Kinetic Resolution of 2-Substituted 1,2-Dihydroquinolines by Rhodium-Catalyzed Asymmetric Hydroarylation?

Article abstract of DOI:10.1002/cjoc.202000742

A highly efficient kinetic resolution of racemic 2-substituted 1,2-dihydroquinolines via Rh-catalyzed asymmetric hydroarylation has been described for the first time. A variety of arylboronic acids coupled with 2-substituted 1,2-dihydroquinolines under mild reaction condition. The transformations into the enantio-enriched 2,3-diaryl-tetrahydroquinolines as well as the recovered chiral 2-aryl-dihydroquinolines were obtained with high yields and excellent enantioselectivities (86%—99% ee, s factor up to 1057).

Full text of DOI:10.1002/cjoc.202000742

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Kinetic Resolution of 2-Substituted 1,2-Dihydroquinolines by Rhodium-
Catalyzed Asymmetric Hydroarylation
Authors: Baohua Cai, Qingjing Yang, Ling Meng and Jun (Joelle) Wang*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2021, 39, 10.1002/cjoc.202000742.
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.202000742.
ISSN 1001-604X • CN 31-1547/O6
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www.cjc.wiley-vch.de

Wang Jun (Orcid ID: 0000-0001-9723-4054)
Cite this paper: Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Kinetic Resolution of 2-Substituted 1,2-Dihydroquinolines by
Rhodium-Catalyzed Asymmetric Hydroarylation
Baohua Cai,a Qingjing Yang,a Ling Menga,b and Jun (Joelle) Wang*,a,b
a Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China
b Department of Chemistry, Hong Kong Baptist University, Kowloon, Hong Kong
Dedicated to the 10th anniversary of Department of Chemistry, SUSTech.
Keywords
Kinetic resolution | Hydroarylation | Tetrahydroquinoline | Asymmetric catalysis | Transition metal
Main observation and conclusion
A highly efficient kinetic resolution of racemic 2-substituted 1,2-dihydroquinolines via Rh-catalyzed asymmetric hydroarylation has been
described for the first time. A variety of arylboronic acids coupled with 2-substituted 1,2-dihydroquinolines under mild reaction condi-
tion. The transformations into the enantio-enriched 2,3-diaryl-tetrahydroquinolines as well as the recovered chiral 2-aryl-dihydroquin-
olines were obtained with high yields and excellent enantioselectivities (86-99% ee, s factor up to 1057).
Comprehensive Graphic Content
O
Ar
F
mol
%)
mol
[Rh(cod)Cl]2 (5
R3
R3
R3
R
%)
F
(
)-DifluorPhos (12
+
O
O
+
N
R2
PPh2
PPh2
ArB(OH)2
N
R2
N
R2
KOH, toluene, 30-50 °C
R1
R1
R1
F
O
O
O
O
O
O
F
unactivated double bond
O
R1 Me, Bn, Ph,
H4
=
4-ClC6
42-49%
88-99%
19:1 dr
35-49%
65-99%
yield
ee
yield
ee
scope
wide substrate
mild condition
R
R2 Me, Ar
(
)-Difluorphos
=
>
R3 Me,
=
Cl, OMe
enantioselectivity
high
excellent diastereoselectivity
nitrogen heterocyclic
with two vicinal stereogenic centers
products
s
efficient kenetic resolution: factor 48-1057
highly
*E-mail: E-mail: junwang@hkbu.edu.hk
View HTML Article
Supporting Information
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.202000742
This article is protected by copyright. All rights reserved.

First author et al.
Report
Scheme 1 Synthesis of chiral THQs by kinetic resolution
Background and Originality Content
secondary
and
Liu)
of monosubstituted
via kinetic resolution of
amine
(Akiyama,
THQs
a) Synthesis
R2
cyclic
The structural motifs of optically active 1,2,3,4-tetrahydroquin-
olines (THQs) exist in a wide range of natural products, pharmaceu-
tical molecules and even ligands could be employed in the catalytic
reactions (Figure 1).[1] Furthermore, the THQs can serve as versatile
synthetic intermediates for synthesis of bioactive compounds. In
this context, developing efficient synthetic approaches for access to
chiral THQs has become an important research area and attracted
great attention from many scientists from the areas of chemical syn-
thesis, medicinal chemistry and bioactivity investigation.[2]
O
or
cat*
R2
CPA Fe
+
R2
N
H
R1
N
R1
N
R1
Oxidant
H
and
α,α−
of
disubstituted
via kinetic resolution of amines
Coldham,
Cai)
THQs
b) Synthesis
R3
(Yang,
BuLi
n
R3
CPA
R3
(-)-sparteine
(R2)+
R2
R1
R2
R1
N
H
N
H
Cbz
N
N
R1
N
PG
Cbz
CuCl
R)-BINOL
(
I
R3
R2
R1
H2N
O
CF3
MeO
N
O
H
access α,β−
H
Kinetic resolution-borylation to
R2
disubstituted
THQs
c)
d)
(Hou)
F3C
CuCl
R,Sp
Bpin
H
H
R2
)-JosiPhos
R2
+
(
CF3
+
B
2pin2
N
Et
N
H
N
R1
R1
N
R1
N
N
PG
O
OEt
PG
PG
OMe
Me
O
work
This
Torcetrapib
neurotrophic
hepatoprotective
agent
[Rh(cod)Cl]2
Ar
R
2
R2
(
)-DifluorPhos
R2
+
R1
+
R
1-NaPh
ArB(OH)2
∗
KOH
R1
N
R1
O
N
N
N
P
O
PPh2
PG
PG
PG
O
O
N
Me
−
(
)-Galipinine
Dihydro-Quinaphos
Results and Discussion
Figure 1 Representative compounds with THQ scaffolds
To begin the study, we embarked our investigation by using ra-
cemic methyl 2-phenylquinoline-1(2H)-carboxylate (rac-1a) and
phenylboronic acid 2a as model substrates (Table 1). To our delight,
the hydroarylated product 3aa was obtained as a single diastere-
omer (dr > 99:1) in 30% yield with 83% ee in the presence of 5 mol %
[Rh(cod)Cl]2/(R)-Binap complex when 2.4 equiv phenylboronic acid
2a was used, accompanying a recovery of 1a in 51% yield with 40%
ee (entry 1). This preliminary result encouraged us to evaluate other
C2-symmetric bisphosphorus ligands, namely (R)-Biphep, (R)-
Segphos and the electro-deficient (R)-Difluorphos. All of the ligands
provided the desired product 3aa in 30-48 % yields with 80-91 % ee
(s factor 13-48). Meanwhile, the substrate 1a was recovered in 43-
51 % yields and 40-80 % ee (entries 1-4). (R)-Difluorphos (L4), offer-
ing the product in 41% yield with the highest enantioselectivity (91%
ee), was identified as the superior ligand for the reaction (entry 4).
Next, other rhodium(I) species [Rh(cod)OH]2 and Rh(cod)2OTf with
coordination of the ligand L4 were tested for the hydroarylation. Di-
minished reactivity and enantioselectivity of the reaction were ob-
served (entries 5-6). The alternative Lewis base K3PO4 improved the
product yield but decreased the enantioselectivity of (49% yield, 84%
ee) (entry 7). Finally, the optimal reaction conditions were achieved
as shown in the entry 4: 5 mol % [Rh(cod)Cl]2 combined with 12
mol % (R)-Difluorphos in toluene at 30 oC, using 2.5 equivalents of
KOH as the base. The configuration of the recovered 1a was con-
firmed to be 2R by comparing with the literature.[6] So that, the con-
figuration of the product 3aa was confirmed to be 2S. According to
1D NOESY, the 3aa was the trans isomers with the configuration
2S,3R (see the Supporting Information).
To date, a great number of methods for the synthesis of THQs
have been successfully developed, including Pavarov reaction, Mi-
chael addition, intramolecular C−H functionalization, direct func-
tionalization of THQs, kinetic resolution of THQs, hydrogenation of
quinolines, Reissert-type reaction, and so forth.[3] Compared with
these methods, kinetic resolution is still underdeveloped and high
resolution efficiency is always of great challenge. However, kinetic
resolution, which provides a simple and efficient way to access both
the chiral products and recover the starting materials, has attracted
considerable attention from academy and industry. Some elegant
kinetic resolution studies related to THQs have been reported. In
2015, Akiyama developed a chiral phosphoric acid (CPA) catalyzed
oxidative kinetic resolution of racemic 2-substituted tetrahydro-
quinolines, providing the monosubstituted THQs with outstanding
enantioselectivity (61->99% ee). [4a] In 2019, Liu reported a high ef-
ficient iron-catalyzed dehydrogenative kinetic resolution of 1,2-di-
hydroquinolines using air as an oxidant (Scheme 1a).[4b] With re-
spect to the synthesis of α,α-disubstituted THQs, Yang, Coldham,
and Cai employed chiral phosphoric acid, chiral tertiary amine and
transition metal respectively to catalyze kinetic resolution-transfor-
mations of amines (Scheme 1b).[5] In 2017, Hou and co-workers re-
ported kinetic resolution of 2-substituted 1,2-dihydroquinolines via
Cu-catalyzed asymmetric borylation, furnishing THQs containing
two vicinal stereogenic centers in 43-48% yield with 90-99% ee
(Scheme 1c).[6] Nevertheless, methods to the direct synthesis of tet-
rahydroquinolines with two vicinal aromatic groups has not been
investigated. To the best of our knowledge, one of the most effi-
cient strategy to introduce aromatic groups is asymmetric hy-
droarylation catalyzed by transition metal catalysis. Recently, our
group reported a highly efficient kinetic resolution of chromene via
rhodium-catalyzed asymmetric hydroarylation.[7] Based on these
prior research and our continuous interests on the nitrogen heter-
ocyclic compounds,[8] we envisioned to investigate a kinetic resolu-
tion-hydroarylation of racemic 1,2-dihydroquinolines for the ac-
cessing to THQs with two vicinal aryl groups (Scheme 1d).
Table 1 Optimization of the reaction conditionsa
mol
Ph
Ph
%)
mol
[Rh] (10
L
%)
Ligand ( ) (12
+
+
PhB(OH)2
N
Ph
N
Ph
N
base
(2.5 equiv)
toluene, 30 o
24 h
C
O
O
O
O
O
O
-
2a
rac
1a
3aa
1a
R
)-
(
O
O
F
F
O
O
O
O
PPh2
PPh2
H3CO
H3CO
PPh2
PPh2
PPh2
PPh2
PPh2
PPh2
F
F
O
O
L1
)
L2
)
L3
)
L4
)
R
R
R
R
( )-Difluorphos (
(
)-Binap (
(
)-Biphep (
(
)-Segphos (
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
The substituent effect of R1
Ph
Ph
Ph
1a
1a
3aa
3aa
N
N
N
Conv.
(%)e
entry
[Rh]
L
yield
ee
yield
ee
sf
Bn
Ph
Cl
O
O
O
O
O
O
(%)b (%)c,d (%)b (%)c,d
conv =
21
h,
s =
ee
52%,
35% 99%
yield,
90
conv =
s =
ee
18
1b
44%,
76%
90
conv
=
h,
s =
206
ee
ee
18
1c
51%,
99%
h,
37%
3ba
1d
3da
41%
3ca 47%
yield,
32%
yield,
1
2
3
4
5
6
[Rh(cod)Cl]2 L1
[Rh(cod)Cl]2 L2
[Rh(cod)Cl]2 L3
[Rh(cod)Cl]2 L4
[Rh(cod)OH]2 L4
Rh(cod)2OTf L4
51
49
47
43
49
52
43
40
53
80
75
53
65
83
30
38
48
41
38
38
49
83
80
84
91
80
87
84
33
40
49
45
40
43
49
16
15
28
48
15
28
30
ee
89%
49%
ee
yield,
95%
95%
yield,
yield,
The substituent effect of R2
Ph
Ph
Ph
Me
Me
N
O
N
O
N
Ph
Ph
O
Ph
O
Me
206
O
O
Me
conv =
18
h,
s =
ee
conv =
48%
yield,
s =
51%,
99%
conv =
s =
111
ee
24
40%,
67%
402
18
1e
52%,
99%
h,
h,
35%
3ea 41%
1g
ee
38%
44%
1f
yield,
yield,
yield,
ee
95%
ee
99%
yield,
ee
3fa 41%
3ga
91%
yield,
7g [Rh(cod)Cl]2 L4
Ph
Ph
Ph
a Reaction Conditions: [Rh] (10 mol %) and L (12 mol %) in toluene (1 mL)
were stirred at RT for 30 min under argon. rac-1a (0.2 mol), 2a (0.48 mol),
KOH (0.5 mmol) were then added. The resulting mixture was stirred at 30 ℃
for 24 h. b Isolated yield. c Determined by chiral HPLC analysis. d Diastereo-
meric ratio (dr) > 99:1 (determined by 1H NMR). e Calculated conversion, C =
ee1a/(ee1a + ee3aa). f Selectivity factor(s) = ln [(1 – C) (1 – ee1a)]/ln [(1 – C) (1 +
ee1a)]. g K3PO4 was used instead of KOH.
N
N
N
O
Me
Ph
O
Ph
Ph
O
Cl
O
O
tBu
O
conv =
s =
ee
ee
conv =
50%,
98%
yield,
yield,
s =
ee
18
51%,
99%
259
24
1i
303
h,
h,
40%
conv =
s =
ee
99%
93%
21
1h
145
52%,
h,
1j
40%
yield,
42%
38%
yield,
3ha 47%
ee
97%
96%
3ia
45%
3ja
yield,
ee
yield,
The substituent effect of R3
Me Ph
MeO
Ph
Cl
Ph
N
N
O
Having established the optimized reaction conditions, we next
tested the scope of 1,2-dihydroquinolines to evaluate the efficiency
of the established catalytic system (Scheme 2). The substrates bear-
ing different nitrogen protecting groups, including -CO2Me, -CO2Bn,
-CO2Ph and -CO2(4-ClC6H4), can furnish the corresponding products
3aa-da in 32-49% yields with excellent enantioselectivities (89-95%
ee), accompanying the recovery of (R)-1,2-dihydroquinolines 1a-d
in 35-43% yields and 75-99% ee (s factor 48-206), among which the
substrate rac-1c with carbamate moiety -CO2Ph gave the best reac-
tivity and enantioselectivity with a selectivity factor of 206. It was
found that the position of substituents of C2-benzene rings have no
significant impact on the reactivity as well as the enantioselectivity
of the reaction, affording the arylation products 3ea-ga in 41-44%
yields with 91-99% ee. Racemic 1,2-dihydroquinolines with bulky
tert-butyl and electron-withdrawing chloro groups on C2-benzene
ring can also afford the corresponding products 3ha-ia in excellent
yields (45-47%) and enantiomeric excesses (93-97%). The hydroary-
lations of 1,2-dihydroquinolines with either electron-rich or elec-
tron-deficient groups on the 6-positions were found successful and
furnished the targeted products 3ka-ma in 43-45% yields with ex-
cellent enantioselectivities (92-99% ee with s factors 48-1057). To
our delight, it was found that the 2-alkyl-1,2-dihydroquinolines (1j)
could be resolved smoothly with a selectivity factor of 259 to afford
the chiral THQs (3ja) in 42% yield with 96% ee.
N
Ph
Ph
Ph
O
O
O
O
O
conv =
s =
ee
ee
conv =
s =
ee
ee
24
1k
3ka
712
conv =
s =
51%,
1057
48%,
94%
48
18
1l
3la
42%,
67%
h,
49%
18
h,
h,
1m
ee
ee
99%
48%
38%
99%
yield,
45%
yield,
45%
yield,
3ma
43%
99%
92%
yield,
yield,
yield,
a Reaction Conditions: [Rh(cod)Cl]2 (5 mol %) and (R)-Difluorphos (12 mol %)
in toluene (1 mL) were stirred at RT for 30 min under argon. rac-1a-1m (0.2
mol), 2a (0.48 mol), KOH 0.5 mmol) were then added. The mixture was
stirred at 30 °C for the indicated period of time. Isolated yields of products
were given. The ee values were determined by HPLC analysis.
Next, we investigated the hydroarylation reaction of 1c with dif-
ferent arylboronic acids (Scheme 3). All of the arylboronic acids
tested in the reaction afforded the desired THQs in good to high
reactivity (34-52% yields) with high enantioselectivities (86-96% ee),
and the starting materials were recovered in 38-48% yields with 87-
99% ee (s factor is 68-193). Arylboronic acids bearing either elec-
tron-donating (-Me and -tBu) or electron-withdrawing group (-F and
-CF3) were all well tolerated in the hydroarylation (3cb-3cd, 3cf-
3ch). In general, arylboronic acids with substituents on 3-position
of aromatic rings provided higher enantioselectivities than those
with substituents on 4-position without scarifying reactivity (3cg-h
vs 3cb-c). Expectedly, no reaction was observed when 2-substituted
phenylboronic acid was employed under the present reaction con-
dition.
Scheme 2 The scope of the 1,2-dihydroquinolines
Scheme 3 The scope of the arylboronic acids
Ph
R2
mol
%)
mol
[Rh(cod)Cl]2 (5
Ar
mol
%)
mol
R3
R3
R3
[Rh(cod)Cl]2 (5
R
%)
(
)-DifluorPhos (12
+
+
R
%)
(
)-DifluorPhos (12
N
R2
N
R2
N
+
PhB(OH)2
+
Ph
ArB(OH)2
N
-
Ph
N
N
Ph
KOH, toluene, 30 °C
KOH, toluene
R1
-
R1
R1
Ph
Ph
Ph
O
O
O
O
O
O
O
O
O
(
O
O
O
2a
3aa-3ma
R
)-
1a-1m
rac
1a-1m
(
rac
1c
2a-h
3ca-3ch
1c
R
)-
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

First author et al.
Report
General procedures for synthesis of 1
CF3
Me
tBu
The quinoline or substituted quinoline (10 mmol) were dis-
o
solved in dry THF (20 mL) at -78 C under a nitrogen atmosphere,
and RMgBr (12 mmol, 1 M solution in Et2O) was slowly added. After
2h at -78 oC, ClCO2R (12 mmol) was added. After 30 min, the solu-
tion was quenched with a solution of NH4Cl. The solution was ex-
tracted with EtOAc, and the organic layer was washed with brine,
dried over anhydrous Na2SO4, and evaporated. Purification of the
residue by column chromatography over silica gel eluted the sub-
strates 1
N
N
N
N
Ph
Ph
Ph
Ph
O
O
O
O
O
O
O
O
30 o 24 h
50 o 24 h
conv =
51%,
C,
50 o 6 h
50 o 6 h
C,
C,
C,
conv =
s =
49%,
68
ee
s =
conv =
s =
99%
86%
conv =
s =
52%,
yield,
49%
145
ee
99%
53%,
yield,
49%
69
ee
ee
92
ee
88%
1c
48%
87%
ee
92%
1c
1c
1c
38%
44%
41%
99%
yield,
49%
yield,
ee 3cd
49%
ee
3cb
3cc
93%
3ce
yield,
yield,
yield,
yield,
Me
F
CF3
General procedures for kinetic resolution of racemic 1
In an argon-filled glovebox, an oven-dried vial fitted with a stir-
rer bar was charged with [Rh(cod)Cl]2 (0.01 mmol) and (R)-Difluor-
phos (0.024 mmol) in toluene (0.5 mL) and the mixture was stirred
at room temperature for 30 min. Then racemic methyl 2-phe-
nylquinoline-1(2H)-carboxylate (rac-1) (0.20 mmol) was added and
the mixture was stirred for another 20 min. KOH (0.50 mmol), phe-
nylboronic acid 2 (0.48 mmol) and toluene (0.5 mL) were added.
The Schleck reaction vial was sealed with a rubber plug and taken
out glovebox. The tube was then placed into a preheated oil bath
(30 °C) and stirred for 24 h. The reaction mixture was diluted with
EtOAc and H2O. The aqueous layer was extracted with EtOAc. The
organic layer was dried over anhydrous Na2SO4, filtered, and con-
centrated under vacuum. The residue was chromatographed on sil-
ica gel to get the corresponding arylation product 3 and the recov-
ered starting material (R)-1.
N
N
N
Ph
Ph
Ph
O
O
O
O
O
O
30 o 24 h
conv =
49%,
30 o 24 h
conv =
50%,
30 o 24 h
C,
C,
C,
s =
s =
68
ee
193
ee
conv =
s =
170
ee
60
h,
1c 41%
51%,
1c
47%
49%
87%
1c
46%
96%
yield,
yield,
99%
yield,
3ch
34%
yield,
52%
ee
3cf
ee
92%
96%
yield,
ee
3cg
94%
yield,
a Reaction Conditions: [Rh(cod)Cl]2 (5 mol %) and (R)-Difluorphos (12 mol %)
in toluene (1 mL) were stirred at rt for 30 min under argon. rac-1c (0.2 mol),
2b-2h (0.48 mol), KOH (0.5 mmol) were then added. The mixture was stirred
for the indicated period of time. Isolated yields of products were given. The
ee values were determined by HPLC analysis.
On the basis of the previous studies of our group[7] and the lit-
eratures, [9] the mechanism of the hydroarylation is proposed and is
shown in Scheme 4. The chiral species A, formed by the ligand ex-
change of the rhodium precursor with (R)-Difluorphos and KOH, un-
dergoes transmetalation with phenylboronic acid to form the phe-
nylrhodium species B. Then the coordination and syn-insertion of
the double bond of rac-1a occurs, generating the complex C by syn-
addition and along with the chiral recovered starting material (R)-
1a. Subsequently, 1,4-Rh shift takes place within the complex C to
generate a more thermodynamically stable intermediate D, of
which hydrolysis leads to the formation of final product and regen-
erates the species A engaging in next catalytic cycle. The excellent
regioselectivity is resulted from the syn-addition of the Rh-Ph and
the rigid conformation of the substrates.
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2021xxxxx.
Acknowledgement (optional)
We gratefully acknowledge Shenzhen Overseas High-level Talents
Innovation
Plan
of
Technical
Innovation
Project
(KQJSCX20180319114439973) for financial support. This paper is
dedicated to the 10th anniversary of Department of Chemistry, SUS-
Tech.
Scheme 4 The proposed mechanism
P
References
+
R
( )-Difluorphos
*
[Rh(cod)Cl]2
Ph
P
KOH
OH
N
Ph
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ramidites and Their Applications in Iridium-Catalyzed Allylic Alkylation
of Indoles. Synthesis 2009, 2009, 2076-2082; (b) Gore, V. K.; Ma, V. V.;
Yin, R.; Ligutti, J.; Immke, D.; Doherty, E. M.; Norman, M. H. Structure-
activity relationship (SAR) investigations of tetrahydroquinolines as
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3aa
CO2Me
P
*
P
Rh
H2O
PhB(OH)2
A
P
*
P
Rh
Ph
P
P
*
Rh
*
B
P
N
Ph
P
Rh
CO2Me
D
N
Ph
CO2Me
-
N
Ph
rac
1a
N
Ph
CO2Me
C
CO2Me
1a
R
(
)-
Conclusions
In summary, a highly efficient kinetic resolution of racemic 2-
substituted 1,2-dihydroquinolines was successfully established via
rhodium-catalyzed asymmetric hydroarylation. This method pro-
vides a new strategy for the direct access to various 2,3-diaryl tet-
rahydroquinolines in high reactivity with excellent enantioselectiv-
ity.
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Chin. J. Chem. 2021, 39, XXX－XXX

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(The following will be filled in by the editorial staff)
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Manuscript received: XXXX, 2021
Manuscript revised: XXXX, 2021
Manuscript accepted: XXXX, 2021
Accepted manuscript online: XXXX, 2021
Version of record online: XXXX, 2021
(a) Yang, Q.; Li, S.; Wang, J. Asymmetric Synthesis of Chiral Chromanes
Chin. J. Chem. 2021, 39, XXX－XXX
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First author et al.
Report
Entry for the Table of Contents
Kinetic Resolution of 2-Substituted 1,2-Dihydroquinolines by Rhodium-Catalyzed Asymmetric Hydroarylation
Baohua Cai, Qingjing Yang, Ling Meng and Jun (Joelle) Wang
Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Ar
mol
%)
mol
[Rh(cod)Cl]2 (5
R3
R3
R3
R
%)
(
)-DifluorPhos (12
+
+
R2
N
R2
N
R2
ArB(OH)2
N
KOH, toluene, 30 °C
R1
R1
R1
O
O
O
O
O
O
35-49%
65-99%
42-49%
88-99%
yield
ee
yield
ee
s
factor 48-1057
Kinetic Resolution: A highly efficient kinetic resolution of racemic 2-substituted 1,2-dihydroquinolines via Rh-catalyzed asymmetric hydroarylation has
been described for the first time. A variety of arylboronic acids coupled with 2-substituted 1,2-dihydroquinolines under mild reaction condition to give
the enantio-enriched 2,3-diaryl-tetrahydroquinolines as well as the recovered chiral 2-aryl-dihydroquinolines were obtained with high yields and excel-
lent enantioselectivities (86-99% ee, s factor up to 1057).
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© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX