Aziridine-derived iminophosphine ligands in palladium-catalyzed allylic substitution

Article abstract of DOI:10.1016/j.jorganchem.2004.07.066

New iminophosphines have been synthesized from (R,R)-1-amino-2-diphenylphosphino cyclohexane (R.R)-1 in good to excellent yields. The catalysts obtained from iminophosphines 3a-g and [Pd(C₃H₅)Cl]₂ promote the enantioselective allylic substitution of 1,3-diphenyl-2-propenyl acetate (6) with diethyl malonate with good enantioselectivity. The air-stable complex PdCl₂[κ²-P,N-(R,R) -2-Ph₂PC₆H₁₀N = CHPh] (4) has been prepared and structurally characterized by X-ray crystallography.

Full text of DOI:10.1016/j.jorganchem.2004.07.066

Journal of Organometallic Chemistry 689 (2004) 3604–3611
www.elsevier.com/locate/jorganchem
Aziridine-derived iminophosphine ligands in palladium-catalyzed
allylic substitution
*
Shadi Dalili, Aldo Caiazzo, Andrei K. Yudin
Department of Chemistry, Davenport Research Laboratories, University of Toronto, 80 St. George St., Toronto, Ont., Canada M5S 3H6
Received 19 May 2004; accepted 22 July 2004
Available online 17 September 2004
Abstract
New iminophosphines have been synthesized from (R,R)-1-amino-2-diphenylphosphino cyclohexane (R.R)-1 in good to excellent
yields. The catalysts obtained from iminophosphines 3a–g and [Pd(C3H5)Cl]2 promote the enantioselective allylic substitution of 1,3-
diphenyl-2-propenyl acetate (6) with diethyl malonate with good enantioselectivity. The air-stable complex PdCl2[j2-P,N-(R,R)-2-
Ph2PC6H10N@CHPh] (4) has been prepared and structurally characterized by X-ray crystallography.
ꢀ 2004 Elsevier B.V. All rights reserved.
Keywords: Iminophosphines; Allylic substitution; P,N ligands; Palladium catalysis; Bidentate ligands; Square-planar complexes
1. Introduction
tions, such as cross-coupling involving organostannanes
[6], oligomerization of olefins [7], copolymerization of
CO with olefins [8], Heck reaction [9], transfer hydro-
genation [10], and Suzuki coupling [11]. In several cases,
the iminophosphines exhibit different reactivity from the
conventional chelating diphosphines. For instance, Shi-
rakawa reported that N-(2-diphenylphosphinobenzylid-
ene)-2-phenylethylamine possesses higher activity than
DPPP in the cross-coupling reaction between organo-
stannanes and aryl iodides. This phenomenon was
attributed to an alternative catalytic cycle, where the
P,N-coordinated palladium undergoes oxidative addi-
tion to the tin reagent rather than to the aryl halide [6].
The literature reports on iminophosphines with an
alkyl backbone are quite scarce. One of the notable exam-
ples is the P,N-ligand based on the chiral 1-diph-
enylphosphino-2-amino-3-methylbutane scaffold, which
has been used in several examples of allylic substitution
reactions with enantioselectivities reaching 95% [12].
We recently reported [13] the synthesis of a new class
of P,N-ligands based on trans-1-amino-2-diph-
enylphosphino cyclohexane backbone. The resolution of
trans-1-amino-2-diphenylphosphino cyclohexane (1) was
Many industrial processes require access to chiral cat-
alysts, which are used in enantioselective transforma-
tions of broad classes of substrates [1]. As the catalyst
is typically composed of a metal ion surrounded by a
chiral ligand, development of new and improved ligands
is prerequisite to fast progress in the field of asymmetric
synthesis. Bidentate ligands are ubiquitous components
of many transition-metal-based catalysts [2]. Among
them, chiral P,N ligands have found applications in a
variety of asymmetric processes ranging from allylic
substitution to hydrogenation of ketones [3]. From the
standpoint of reactivity, a P,N-ligand is a combination
of hard (nitrogen) and soft (phosphorus) centers. Within
this environment, metal ions can be stabilized in their
low oxidation states by the p-accepting character of
the softer phosphorus site. On the other hand, the harder
nitrogen site better stabilizes higher oxidation states
[4,5]. These properties have been explored in many reac-
*
Corresponding author. Tel.: +4169465042; fax: +4169467676.
E-mail address: ayudin@chem.utoronto.ca (A.K. Yudin).
0022-328X/$ - see front matter ꢀ 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.07.066

S. Dalili et al. / Journal of Organometallic Chemistry 689 (2004) 3604–3611
3605
Ar
NH3+ T-
NH2
PPh2
N
(D)-tartaric acid
ArCHO (1 eq), K2CO3
THF, reflux
H2O, 80˚ C
PPh2
PPh2
2
3
1
3a: Ar = Ph
3b: Ar = o-OCH3C6H4
3c: Ar = o-FC6H4
3d: Ar = 2-Pyridyl
3e: Ar = 9-anthryl
3f: Ar = o-OHC6H4
3g: Ar = o-OH(m-OMe)C6H3
T- = (D)-tartrate
Scheme 1.
accomplished via the (
D
)-tartrate salts (2). The possibil-
dichloromethane) to light yellow was observed in the
course of the process.
ity of further derivatizing the primary amino group in
(1) using a series of aldehydes in order to prepare new
iminophosphines led us to synthesize (R,R)-1-(N-benzy-
lideneamino)-2-(diphenylphosphino)-cyclohexane (3a).
The coordination ability of 3a was explored by prepar-
ing the RuCl2[j2-P,N-(R,R)-2-Ph2PC6H10N@CHPh)]-
(j-P-PPh3), a stable Ru(II) complex [14].
In this paper, we report the synthesis of several (R,R)-
1-(N-arylideneamino)-2-(diphenylphosphino)-cyclohex-
anes (3a–g) obtained by condensation of (R.R)-1 with
aldehydes (Scheme 1). The structural features of the
complex between iminophosphine (3a) and Pd (II) are
presented and catalytic activity of the in situ formed
complexes is described.
The 31P{1H} NMR spectrum in CD2Cl2 shows a sin-
glet at 46.6 ppm, which accounts for the coordination of
the phosphorous atom to palladium. The 1H NMR
(CD2Cl2) shows a singlet at 8.58 ppm, due to the C–H
imine proton and a downfield quartet at 4.48 ppm due
to the methine cyclohexane proton at the a position to
the imine moiety. The complex was obtained as an air-
stable yellow solid in 65% yield. The X-ray structure
determination was carried out on crystals grown from
CH3NO2/ether mixture and a perspective view of the
molecular structure along with the atomic numbering
scheme is shown in Fig. 1. A selection of bond lengths
and angles for the molecule is listed in Table 1.
The key geometric parameters of complex 4 are sim-
ilar to PdCl2[j2-P,N-2-Ph2PC6H4N@CHPh)] (5), which
contains a phenyl ring in place of the cyclohexane moi-
ety [11]. The coordination around palladium is close
to square-planar [N(1)–Pd(1)–Cl(1) = 170.14(7)ꢁ and
P(1)–Pd(1)–Cl(2) = 177.68(3)ꢁ] while the bite angle
N(1)–Pd(1)–P(1) is 81.06(7)ꢁ which is similar to the anal-
ogous angle in 5 [82.10(6)ꢁ]. The stronger trans influence
of the phosphorous atom with respect to the nitrogen is
2. Results and discussion
Iminophosphines 3 were prepared by refluxing the
(D)-tartrate of (R,R)-1-amino-2-diphenylphosphino
cyclohexane (2) with the corresponding aldehyde in
THF in the presence of K2CO3 (Scheme 1). The final
products were recovered sufficiently pure for the subse-
quent catalytic studies or purified by crystallization.
The iminophosphines proved to be stable to oxidation
for several days even if no particular precaution was ta-
ken for their storage.
The addition of a dichloromethane solution of imino-
phosphine 3a to a dichloromethane solution of PdCl2-
(PhCN)2 led to quantitative formation of PdCl2[j2-P,
N-(R,R)-2-Ph2PC6H10N@CHPh] (4) (Scheme 2). A quick
color change from deep orange (palladium precursor in
Ph
Ph
Pd
N
N
P
Cl
Cl
CH2Cl2
+ PdCl2(PhCN)2
PPh2
Ph2
3a
4
Fig. 1. X-ray crystallographic structure of PdCl2[j2-P,N-(R,R)-2-
Ph2PC6H10N@CHPh].
Scheme 2.

3606
S. Dalili et al. / Journal of Organometallic Chemistry 689 (2004) 3604–3611
Table 1
Table 2
Crystallographic data for compound 4
˚
Selected bond distances (A) and angles (ꢁ) for compound 4
Bond lengths
Bond angles
Empirical formula
C25H26Cl2NPPd
Pd(1)–N(1)
Pd(1)–P(1)
Pd(1)–Cl(1)
Pd(1)–Cl(2)
P(1)–C(20)
P(1)–C(14)
P(1)–C(1)
2.057(2)
2.2165(8)
2.2966(11)
2.3825(8)
1.800(3)
1.806(3)
1.857(3)
1.279(4)
1.487(4)
N(1)–Pd(1)–P(1)
N(1)–Pd(1)–Cl(1)
P(1)–Pd(1)–Cl(1)
N(1)–Pd(1)–Cl(2)
P(1)–Pd(1)–Cl(2)
Cl(1)–Pd(1)–Cl(2)
C(20)–P(1)–C(14)
C(1)–P(1)–Pd(1)
C(7)–N(1)–Pd(1)
81.06(7)
170.14(7)
89.15(3)
96.78(7)
177.68(3)
92.99(3)
109.56(15)
102.90(10)
131.9(2)
Formula weight
Temperature (K)
˚
Wavelength (A)
548.74
150 (1)
0.71073
Monoclinic
P2(1)
Crystal system
Space group
Unit cell dimensions
˚
a (A)
7.7247(15)
15.761(3)
˚
N(1)–C(7)
N(1)–C(6)
b (A)
˚
c (A)
10.035(2)
90
a (ꢁ)
b (ꢁ)
106.98(3)
90
1168.6(4)
c (ꢁ)
˚
reflected in the longer Pd(1)–Cl(2) bond [2.3825(8) A]
˚
with respect to Pd(1)–Cl(1) bond [2.2966(11) A]. This
3
V (A )
˚
Z
2
1.56
Dcalc (mg/m3)
is a typical feature of P,N-coordinated systems [15]
which can be found in the complex 5 and in trans-1-[2-
diphenylphosphinocyclohexyl]-3,5-dimethyl-1H-pyrazole]
palladium(II) dichloride, previously reported by us [13].
The Pd(1)–Cl(2) bond length is in the range expected for
the palladium complexes of iminophosphines [7,11]. To
the best of our knowledge, this is the first reported X-ray
structure of a Pd(II) complex containing a c-iminophos-
phine ligand with an alkyl backbone. Crystallographic
data for compound 4 is included in Table 2.
In order to examine the catalytic efficiency of the
newly synthesized iminophosphines 3, the allylic substi-
tution reaction was chosen as a test reaction, using
1,3-diphenyl-2-propenyl acetate (6) as a substrate and
dialkyl malonates as pro-nucleophiles under the stand-
ard experimental conditions (Scheme 3) [16]. The results
are summarized in Table 3.
The first nucleophile used for this investigation was
the sodium salt of diethyl malonate and the reactions
were carried out in the presence of several catalyst pre-
cursors. The best palladium catalyst precursor in terms
of yield and enantioselectivity turned out to be
[PdCl(C3H5)]2 (entry 2), and only Pd2(dba)3 provided
comparable results (entry 3). Pd(OAc)2 showed poor
activity (entry 4), while the catalyst derived from
Pd(PhCN)2Cl2 did not catalyze the process at all (entry
5). By switching the nucleophile to diethyl malonate
along with N,O-bistrimethyl silyl acetamide (BSA) and
increasing the substrate/nucleophile ratio to 1:3, the
enantioselectivity increased to 87% (entry 6). In addi-
tion, the reaction time was decreased to 4–5 h compared
to 12 h for reactions using the sodium salt of diethyl
malonate. Raising the temperature to 60 ꢁC or decreas-
l (mmꢀ1
F(000)
)
1.104
556
Crystal size (mm3)
hmax
Index ranges
0.24 · 0.20 · 0.10
27.49ꢁ
ꢀ10 6 h 6 9,
ꢀ20 6 k 6 20,
ꢀ12 6 l 6 13
9383
Reflections measured
Independent reflections
Completeness to theta = 27.49ꢁ
Absorption correction
4816
99.5%
Semi-empirical from
equivalents
0.853–0.896
Full-matrix least-squares
on F2
Transmission
Refinement method
Number of parameters
Goodness-of-fit on F2
Final R indices [I > 2r(I)]
R indices (all data)
272
1.040
R1 = 0.0279, wR2 = 0.0603
R1 = 0.0314, wR2 = 0.0620
ꢀ0.04(2)
Absolute structure parameter
Extinction coefficient
Largest difference peak and hole (e A
0.0057(8)
ꢀ3
˚
)
0.777 and ꢀ0.717
ing it to ꢀ10 ꢁC did not dramatically affect the outcome
(entries 8 and 10). Changing the palladium precursor to
Pd2(dba)3 had a detrimental effect as can be seen in entry
11. Dimethyl malonate provided a slightly lower enan-
tioselectivity (81%) but similar yield (85%) compared
to diethyl malonate (entry 9). The free amine ligand
(R,R)-1-amino-2-diphenylphosphino cyclohexane (R.R)-1
was also active in this reaction albeit in low yield and
enantioselectivity (entry 1). The pre-formed complex 4
was also tested under these experimental conditions,
but it only led to traces of 7 after 48 h with large
amounts of unidentified byproducts. A 2:1 ratio of
ROOC
Ph
COOR
Ph
OAc
[PdCl(C3H5)]2 (2%), 3 (2%)
KOAc, THF, rt
CHX(COOR)2
+
Ph
Ph
*
X = H, Na
R = Me, Et
7
6
Scheme 3.

S. Dalili et al. / Journal of Organometallic Chemistry 689 (2004) 3604–3611
3607
Table 3
Palladium-catalyzed allylic substitution in the presence of iminophosphine 3a: the influence of experimental parametersa
Entry
Nucleophile
Pd precursor
Ligand
T (ꢁC)
Substrate/nucleophile
Yieldb (%)
eec (%)
1
NaCH(COOEt)2
NaCH(COOEt)2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
Pd2(dba)3
(R.R)-1
3a
3a
rt
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:3
45
76
70
43
–
30 (S)
66 (R)
61 (R)
19 (S)
–
2
rt
3
NaCH(COOEt)2
NaCH(COOEt)2
NaCH(COOEt)2
rt
4
Pd(OAc)2
3a
3a
rt
5
PdCl2(PhCN)2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
Pd2(dba)3
rt
6
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
CH2(COOMe)2/BSA
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
3a
3a
rt
89
80
83
85
90
57
87 (R)
50 (R)
76 (R)
81 (R)
75 (R)
51 (R)
7d
8
rt
1:3
1:3
3a
3a
60
60
ꢀ10
rt
9
1:3
1:3
10
11
a
3a
3a
1:3
Reactions were carried under glove box atmosphere (argon) and monitored via TLC analysis. Solvent: THF. Pd/L = 1:1.
Isolated yields based on 1,3-diphenylprop-2-enyl acetate (6).
Determined on HPLC (chiralcel OJ column); hexane/AcOEt:95/5. Configuration assigned through comparison with HPLC data reported in the
b
c
literature [17].
d
The Pd/L ratio is 1:2.
ligand 3a to [PdCl(C3H5)]2 also catalyzed the reaction,
although the final product 7 was obtained in lower
enantioselectivity compared to a 1:1 ratio of ligand:Pd
(entry 7).
The selectivity observed in the presence of ligand 3a
can be explained on the basis of the relative rates of
reaction at C1 and C3 positions of the diasteromeric
p-allyl intermediates 8a (endo) and 8b (exo) arising from
the reaction between the catalyst and allyl acetate 6
(Scheme 4) [3f,18,19].
Previous mechanistic studies on allylic substitution
reactions provide evidence that the attack trans to the
Pd–P bond is more facile than the attack trans to the
Pd–N bond, as was shown by Pfaltz and coworkers with
Pd complexes of C2-symmetric bis(oxazoline) ligands. In
this case, the reaction at the allylic carbon connected to
the weaker (longer) Pd–P bond was demonstrated [20].
The major enantiomer of the final product (R configura-
tion) can only arise from the attack of malonate on
intermediate 8b. The differentiation between 8a and 8b
accounts for the observed enantioselectivity in our sys-
tem. Presumably, the favorable stacking interaction be-
tween the phenyl ring in C3 position of the allyl moiety
in 8b and the imine aryl substituent positioned over the
plane of the complex shifts the equilibrium towards 8b
leading to the major enantiomer observed.
Other iminophosphines 3b–g were tested in the same
reaction using the diethyl malonate/BSA method, in or-
der to investigate the effect of different aryl rings in the
imine moiety on enantioselectivity. The results are sum-
marized in Table 4.
The selectivity obtained in the presence of ligand 3b is
similar to the selectivity observed using 3a (entry 1).
This means that the presence of an electron-donating
methoxy group at the ortho position to the imine moiety
neither enhances nor decreases the yield and enantiose-
lectivity of the reaction, thereby not affecting equilib-
rium between the two p-allyl intermediates 8a and 8b.
In the case of electron-withdrawing substituents in the
ortho position to the imine moiety such as in compound
3c, the enantioselectivity is significantly decreased (entry
2). In addition, the final product is formed with opposite
selectivity (S) as opposed to the predominantly formed
(R) configuration in all other instances. The same out-
come is obtained in the case of 3d, where the pyridine
nitrogen may engage in side coordination (entry 3). In
the case of ligand 3e, the reactivity of the catalyst is
significantly enhanced with the reaction reaching com-
pletion after only five minutes, although enantioselectiv-
ities are diminished (entry 4). This is most likely due to
unfavorable destabilizing interactions in the p-allyl
intermediates between the bulky anthracenyl substituent
and the phenyl groups of the acetate. The ligands with
ortho-OH groups (compounds 3f and 3g) catalyzed the
reaction with good yield but low enantioselectivity and
longer reaction times (entries 7 and 8).
Ph2P
Pd
Ph2P
N
N
Ph
1
Pd
1
Ph
Ph
Ph
3
Ph
Ph
3
8b (exo)
8a (endo)
Nuc
Ph
Nuc
Ph
(R)-7 (major)
(S)-7 (minor)
Nuc
Ph
Ph
Nuc
Scheme 4.

3608
S. Dalili et al. / Journal of Organometallic Chemistry 689 (2004) 3604–3611
Table 4
Palladium-catalyzed allylic substitution in the presence of iminophosphines 3b–ga
Entry
Nucleophile
Pd precursor
Ligand
Substrate/nucleophile
Yieldb (%)
eec (%)
1
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
CH2(COOEt)2/BSA
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
[PdCl(C3H5)]2
3b
3c
3d
3e
3e
3e
3f
1:3
1:3
1:3
1:3
1:3
1:3
1:3
1:3
84
83
60
70
69
70
75
80
76 (R)
18 (S)
51 (S)
21 (R)
30 (R)
36 (R)
20 (R)
25 (R)
2
3
4d
5e
6f
7g
8g
a
3g
Reactions were carried out under glove box atmosphere (argon) and monitored via TLC analysis. Solvent: THF. Pd/L = 1:1. Unless otherwise
mentioned, all reactions went to completion in 4–5 h.
b
Isolated yields based on 1,3-diphenylprop-2-enyl acetate (6).
Determined on HPLC (chiralcel OJ column); hexane/AcOEt:95/5. Configuration assigned through comparison with HPLC data reported in the
c
literature [17].
d
Reaction went to completion after only 5 min.
Reaction was carried out at ꢀ10 ꢁC.
e
f
Reaction was carried out at ꢀ30 ꢁC.
g
Reactions went to completion after 48 h.
3. Conclusions
permanganate, and cerium. Column chromatography
was carried out using Silicycle 230–400 mesh silica gel
or aluminum oxide, neutral, Brockman type 1. High-
performance liquid chromatography (HPLC) was per-
formed on HP-1100 series instrument using 4.6
mm · 25 cm Daicel CHIRALPAK OJ column. Gas–liq-
uid-phase chromatography (GC) was done with HP-
6890 series GC system using high performance capillary
column HP-5. 1H NMR spectra were referenced to
residual CHCl3 (d 7.27 ppm), 13C NMR spectra were
referenced to CDCl3 (d 77.23 ppm), 19F NMR were ref-
erenced to CFCl3 (d 0 ppm) and 31P NMR spectra were
referenced to 85% H3PO4 as internal standard (d 0
ppm).
Novel iminophosphines 3 have been synthesized
from (R,R)-1-amino-2-diphenylphosphino cyclohexane
(R.R)-1 in good yields. The complexation chemistry of
Pd(II) with 3a was investigated by preparing the air
stable complex PdCl2[j2-P,N-(R,R)-2-Ph2PC6H10N@
CHPh)] (4). In the allylic substitution reaction of 1,3-
diphenyl-2-propenyl acetate, the ligands 3a and 3b
provided the best results. The main advantage of these
systems is their modular nature, which allows for a
potentially wide screening of different aldehydes and
consequently the possibility of fine tuning the electronic
and steric properties of the ligands. Further studies and
improvement on the catalytic activity of these ligands
are currently under investigation.
4.2. General synthesis of iminophosphine ligands
To a solution of K2CO3 (105 mg, 0.762 mmol) and
(R,R)-1-amino-2-diphenylphosphino tartrate salt (2)
[13] (300 mg, 0.693 mmol) in degassed H2O (5 mL)
was added degassed THF (2.1 mL), and the solution
was heated to reflux. A solution of aldehyde (0.762
mmol) in degassed THF (1 mL) was added dropwise.
The addition funnel was washed with 1 mL degassed
THF and the reaction was stirred at reflux for 2 h. After
cooling the reaction mixture to room temperature, the
solution was poured into degassed Et2O (10 mL) and
the organic layer was separated. The aqueous layer
was extracted with degassed Et2O (3 · 2 mL), and the
combined organic layers were washed with degassed
H2O (3 mL), dried over Na2SO4, filtered, and concen-
trated in vacuo.
4. Experimental
4.1. General
Chemicals were purchased from Aldrich Chemical
Co., Strem Chemical Co., Fischer Scientific Ltd. and
Lancaster and used without further purification. In
experiments requiring dry solvents, ether, toluene, hexa-
nes, acetonitrile, dichloromethane were purchased in
anhydrous form from Aldrich Chemical Co. Tetra-
hydrofuran (THF) was distilled over sodium-benzophe-
none ketyl under argon. Unless otherwise stated, all
reactions were performed under nitrogen or argon
atmosphere using flame-dried glassware and standard
syringe-pump techniques. Analytical thin layer chroma-
tography (TLC) was performed on Macherey Nagel pre-
coated glass-backed TLC plates (SIL G/UV254, 0.25
mm) purchased from Rose Scientific Limited and visual-
ized by UV lamp (254 nm), iodine, ninhydrin, potassium
4.2.1. Trans-N-benzylidene-1-amino-2-diphenlyphosphino
cyclohexane (3a)
Crystallized using degassed EtOH and obtained as a
white solid (177 mg, 89% yield). 1H NMR (CDCl3,

S. Dalili et al. / Journal of Organometallic Chemistry 689 (2004) 3604–3611
3609
400 MHz): d 8.13 ppm (s, 1H), 7.42–7.51 ppm (m, 5H),
7.13–7.36 ppm (m, 10H), 3.2–3.3 ppm (m, 1H), 2.68–
2.78 ppm (m, 1H), 1.7–1.9 ppm (m, 4H), 1.58–1.66
ppm (m, 1H), 1.1–1.46 ppm (m, 3H); 13C NMR (CDCl3,
100 MHz): d 159.8 (s), 135.0 (d, J = 20.5 Hz), 133.4 (d,
J = 19 Hz), 130.4 (s), 128.9 (s), 128.3 (d, J = 3 Hz),
128.2 (s), 128.1 (d, J = 6.9 Hz), 127.9 (s), 74.4 (s), 74.2
(s), 40.5 (d, J = 12.9 Hz), 35.5 (s), 35.4 (s), 27.9 (s),
1H), 1.64–1.82 (m, 4H), 1.32–1.43 (m, 4H); 13C NMR
(CDCl3, 75 MHz): d 160.7 (s), 149.2 (s), 136.3 (s),
134.9 (d, J = 20.8 Hz), 133.4 (d, J = 18.8 Hz), 128.9
(s), 128.3 (d, J = 15 Hz), 128.2 (d, J = 14.2 Hz), 127.9
(s), 124.6 (s), 121.5 (s), 73.6 (s), 73.4 (s), 40.3 (d,
J = 13.0 Hz), 35.2 (s), 35.1 (s), 27.6 (s), 27.5 (s), 26.2
(d, J = 6.6 Hz), 24.7 (s); 31P NMR (CDCl3, 300 MHz):
25
D
d ꢀ4.957 ppm; ½aꢁ ¼ ꢀ40:6 (c 1.0, EtOH); m.p. 65–67
27.8 (s), 26.3 (d, J = 6.8 Hz), 24.9 (s); 31P NMR (CDCl3,
ꢁC; HR-MS (FAB) m/z: Calc. for C24H25N2P,
372.4498. Found: 372.4486.
25
D
300 MHz): d ꢀ4.372 ppm; ½aꢁ ¼ ꢀ31:7 (c 1.0, EtOH);
m.p. 94–96 ꢁC; HR-MS (FAB) m/z: Calc. for
C25H26NP, 371.1803. Found: 371.1808.
4.2.5. Trans N-anthracenyl-1-amino-2-diphenlyphosphino
cyclohexane (3e)
1
Obtained as a yellowish-white solid in 89% yield. H
4.2.2. Trans N-(20-methoxybenzylidene)-1-amino-2-diph-
enylphosphino cyclohexane (3b)
NMR (CDCl3, 400 MHz): d 9.44 (s, 1H), 8.65–8.68 (m,
2H), 8.47 (s, 1H), 7.98–8.01 (m, 2H), 7.43–7.56 (m,8H),
7.34–7.36(m, 3H), 7.13–7.22 (m, 3H), 3.44–3.54 (m, 1H),
2.77–2.85 (m, 1H), 1.82–2.05 (m, 1H), 1.25–1.46 (m,
8H); 13C NMR (CDCl3, 100 MHz): d 159.7 (s), 135.5
(d, J = 20.9 Hz), 132.7 (d, J = 16.5 Hz), 131.5 (s),
130.2 (s), 129.2 (s), 128.9 (s), 128.4 (s), 128.3 (s),
128.26 (s), 128.2 (s), 127.6 (s), 126.7 (s), 125.6 (d,
J = 4.2 Hz), 125.4 (s), 73.9 (s), 73.8 (s), 40.9 (d,
J = 14.8 Hz), 36.3 (s), 36.2 (s), 27.0 (s), 26.2 (d, J = 3.4
Obtained as clear oil (177 mg, 80% yield) after chro-
matography on basic alumina column with hexa-
1
nes:ethyl acetate (7:3). H NMR (CDCl3, 400 MHz): d
8.63 ppm (s, 1H), 7.55–7.43 ppm (m, 5H), 7.17–7.29
ppm (m, 7H), 6.81 ppm (d, J = 8 Hz, 1H), 6.73 (t,
J = 7.6 Hz, 1H), 3.83 ppm (s, 3H), 3.21–3.29 ppm (m,
1H), 2.69–2.76 ppm (m, 1H), 1.60–1.81 ppm (m, 6H),
1.31–1.40 ppm (m, 2H); 13C NMR (CDCl3, 100 MHz):
d 155.9 (s), 135.1 (d, J = 20.5 Hz), 133.4 (d, J = 18.2
Hz), 131.5 (s), 128.9 (s), 128.25 (s), 128.17 (s), 128.1
(s), 128.06 (s), 127.8 (d, J = 9.1 Hz), 120.6 (s), 110.7
(s), 74.5 (s), 74.4 (s), 55.6 (s), 40.5 (d, J = 13 Hz),
35.7 (s), 35.6 (s), 27.8 (s), 27.7 (s), 26.3 (d, J = 6.1 Hz),
Hz), 24.8 (s); 31P NMR (CDCl3, 100 MHz): d ꢀ5.149
25
ppm; ½aꢁ ¼ ꢀ41:5 (c 1.0, EtOH); HR-MS (FAB) m/z:
D
Calc. for C33H30NP, 471.5817. Found: 471.5825.
24.9 (s); 31P NMR (CDCl3, 300 MHz): d ꢀ4.617 ppm;
4.2.6. Trans N-(20-hydroxobenzylidene)-1-amino-2-diph-
enylphosphino cyclohexane (3f)
25
½aꢁ ¼ ꢀ34:8 (c 1.0, EtOH); HR-MS (FAB) m/z: Calc.
D
for C26H28NPO, 401.1908. Found: 401.1898.
Obtained as a yellow oil in 88% yield. 1H NMR
(CDCl3, 400 MHz): d 8.19 (s, 1H), 7.41–7.49 (m, 4H),
7.11–7.32 (m, 8H), 6.80–6.83 (m, 2H), 3.22–3.28 (m,
1H), 2.60–2.65 (m, 1H), 1.93–1.96 (m, 1H), 1.66–1.81
(m, 3H), 1.21–1.44 (m, 5H); 13C NMR (CDCl3, 100
MHz): d 163.5 (s), 134.8 (d, J = 21.2 Hz), 133.3 (d,
J = 19.8 Hz), 132.1 (s), 131.5 (s), 129.2 (s), 128.6 (s),
128.5 (d, J = 3 Hz), 128.4 (s), 128.3 (s), 118.4 (s), 117.0
(s), 71.1 (s), 70.9 (s), 40.5 (d, J = 13.6 Hz), 34.7 (s),
34.6 (s), 27.0 (s), 26.9 (s), 25.4 (d, J = 6 Hz), 24.2 (s);
4.2.3. Trans N-(20-fluorobenzylidene)-1-amino-2-diph-
enylphosphino cyclohexane (3c)
Obtained as yellow oil (yield 70%). 1H NMR (CDCl3,
400 MHz): d 8.48 ppm (s, 1H), 7.52–7.41 ppm (m, 4H),
7.21–7.13 ppm (m, 7H), 6.97–6.90 ppm (m, 3H), 3.25–
3.31 ppm (m, 1H), 2.70–2.76 ppm (m, 1H), 1.85–1.62
ppm (m, 6H), 1.15–1.43 ppm (m, 2H); 13C NMR
(CDCl3, 75 MHz): d 153.1 (d, J = 5.4 Hz), 134.9 (d,
J = 20.7 Hz), 133.4 (d, J = 19 Hz), 128.9 (s), 128.3 (s),
128.2 (s), 128.1 (s), 128.0 (s), 127.8 (s), 124.0 (d, J = 4
Hz), 115.5 (s), 115.2 (s), 74.7 (s), 74.5 (s), 40.2 (d,
J = 13 Hz), 35.5 (s), 35.3 (s), 27.8 (s), 27.7 (s), 26.2 (d,
J = 6.8 Hz), 24.8 (s); 31P NMR (CDCl3, 300 MHz): d
31P NMR (CDCl3, 100 MHz):
d
ꢀ6.895 ppm;
25
D
½aꢁ ¼ ꢀ95:2 (c 1.0, EtOH); HR-MS (FAB) m/z: Calc.
for C25H26NPO, 387.4614. Found: 387.4612.
4.2.7. Trans N-(20-hydroxo-30-methoxybenzylidene)-1-
amino-2- diphenylphosphino cyclohexane (3g)
ꢀ4.521 ppm; 19F NMR (CDCl3, 300 MHz): d ꢀ122.77
25
ppm (dd, J1 = 11.7 Hz, J2 = 5.7 Hz); ½aꢁ ¼ ꢀ28:5 (c
1
Obtained as a yellowish-white solid in 89% yield. H
D
1.0, EtOH); HR-MS (FAB) m/z: Calc. for C25H25NPF,
389.4524. Found: 389.6638.
NMR (CDCl3, 400 MHz): d 8.16 (s, 1H), 7.42–7.48 (m,
4H), 7.30–7.32 (m, 2H), 7.14–7.22 (m, 2H), 6.87 (dd,
J1 = 7.2 Hz, J2 = 2.4 Hz, 1H), 6.73–6.77 (m, 1H), 3.88
(s, 3H), 3.24–3.30 (m, 1H), 2.60–2.64 (m, 1H), 1.99–
2.04 (m, 1H), 1.81–1.83 (m, 3H), 1.39–1.46 (m, 8H);
13C NMR (CDCl3, 100 MHz): d 163.4 (s), 134.6 (d,
J = 20.5 Hz), 133.3 (d, J = 19.7 Hz), 129.2 (s), 128.6
(s), 128.56 (s), 128.52 (s), 128.49 (s), 128.46 (s), 123.2
(s), 117.7 (s), 114.2 (s), 95.7 (s), 69.7 (s), 69.6 (s), 56.4
4.2.4. Trans N-(20-pyridinyl)-1-amino-2-diphenylphosph-
ino cyclohexane (3d)
Obtained as a yellow solid after column chromatog-
raphy on alumina, hexanes: ethyl acetate (8:2) in 80%
yield. 1H NMR (CDCl3, 400 MHz): d 8.28 (s, 1H),
7.15–7.53 (m, 14H), 3.33–3.41 (m, 1H), 2.70–2.78 (m,

3610
S. Dalili et al. / Journal of Organometallic Chemistry 689 (2004) 3604–3611
(s), 40.5 (d, J = 13.7 Hz), 33.9 (s), 29.9 (s), 26.5 (s), 24.9
(s), 23.7 (s); 31P NMR (CDCl3, 100 MHz): d ꢀ8.30 ppm;
ture inside the glovebox. The reactions were followed
by TLC (9:1 hexanes/ethyl acetate) and GC until com-
pletion. The reaction mixture was quenched with H2O
(5 mL), and extracted with ether (3 · 5 mL). The com-
bined organic layers were dried with MgSO4, filtered,
and evacuated under vacuum.
25
½aꢁ ¼ ꢀ71:7 (c 1.0, EtOH); HR-MS (FAB) m/z: Calc.
D
for C26H28NPO2, 417.4877. Found: 417.4870.
4.3. Synthesis of PdCl2[j2-P-N-(R,R)-2-Ph2PC6H10N@
CHPh] (4)
Method B: [Pd(p-allyl)Cl]2 (2 mol%, 1.81 mg) from a
stock solution in dry THF (0.033 M) and the iminophos-
phine ligand (2 mol%) also from a stock solution in dry
THF (0.022 M) were mixed together in a 25 mL vial
equipped with a stir bar inside the glove box. After stir-
ring at room temperature for approximately 10 min, 1,3-
diphenyl-2-propenyl acetate (0.496 mmol, 125 mg) was
added to the Pd/ligand mixture from a stock solution
in dry THF (0.5 M). After stirring the mixture again
at room temperature for approximately 10 min, diethyl
malonate (1.488 mmol, 238 mg), N,O-bis trimethylsilyl
acetamide (1.488 mmol, 332.5 mg) and potassium ace-
tate (10 mg) were added to the vial and the reaction
was stirred at room temperature inside the glovebox.
The reactions were followed by TLC (9:1 hexanes/ethyl
acetate) and GC until completion. The reaction mixture
was quenched with H2O (5 mL), and extracted with
ether (3 · 5 mL). The combined organic layers were
dried with MgSO4, filtered, and evacuated under vac-
uum. The final product was purifed by flash column
chromatography (silica gel, hexanes: ethyl acetate 9:1).
The enantioselectivity was determined by chiracel
HPLC OJ column, 95:5 hexanes:isopropanol, flow rate
0.5 ml/min.
PdCl2(PhCN)2 (16.5 mg, 43 lmol) was dissolved in 1
mL of CH2Cl2, and a solution ligand 3a (18 mg, 48
lmol) in CH2Cl2 was added dropwise, providing a yel-
low solution after 1 min. After 2 h, the solvent was evac-
uated and the residual orange solid was washed with
ether three times. The complex was crystallized by slow
diffusion of ether into a nitromethane solution of the
complex. Crystals suitable for X-ray crystallography
were obtained in 65% yield. 1H NMR (CD2Cl2, 400
MHz): d 8.49 (s, 1H), 8.40 (d, J = 7.6 Hz, 1H), 8.10–
8.14 (m, 2H), 7.81–7.86 (m, 2H), 7.47–7.68 (m, 10H),
4.40–4.43 (m, 1H), 2.53–2.56 (m, 1H), 2.22–2.28 (m,
2H), 1.63–1.83 (m, 2H), 1.23–1.37 (m, 2H), 0.88–0.98
(m, 2H)); 13C NMR (CD2Cl2, 125 MHz): d 167.8 (s),
135.0 (d, J = 19 Hz), 133.9 (s), 133.6 (s), 133.5 (d,
J = 15.75 Hz), 132.7 (s), 131.6 (s), 130.1 (s), 129.9
(s), 129.6 (s), 129.1 (d, J = 20.4 Hz), 128.7 (s), 76.4 (s),
47.9 (s), 47.5 (s), 32.8 (s), 32.6 (s), 30.5 (s), 30.2 (s),
26.8 (d, J = 13.75 Hz), 24.1; 31P NMR (CD2Cl2, 100
MHz): d 46.6 ppm; m.p. 278–279 ꢁC
4.4. Crystallographic data measurements
Diethyl 1-(1,3-diphenylprop-2-enyl)malonate: 1H
NMR (CDCl3): d 1.02 (t, J = 7.1 Hz, 3H), 1.22 (t, J =
7.1 Hz, 3H), 3.98 (d, J = 10.9 Hz, 1H), 3.99 (q, J = 7.1
Hz, 2H), 4.19 (q, J = 7.1 Hz, 2H), 4.28 (dd, J = 8.2,
10.9 Hz, 1H), 6.38 (dd, J = 8.2, 15.7 Hz, 1H), 6.49 (d,
J = 15.7 Hz, 1H), 7.20–7.32 (m, 10H).
Data were collected on a Nonius Kappa-CCD dif-
fractometer using monochromated Mo Ka radiation.
Each data set was measured using a combination of /
scans and x scans with j offsets, to fill the Ewald sphere.
The data were proceesed using the Denzo-SMN package
[21]. Absorption corrections were carried out using SOR-
TAV [22]. The structure was solved and refined using
SHELXTL V6.1 [23] for full-matrix least-squares refine-
ment that was based on F2. Crystallographic data for
the compound is given in Tables 1 and 2.
5. Supplementary material
Crytallographic data for the structural analysis has
been deposited with the Cambridge Crystallographic
Data Centre, CCDC No. 232269 for compound (4). Cop-
ies of this information may be obtained free of charge
from The Director, CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK. (fax: +44-1223-336033; e-mail: depos-
it@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
4.5. General procedure for allylic alkylation reactions
Method A: Pd(p-allyl)Cl]2 (2 mol%) from a stock
solution in dry THF (0.033 M) and the iminophosphine
ligand (2 mol%) also from a stock solution in dry THF
(0.022 M) were mixed together in a 25 mL vial equipped
with a stir bar inside the glove box. After stirring at
room temperature for approximately 10 min, 1,3-diphe-
nyl-2-propenyl acetate (0.496 mmol, 125 mg) was added
to the Pd/ligand mixture from a stock solution in dry
THF (0.5M). After stirring the mixture again at room
temperature for approximately 10 min, sodium salt of
diethyl malonate (0.99 mmol, 2 equiv.) was added to
the vial and the reaction was stirred at room tempera-
Acknowledgements
We thank NSERC, Amgen CFI, ORDCF, ACS-
PRF, the University of Toronto, and Affinium Pharma-
ceuticals for financial support. A.Y. is a Cottrell Scholar
of Research Corporation.

S. Dalili et al. / Journal of Organometallic Chemistry 689 (2004) 3604–3611
3611
(c) A. Scrivanti, U. Matteoli, V. Beghetto, S. Antonaroli, B.
Crociani, Tetrahedron 58 (2002) 6881;
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