Biomimetic reduction of imines and heteroaromatics with chiral and regenerable [2.2]Paracyclophane-Based NAD(P)H model CYNAM

Article abstract of DOI:10.1016/j.tet.2021.131968

In our previous work, we reported the synthesis of chiral and regenerable [2.2]paracyclophane-derived NAD(P)H models CYNAMs and their application in biomimetic asymmetric reduction of tetrasubstituted olefins. Herein, the biomimetic asymmetric reduction o

Full text of DOI:10.1016/j.tet.2021.131968

Tetrahedron 83 (2021) 131968
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Tetrahedron
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Biomimetic reduction of imines and heteroaromatics with chiral and
regenerable [2.2]Paracyclophane-Based NAD(P)H model CYNAM
,
,
, b, *
Zhou-Hao Zhu a c, Yi-Xuan Ding a c, Yong-Gui Zhou a
a State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
b Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, 116024, China
c University of Chinese Academy of Sciences, Beijing, 100049, China
a r t i c l e i n f o
a b s t r a c t
Article history:
In our previous work, we reported the synthesis of chiral and regenerable [2.2]paracyclophane-derived
NAD(P)H models CYNAMs and their application in biomimetic asymmetric reduction of tetrasubstituted
olefins. Herein, the biomimetic asymmetric reduction of imines and heteroaromatics has been suc-
cessfully achieved using the chiral and regenerable CYNAMs and simple achiral phosphoric acid as the
transfer catalyst, providing the chiral amines with up to 99% yield and 99% ee.
Received 1 December 2020
Received in revised form
21 January 2021
Accepted 23 January 2021
Available online 9 February 2021
© 2021 Elsevier Ltd. All rights reserved.
Keywords:
Chiral NAD(P)H Model
Biomimetic reduction
Paracyclophanes
Imines
Heteroaromatics
Simple phosphoric acid
1. Introduction
generation represented by dihydrophenanthridine (DHPD, Scheme
1a) appears, due to the good regenerability of DHPD [27e31] under
Bionics is a novel discipline that utilizes biological structures
and function principles to develop machinery or various new
technologies. Additionally, as coenzymes that transfer protons and
electrons, the reduced nicotinamide adenine dinucleotide (NADH)
and nicotinamide adenine dinucleotide phosphate (NADPH)
participate in most of the redox metabolisms of the human body,
such as citric acid cycle, glycolysis and amino acid decomposition
[1e6]. Consequently, the biomimetic method of asymmetric
transfer hydrogenation has been an important method for the
synthesis of chiral molecules and various biomimetic asymmetric
transfer hydrogenations based on coenzyme NAD(P)H have been
studied in depth rapidly [7e10]. The first generation of biomimetic
asymmetric reduction (BMAR) system is represented by Hantzsch
ester (HEH, Scheme 1a) [11e21]. But the biggest disadvantage is
that it’s hard to realize the regeneration of NAD(P)H analogue
[22e26] so that it normally needs stoichiometric NAD(P)H
analogue to participate in the reactions. When the second
hydrogen gas, the catalytic BMAR of imines and heteroaromatics
can be achieved using either a homogeneous ruthenium or iron
catalyst. However, it is still difficult to synthesize and screen chiral
organocatalysts or metal catalysts bearing complex structures,
which hinders the practicability of the reaction. Very recently, our
group has reported a new type of regenerable and planarly chiral
ferrocene-based NAD(P)H models (FENAM, Scheme 1a). Accord-
ingly, the BMAR of heteroaromatics, alkenes and imines has been
realized using bench-stable simple Lewis acids, Brønsted acids or
organic hydrogen bonding catalysts as hydrogen transfer catalysts
[32e34]. In spite of remarkable contributions, an obvious drawback
that the ferrocene skeleton is not resistant to strong Brønsted acids,
Lewis acids and oxidative condition limits the further application in
the biomimetic chemistry based on the coenzyme NAD(P)H.
In order to solve the problems above, we have designed and
synthesized a more stable, rigid and sterically hindered regenerable
and chiral [2.2]paracyclophane-based NAD(P)H models (CYNAMs,
Scheme 1a) [35]. With simple achiral Lewis acid as the hydrogen
transfer catalyst, it has been successfully applied to BMAR of tet-
rasubstituted olefins flavonoids (Scheme 1b) [35]. In order to
further investigate the application prospects of CYNAMs, we elec-
ted to pursue this model for the BMAR of imines and
* Corresponding author. State Key Laboratory of Catalysis, Dalian Institute of
Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
E-mail address: ygzhou@dicp.ac.cn (Y.-G. Zhou).
https://doi.org/10.1016/j.tet.2021.131968
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

Z.-H. Zhu, Y.-X. Ding and Y.-G. Zhou
Tetrahedron 83 (2021) 131968
Table 1
Optimization of reaction parameters.a.
Scheme 1. A new type of NAD(P)H models and application in biomimetic asymmetric
reduction (BMAR).
Entry
Solvent
Acid
Model
Conv. (%)b
Ee (%)c
1d
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
THF
EtOAc
Toluene
MeOH
1,4-Dioxane
Benzene
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
4a
4a
–
(Sp)-3a
e
<5
<5
10
94
89
11
52
67
90
20
70
85
84
82
13
94
88
>95
98e
e
e
heteroaromatics. Finally, under the bench-stable simple Brønsted
acid as the hydrogen transfer catalyst, the BMAR of imines and
heteroaromatics could be achieved concisely with high yields and
enantioselectivities (Scheme 1c).
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3a
(Sp)-3b
(Sp)-3c
(Sp)-3d
(Sp)-3d
93
98
98
72
95
98
14
83
97
98
98
98
93
99
99
99
>99
4a
4a
4a
4a
4a
4a
4a
4a
4b
4c
4d
4e
4a
4a
4a
4a
2. Results and discussion
To verify the efficiency of new planar chiral NAD(P)H models,
quinoxalinone 1a was chosen as the model substrate [36,37] for
biomimetic asymmetric reduction with commercially available
achiral diphenyl hydrogen phosphate 4a as the transfer catalyst
(Table 1).
CHCl3
CHCl3
CHCl3
First, the reduction was carried out in chloroform without
ruthenium (II) complex as the regeneration catalyst or any NAD(P)H
models CYNAMs respectively. As expected, there was no desired
product obtained (<5% conv., entry 1 and 2). However, when
ruthenium (II) complex and NAD(P)H models CYNAMs were used
but without any Brønsted acids, few desired product was obtained
in 93% ee (10% conv., entry 3). To our delight, when Brønsted acid 4a
was added, the reduction could proceed smoothly (94% conv., 98%
ee, entry 4). Then we set out to study the optimal reaction condi-
tion. In the first place, the evaluation of solvents suggested chlo-
roform was optimal with regard to enantioselectivity and reactivity
(entries 4e11). With the optimal solvent chloroform, further opti-
mization of Brønsted acids was conducted. When employing a
strong Brønsted acid (4a-4d) as the transfer catalyst, the enantio-
selectivity and reactivity could be enhanced (entries 4 and 12e14).
On the contrary, when a weak Brønsted acid (4e) was used, the
enantioselectivity and reactivity were not improved relative to the
background reaction (entries 15) documenting the significance of
acidity. Therefore, Brønsted acid 4a was chosen to be the most
suitable transfer catalyst. The reactivity and enantioselectivity
could be improved to >95% and 99% ee respectively using NAD(P)H
models CYNAMs (Sp)-3d (entries 16e18). Excellent isolated yield of
2a (0.15 mmol) was achieved by prolonging the reaction time from
22 h to 48 h (98% yield, entry 19). At length, the optimal reaction
a
Reactions were carried with 1a (0.1 mmol), [Ru (p-cymene)I2]2 (0.5 mol%), 3
(10 mol%), Acid 4 (4 mol%), Solvent (2 mL), H2 (500 psi), 40 ꢀC, 22 h.
b
Conversion was measured by analysis of 1H NMR spectra of unpurified mixtures.
Enantiomeric excess (Ee) values were determined by HPLC analysis with chiral
c
column.
d
e
[Ru (p-cymene)I2]2 was not used.
0.15 mmol scale for 48 h.
Isolated yield for the reaction with
quinoxalinones was then explored (Scheme 2). In accordance with
expectation, quinoxalinones 1 performed well under the optimized
conditions. First, the steric and electronic properties of the sub-
stituent on aryl group were investigated. Either electron-donating
or electron-withdrawing substituents on aryl group in para-posi-
tion could both achieve excellent results (2b-2d). In terms of steric
hindrance, the substituents on aryl group in meta or ortho-position
rarely influenced the reaction, resulting in high yields and enan-
tioselectivities (2e and 2f). Similarly, the benzyl and allyl sub-
stituents on the nitrogen had no effect on the reaction. Both of
excellent yields and enantioselectivities were obtained (2g and 2h).
As for the alkyl-substituted substrates, good reactivity could be
obtained (2i-2l). In addition, along with the enhancement of steric
hindrance of alkyl substituents, higher enantioselectivity could be
achieved. In addition, quinoxalinone with free NeH 1m could work
smoothly under the optimized condition as well (2m). Last but not
least, the aryl substituent on the nitrogen had no effect on the re-
action too (2n).
condition was identified:
1 (0.15 mmol), [Ru (p-cymene)I2]2
(0.5 mol%), CYNAM (Sp)-3d (10 mol%), achiral transfer catalyst
Brønsted acid 4a (4 mol%), H2 (500 psi), chloroform, 40 ꢀC and 48 h.
With the optimized conditions in hand, the substrate scope of
2

Z.-H. Zhu, Y.-X. Ding and Y.-G. Zhou
Tetrahedron 83 (2021) 131968
Scheme 3. The BMAR of other imines or heteroaromatics.
reduction comprised two cascade redox cycles promoted by two
achiral catalysts. Firstly, chiral NAD(P)H model (Sp)-CYNAM 3 could
be reduced to (Sp)-CYNAM 3-H in situ by ruthenium (II) complex
and hydrogen gas. Then, the reduced (Sp)-CYNAM 3-H could realize
enantioselective reduction of imines and heteroaromatics via co-
ordination activation in the presence of the simple and achiral
transfer catalyst Brønsted acid (Scheme 4).
3. Conclusion
In conclusion, we have successfully applied the new type of
chiral and regenerable NAD(P)H models CYNAMs based on planar-
Scheme 2. The BMAR of quinoxalinones.
Motivated by the above results, in order to further demonstrate
the practicality of this strategy, we extended the biomimetic
asymmetric reduction to other imines and heteroaromatic com-
pounds, such as benzoxazinones [38e40], benzoxazines [41e44],
alkynyl-substituted fluorinated ketimines [29,45] and hetero-
aromatic quinolines [38,46e55] (Scheme 3). Fortunately, these
imines and heteroaromatics could be well compatible with this
catalytic system. For benzoxazinones, whether it was an alkyl-
substituted or aryl-substituted substrate, good yield and excellent
enantioselectivity could be achieved (6a-6c). As the substrate of
simple benzoxazine 7, the reaction could also proceed smoothly,
finally obtaining 98% yield and 96% enantioselectivity (8). More-
over, the carbon-nitrogen double bonds of linear alkynyl-
substituted fluorinated ketimines could be selectively reduced
with superior results (10a-10c). Last but not least, after fine-tuning
the solvent, the 2-substituted heteroaromatic quinolines could also
be reduced to the corresponding tetrahydroquinoline products
with good yields and enantioselectivities (12a and 12b).
Based on the experimental results and putative mechanism of
NAD(P)H model-promoted biomimetic asymmetric reduction
[27,33], a plausible mechanism for the chiral and regenerable [2.2]
paracyclophane-based NAD(P)H model-enabled biomimetic
asymmetric reduction of imines and heteroaromatics was illus-
trated (Scheme 4). In general, this catalytic biomimetic asymmetric
Scheme 4. Proposed mechanism and transition state.
3

Z.-H. Zhu, Y.-X. Ding and Y.-G. Zhou
Tetrahedron 83 (2021) 131968
chiral [2.2]paracyclophane skeleton to biomimetic asymmetric
reduction of imines and heteroaromatics with simple and achiral
Brønsted acid as a transfer catalyst. A broad range of highly enan-
tiomerically enriched amines could be conveniently prepared with
up to 99% yield and 99% ee. Efforts are underway to expand the
applications of CYNAMs to other transformations in our laboratory.
1H), 4.04 (br s, 1H), 3.27 (s, 3H), 2.21 (s, 3H); 13C NMR (100 MHz,
CDCl3)
d 166.3, 138.1, 136.2, 134.6, 129.4, 128.4, 127.0, 123.7, 119.4,
114.8, 114.0, 60.6, 29.2, 21.1. HPLC (AD-H, elute: n-Hexane/i-
PrOH ¼ 80/20, detector: 230 nm, 30 ꢀC, flow rate: 1.0 mL/min),
t1 ¼ 11.2 min (major), t2 ¼ 15.0 min.
4.2.3. (þ)-(S)-3-(4-Methoxyphenyl)-1-methyl-3,4-
dihydroquinoxalin-2(1H)-one (2c)
4. Experimental section
37 mg, 92% yield, pale yellow solid, known compound, Rf ¼ 0.30
20
4.1. General methods
(hexanes/ethyl acetate 5/1), 98% e. e., [
a
]
¼ þ130.15 (c 0.64,
D
20
CHCl3), [lit [37].: [
a
]
¼ þ120.9 (c 0.4, CHCl3) for 90% e. e.]; 1H NMR
D
All reactions were carried out under an atmosphere of nitrogen
gas using the standard Schlenk techniques, unless otherwise noted.
Commercially available reagents were used without further puri-
fication. Solvents were treated prior to use according to the stan-
dard methods. 1H NMR, 13C NMR spectra were recorded at 400 MHz
and 100 MHz with Brucker spectrometer. 19F was recorded at
376 MHz with Brucker spectrometer. Chemical shifts are reported
in ppm using tetramethylsilane (0) as internal standard when using
CDCl3 as solvent for 1H NMR spectra. The following abbreviations
were used to symbolize the multiplicities: s ¼ singlet, d ¼ doublet,
t ¼ triplet, q ¼ quartet, m ¼ multiplet, br ¼ broad. Flash column
chromatography was performed on silica gel (200e300 mesh). All
reactions were monitored by TLC analysis. Optical rotations were
measured by polarimeter. Enantiomeric excess was determined by
HPLC analysis using chiral column described below in detail. The
NADPH Models CYNAMs 3a-3d could be synthesized according to
the known literature procedure [35]. All Brønsted acids were
commercially available and could be used without further
purification.
(400 MHz, CDCl3) d 7.21e7.16 (m, 2H), 6.90e6.82 (m, 2H), 6.80e6.70
(m, 3H), 6.64 (dd, J ¼ 7.5,1.1 Hz,1H), 4.89 (s,1H), 3.67 (s, 3H), 3.29 (s,
3H); 13C NMR (100 MHz, CDCl3)
166.4, 159.6, 134.6, 131.2, 128.4,
128.4, 123.7, 119.5, 114.8, 114.1, 114.0, 60.3, 55.3, 29.2. HPLC (AD-H,
elute: n-Hexane/i-PrOH ¼ 80/20, detector: 230 nm, 30 ꢀC, flow rate:
1.0 mL/min), t1 ¼ 16.9 min (major), t2 ¼ 20.0 min.
d
4.2.4. (þ)-(S)-3-(4-Bromophenyl)-1-methyl-3,4-
dihydroquinoxalin-2(1H)-one (2d)
44 mg, 92% yield, pale yellow solid, known compound, Rf ¼ 0.60
20
(hexanes/dichloromethane 1/3), 99% e. e., [
a]
¼ þ131.27 (c 0.86,
D
20
CHCl3), [lit [37].: [
(400 MHz, CDCl3)
a]
d
¼ þ122.1 (c 0.4, CHCl3) for 94% e. e.]; 1H NMR
D
7.39e7.32 (m, 2H), 7.21e7.15 (m, 2H), 6.91e6.78
(m, 3H), 6.68 (dd, J ¼ 7.7, 1.3 Hz, 1H), 4.93 (s, 1H), 3.30 (s, 3H); 13C
NMR (100 MHz, CDCl3)
d 165.6, 137.9, 134.0, 131.8, 128.9, 128.4,
123.9, 122.4, 112.0, 114.9, 114.2, 60.3, 29.3. HPLC (OD-H, elute: n-
Hexane/i-PrOH ¼ 80/20, detector: 230 nm, 30 ꢀC, flow rate: 1.0 mL/
min), t1 ¼ 10.3 min, t2 ¼ 16.4 min (major).
4.2.5. (þ)-(S)-3-(3-Fluorophenyl)-1-methyl-3,4-di-
hydroquinoxalin-2(1H)-one (2e)
4.2. General procedure for Brønsted acid-promoted biomimetic
reduction of quinoxalinones
36 mg, 94% yield, pale yellow solid, known compound, Rf ¼ 0.50
20
(hexanes/ethyl acetate 5/1), >99% e. e., [
a
]
D
¼ þ145.41 (c 0.72,
20
A mixture of [Ru (p-cymene)I2]2 (0.7 mg, 0.00075 mmol),
diphenyl hydrogen phosphate (1.5 mg, 0.006 mmol), (Sp)-CYNAM
3d (5.1 mg, 0.015 mmol) and quinoxalinones 1 (0.15 mmol) in
chloroform (3 mL) was stirred at room temperature for 5 min in
glove box and then the mixture was transferred to an autoclave.
The hydrogenation was performed at 40 ꢀC under hydrogen gas
(500 psi) for 48 h. After carefully release of the hydrogen, the
autoclave was opened and the reaction mixture was directly puri-
fied by column chromatography on silica gel using hexanes and
ethyl acetate to give the reductive products 2. The enantiomeric
excesses were determined by chiral HPLC.
CHCl3), [lit [37].: [
a
]
¼ þ121.8 (c 0.4, CHCl3) for 91% e. e.]; 1H NMR
7.23e7.15 (m, 1H), 7.08 (d, J ¼ 7.7 Hz, 1H),
D
(400 MHz, CDCl3)
d
7.05e6.99 (m, 1H), 6.92e6.84 (m, 3H), 6.82e6.76 (m, 1H), 6.67 (dd,
J ¼ 7.7, 1.3 Hz, 1H), 4.97 (s, 1H), 4.34 (br s, 1H), 3.30 (s, 3H); 13C NMR
3
(100 MHz, CDCl3)
d
165.5, 162.9 (d, 1JF-C ¼ 245.2 Hz), 141.5 (d, JF-
¼ 6.7 Hz), 134.1, 130.2 (d, 3JF-C ¼ 8.1 Hz), 128.2, 123.9, 122.8 (d, 4JF-
C
¼ 2.9 Hz), 119.8, 115.2 (d, 2JF-C ¼ 21.1 Hz), 114.9, 114.3, 114.1, 60.3 (d,
C
4JF-C ¼ 1.7 Hz), 29.3; 19F NMR (376 MHz, CDCl3)
d
ꢁ112.17. HPLC (AD-
H, elute: n-Hexane/i-PrOH ¼ 85/15, detector: 230 nm, 30 ꢀC, flow
rate: 1.0 mL/min), t1 ¼ 13.2 min (major), t2 ¼ 17.1 min.
4.2.6. (ꢁ)-(S)-3-(2-Methoxyphenyl)-1-methyl-3,4-
dihydroquinoxalin-2(1H)-one (2f)
4.2.1. (þ)-(S)-1-Methyl-3-phenyl-3,4-dihydroquino-xalin-2(1H)-
one (2a)
38 mg, 95% yield, pale yellow solid, known compound, Rf ¼ 0.40
20
35 mg, 98% yield, pale yellow solid, known compound, Rf ¼ 0.45
(hexanes/ethyl acetate 5/1), 98% e. e., [
a]
¼ ꢁ195.91 (c 0.76,
D
¼ ꢁ168.4 (c 0.4, CHCl3) for 74% e. e.]; 1H NMR
20
20
(hexanes/ethyl acetate 5/1), >99% e. e., [
a
]
¼ þ131.66 (c 0.66,
CHCl3), [lit [37].: [
a]
D
D
20
CHCl3), [lit [37].: [
a
]
¼ þ153.0 (c 0.4, CHCl3) for 92% e. e.]; 1H NMR
(400 MHz, CDCl3)
d
7.30e7.21 (m, 1H), 7.04 (dd, J ¼ 7.5, 1.4 Hz, 1H),
D
(400 MHz, CDCl3)
d
7.32e7.26 (m, 2H), 7.26e7.17 (m, 3H), 6.93e6.82
6.98 (dd, J ¼ 7.6, 1.5 Hz, 1H), 6.94e6.82 (m, 4H), 6.61 (dd, J ¼ 7.3,
(m, 2H), 6.82e6.73 (m, 1H), 6.66 (d, J ¼ 7.7 Hz, 1H), 4.97 (s, 1H), 3.30
1.5 Hz,1H), 5.47 (s,1H), 3.88 (s, 3H), 3.51 (s, 3H); 13C NMR (100 MHz,
(s, 3H); 13C NMR (100 MHz, CDCl3)
d
166.0, 139.1, 134.4, 128.7, 128.4,
CDCl3) d 166.4, 157.2, 134.7, 129.4, 128.8, 127.5, 126.7, 123.6, 120.7,
128.3, 127.2, 123.8, 119.6, 114.8, 114.1, 60.8, 29.3. HPLC (AD-H, elute:
n-Hexane/i-PrOH ¼ 80/20, detector: 254 nm, 30 ꢀC, flow rate:
1.0 mL/min), t1 ¼ 11.1 min (major), t2 ¼ 14.0 min.
119.4, 114.6, 114.5, 110.9, 55.8, 55.6, 29.2. HPLC (OD-H, elute: n-
Hexane/i-PrOH ¼ 80/20, detector: 230 nm, 30 ꢀC, flow rate: 1.0 mL/
min), t1 ¼ 13.5 min (major), t2 ¼ 16.4 min.
4.2.2. (þ)-(S)-1-Methyl-3-(p-tolyl)-3,4-dihydroqui-noxalin-2(1H)-
one (2b)
4.2.7. (þ)-(S)-1-Benzyl-3-phenyl-3,4-dihydroquino-xalin-2(1H)-
one (2g)
37 mg, 98% yield, white solid, known compound, Rf ¼ 0.56
47 mg, 99% yield, white solid, known compound, Rf ¼ 0.50
20
20
(hexanes/ethyl acetate 5/1), 99% e. e., [
a
]
¼ þ129.99 (c 0.74,
(hexanes/ethyl acetate 5/1), 99% e. e., [
a
]
¼ þ94.99 (c 0.94, CHCl3),
D
D
20
20
CHCl3), [lit [37].: [
a
]
¼ þ106.2 (c 0.4, CHCl3) for 89% e. e.]; 1H NMR
7.18e7.13 (m, 2H), 7.02 (d, J ¼ 7.9 Hz, 2H),
[lit [37].: [
a]
¼ þ79 (c 0.2, CHCl3) for 91% e. e.]; 1H NMR (400 MHz,
D
D
(400 MHz, CDCl3)
d
CDCl3) d 7.36e7.31 (m, 2H), 7.26e7.20 (m, 3H), 7.17e7.10 (m, 3H),
6.88e6.81 (m, 2H), 6.80e6.73 (m, 1H), 6.67e6.60 (m, 1H), 4.90 (s,
7.08e7.04 (m, 2H), 6.83e6.78 (m,1H), 6.75e6.71 (m,1H), 6.67e6.59
4

Z.-H. Zhu, Y.-X. Ding and Y.-G. Zhou
Tetrahedron 83 (2021) 131968
(m, 2H), 5.19 (d, J ¼ 16.1 Hz,1H), 5.06 (s,1H), 4.98 (d, J ¼ 16.1 Hz,1H),
(t, J ¼ 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 167.9, 134.4, 129.0,
3.95 (br s, 1H); 13C NMR (100 MHz, CDCl3)
d
166.2, 138.9, 136.7,
123.5, 119.6, 114.6, 114.4, 56.7, 31.3, 29.0, 27.6, 22.5, 14.0. HPLC (AD-
H, elute: n-Hexane/i-PrOH ¼ 85/15, detector: 230 nm, 30 ꢀC, flow
rate: 1.0 mL/min), t1 ¼ 8.0 min (major), t2 ¼ 9.7 min.
134.6, 128.8,128.7, 128.4, 127.6, 127.2, 127.1, 126.5, 123.9, 119.6, 115.7,
114.3, 60.8, 45.9. HPLC (AD-H, elute: Hexanes/i-PrOH ¼ 80/20, de-
tector: 230 nm, 30 ꢀC, flow rate: 1.0 mL/min), t1 ¼18.6 min (major),
t2 ¼ 20.3 min.
4.2.13. (þ)-(S)-3-(p-Tolyl)-3,4-dihydroquinoxalin-2(1H)-one (2m)
32 mg, 90% yield, pale yellow solid, known compound,
mp ¼ 149e150 ꢀC, Rf ¼ 0.40 (hexanes/ethyl acetate 3/1), 99% e. e.,
4.2.8. (þ)-(S)-1-Allyl-3-phenyl-3,4-dihydroquinoxa-lin-2(1H)-one
(2h)
20
25
D
[
a
]
D
¼ þ72.67 (c 0.56, CHCl3), [lit [58].: [
a
]
¼ þ81.2 (c 1.00, CHCl3)
38 mg, 96% yield, pale yellow solid, known compound, Rf ¼ 0.52
for 99% e. e.]; 1H NMR (400 MHz, CDCl3)
d
9.01 (br s, 1H), 7.28 (d,
20
(hexanes/ethyl acetate 5/1), >99% e. e., [
a
]
¼ þ119.72 (c 0.74,
J ¼ 8.0 Hz, 2H), 7.12 (d, J ¼ 7.9 Hz, 2H), 6.92e6.86 (m, 1H), 6.72 (d,
D
20
CHCl3), [lit [37].: [
a
]
¼ þ93.0 (c 0.2, CHCl3) for 91% e. e.]; 1H NMR
J ¼ 4.2 Hz, 2H), 6.67 (d, J ¼ 7.8 Hz, 1H), 5.01 (s, 1H), 4.25 (br s, 1H),
D
(400 MHz, CDCl3)
d
7.33e7.26 (m, 2H), 7.26e7.17 (m, 3H), 6.90e6.80
2.31 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 167.5, 138.3, 136.1, 133.0,
(m, 2H), 6.77e6.70 (m, 1H), 6.66 (d, J ¼ 7.6 Hz, 1H), 5.85e5.70 (m,
129.5, 127.1, 124.8, 124.0, 119.3, 115.7, 113.7, 60.5, 21.2. HPLC (AD-H,
elute: n-Hexane/i-PrOH ¼ 80/20, detector: 230 nm, 30 ꢀC, flow rate:
1.0 mL/min), t1 ¼ 14.5 min (major), t2 ¼ 18.1 min.
1H), 5.10e4.95 (m, 3H), 4.61e4.52 (m, 1H), 4.43e4.35 (m, 1H), 3.88
(br s, 1H); 13C NMR (100 MHz, CDCl3)
d 165.7, 138.9, 134.6, 132.0,
128.7, 128.3, 127.5, 127.1, 123.8, 119.6, 116.7, 115.4, 114.3, 60.7, 44.7.
HPLC (AD-H, elute: n-Hexane/i-PrOH ¼ 80/20, detector: 230 nm,
30 ꢀC, flow rate: 1.0 mL/min), t1 ¼ 10.6 min (major), t2 ¼ 16.4 min.
4.2.14. (ꢁ)-3-Phenyl-1-(p-tolyl)-3,4-dihydroquinox-alin-2(1H)-one
(2n)
46 mg, 98% yield, pale yellow solid, new compound,
4.2.9. (þ)-(S)-1,3-Dimethyl-3,4-dihydroquinoxalin-2(1H)-one (2i)
mp ¼ 160e161 ꢀC, Rf ¼ 0.31 (hexanes/ethyl acetate 5/1), >99% e. e.,
20
26 mg, 98% yield, pale yellow oil, known compound, Rf ¼ 0.40
[
a
]
D
¼ ꢁ16.52 (c 0.92, CHCl3), 1H NMR (400 MHz, CDCl3)
d 7.44 (d,
20
(hexanes/ethyl acetate 5/1), 97% e. e., [
a
]
¼ þ104.99 (c 0.42,
J ¼ 6.7 Hz, 2H), 7.35e7.26 (m, 5H), 7.10 (d, J ¼ 7.9 Hz, 2H), 6.90 (t,
J ¼ 7.3 Hz, 1H), 6.75 (d, J ¼ 7.2 Hz,1H), 6.63 (t, J ¼ 7.7 Hz,1H), 6.33 (d,
J ¼ 7.9 Hz, 1H), 5.17 (s, 1H), 4.47 (br s, 1H), 2.40 (s, 3H); 13C NMR
D
20
CHCl3), [lit [37].: [
a
]
D
¼ þ65.0 (c 0.2, CHCl3) for 8% e. e.]; 1H NMR
(400 MHz, CDCl3)
d
6.89e6.82 (m, 2H), 6.81e6.75 (m, 1H),
6.67e6.62 (m, 1H), 3.87 (q, J ¼ 6.6 Hz, 1H), 3.77 (br s, 1H), 3.28 (s,
(100 MHz, CDCl3) d 165.8, 139.0, 138.3, 134.8, 134.0, 130.5, 129.6,
3H), 1.36 (d, J ¼ 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
168.4,
128.8, 128.6, 128.3, 127.0, 123.8, 119.3, 116.9, 114.3, 61.1, 21.3. HPLC
(OD-H, elute: n-Hexane/i-PrOH ¼ 80/20, detector: 230 nm, 30 ꢀC,
flow rate: 1.0 mL/min), t1 ¼ 11.3 min, t2 ¼ 17.0 min (major). HRMS
Calculated for C21H19N2O [MþH]þ 315.1492, found: 315.1492.
135.0, 129.2, 123.5, 119.7, 114.7, 114.2, 52.2, 29.1, 17.9. HPLC (AD-H,
elute: n-Hexane/i-PrOH ¼ 85/15, detector: 230 nm, 30 ꢀC, flow rate:
1.0 mL/min), t1 ¼ 7.9 min (major), t2 ¼ 8.4 min.
4.2.10. (þ)-(S)-3-Ethyl-1-methyl-3,4-dihydroquino-xalin-2(1H)-
one (2j)
4.3. General procedure for Brønsted acid-promoted biomimetic
reduction of benzoxazinones
27 mg, 95% yield, pale yellow oil, known compound, Rf ¼ 0.41
20
(hexanes/ethyl acetate 5/1), 99% e. e., [
a]
¼ þ37.22 (c 0.54, CHCl3),
A mixture of [Ru (p-cymene)I2]2 (0.7 mg, 0.00075 mmol),
diphenyl hydrogen phosphate (1.5 mg, 0.006 mmol), (Sp)-CYNAM
3d (5.1 mg, 0.015 mmol) and benzoxazinones 5 (0.15 mmol) in
chloroform (3 mL) was stirred at room temperature for 5 min in
glove box and then the mixture was transferred to an autoclave.
The hydrogenation was performed at 40 ꢀC under hydrogen gas
(500 psi) for 48 h. After carefully release of the hydrogen, the
autoclave was opened and the reaction mixture was directly puri-
fied by column chromatography on silica gel using hexanes and
ethyl acetate to give the reductive products 6. The enantiomeric
excesses were determined by chiral HPLC.
D
20
[lit [33].: [
a
]
D
¼ ꢁ59.82 (c 0.56, CHCl3) for 97% e. e.]; 1H NMR
(400 MHz, CDCl3)
d 6.86e6.79 (m, 2H), 6.78e6.71 (m, 1H),
6.66e6.60 (m, 1H), 3.90 (br s, 1H), 3.72 (dd, J ¼ 7.9, 4.7 Hz, 1H), 3.27
(s, 3H), 1.81e1.70 (m, 1H), 1.69e1.58 (m, 1H), 0.92 (t, J ¼ 7.5 Hz, 3H);
13C NMR (100 MHz, CDCl3)
d 167.8, 134.4, 129.0, 123.5, 119.5, 114.6,
114.3, 57.9, 29.0, 24.8, 9.8. HPLC (AD-H, elute: n-Hexane/i-
PrOH ¼ 85/15, detector: 230 nm, 30 ꢀC, flow rate: 1.0 mL/min),
t1 ¼ 7.7 min (major), t2 ¼ 9.0 min.
4.2.11. (þ)-(S)-3-Isopropyl-1-methyl-3,4-dihydroq-uinoxalin-
2(1H)-one (2k)
30 mg, 98% yield, colorless oil, known compound, Rf ¼ 0.60
4.3.1. (þ)-(S)-3-Phenyl-3,4-dihydro-2H-benzo[b] [1,4]oxazin-2-one
(6a)
20
(hexanes/ethyl acetate 5/1), >99% e. e., [
a
]
¼ þ15.52 (c 0.58,
D
20
CHCl3), [lit [33].: [
a
]
D
¼ ꢁ18.03 (c 0.56, CHCl3) for 99% e. e.]; 1H
32 mg, 95% yield, white solid, known compound, Rf ¼ 0.60
20
NMR (400 MHz, CDCl3)
d
6.86e6.78 (m, 2H), 6.77e6.70 (m, 1H),
(hexanes/ethyl acetate 5/1), 98% e. e., [
a
]
¼ þ117.18 (c 0.64, CHCl3),
D
20
6.66e6.59 (m, 1H), 3.77 (br s, 1H), 3.61 (d, J ¼ 6.0 Hz, 1H), 3.29 (s,
[lit [37].: [
a]
¼ þ106.5 (c 0.4, CHCl3) for 97% e. e.]; 1H NMR
D
3H), 2.15e2.05 (m, 1H), 0.93 (d, J ¼ 6.9 Hz, 3H), 0.85 (d, J ¼ 6.7 Hz,
(400 MHz, CDCl3)
d 7.33e7.23 (m, 5H), 6.98e6.89 (m, 2H),
3H); 13C NMR (100 MHz, CDCl3)
d
166.9, 134.5, 128.6, 123.5, 119.2,
6.80e6.74 (m, 1H), 6.71 (d, J ¼ 7.9 Hz, 1H), 4.94 (s, 1H), 3.91 (br s,
114.5, 113.9, 62.1, 30.3, 29.0, 19.1, 17.7. HPLC (AD-H, elute: n-Hexane/
i-PrOH ¼ 85/15, detector: 230 nm, 30 ꢀC, flow rate: 1.0 mL/min),
t1 ¼ 7.5 min (major), t2 ¼ 9.4 min.
1H); 13C NMR (100 MHz, CDCl3)
d
165.3, 140.9, 136.4, 132.4, 129.0,
127.5, 125.2, 120.4, 117.0, 115.0, 59.3. HPLC (OD-H, elute: n-Hexane/
i-PrOH ¼ 70/30, detector: 230 nm, 30 ꢀC, flow rate: 0.7 mL/min),
t1 ¼ 10.8 min, t2 ¼ 14.6 min (major).
4.2.12. (þ)-(S)-3-Butyl-1-methyl-3,4-dihydroquino-xalin-2(1H)-
one (2l)
4.3.2. (þ)-(S)-6-Chloro-3-phenyl-3,4-dihydro-2H-benzo[b] [1,4]-
oxazin-2-one (6b)
31 mg, 95% yield, pale yellow oil, known compound, Rf ¼ 0.57
20
(hexanes/ethyl acetate 5/1), 98% e. e., [
a
]
¼ þ30.16 (c 0.60, CHCl3),
36 mg, 92% yield, white solid, known compound, Rf ¼ 0.60
D
20
20
[lit [33].: [
a]
¼ ꢁ35.15 (c 0.64, CHCl3) for 96% e. e.]; 1H NMR
(hexanes/dichloromethane 1/1), >99% e. e., [
a]
¼ þ142.35 (c 0.72,
D
D
15
(400 MHz, CDCl3)
d
6.87e6.81 (m, 2H), 6.80e6.74 (m, 1H),
CHCl3), [lit [27].: [
a]
¼ ꢁ109.9 (c 0.90, CHCl3) for 89% e. e.]; 1H
D
6.66e6.61 (m, 1H), 3.78 (dd, J ¼ 8.3, 4.7 Hz, 1H), 3.73 (br s, 1H), 3.28
NMR (400 MHz, CDCl3)
d
7.42e7.37 (m, 5H), 6.97 (d, J ¼ 8.2 Hz, 1H),
(s, 3H),1.78e1.70 (m,1H),1.64e1.55 (m,1H),1.37e1.24 (m, 4H), 0.83
6.88e6.80 (m, 2H), 5.09 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 164.5,
5

Z.-H. Zhu, Y.-X. Ding and Y.-G. Zhou
Tetrahedron 83 (2021) 131968
139.3, 136.0, 133.2, 130.2, 129.2, 129.1, 127.3, 120.1, 118.0, 114.7, 58.8.
HPLC (OD-H, elute: n-Hexane/i-PrOH ¼ 70/30, detector: 230 nm,
30 ꢀC, flow rate: 0.7 mL/min), t1 ¼ 10.4 min, t2 ¼ 14.9 min (major).
1H); 13C NMR (100 MHz, CDCl3)
d
154.2, 138.8, 132.0, 129.1, 128.4,
123.8 (q, J ¼ 279.9 Hz), 121.5, 119.58, 117.0, 114.9, 86.3, 80.8 (q,
J ¼ 2.1 Hz), 55.7, 52.2 (q, J ¼ 33.8 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢁ75.64. HPLC (AD-H, elute: n-Hexane/i-PrOH ¼ 95/5, detector:
4.3.3. (þ)-(S)-3-Butyl-3,4-dihydro-2H-benzo[b] [1,4]oxazin-2-one
(6c)
254 nm, 30 ꢀC, flow rate: 0.8 mL/min), t1 ¼ 11.3 min, t2 ¼ 12.2 min
(major).
28 mg, 91% yield, white solid, known compound, Rf ¼ 0.70
20
(hexanes/ethyl acetate 10/1), >99% e. e., [
a]
¼ þ26.25 (c 0.56,
4.5.2. (ꢁ)-(R)-4-Methoxy-N-(1,1,1-trifluoro-4-(p-tolyl)but-3-yn-2-
yl)aniline (10b)
D
20
CHCl3), [lit [33].: [
a
]
D
¼ ꢁ43.75 (c 0.56, CHCl3) for 99% e. e.]; 1H
NMR (400 MHz, CDCl3)
d
6.97e6.87 (m, 2H), 6.80e6.73 (m, 1H),
45 mg, 94% yield, pale yellow oil, known compound, Rf ¼ 0.70
20
6.73e6.68 (m, 1H), 3.84 (dd, J ¼ 7.7, 5.2 Hz, 1H), 3.56 (br s, 1H),
(hexanes/dichloromethane 1/1), >99% e. e., [
a]
¼ ꢁ261.29 (c 0.84,
D
20
1.90e1.80 (m, 1H), 1.75e1.65 (m, 1H), 1.42e1.26 (m, 4H), 0.85 (t,
CHCl3), [lit [31].: [
a]
¼ ꢁ288.76 (c 0.90, CHCl3) for 95% e. e.]; 1H
D
J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
166.7, 141.1, 132.3,
NMR (400 MHz, CDCl3)
d
7.31 (d, J ¼ 7.5 Hz, 2H), 7.11 (d, J ¼ 7.7 Hz,
125.0, 120.3, 116.8, 115.1, 54.8, 30.9, 27.4, 22.4, 13.9. HPLC (OD-H,
elute: n-Hexane/i-PrOH ¼ 95/5, detector: 230 nm, 30 ꢀC, flow rate:
0.7 mL/min), t1 ¼ 18.1 min, t2 ¼ 23.4 min (major).
2H), 6.86e6.72 (m, 4H), 4.80e4.67 (m, 1H), 3.76 (s, 3H), 3.76 (br s,
1H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
154.2, 139.4, 139.0,
131.9, 129.1, 123.8 (q, J ¼ 280.2 Hz), 118.4, 116.9, 114.9, 86.5, 80.2 (d,
J ¼ 2.0 Hz), 55.7, 52.2 (q, J ¼ 33.7 Hz), 21.5; 19F NMR (376 MHz,
4.4. General procedure for Brønsted acid-promoted biomimetic
reduction of benzoxazine
CDCl3)
d
ꢁ75.72. HPLC (AS-H, elute: n-Hexane/i-PrOH ¼ 95/5, de-
tector: 254 nm, 30 ꢀC, flow rate: 0.8 mL/min), t1 ¼ 8.5 min,
t2 ¼ 9.4 min (major).
A mixture of [Ru (p-cymene)I2]2 (0.7 mg, 0.00075 mmol),
diphenyl hydrogen phosphate (1.5 mg, 0.006 mmol), (Sp)-CYNAM
3d (5.1 mg, 0.015 mmol) and 3-phenyl-2H-benzo [b] [1,4]oxazine 7
(0.15 mmol) in chloroform (3 mL) was stirred at room temperature
for 5 min in glove box and then the mixture was transferred to an
autoclave. The hydrogenation was performed at 40 ꢀC under
hydrogen (500 psi) for 48 h. After carefully release of the hydrogen,
the autoclave was opened and the reaction mixture was directly
purified by column chromatography on silica gel using hexanes and
ethyl acetate to give the reductive product 8. The enantiomeric
excesses were determined by chiral HPLC.
4.5.3. (ꢁ)-(R)-4-Methoxy-N-(1,1,1-trifluoro-4-(4-methoxyphenyl)-
but-3-yn-2-yl)aniline (10c)
50 mg, 99% yield, pale yellow oil, known compound, Rf ¼ 0.70
20
(hexanes/dichloromethane 2/5), >99% e. e., [
a]
¼ ꢁ236.88 (c 1.00,
D
20
CHCl3), [lit [31].: [
a
]
D
¼ ꢁ239.65 (c 1.20, CHCl3) for 95% e. e.]; 1H
NMR (400 MHz, CDCl3)
d
7.36 (d, J ¼ 8.3 Hz, 2H), 6.93e6.66 (m, 6H),
4.83e4.62 (m, 1H), 3.79 (s, 3H), 3.76 (s, 4H); 13C NMR (100 MHz,
CDCl3)
160.2, 154.1, 139.0, 133.5, 123.8 (q, J ¼ 280.0 Hz), 116.9,
d
114.9, 114.0, 113.5, 86.3, 79.5 (d, J ¼ 1.8 Hz), 55.7, 55.3, 52.2 (q,
J ¼ 33.7 Hz); 19F NMR (376 MHz, CDCl3)
d
ꢁ75.74. HPLC (AD-H,
elute: n-Hexane/i-PrOH ¼ 95/5, detector: 254 nm, 30 ꢀC, flow rate:
4.4.1. (þ)-(S)-3-Phenyl-3,4-dihydro-2H-benzo[b] [1,4]oxazine (8)
0.8 mL/min), t1 ¼ 20.3 min, t2 ¼ 21.7 min (major).
31 mg, 98% yield, pale yellow oil, known compound, Rf ¼ 0.80
20
(hexanes/dichloromethane 2/5), 96% e. e., [
a
]
¼ þ153.22 (c 0.62,
4.6. General procedure for Brønsted acid-promoted biomimetic
reduction of quinolines
D
22
CHCl3), [lit [57].: [
a]
¼ ꢁ147.8 (c 1.14, CHCl3) for 98% e. e.]; 1H NMR
D
(400 MHz, CDCl3)
d
7.34e7.23 (m, 5H), 6.79e6.69 (m, 2H),
6.65e6.55 (m, 2H), 4.43e4.38 (m,1H), 4.22e4.17 (m,1H), 3.94e3.88
A mixture of [Ru (p-cymene)I2]2 (0.7 mg, 0.00075 mmol),
diphenyl hydrogen phosphate (1.5 mg, 0.006 mmol), (Sp)-CYNAM
3d (5.1 mg, 0.015 mmol) and quinolines 11 [56] (0.15 mmol) in
CHCl3/THF (3:1) (3 mL) was stirred at room temperature for 5 min
in glove box and then the mixture was transferred to an autoclave.
The hydrogenation was performed at 40 ꢀC under hydrogen (500
psi) for 48 h. After carefully release of the hydrogen, the autoclave
was opened and the reaction mixture was directly purified by
column chromatography on silica gel using hexanes and ethyl ac-
etate to give the reductive products 12. The enantiomeric excesses
were determined by chiral HPLC.
(m, 1H); 13C NMR (100 MHz, CDCl3)
d
143.6, 139.1, 133.7, 128.9,
128.4, 127.3, 121.5, 119.1, 116.7, 115.5, 70.9, 54.3. HPLC (OD-H, elute:
n-Hexane/i-PrOH ¼ 70/30, detector: 230 nm, 30 ꢀC, flow rate:
0.7 mL/min), t1 ¼ 11.9 min, t2 ¼ 15.7 min (major).
4.5. General procedure for Brønsted acid-promoted biomimetic
reduction of alkynyl ketimines
A mixture of [Ru (p-cymene)I2]2 (0.7 mg, 0.00075 mmol),
diphenyl hydrogen phosphate (1.5 mg, 0.006 mmol), (Sp)-CYNAM
3d (5.1 mg, 0.015 mmol) and alkynyl ketimines 9 (0.15 mmol) in
chloroform (3 mL) was stirred at room temperature for 5 min in
glove box and then the mixture was transferred to an autoclave.
The hydrogenation was performed at 40 ꢀC under hydrogen gas
(500 psi) for 48 h. After carefully release of the hydrogen, the
autoclave was opened and the reaction mixture was directly puri-
fied by column chromatography on silica gel using hexanes and
ethyl acetate to give the reductive products 10. The enantiomeric
excesses were determined by chiral HPLC.
4.6.1. (þ)-(R)-2-Phenyl-1,2,3,4-tetrahydroquinoline (12a)
30 mg, 96% yield, colorless oil, the known compound, Rf ¼ 0.70
20
(hexanes/ethyl acetate 10/1), 97% e. e., [
a]
¼ þ39.50 (c 0.60,
D
19
CHCl3), [lit [27].: [
(400 MHz, CDCl3)
a
d
]
¼ ꢁ35.7 (c 0.80, CHCl3) for 91% e. e.]; 1H NMR
D
7.33e7.23 (m, 4H), 7.22e7.17 (m, 1H), 6.97e6.87
(m, 2H), 6.57 (t, J ¼ 7.4 Hz, 1H), 6.45 (d, J ¼ 7.8 Hz, 1H), 4.34 (dd,
J ¼ 9.3, 3.1 Hz, 1H), 4.11 (br s, 1H), 2.88e2.79 (m, 1H), 2.68e2.61 (m,
1H), 2.07e2.00 (m, 1H), 1.96e1.86 (m, 1H); 13C NMR (100 MHz,
CDCl3)
d 144.7, 144.6, 129.4, 128.7, 128.6, 127.5, 127.0, 126.6, 121.1,
4.5.1. (ꢁ)-(R)-4-Methoxy-N-(1,1,1-trifluoro-4-phenylbut-3-yn-2-
yl)aniline (10a)
117.4, 114.2, 56.3, 31.0, 26.4. HPLC (AS-H, elute: n-Hexane/i-
PrOH ¼ 85/15, detector: 254 nm, 30 ꢀC, flow rate: 0.7 mL/min),
t1 ¼ 7.1 min (major), t2 ¼ 15.9 min.
44 mg, 96% yield, yellow oil, known compound, Rf ¼ 0.80
20
(hexanes/ethyl acetate 30/1), >99% e. e., [
a
]
¼ ꢁ255.32 (c 0.88,
D
20
CHCl3), [lit [31].: [
a
]
¼ ¼ ꢁ231.28 (c 1.16, CHCl3) for 95% e. e.]; 1H
4.6.2. (þ)-(R)-2-(4-Chlorophenyl)-1,2,3,4-tetrahydroquinoline
(12b)
D
NMR (400 MHz, CDCl3)
d
7.40e7.32 (m, 2H), 7.29e7.18 (m, 3H),
6.78e6.66 (m, 4H), 4.67 (q, J ¼ 6.2 Hz, 1H), 3.68 (s, 3H), 3.40 (br s,
34 mg, 93% yield, white solid, the known compound, Rf ¼ 0.70
6

Z.-H. Zhu, Y.-X. Ding and Y.-G. Zhou
Tetrahedron 83 (2021) 131968
20
[20] A.M.F. Phillips, A.J.L. Pombeiro, Org. Biomol. Chem. 15 (2017) 2307e2340.
[21] Z.-L. Xia, C. Zheng, S.-G. Wang, S.-L. You, Angew. Chem. Int. Ed. 57 (2018)
2653e2656.
[22] H.C. Lo, R.H. Fish, Angew. Chem. Int. Ed. 41 (2002) 478e481.
[23] H.-J. Xu, Y.-C. Liu, Y. Fu, Y.-D. Wu, Org. Lett. 8 (2006) 3449e3451.
[24] B. Procuranti, S.J. Connon, Chem. Commun. (2007) 1421e1423.
[25] Q.-A. Chen, M.-W. Chen, C.-B. Yu, L. Shi, D.-S. Wang, Y. Yang, Y.-G. Zhou, J. Am.
Chem. Soc. 133 (2011) 16432e16435.
(hexanes/ethyl acetate 20/1), 95% e. e., [
a
]
¼ þ42.64 (c 0.68,
D
20
CHCl3), [lit [27].: [
a]
¼ ꢁ36.0 (c 0.92, CHCl3) for 91% e. e.]; 1H NMR
D
(400 MHz, CDCl3)
d
7.26e7.19 (m, 4H), 6.96e6.87 (m, 2H), 6.58 (t,
J ¼ 7.4 Hz, 1H), 6.45 (d, J ¼ 7.9 Hz, 1H), 4.32 (dd, J ¼ 9.1, 3.2 Hz, 1H),
4.01 (br s, 1H), 2.86e2.76 (m, 1H), 2.65e2.58 (m, 1H), 2.04e1.96 (m,
1H), 1.91e1.81 (m, 1H); 13C NMR (100 MHz, CDCl3)
d 144.3, 143.3,
[26] L. Zhao, J. Wei, J. Lu, C. He, C. Duan, Angew. Chem. Int. Ed. 56 (2017)
8692e8696.
[27] Q.-A. Chen, K. Gao, Y. Duan, Z.-S. Ye, L. Shi, Y. Yang, Y.-G. Zhou, J. Am. Chem.
Soc. 134 (2012) 2442e2448.
[28] L.-Q. Lu, Y. Li, K. Junge, M. Beller, Angew. Chem. Int. Ed. 52 (2013) 8382e8386.
[29] Z.-P. Chen, M.-W. Chen, R.-N. Guo, Y.-G. Zhou, Org. Lett. 16 (2014) 1406e1409.
[30] L.-Q. Lu, Y. Li, K. Junge, M. Beller, J. Am. Chem. Soc. 137 (2015) 2763e2768.
[31] M.-W. Chen, B. Wu, Z.-P. Chen, L. Shi, Y.-G. Zhou, Org. Lett. 18 (2016)
4650e4653.
[32] J. Wang, Z.-H. Zhu, M.-W. Chen, Q.-A. Chen, Y.-G. Zhou, Angew. Chem. Int. Ed.
58 (2019) 1813e1817.
[33] J. Wang, Z.-B. Zhao, Y. Zhao, G. Luo, Z.-H. Zhu, Y. Luo, Y.-G. Zhou, J. Org. Chem.
85 (2020) 2355e2368.
133.1, 129.4, 128.7, 128.0, 127.0, 120.9, 117.6, 114.2, 55.6, 31.0, 26.2.
HPLC (AS-H, elute: n-Hexane/i-PrOH ¼ 85/15, detector: 254 nm,
30 ꢀC, flow rate: 0.8 mL/min), t1 ¼ 8.0 min (major), t2 ¼ 15.7 min.
Declaration of competing interest
The authors declare that they have no known competing
financialinterestsor personal relationships that could have
appeared to influence the work reported in this paper.
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Acknowledgments
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We thank the National Natural Science Foundation of China
(21532006) for financial support.
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Appendix A. Supplementary data
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