Kinetic Resolution of 2,2-Disubstituted Dihydroquinolines through Chiral Phosphoric Acid-Catalyzed C6-Selective Asymmetric Halogenations

Letter

Kinetic Resolution of 2,2-Disubstituted Dihydroquinolines through

Chiral Phosphoric Acid-Catalyzed C6-Selective Asymmetric

Halogenations

Chaofan Zhu, Wei Liu, Fei Zhao, Yunrong Chen,* Houchao Tao,* Yu-Peng He,* and Xiaoyu Yang*

Cite This: Org. Lett. 2021, 23, 4104 −4108

Read Online

ACCESS

Metrics & More

Article Recommendations

sı Supporting Information

ABSTRACT: A novel kinetic resolution of 2,2-disubstituted dihydroquinolines was achieved by regioselective asymmetric

halogenations enabled by chiral phosphoric acid catalysis. A series of dihydroquinolines bearing 2,2-disubstitutions were well-

tolerated in these reactions, generating both the recovered dihydroquinolines and C-6-brominated products with high

enantioselectivities, with s-factors up to 149. In addition, this kinetic resolution protocol is also applicable for 2,2-disubstituted

tetrahydroquinoline and asymmetric iodonation reaction.

he electrophilic aromatic halogenation reaction is one of

the most fundamental organic reactions, and aryl halides

The tetrahydroquinoline (THQ) scaﬀolds are widely

present in a variety of biologically active natural products

and small molecules, and consequently the asymmetric

represent key building blocks in modern organic synthesis,

especially with the emergence of transition-metal-catalyzed

synthesis of THQs has drawn considerable research interests.

cross-coupling reactions. Despite the fact that no chiral

However, the asymmetric synthesis of 2,2-disubstituted THQs

was more challenging, compared to the asymmetric con-

structions of 2-substituted THQ analogues, and only limited

number of methods have been developed with limited

stereocenter is generated in these reactions, researchers have

developed several ingenious strategies to utilize these reactions

in asymmetric catalysis. Pioneered by Miller and co-workers,

chiral peptide-catalyzed asymmetric brominations of phenols

have been used for the asymmetric synthesis of atropoisomers,

substrate scope as well. Kinetic resolution (KR) is a

practicable method to produce enantioenriched N-hetero-

cycles, and a series of diﬀerent reactions have been utilized for

including biaryl, benzamide, and quinazolinone-type N−C

atropoisomers (Figure 1a). Asano and Matsubara and co-

workers reported the atroposelective synthesis of axially chiral

isoquinoline N-oxides and 8-arylquinolines via asymmetric

brominations of phenol derivatives enabled by chiral bifunc-

tional organocatalysts. Akiyama and co-workers reported the

asymmetric synthesis of multisubstituted biaryl skeletons by

chiral phosphoric acid (CPA)-catalyzed desymmetrization and

KR of N-heterocycles, including asymmetric acylations,

asymmetric hydrogen transfers, and others. However, it

was not until recently that the KR of 2,2-disubstituted

hydroquinolines was achieved. With our continuous interest

in development of novel asymmetric reactions via CPA-

catalyzed amination of anilines with azodicarboxylates, we

disclosed the ﬁrst KR of 2,2-disubstituted hydroquinolines via

kinetic resolution reactions via asymmetric brominations. Tse

asymmetric remote aminations with azodicarboxylates

and Yeung and co-workers disclosed an ingenious desymme-

trizing asymmetric ortho-selective halogenations of phenol

derivatives, which gave access to potent chiral bisphenol

(

Figure 1d). Although excellent KR performances were

obtained in these reactions, the transformations of the

ligands (Figure 1b). Recently, Li and co-workers reported the

Received: March 22, 2021

Published: May 17, 2021

asymmetric synthesis of P-stereogenic phosphine oxides

through asymmetric organocatalyzed asymmetric ortho-bromi-

nations (Figure 1c). Interestingly, all these above-mentioned

examples utilized the electron-rich phenols as substrates;

however, another type of electron-rich arene, namely, aryl-

amine, has not been exploited in these reactions.

2021 American Chemical Society

104

Org. Lett. 2021, 23, 4104−4108

Organic Letters

Letter

Table 1. Reaction Condition Optimizations

Enantio-

meric

Excess, ee

(

variation from the

standard conditions

(S)-

conversion,

selectivity

entry

C (%)

factor, s

None

116

1.7

1.8

6.4

A2 instead of A1

A3 instead of A1

A4 instead of A1

A5 instead of A1

A6 instead of A1

A7 instead of A1

A8 instead of A1

B1 instead of A1

DCM instead of Tol

7.2

1.4

7.5

101

Et O instead of Tol

CHCl instead of Tol

−60 °C instead of

Figure 1. Asymmetric halogenations of electron-rich arenes and

−

78 °C

kinetic resolution of hydroquinolines.

−40 °C instead of

−

78 °C

Reactions were run with 1a (0.1 mmol), NBS (0.06 mmol) with

CPA catalyst (0.005 mmol, 5 mol %) in solvents (5 mL) at designated

temperatures. Determined by HPLC analysis on a chiral stationary

phase. Conversion (C) = ee /(ee + ee ). Selectivity factor (s) =

introduced hydrazine motif were relatively limited, which

could only be removed or converted to amino groups. Herein,

we report the ﬁrst KR of 2,2-disubstituted hydroquinolines via

CPA catalyzed C6-selective asymmetric halogenations with

high stereoselectivities, which also represent the ﬁrst

application of asymmetric electrophilic aromatic halogena-

ln[(1 − C)(1 − ee )]/ln[(1 − C)(1 + ee )]. At −60 °C.

tions of nonphenol-type substrates (Figure 1e).

With the optimal KR conditions in hand, we set out to

explore the scope of this reaction (Scheme 1). A series of para-

and meta-substituted phenyl groups at the 2-position of DHQs

were ﬁrst studied, which were well-tolerated with the standard

conditions, giving s-factors up to 149 (1b−1g). The absolute

conﬁgurations of the bromination products were assigned by

analogy to (S)-2a, whose structure was unambiguously

determined by X-ray crystallography. Disubstituted phenyl

groups were also amenable to this KR reaction, albeit providing

slightly diminished KR performances (1h and 1i). Because of

the limitation of the protocol for the preparation of the racemic

substrates, the electron-deﬁcient aryl-substituted dihydroqui-

nolines were not investigated under the standard conditions.

However, the tetrahydroquinolines bearing α-electron-deﬁ-

cient aryl substitutions only aﬀorded poor KR performances

under these conditions. Furthermore, the heteroaryl groups,

such as furan and thiophene, were compatible with the

standard conditions as well, which generated both recovered

DHQs and bromination products with high enantioselectivities

(1j and 1k). Note that no other brominated side products

occurring at the highly nucleophilic heteroaryl groups was

detected in these reactions. With the excellent compatibility of

the 2-aryl groups in these reactions, we turned our attention to

the 2-alkyl groups of DHQs. Switching the 2-Me group to a 2-

We started our studies by choosing racemic 2-methyl-2-

phenyl substituted dihydroquinoline (DHQ) 1a as model

substrate. After careful optimizations of the reaction con-

ditions, the optimal KR condition was determined. In the

presence of spirocyclic CPA A1 (5 mol %), treatment of

racemic 1a with NBS (0.6 equiv) in toluene at −78 °C for 24 h

aﬀorded the recovered (R)-1a with 97% ee and the C-6

brominated product (S)-2a with 93% ee, corresponding to a

selectivity factor (s) of 116 (Table 1, entry 1). Note that the

bromination reaction proceeded with excellent regioselectivity,

and no C-8 brominated DHQ was observed. Variation of the

CPA catalysts was studied (Table 1, entries 2−8), which

suggested that only sterically hindered catalysts provided

decent KR performances (Table 1, entries 6−8). Switching the

chiral scaﬀold of CPA A1 from SPINOL-type to BINOL-type

led to signiﬁcant diminishment of the selectivity factor (Table

, entry 9), which suggested the critical role of the chiral

spirocyclic scaﬀold of the catalyst. However, a series of solvents

were also screened at low temperatures, which aﬀorded poor

KR performances (Table 1, entries 10−12). The reaction

temperature was also evaluated, which indicated that −78 °C

was optimal and increases in the reaction temperature led to

erosion of the selectivity factors (Table 1, entries 13−14).

105

Org. Lett. 2021, 23, 4104−4108

Organic Letters

Letter

Scheme 1. Substrate Scope for KR 2,2-Disubstituted

Hydroquinolines

Scheme 2. KR of 2,2-Disubstituted Dihydroquinolines via

CPA-Catalyzed Asymmetric Iodonation

using NCS as halogenation reagent under the same conditions

could not produce the desired chlorinated product.

To demonstrate the utilities of these KR reactions,

derivatizations of the chiral products were investigated

(

Scheme 3). Boronation of the 6-bromo-substitued DHQ

Scheme 3. Derivatizations of Chiral Products

Reactions were run with 1 (0.2 mmol), NBS (0.12 mmol) with CPA

(

R)-A1 (0.01 mmol, 5 mol %) in toluene (10 mL) at −78 °C for 12−

4 h. Isolated yields were noted. Enantiometric excess (ee) values

were determined by HPLC analysis on a chiral stationary phase. s =

ln[(1 − C)(1 − ee )]/ln[(1 − C)(1 + ee )]. Conversion (C) = ee /

(

ee + ee ).

s p

(

S)-2a with B Pin in the presence of Pd-catalyst generated the

2 2

Et group in the substrates was tolerated, albeit giving erosive s-

factors, compared to their 2-Me-substituted analogous (1l to

6-BPin-substituted DHQ 4a in 70% yield with retained ee

value, representing a valuable chiral building block for

diversiﬁcation of THQ derivatives as well (Scheme 3a).

Furthermore, a one-pot stepwise brominative KR and

boronation reactions were performed for racemic DHQ 1p

and 1q, which produced both the recovered starting material

(SM) and 6-BPin-substituted products with high enantiose-

lectivities, corresponding to good s-factors (Scheme 3b). Note

that this one-pot stepwise KR protocol could overcome the

diﬃculties encountered in separating the SM and brominated

products for certain substrates. The functionalizations of the

alkene moiety in the DHQ products were also studied for

asymmetric synthesis of diversiﬁed THQ products. Treatment

of the chiral brominated product (S)-2a with ICl in MeOH

readily produced the iodoetheriﬁcation product 5a in 95%

n). Finally, the 2,2-disubstituted THQ 1o was also evaluated

under the optimal conditions, which provided satisfactory KR

performance as well (with an s-factor of 50). Interestingly,

treatment of 2-monosubstittued dihydroquinoline with the

standard condition did not provide the desired C6-brominated

DHQ, which actually generated the aromatized quinoline as

the product and almost no KR performance was observed in

this reaction.

To further extend the scope of these KR reactions for 2,2-

disubstituted DHQs, we turned our attention to other

electrophilic halogenation reagents (Scheme 2). Satisfyingly,

the kinetic resolution of racemic 1a using NIS as the

halogenation reagent enabled by CPA (R)-A1 (5 mol %) in

toluene at −40 °C produced the recovered (R)-1a in 40% yield

with 84% ee and the C-6-idonated product (S)-3a in 37% yield

with 79% ee, corresponding to an s-factor of 22. However,

yield with high diastereoselectivity (Scheme 3c). In addition,

applying the same conditions on brominated THQ (S)-2o

produced the 8-iodonated THQ 6a in 75% yield, which would

106

Org. Lett. 2021, 23, 4104−4108

Organic Letters

Letter

be a valuable building block for derivatizations of THQ, since

it bears two diﬀerent halide handles.

Notes

The authors declare no competing ﬁnancial interest.

In conclusion, we disclosed the ﬁrst halogenative kinetic

resolution of 2,2-disubstituted hydroquinolines enabled by

chiral phosphoric acid catalyzed C6-selective asymmetric

brominations and iodonations. A series of 2-aryl and 2-alkyl

groups were very compatible with the optimal KR conditions,

which generated both the recovered hydroquinolines and 6-

halogenated products with high enantioselectivities (with s-

factors up to 149). In addition, the one-pot stepwise

brominative kinetic resolution and boronation protocol was

developed, which also exhibited high KR performances.

Further applications of this asymmetric strategy in kinetic

resolution of arylamines and N-heterocycles are currently

ongoing in our laboratory.

ACKNOWLEDGMENTS

■

We gratefully acknowledge NSFC (Grant Nos. 21702138,

1901162), National Key R&D Program of China (No.

018YFA0507000), and ShanghaiTech University start-up

funding for ﬁnancial support. The authors thank the support

from Analytical Instrumentation Center (No. SPST-

AIC10112914), SPST, ShanghaiTech University and Dr. Na

Yu (ShanghaiTech University) for the X-ray crystallographic

analysis.

REFERENCES

■

1) (a) Saikia, I.; Borah, A. J.; Phukan, P. Use of Bromine and

Bromo-Organic Compounds in Organic Synthesis. Chem. Rev. 2016,

16, 6837−7042. (b) Voskressensky, L. G.; Golantsov, N. E.;

Maharramov, A. M. Recent Advances in Bromination of Aromatic

ASSOCIATED CONTENT

■

sı Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.orglett.1c00978.

and Heteroaromatic Compounds. Synthesis 2016, 48 , 615 −643.

2) Gustafson, J. L.; Lim, D.; Miller, S. J. Dynamic Kinetic

Resolution of Biaryl Atropisomers via Peptide-Catalyzed Asymmetric

Full experiments and characterization data including H

Bromination. Science 2010, 328, 1251 −1255.

and C NMR spectra and HPLC for the synthesized

(3) Barrett, K. T.; Miller, S. J. Enantioselective Synthesis of

products ((S)-1a−1q, 2a−2o, 3a, 4a, 4p, 4q, 5a, and

Atropisomeric Benzamides through Peptide-Catalyzed Bromination. J.

Am. Chem. Soc. 2013, 135, 2963−2966.

o) (PDF)

4) Diener, M. E.; Metrano, A. J.; Kusano, S.; Miller, S. J.

Accession Codes

Enantioselective Synthesis of 3-Arylquinazolin-4(3H)-ones via Pep-

tide-Catalyzed Atroposelective Bromination. J. Am. Chem. Soc. 2015,

CCDC 2067699 contains the supplementary crystallographic

data for this paper. These data can be obtained free of charge

via www.ccdc.cam.ac.uk/data_request/cif, or by emailing

data_request@ccdc.cam.ac.uk, or by contacting The Cam-

bridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.

5) Miyaji, R.; Asano, K.; Matsubara, S. Bifunctional Organocatalysts

37, 12369−12377.

for the Enantioselective Synthesis of Axially Chiral Isoquinoline N-

Oxides. J. Am. Chem. Soc. 2015, 137, 6766 −6769.

(6) Miyaji, R.; Asano, K.; Matsubara, S. Induction of Axial Chirality

in 8-Arylquinolines through Halogenation Reactions Using Bifunc-

tional Organocatalysts. Chem. - Eur. J. 2017, 23, 9996−10000.

(7) Mori, K.; Ichikawa, Y.; Kobayashi, M.; Shibata, Y.; Yamanaka,

M.; Akiyama, T. Enantioselective Synthesis of Multisubstituted Biaryl

Skeleton by Chiral Phosphoric Acid Catalyzed Desymmetrization/

Kinetic Resolution Sequence. J. Am. Chem. Soc. 2013, 135, 3964−

3970.

AUTHOR INFORMATION

■

Corresponding Authors

Yunrong Chen − School of Physical Science and Technology,

ShanghaiTech University, Shanghai 201210, China;

Email: chenyr@shanghaitech.edu.cn

Houchao Tao − iHuman Institute, ShanghaiTech University,

Shanghai 201210, China; orcid.org/0000-0001-7598-

(8) Xiong, X.; Zheng, T.; Wang, X.; Tse, Y.-L. S.; Yeung, Y.-Y.

Access to Chiral Bisphenol Ligands (BPOL) through Desymmetrizing

Asymmetric Ortho-Selective Halogenation. Chem. 2020, 6, 919−932.

(9) Huang, Q.-H.; Zhou, Q.; Yang, C.; Chen, L.; Cheng, J.-P.; Li, X.

275; Email: taohch@shanghaitech.edu.cn

Access to P-Stereogenic Compounds via Desymmetrizing Enantiose-

Yu-Peng He − Key Laboratory of Petrochemical Catalytic

Science and Technology, Liaoning Shihua University, Fushun

lective Bromination. Chem. Sci. 2021, 12, 4582−4587.

(10) (a) Muthukrishnan, I.; Sridharan, V.; Menéndez, J. C. Progress

13001, China; orcid.org/0000-0002-0676-6627;

in the Chemistry of Tetrahydroquinolines. Chem. Rev. 2019, 119,

5057 −5191. (b) Sridharan, V.; Suryavanshi, P. A.; Menéndez, J. C.

Advances in the Chemistry of Tetrahydroquinolines. Chem. Rev. 2011,

111, 7157−7259.

Email: yupeng.he@lnpu.edu.cn

Xiaoyu Yang − School of Physical Science and Technology,

ShanghaiTech University, Shanghai 201210, China;

orcid.org/0000-0002-0756-0671; Email: yangxy1@

shanghaitech.edu.cn

(11) (a) Carter, N.; Li, X.; Reavey, L.; Meijer, A. J. H. M.; Coldham,

I. Synthesis and kinetic resolution of substituted tetrahydroquinolines

by lithiation then electrophilic quench. Chem. Sci. 2018 , 9 , 1352 −

357. (b) Hopkins, B. A.; Wolfe, J. P. Enantioselective synthesis of

Authors

tetrahydroquinolines, tetrahydroquinoxalines, and tetrahydroisoqui-

Chaofan Zhu − Key Laboratory of Petrochemical Catalytic

Science and Technology, Liaoning Shihua University, Fushun

nolines via Pd-Catalyzed alkene carboamination reactions. Chem. Sci.

2014 , 5 , 4840 −4844. (c) Yang, W.; Long, Y.; Zhang, S.; Zeng, Y.; Cai,

13001, China; School of Physical Science and Technology,

Q. Copper-Catalyzed Enantioselective Intramolecular N-Arylation, an

Efficient Method for Kinetic Resolutions. Org. Lett. 2013 , 15 , 3598 −

3601. (d) Shi, F.; Xing, G.-J.; Zhu, R.-Y.; Tan, W.; Tu, S. A Catalytic

Asymmetric Isatin-Involved Povarov Reaction: Diastereo- and

Enantioselective Construction of Spiro[indolin-3,2 ’-quinoline] Scaf-

fold. Org. Lett. 2013 , 15 , 128 −131. (e) Luo, C.; Huang, Y. A Highly

Diastereo- and Enantioselective Synthesis of Tetrahydroquinolines:

Quaternary Stereogenic Center Inversion and Functionalization. J.

Am. Chem. Soc. 2013, 135, 8193−8196. (f) Xu, Z.; Shen, C.; Zhang,

ShanghaiTech University, Shanghai 201210, China

Wei Liu − School of Physical Science and Technology,

ShanghaiTech University, Shanghai 201210, China

Fei Zhao − iHuman Institute, ShanghaiTech University,

Shanghai 201210, China

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.orglett.1c00978

107

Org. Lett. 2021, 23, 4104−4108

Organic Letters

H.; Wang, P.; Dong, K. Constructing chiral aza-quaternary carbon

Letter

centers by enantioselective carbonylative Heck reaction of o-

iodoanilines with allenes. Org. Chem. Front. 2021 , 8 , 1163 −1169.

Organocatalyzed Kinetic Resolution. Angew. Chem., Int. Ed. 2021,

60, 5268−5272.

(18) For pioneer work on CPA catalysis, see: (a) Akiyama, T.; Itoh,

J.; Yokota, K.; Fuchibe, K. Enantioselective Mannich-Type Reaction

Catalyzed by a Chiral Brønsted Acid. Angew. Chem., Int. Ed. 2004 , 43 ,

1566 −1568. (b) Uraguchi, D.; Terada, M. Chiral Brønsted Acid-

Catalyzed Direct Mannich Reactions via Electrophilic Activation. J.

Am. Chem. Soc. 2004, 126, 5356 −5357. For a recent review on CPA

catalysis, see: (c) Akiyama, T. Stronger Brønsted Acids. Chem. Rev.

2007 , 107 , 5744 −5758. (d) Terada, M. Chiral Phosphoric Acids as

Versatile Catalysts for Enantioselective Carbon-Carbon Bond

Forming Reactions. Synthesis 2010, 2010 , 1929 −1982. (e) Parmar,

D.; Sugiono, E.; Raja, S.; Rueping, M. Complete Field Guide to

Asymmetric BINOL-Phosphate Derived Brønsted Acid and Metal

Catalysis: History and Classification by Mode of Activation; Brønsted

Acidity, Hydrogen Bonding, Ion Pairing, and Metal Phosphates.

Chem. Rev. 2014 , 114 , 9047 −9153. (f) Akiyama, T.; Mori, K. Stronger

Brønsted Acids: Recent Progress. Chem. Rev. 2015, 115 , 9277 −9306.

(12) (a) Vedejs, E.; Jure, M. Efficiency in Nonenzymatic Kinetic

Resolution. Angew. Chem., Int. Ed. 2005 , 44 , 3974 −4001. (b) Muller,

C. E.; Schreiner, P. R. Organocatalytic Enantioselective Acyl Transfer

onto Racemic as well as meso Alcohols, Amines, and Thiols. Angew.

Chem., Int. Ed. 2011 , 50 , 6012 −6042. (c) Pellissier, H. Catalytic Non-

Enzymatic Kinetic Resolution. Adv. Synth. Catal. 2011 , 353 , 1613 −

1666. (d) Krasnov, V. P.; Gruzdev, D. A.; Levit, G. L. Nonenzymatic

Acylative Kinetic Resolution of Racemic Amines and Related

Compounds. Eur. J. Org. Chem. 2012 , 2012 , 1471 −1493. (e) Petersen,

K. S. Chiral Brønsted Acid Catalyzed Kinetic Resolutions. Asian J.

Org. Chem. 2016 , 5 , 308 −320. (f) Liu, W.; Yang, X. Recent Advances

in (Dynamic) Kinetic Resolution and Desymmetrization Catalyzed by

Chiral Phosphoric Acids. Asian J. Org. Chem. 2021, 10, 692−710.

(

13) (a) Murray, J. I.; Flodén, N. J.; Bauer, A.; Fessner, N. D.;

Dunklemann, D. L.; Bob-Egbe, O.; Rzepa, H. S.; Burgi, T.;

g) Parmar, D.; Sugiono, E.; Raja, S.; Rueping, M. Addition and

Richardson, J.; Spivey, A. C. Kinetic Resolution of 2-Substituted

Indolines by N-Sulfonylation using an Atropisomeric 4-DMAP-N-

oxide Organocatalyst. Angew. Chem., Int. Ed. 2017 , 56 , 5760 −5764.

Correction to Complete Field Guide to Asymmetric BINOL-

Phosphate Derived Brønsted Acid and Metal Catalysis: History and

Classification by Mode of Activation; Brønsted Acidity, Hydrogen

Bonding, Ion Pairing, and Metal Phosphates. Chem. Rev. 2017 , 117 ,

(b) Binanzer, M.; Hsieh, S.-Y.; Bode, J. W. Catalytic Kinetic

Resolution of Cyclic Secondary Amines. J. Am. Chem. Soc. 2011,

0608 −10620. (h) Li, X.; Song, Q. Recent advances in asymmetric

33, 19698−19701. (c) Birman, V. B.; Jiang, H.; Li, X.; Guo, L.;

reactions catalyzed by chiral phosphoric acids. Chin. Chem. Lett. 2018,

Uffman, E. W. Kinetic Resolution of 2-Oxazolidinones via Catalytic,

9, 1181−1192. (i) Merad, J.; Lalli, C.; Bernadat, G.; Maury, J.;

Enantioselective N-Acylation. J. Am. Chem. Soc. 2006 , 128 , 6536 −

Masson, G. Enantioselective Brønsted Acid Catalysis as a Tool for the

6537. (d) Arp, F. O.; Fu, G. C. Kinetic Resolutions of Indolines by a

Synthesis of Natural Products and Pharmaceuticals. Chem. - Eur. J.

Nonenzymatic Acylation Catalyst. J. Am. Chem. Soc. 2006, 128,

4264−14265.

14) (a) Lu, R.; Cao, L.; Guan, H.; Liu, L. Iron-Catalyzed Aerobic

(

018, 24, 3925−3943.

X.-W.; Zheng, C.; You, S.-L. Dearomatization through Halofunction-

19) For a recent review on asymmetric halogenations, see: Liang,

Dehydrogenative Kinetic Resolution of Cyclic Secondary Amines. J.

Am. Chem. Soc. 2019 , 141 , 6318 −6324. (b) Saito, K.; Akiyama, T.

Chiral Phosphoric Acid Catalyzed Kinetic Resolution of Indolines

Based on a Self-Redox Reaction. Angew. Chem., Int. Ed. 2016, 55,

alization Reactions. Chem. - Eur. J. 2016 , 22 , 11918 −11933.

(20) (a) Rahman, A.; Lin, X. Development and application of chiral

spirocyclic phosphoric acids in asymmetric catalysis. Org. Biomol.

Chem. 2018 , 16 , 4753 −4777. (b) Coric, I.; Muller, S.; List, B. Kinetic

148−3152. (c) Horiguchi, K.; Yamamoto, E.; Saito, K.; Yamanaka,

Resolution of Homoaldols via Catalytic Asymmetric Transacetaliza-

tion. J. Am. Chem. Soc. 2010, 132, 17370−17373. (c) Xu, F.; Huang,

D.; Han, C.; Shen, W.; Lin, X.; Wang, Y. SPINOL-Derived

Phosphoric Acids: Synthesis and Application in Enantioselective

Friedel −Crafts Reaction of Indoles with Imines. J. Org. Chem. 2010,

M.; Akiyama, T. Dynamic Kinetic Resolution Approach for the

Asymmetric Synthesis of Tetrahydrobenzodiazepines Using Transfer

Hydrogenation by Chiral Phosphoric Acid. Chem. - Eur. J. 2016 , 22 ,

8078 −8083. (d) Saito, K.; Miyashita, H.; Akiyama, T. Chiral

phosphoric acid catalyzed oxidative kinetic resolution of cyclic

secondary amine derivatives including tetrahydroquinolines by

hydrogen transfer to imines. Chem. Commun. 2015, 51, 16648 −

(

5, 8677−8680.

21) Kagan, H. B.; Fiaud, J. C. Kinetic Resolution. Topics in

Stereochemistry, Vol. 18; Eliel, E. L., Wilen, S. H., Eds.; Wiley: New

16651. (e) Saito, K.; Shibata, Y.; Yamanaka, M.; Akiyama, T. Chiral

York, 1988; pp 249 −330.

Phosphoric Acid-Catalyzed Oxidative Kinetic Resolution of Indolines

Based on Transfer Hydrogenation to Imines. J. Am. Chem. Soc. 2013,

(22) See the Supporting Information for details.

15) (a) Kong, D.; Han, S.; Wang, R.; Li, M.; Zi, G.; Hou, G. Kinetic

35, 11740−11743.

resolution of racemic 2-substituted 1,2-dihydroquinolines via

asymmetric Cu-catalyzed borylation. Chem. Sci. 2017 , 8 , 4558 −

4564. (b) Wang, M.; Huang, Z.; Xu, J.; Chi, Y. R. N-Heterocyclic

Carbene-Catalyzed [3 + 4] Cycloaddition and Kinetic Resolution of

Azomethine Imines. J. Am. Chem. Soc. 2014 , 136 , 1214 −1217.

Substituted 1,2-Dihydroquinolines by Rhodium-Catalyzed Asymmet-

ric Hydroarylation. Chin. J. Chem. 2021, 39, DOI: 10.1002/

cjoc.202000742.

(16) (a) Wang, D.; Jiang, Q.; Yang, X. Atroposelective synthesis of

configurationally stable nonbiaryl N −C atropisomers through direct

asymmetric aminations of 1,3-benzenediamines. Chem. Commun.

2020 , 56 , 6201 −6204. (b) Liu, W.; Jiang, Q.; Yang, X. A Versatile

Method for Kinetic Resolution of Protecting-Group-Free BINAMs

and NOBINs through Chiral Phosphoric Acid Catalyzed Triazane

Formation. Angew. Chem., Int. Ed. 2020, 59 , 23598 −23602. (c) Wang,

D.; Liu, W.; Tang, M.; Yu, N.; Yang, X. Atroposelective Synthesis of

Biaryl Diamines and Amino Alcohols via Chiral Phosphoric Acid

Catalyzed para-Aminations of Anilines and Phenols. iScience 2019, 22,

95−205.

17) Chen, Y.; Zhu, C.; Guo, Z.; Liu, W.; Yang, X. Asymmetric

Synthesis of Hydroquinolines with α ,α -Disubstitution through

108