Enantioselective and α-regioselective allylic amination of Morita-Baylis-Hillman acetates with simple aromatic amines catalyzed by planarly chiral ligand/palladium catalyst

Article abstract of DOI:10.1002/cjoc.201200771

An asymmetric allylic amination of Morita-Baylis-Hillman acetates with simple aromatic amines catalyzed by planarly chiral ligand/palladium-catalyst was developed in good yield with excellent α-regioselectivity (α/γ up to 30:1) and moderate enantioselecti

Full text of DOI:10.1002/cjoc.201200771

FULL PAPER
DOI: 10.1002/cjoc.201200771
Enantioselective and α-Regioselective Allylic Amination of
Morita-Baylis-Hillman Acetates with Simple Aromatic Amines
Catalyzed by Planarly Chiral Ligand/Palladium Catalyst
Wang, Yana,b(王炎)
Zhang, Taoa,b(张涛)
Liu, Li*,a(刘利)
Wang, Donga(王东)
Chen, Yongjuna(陈拥军)
a Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition
and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
b Graduate School of Chinese Academy of Sciences, Beijing 100049, China
An asymmetric allylic amination of Morita-Baylis-Hillman acetates with simple aromatic amines catalyzed by
planarly chiral ligand/palladium-catalyst was developed in good yield with excellent α-regioselectivity (α/γ up to
30∶1) and moderate enantioselectivity (up to 70% ee).
Keywords asymmetric allylic amination, Morita-Baylis-Hillman adducts, aromatic amines, palladium catalysis,
diphosphine ligands
Introduction
catalyzed α-regioselective and enantioselective allylic
substitution with O-nucleophile such as phenols and
alcohols. However, there were only two examples of
MBH adducts in Pd-catalyzed allylic amination.[6] In
2002, Iqbal and co-workers[7] firstly reported the palla-
dium-catalyzed allylic amination of MBH acetates, but
with the moderate regioselectivity (α/γ＝3∶1 to 6∶1)
and no enantioselectivity. Hamada and coworkers[8] re-
alized the asymmetric allylic amination reactions of
MBH adducts, but evaded a problem of the regioselec-
tivity due to the symmetry of the substrates used. Herein,
we reported α-regioselective and enantioselective allylic
amination of MBH acetates with the simple aromatic
amines catalyzed by planarly chiral ligand/palladium
catalysts.
The Morita-Baylis-Hillman (MBH) reactions have
been proved to be one of the most successful methods
for C—C bond forming reaction.[1] Since three func-
tionalized groups, the hydroxyl group, the double bond,
and the carbonyl (cyano) group, lie closely in one mo-
lecule, the MBH adducts provide an opportunity for
developing methodology in organic synthesis by ma-
nipulating the functional groups.[1b] Among the trans-
formations of the MBH adduct,[2] the palladium-cata-
lyzed allylic substitution reaction has attracted consid-
erable attentions.[3] This type of reaction could proceed
in two regioselective ways to give α- and γ-products
because of the unsymmetrical allylic unit in the MBH
adduct molecule (Scheme 1). Regioselective introduc-
tion of nucleophile to either the α- or γ-position of the
allylic moiety seems to be an urgent requirement and is
becoming a power tool in synthetic organic chemistry.
For the α-product, the enantioselective control is an-
other challenge problem. Accordingly, simultaneously
regioselective and enantioselective allylic substitution
reaction of MBH adduct has been becoming an attrac-
tive and challenge subject to the chemist in organic
synthesis. Although asymmetric allylic amination of
MBH adducts with nitrogen nucleophiles such as cyclic
imides or aliphatic amines catalyzed by organocatalysts
has been reported,[4] the enantioselective amination us-
ing less active simple aromatic amines was still unde-
veloped. Trost and coworkers[5] reported palladium
Scheme 1 Allylic substitution of Morita-Baylis-Hillman adduct
Nu
*
O
O
Pd-Catalyzed
allylic substitution
OR
O
R1
R2
R1
R2
+
R1
R2
NuH
Nu
MBH Adduct
α-product
γ-product
Results and Discussion
Initially, we selected the allylic amination of MBH
acetate 1a with aniline 2a as the model reaction. Using
Pd2(dba)3 as a catalyst, various diphosphine ligands
were tested. As shown in Table 1, ligands L1—L4 were
*
E-mail: lliu@icca.ac.cn
Received July 26, 2012; accepted September 7, 2012; published online October 30, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200771 or from the author.
Chin. J. Chem. 2012, 30, 2641—2646
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2641

Wang et al.
FULL PAPER
Table 1 Optimization of the ligandsa
conversion was offered with poor α-regioselectivity
(Entries 5—7). The ligand L8 with planar chirality
showed the best α-regioselectivity (α∶γ＝20∶1) and
enantioselectivity (63% ee) (Entry 8). Ligand L9 having
more steric hindrance was then used to increase the en-
antioselectivity (Entry 9). However, the γ-product 4a
was obtained as the major product in 26% conversion,
and for α-product 3a only with 36% ee.
NH2
OAc O
Pd2(dba)3 (5 mol%)
ligand (12.5 mol%)
OMe
+
K2CO3 (1 mol/L), DCM, r.t.
1a
2a
O
Subsequently, several metallic catalysts, bases and
solvents were examined (Table 2). In contrast with other
Pd-catalysts, Pd2(dba)3 could give the better α-regio-
selectivity and enantioselectivity (Entries 4 vs. 1—3).
KOH was better than K2CO3 with excellent α-regio-
selectivity (α∶γ＝30∶1) and better enantioselectivity
(66% ee) (Entry 8). Taking account of both regioselec-
tivity and enantioselectivity, DCM was the best choice.
NH
O
OMe
+
OMe
N
H
4a
3a
Me
P
PPh2
PPh2
Me
PPh2
PPh2
Me
Table 2 Optimization of other reaction conditionsa
P
Me
P
NH2
OAc O
L8 (12.5 mol%)
Pd (10 mol%)
L1
L2
L3
OMe
+
Base (1 mol/L), Sol., r.t.
Bu-t
Ph
Ph
1a
2a
R
H
P
O
O
Bu-t
Ph2P
Ph2P
Fe
P
Fe
R
O
CH3
CH3
PPh2
NH
O
L4
OMe
L5
R = 3,5-dimethylphenyl
+
OMe
N
H
L6
i-Pr
4a
3a
P
PR2
PR2
PPh2
PPh2
Entry Pd
Base
Sol.
t/h Conv.b/% 3a∶4ab eec/%
Pr-i
Fe
Pr-i
1
2
3
4
5
6
7
8
9
Pd2(dba)3CHCl3 K2CO3 DCM 20
100
100
100
100
100
100
97
9.3∶1
5∶1
60
55
39
63
P
Pd(acac)2
[Pd(C3H5)Cl]2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
K2CO3 DCM 20
K2CO3 DCM 16
K2CO3 DCM 24
KOtBu DCM 24
KOAc DCM 24
KHCO3 DCM 24
R = 3,5-dimethylphenyl
Pr-i
L8
2.7∶1
20∶1
L7
L9
13.8∶1 62
1∶2.8 3.3
24.3∶1 65
Entry
Ligand
L1
t/h
Conv.b/%
30
3a∶4ab
1∶1
eec/%
NDd
ND
ND
ND
ND
20
1
2
3
4
5
6
7
8
9
48
4
L2
70
1∶9
KOH
DCM 24
100
97
30∶1
1.5∶1
10∶1
66
4
L3
48
48
12
12
48
48
48
38
1∶5.2
1∶2
DABCO DCM 24
L4
17
10 Pd2(dba)3
11 Pd2(dba)3
12 Pd2(dba)3
13 Pd2(dba)3
14 Pd2(dba)3
15 Pd2(dba)3
NEt3
DCM 24
THF 24
100
100
97
60
L5
100
100
100
100
26
1∶1.7
1∶1
KOH
KOH
KOH
KOH
KOH
32.6∶1 62
11.4∶1 49
L6
toluene 24
MeOH 24
acetone 24
L7
1∶1.2
20∶1
1∶4.5
17
low
100
100
—
—
—
—
L8
63
L9
35
EA
24
13.8∶1 49
a
All reactions were performed with 1a (0.1 mmol), 2a (0.3
a
All reactions were performed with 1a (0.1 mmol), 2a (0.3
mmol), K2CO3 (0.3 mmol), in DCM (2 mL) at 25 ℃ in nitrogen
atmosphere. Pd2(dba)3 (5 mol%) and ligand (12.5 mol%) were
used. b Determined by 1H NMR of the mixture of crude products.
c Determined by chiral HPLC.
mmol), base (0.3 mmol), in solvents (2 mL) at 25 ℃ in nitrogen
atmosphere. Pd catalyst (10 mol%) and ligand (12.5 mol%) were
used. b Determined by 1H NMR of the mixture of crude products.
c Determined by chiral HPLC.
not quite effective for this reaction and afforded the
poor conversion (Table 1, Entries 1—4) probably be-
cause of the short distance between the two phosphine
units in the ligands. Switching to L5—L7, which have
longer distance between the two phosphine units, full
With the optimized catalyst and reaction conditions
in hand, we then investigated the substrate scope of al-
lylic amination. Various MBH acetates were employed
in the reaction (Table 3). When R2 was ethyl, the best
2642
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2641—2646

Enantioselective and α-Regioselective Allylic Amination of Morita-Baylis-Hillman Acetates
Table 3 Substrate scope of the allylic aminationa
R3
O
NH
O
Pd2(dba)3 5 mol%
L8 12.5 mol%
OAc O
R1
OR2
R1
OR2
R3 NH2
R1
OR2
+
+
N R3
H
KOH, DCM, r.t.
2
3
1
4
Entry
1
1, R1
R2
2, R3
3∶4b
30∶1
25∶1
1∶1
3, Yieldc/%
3a, 88
3b, 90
3c, 48
3d, 88
3e, 75
3f, 91
eed/%
66
70
60
64
37
60
61
66
63
54
57
62
41
1a, phenyl
1b, phenyl
Me
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
2a, phenyl
2
2a, phenyl
3
1c, 3-Br-phenyl
1d, 4-Br-phenyl
1e, 4-Me-phenyl
1f, 4-Cl-phenyl
1g, naphthyl
1b, phenyl
2a, phenyl
4
2a, phenyl
13∶1
6∶1
5
2a, phenyl
6
2a, phenyl
27∶1
20∶1
15∶1
20∶1
26∶1
21∶1
20∶1
24∶1
7
2a, phenyl
3g, 89
3h, 88
3i, 85
8
2b, 3-Cl-phenyl
2c, 3,5-Cl2-phenyl
2d, 4-Cl-phenyl
2e, 3-CF3-phenyl
2f, 2-Me-phenyl
2g, naphthyl
9
1b, phenyl
10
11
12
1b, phenyl
3j, 86
1b, phenyl
3k, 89
3l, 87
1b, phenyl
13
1b, phenyl
3m, 90
a
All reactions were performed with 1 (0.1 mmol), 2 (0.3 mmol), KOH (0.3 mmol), in DCM (2 mL) at 25 ℃ in nitrogen atmosphere.
Pd2(dba)3 catalyst (5 mol%) and ligand L8 (12.5 mol%) were used. b Determined by 1H NMR of the mixture of crude products. c isolated
yield. d Determined by chiral HPLC.
the allylic intermediate from α-position and Si-face
leading to the S enantiomer of the product.
enantioselectivity was observed (Entry 2). The regiose-
lectivity disappeared completely using the MBH acetate
1c derived from 3-Br-benzaldehyde (Entry 3). For the
MBH acetate 1e, the enantioselectivity decreased to
37% (Entry 5). Various aniline derivatives tolerated this
reaction and afforded the excellent α-regioselectivities
and moderate enantioselectivities. When R3 was
naphthyl, the enantioselectivity dropped slightly to 41%
(Enrty 13).
Conclusions
In conclusion, the Morita-Baylis-Hillman acetates
have been successfully employed in a planarly chiral
ligand (L8)/palladium-catalyzed asymmetric allylic
amination reaction with a variety of simple amines, ani-
line derivatives, in good yields with excelllent α-regio-
selectivity and moderate enantioselectivity. This reac-
tion provides an efficient method access to optically
β-arylamino acid esters[1a,1d,2b,10] that could be readily
transformed into corresponding β-lactam derivatives.
Compared with the known compound,[9] the con-
figuration of a newly created chiral center of 3b was
deduced as S. The transition state of the allylic amina-
tion reaction was proposed in Figure 1. After removing
OAc, the MBH acetate 3 forms π-allylpalladium com-
plex with Pd catalyst and the ligand. The palladium
could also coordinate with the ethyl ester of MBH ad-
duct to preferentially adopt the anti-π-allyl geometry
and the bulky phanephos ligand approached to the less
steric hindrance γ-position easily. Thus, the steric hin-
drance in α-position appeared to be less, aniline attacks
Experimental
General methods
1
The H NMR and 13C NMR spectra were recorded
on Bruker-AV 300 spectrometer and chemical shift re-
ported in CDCl3 with tetramethylsilane as an internal
standard. IR spectra were recorded on a Bruker tensor
27 infrared spectrometer. HRMS spectra were recorded
on GCT-Mass Micromass spectrometer. All reactions
were carried out in oven dried flasks. Common reagents
were purchased from commercial sources and were used
without further purification. The Morita-Baylis-Hillman
acetates were prepared according to literature meth-
ods.[11] All reactions were performed under nitrogen
atmosphere.
*
P
P
Pd
O
Ar
Si
PhNH2
OEt
Figure 1 Proposed transition state.
Chin. J. Chem. 2012, 30, 2641—2646
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2643

Wang et al.
FULL PAPER
Typical experimental procedures for allylic amina-
tion reaction
(S)-Ethyl 2-((4-bromophenyl)(phenylamino)-
methyl)acrylate (3d) Compound 3d was isolated as a
1
yellow oil, [α]D25 ＋57.6 (c 0.50, CH2Cl2), 64% ee; H
A solution of 5 mol% Pd2(dba)3 catalyst and 12.5
mol% ligand L8 in 1 mL DCM was stirred at 25 ℃ for
0.5 h. Followed by a solution of MBH acetates 1a (0.1
mmol) and aniline 2a (0.3 mmol) in 1 mL DCM, 0.3
mmol KOH (1 mol/L) were added. The reaction mixture
was stirred at 25 ℃ and monitored by TLC until the
starting material disappeared. Then the reaction mixture
was extracted by ethyl acetate. The organic phase was
dried by Na2SO4, filtered and evaporated to afford a
mixture of the crude products. The ratio of α- to
NMR (CDCl3, 300 MHz) δ: 1.22 (t, J＝7.2 Hz, 3H),
4.11—4.19 (m, 3H), 5.36 (d, J＝5.4 Hz, 1H), 5.91 (s,
1H), 6.39 (s, 1H), 6.56 (d, J＝8.1 Hz, 2H), 6.73 (t, J＝
7.2 Hz, 1H), 7.16 (t, J＝7.8 Hz, 2H), 7.25 (d, J＝7.2 Hz,
2H), 7.46 (d, J＝8.4 Hz, 2H); 13C NMR (CDCl3, 75
MHz) δ: 14.1, 58.6, 61.0, 113.6, 118.2, 121.7, 126.5,
129.3, 131.9, 139.9, 140.0, 146.5, 166.0; IR (KBr) νmax
:
－
1
3391, 2981, 1711, 1502 cm ; ESI-HRMS m/z calcd for
C18H19BrNO2 360.0594 (M＋), found 360.0588. The en-
antiomeric ratio was determined by HPLC on Chiralpak
AS column (5/95, 2-propanol/hexane, 0.6 mL/min),
1
γ-isomer was determined by H NMR of the mixture at
δ 5.41 and δ 7.91. The crude product was purified by
flash column chromatography over silica gel (eluent:
PE∶EA＝30∶1) to give 3a as a yellow oil (24 mg,
88%).
t
major＝11.2 min, tminor＝12.8 min.
(S)-Ethyl 2-((phenylamino)(p-tolyl)methyl)-
acrylate (3e) Compound 3e was isolated as a yellow
1
oil, [α]D25 ＋76.8 (c 0.42, CH2Cl2), 37% ee; H NMR
(S)-Methyl 2-[(phenylamino)(phenyl)methyl]-
acrylate (3a)[12] Compound 3a was isolated as a yel-
(CDCl3, 300 MHz) δ: 1.13 (t, J＝7.2 Hz, 3H), 2.25 (s,
3H), 4.00—4.11 (m, 3H), 5.29 (s, 1H), 5.85 (s, 1H),
6.28 (s, 1H), 6.48 (d, J＝8.1 Hz, 2H), 6.62 (t, J＝7.5 Hz,
1H), 7.04—7.09 (m, 4H), 7.18 (d, J＝8.1 Hz, 2H); 13C
NMR (CDCl3, 75 MHz) δ: 14.1, 21.2, 58.7, 60.8, 113.4,
117.8, 125.7, 127.5, 129.2, 129.4, 137.5, 137.8, 140.4,
146.8, 166.3; IR (KBr) νmax: 3437, 2982, 1713, 1504
1
low oil, [α]D25 ＋71.3 (c 0.48, CH2Cl2), 66% ee; H
NMR (CDCl3, 300 MHz) δ: 3.69 (s, 3H), 4.15 (s, 1H),
5.41 (s, 1H), 5.96 (s, 1H), 6.38 (s, 1H), 6.55—6.58 (m,
2H), 6.69—6.74 (m, 1H), 7.13—7.18 (m, 1H),
7.27—7.38 (m, 5H); 13C NMR (CDCl3, 75MHz) δ: 52.0,
59.0, 113.5, 117.9, 126.2, 127.6, 127.9, 128.8, 129.2,
140.0, 140.6, 146.7, 166.7. The enantiomeric ratio was
determined by HPLC on Chiralpak AS column (10/90,
2-propanol/hexane, 0.3 mL/min), tmajor＝9.7 min, tminor
＝11.4 min.
－
1
cm ; ESI-HRMS m/z calcd for C19H22NO2 296.1645
(M＋), found 296.1642. The enantiomeric ratio was de-
termined by HPLC on Chiralpak AS column (5/95,
2-propanol/hexane, 0.6 mL/min), tmajor＝8.8 min, tminor
＝9.9 min.
(S)-Ethyl 2-(phenyl(phenylamino)methyl)acrylate
(S)-Ethyl 2-((4-chlorophenyl)(phenylamino)-
methyl)acrylate (3f) Compound 3f was isolated as a
(3b)[12] Compound 3b was isolated as a yellow oil,
1
[α]D25 ＋81.8 (c 0.50, CH2Cl2), 70% ee; H NMR
1
yellow oil, [α]D25 ＋71.6 (c 0.50, CH2Cl2), 54% ee; H
(CDCl3, 300 MHz) δ: 1.20 (t, J ＝ 7.2 Hz, 3H),
4.08—4.19 (m, 3H), 5.41 (s, 1H), 5.93 (s, 1H), 6.38 (s,
1H), 6.57 (d, J＝7.8 Hz, 2H), 6.71 (t, J＝7.2 Hz, 1H),
7.15 (t, J＝7.8 Hz, 2H), 7.27—7.33 (m, 5H); 13C NMR
(CDCl3, 75MHz) δ: 14.1, 59.0, 60.8, 113.5, 117.9, 126.0,
127.6, 127.8, 128.8, 129.2, 140.3, 140.8, 146.8, 166.2.
The enantiomeric ratio was determined by HPLC on
Chiralpak AS column (10/90, 2-propanol/hexane, 0.3
mL/min), tmajor＝9.4 min, tminor＝11.6 min.
NMR (CDCl3, 300 MHz) δ: 1.22 (t, J＝7.2 Hz, 3H),
4.11—4.19 (m, 3H), 5.38 (s, 1H), 5.92 (s, 1H), 6.39 (s,
1H), 6.57 (d, J＝7.8 Hz, 2H), 6.73 (t, J＝7.2 Hz, 1H),
7.16 (t, J＝7.5 Hz, 2H), 7.31 (s, 4H); 13C NMR (CDCl3,
75 MHz) δ: 14.1, 58.5, 61.0, 113.5, 118.1, 126.4, 128.9,
129.2, 133.5, 139.3, 140.1, 146.5, 166.0; IR (KBr) νmax
:
－
1
3402, 2961, 1711, 1501 cm ; ESI-HRMS m/z calcd for
C18H19ClNO2 316.1098 (M＋), found 316.1094. The en-
antiomeric ratio was determined by HPLC on Chiralpak
AS column (5/95, 2-propanol/hexane, 0.6 mL/min),
(S)-Ethyl 2-((3-bromophenyl)(phenylamino)-
methyl)acrylate (3c) Compound 3c was isolated as a
t
major＝11.0 min, tminor＝12.5 min.
1
yellow oil, [α]D25 ＋47.1 (c 0.24, CH2Cl2), 60% ee; H
(S)-Ethyl 2-[(naphthalen-2-yl)(phenylamino)-
NMR (CDCl3, 300 MHz) δ: 1.23 (t, J＝7.2 Hz, 3H),
4.14—4.19 (m, 3H), 5.37 (d, J＝5.4 Hz, 1H), 5.92 (s,
1H), 6.41 (s, 1H), 6.57 (d, J＝7.8 Hz, 2H), 6.73 (t, J＝
7.5 Hz, 1H), 7.13—7.17 (m, 3H), 7.19 (d, J＝3.3 Hz,
1H), 7.23 (d, J＝5.4 Hz, 1H), 7.30 (s, 1H); 13C NMR
(CDCl3, 75MHz) δ: 14.1, 58.6, 61.0, 113.5, 118.2, 122.8,
126.2, 126.7, 129.3, 130.3, 130.5, 130.9, 139.9, 143.1,
146.5, 165.9; IR (KBr) νmax: 3475, 2981, 1699, 1509
cm ; ESI-HRMS m/z calcd for C18H19BrNO2 360.0594
(M＋), found 360.0588. The enantiomeric ratio was de-
termined by HPLC on Chiralpak AS column (5/95,
2-propanol/hexane, 0.6 mL/min), tmajor＝10.5 min,
methyl]acrylate (3g) Compound 3g was isolated as a
yellow oil, [α]D25 ＋128.8 (c 0.52, CH2Cl2), 61% ee;
1H NMR (CDCl3, 300 MHz) δ: 1.19 (t, J＝7.2 Hz, 3H),
4.09—4.17 (m, 2H), 4.24 (br, 1H), 5.58 (s, 1H), 5.99 (s,
1H), 6.44 (s, 1H), 6.62 (d, J＝7.8 Hz, 2H), 6.73 (t, J＝
7.5 Hz, 1H), 7.14—7.19 (m, 2H), 7.46—7.48 (m, 3H),
7.79—7.84 (m, 4H); 13C NMR (CDCl3, 75 MHz) δ:
14.1, 59.1, 60.9, 113.5, 118.0, 125.8, 126.1, 126.2,
127.7, 128.1, 128.6, 129.2, 133.0, 133.4, 138.1, 140.4,
146.8, 166.3; IR (KBr) νmax: 3407, 2980, 1711, 1502
－
1
－
1
cm ; ESI-HRMS m/z calcd for C22H22NO2 332.1645
(M＋), found 332.1641. The enantiomeric ratio was de-
termined by HPLC on Chiralpak AS column (5/95,
t
minor＝12.4 min.
2644
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2641—2646

Enantioselective and α-Regioselective Allylic Amination of Morita-Baylis-Hillman Acetates
2-propanol/hexane, 0.6 mL/min), tmajor＝12.0 min,
was determined by HPLC on Chiralpak AS column
(5/95, 2-propanol/hexane, 0.6 mL/min), tmajor＝8.4 min,
t
minor＝14.4 min.
(S)-Ethyl 2-[((3-chlorophenyl)amino)(phenyl)-
t
minor＝9.3 min.
methyl]acrylate (3h) Compound 3h was isolated as a
(S)-Ethyl 2-((o-tolylamino)(phenyl)methyl)-
1
yellow oil, [α]D25 ＋86.4 (c 0.50, CH2Cl2), 66% ee; H
acrylate (3l) Compound 3l was isolated as a yellow
1
NMR (CDCl3, 300 MHz) δ: 1.21 (t, J＝7.2 Hz, 3H),
4.10—4.27 (m, 3H), 5.37 (d, J＝5.4 Hz, 1H), 5.89 (s,
1H), 6.40 (s, 1H), 6.42—6.46 (m, 1H), 6.54—6.56 (m,
1H), 6.66—6.69 (m, 1H), 7.05 (t, J＝8.1 Hz, 1H),
7.29—7.30 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ:
14.4, 59.3, 61.2, 112.0, 113.5, 118.1, 126.4, 127.8,
oil, [α]D25 ＋62.0 (c 0.46, CH2Cl2), 62% ee; H NMR
(CDCl3, 300 MHz) δ: 1.24 (t, J＝7.2 Hz, 3H), 2.18 (s,
3H), 4.08 (br, 1H), 4.11—4.24 (m, 2H), 5.50 (s, 1H),
5.93 (s, 1H), 6.41 (s, 1H), 6.54 (d, J＝7.8 Hz, 1H), 6.70
(d, J＝7.2 Hz, 1H), 7.08—7.13 (m, 2H), 7.28—7.33 (m,
4H); 13C NMR (CDCl3, 75 MHz) δ: 14.4, 17.9, 59.2,
61.1, 111.3, 117.8, 122.5, 126.2, 127.3, 127.8, 129.1,
130.4, 140.7, 141.2, 145.0, 166.6; IR (KBr) νmax: 3412,
2981, 1712, 1510; ESI-HRMS m/z calcd for C19H22NO2
296.1645 (M＋), found 296.1641. The enantiomeric ratio
was determined by HPLC on Chiralpak AS column
(5/95, 2-propanol/hexane, 0.6 mL/min), tmajor＝7.5 min,
128.3, 129.2, 130.5, 135.3, 140.3, 140.5, 148.2, 166.4;
IR (KBr) νmax: 3415, 2990, 1703, 1595 cm－
;
1
ESI-HRMS m/z calcd for C18H19ClNO2 316.1099 (M＋),
found 316.1093. The enantiomeric ratio was determined
by HPLC on Chiralpak AS column (5/95, 2-propanol/
hexane, 0.6 mL/min), tmajor＝10.6 min, tminor＝12.2 min.
(S)-Ethyl 2-[((3,5-dichlorophenyl)amino)(phenyl)-
methyl]acrylate (3i) Compound 3i was isolated as a
t
minor＝8.0 min.
(S)-Ethyl 2-[((naphthalen-1-yl)amino)(phenyl)-
1
yellow oil, [α]D25 ＋76.8 (c 0.60, CH2Cl2), 63% ee; H
methyl]acrylate (3m) Compound 3m was isolated as
a yellow oil, [α]2D5 ＋26.3 (c 0.40, CH2Cl2), 41% ee;
1H NMR (CDCl3, 300 MHz) δ: 3.73 (s, 3H), 4.91—4.92
(d, J＝3.9 Hz, 1H), 5.62 (d, J＝4.2 Hz, 1H), 6.00 (s,
1H), 6.40 (s, 1H), 6.51 (d, J＝7.2 Hz, 1H), 7.23—7.47
(m, 9H), 7.78—7.80 (m, 2H); 13C NMR (CDCl3, 75
MHz) δ: 52.0, 59.1, 106.0, 118.0, 119.9, 123.4, 124.9,
125.8, 126.2, 126.5, 127.7, 128.0, 128.8, 128.9, 134.3,
139.6, 140.6, 141.6, 166.8; IR (KBr) νmax: 3419, 2980,
NMR (CDCl3, 300 MHz) δ: 1.21 (t, J＝7.2 Hz, 3H),
4.10—4.21 (m, 2H), 4.37 (d, J＝6.0 Hz, 1H), 5.35 (d,
J＝6.0 Hz, 1H), 5.86 (s, 1H), 6.41 (s, 1H), 6.43 (s, 2H),
6.69 (s, 1H), 7.32—7.36 (m, 5H); 13C NMR (CDCl3, 75
MHz) δ: 14.0, 58.9, 61.0, 111.6, 117.7, 126.3, 127.3,
128.1, 128.9, 135.4, 139.6, 139.7, 148.3, 165.9; IR (KBr)
－
1
νmax: 3414, 2981, 1710, 1591 cm ; ESI-HRMS m/z
calcd for C18H18Cl2NO2 350.0709 (M＋), found
350.0705. The enantiomeric ratio was determined by
HPLC on Chiralpak AS column (5/95, 2-propanol/
hexane, 0.6 mL/min), tmajor＝10.1 min, tminor＝11.4 min.
(S)-Ethyl 2-[((4-chlorophenyl)amino)(phenyl)-
methyl]acrylate (3j) Compound 3j was isolated as a
－
1
1711, 1580 cm ; ESI-HRMS m/z calcd for C21H20NO2
318.1408 (M＋), found 318.1405. The enantiomeric ratio
was determined by HPLC on Chiralpak AS column
(5/95, 2-propanol/hexane, 0.6 mL/min), tmajor＝8.9 min,
t
minor＝10.3 min.
1
yellow oil, [α]D25 ＋80.2 (c 0.46, CH2Cl2), 54% ee; H
NMR (CDCl3, 300 MHz) δ: 1.21 (t, J＝7.2 Hz, 3H),
4.10—4.20 (m, 3H), 5.34 (s, 1H), 5.88 (s, 1H), 6.38 (s,
1H), 6.49 (d, J＝8.7 Hz, 2H), 7.091 (d, J＝9.0 Hz, 2H),
7.28—7.34 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ:
14.1, 59.1, 60.9, 114.6, 122.5, 126.0, 127.5, 127.9,
128.5, 128.8, 129.0, 140.1, 140.3, 145.3, 166.1; IR (KBr)
Acknowledgement
We are grateful to National Natural Science Founda-
tion of China, Ministry of Science and Technology (No.
2010CB833300) and the Chinese Academy of Sciences
for the financial support.
－
1
νmax: 3413, 2982, 1712, 1497 cm ; ESI-HRMS m/z
calcd for C18H19ClNO2 316.1099 (M＋), found 316.1093.
The enantiomeric ratio was determined by HPLC on
Chiralpak AS column (5/95, 2-propanol/hexane, 0.6
mL/min), tmajor＝11.0 min, tminor＝12.5 min.
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2641—2646