Highly enantioselective transfer hydrogenation catalyzed by diasteromeric mixtures of axially chiral (aR,S)- and (aS,S)-Biscarbolines

Article abstract of DOI:10.1016/j.tet.2021.131924

The mixtures of axially chiral (aR,S)- and (aS,S)-biscarboline alcohols were firstly used as catalysts in enantioselective 1,2- and 1,4-transfer hydrogenations of ketimines and β-enamino esters, respectively. This mixed axially chiral catalysts exhibited

Full text of DOI:10.1016/j.tet.2021.131924

Tetrahedron 82 (2021) 131924
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Tetrahedron
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Highly enantioselective transfer hydrogenation catalyzed by
diasteromeric mixtures of axially chiral (aR,S)- and (aS,S)-Biscarbolines
,
b
,
,
b
,
,
,
, b
Mengxian Dong a 1, Xinyue Gao a 1, Ying Xiang b c, Longfei Li a b, Shengnan Li a
,
Xuxin Wang a b, Zhenqiu Li b c, Huajie Zhu a
,
,
, b, *
a College of Pharmacy, Hebei University, Baoding, 071002, PR China
b Institute of Life Science and Green Development, PR China
c College of Life Science, Hebei University, Baoding, 071002, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The mixtures of axially chiral (aR,S)- and (aS,S)-biscarboline alcohols were firstly used as catalysts in
enantioselective 1,2- and 1,4-transfer hydrogenations of ketimines and -enamino esters, respectively.
This mixed axially chiral catalysts exhibited excellent enantioselectivity (up to 98%ee) in the transfer
hydrogenations under mild reaction conditions.
Received 25 October 2020
Received in revised form
30 December 2020
Accepted 3 January 2021
Available online 23 January 2021
b
© 2021 Elsevier Ltd. All rights reserved.
Keywords:
Biscarboline
Diasteromeric mixture
NeO alcohols
Transfer hydrogenation
Enantioselectivity
1. Introduction
with HSiCl3 or ammonia borane reported recently [14a] exhibited
very good enantioselectivities catalyzed by chiral optically pure
Hundreds of chiral catalysts have been developed [1e4], for
example, axial acids (1) [5], phosphoric acids derivatives of BINOL
and BINAP (2e3) [6], spiral ligands (4) [7], including P-containing
piperazine (5) [8], Fe-, Ru-, and other ion-containing ligands (6e7),
and have been widely applied for various asymmetric reactions [9].
The combined axial structures and active NeO functionality (8-10)
have attracted many researchers’ attentions (Fig. 1) [10]. Until now,
all of the chiral catalysts reported and used in various asymmetric
reactions are optically pure [11], such as the catalysts used in
enantioselective transfer hydrogenations of ketimines with HSiCl3
to produce chiral amines [12]. Among different reactions catalyzed
by various chiral catalysts, an important asymmetric reduction led
to the synthesis of chiral calcimimetic NPS R-568, an effective drug
against hyperparathyroidism [13a,b]. Indeed, bioactive natural
products with different absolute configurations may be synthetic
ligands [14]. No doubt, to use optically pure chiral catalysts is based
on a common sense that different stereogenic catalysts can control
different transition state (TS) structure formations. These TS
structures may have different TS barriers and form products with
various absolute configurations. Few reports have shown that
mixtures of axially chiral compounds can promote asymmetric
reactions with high enantioselectivities until now.
Theoretically, if (1) two axially diastereomeric catalysts have
high enough transition state (TS) barriers, which may guarantee the
reaction to have high enantioselectivity, in catalytic procedures,
and (2) both diastereomeric ligands promote the reactions to afford
the same absolute configuration products. In this case, the mixtures
of both diastereomeric catalysts may catalyze the asymmetric re-
actions in good enantioselectivities. Indeed, it is not very easy to
obtain the optical pure chiral catalysts when chiral ligands have
close polarities. Thus, to use mixtures of the diastereogenic cata-
lysts is easy and economical in asymmetric reactions under this
situation. It brings the convenience for some researchers to use
mixtures of the diastereogenic catalysts. However, this is a chal-
lenge to find such mixtures of the diastereogenic catalysts in
experiments.
targets [13c]. Some transfer hydrogenations of b-enamino esters
* Corresponding author. College of Pharmacy, Hebei University, Baoding, 071002,
PR China.
E-mail address: zhuhuajie@hotmail.com (H. Zhu).
The authors have the equal contributions to the study.
1
https://doi.org/10.1016/j.tet.2021.131924
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

M. Dong, X. Gao, Y. Xiang et al.
Tetrahedron 82 (2021) 131924
Table 1
Effect of the different ratio of (aR,S)-11 to (aS,S)-11 on the enantioselectivity in 1,2-
transfer hydrogenations of N-(1-phenylethylidene)aniline (12).
Entry
(aR,S)-11: (aS,S)-11
Yield (%)
Ee(%)
Config.
1
2
3
4
5
6
7
8
9
10
1:5
2:5
3:5
4:5
5:5
5:4
5:3
5:2
91
89
92
91
93
90
92
92
93
90
94
93.5
95
96
94
95
94.5
92
94.5
95
S
S
S
S
S
S
S
S
S
5:1
ref.17
Fig. 1. Some typical previous effective catalysts.
Optically pure (aS,S)-11
S
2. Results and discussion
axially chiral (aR,S)-11 and (aS,S)-11 after the hydrogenations using
optically pure (aR,S)-11 as chiral catalyst was reported [17].
The mixtures of (aR,S)-11 and (aS,S)-11 were obtained with a
ratio of 4:3 after the corresponding biscarboline alcohols reacted
with m-CPBA (see SM for details) [16e]. Both could be separated by
column chromatography from each other. Thus, the effect of
different ratio of (aR,S)-11 to (aS,S)-11 on the enantioselective
transfer hydrogenations was investigated first (Table 1). Interest-
ingly, no matter what the ratio was used in experiments, the
enantioselectivities were almost in the range of 92%e96%ee
(Table 1, entries 1 to 9).
These good results encouraged us to investigate the enantiose-
lectivities of 1,2-transfer hydrogenations using other ketimines
catalyzed by the mixtures of (aR,S)-11 and (aS,S)-11. Other thirteen
ketimines were synthesized and used in the 1,2-transfer hydroge-
nations. As the expected, the enantioselectivities reached high up
to 98%ee when substrates 19 and 20 were used (Table 2, entries 8
and 9). The lowest enantioselectivity was 91%ee (Table 2, entries 13
The asymmetric transfer hydrogenations have successfully
attracted many researchers’ attentions [15], including their uses in
drug syntheses [13]. In our series of study of biscarboline ligands
derived from L-tryptophane, we synthesized some derivatives and
successfully achieved high enantioselectivities in reactions using
these derivatives as chiral catalysts [16]. In our recent report,
optically pure chiral catalyst (aR,S)-11 exhibited excellent enan-
tioselectivity in the 1,2- and 1,4-transfer hydrogenations of keti-
mines and b-enamino esters, respectively [17]. In the study, the
predicted TS barriers showed that both catalysts, (aR,S)-11 and
(aS,S)-11, had relatively high barriers: 1.211 and 1.112 kcal/mol, at
the B3LYP/6e311þþG(2d,p) level (Fig. 2B and C). Importantly, it is
predicted that both (aR,S)-11 and (aS,S)-11 may catalyze the re-
actions to afford (S)-product with 87.7%ee and 88.5%ee, theoreti-
cally. Thus, this matches the two key conditions to use mixtures as
chiral catalysts to afford high %ee values mentioned above.
In our initial tests, high up to 95% enantioselectivity was
recorded in the 1,2-transfer hydrogenations of N-(1-
phenylethylidene)aniline using (aS,S)-11. This 95%ee is very close
to 93%ee catalyzed by (aR,S)-11. Therefore, the questions emerged:
did the high enantioselectivity achieved just happened occasionally
using this specific substrate? Could it be widely applied for other
substrates? It may be a good chance to study the diastereomeric
mixtures of both (aR,S)-11 and (aS,S)-11 as catalysts in the transfer
hydrogenations. In view of this point, we performed the transfer
hydrogenations using the mixtures of axially chiral (aR,S)-11 and
(aS,S)-11, also the optically pure (aR,S)-11 as chiral catalysts,
Table 2
Enantioselectivity in 1,2-transfer hydrogenations of ketimines using the mixtures of
(aR,S)-11 and (aS,S)-11 (nearly 4:3).
respectively. The same ketimines and b-enamino esters were used
in the hydrogenations using both mixtures and optically pure
(aR,S)-11. Here we report the hydrogenations using mixtures of
Entry Comp. R [1], R2, R3
Prod. Yield (%) Ee (%) Config
1
12
13
14
15
16
17
18
19
20
21
22
23
24
25
Ph, Ph, Me
26
27
28
29
30
31
32
33
34
35
36
37
38
90
91
90
91
90
90
92
93
94
90
91
92
89
90
95
93
95
94
93
92
93
98
98
92
94
95
91
91
S
S
S
S
R
R
S
S
S
R
S
R
S
S
2
3
4
5
6
7
8
9
10
11
12
13
14
4-F-Ph,Ph, Me
4-Cl-Ph,Ph, Me
4-Br-Ph, Ph, Me
4-NO2-Ph,Ph,Me
4-Me-Ph, Ph, Me
4-MeO-Ph,Ph,Me
Ph, 4-MeO-Ph, Me
Ph, 4-EtO-Ph, Me
Ph, 4-Me-Ph, Me
Ph, 4- Et-Ph, Me
Ph, 4-Br-Ph, Me
Ph, Ph, Et
Fig. 2. (A) Axially chiral biscarboline alcohols (aR,S)-11 and (aS,S)-11. (B) and (C) Two
TS structures and their catalytic activation energy in 1,2-transfer hydrogenations of N-
(1-phenylethylidene)aniline and the predicted %ee values. Plots B and C are copied
from Ref.17 and modified here.
4-MeO-Ph,4-MeO-Ph,Me 39
2

M. Dong, X. Gao, Y. Xiang et al.
Tetrahedron 82 (2021) 131924
achieved. This result gives us a clue that some diastereogenic
mixtures may be directly used in asymmetric reactions without
further isolations economically.
4. Experimental
All reactions were carried out in oven-dried glassware and were
allowed to proceed under a dried argon atmosphere with magnetic
stirring. All solvents for the reactions were of reagent grade and
were dried and distilled before use (dichloromethane from calcium
hydride, DMF were stored with 4 Å MS). Thin layer chromatography
was performed on TLC plates (GF254). Flash column chromatog-
raphy was performed with silica gel (300e400 mesh). Enantio-
meric excess was determined using chiral HPLC. Concentration unit
Fig. 3. The structures of 16 b-enamino esters (40 to 50).
for [a]D is g/100 mL.
Table 3
Enantioselectivities of sixteen b-enamino esters in 1,4-transfer hydrogenations us-
ing the mixtures of (aR,S)-11 and (aS,S)-11 with a ratio of 4:3.
4.1. Synthesis of chiral catalyst 11
3-Chloroperoxybenzoic acid (4e8 equiv.) was added slowly to
the anhydrous dichloromethane (60 mL) of intermediate 9,90-
dimethyl-9H,
90H-[1,10-bipyrido[3,4-b]indole]-3,30-dicarboxylic
acid (300 mg) in dichloromethane at room temperature. The so-
lution was stirred for 10e32 h. The aqueous saturated solution of
NaHCO3 was added to quench the reaction at 0 ꢀC after the reaction
finished by TLC analysis. The organic phase was separated from
water and the aqueous phase was then extracted three times with
dichloromethane. The combined organic layers were washed with
brine (15 ꢁ 3 mL) and dried over anhydrous Na2SO4. The solvent
was evaporated under reduced pressure. Yellow products (aR,S)-11
and (aS,S)-11 were obtained by column chromatography or plate
chromatgraphy first. The isolated ratio was 4:3. Both were used to
prepare mixture of (aR,S)-11 and (aS,S)-11 with different ratio (1:5
to 5:1) for catalystic reactions. Fianlly, the mixture of (aR,S)-11 and
(aS,S)-11 were obtained by column chromatography and directly
used in hydrogenations.
Entry
Comp.
R [1], R2
Prod.
Yield (%)
Ee (%)
Config.
1
2
3
4
5
6
7
8
40
41
42
43
44
45
46
47
48
49
50
Ph, Ph
51
52
53
54
55
56
57
58
59
60
61
90
91
89
91
91
90
95
95
89
92
92
96
95
92
95
96
92
92
92
91
97
96
S
S
S
S
S
S
S
S
S
S
S
Ph, 4-Br-Ph
Ph, 4-Me-Ph
Ph, 4-Et-Ph
Ph, 4-MeO-Ph
Ph, -Bn, Ph
4-F-Ph, Ph,
4-Cl-Ph, Ph
4-Br-Ph, Ph
4-Me-Ph, Ph
4-MeO-Ph, Ph
9
10
11
(aS,S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-
carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-
and 14). Most of the %ee values recorded in the 1,2-transfer hy-
drogenations are slightly smaller than those catalyzed by the single
optically pure (aR,S)-11 under similar reaction conditions [17].
That the high enantioselectivities obtained in the 1,2-transfer
hydrogenations of ketimines may not hint the mixtures can be
successfully used in 1,4-transfer hydrogenations with high %ee
oxide ((aS,S)-11): yield of 31%, [
a
]
¼ ꢂ52.2 (c 0.36, CH2Cl2), HR-
D
MS-ESI m/z calcd for C38H40N6O5, [MþNa]þ 655.2639, found:
655.2618. 1H NMR (600 MHz, CDCl3)
d 8.27 (s, 1 H, ArCH), 8.12 (m,
1H, ArCH), 8.07 (m, 2 H, ArCH), 7.61e7.58 (m, 2 H, ArCH), 7.37 (dd,
J ¼ 7.2, 4.0 Hz, 4 H, ArCH), 3.96 (dd, J ¼ 20.6, 12.6 Hz, 2 H, CH), 3.83
(dd, J ¼ 12.4, 7.6 Hz, 4 H, CH2), 3.73e3.55 (m, 4 H, CH2), 3.54 (s, 6 H,
CH3), 2.18e2.02 (m, 4 H, CH2), 2.01e1.89 (m, 4 H, CH2). 13C NMR
values since the
b-enamino esters have larger steric hinderance
than the ketimines. The steric hinderance of substrates may lead to
higher TS barriers when using the diastereomeric mixtures. Thus,
they might not promote the enantioselective reactions with high
(151 MHz, CDCl3)
d 171.52 (CO), 166.55 (CO), 158.89 (ArC), 155.99
(ArC), 143.79 (ArC), 143.75 (2 ꢁ ArCH), 143.00 (ArC), 140.13 (ArC),
129.84 (ArC), 129.14 (2 ꢁ ArCH), 126.37 (ArCH), 121.79 (2 ꢁ ArCH),
120.96 (2 ꢁ ArCH), 120.00 (2 ꢁ ArCH), 114.14 (ArCH), 109.68
(2 ꢁ ArCH), 106.93 (2 ꢁ ArCH), 68.02 (CH), 63.71 (CH2), 53.43 (CH2),
32.00 (CH3), 27.70 (CH2), 21.69 (CH2).
enantioselectivities. Thus, further total 16 b-enamino esters (40 to
50) were used in the 1,4-transfer hydrogenations and the %ee
values were examined. The enantioselectivities reached high up to
97% in the 1,4-transfer hydrogenations. The specific substrate
structures are illustrated below (Fig. 3).
The catalyst mixtures exhibited very high enantioselectivities
from 90%ee to 97%ee in the 1,4-transfer hydrogenations using
eleven substrates 40e50 (Table 3).
(aR,S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-
carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-
oxide ((aR,S)-11), yield of 23%, [
a
]
¼ þ30.2 (c 0.35, CH2Cl2), HR-
D
MS-ESI m/z calcd for C38H40N6O5, [MþNa]þ 655.2639, found:
655.2621. 1H NMR (600 MHz, CDCl3)
d 9.10 (s,1 H, ArCH), 8.36 (s,1H,
ArCH), 8.17 (d, J ¼ 7.6 Hz, 2 H, ArCH), 7.60 (m, 2 H, ArCH), 7.36 (m,
4 H), 3.95 (dd, J ¼ 9.2, 5.5 Hz, 4 H, CH2), 3.69 (m, 2 H, CH), 3.66e3.58
(m, 4 H, CH2), 3.26 (s, 6 H, CH3), 1.75 (dd, J ¼ 11.6, 7.9 Hz, 4 H, CH2),
3. Summary
This is the first trial to use the diastereomeric mixtures of axially
chiral biscarbolines as catalysts. The experimental results exhibited
that the mixtures of (aR,S)-11 and (aS,S)-11 can catalyze 1,2-transfer
hydrogenations of ketimines and 1,4-transfer hydrogenations of b-
enamino esters with high enantioselectivities. Total 25 substrates
were tested. Excellent enantioselectivities up to 98%ee were
1.56e1.50 (m, 4 H, CH2). 13C NMR (151 MHz, CDCl3)
d 170.75 (CO),
166.26 (CO), 157.16 (ArC), 154.50 (ArC), 145.85 (ArC), 143.05
(2 ꢁ ArCH), 140.28 (ArC), 138.29 (ArC), 129.09 (ArC), 128.52
(2 ꢁ ArCH), 127.00 (ArCH), 121.67 (2 ꢁ ArCH), 120.94 (2 ꢁ ArCH),
119.79 (2 ꢁ ArCH), 113.99 (ArCH), 109.66 (2 ꢁ ArCH), 107.66
(2 ꢁ ArCH), 68.02 (CH), 63.28 (CH2), 55.73 (CH2), 38.16 (CH3), 32.03
3

M. Dong, X. Gao, Y. Xiang et al.
Tetrahedron 82 (2021) 131924
(CH2), 26.19 (CH2).
(2 ꢁ ArCH), 124.73 (2 ꢁ ArCH), 113.90 (ArCH), 107.86 (2 ꢁ ArCH),
52.48 (CH), 23.85 (CH3).
Reductions of ketimines The ketimine (50 mg) and catalyst
(6 mg) mixture of (aS,S)-11 and (aR,S)-11 were dissolved in anhy-
drous dichloromethane (20 mL) under nitrogen atmosphere and
cooled to ꢂ10 ꢀC. Trichlorosilane (2 equiv.) was added to the so-
lution and stirred at ꢂ10 ꢀC. After 24 h later, aqueous saturated
solution of NaHCO3 was added to quench the reaction after the
reaction finished that was checked by TLC. The organic layer was
separated from water and the aqueous phase was extracted with
dichloromethane (15 ꢁ 3 mL). The combined organic layers were
washed with brine (15 ꢁ 3 mL), and dried over anhydrous Na2SO4.
The solvent was evaporated under vacuum. The product was ob-
tained by column chromatography. These reactions were per-
formed using both of the mixtures of (aR,S)-11 and (aS,S)-11 and
optically pure (aR,S)-11, respectively, in a same low temperature
equipment [17]. By checking with the TLC, the Rf values of the re-
action products catalyzed by the either mixture of (aR,S)-11 and
(aS,S)-11 or the optically pure 11 were the same. Chiral HPLC
analysis for racemic products and the products indicated that the
retention times are almost the same. The optical rotation (OR)
values are almost the same with the reports and the OR signs for all
products are the same with the reports too [17]. All results
confirmed that the products catalyzed by either mixture of (aR,S)-
11 and (aS,S)-11 or the optically pure (aR,S)-11 are the same.
(S)eN-(1-phenylethyl)aniline (26): Light yellow viscous, yield
(R)-N-(1-(p-tolyl)ethyl)aniline (31): Light yellow oil, yield of
90%, 92% ee, [
a
]
¼ þ13.3 (c 0.055, EtOH). 1H NMR (600 MHz, CDCl3)
D
d
7.15 (d, J ¼ 7.2 Hz, 2 H, ArCH), 7.03 (t, J ¼ 7.4 Hz, 2 H, ArCH), 7.00
(m, 2 H, ArCH), 6.57e6.54 (m, 1 H, ArCH), 6.44e6.42 (m, 2 H, ArCH),
4.37 (q, J ¼ 6.7 Hz, 1 H, CH), 3.87 (s, 1 H, NH), 2.22 (s, 3 H, CH3), 1.40
(d, J ¼ 6.7 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d 147.45 (ArC),
142.31 (ArC), 136.45 (ArC), 129.39 (2 ꢁ ArCH), 129.16 (2 ꢁ ArCH),
125.84 (2 ꢁ ArCH), 117.24 (ArCH), 113.37 (2 ꢁ ArCH), 53.21 (CH),
25.07 (CH3), 21.13 (CH3).
(S)eN-(1-(4-methoxyphenyl)ethyl)aniline (32): Light yellow
oil, yield of 92%, 92%ee, [
(600 MHz, CDCl3)
a
]
¼ ꢂ14.9 (c 0.039, EtOH). 1H NMR
D
d
7.21e7.18 (m, 2 H, ArCH), 7.01 (t, J ¼ 7.0 Hz, 2H,
ArCH), 6.78 (d, J ¼ 8.0 Hz, 2 H, ArCH), 6.57 (d, J ¼ 6.8 Hz, 1 H, ArCH),
6.44 (d, J ¼ 7.6 Hz, 2 H, ArCH), 4.37 (d, J ¼ 6.2 Hz, 1 H, CH), 4.19 (s,
1 H, NH), 3.71 (s, 3 H, CH3), 1.42 (d, J ¼ 6.2 Hz, 3 H, CH3). 13C NMR
(151 MHz, CDCl3)
d 157.54 (ArC), 146.39 (ArC), 136.30 (ArC), 128.07
(2 ꢁ ArCH), 125.90 (2 ꢁ ArCH), 116.21 (ArCH), 113.04 (2 ꢁ ArCH),
112.37 (2 ꢁ ArCH), 54.25 (CH), 51.86 (CH3), 23.91 (CH3).
(S)-4-methoxy-N-(1-phenylethyl)aniline (33): Light yellow oil,
yield of 93%, 98% ee, [
CDCl3)
a
]
¼ ꢂ7.5 (c 0.05, EtOH). 1H NMR (600 MHz,
D
d
7.28 (d, J ¼ 7.6 Hz, 2 H, ArCH), 7.23 (t, J ¼ 7.5 Hz, 2 H, ArCH),
7.14 (t, J ¼ 7.2 Hz, 1 H, ArCH), 6.61 (d, J ¼ 8.8 Hz, 2 H, ArCH), 6.39 (d,
J ¼ 8.8 Hz, 2 H, ArCH), 4.33 (q, J ¼ 6.7 Hz, 1 H, CH), 3.61 (s, 3 H, CH3),
of 90%, 95%ee, [
CDCl3)
a
]
¼ ꢂ13.1 (c 0.45, EtOH). 1H NMR (600 MHz,
1.42 (d, J ¼ 6.7 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d 151.01
D
d
7.29 (d, J ¼ 5.5 Hz, 3 H, ArCH), 7.24 (t, J ¼ 7.6 Hz, 2 H, ArCH),
(ArC), 144.44 (ArC), 140.52 (ArC), 127.58 (2 ꢁ ArCH), 125.81
(2 ꢁ ArCH), 124.90 (ArCH), 113.80 (2 ꢁ ArCH), 113.65 (2 ꢁ ArCH),
54.74 (CH), 53.33 (CH3), 24.01 (CH3).
7.05e7.01 (m, 2 H, ArCH), 6.56 (t, J ¼ 7.3 Hz, 1 H, ArCH), 6.44 (d,
J ¼ 8.1 Hz, 2 H, ArCH), 4.41 (q, J ¼ 6.7 Hz, 1 H, CH), 1.44 (d, J ¼ 6.7 Hz,
3 H, CH3). 13C NMR (151 MHz, CDCl3)
d
147.31 (ArC), 145.24 (ArC)
(S)-4-ethoxy-N-(1-phenylethyl)aniline(34): Light yellow oil,
129.08 (2 ꢁ ArCH), 128.79 (2 ꢁ ArCH), 128.61 (2 ꢁ ArCH), 125.90
(ArCH), 122.22 (ArCH), 113.32 (2 ꢁ ArCH), 65.54 (CH), 19.18 (CH3).
(S)eN-(1-(4-fluorophenyl)ethyl)aniline (27): Light yellow
yield of 94%, 98%ee, [
a
]
¼ ꢂ18.3 (c 0.035, EtOH). 1H NMR
D
(600 MHz, CDCl3)
d
7.29 (d, J ¼ 7.6 Hz, 2 H, ArCH), 7.23 (t, J ¼ 7.6 Hz,
2 H, ArCH), 7.14 (t, J ¼ 7.3 Hz, 1 H, ArCH), 6.61 (d, J ¼ 8.9 Hz, 2 H,
ArCH), 6.45 (d, J ¼ 8.5 Hz, 2 H, ArCH), 4.34 (q, J ¼ 6.7 Hz, 1 H, CH),
3.83 (q, J ¼ 7.0 Hz, 2 H, CH2), 1.46 (d, J ¼ 6.7 Hz, 3 H, CH3), 1.26 (t,
viscous, yield of 91%, 93%ee, [
(600 MHz, CDCl3)
a
]
¼ ꢂ18.2 (c 0.055, EtOH). 1H NMR
D
d
7.24 (dd, J ¼ 8.2, 5.6 Hz, 2 H, ArCH), 7.01 (t,
J ¼ 7.8 Hz, 2 H, ArCH), 6.91 (t, J ¼ 8.6 Hz, 2 H, ArCH), 6.57 (t,
J ¼ 7.3 Hz, 1 H, ArCH), 6.40 (d, J ¼ 8.0 Hz, 2 H, ArCH), 4.38 (q,
J ¼ 7.0 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d 151.78 (ArC),
144.80 (ArC), 140.85 (ArC), 128.58 (2 ꢁ ArCH), 126.95 (2 ꢁ ArCH),
126.12 (2 ꢁ ArCH), 115.62 (ArCH), 114.38 (2 ꢁ ArCH), 64.04 (CH),
55.03 (CH3), 14.96 (CH2), 8.61 (CH3).
J ¼ 6.7 Hz,1 H, CH), 3.90 (s, 1 H, NH),1.40 (d, J ¼ 6.7 Hz, 3 H, CH3). 13
C
NMR (151 MHz, CDCl3)
d 160.99 (ArC), 147.14 (ArC), 140.92 (ArC),
129.15 (2 ꢁ ArCH), 127.37 (2 ꢁ ArCH), 117.48 (ArC), 115.37
(R)-4-methyl-N-(1-phenylethyl)aniline (35): Light yellow oil,
(2 ꢁ ArCH), 113.38 (2 ꢁ ArCH), 52.93 (CH), 25.13 (CH3).
yield of 90%, 92%ee, [
(600 MHz, CDCl3)
a
]
¼ þ10.2 (c 0.035, EtOH). 1H NMR
D
(S)eN-(1-(4-chlorophenyl)ethyl)aniline (28): Yellow viscous,
d
7.28 (d, J ¼ 7.4 Hz, 2 H, ArCH), 7.23 (t, J ¼ 7.6 Hz,
yield of 90%, 95% ee, [
CDCl3)
a
]
¼ ꢂ13.0 (c 0.05, EtOH). 1H NMR (600 MHz,
2 H, ArCH), 7.14 (dd, J ¼ 12.5, 5.2 Hz, 1 H, ArCH), 6.82 (d, J ¼ 8.1 Hz,
2 H, ArCH), 6.35 (d, J ¼ 8.3 Hz, 2 H, ArCH), 4.37 (q, J ¼ 6.7 Hz, 1 H,
CH), 2.10 (s, 3 H, CH3), 1.42 (d, J ¼ 6.7 Hz, 3 H, CH3). 13C NMR
D
d
7.20e7.15 (t, J ¼ 7.6 Hz, 4 H, ArCH), 6.99 (m, 2H, ArCH),
6.58e6.53 (m, 1 H, ArCH), 6.39e6.35 (d, J ¼ 8.3 Hz, 2H, ArCH),
4.35e4.31 (q, J ¼ 6.7 Hz, 1 H, CH), 1.36 (d, J ¼ 6.7 Hz, 3H, CH3). 13
C
(151 MHz, CDCl3)
d
144.40 (ArC), 144.00 (ArC), 128.56 (2 ꢁ ArCH),
NMR (151 MHz, CDCl3)
d
147.08 (ArC), 143.93 (ArC), 132.47 (ArC),
127.57 (ArC), 125.76 (2 ꢁ ArCH), 125.36 (2 ꢁ ArCH), 124.84 (ArCH),
129.23 (2 ꢁ ArCH), 128.87 (2 ꢁ ArCH), 127.34 (2 ꢁ ArCH), 117.60
112.43 (2 ꢁ ArCH), 52.67 (CH), 23.98 (CH3), 19.30 (CH3).
(ArCH), 113.42 (2 ꢁ ArCH), 53.04 (CH), 25.12 (CH3).
(S)-4-ethyl-N-(1-phenylethyl)aniline (36): Light yellow oil,
(S)eN-(1-(4-bromophenyl)ethyl)aniline (29): Light yellow oil,
yield of 91%, 94%ee, [
CDCl3)
a
]
¼ ꢂ8.0 (c 0.042, EtOH). 1H NMR (600 MHz,
D
yield of 91%, 94% ee, [
a
]
¼ ꢂ18.0 (c 0.046, EtOH). 1H NMR
d
7.26 (d, J ¼ 7.6 Hz, 2 H, ArCH), 7.20 (t, J ¼ 7.5 Hz, 2 H, ArCH),
D
(600 MHz, CDCl3)
d
7.43 (d, J ¼ 8.4 Hz, 2 H, ArCH), 7.24 (d, J ¼ 8.6 Hz,
7.11 (t, J ¼ 7.2 Hz, 1 H, ArCH), 6.83 (d, J ¼ 8.2 Hz, 2 H, ArCH), 6.36 (d,
J ¼ 8.3 Hz, 2 H, ArCH), 4.35 (q, J ¼ 6.7 Hz, 1 H, CH), 3.77 (s, 1 H, NH),
2.39 (q, J ¼ 7.6 Hz, 2 H, CH2), 1.39 (d, J ¼ 6.7 Hz, 3 H, CH3), 1.05 (t,
2 H, ArCH), 7.09 (dd, J ¼ 8.4, 7.5 Hz, 2 H, ArCH), 6.65 (t, J ¼ 7.3 Hz,1 H,
ArCH), 6.47 (d, J ¼ 7.7 Hz, 2 H, ArCH), 4.43 (q, J ¼ 6.7 Hz, 1 H, CH2),
1.48 (d, J ¼ 6.7 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d
146.96
J ¼ 7.6 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d 144.48 (ArC),
(ArC), 144.38 (ArC), 131.75 (2 ꢁ ArCH), 129.15 (2 ꢁ ArCH), 127.64
(2 ꢁ ArCH), 120.49 (ArC), 117.55 (ArCH), 113.32 (2 ꢁ ArCH), 53.06
(CH), 25.05 (CH3).
144.27 (ArC), 131.98 (ArC), 127.56 (2 ꢁ ArCH), 127.37 (2 ꢁ ArCH),
125.76 (2 ꢁ ArCH), 124.85 (ArCH), 112.40 (2 ꢁ ArCH), 52.70 (CH),
26.84 (CH2), 23.96 (CH3), 14.79 (CH3).
(R)-N-(1-(4-nitrophenyl)ethyl)aniline (30): Light yellow oil,
(R)-4-bromo-N-(1-phenylethyl)aniline(37): Light yellow oil,
yield of 90%, 93%ee, [
(600 MHz, CDCl3)
a
]
¼ þ18.3 (c 0.039, EtOH). 1H NMR
yield of 92%, 95% ee, [
a
]
¼ þ31.3 (c 0.026, EtOH). 1H NMR
D
D
d
7.22 (dd, J ¼ 9.0, 5.2 Hz, 4 H, ArCH), 7.13 (dt,
(600 MHz, CDCl3)
d
7.25e7.21 (m, 4 H, ArCH), 7.14 (dt, J ¼ 8.5, 2.9 Hz,
J ¼ 5.8, 2.5 Hz, 1 H, ArCH), 7.05 (d, J ¼ 8.8 Hz, 2 H, ArCH), 6.27 (d,
1 H, ArCH), 7.06 (d, J ¼ 8.8 Hz, 2 H, ArCH), 6.28 (d, J ¼ 8.8 Hz, 2 H,
J ¼ 8.8 Hz, 2 H, ArCH), 4.33 (q, J ¼ 6.7 Hz, 1 H, CH), 3.94 (s, 1 H, NH),
ArCH), 4.33 (q, J ¼ 6.7 Hz, 1 H, CH2), 3.95 (s, 1 H, NH), 1.41 (d,
1.40 (d, J ¼ 6.7 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d
145.19
J ¼ 6.7 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d 145.15 (ArC),
(ArC), 143.60 (ArC), 130.75 (ArC), 127.69 (2 ꢁ ArCH), 126.01
143.57 (ArC), 130.73 (2 ꢁ ArCH), 127.68 (2 ꢁ ArCH), 126.00
4

M. Dong, X. Gao, Y. Xiang et al.
Tetrahedron 82 (2021) 131924
(2 ꢁ ArCH), 124.71 (ArCH), 113.87 (ArC), 107.76 (2 ꢁ ArCH), 52.45
(CH), 23.88 (CH3).
J ¼ 6.7 Hz, 1 H, CH), 4.02 (qd, J ¼ 7.1, 4.7 Hz, 2 H, CH2), 2.73e2.68 (m,
2 H, CH2), 2.10 (s, 3 H, CH3), 1.10 (t, J ¼ 7.1 Hz, 3 H, CH3). 13C NMR
(S)eN-(1-phenylpropyl)aniline(38): Light yellow oil, yield of
(151 MHz, CDCl3) d 171.21 (CO), 144.56 (ArC), 142.38 (ArC), 129.65
89%, 91% ee, [
a
]
¼ ꢂ47.2 (c 0.01, EtOH). 1H NMR (600 MHz, CDCl3)
(2 ꢁ ArCH), 128.73 (ArC), 127.38 (2 ꢁ ArCH), 126.97 (2 ꢁ ArCH),
126.30 (ArC), 113.87 (2 ꢁ ArCH), 60.76 (CH2), 55.31 (CH), 42.96
(CH2), 20.31 (CH3), 14.15 (CH3).
D
d
7.25 (dt, J ¼ 15.0, 7.5 Hz, 4 H, ArCH), 7.15 (t, J ¼ 6.9 Hz, 1 H, ArCH),
7.00 (t, J ¼ 7.9 Hz, 2 H, ArCH), 6.55 (t, J ¼ 7.3 Hz, 1 H, ArCH), 6.44 (d,
J ¼ 7.8 Hz, 2 H, ArCH), 4.15 (t, J ¼ 6.7 Hz, 1 H, CH), 3.67 (s, 1 H, NH),
1.75 (m, 2 H, CH2), 0.88 (t, J ¼ 7.4 Hz, 3 H, CH3). 13C NMR (151 MHz,
(S)-Ethyl 3-((4-ethylphenyl)amino)-3-phenylpropanoate(54):
Light yellow solid, yield of 91%, 95%ee, [
a
]
¼ ꢂ10.4 (c 0.45, CH2Cl2),
D
CDCl3)
d
146.51 (ArC), 142.91 (ArC), 128.05 (2 ꢁ ArCH), 127.47
HR-MS-ESI m/z calcd for C19H23NO2, [MþNa]þ 320.1621, found:
(2 ꢁ ArCH), 125.85 (2 ꢁ ArCH), 125.46 (ArCH), 116.10 (ArCH), 112.22
320.1611. 1H NMR (600 MHz, CDCl3)
d
7.29 (d, J ¼ 7.4 Hz, 2 H, ArCH),
(2 ꢁ ArCH), 58.71 (CH), 30.64 (CH2), 9.79 (CH3).
7.22 (t, J ¼ 7.6 Hz, 2 H, ArCH), 7.14 (t, J ¼ 7.3 Hz, 1 H, ArCH), 6.85 (d,
J ¼ 8.3 Hz, 2 H, ArCH), 6.42 (d, J ¼ 8.4 Hz, 2 H, ArCH), 4.71 (t,
J ¼ 6.7 Hz, 1 H, CH), 4.03e3.97 (m, 2 H, CH2), 2.69 (dd, J ¼ 7.9, 6.4 Hz,
2 H, CH2), 2.40 (q, J ¼ 7.6 Hz, 2 H, CH2), 1.09 (t, J ¼ 7.1 Hz, 3 H, CH3),
(S)-4-methoxy-N-(1-(4-methoxyphenyl)ethyl)aniline(39):
Light yellow oil, yield of 90%, 91% ee, [
a
]
¼ þ18.3 (c 0.016, EtOH).
D
1H NMR (600 MHz, CDCl3)
d
7.11 (dd, J ¼ 13.9, 7.7 Hz, 3 H, ArCH),
7.04 (t, J ¼ 7.6 Hz, 2 H, ArCH), 6.86e6.83 (m, 1 H, ArCH), 6.81 (d,
J ¼ 7.2 Hz, 2 H, ArCH), 4.12 (q, J ¼ 6.7 Hz, 1 H, CH), 2.09 (s, 6H, CH3),
1.06 (t, J ¼ 7.6 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d 171.22
(CO), 144.81 (ArC), 142.51 (ArC), 133.58 (2 ꢁ ArCH), 128.75 (ArC),
128.48 (2 ꢁ ArCH), 127.40 (2 ꢁ ArCH), 126.33 (ArC), 113.84
(2 ꢁ ArCH), 60.77 (CH2), 55.35 (CH), 43.01 (CH2), 27.91 (CH2), 15.86
(CH3), 14.17 (CH3).
1.24 (t, J ¼ 6.7 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d 162.51
(ArC), 154.84 (ArC), 144.11 (ArC), 138.72 (ArC), 129.57 (2 ꢁ ArCH),
119.85 (2 ꢁ ArCH), 113.26 (2 ꢁ ArCH), 112.70 (2 ꢁ ArCH), 62.20 (CH),
54.45 (CH3), 50.42 (CH3), 25.27 (CH3).
(S)-Ethyl 3-(benzylamino)-3-phenylpropanoate(56): Light
yellow solid, yield of 90%, 92%ee, [
a
]
¼ þ27.3 (c 0.47, CH2Cl2), HR-
D
4.2. Reduction of
b-enamino esters
MS-ESI m/z calcd for
C
18H21NO2, [MþNa]þ 306.1465, found:
306.1456. 1H NMR (600 MHz, CDCl3)
d 7.30e7.16 (m, 10 H), 4.60 (t,
b
-Keto ester (50 mg), catalyst mixture 11 (6 mg) were dissolved
J ¼ 6.4 Hz, 1 H, CH), 4.19 (d, J ¼ 6.4 Hz, 2 H, CH2), 4.10e4.06 (m, 2 H,
in anhydrous dichloromethane (30 mL). The mixture was stirred
until it completely dissolved at room temperature. The solution was
then cooled to ꢂ10 ꢀC. Trichlorosilane (2 equiv.) was added into the
solution and it was stirred at ꢂ10 ꢀC for 24 h. The reaction was
quenched with saturated solution of NaHCO3 after reaction finished
checked by TLC. The organic layer was separated from the aqueous
phase and the aqueous layer was extracted by dichloromethane
(15 ꢁ 3 mL). The combined organic layers were washed with brine
(15 ꢁ 3 mL) and dried over anhydrous Na2SO4. The solvent was
evaporated under reduced pressure. White material was obtained
by column chromatography.
CH2), 1.20 (t, J ¼ 7.1 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d
169.36 (CO), 138.26 (ArC), 135.00 (ArC), 128.23 (2 ꢁ ArCH), 127.59
(2 ꢁ ArCH), 127.36 (2 ꢁ ArCH), 126.89 (2 ꢁ ArCH), 125.87
(2 ꢁ ArCH), 60.45 (CH2), 57.76 (CH), 52.38 (CH2), 47.36 (CH2), 13.57
(CH3).
(S)-ethyl
3-((4-methoxyphenyl)amino)-3-
phenylpropanoate(55): Light yellow solid, yield of 91%, 96%ee,
[
a
]
¼ ꢂ14.2 (c 0.58, CH2Cl2). HR-MS-ESI m/z calcd for C18H21NO3,
D
[MþNa]þ 322.1414, found: 322.1401. 1H NMR (600 MHz, CDCl3)
d
7.36 (d, J ¼ 7.4 Hz, 2 H, ArCH), 7.31 (t, J ¼ 7.6 Hz, 2 H, ArCH), 7.23 (t,
J ¼ 7.3 Hz, 1 H, ArCH), 6.73e6.65 (m, 2 H, ArCH), 6.52 (d, J ¼ 8.9 Hz,
2 H, ArCH), 4.74 (t, J ¼ 6.7 Hz, 1 H, CH), 4.10 (m, 2 H, CH2), 3.69 (s,
3 H, CH3), 2.78 (d, J ¼ 6.7 Hz, 2 H, CH2), 1.19 (t, J ¼ 7.1 Hz, 3 H, CH3).
(S)-Ethyl 3-phenyl-3-(phenylamino)propanoate(51)：Light
yellow solid, yield of 90%, 96% ee, [
a
]
¼ ꢂ1.8 (c 0.55, CH2Cl2), HR-
D
MS-ESI m/z calcd for
C
17H19NO2, [MþNa]þ 292.1308, found:
13C NMR (151 MHz, CDCl3)
d 170.23 (CO), 151.38 (ArC), 141.37 (ArC),
292.1298. 1H NMR (600 MHz, CDCl3)
d
7.30 (d, J ¼ 7.4 Hz, 2 H, ArCH),
139.90 (ArC), 127.70 (2 ꢁ ArCH), 126.38 (2 ꢁ ArCH), 125.32 (ArCH),
114.23 (2 ꢁ ArCH), 113.75 (2 ꢁ ArCH), 59.72 (CH2), 55.04 (CH), 54.69
(CH3), 41.89 (CH2), 13.12 (CH3).
7.24 (t, J ¼ 7.6 Hz, 2 H, ArCH), 7.17e7.14 (m, 1 H, ArCH), 7.02 (dd,
J ¼ 8.4, 7.5 Hz, 2 H, ArCH), 6.62e6.57 (m, 1 H, ArCH), 6.48 (d,
J ¼ 7.8 Hz, 2 H, ArCH), 4.77e4.74 (t, J ¼ 6.1, 1 H, CH), 4.02 (pd, J ¼ 7.7,
3.7 Hz, 2 H, CH2), 2.75e2.69 (m, 2 H, CH2), 1.10 (t, J ¼ 7.1 Hz, 3 H,
(S)-Ethyl
3-(4-fluorophenyl)-3-(phenylamino)prop-
anoate(57): Light yellow solid, yield of 95%, 92%ee, [
a
]
¼ þ5.0 (c
D
CH3). 13C NMR (151 MHz, CDCl3)
d
170.13 (CO), 145.80 (ArC), 141.18
0.57, CH2Cl2), HR-MS-ESI m/z calcd for C17H18FNO2, [MþNa]þ
(ArC), 128.11 (2 ꢁ ArCH), 127.72 (2 ꢁ ArCH), 126.40 (2 ꢁ ArCH),
125.23 (ArCH), 116.74 (ArCH), 112.65 (2 ꢁ ArCH), 59.77 (CH2), 53.99
(CH), 41.90 (CH2), 13.10 (CH3).
310.1214, found: 310.1206. 1H NMR (600 MHz, CDCl3)
d 7.25 (m, 2 H,
ArCH), 7.01 (t, J ¼ 7.8 Hz, 2 H, ArCH), 6.90 (t, J ¼ 8.6 Hz, 2 H, ArCH),
6.59 (t, J ¼ 7.3 Hz, 1 H, ArCH), 6.45 (d, J ¼ 8.2 Hz, 2 H, ArCH), 4.72 (t,
J ¼ 6.6 Hz, 1 H, CH), 4.48 (t, J ¼ 6.6 Hz, 1 H, CH), 4.04e3.98 (m, 2 H,
(S)-Ethyl
3-((4-bromophenyl)amino)-3-
phenylpropanoate(52): Light yellow solid, yield of 91%, 95%ee,
CH2), 2.68 (d, J ¼ 6.6 Hz, 2 H, CH2), 1.09 (t, J ¼ 7.1 Hz, 3 H, CH3). 13
C
[
a
]
¼ þ15.0 (c 0.58, CH2Cl2), HR-MS-ESI m/z calcd for C17H18BrNO2,
NMR (151 MHz, CDCl3) d 170.93 (CO), 162.91 (ArC), 146.69 (ArC),
D
[MþNa]þ 370.0413, found: 370.0399. 1H NMR (600 MHz, CDCl3)
137.95 (ArC), 129.19 (2 ꢁ ArCH), 127.94 (2 ꢁ ArCH), 118.00 (ArCH),
115.67 (2 ꢁ ArCH), 113.76 (2 ꢁ ArCH), 60.82 (CH3), 54.44 (CH), 42.90
(CH2), 14.13 (CH3).
d
7.28e7.23 (m, 2 H, ArCH), 7.01 (t, J ¼ 7.8 Hz, 2 H, ArCH), 6.91 (t,
J ¼ 8.5 Hz, 2 H, ArCH), 6.59 (t, J ¼ 7.3 Hz, 1 H, ArCH), 6.45 (d,
J ¼ 7.8 Hz, 2 H, ArCH), 4.72 (t, J ¼ 6.5 Hz, 1 H, CH), 4.04e3.98 (m, 2 H,
CH2), 4.48 (s, 1 H, NH), 2.68 (m, 2 H, CH2), 1.09 (t, J ¼ 7.1 Hz, 3 H,
(S)-Ethyl
3-(4-chlorophenyl)-3-(phenylamino)prop-
anoate(58): Light yellow solid, yield of 95%, 92%ee, [
a
]
¼ ꢂ13.2 (c
D
CH3). 13C NMR (151 MHz, CDCl3)
d
170.94 (CO), 146.68 (ArC), 137.96
0.5, CH2Cl2), HR-MS-ESI m/z calcd for C17H18ClNO2, [MþNa]þ
(ArC), 129.19 (2 ꢁ ArCH), 127.88 (2 ꢁ ArCH), 118.00 (ArCH), 115.67
(2 ꢁ ArCH), 115.53 (ArC),113.75 (2 ꢁ ArCH), 60.83 (CH2), 54.43 (CH),
42.90 (CH2), 14.13 (CH3).
(S)-Ethyl 3-phenyl-3-(p-tolylamino)propanoate(53): Light
yellow solid, yield of 89%, 92%ee, [
326.0918, found: 326.0911. 1H NMR (600 MHz, CDCl3)
d 7.22 (dd,
J ¼ 20.1, 8.5 Hz, 4 H, ArCH), 7.02 (t, J ¼ 7.9 Hz, 2 H, ArCH), 6.60 (t,
J ¼ 7.3 Hz, 1 H, ArCH), 6.44 (d, J ¼ 7.9 Hz, 2 H, ArCH), 4.71 (t,
J ¼ 6.6 Hz, 1 H, CH), 4.50 (s, 1 H, NH) 4.05e3.99 (m, 2 H, CH2),
2.72e2.66 (m, 2 H, CH2), 1.11 (t, J ¼ 7.1 Hz, 3 H, CH3). 13C NMR
a
]
¼ ꢂ9.1 (c 0.55, CH2Cl2), HR-
D
MS-ESI m/z calcd for
C
18H21NO2, [MþNa]þ 306.1465, found:
(151 MHz, CDCl3) d 170.84 (CO), 146.57 (ArC), 140.82 (ArC), 133.13
306.1454. 1H NMR (600 MHz, CDCl3)
d
7.29 (d, J ¼ 7.6 Hz, 2 H, ArCH),
(ArC), 129.20 (2 ꢁ ArCH), 128.93 (2 ꢁ ArCH), 127.73 (2 ꢁ ArCH),
118.07 (ArCH), 113.73 (2 ꢁ ArCH), 60.89 (CH2), 54.48 (CH), 42.74
(CH2), 14.13 (CH3).
7.23 (t, J ¼ 7.6 Hz, 2 H, ArCH), 7.15 (dd, J ¼ 11.6, 4.0 Hz, 1 H, ArCH),
6.83 (d, J ¼ 8.2 Hz, 2 H, ArCH), 6.40 (d, J ¼ 8.3 Hz, 2 H, ArCH), 4.72 (t,
5

M. Dong, X. Gao, Y. Xiang et al.
Tetrahedron 82 (2021) 131924
35 (2019) 604e608;
(g) L. Peng, K. Li, C.D. Xie, S. Li, D. Xu, W.L. Qin, H.L. Yan, Angew. Chem. Int. Ed.
58 (48) (2019) 17199e17204.
(S)-Ethyl
3-(4-bromophenyl)-3-(phenylamino)prop-
anoate(59): Light yellow solid, yield of 89%, 91%ee, [
a
]
¼ ꢂ14.0 (c
D
0.65, CH2Cl2), HR-MS-ESI m/z calcd for C17H18BrNO2, [MþNa]þ
[2] For catalyst reviews, see. (a) Z. Wang, G. Chen, K.L. Ding, Chem. Rev. 109
(2009) 322e359;
370.0413, found: 370.0406. 1H NMR (600 MHz, CDCl3)
d 7.35 (d,
(b) H.J. Zhu, J.X. Jiang, J. Ren, Y.M. Yan, C.U. Pittman Jr., Curr. Org. Synth. 2
(2005) 547e587;
(c) D. Parmar, E. Sugiono, S. Raja, M. Rueping, Chem. Rev. 114 (2014)
9047e9153;
J ¼ 8.3 Hz, 2 H, ArCH), 7.19e7.16 (m, 2 H, ArCH), 7.02 (t, J ¼ 7.8 Hz,
2 H, ArCH), 6.60 (t, J ¼ 7.3 Hz, 1 H, ArCH), 6.44 (d, J ¼ 8.1 Hz, 2 H,
ArCH), 4.69 (t, J ¼ 6.6 Hz, 1 H, CH), 4.50 (s, 1 H, NH), 4.02 (qd, J ¼ 7.1,
3.1 Hz, 2 H, CH2), 2.71e2.65 (m, 2 H, CH2), 1.11 (t, J ¼ 7.1 Hz, 3 H,
(d) K. Zheng, X.H. Liu, X.M. Feng, Chem. Rev. 118 (2018) 7586e7656.
[3] For selected reviews on asymmetric reductions of imines, see:. (a) J.H. Xie,
S.F. Zhu, Q.L. Zhou, Chem. Rev. 111 (2011) 1713e1760;
(b) Q.-A. Chen, Z.S. Ye, Y. Duan, Y.G. Zhou, Chem. Soc. Rev. 42 (2013) 497e511;
(c) J.H. Schrittwieser, S. Velikogne, W. Kroutil, Adv. Catal. Synth. 357 (2015)
1655e1685.
[4] For reviews on the transition metal mediated reduction of ketimines, see:. (a)
W. Tang, X. Zhang, Chem. Rev. 103 (2003) 3029e3069;
(b) P. Roszkowski, Z. Czarnocki, Org. Chem. 4 (2007) 190e200;
(c) T.C. Nugent, M. El-Shazly, Adv. Synth. Catal. 352 (2010) 753e819;
(d) For reviews, see (a) T. Akiyama, Chem. Rev. 107 (2007) 5744e5758;
(e) M. Rueping, A. Kuenkel, I. Atodiresei, Chem. Soc. Rev. 40 (2011)
4539e4549.
[5] (a) H. Takuya, M. Keiji, J. Am, Chem. Soc. 129 (2007) 10054e10055;
(b) H.F. He, M.Q. Hou, Z.X. Zhu, Z.H. Gu, ACS Catal. 7 (2017) 5316e5320.
[6] X.F. Zeng, K.H. Ye, M. Lu, P.J. Chua, B. Tan, G.F. Zhong, Org. Lett. 12 (2010)
2414e2417.
[7] Y.P. Li, S.F. Zhu, Q.L. Zhou, Org. Lett. 21 (23) (2019) 9391e9395.
[8] T. Masahiro, S. Keiichi, Daisuke U. Synlett. 1 (2006) 133e136.
[9] (a) G.H. Hou, W. Li, M.F. Ma, X.W. Zhang, X.M. Zhang, J. Am. Chem. Soc. 132
(2010) 12844e12846;
CH3). 13C NMR (151 MHz, CDCl3)
d 169.78 (CO), 145.51 (ArC), 140.34
(ArC), 130.84 (2 ꢁ ArCH), 128.17 (2 ꢁ ArCH), 127.07 (2 ꢁ ArCH),
120.18 (ArC), 117.05 (ArCH), 112.70 (2 ꢁ ArCH), 59.87 (CH2), 53.50
(CH), 41.65 (CH2), 13.11 (CH3).
(S)-Ethyl 3-(phenylamino)-3-(p-tolyl)propanoate(60): Light
yellow solid, yield of 92%, 97%ee, [
a
]
D
¼ ꢂ15.2 (c 0.65, CH2Cl2), HR-
MS-ESI m/z calcd for
C
18H21NO2, [MþNa]þ 306.1465, found:
306.1456. 1H NMR (600 MHz, CDCl3)
d 7.17 (m, 2 H, ArCH),
7.05e6.99 (m, 4 H, ArCH), 6.57 (t, J ¼ 7.3 Hz, 1 H, ArCH), 6.47 (d,
J ¼ 7.9 Hz, 2 H, ArCH), 4.72 (t, J ¼ 6.7 Hz, 1 H, CH), 4.43 (s, 1 H, NH),
4.04e3.98 (m, 2 H, CH2), 2.71e2.68 (m, 2 H, CH2), 2.22 (s, 3 H, CH3),
1.10 (t, J ¼ 7.1 Hz, 3 H, CH3). 13C NMR (151 MHz, CDCl3)
d 170.13 (CO),
145.94 (ArC), 138.23 (ArC), 135.97 (ArC), 128.40 (2 ꢁ ArCH), 128.10
(2 ꢁ ArCH), 125.15 (2 ꢁ ArCH), 116.70 (ArCH), 112.69 (2 ꢁ ArCH),
59.68 (CH2), 53.77 (CH), 41.91 (CH2), 20.01 (CH3), 13.11 (CH3).
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63e66;
(S)-Ethyl
3-(4-methoxyphenyl)-3-(phenylamino)prop-
anoate(61): Light yellow oil, yield of 92%, 96%ee, [
a]
¼ ꢂ22.3 (c
D
0.55, CH2Cl2), HR-MS-ESI m/z calcd for C18H21NO3, [MþNa]þ
322.1414, found: 322.1407. 1H NMR (600 MHz, CDCl3)
d 7.21 (t,
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J ¼ 6.8 Hz, 2 H, ArCH), 7.02 (t, J ¼ 6.2 Hz, 2 H, ArCH), 6.77 (d,
J ¼ 6.9 Hz, 2 H, ArCH), 6.58 (t, J ¼ 6.2 Hz, 1 H, ArCH), 6.48 (d,
J ¼ 7.2 Hz, 2 H, ArCH), 4.71 (s,1 H, CH), 4.43 (s,1 H, NH), 4.02 (m, 2 H,
CH2), 3.69 (s, 3 H, CH3), 2.70 (d, J ¼ 3.9 Hz, 2 H, CH2), 1.11 (t,
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Declaration of competing interest
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Acknowledgements
The National Natural Science Foundation of China (NSFC) is
thanked for the financial supports (#21877025, #21903018). The
Key Project of Joint Medicines of Hebei Province from the Com-
mittee of Science and Technology of Hebei Province
(#H2020201029).
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Appendix A. Supplementary data
Supplementary data to this article can be found online at
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