Enantioselective Synthesis of Tetrahydroquinolines via One-Pot Cascade Biomimetic Reduction?

Article abstract of DOI:10.1002/cjoc.202000409

A novel and efficient protocol for the synthesis of chiral tetrahydroquinoline derivatives with excellent enantioselectivities and high yields has been developed through one-pot cascade biomimetic reduction. The detailed reaction pathway includes the acid-catalyzed and ruthenium-catalyzed formation of aromatic quinoline intermediates and biomimetic asymmetric reduction.

Full text of DOI:10.1002/cjoc.202000409

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Enantioselective Synthesis of Tetrahydroquinolines via One-pot Cascade
Biomimetic Reduction
Authors: Zi-Biao Zhao, Xiang Li, Mu-Wang Chen, Bo Wu, and Yong-Gui Zhou*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2020, 38, 10.1002/cjoc.202000409.
The final Version of Record (VoR) of it with formal page numbers will soon be
published online in Early View: http://dx.doi.org/10.1002/cjoc.202000409.
ISSN 1001-604X • CN 31-1547/O6
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Chinese Journal
of Chemistry
Report
Biomimetic synthesis, Chirality, Reduction, Tetrahydroquinolines
CJC
中
国 化 学 - An International Journal
Enantioselective Synthesis of Tetrahydroquinolines via One-pot Cascade
Biomimetic Reduction
Zi-Biao Zhao,a Xiang Li,a Mu-Wang Chen, a Bo Wu, a and Yong-Gui Zhou*, a,b
aState Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. China.
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China.
Cite this paper: Chin. J. Chem. 2020, 38, XXX—XXX. DOI: 10.1002/cjoc.202000XXX
Summary of main observation and conclusion A novel and efficient protocol for the synthesis of chiral tetrahydroquinoline derivatives with excellent
enantioselectivities and high yields has been developed through one-pot cascade biomimetic reduction. The detailed reaction pathway includes the
acid-catalyzed and ruthenium-catalyzed formation of aromatic quinoline intermediates and biomimetic asymmetric reduction.
reaction, aromatic compounds such as quinolines need to be
synthesized in advance.
Background and Originality Content
Tetrahydroquinolines are identified as significant and prevalent
structural motifs in bioactive natural products and pharmaceutical
molecules.1 Many molecules exhibit diverse biological activities
such as antihypertensive, antidiabetic, antibacterial and antimala-
rial activity. 1-2 For example, it also could be used as androgen
receptor agonist and progesterone receptor antagonist.2 All these
molecules have a core skeleton of tetrahydroquinoline (Figure 1).
In addition, tetrahydroquinolines could also be served as one
class of valuable synthetic intermediates for organic synthesis and
industrial applications.1
The combination of two different catalytic processes in one-pot
reaction, which the intermediates separation was not required,
could significantly increase the synthetic efficiency.6 In the field of
tetrahydroquinolines synthesis, many methods such as catalytic
cascade reactions from easily available starting materials have
also been successfully developed.7 According to retrosynthetic
analysis, 2-aminochalcones also might be a good choice as the
substrate for consecutive one-pot catalytic reaction.8 Using this
strategy, in 2013, Rueping’s group reported the reaction for
synthesis of chiral tetrahydroquinolines via consecutive
photocyclization/asymmetric transfer hydrogenation. 9 Soon
after, Yang and coworkers developed a similar approach through
visible-light-induced cyclization/chiral phosphoric acid-catalyzed
transfer hydrogenation.10 In 2018, Cheon’s group also reported
the two step one-pot consecutive process including cyclization/
asymmetric reduction using chiral phosphoric acid as the sole
catalyst (Scheme 1).11 However, these reactions all required the
stoichiometric amount of NAD(P)H model Hantzsch esters (HEH)
as hydrogen source in the reduction and suffered from restriction
on the HEH regeneration, leading to low atomic economy and
difficulty in product isolation. Therefore, it is necessary to develop
a novel and efficient method using the catalytic amount of
NAD(P)H model in the presence of hydrogen gas. Furthermore,
the one-pot multi-step reaction for synthesis of chiral
R
Ph
R
O
N
N
O
N
N
O
H
n
ac er a ac
v
n
ac er a ac
v
I
( )
A
tib
t
i l ti ity
II
( )
A
tib
t
i l ti ity
e
M
e
M
O2N
NC
S
N
O
H
e
M
e
H
N
H
M
n
ro en rece or a on s
ro es erone rece or an a on s
pt
P t g i t
)
II
( )
A
d
g
pt
g
i t IV
g
t
(
Figure 1 Bioactive molecules containing the tetrahydroquinoline motif.
tetrahydroquinolines employing the regenerable hydrogen
sources has not been reported up to date.
Owing to the remarkable significance, a variety of powerful and
efficient approaches have been developed for synthesis of chiral
tetrahydroquinolines.3 Among the various methods, enantiosele-
ctive hydrogenation of aromatic quinolines was considered as the
most straightforward access to produce the chiral compounds. A
series of catalytic hydrogenation systems have been established
in terms of this field. 4-5 Despite the success of the hydrogenation
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differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.202000409
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Zhao et al.
Report
Scheme 1. Catalytic enantioselective synthesis of tetrahydroquinolines.
5
6
(S)-3e
(R)-3f
(R)-3g
(R)-3d
Toluene
Toluene
Toluene
p-Xylene
>95
>95
>95
>95
>95
73
48
70
62
85
86
73
76
57
88
87
88
90
43
31
66
60
57
52
80
39
65
91
93
86
as
Previous Works: Using Stoichiometric HEH
Source
Hydrogen
O
O
7
O
Blue LEDs/ hv & CPA
or
only CPA
RO
OR
Me
R
8
as
HEH
Source
Hydrogen
N
R
Me
N
H
NH2
H
(Stoichiometric)
HEH
9
(R)-3d Mesitylene
10
11
12
13e
14f
15g
16h
(R)-3d
(R)-3d
(R)-3d
DCM
EtOAc
THF
This Work: Using
Amount
PD in the Presence
of
Hydrogen
Catalytic
of
84
O
R'
p
CPA
,
]
-cymene)I2 2
[Ru(
PD
R
46
R'
NH2
H
mol%),
psi)
(20
2 (500
N
R
PD
N
H
(R)-3d Mesitylene
(R)-3d Mesitylene
(R)-3d Mesitylene
(R)-3d Mesitylene
>95
>95
>95
>95
♣
♣
♣
Challenges:
of
Two
Catalytic
Compatibility
Systems
The
Reaction
Background
Control of the Enantioselectivity
Recently, biomimetic asymmetric hydrogenation of imines and
heteroaromatics with catalytic amount of NAD(P)H models such
as phenanthridine (PD) has been successfully reported.12-13
Hence, we envisaged chiral tetrahydroquinolines could be
obtained by one-pot cascade reaction from readily available
2-aminochalcones using the PD instead of HEH in the catalytic
amount (Scheme 1). It was noted that there might be many
challenges in this reaction. Firstly, the major challenge was
compatibility between two catalytic systems for regeneration and
transfer hydrogenation. Secondly, how to control the
enantioselectivity and the background reaction also should be
solved.
a Reaction conditions: 1a (0.10 mmol), [Ru(p-cymene)I2]2 (0.5 mol%), PD
(20 mol%), solvent (2.0 mL), H2 (500 psi), CPA (10 mol%), 4 Å MS (30 mg),
40 oC, 42 h. b Measured by analysis of 1H NMR. c Determined by chiral
HPLC. d Measured by analysis of 1H NMR. e 5 Å MS (30 mg). f 5 Å MS (30
mg), [Ru(p-cymene)I2]2 (4.0 mol%). g 5 Å MS (30 mg), [Ru(p-cymene)I2]2
(4.0 mol%), 72 h. h 5 Å MS (30 mg), [Ru(p-cymene)I2]2 (4.0 mol%), 30 oC, 72
h.
At the outset, we chose easily available 2-aminochalcone (1a)
as model substrate for this one-pot reaction. The results of
condition optimization were summarized in Table 1. This reaction
was initially studied by employing different chiral phosphoric
acids in the toluene (Table 1，entries 1-7). It was found that the
substrate 1a could be completely converted into quinoline and
tetrahydroquinoline. Among these tested chiral phosphoric acids,
phosphoric acid (R)-3d proved best, 73% yield and 84% ee were
observed (entry 4). Next, we turned our attention to the solvent
effect. Pleasingly, this reaction proceeded smoothly in the
different aromatic solvents, the substrate could be completely
consumed (entries 4, and 8-9). Considering the enantioselectivity,
mesitylene was the best choice. A series of other solvents such as
DCM, EtOAc and THF were proved to be ineffective, and lower
enantioselectivities were obtained (entries 10-12). Subsequently,
considering the fact that different molecular sieves might have
effect on the yield and enantioselectivity, the other molecular
sieves was evaluated. The desired product was observed in 65%
yield and 88% ee value by utilizing 5 Å molecular sieves (entry 13).
When the one-pot reaction was performed in the presence of 5 Å
molecular sieves, the metal catalyst loading was also tested.
Fortunately, the increase of metal catalyst loading could
Results and Discussion
Table 1 Optimization of reaction parameters.a
O
p
CPA
,
]
-cymene)I2 2
[Ru(
Ph
*
+
PD, H
Solvent
MS, t
N
H
Ph
N
Ph
2 (500 psi),
NH2
4
T,
Å
1a
2a
2aa
:
:
:
=
=
R
R
R
R
S
Ar
Ar
C6
H
5 [H8]
Ar
(
(
(
(
(
(
(
)-3a
)-3b
)-3c
4-MeO-C6
H
4 [H8]
4 [H8]
-C
=
Ar 4-F-C6H
O
O
O
P
:
:
=
=
=
Ar
Ar
Ar
Ar
6H
3 [H8]
3,5-F2
)-3d
OH
2-C
6H
3 [H8]
6H3
3-C
iPr) 6H2
3,5-(CF3
-C
3,5-F2
2,4,6-(
)-3e
)-3f
)
:
R
R
Ar
3
:
=
)-3g
entry
CPA
solvent
conv. (%)b ee 2a (%)c yield 2a (%)d
1
2
3
4
(R)-3a
(R)-3b
(R)-3c
(R)-3d
Toluene
Toluene
Toluene
Toluene
>95
>95
>95
>95
74
74
82
84
49
40
63
73
significantly improve the yield. This reaction provided the best
result with 91% yield and 87% ee value at 4.0 mol% metal catalyst
(entry 14). To our delight, prolonging time of the reaction could
get excellent yield and slightly higher 88% ee value (entry 15).
Furthermore, when the temperature was lowered to 30 oC, the ee
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Enantioselective Synthesis of Tetrahydroquinolines
Chin. J. Chem.
value of 2a could be further improved to 90% ee with slightly low
86% yield (entry 16). Therefore, considering the enantioselectivity
and yield, the optimal reaction temperature was 40 oC.
participate in this reaction, satisfied result with high yields and up
to 90% ee value could be obtained (2g-2h). Disubstituted
substrates could also proceed smoothly under the optimal
conditions (2i-2j). A range of halogen substituted substrates were
also well-tolerated to produce the corresponding chiral products,
respectively, in moderate yields and excellent enantioselectivities
(2k-2m). Notably, naphthyl substituted substrate proceeded
smoothly to afford the desired products in 96% yield and 90% ee
value (2o). In addition, the substrates bearing furanyl and alkyl
groups were well compatible in this system, the desired products
were obtained in good yields (2p-2q).
Table 2 Substrate scope.a
O
R
3d PD
,
p
,
R
-cymene)I2 2
]
H2
psi)
[Ru(
(
)-
MS, 72 h
Å
+
40 o
5
(500
N
H
R
C,
Mesitylene,
NH2
1
2
entry
R
ee (%)b
yield (%)c
Scheme 2 Substrate scope.a
1
2
Ph
87
91
87
78
86
80
90
85
87
84
89
92
91
86
90
83
36
91 (2a)
94 (2b)
96 (2c)
92 (2d)
89 (2e)
96 (2f)
92 (2g)
92 (2h)
95 (2i)
82 (2j)
86 (2k)
86 (2l)
83 (2m)
88 (2n)
96 (2o)
93 (2p)
85 (2q)
O
R
3d PD
p
,
,
-cymene)I2 2
]
[Ru(
(
)-
H2
psi)
Ar
+
Ph
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-CyC6H4
40 o
5
MS
Å
Ar
(500
N
H
Ph
C,
Mesitylene,
NH2
3
1
2
MeO
F
Cl
4
N
N
H
N
H
H
5
2r
ee,
2s
2t
ee,
ee,
74%
85%
88%
87%
56%
81%
86%
40%
yield
yield
yield
yield
yield
6
4-t-BuC6H4
4-MeOC6H4
3-MeOC6H4
3,4-Me2C6H3
3,5-(MeO)2C6H3
4-FC6H4
Br
7
N
Cl
N
Br
N
H
H
H
2u
ee,
2v
ee,
2w
8
ee,
61%
yield
84%
78%
66%
9
a Conditions: 1 (0.20 mmol), [Ru(p-cymene)I2]2 (4.0 mol%), PD (20 mol%),
mesitylene (3.0 mL), H2 (500 psi), (R)-3d (10 mol%), 5 Å MS (30 mg), 40 oC,
72-96 h.
10
11
12
13
14
15
16
17
Next, we explored the substrate scope of different substituents
on the benzo ring (Scheme 2). Various substrates, such as
methoxyl group and halogen group, all performed very well under
the optimized conditions, the products were obtained in good
yields and enantioselectivities (2r-2u). In addition, the positions of
the substituent show obvious influence on the yields and
enantioselectivities (2v-2w). For example, when the chloro group
was at the 7-position, the ee value obviously decreased to the
56%, compared with the result of the chloro group at the
6-position (86% ee). To further demonstrate the versatility of our
method, 2,3-disubstituted tetrahydroquinolines were also
obtained under the standard reaction conditions (Scheme 3).
4-ClC6H4
4-BrC6H4
3-ClC6H4
2-Naphthyl
2-Furanyl
Methyl
a Conditions: 1 (0.20 mmol), [Ru(p-cymene)I2]2 (4.0 mol%), PD (20 mol%),
mesitylene (3.0 mL), H2 (500 psi), (R)-3d (10 mol%), 5 Å MS (30 mg), 40 oC,
72 h. b Determined by chiral HPLC. c Isolated yields.
With the optimized conditions in hand, a variety of substrates
were investigated (Table 2). When introducing the methyl group
to the para-position of the phenyl ring, the reaction gave the
desired product in good yield and high enantioselectivity (2b). The
enantioselectivities slightly decreased when the methyl group
was at the ortho-position or meta-position (2c-2d). Different
groups at the para-position all could furnish products in good
yields and moderate enantioselectivities (2e-2f). When the
substrates with more electron-donating groups such as methoxyl
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Report
Scheme 3 Enantioselective synthesis of 2,3-disubstituted tetrahydro-
Scheme 4 The control experiments.
quinolines.a
Under the Standard Conditions:
O
O
p
-cymene)I2 2
[Ru(
3d PD, H
]
Me
Ph
Me
Ph
R
3d
,
-cymene)I2 2
]
( )-
p
[Ru(
Ph
R
)-
,
psi)
Ph
(
2 (500
40 o
(a)
+
Me
NH2
N
H
Ph
ee
PD, H
NH2
conv
2 (500 psi), Mesitylene
C
N
H
N
H
Mesitylene,
MS, 72 h
40 o
5
MS, 72 h
C,
Å
5
Å
.
>95%
93%
95%
88%
yield,
1x
=
:1
2x
56%
2x'
d.r. 8.5
as
ee,
ee,
Starting Material:
68%
90%
7%
Quinoline
yield
yield
R
3d
p
,
-cymene)I2 2
[Ru(
]
(
)-
O
(b)
p
-cymene)I2 2
[Ru(
)-
]
PD, H2
Mesitylene
MS,
72 h
N
Ph
N
H
Ph
psi),
R
3d PD, H
,
(500
psi)
(
2 (500
40 o
40 o
5
Å
+
C,
as
ee
88%
yield,
C
N
N
H
Mesitylene,
MS, 72 h
NH2
Source:
Dihydrophenanthridine
(H-PD)
Hydrogen
H
5
Å
1y
2y
ee,
=
:1
d.r. 2.5
2y'
O
ee,
20%
yield
30%
45%
59%
R
3d H-PD,
Mesitylene
MS, 72 h
Å
yield
,
(
)-
40 o
Ph
(c)
N
H
Ph
ee
5
a Conditions: 1 (0.20 mmol), [Ru(p-cymene)I2]2 (4.0 mol%), PD (20 mol%),
mesitylene (3.0 mL), H2 (500 psi), (R)-3d (10 mol%), 5 Å MS (30 mg), 40 oC,
72 h.
C,
N
H
NH2
H
.
conv
46%
36%
90%
H-PD
yield,
and
the Role of CPA:
Investigation of
Reaction
Background
O
To clarify the detailed reaction mechanism, several control
experiments were carried out, as shown in Scheme 4. First,
2-aminochalcone was conducted under the standard conditions,
affording chiral product in 93% yield and 88% ee (Scheme 4a).
When 2-aminochalcone is replaced with quinoline, this reaction
could give the similar yield and enantioselectivity (Scheme 4b).
The comparison of result reflects that quinoline was the reaction
intermediate. In addition, quinoline could be isolated, which
further confirms this conclusion. When 2-aminochalcone was
served as substrate and dihydrophenanthridine (H-PD) was used
as hydrogen source, the reaction furnished the target product in
36% yield and 90% ee (Scheme 4c). Compared with previous 88%
ee value, this result reveals that this system might have
background reaction. Subsequently, the background reaction was
investigated. These results demonstrate that there is obvious
background reaction in this system. When chiral phosphoric acid
was added to the reaction, it was noted that the background
reaction was more serious, delivering tetrahydroquinoline in 91%
yield (Scheme 4d-4g). In addition, quinoline could be hydro-
genated using ruthenium and hydrogen gas (Scheme 4f-4g). Using
2-aminochalcone as substrate and hydrogen balloon instead of
high pressure, only quinoline product was obtained (Scheme 4h).
It should be concluded that the carbon-carbon double bond could
be hydrogenated from analysis of the two reactions (Scheme 4d,
4h). Besides, chiral phosphoric acid also promotes the formation
of quinoline (Scheme 4i). In the sole solvent of mesitylene, the
product quinoline cannot be generated (Scheme 4j).
p
-cymene)I2 2
[Ru(
]
Ph
+
(d)
H
Mesitylene
NH2
2 (500 psi),
N
Ph
N
Ph
40 o 72 h
H
C,
.
conv
>95%
76%
24%
yield
yield
O
R
3d
,
-cymene)I2 2
]
( )-
p
[Ru(
Ph
+
(e)
H
Mesitylene
MS, 72 h
Å
2 (500 psi),
NH2
conv
N
Ph
N
Ph
ee
40 o
5
H
C,
.
>95%
9%
91%
2%
yield,
yield
p
-cymene)I2 2
[Ru(
]
(f)
H
Mesitylene
N
Ph
Ph
2 (500 psi),
N
Ph
40 o 72 h
H
C,
23%
yield
R
3d
,
-cymene)I2 2
]
( )-
p
[Ru(
H
(g)
N
psi), Mesitylene
N
Ph
ee
2 (500
40 o 72 h
C,
H
91%
2%
yield,
Investigation of the Formation Pathway of Intermediate
Quinoline
O
p
-cymene)I2 2
[Ru(
]
Ph
+
(h)
40 o Mesitylene
C,
2 balloon, 72 h
N
Ph
N
H
Ph
NH2
H
42%
70%
Not detected
yield
O
O
R
3d
Mesitylene
,
(
)-
Ph
Ph
(i)
(j)
40 o 72 h
C,
N
Ph
Ph
NH2
NH2
yield
Mesitylene
40 o 72 h
C,
N
Not detected
According to above experimental results and previous related
studies, a plausible reaction mechanism is proposed (Figure 2).
First, 2-aminochalcone exists in the stable (E)-configuration under
the normal conditions, then the amino group cannot approach
the carbonyl group for the next condensation reaction. There are
two paths to form quinoline intermediate. On the one hand,
chiral phosphoric acids could promote conversion of the stable
but unreactive (E)-configuration into the unstable but reactive
(Z)-configuration. The detailed process includes: protonation of
the carbonyl group, and then the formation of iminium ion with
electron transfer. Next, the carbon-carbon bond could rotate
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Enantioselective Synthesis of Tetrahydroquinolines
Chin. J. Chem.
quickly.14 Subsequently, isomerization, dehydration and
cyclization proceed smoothly, providing the aromatic quinolines.
On the other hand, the carbon-carbon double bond could be
hydrogenated using ruthenium and hydrogen gas. Hence, the
carbon-carbon bond could rotate quickly. The amino group could
approach the carbonyl group for the next dehydration and
dehydrogenation. Besides, PD could be reduced in situ by
ruthenium complex and hydrogen gas. The reduced PD could
accomplish biomimetic asymmetric reduction of quinoline
intermediates in the presence of chiral phosphoric acids.
Meanwhile, the PD was regenerated with ruthenium metal and
hydrogen gas for the next catalytic cycle.
phenanthridine (7.2 mg, 0.04 mmol, 20 mol %), 5 Å molecular
sieves (30 mg) and substrates 1 (0.20 mmol) in mesitylene (3.0
mL) was stirred at room temperature for 5 min in glove box and
then the reaction mixture was transferred to an autoclave. The
hydrogenation was performed at 40 oC (oil bath temperature)
under hydrogen gas (500 psi) for 72-96 h. After careful release of
the hydrogen gas, the autoclave was opened and the reaction
mixture was directly purified by column chromatography on silica
gel using hexanes and ethyl acetate as eluent to give the desirable
chiral products 2. The enantiomeric excesses were determined by
chiral HPLC.
The full experimental details can be found in the Supporting
Information.
Figure 2 Plausible reaction mechanism.
O
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
O
P
O
OH
Ru-H
*
R
O
E
(
)
NH2
O
R
Acknowledgement
Z
(
)
R
O
Financial support from the National Natural Science
Foundation of China (21532006, 21690074) and Chinese Academy
of Sciences (XDB17020300, QYZDJ-SSW-SLH035, DICP I202002) is
acknowledged.
NH2
NH2
and
R
H2O
H2
H2O
N
References
[1] For reviews see: (a) Sridharan, V.; Suryavanshi, P. A.; Menéndez, J. C.
Advances in the Chemistry of Tetrahydroquinolines. Chem. Rev. 2011,
111, 7157–7259. For selected examples, see: (b) Ding, C. Z.; Hunt, J. T.;
Ricca, C.; Manne, V.
N
R
R
N
H
O
O
O
*
P
Ru(II)
OH
3-Imidazolylmethylaminophenylsulfonyltetrahydroquino -lines, a Novel
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H2
N
H
N
Conclusions
In summary, we have developed a facile synthesis of chiral
tetrahydroquinolines with high yields and enantioselectivities via
one-pot cascade biomimetic reduction. This efficient method
employs easily available starting materials 2-aminochalcones
served as substrates and catalytic amount of phenanthridine as
regenerable NAD(P)H model. Furthermore, the reaction process
and mechanism are clearly explained. The mechanistic studies
suggest two separate pathways for formation of intermediate
quinoline from the stable (E)-configuration of 2-aminochalcones.
Further researches of other one-pot biomimetic reactions are
under investigation by our group, and will be reported in due
course.
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Experimental
General procedure for synthesis of tetrahydroquinolines: A
mixture of [Ru(p-cymene)I2]2 (7.8 mg, 0.008 mmol, 4.0 mol%),
chiral phosphoric acid (R)-3d (11.6 mg, 0.02 mmol, 10 mol%),
Chin. J. Chem. 2019, 37, XXX－XXX
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Chin. J. Chem. 2019, 37, XXX－XXX
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(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2019
Manuscript revised: XXXX, 2019
Manuscript accepted: XXXX, 2019
Accepted manuscript online: XXXX, 2019
Version of record online: XXXX, 2019
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Entry for the Table of Contents
Page No.
Enantioselective Synthesis of Tetrahydroquino-
lines via One-pot Cascade Biomimetic Reduction
O
p
CPA
,
]
-cymene)I2 2
[Ru(
R'
R
R
Ar
Ar
R'
NH2
PD, H
psi)
2 (500
5
N
N
PD
MS
Å
Mesitylene,
H
25 Examples
ee
Regenerable
to 92%
up
model
NAD(P)H
A novel and efficient approach to chiral tetrahydroquinolines with excellent enantioselectivities
and high yields has been described via one-pot cascade biomimetic reduction. Furthermore, the
detailed reaction pathway includes the acid-catalyzed and ruthenium-catalyzed formation of
aromatic quinoline intermediates and biomimetic asymmetric reduction.
Zi-Biao Zhao, Xiang Li, Mu-Wang Chen, Bo Wu
and Yong-Gui Zhou
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.