3): dꢂ
/
7.21ꢃ7.34 (m, 5H, Ph); 3.98
/
2
(t, 1H, PhCH, JHH
1H-NMR (CDCl3): dꢂ
/
3.67 (s, 3H, COOCH3); 2.64ꢃ
2.73 (m, 1H, CHCH3); 2.59 (dd, 1H, NCH2CH, 1JHH
8.6 Hz, 2JHH
12.2 Hz); 2.27ꢃ2.39 (m, 4H, piperidinyl);
2.26 (dd, 1H, NCH2CH, JHH
Hz); 1.48ꢃ1.55 (m, 4H, piperidinyl); 1.34ꢃ
piperidinyl); 1.11 (d, 3H, CHCH3, JHH
13C{1H}-NMR (CDCl3): dꢂ
177.7, 63.2, 55.5, 52.4,
38.8, 26.9, 25.2, 16.6.
/
ꢂ
/
7.7 Hz); 3.59 (s, 3H, COOCH3);
2
7.7 Hz, JHH
1
2.99 (dd, 1H, PhCHCH2, JHH
ꢂ
/
ꢂ
/
ꢂ14.9
/
1
2
ꢂ
/
/
Hz); 2.70 (dd, 1H, PhCHCH2, JHH
14.9 Hz); 2.36ꢃ2.42 (m, 2H, piperidinyl); 2.25ꢃ
2H, piperidinyl); 1.43ꢃ1.58 (m, 4H, piperidinyl); 1.29ꢃ
1.35 (m, 2H, piperidinyl). 13C{1H}-NMR (CDCl3): dꢂ
ꢂ
/
7.7 Hz, JHH
ꢂ
/
1
2
ꢂ
/
6.4 Hz, JHH
1.41 (m, 2H,
6.8 Hz).
ꢂ
/
12.2
/
/2.31 (m,
/
/
/
/
2
ꢂ
/
/
/
173.0, 139.1, 128.7, 128.3, 127.7, 66.7, 51.9, 51.3, 38.3,
26.8, 24.9.

K. Li et al. / Journal of Organometallic Chemistry 665 (2003) 250ꢃ
/257
257
4.2.13. 3-Pyrrolindin-1-yl-butyric acid methyl ester (15)
[22]
Acknowledgements
1H-NMR (CDCl3): dꢂ
/
3.67 (s, 3H, COOCH3); 2.84ꢃ
/
We thank the EPSRC for postdoctoral funding
(ROPA award, Grant No.: GR/R50332/01) and John-
son Matthey, Plc. for the generous loan of palladium
salts.
2.93 (m, 1H, NCH); 2.68 (dd, 1H, NCHCH2, 1JHH
ꢂ4.5
/
2
Hz, JHH
ꢂ
/
15.0 Hz); 2.55ꢃ2.60 (m, 4H, pyrrolindinyl);
/
1
2.29 (dd, 1H, NCHCH2, JHH
2
8.6 Hz, JHH
ꢂ
/
ꢂ15.0
/
Hz); 1.75ꢃ1.79 (m, 4H, pyrrolindinyl); 1.15 (d, 3H,
/
2
CHCH3, JHH
173.2, 55.9, 51.8, 51.1, 40.4, 23.7, 19.0.
ꢂ
/
6.4 Hz). 13C{1H}-NMR (CDCl3): dꢂ
/
References
[1] (a) D.M. Roundhill, Catal. Today 37 (1997) 155;
(b) T.E. Muller, M. Beller, Chem. Rev. 98 (1998) 675.
¨
[2] X. Cheng, K.K. Hii, Tetrahedron 57 (2001) 5445.
4.2.14. N-Phenyl-b-alanine methyl ester (16) [23]
2
7.19 (t, 2H, Ph, JHH
1H-NMR (CDCl3): dꢂ
Hz); 6.73 (t, 1H, Ph, JHH
/
ꢂ/7.3
[3] M. Nobis, B. Driessen-Holscher, Angew. Chem. Int. Ed. Engl. 40
(2001) 3983(references cited therein).
2
ꢂ7.3 Hz); 6.63 (d, 2H, Ph,
/
[4] M. Kawatsura, J.F. Hartwig, J. Am. Chem. Soc. 122 (2000) 9546
The reaction of aniline to 4-trifluoromethylstyrene catalysed by
[((R)-BINAP)Pd(OTf)2] gave the addition product in 81% ee.
[5] M. Kawatsura, J.F. Hartwig, Organometallics 20 (2001) 1960.
[6] The uncatalysed addition of piperidine to methyl crotonate at
20 8C requires 7 days to reach 85% yield, see ref. [20].
[7] R. Hooft, B.V. Nonius, Data collection software, 1998.
[8] Z. Otwinowski, W. Minor, Methods in Enzymology, in: C.W.
Carter, Jr., R.M. Sweet (Eds.), Macromolecular Crystallography,
2JHH
ꢂ7.3 Hz); 4.02 (s, br, 1H, NH); 3.70 (s, 3H,
/
COOCH3); 3.46 (t, 2H, NHCH2, 2JHH
ꢂ6.4 Hz); 2.64 (t,
/
ꢂ
6.4 Hz). 13C{1H}-NMR
173.2, 148.0, 129.7, 118.1, 113.4, 52.2,
/
2
2H, NHCH2CH2, JHH
(CDCl3): dꢂ
/
39.8, 34.1.
Part A, vol. 276, Academic Press, New York, 1997, pp. 307ꢃ
[9] G.M. Sheldrick, Acta Crystallogr. A 46 (1990) 467.
[10] G.M. Sheldrick, University of Gottingen, Germany, 1997.
/
326.
4.2.15. N-Phenyl-b-alanine nitrile (17) [24]
2
1H-NMR (CDCl3): dꢂ
/
7.22 (t, 2H, Ph, JHH
Hz); 6.79 (t, 1H, Ph, JHH 7.3 Hz); 6.62 (d, 2H, Ph,
2JHH
7.3 Hz); 3.99 (s, br, 1H, NH); 3.53 (m, 2H,
NHCH2); 2.64 (t, 2H, CH2CN, JHH
13C{1H}-NMR (CDCl3): dꢂ
146.6, 130.0, 119.0, 118.7,
ꢂ7.3
/
¨
2
ꢂ
/
[11] Y. Motoyama, Y. Mikami, H. Kawakami, H. Nishiyama,
Organometallics 18 (1999) 3584.
ꢂ
/
2
[12] K. Tomoka, I. Inoue, M. Shindo, K. Koga, Tetrahedron Lett. 32
(1991) 1095.
ꢂ6.4 Hz).
/
/
[13] I. Lee, H.Y. Kim, H.K. Kang, H.W. Lee, J. Org. Chem. 53 (1988)
2678.
113.5, 40.2, 18.5.
[14] T. Kawakami, T. Sugimoto, I. Shibata, A. Baba, H. Matsuda, N.
Sonoda, J. Org. Chem. 60 (1995) 2677.
[15] S. Talukdar, A. Banerji, J. Org. Chem. 63 (1998) 3468.
[16] S.J. Dominianni, R.P. Pioch, R.L. Young, P.J. Stimart, J. Med.
Chem. 14 (1971) 1009.
5. Supplementary material
[17] R.B. Moffett, R.E. Strube, L. Skaletzky, J. Med. Chem. 14 (1971)
1088.
Crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic
Data Centre, CCDC nos. 193997 and 193998 for
compounds 2c and 2e, respectively. Copies of this
information may be obtained free of charge from The
Director, CCDC, 12 Union Road, Cambridge CB2 1EZ,
[18] G.M. Salamonczyk, K. Han, Z.-W. Guo, C.J. Sih, J. Org. Chem.
61 (1996) 6893.
[19] R.B. Moffett, J. Org. Chem. 14 (1949) 862.
[20] M.Y.H. Essawi, Pharmazie 54 (1999) 575.
[21] C.B. Pollard, G.C. Mattson, J. Am. Chem. Soc. 78 (1956) 4089.
[22] S. Carlsson, S.-O. Lawesson, Tetrahedron 38 (1982) 413.
[23] J. Barluenga, J. Villamana, M. Yus, Synthesis 5 (1981) 375.
[24] M.F. Simeonov, I.P. Bangov, S.I. Spassov, R. Radeglia, J. Mol.
Struct. 65 (1980) 189.
UK (Fax: ꢀ
/
44-1223-336033; e-mail: deposit@ccdc.cam.
ac.uk or www: http://www.ccdc.cam.ac.uk).