Enantioselective Pd-catalyzed allylic amination with self-assembling and non-assembling monodentate phosphine ligands

Article abstract of DOI:10.1016/j.tetasy.2007.08.026

New chiral phospholanes were prepared by coupling of bromo-substituted heterocycles with the enantiopure, building block (2R,5R)-2,5-dimethyl-1-chlorophospholane. Some of the new phosphine ligands have the potential for self-assembling via hydrogen bondings in a metal complex. By application of these and related ligands in the palladium catalyzed allylic amination reaction, high enantioselectivities (up to 99%) were achieved. The influence of the construction of the cyclic phosphine ligands on the enantioselectivity is analyzed.

Full text of DOI:10.1016/j.tetasy.2007.08.026

Tetrahedron: Asymmetry 18 (2007) 2055–2060
Enantioselective Pd-catalyzed allylic amination with self-assembling
and non-assembling monodentate phosphine ligands
Mandy-Nicole Birkholz,a Natalia V. Dubrovina,a Ivan A. Shuklov,a Jens Holz,a
Rocco Paciello,b Christoph Waloch,c Bernhard Breitc,* and Armin Bo¨rnera,d,
*
aLeibniz-Institut fu¨r Katalyse an der Universita¨t Rostock e.V., A.-Einstein-Str. 29a, 18059 Rostock, Germany
bBASF AG, Basic Chemical Research, GCB/O-M313, 67059 Ludwigshafen, Germany
cInstitut fu¨r Organische Chemie und Biochemie, Albert-Ludwigs-Universita¨t Freiburg, Albertstrasse 21, 79104 Freiburg, Germany
dInstitut fu¨r Chemie der Universita¨t Rostock, A.-Einstein-Str. 3a, 18059 Rostock, Germany
Received 4 July 2007; accepted 21 August 2007
Abstract—New chiral phospholanes were prepared by coupling of bromo-substituted heterocycles with the enantiopure, building block
(2R,5R)-2,5-dimethyl-1-chlorophospholane. Some of the new phosphine ligands have the potential for self-assembling via hydrogen bon-
dings in a metal complex. By application of these and related ligands in the palladium catalyzed allylic amination reaction, high enantio-
selectivities (up to 99%) were achieved. The influence of the construction of the cyclic phosphine ligands on the enantioselectivity is
analyzed.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
properties in a range of different catalytic reactions, for
example, Rh-catalyzed hydrogenations.2
Chiral heterocyclic phosphines, such as phosphetanes,
phospholanes, phosphinanes or phosphepines play a cen-
tral role as ligands in homogeneous metal catalyzed reac-
tions.1 In most cases, bidentate ligands bearing these
heterocycles have been used, but also monodentate ligands
may induce high enantioselectivities. In particular, bulky
monodentate phosphepines, developed by Gladiali et al.
and Beller et al., showed excellent stereodiscriminating
For sometime we have been interested in finding correla-
tions between steric and electronic features in the ligand
and the degree of enantioselectivity induced in the chiral
product.3 In a recent approach, we showed evidence that
self-assembling catalysts (Scheme 1) based on P-pyridone
phosphines 4b, 5b and 6b (Scheme 2) can be used for
efficient stereocontrol in the Rh-catalyzed asymmetric
O
H
N
(t-Bu)O
(t-Bu)O
N
N
P*
P*
P*
P*
Rh(I)
R = H
Rh(I)
R = t-Bu
2
Rh(I)
Rh(I)
H
N
RO
N
P*
O
P* = chiral phosphine unit
B
A
Scheme 1. Coordination behaviour of self-assembling ligands versus monodentate ligands.
*
Corresponding authors. Fax: +49 381 1281 5202 (A.B.); fax: +49 761 203 8715 (B.B.); e-mail addresses: bernhard.breit@organik.chemie.uni-freiburg.de;
armin.boerner@catalysis.de
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.08.026

2056
M.-N. Birkholz et al. / Tetrahedron: Asymmetry 18 (2007) 2055–2060
S
P
P
P
N
N
N
NH(Piv)
NH(Piv)
O(t-Bu)
1
3a
2
Ph
P
P
P
P
HN
3b
N
HN
4b
N
O
O(t-Bu)
O
O(t-Bu)
Ph
4a
5a
Ph
P
P
P
HN
5b
N
HN
O
Ph
O(t-Bu)
O
6b
6a
Scheme 2. Ligands tested in the asymmetric allylic amination.
hydrogenation.4 The general concept of self-assembling
catalysts was developed by one of us (B.B.) and successfully
applied to numerous catalytic reactions.5
chinoyl-2-on)-phospholane 3b. Syntheses of ligands 4a
and 4b, 5a and 5b and 6a and 6b were reported recently.4
2.2. Enantioselective allylic amination
Our hydrogenation studies revealed that hydrogen bonding
between parts of the ligand in the relevant Rh(I)-catalysts
(A, Scheme 1) can significantly enhance the enantioselecti-
vity of the hydrogenation of a-(Z)-N-acetamido acrylates
and dimethyl itaconate. Whereas catalysts based on
common monodentate ligands (B, Scheme 1) gave inferior
results.4
With these ligands in hand, we evaluated their enantio-
selective discrimination ability in the allylic amination. As
a benchmark test, we studied the reaction of rac-(E)-1,3-di-
phenyl-3-acetoxyprop-1-ene with benzylamine.10
In most cases, the required precatalysts were prepared
in situ from 2 equiv of the ligands and 1 equiv of the metal
precursor (Pd2(dba)3ÆCHCl3 and [PdCl(allyl)]2), respec-
tively. In the catalytic reaction, in addition to the effect
of different ligands, the influence of the solvent was studied.
In particular, in non-polar solvents, ligands 4b, 5b and 6b
were superior in comparison to their O-tert-Bu-protected
pyridinol analogues 4a, 5a and 6a, which are not capable
of self-assembling. Moreover, these studies showed that
the size of the phosphine heterocycle is crucial for the
achievement of high ee-values. Thus, ligands with the bulky
phosphepine ligands induced the highest enantioselecti-
vities in the product (99% ee).
In general, in all trials, full conversion was observed under
the conditions displayed in Table 1. Due to the low solu-
bility of catalysts derived from phosphepine ligands 6,
higher substrate:catalyst ratios were necessary. The enantio-
selectivites achieved with this set of 10 related ligands var-
ied over a range of 3–99% ee.
In order to enlarge the family of self-associating phosphine
ligands, and to study this particular effect in other asym-
metric transformations, we herein report on the synthesis
of phospholanes 1, 2 and 3a and 3b. The new ligands were
tested together with phosphines of types 4–6 in the asym-
metric allylic amination (Tsuji–Trost reaction).6,7
To our surprise, the highest enantioselectivity (99% ee, run
3) was obtained with the ‘small’ 2,5-dimethyl substituted
phospholane ligand 3a in toluene as a solvent. It should
be noted that due to the O-tert-Bu protection, this mono-
dentate ligand cannot aggregate with a second ligand at
the palladium centre by hydrogen bonding. Incorporation
of isochinolone backbone 3b decreased the enantioselectiv-
ity (run 4). Lower ee-values, but similar tendencies have
been noted for the 2-(O-tert-Bu)-pyridinol/pyridone-based
pair of phospholanes 4a and 4b (runs 5 and 6). Replace-
ment of the methyl groups at the 2,5-position of the phos-
pholane by phenyls, 5a and 5b, further diminished the ee.
In contrast to the ligands of types 3 and 4, the relevant
P-pyridone ligand 5b was superior in comparison to the
P-(O-tert-Bu-pyridinol) ligand 5a (runs 7 and 8). Unexpect-
edly, inferior enantioselectivities were also observed with
the bulky phosphepines 6a and 6b. Poor ee-values are char-
acteristic for P-(O-tert-Bu-pyridinol) ligand 6a (runs 9 and
10). Enhancement of the ee was obtained by employing the
2. Results and discussion
2.1. Synthesis
The new phospholanes 1, 2 and 3a and 3b were synthesized
in one step by coupling of the enantiopure P-chloro-
dimethylphospholane 8,8 easily available from 2,5-
dimethyl-1-trimethylsilyl-phospholane9 7 by treatment with
hexachloroethane in CH2Cl2 at reflux, with the correspond-
ing bromides 9, 10 and 11 in yields of 30–72% (Scheme 3).
Cleavage of the tert-butyl ether in 3a with concentrated
formic acid furnished (2R,5R)-2,5-dimethyl-1-(1H-iso-

M.-N. Birkholz et al. / Tetrahedron: Asymmetry 18 (2007) 2055–2060
2057
NH(Piv)
N
NH(Piv)
P
N
Br
1
9
S
N
Br
NH(Piv)
O(t-Bu)
S
10
P
P
Cl
P
TMS
N
NH(Piv)
N
Br
7
8
2
11
O
O(t-Bu)
HN
N
HCOOH
P
P
3b
3a
Scheme 3. Convergent synthesis of phospholanes 1, 2 and 3a and 3b.
Table 1. Pd-catalyzed enantioselective allylic amination of rac-(E)-1,3-diphenyl-3-acetoxyprop-1-ene using phosphines 1–6 as ligands
1-2 mol % [Pd], 2-4mol % L
Ph
Ph
NH
OAc
Ph
3 equiv. benzylamine
*
Ph
Ph
Run
Ligand
Pd precursor
Solvent
L/[Pd]
% eea
1
2
3
4
5
6
7
8
(R,R)-1b
(R,R)-2b
(R,R)-3ab
(R,R)-3bb
(R,R)-4ab
(R,R)-4bb
(S,S)-(ꢀ)-5ab
(S,S)-(ꢀ)-5bb
(S)-6ac
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
[PdCl(allyl)]2
Pd2(dba)3ÆCHCl3
[PdCl(allyl)]2
Pd2(dba)3ÆCHCl3
[PdCl(allyl)]2
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
[PdCl(allyl)]2
[PdCl(allyl)]2
Pd2(dba)3ÆCHCl3
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
1,2-Dichloroethane
CH2Cl2
CH2Cl2
Toluene
Toluene
2
2
2
2
2
2
2
2
2
2
2
2
2
4
2
2
2
2
2
76 (R)
20 (S)
99 (R)
91 (R)
92 (R)
83 (R)
8 (S)
45 (R)
3 (R)
9
10
11
12
13
14
15
16
17
18
19
(S)-6ac
14 (S)
82 (S)
82 (S)
40 (S)
42 (S)
40 (S)
41 (S)
57 (S)
87 (S)
84 (S)
(S)-6bc
(S)-6bc
(S)-6bc
(S)-6bc
(S)-6bc
Toluene
THF
THF
1,2-Dichloroethane
1,2-Dichloroethane
(S)-6bc
(S)-6bc
(S)-6bc
(S)-6bc
a Determined by HPLC analysis, Chiracel OJ-H.
b Reaction conditions: 0.5 mmol substrate, 0.005 mmol Pd2ðdbaÞ3ꢁCHCl3, 0.01 mmol ligand, 1.5 mL solvent; 25 ꢁC.
c Reaction conditions: 0.32 mmol substrate, 0.0064 mmol Pd precursor, 0.0128 mmol ligand, 3.5 mL solvent; 25 ꢁC.
P-pyridone-based ligand 6b (runs 11–19). As shown the reac-
tion is rather sensitive to the solvent used; best ee-values
were observed in 1,2-dichloroethane (up to 87% ee, runs
18 and 19), but did not reach the value obtained with
ligand 3a. Apparently, the amination reaction gets benefit
from a small cyclic phospholane unit, but a large N-hetero-
cycle. Thus, the isochinoline ligand 3b gave higher enantio-
selectivities than the pyridine-based phosphine 4b (runs 3
and 5). The same trend was observed for the related pair
3a and 4a (runs 4 and 6). An exchange of the pyridinol/
pyridinone substituent at the phosphorus atom with other
heterocycles (ligands 1 or 2) did not improve the results
(runs 1 and 2).
3. Conclusion
Some new chiral phospholanes have been prepared by a
convergent approach using enantiopure P-chloro-dimeth-
ylphospholane as a building block. The new ligands were
tested together with related and known heterocyclic phos-
phines in the Pd-catalyzed asymmetric amination. Excel-

2058
M.-N. Birkholz et al. / Tetrahedron: Asymmetry 18 (2007) 2055–2060
lent enantioselectivities (up to 99%) were obtained in this
reaction. Surprisingly, ligands 3a and 4a based on small
heterocyclic phosphines provided the highest ee-values.
Interestingly, these ligands were not capable of self-assem-
bling. Conversely large phosphine ligands 5b and 6b take
profit from the property of self-assembling. This is in
strong contrast to the results recently observed in the Rh-
catalyzed asymmetric hydrogenation.4
1H), 2.25–2.08 (m, 2H), 1.82–1.74 (m, 1H), 1.58–1.47 (m,
1H), 1.36 (dd, CH3–CP, J = 18.3 Hz, J = 7.3 Hz, 3H),
1.25–1.15 (m, 1H), 0.96 (s, CH3, 9H), 0.89 (dd, CH3–CP,
J = 10.1 Hz, J = 7.0 Hz, 3H). 13C NMR (101 MHz,
C6D6) d 176.9 (s, C@O), 161.9 (d, J = 24.5 Hz, arom.
C–NH), 152.7 (d, J = 4.1 Hz, arom. C–P), 137.1 (d,
J = 8.5 Hz, arom. CH), 127.4 (d, J = 34.0 Hz, arom.
CH), 113.3 (s, arom. CH), 40.1 (s, CH2), 38.0 (d,
J = 2.6 Hz, CH2), 37.1 (d, J = 13.5 Hz, CH–P), 33.6 (d,
J = 8.9 Hz, CH–P), 30.7 (s, quat. C), 27.8 (s, C(CH3)3),
20.8 (d, J = 33.8 Hz, CH3), 15.7 (s, CH3). 31P NMR
(122 MHz, C6D6) d 10.6. MS (CI, NH3) m/z (%) 309
[M+O]+ (100), 293 [M]+ (14), 225 (15), 179 (72), 150
(29), 133 (52). HRMS (CI) calcd for C16H25N2OP:
292.1704. Found: 292.1708. Elemental Anal. Calcd for
C16H25N2OP (M = 292.36): C, 65.73; H, 8.62; P, 9.58.
Found: C, 65.22; H, 8.72; P, 9.43.
4. Experimental
General: All reagents unless otherwise mentioned were pur-
chased from commercial sources and used without addi-
tional purification. The solvents were dried and freshly
distilled under argon before use. All reactions involving
phosphines were performed under an argon atmosphere
by using standard Schlenk techniques. Elementary analyses
were performed on an elementar vario (Fa. Elementar
Analysensysteme GmbH). Optical rotations were measured
on a Perkin–Elmer 241 polarimeter. NMR spectra were
recorded on the following spectrometers: Varian Mercury
spectrometer (300 MHz, 121 MHz and 75 MHz for 1H,
31P and 13C, respectively), Bruker AMX 400 (400 MHz,
4.3. (2R,5R)-2,5-Dimethyl-1-(30-pivaloylamino-thiazol-40-
yl)-phospholane 2
The crude product was purified by bulb to bulb distillation
(160 ꢁC, 10ꢀ3 mbar) and subsequent flash chromatography
(CH2Cl2/petrol ether 9/1) to give a white solid. Yield:
19
1
162 MHz and 100 MHz for H, 31P and 13C, respectively)
0.70 g (30%); Mp 117–120 ꢁC, ½aꢂD ¼ ꢀ61 (c 1, CHCl3).
and Bruker DRX 500 (500 MHz, 202 MHz and 125 MHz
for 1H, 31P and 13C, respectively) and are referenced
according to residual proton solvent signals. Chemical
1H NMR (500 MHz, C6D6) d 8.22 (br s, NH, 1H), 8.09
(s, arom. H, 1H), 3.10–3.01 (m, CH, 1H), 2.15–2.08 (m,
CH2, 1H), 2.00–1.88 (m, CH, 1H), 1.76–1.70 (m, CH2,
1H), 1.66–1.57 (m, CH2, 1H), 1.24 (dd, J = 19.2 Hz,
J = 7.3 Hz, CH3, 3H), 1.08–1.00 (m, CH2, 1H), 0.95 (dd,
J = 11.3 Hz, J = 6.9 Hz, CH3, 3H), 0.92 (s, C(CH3)3,
9H). 13C NMR (126 MHz, C6D6) d 175.2 (s, C@O), 168.5
(d, J = 46.2 Hz, arom. C–P), 151.2 (d, J = 6.5 Hz, arom.
C), 105.9 (s, arom. CH), 39.6 (s, quat. C), 38.0 (s, CH2),
37.9 (d, J = 3.2 Hz, CH2), 37.8 (d, J = 4.3 Hz, CH–P),
37.7 (d, J = 7.5 Hz, CH), 27.8 (s, C(CH3)3), 21.3 (d,
J = 33.3 Hz, CH3), 15.5 (s, CH3). 31P NMR (122 MHz,
C6D6) d 6.2. MS (CI, NH3) m/z (%) 314 [M+O]+ (13),
298 [M]+ (71), 198 (23), 57 (100) HRMS (CI) calcd for
C14H23N2OPS: 298.1261. Found: 298.1269. Elemental
Anal. Calcd for C14H23N2OPS (M = 298.39): C, 56.35;
H, 7.77; N, 9.39; S, 10.75. Found: C, 56.61; H, 7.87; N,
9.23; S, 10.87.
1
shifts of H, 13C and 31P NMR spectra are reported in
ppm. Chemical shifts of 31P NMR spectra are referred to
H3PO4 as an external standard. Elemental analyses were
performed with a LECO CHNS-932. High-resolution mass
spectra were obtained on a Finnigan MAT 8200 instrument
and ESI mass spectrometry was performed on a Finnigan
LCQ Advantage.
4.1. General procedure for the preparation of phospholanes
1, 2 and 3a
To a solution of bromide 9 or 10 or 11 (7.78 mmol) in dry
THF (40 ml), a solution of nBuLi [1.6 M in hexane; for 9
and 10 9.72 ml (15.56 mmol); for 11 4.86 ml (7.78 mmol),
respectively] was added dropwise under stirring at
ꢀ110 ꢁC. The reaction mixture was stirred for 1 h at this
temperature. It was then warmed up to ambient tempera-
ture and stirred for a further 1.5 h. A solution of
4.4. (2R,5R)-2,5-Dimethyl-1-(10-tert-butoxy-isoquinolin-30-
yl)-phospholane 3a
(2R,5R)-2,5-dimethyl-1-chlorophospholane8
8
(1.17 g,
7.78 mmol) in dry THF (10 ml) was then slowly added.
The solution was warmed up to ꢀ40 ꢁC and quenched with
water (0.14 ml, 7.78 mmol). The mixture was concentrated
in vacuum. After the addition of pentane the suspension
was filtered. The solution was concentrated in vacuum to
give the crude products.
The crude product was purified by bulb to bulb distillation
(160 ꢁC, 10ꢀ3 mbar) and subsequent flash chromatography
(CH2Cl2/petrol ether 9/1, Rf 0.19) to give a white solid.
19
Yield: 1.77 g (72%); ½aꢂD ¼ ꢀ97 (c 0.65, CHCl3). 1H
NMR (500 MHz, C6D6) d 8.31–8.27 (m, arom. H, 1H),
7.68 (d, J = 8.5 Hz, arom. H, 1H), 7.34–7.31 (m, arom.
H, 1H), 7.24–7.18 (m, arom. H, 2H), 3.44–3.35 (m, CH–
P, 1H), 2.40–2.20 (m, CH–P and CH2, 2H), 1.96–1.92 (m,
CH2, 2H), 1.67 (br s, C(CH3)3, 9H), 1.46 (dd,
J = 18.5 Hz, J = 6.9 Hz, CH3–CP, 3H) 1.38–1.30 (m,
1H), 0.98 (dd, J = 11.3 Hz, J = 6.9 Hz, CH3–CP, 3H).
13C NMR (126 MHz, C6D6) d 159.6 (d, J = 3.2 Hz, arom.
C–O), 152.3 (d, J = 24.8 Hz, arom. C–P), 138.4 (d,
J = 12.9 Hz, quart. C), 131.0 (s, arom. CH), 127.6 (s, arom.
CH), 126.9 (s, arom. CH), 125.7 (s, arom. CH), 125.0 (d,
4.2. (2R,5R)-2,5-Dimethyl-1-(20-pivaloylamino-pyrid-60-yl)-
phospholane 1
The crude product was purified by bulb to bulb distillation
(180 ꢁC, 10ꢀ3 mbar) to give a white solid. Yield: 1.22 g
19
(54%); Mp 55–58 ꢁC, ½aꢂD ¼ ꢀ74 (c 1.0, CHCl3). 1H
NMR (400 MHz, C6D6) d 8.52–8.49 (m, CH, 1H), 7.92
(br s, NH, 1H), 7.12–7.07 (m, CH, 2H), 3.39–3.27 (m,

M.-N. Birkholz et al. / Tetrahedron: Asymmetry 18 (2007) 2055–2060
2059
J = 46.2 Hz, arom. CH), 121.7 (s, quat. C), 80.5 (s, quat.
4.7. Procedure for the Pd-catalyzed asymmetric allylic
amination (with ligands 6a and 6b)
C), 38.7 (s, CH2), 38.5 (d, J = 4.7 Hz, CH2), 37.3 (d,
J = 11.83 Hz, CH–P), 35.2 (d, J = 8.7 Hz, CH–P), 29.3
(s, C(CH3)3), 21.2 (d, J = 33.3 Hz, CH3), 16.1 (s, CH3).
31P NMR (122 MHz, C6D6) d 13.9. MS (EI) m/z (%) 315
[M]+ (25), 259 (100), 217 (54), 186 (53). HRMS (EI) calcd
for C19H26NOP: 315.1747. Found: 315.1745. Elemental
Anal. Calcd for C19H26NOP (M = 315.39): C, 72.36; H,
8.31; N, 4.44. Found: C, 72.06; H, 8.51; N, 4.36.
Due to the low solubilities of 6a and 6b in nonpolar sol-
vents, the procedure for Pd-catalyzed asymmetric allylic
amination was modified.
A mixture of the Pd precursor (0.0064 mmol) and chiral
ligand (0.0128 mmol) in a solvent (3.5 ml) was stirred at
room temperature for 30 min. rac-(E)-1,3-Diphenyl-3-acet-
oxyprop-1-ene (0.32 mmol) and benzylamine (0.103 g,
0.96 mmol) were then added and the resulting mixture
was stirred for 12 h. The reaction mixture was then
quenched with saturated aqueous NH4Cl solution and
diethyl ether (10 ml) was added. The organic layer was
extracted twice with Et2O. The combined organic layers
were dried over Na2SO4 and concentrated in vacuum to
give the crude product.
4.5. (2R,5R)-2,5-Dimethyl-1-(10-oxo-10,20-dihydro-isoquino-
lin-30-yl)-phospholane 3b
A mixture of (2R,5R)-3,5-dimethyl-1-(10-tert-butoxy-iso-
quinolin-3-yl)-phospholane 3a (0.35 g, 1.11 mmol) in concd
formic acid (5 ml) was stirred at ambient temperature for
10 min. The solvent was then evaporated. The residue
was dried in vacuum at 40 ꢁC for 1 h. Subsequently, the
substance was crystallized from 10 ml of dry diethyl ether
and filtered. The crude product was purified by flash chro-
matography (CH2Cl2/ethyl acetate 1/1, Rf 0.38) to give a
white solid. Yield: 0.273 g (95%); Mp 161–162 ꢁC,
Acknowledgements
The authors are grateful to BASF AG (Ludwigshafen) for
the financial support of this work. We thank Dr. C. Fischer
and Mrs. S. Buchholz for the analysis of the chiral amina-
tion products.
19
1
½aꢂD ¼ ꢀ129 (c 1.0, CHCl3) H NMR (400 MHz, C6D6) d
11.80 (br s, NH, 1H), 8.70 (d, J = 7.3 Hz, arom. H, 1H),
7.28–7.18 (m, arom. H, 3H), 6.76 (d, J = 8.3 Hz, arom.
H, 1H), 3.08–2.98 (m, CH–P, 1H), 2.42–2.33 (m, CH2,
1H), 2.26–2.09 (m, CH–P, 1H), 1.88–1.79 (m, CH2, 2H),
1.32 (dd, J = 19.2 Hz, J = 7.2 Hz, CH3, 3H), 1.26–1.13
(m, CH2, 1H), 0.97 (dd, J = 10.4 Hz, J = 7.1 Hz, CH3,
3H). 13C NMR (101 MHz, C6D6) d 165.7 (s, arom.
C@O), 140.7 (d, J = 44.0 Hz, arom. C–P), 138.4 (d,
J = 11.5 Hz, quat. C), 133.2 (s, arom. CH), 128.3. (s, arom.
CH), 127.7 (s, arom. CH), 127.3 (s, quat. C), 126.9 (s,
arom. CH), 116.5 (d, J = 30.6 Hz, arom. CH), 38.4 (d,
J = 3.9 Hz, CH2), 38.2 (s, CH2), 36.6 (d, J = 11.5 Hz,
CH–P), 33.7 (d, J = 8.7 Hz, CH–P), 21.3 (d, J = 34.5 Hz,
CH3), 16.0 (s, CH3). 31P NMR (122 MHz, C6D6) d 10.8.
MS (CI, NH3) m/z (%) 259 [M]+ (100), 202 (96), 186
(60), 176 (51). HRMS (CI) calcd for C15H18NOP:
259.1121. Found: 259.1112. Elemental Anal. Calcd for
C15H18NOP (M = 259.28): C, 69.48; H, 7.00; N, 5.40.
Found: C, 69.27; H, 7.17; N, 5.31.
References
1. For recent reviews, see: Clark, T. P.; Landis, C. R. Tetrahe-
dron: Asymmetry 2004, 15, 2123–2137; Holz, J.; Gensow, M.-
N.; Zayas, O.; Bo¨rner, A. Curr. Org. Chem. 2007, 11, 61–106.
2. Gladiali, S.; Dore, A.; Fabbri, D.; De Lucci, O.; Manassero,
M. Tetrahedron: Asymmetry 1994, 5, 511–514; Junge, K.;
Oehme, G.; Monsees, A.; Riermeier, T.; Dingerdissen, U.;
Beller, M. Tetrahedron Lett. 2002, 43, 4977–4980; Junge, K.;
Hagemann, B.; Enthaler, S.; Oehme, G.; Michalik, M.;
Monsees, A.; Riermeier, T.; Dingerdissen, U.; Beller, M.
Angew. Chem. 2004, 116, 5176–5179; Angew. Chem., Int. Ed.
2004, 43, 5066–5069; Junge, K.; Hagemann, B.; Enthaler, S.;
Spannenberg, A.; Michalik, M.; Oehme, G.; Monsees, A.;
Riermeier, T.; Beller, M. Tetrahedron: Asymmetry 2004, 15,
2621–2631; Hagemann, B.; Junge, K.; Enthaler, S.; Michalik,
M.; Riermeier, T.; Monsees, A.; Beller, M. Adv. Synth. Catal.
2005, 347, 1978–1986; Enthaler, S.; Hagemann, B.; Junge, K.;
Erre, G.; Beller, M. Eur. J. Org. Chem. 2006, 2912–2917;
Enthaler, S.; Erre, G.; Junge, K.; Holz, J.; Bo¨rner, A.;
Alberico, E.; Nieddu, I.; Gladiali, S.; Beller, M. Org. Process
Res. Dev. 2007, 11, 568–577.
4.6. Pd-catalyzed asymmetric allylic amination (with ligands
1–5)
3. See, for example, Dubrovina, N. V.; Tararov, V. I.; Kadyr-
ova, Z.; Monsees, A.; Bo¨rner, A. Synthesis 2004, 2047–2051;
Dubrovina, N. V.; Tararov, V. I.; Monsees, A.; Spannenberg,
A.; Kostas, I. D.; Bo¨rner, A. Tetrahedron: Asymmetry 2005,
16, 3640–3649; Holz, J.; Zayas, O.; Jiao, H.; Baumann, W.;
Spannenberg, A.; Monsees, A.; Riermeier, T. H.; Almena, J.;
Kadyrov, R.; Bo¨rner, A. Chem. Eur. J. 2006, 12, 5001–5013.
4. Birkholz, M.-N.; Dubrovina, N. V.; Jiao, H.; Michalik, D.;
Holz, J.; Paciello, R.; Breit, B.; Bo¨rner, A. Chem. Eur. J.
2007, 13, 5896–5907.
5. Breit, B.; Seiche, W. J. Am. Chem. Soc. 2003, 125, 6608–6609;
Breit, B.; Seiche, W. Angew. Chem. 2005, 117, 1666–
1669; Angew. Chem., Int. Ed. 2005, 44, 1640–1643; Seiche,
W.; Schuschkowski, A.; Breit, B. Adv. Synth. Catal. 2005,
347, 1488–1494; Breit, B. Angew. Chem. 2005, 117, 6928–
A mixture of Pd precursor (0.005 mmol), chiral ligand
(0.01 mmol) and rac-(E)-1,3-diphenyl-3-acetoxyprop-1-ene
(0.5 mmol) in a solvent (1.5 ml) was stirred at room tem-
perature for 20 min. Benzylamine (0.160 g, 1.50 mmol)
was then added and the resulting mixture was stirred for
12 h. The reaction mixture was quenched with saturated
aqueous NH4Cl solution (15 ml) and diethyl ether (10 ml)
was added. The organic layer was extracted with Et2O
(3 · 10 ml). The combined organic layers were dried over
Na2SO4 and concentrated in vacuum to give the crude
product. Ee values were determined by chiral HPLC on a
Chiralcel OJ column (hexane/i-propanol 80/20, 0.5 ml/
min).

2060
M.-N. Birkholz et al. / Tetrahedron: Asymmetry 18 (2007) 2055–2060
6976; Angew. Chem., Int. Ed. 2005, 44, 6816–6825; Breit, B.;
Rev. 2003, 103, 2921–2943; Miyabe, H.; Takemoto, Y. Synlett
2005, 1641–1655.
Seiche, W. Pure Appl. Chem. 2006, 78, 249–256; Chevallier,
F.; Breit, B. Angew. Chem. 2006, 118, 1629–1632; Angew.
Chem., Int. Ed. 2006, 45, 1599–1602; Weis, M.; Walloch, C.;
Seiche, W.; Breit, B. J. Am. Chem. Soc. 2006, 128, 4188–
´
7. This work is part of the Ph.D. thesis of Birkholz (nee
Gensow), M.-N., Rostock, 2006.
8. Holz, J.; Monsees, A.; Kadyrov, R.; Bo¨rner, A. Synlett 2007,
599–602.
ˇ
4189; Smejkal, T.; Breit, B. Organometallics 2007, 26, 2461–
2464.
9. Holz, J.; Monsees, A.; Jiao, H.; You, J.; Komarov, I. V.;
Fischer, C.; Drauz, K.; Bo¨rner, A. J. Org. Chem. 2003, 68,
1701–1707.
10. Trost, B. M.; Murphy, D. J. Organometallics 1985, 4, 1143–
1145.
6. Pfalz, A.; Lautens, M. In Comprehensive Asymmetric Catal-
ysis I–III; Springer: New York, 1999; Vol. 2, pp 833–884; For
reviews, see: Johannsen, M.; Jørgensen, K. A. Chem. Rev.
1998, 98, 1689–1708; Trost, B. M.; Crawley, M. L. Chem.