Pd-catalyzed asymmetric allylic amination using easily accessible metallocenyl P,N-ligands

Article abstract of DOI:10.1039/c5ob00032g

Compared to their C₁-symmetric counterparts, planar chiral C₂-symmetric metallocenyl P,N-ligands are efficient chiral ligands for Pd-catalyzed asymmetric allylic aminations, providing a number of amination products with high enantios

Full text of DOI:10.1039/c5ob00032g

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ARTICLE TYPE
Pd-Catalyzed Asymmetric Allylic Amination Using Easily Accessible
Metallocenyl P,N-Ligands
a
a
a
a
b,
a,b,
Hongwei Wu, Fang Xie, Yanlan Wang, Xiaohu Zhao, Delong Liu * and Wanbin Zhang *
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI:
Compared to their C ꢀsymmetric counterparts, planar chiral C ꢀsymmetric metallocenyl P,Nꢀligands are
1
2
efficient chiral ligands for Pdꢀcatalyzed asymmetric allylic aminations, providing a number of amination
products with high enantioselectivities. A nonꢀC ꢀsymmetric ferrocenyl P,Nꢀligand (a byꢀproduct
2
obtained during the synthesis of the above C ꢀsymmetric species) was also found to be an efficient ligand
2
for asymmetric allylic aminations. A mixed ligand system consisting of both C ꢀ and nonꢀC ꢀsymmetric
2
2
ferrocene complexes was examined and showed high catalytic activity with the amination product being
obtained with excellent enantioselectivity.
1
. Introduction
different reaction activities and enantioselectivities were
observed for the asymmetric allylic aminations when these
planar chiral metallocenyl P,Nꢀligands were used. We herein
disclose a detailed account of the Pdꢀcatalyzed asymmetric
allylic amination using a series of planar chiral metallocenyl
phosphinooxazolines as chiral ligands.
Transition metalꢀcatalyzed asymmetric allylic substitution has
become a powerful and versatile synthetic method in organic
synthesis. In particular, Pdꢀcatalyzed asymmetric allylic
amination reactions have attracted extensive attention because
they can be used to easily obtain chiral allylic amines,
structures which are ubiquitous in biologically active
1
1,2
compounds.
The search for efficient chiral ligands for
asymmetric allylic aminations has therefore received much
3
attention.
For more than ten years, our group has focused on the
synthesis and application of C ꢀsymmetric planar chiral
metallocenyl ligands. Of these ligands, the chiral (Sp,Sp,S,S)ꢀ
C ꢀsymmetric phosphinooxazolines 1 and 2 (Figure 1) have
2
2
Figure 1 Planar chiral metallocenyl ligands
4
2. Results and Discussion
been tested to be efficient chiral ligands and have shown
excellent catalytic behavior in many asymmetric catalytic
reactions. Both 1 and 2 possess dual reaction sites and greater
Originally, the asymmetric allylic amination of 1,3ꢀdiphenylꢀ2ꢀ
propenyl acetate with benzylamine was carried out using the
C ꢀsymmetric ferrocenyl phosphinooxazoline 1a as a chiral
2
5
steric effects and so provide higher catalytic efficiency and
enantioselectivity in several asymmetric reactions. We
therefore envisaged that they would be efficient chiral ligands
for Pdꢀcatalyzed asymmetric allylic aminations. For
ligand in PhCH3 at room temperature. To our delight, the
reaction went to completion within 1 h, providing the
amination product in 90% yield and with 86% ee (Table 1,
entry 1). In our previous work, CH Cl proved to be the best
2
2
comparison,
the
corresponding
(Sp,S)ꢀC ꢀsymmetric
solvent with a positive solvent effect being observed when
1
5
h
metallocenyl phosphinooxazolines 3 and 4 (Figure 1) have also
been examined, which have previously shown to be excellent
metallocenyl ligands were used. Therefore, the reaction was
also carried out in CH Cl solvent and a slightly lower catalytic
activity and enantioselectivity were observed (83% ee, entry 2).
2
2
chiral
ligands
in
both
Ruꢀcatalyzed
asymmetric
6
C ꢀsymmetric chiral ruthenocenyl P,Nꢀligand 2a was then
hydrogenations
and Pdꢀcatalyzed asymmetric allylic
2
7
utilized because of its successful application in asymmetric
alkylations. As a result, different reaction activities and
5
eꢀm
catalysis.
to 89% ee) were obtained when the reactions were carried out
in both PhCH and CH Cl solvents (entries 3 and 4). Steric
High reaction activity and enatioselectivities (up
a
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong
University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
3
2
2
b
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan
hindrance effects of the oxazoline ring were examined. Both 1b
and 2b bearing bulky substituents on the oxazolinyl ring gave
higher enantioselectivities than their corresponding ligands 1a
and 2a, and 96% ee was obtained when the reaction was carried
Road, Shanghai 200240, P. R. China. Fax: +86ꢀ21ꢀ5474ꢀ3265; Tel:
+86ꢀ21ꢀ5474ꢀ3265; Eꢀmail:wanbin@sjtu.edu.cn; dlliu@sjtu.edu.cn.
†
Electronic Supplementary Information (ESI) available: [details of
any supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
out using 1b as a chiral ligand in PhCH (entries 5 and 6).
3
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a
5f,g
Table 1 Chiral ligand screening
ligand.
However, the yield and enentioselectivity were
similar to that obtained in previous reactions. Increasing the
3
amount of [Pd(η ꢀC H )Cl] to 1.1 mol% to ensure complete
3
5
2
formation of the P,Nꢀchelated Pdꢀcomplex, also led to similar
results. Therefore, the excellent asymmetric behavior of ligand
1
is due to its greater steric effect other than the formation of a
b
c,d
Entry
Ligand
Solvent
PhCH
CH Cl
PhCH
CH Cl
PhCH
CH Cl
PhCH
CH Cl
PhCH
Time (h) Yield (%)
Ee (%)
small amount of P,Pꢀchelated Pdꢀcomplex from 1.
1
2
3
4
5
6
7
8
9
1a
1a
2a
2a
1b
2b
3
3
4
4
3
2
90
87
92
96
93
92
28
31
40
35
86
83
81
89
96
94
32
41
19
38
a
Table 2 Solvent and temperature screening
2
2
2
1
1
1
3
2
2
3
2
2
1
3
12
24
12
24
o
b
c,d
Entry
Solvent
PhCH
CH Cl
THF
Et
Time (h) T ( C)
Yield (%) Ee (%)
2
2
3
1
2
3
4
5
6
7
8
9
3
1
1
2
1
2
5
6
6
6
25
25
25
25
25
0
93
94
92
93
91
78
65
47
35
96
91
96
95
95
96
95
95
95
1
0
CH
2
Cl
2
2
2
a
3
Molecular ratio: [Pd(η ꢀC
3
H
5
)Cl]
/ligand (3 or 4)/5a/6a = 1/ 2.2/100/300.
Reactions were carried out under N atmosphere at 25 °C. The catalysts
)Cl] with ligands in a suitable
2
/ligand (1 or 2)/5a/6a = 1/1.1/100
O
3
2
/
3 5 2
300 or [Pd(η ꢀC H )Cl]
DMF
2
PhCH
PhCH
PhCH
PhCH
3
3
3
3
3
were prepared by treating [Pd(η ꢀC
H
3 5
2
ꢀ15
ꢀ40
ꢀ78
b
c
solvent at 25 °C for 1 h before use. Isolated yield. Determined by the
HPLC using chiral OJꢀH chiral column. The absolute configurations
were assigned as R via comparison of specific rotations with the
d
8
a
3
literature data.
Molecular ratio: [Pd(η ꢀC
3
H
5
)Cl]
2
/1b/5a/6a
= 1/1.1/100/300.
Reactions were carried out under N
temperature. The catalysts were prepared by treating [Pd(η ꢀC H )Cl]
2
2
atmosphere at a certain
3
The C ꢀsymmetric chiral ferrocene P,Nꢀligand 3 was also
applied to the reaction. Poor enantioselectivities were observed
with the ligand showing lower catalytic activity compared to its
C ꢀsymmetric chiral ferrocene counterpart 1a (entries 1, 7 and
). When the C ꢀsymmetric chiral ruthenocene P,Nꢀligand 4
1
1
3
5
b
with 1b in a suitable solvent at 25 °C for 1 h before use. Isolatedd
c
yield. Determined by the HPLC using chiral OJꢀH chiral column.
The absolute configurations were assigned as R via comparison of
8
2
specific rotations with the literature data.
8
The asymmetric amination was not particularly sensitive to
solvent changes; nonpolar and polar solvents could all be used
was used, only up to 38% ee was obtained even with a
prolonged reaction time (entries 9 and 10). Therefore, the
following reactions were carried out using 1b as a chiral ligand
(Table 2, entries 1~5). Toluene proved to be the best choice of
solvent based on both activity and enantioselectivity when 1b
was used as a chiral ligand (entry 1). Temperature had no effect
on enantioselectivities but a more pronounced effect on
reaction activities was observed (entries 6~9). These results
in PhCH solvent at 25 °C.
3
An explanation as to why the C ꢀsymmetric chiral ligands 1
and 2 showed significant effects in the asymmetric catalysis
2
compared to the C ꢀsymmetric ligands 3 and 4 is not entirely
1
suggested that C ꢀsymmetrical chiral metallocenyl P,Nꢀligands
2
clear. Efforts towards the preparation of single crystals of 1a
are highly efficient ligands for Pdꢀcatalyzed asymmetric allylic
aminations.
and 2a with
[Pd(l,3ꢀdiphenylꢀπꢀallyl)]2 for Xꢀray
crystallography were unsuccessful. Since both C ꢀ and C ꢀ
1
2
The reactions of different amines were examined using the
optimal reactions conditions and the results are shown in Table
symmetric ligands (1ꢀ4) possess the same central and planar
chirality, either the greater steric hindrance of 1 and 2 and/or
the possible formation of a small amount of P,Pꢀchelated Pdꢀ
complex from 1 and 2, may be responsible for the excellent
3
. The majority of substrates could be converted to their
corresponding products in high yields and with excellent
enantioselectivities. Primary amines, benzylamine and
cyclohexylamine, reacted smoothly to produce the
corresponding allylic amines with excellent enantioselectivities
9
asymmetric behavior.
(
entries 1 and 2, 96% ee). Generally, it is difficult to prepare
1
0
chiral tertiary allylic amines via asymmetric catalysis. Under
these reaction conditions, however, the use of the secondary
amines
pyrrolidine,
piperidine,
morpholine,
Nꢀ
methylcyclohexylamine and diethylamine as substrates gave
the desired chiral tertiary allylic amine products with good
activities and good to excellent enantioselectivities (entries 3~7,
up to 92% ee).
Scheme 1 The examination of catalyst system
We therefore carried out the asymmetric amination of 1,3ꢀ
diphenylꢀ2ꢀpropenyl acetate with benzylamine using different
Cyclohexenꢀ1ꢀyl acetate is a substrate which has been
extensively utilized in Pdꢀcatalyzed allylic substitution
reactions. Compared to amination reactions involving 1,3ꢀ
diphenylꢀ2ꢀpropenyl acetate, cyclohexenꢀ1ꢀyl acetate has
3
molar ratios of 1b and [Pd(η ꢀC H )Cl] in PhCH at room
3
5
2
3
temperature (Scheme 1). Increasing the amount of 1b to 2.0
mol% (Table 1, entry 5) may increase the amount of possible
P,Pꢀchelated Pdꢀcomplex that is formed by the excess chiral
11
proven to be a more challenging substrate. However, with our
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a
Table 3 Amination with different amines
bis(oxazoliny)ferrocene, followed by the addition of
diphenylphosphine chloride (Scheme 2). During the lithiation
5c
process, a non-C ꢀsymmetric chiral ferrocene 8 byꢀproduct is
2
produced in an approximately 4 : 1 molar ratio of 1 and 8,
resulting in a potential waste of reagents. The similar polarities
of 1 and 8 make them extremely difficult to separate thus a
significant amount of product containing both isomers is
obtained during column chromatography. When 8 was treated
1
2
b
c,d
Entry
1
HNR R
Time (h) Yield (%)
Ee (%)
with
an
adequate
amount
of
1
3
96
93
96
dichlorobis(acetonitrile)palladium(II), only a 1 : 1 P,Nꢀchelate
species with a Rpꢀconfiguration was generated due to its own
2b,5a
2
3
96
92
steric hindrance.
It has been reported that the planar
chirality of the C ꢀsymmetric ferrocenes plays an important
1
role in asymmetric induction and the counterpart of (S,Sp)ꢀ3,
3
3
94
90
(
S,Rp)ꢀ3 possessing a Rpꢀconfiguration, provided the amination
product with much higher reaction activity and
a
9
4
5
69
91
enantionselectivity than that of (S,Sp)ꢀ3. If 8 showed similar or
even better catalytic behavior than 1, the ligands could be used
as a mixture thus simplifying the purification process and
minimizing material waste.
3
3
95
92
6
87
7
Et
2
NH
3
89
90
a
3
Molecular ratio: [Pd(η ꢀC
3
H
5
)Cl]
2
/1b/5a/6 = 1/1.1/100/300. Reactions
atmosphere at 25 °C. The catalysts
)Cl] with 1b in PhCH at 25 °C
for 1 h before use. Isolated yield. Determined by the HPLC using
Scheme 2 The synthesis of 1 and 8
were carried out in PhCH
were prepared by treating [Pd(η ꢀC
3 2
under N
3
The asymmetric allylic amination of 1,3ꢀdiphenylꢀ2ꢀ
propenyl acetate with benzylamine was therefore carried out
using 8b as a chiral ligand in different solvents at 25 C. As can
be seen in Table 5, the desired product was obtained with more
than 90% ee irrespective of reaction solvent, with diethyl ether
providing the best result (entries 1ꢀ6). Temperature had an
obvious effect on the reaction and low reaction reactivity and
3
H
5
2
3
b
c
d
o
chiral ADꢀH, ODꢀH and OJꢀH chiral column.
configurations were assigned as R via comparison of specific rotations
with the literature data.
The absolute
8
ligand 1b as a chiral ligand, the catalytic results were also
satisfactory. Using 1 mol% of 1b, allylic substitutions
proceeded smoothly to give the desired products in good yields
and enantioselectivities (Table 4, entries 1ꢀ4).
o
enantioselectivity were observed at 0 C (entries 7ꢀ8).
a
Table 5 Solvent and temperature screening
a
Table 4 Amination with 1,3ꢀdiphenylꢀ2ꢀpropenyl acetate
o
b
c,d
Entry
1
Solvent
PhCH
CH Cl
DMF
THF
Time (h) T ( C) Yield (%)
Ee (%)
95
3
3
25
93
2
3
4
5
6
7
2
2
3
3
3
3
3
12
3
25
25
25
25
25
0
93
94
40
90
96
65
95
93
91
93
96
97
73
93
1
2
b
c,d
Entry
HNR R
Solvent
PhCH
CH Cl
PhCH
Time (h) Yield (%) Ee (%)
1
2
3
BnNH
2
3
12
3
90
88
87
91
92
80
90
79
EtOAc
BnNH
2
2
2
Et O
2
Et
Et
2
O
O
Bn
Bn
2
2
NH
NH
3
12
3
8
2
40
4
CH
2
Cl
2
a
3
Molecular ratio: [Pd(η ꢀC
3
H
5
)Cl]
2
/8b/5a/6a
= 1/2.2/100/300.
a
3
Reactions were carried out under N
catalysts were prepared by treating [Pd(η ꢀC
suitable solvent at 25 °C for 1 h before use. Isolated yield.
2
atmosphere at 25 °C. The
Molecular ratio: [Pd(η ꢀC
3
H
5
)Cl]
atmosphere at 25 °C. The catalysts were
)Cl] with 1b in a suitable solvent at
2
/1b/5b/6 = 1/1.1/100/300. Reactions
3
3
H
5
2
)bCl] with 8b in a
c
were carried out under N
prepared by treating [Pd(η ꢀC
2
using chiral ADꢀH and OJꢀH column. The absolute configurations
were assigned as R via comparison of specific rotations with the
literature data.
2
3
3
H
5
2
d
b
c
Determined by the HPLC using chiral OJꢀH column. The absolute
5 °C for 1 h before use. Isolated yield. Determined by the HPLC
d
configurations were assigned as R via comparison of specific
8
rotations with the literature data.
1
2
A series of amines were than examined using the above
reaction conditions. Both primary amines and secondary
amines could be used as efficient nucleophiles in the Pdꢀ
In our previous work, C ꢀsymmetric planar chiral ferrocenyl
2
ligands 1 were easily synthesized via dilithiation of 1,1'ꢀ
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catalyzed allylic amination (Table 6, entries 1ꢀ7). When
allylamine was used as the nucleophile, the desired product was
obtained in practically quantitative yield with 98% ee (entry 3).
reported
with
excellent
results.
Much
higher
enantioselectivities and catalytic activities were obtained using
C ꢀsymmetric P,Nꢀligands compared to when using their C ꢀ
2
1
symmetric counterparts. Additionally, the nonꢀC ꢀsymmetric
ferroocenyl P,Nꢀligand 8b, a byꢀproduct obtained during the
a
2
Table 6 Amination with different amines
synthesis of C ꢀsymmetric 1b, was also tested to be an efficient
2
ligand in the above asymmetric catalysis. Using a more
accessible mixed ligand system of 1b and 8b, allylic amination
of 1,3ꢀdiphenylꢀ2ꢀpropenyl acetate with benzylamine gave the
desired product in 93% yield and with 95% ee.
1
2
b
c,d
Entry
HNR R
Time (h)
Yield (%)
Ee (%)
4. Experimental
General information
1
2
3
3
3
3
96
95
97
97
91
98
Unless stated otherwise, all reactions were performed under
a nitrogen atmosphere using freshly distilled solvents, and
workups were carried out in air. Toluene, EtOAc, DCM, DMF,
dioxane, Et O and THF were distilled over dehydrating
2
reagents. Commercially available reagents were used without
1
13
further purification. H NMR (400 MHz) and C NMR (100
MHz) spectra were recorded on a Varian MERCURY plusꢀ400
spectrometer with TMS as an internal standard. High resolution
mass spectra (HMRS) were performed at the Instrumental
Analysis Center of Shanghai Jiao Tong University. High
performance liquid chromatography (HPLC) was performed on
a Shimadazu LCꢀ2010A liquid chromatography using Chiracell
ODꢀH, OJꢀH, IC3ꢀH, ADꢀH and IEꢀH columns. The
commercially available reagents were used without further
purification.
4
5
3
3
91
94
82
90
6
3
3
92
95
94
94
7
a
2
Et NH
3
Molecular ratio: [Pd(η ꢀC
3
H
5
)Cl]
2
/8b/5a/6
atmosphere at 25 °C. The
=
1/2.2/100/300.
4.1 General procedure for Pd-catalyzed asymmetric allylic
amination using ligand 1b or 8b.
Reactions were carried out under N
catalysts were prepared by treating [Pd(η ꢀC
at 25 °C for 1 h before use. Isolated yield. Determined by the
2
3
3
H
5
)cCl]
2 2
with 8b in Et O
3
b
Ligand (for 1b 2.2 ꢁmol or 8b 4.4 ꢁmol) and [Pd(η ꢀC H )Cl]
3
5
2
d
HPLC using chiral IC3ꢀH, ODꢀH, ADꢀH and OJꢀH column. The
(1.8 mg, 4.0 ꢁmol) were dissolved in dry PhCH or Et O (3 mL)
3 2
absolute configurations were assigned as R via comparison of
specific rotations with the literature data.
and the mixture was stirred at room temperature under N2
atmosphere for 1 h. To the reaction mixture, 1,3ꢀdiphenylꢀ2ꢀ
propenyl acetate (126 mg, 0.5 mmol) was added over another
8
Since 8b delivered somewhat better catalytic behavior than
that of 1b, we decided to use a mixed ligand system consisting
1
0 min followed by the addition of BnNH2 (0.13 mL, 1.5
o
mmol). Then the reaction was stirred at 25 C and monitored by
TLC until the disappearance of 1,3ꢀdiphenylꢀ2ꢀpropenyl acetate.
of both C ꢀsymmetric 1b and nonꢀC ꢀsymmetric 8b, avoiding
2
2
the problems encountered during their purification. As
expected, the Pdꢀcatalyzed asymmetric allylic amination
proceeded smoothly giving the desired product 7a in 93% yield
and with 95% ee (Scheme 3).
The reaction mixture was diluted with Et O and washed with
2
saturated NH
Cl solution, water and brine. The organic phase
4
was then dried over Na SO and concentrated under reduced
2
4
pressure. The resulting crude product was purified by column
chromatography to give the pure product.
1
3
(
E)-N-Benzyl-1,3-diphenylprop-2-en-1-amine (7a). Yellow
1
oil (1b: 143 mg, 96%; 8b: 143 mg, 96%). H NMR (400 MHz,
CDCl ): δ 7.44 (d, J = 7.4 Hz, 2H), 7.38 – 7.32 (m, 8H), 7.31 –
3
7
6
.24 (m, 4H), 7.23 – 7.20 (m, 1H), 6.59 (d, J = 15.8 Hz, 1H),
3
Molecular ratio: [Pd(η ꢀC
3
H
5
)Cl]
2
/ligands/5a/6a
atmosphere at 25 °C; The catalyst
)Cl] with ligands in PhCH at
5 °C for 1 h before use; Isolated yield; ee was determined by the
= 1/1.1/100/300;
.33 (dd, J = 15.8, 7.4 Hz, 1H), 4.85 – 4.80 (m, 1H), 4.41 (d, J
Reactions were carried out under N
was prepared by treating [Pd(η ꢀC
2
13
3
= 7.4 Hz, 1H), 3.83 – 3.76 (m, 2H); C NMR (100 MHz,
CDCl ): δ 143.0, 140.5, 137.1, 132.7, 130.6, 128.8, 128.7,
1
3
H
5
2
3
2
3
28.6, 128.4, 127.7, 127.6, 127.5, 127.1, 126.6, 64.8, 51.6;
HPLC using chiral OJꢀH chiral column; The absolute configurations
were assigned as R via comparison of specific rotations with the
literature data.
Using chiral OJꢀH (87/13 nꢀhexane/iꢀPrOH, 0.5 mL/min, 254
8
nm, tR1 = 20.8 min (minor), t = 25.5 min (major), 96% ee
R2
2
5
(
1b), 97% ee (8b); [α]
D
= –9.98 (c 0.76, CHCl3).
Scheme 3 The reaction using a mixed chiral ligand
1
4
(
E)-N-(1,3-Diphenylallyl)cyclohexanamine (7b). Yellow oil
1
3
. Conclusions
(1b: 135 mg, 93%; 8b: 138 mg, 95%). H NMR (400 MHz,
CDCl ): δ 7.48 – 7.16 (m, 10H), 6.70 (d, J = 16.0 Hz, 1H), 6.53
3
In summary, a Pdꢀcatalyzed asymmetric allylic amination
(d, J = 16.0 Hz, 1H), 6.36 (ddd, J = 23.2, 15.8, 7.0 Hz, 1H),
using a series of chiral metallocenyl P,Nꢀligands has been
5.39 (d, J = 6.4 Hz, 1H), 4.57 (d, J = 7.4 Hz, 1H), 2.47 (d, J =
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DOI: 10.1039/C5OB00032G
1
3
3
.6 Hz, 1H), 2.03 – 1.52 (m, 6H), 1.21 – 1.09 (m, 4H);
C
(m, 10H), 6.57 (d, J = 15.8 Hz, 1H), 6.30 (dd, J = 15.8, 7.6 Hz,
1H), 5.97 – 5.89 (m, 1H), 5.15 (dd, J = 28.0, 13.8 Hz, 2H), 4.41
(d, J = 7.4 Hz, 1H), 3.67 – 2.95 (m, 2H); C NMR (100 MHz,
NMR (100 MHz, CDCl ): δ 143.5, 137.2, 136.7, 133.3, 131.8,
30.7, 130.1, 128.7, 128.6, 127.9, 127.5, 127.3, 126.8, 126.6,
5.3, 62.1, 53.8, 34.0, 33.8, 26.3, 25.3; Using chiral ADꢀH
99/1 nꢀhexane/iꢀPrOH, 0.5 mL/min, 220 nm, tR1 = 19.5min
5major), tR2 = 22.5 min (minor), 96% ee (1b), 91% ee (8b); [α]
3
13
1
7
(
CDCl ): δ 143.0, 137.1, 136.9, 132.6, 130.6, 128.8, 128.7,
3
+
127.6, 127.5, 126.6, 116.3, 64.9, 50.2; HRMS (EI ) m/z
calculated for C H N [M+1] : 250.1596, found: 250.1600;
+
(
18
20
2
D
= +21.32 (c 0.49, CHCl
3
).
Using chiral IC3ꢀH (98/2 nꢀhexane/iꢀPrOH, 0.2 mL/min, 254
2n5m, t = 23.2 min (minor), tR2 = 26.3 min (major), 98% ee; [α]
D
1
5
R1
(
1
E)-1-(1,3-Diphenylallyl)pyrrolidine (7c). Brown oil (1b:
=
+8.66 (c 0.39, CHCl3).
1
22 mg, 94%; 8b: 119 mg, 91%). H NMR (400 MHz, CDCl ):
δ 7.47 (d, J = 7.2 Hz, 2H), 7.34 (dd, J = 10.6, 7.6 Hz, 3H), 7.29
7.26 (m, 3H), 7.21 (dd, J = 13.8, 6.6 Hz, 2H), 6.58 (d, J =
5.6 Hz, 1H), 6.48 (dd, J = 15.6, 8.4 Hz, 1H), 3.84 (d, J = 8.0
Hz, 1H), 2.65 (s, 2H), 2.54 (s, 2H), 1.83 (s, 4H); C NMR (100
3
11
N-Benzylcyclohex-2-enamine (7i). Yellow oil (1b: 84 mg,
1
–
1
90%). H NMR (400 MHz, CDCl ): δ 7.37 – 7.30 (m, 4H), 7.26
3
– 7.22 (m, 1H), 5.80 – 5.72 (m, 2H), 3.85 (dd, J = 18.8, 13.2
Hz, 2H), 2.02 – 1.98 (m, 2H), 1.94 – 1.87 (m, 1H), 1.80 – 1.71
(m, 2H), 1.62 – 1.44 (m, 2H); Using chiral ADꢀH (99.7/0.3 nꢀ
1
3
MHz, CDCl ): δ 128.9, 128.7, 127.9, 127.8, 127.6, 126.7, 74.6,
3
5
3.3, 23.5; Using chiral ODꢀH (95/5 nꢀhexane/iꢀPrOH, 0.5
hexane/iꢀPrOH, 0.5 mL/min, 220 nm, t = 12.6 min (minor),
R1
2
5
mL/min, 254 nm, tR1 = 7.8 min (minor), t = 8.3 min (major),
9
tR2 = 13.0 min (major), 92% ee; [α]
D
= +1.07 (c 0.52, CHCl3).
R2
D
= +13.75 (c 0.28, CHCl3).
25
2% ee (1b), 82% ee (8b); [α]
11
N,N-Dibenzylcyclohex-2-enamine (7j). Yellow oil (1b: 126
1
6
1
(
E)-1-(1,3-Diphenylallyl)piperidine (7d). Brown oil (1b:
mg, 87%). H NMR (400 MHz, CDCl ): δ 7.41 (d, J = 8.0 Hz,
3
1
1
31 mg, 95%). H NMR (400 MHz, CDCl ): δ 7.41 (t, J = 1.6
4H), 7.32 – 7.28 (m, 4H), 7.23 – 7.20 (m, 2H), 5.85 – 5.82 (m,
1H), 5.75 (d, J = 12.0 Hz, 1H), 3.75 (d, J = 12.0 Hz, 2H), 3.56
(d, J = 16.0 Hz, 2H), 3.37 – 3.34 (m, 1H), 1.99 – 1.95 (m, 3H),
1.93 – 1.90 (m, 1H), 1.58 – 1.54 (m, 1H), 1.53 – 1.44 (m, 1H);
Using chiral OJꢀH (98/2 nꢀhexane/iꢀPrOH, 0.2 mL/min, 220
3
Hz, 1H), 7.39 (d, J = 0.8 Hz, 1H), 7.37 – 7.32 (m, 3H), 7.31 (dd,
J = 7.2, 1.8 Hz, 1H), 7.29 – 7.25 (m, 2H), 7.25 – 7.18 (m, 2H),
6
.57 (d, J = 15.8 Hz, 1H), 6.29 (dd, J = 15.8, 8.8 Hz, 1H), 3.79
(d, J = 8.8 Hz, 1H), 3.75 – 3.68 (m, 4H), 2.63 (s, 1H), 2.54 (s,
1
3
2
H), 2.45 – 2.35 (m, 2H), 2.18 (s, 1H); C NMR (100 MHz,
nm, t = 12.2 min (minor), tR2 = 12.8 min (major), 90% ee; [α]
R1
2
5
CDCl ): δ 141.7, 136.9, 131.8, 131.5, 128.8, 128.7, 128.2,
D
= +2.17 (c 0.49, CHCl3).
3
1
27.7, 127.5, 126.6, 75.0, 67.3, 52.4; Using chiral ADꢀH (97/3
4
.2 General procedure for Pd-catalyzed asymmetric allylic
nꢀhexane/iꢀPrOH, 0.3 mL/min, 254 nm, t =13.7min (minor),
tR2 = 15.8 min (major), 69% ee; [α] = +13.36 (c 0.46, CHCl3).
R1
25
amination using a mixture ligands of 1b and 8b.
D
3
1
7
The mixture of ligands (1b / 8b = 4 : 1, 3.51 mg) and [Pd(η ꢀ
C
room temperature under N2 atmosphere for 1 h and 1,3ꢀ
diphenylꢀ2ꢀpropenyl acetate (100 mg, 0.4 mmol) was added
over 10 min followed by the addition of BnNH (0.11 mL, 1.2
mmol). Then the reaction was stirred at 25 C and monitored by
TLC until the disappearance of 1,3ꢀdiphenylꢀ2ꢀpropenyl acetate.
The reaction mixture was diluted with Et O and washed with
(
E)-4-(1,3-Diphenylallyl)morpholine (7e). Yellow oil (1b:
1
3
H
5
)Cl] (1.7 mg, 3.9 ꢁmol) in toluene (3 mL) were stirred at
2
1
32 mg, 95%; 8b: 131 mg, 94%). H NMR (400 MHz, CDCl ):
3
δ 7.44 – 7.20 (m, 10H), 6.59 (d, J = 15.8 Hz, 1H), 6.31 (dd, J =
1
4
CDCl ): δ 141.7, 136.9, 131.8, 131.5, 128.9, 128.7, 128.2,
1
5.8, 8.8 Hz, 1H), 3.81 (d, J = 8.8 Hz, 1H), 3.73 (t, J = 4.4 Hz,
1
3
2
H), 2.56 (s, 2H), 2.48 – 2.35 (m, 2H); C NMR (100MHz,
o
3
27.8, 127.5, 126.6, 75.0, 67.3, 52.4; Using chiral OJꢀH (95/5
2
nꢀhexane/iꢀPrOH, 0.5 mL/min, 254 nm, tR1 = 21.8 min (minor),
tR2 = 29.8 min (major), 91% ee (1b), 90% ee (8b); [α] = +2.61
2
5
saturated NH
4
Cl solution, water and brine. The organic phase
D
was then dried over Na SO and concentrated under reduced
pressure. The crude product was purified by column
chromatography to give the desired product as a yellow oil
2
4
(
c 0.45, CHCl3).
18
(
E)-N-(1,3-Diphenylallyl)-N-methylcyclohexanamine (7f).
1
(110 mg, yield: 93%, ee: 95%).
Yellow oil (1b: 140 mg, 92%; 8b: 140 mg, 92%). H NMR
400 MHz, CDCl ,): δ 7.42 – 7.19 (m, 10H), 6.53 (d, J = 15.8
(
3
Hz, 1H), 6.39 (s, 1H), 4. 25 (d, J = 12.0 Hz, 1H), 2.61 (t, J =
Acknowledgments
8
1
.0 Hz, 1H), 2.20 (s, 3H), 1.83 – 1.67 (m, 4H), 1.58 – 1.52 (m,
H), 1.40 – 1.25 (m, 2H), 1.16 – 1.10 (m, 3H); C NMR (100
1
3
This work was partially supported by the National Natural
Science Foundation of China (No. 21172143, 21172145,
21372152 and 21232004), Nippon Chemical Industrial Co., Ltd.
and Shanghai Jiao Tong University (SJTU). We thank the
Instrumental Analysis Center of SJTU for HRMS analysis. We
also thank Prof. Tsuneo Imamoto and Dr. Masashi Sugiya of
Nippon Chemical Industrial Co., Ltd. for helpful discussions.
MHz, CDCl ): δ 143.7, 137.4, 133.3, 130.2, 128.8, 128.7, 128.0,
3
1
27.5, 127.1, 126.6, 70.8, 58.5, 34.1, 28.8, 28.4, 26.7, 26.3;
Using chiral IC3ꢀH (99/1 nꢀhexane/iꢀPrOH, 0.3 mL/min, 254
nm, tR1 = 18.4 min (minor), t = 19.4 min (major), 87% ee (1b),
R2
2
5
9
4% ee (8b); [α] = –16.58 (c 0.51, CHCl3).
D
19
(
E)-N,N-Diethyl-1,3-diphenylprop-2-en-1-amine
Yellow oil (1b: 117 mg, 89%; 8b: 121 mg, 95%). H NMR
400 MHz, CDCl ): δ 7.52 – 7.20 (m, 10H), 6.56 (d, J = 15.8
(7g).
1
Notes and references
(
3
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1
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3
1
(
28.0, 127.5, 127.1, 126.5, 69.0, 43.2, 11.7; Using chiral OJꢀH
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5minor), tR2 = 29.0 min (major), 90% ee (1b), 94% ee (8b); [α]
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2
2
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(
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Sci. 2010, 1, 427–440; (i) P. Tosatti, A. Nelson and S. P. Marsden,
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3
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 |
5

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