Copper/GanPhos-Catalyzed 1,3-Dipolar Cycloaddition of Azo?-methine Ylides: An Efficient Access to Chiral Pyrrolidine Spirocycles

Article abstract of DOI:10.1055/s-0040-1706599

A highly efficient copper/GanPhos-catalyzed 1,3-dipolar cyclo?-addition?-of azomethine ylides is reported. This viable transformation provides a series of optically active spiro[dihydronaphthalene-2,3′-pyrrolidine]s, bearing one spiro quaternary and three tertiary stereogenic centers, in good yields and with high ee values. This protocol features high diastereo- A nd enantioselectivity, broad substrate scope and mild reaction conditions.

Full text of DOI:10.1055/s-0040-1706599

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2020, 52, A–J
paper
A
de
Z. Gan et al.
Paper
Synthesis
Copper/GanPhos-Catalyzed 1,3-Dipolar Cycloaddition of Azo-
methine Ylides: An Efficient Access to Chiral Pyrrolidine Spirocycles
Zhenjie Gan*a
Ke Lib
Ph
tBu
Cu(MeCN)4BF4
(3 mol%)
O
*
P
Hui Zhangb
Er-Qing Li*b
L5 (3.3 mol%)
R1
CO2Me
R1
Ph
R2
N
CO2Me
O
+
HN
NaH2PO4 (2.0 equiv)
THF, –20 °C
0
0
0
0
-
0
0
0
3
-1
2
8
6
-
6
8
3
2
S
O
R2
N
H
GanPhos (L5)
a School of Chemical and Printing-Dyeing Engineering,
Henan University of Engineering, Zhengzhou, 451191,
P. R. of China
27 examples, 71–92% yields
>20:1 dr, 80–98% ee
zhenjiegan@163.com
b College of Chemistry, Green Catalysis Center, International
Phosphorus Laboratory, International Joint Research Labo-
ratory for Functional Organophosphorus Materials of
Henan Province, Zhengzhou University, Zhengzhou
450001, P. R. of China
lierqing@zzu.edu.cn
Corresponding Authors
Received: 01.07.2020
Accepted after revision: 20.10.2020
Published online: 17.11.2020
O
N
DOI: 10.1055/s-0040-1706599; Art ID: ss-2020-c0359-op
R
N
R
H
O
MeO
Abstract A highly efficient copper/GanPhos-catalyzed 1,3-dipolar cyclo-
addition of azomethine ylides is reported. This viable transformation
provides a series of optically active spiro[dihydronaphthalene-2,3′-pyr-
rolidine]s, bearing one spiro quaternary and three tertiary stereogenic
centers, in good yields and with high ee values. This protocol features
high diastereo- and enantioselectivity, broad substrate scope and mild
reaction conditions.
Cl
R = (CH2)2
N
N
B
tetracyclic pyrrolidines
A
R
N
O
Key words pyrrolidine spirocycles, 1,3-dipolar cycloaddition, azo-
methine ylides, stereogenic centers, copper, GanPhos
O
NH
O
C
Optically active pyrrolidine derivatives bearing spirocy-
clic skeletons are frequently found in pharmaceuticals, nat-
ural alkaloids, and as fascinating building blocks in organic
synthesis.1 For example, compound A demonstrates potent
anticonvulsant activity,2 tetracyclic pyrrolidines B are a
class of steroidal alkaloids that contain the key BCDE ring
system of (+)-conessine,3 whilst compound C exhibits anti-
microbial activity (Figure 1).4 The abundant applications of
pyrrolidines in organic synthesis, the pharmaceutical in-
dustry, and in peptide chemistry, have promoted the devel-
opment of efficient routes for the stereoselective construc-
tion of diverse pyrrolidine spirocycles.
The metal-catalyzed asymmetric 1,3-dipolar cycloaddi-
tion of azomethine ylides5 with activated olefins has be-
come a very useful and atom-economical strategy for the
enantioselective synthesis of pyrrolidines since Grigg’s pio-
neering work.6 The steric and electronic properties of metal
catalysts can usually be primarily affected by ligands that
coordinate to the metal center.7 In this regard, numerous
structurally diverse ligands including Fesulphos,8 Bipham-
phos,9 MingPhos,10 Deng’s N,O ligands11 and so on12 have
been developed, affording excellent results in 1,3-dipolar
antimicrobial activity
Figure 1 Selected bioactive natural products and synthetic drugs con-
taining pyrrolidine spirocycles
cycloadditions of azomethine ylides and activated alkenes.
However, this type of [3+2] cycloaddition for the precise
synthesis of the polysubstituted pyrrolidines bearing
spiro[naphthalene-2,3′-pyrrolidin]-1-one motifs is an im-
portant yet underdeveloped area.
Recently, we developed novel P-stereogenic phosphine
ligands, bearing a flexible 1-phosphanorbornediene moiety,
named GanPhos, which exhibited good stereoselectivities
in metal-catalyzed asymmetric 1,3-dipolar cycloaddi-
tions.13 Encouraged by these achievements, we envisioned
that easily available (E)-2-arylidene-3,4-dihydronaphtha-
len-1(2H)-ones could be utilized to enable facile access to
enantioenriched spiro[naphthalene-2,3′-pyrrolidin]-1-one
derivatives. Herein, we report the first Lewis acid catalyzed
highly enantioselective construction of spiro[dihydronaph-
thalene-2,3′-pyrrolidine] derivatives containing spiro
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Z. Gan et al.
Paper
Synthesis
Previously reported privileged ligands
CF3
R2
O
S
R
StBu
F3C
N
NH2
N
N
F3C
NHPR2
H
PR2
Fe
OH
Ph
R
PPh2
Ph
CF3
TF-Biphamphos
Deng's N,O ligands
Fesulphos
MingPhos
Our work
tBu
Ph
O
O
R2
CO2Me
P
R1
Cu(I)/GanPhos
R2
N
CO2Me
HN
+
O
Ph
S
R1
N
H
GanPhos
Scheme 1 Examples of privileged ligands utilized for the 1,3-dipolar cycloadditions of azomethine ylides
quaternary stereogenic centers via Cu(I)/Ganphos-
catalyzed 1,3-dipolar cycloaddition with azomethine ylides
(Scheme 1).
GanPhos (L5) (3.3 mol%), NaH2PO4 (20 mol%), THF, –20 °C
(see Table 1, entry 15).
With optimized reaction conditions in hand, we next
turned our attention to explore the scope with respect to
various (E)-2-arylidene-3,4-dihydronaphthalen-1(2H)-ones
1 in reactions with aldimino ester 2a. As summarized in Ta-
ble 2, the experimental results showed that a wide range of
dipolarophiles 1 bearing electron-neutral, electron-rich, or
electron-deficient groups on the phenyl ring reacted with
aldimino ester 2a to afford the corresponding products 3 in
good yields, enantioselectivities and diastereoselectivities
(Table 2, entries 1–10). The dipolarophile 1 bearing 2-Br
and 4-F groups on the phenyl ring also reacted smoothly to
produce the desired adduct 3ka in 91% yield and 90% ee (Ta-
ble 2, entry 11). Noticeably, almost the same high levels of
yields and enantioselectivities were achieved when dipola-
rophiles 1 bearing 1-naphthyl and heteroaromatic (2-furyl,
2-thiophenyl, 3-thiophenyl) groups were used in this reac-
tion, and the desired spirocyclic adducts 3la–oa were ob-
tained in 78–88% yields and 90–97% ee (Table 2, entries 12–
15). Also, the dipolarophile 1p bearing an alkyl substituent
(a cyclohexyl group) gave chiral pyrroloindoline 3pa with
satisfactory enantioselectivity (Table 2, entry 16).
Next, various aldimino esters were investigated under
the optimized experimental conditions to test the scope of
this asymmetric 1,3-dipolar cycloaddition reaction, and
representative results are summarized in Table 3. The elec-
tronic properties of the aromatic substituents influenced
the enantioselectivity, with electron-donating (3-Me, 3-
MeO, and 4-MeO) groups typically resulting in lower enan-
tioselectivities compared to electron-withdrawing substit-
uents (2-F, 3-F, 2-Cl, 3-Cl, 4-Cl, 4-Br and 3-CF3) (Table 3,
entries 1–10). Remarkably, an aliphatic aldimino ester
With this background in mind, and in continuation of
our efforts on cycloaddition reactions, we initially opti-
mized the reaction conditions (Table 1).14 (E)-2-Ben-
zylidene-3,4-dihydronaphthalen-1(2H)-one (1a) and ald-
imino ester 2a were chosen as the model substrates to ex-
amine the [3+2] cycloaddition. Screening of solvents and
bases at room temperature revealed that THF as the solvent
and NaH2PO4 as the base were the best choices (see Table S1
in the Supporting Information). Gratifyingly, the reaction
was complete in 12 hours when using a catalytic amount of
Cu(CH3CN)4BF4/GanPhos (L5) as the catalyst system at room
temperature in THF, affording the desired adduct 3aa in 80%
yield, excellent diastereoselectivity (dr > 20:1) and high en-
antioselectivity (84% ee) (Table 1, entry 1). Encouraged by
this result, we then tested the effects of different metal
salts, and found that Cu(CH3CN)4BF4 was the best catalyst
leading to the highest asymmetric induction (Table 1,
entries 1–6). Next, various P-stereogenic ligands (L1–L6),
as reported by our group,13 were screened with
Cu(CH3CN)4BF4 as the metal catalyst to compare their cata-
lytic activity, with the combination of Cu(CH3CN)4BF4/
GanPhos (L5) exhibiting the best asymmetric induction
ability (Table 1, entries 1 vs 7–11). Examination of the cata-
lyst loading showed that the use of Cu(CH3CN)4BF4 (3 mol%)
led to slightly elevated ee values (Table 1, entries 1 vs 12
and 13). Reducing the reaction temperature from room
temperature to –20 °C led to completion of the reaction
with an excellent enantioselectivity of 92% ee (Table 1, en-
tries 13 and 14 vs 15). Therefore, the optimized reaction
conditions were as follows: Cu(CH3CN)4BF4 (3 mol%)/
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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Z. Gan et al.
Paper
Synthesis
Table 1 Optimization of the Reaction Conditionsa
Cu(CH3CN)4BF4 (3 mol%)/GanPhos (L5) (3.3 mol%) in THF at
–20 °C, the reaction proceeded smoothly to afford the de-
sired adduct 3aa in 65% yield and 90% ee (Scheme 2).
O
Ph
O
Cat. (5 mol% )
GanPhos (L5; 5.5 mol%)
1a
Ph
Ph
CO2Me
+
NaH2PO4 (20 mol%)
O
Ph
N
H
Cu(CH3CN)4BF4
(3 mol%)
L5 (3.3 mol%)
Ph
N
CO2Me
solvent, rt
1a
(0.72 g, 3 mmol)
2a
3aa
Ph
+
Ph
L1 Ar = Ph
NaH2PO4 (2.0 equiv)
THF, –20 °C
O
CO2Me
3aa
Ph
N
CO2Me
L2 Ar = 4-MeC6H4
L3 Ar = 4-MeOC6H4
L4 Ar = 4-nBuC6H4
L5 Ar = 4-tBuC6H4
L6 Ar = 4-CyC6H4
N
P
Ph
H
Ar
2a
Ph
(1.06 g, 6 mmol)
O
HN
0.8 g, 65% yield
90% ee
S
Scheme 2 A gram-scale preparation of adduct 3aa
Entry
Catalyst
Ligand
Yield (%)b
ee (%)c
Table 2 Substrate Scope of Various (E)-2-Arylidene-3,4-dihydronaph-
thalen-1(2H)-ones 1a
1
2
Cu(CH3CN)4BF4
Cu(CH3CN)4PF6
Cu(OTf)2
L5
L5
L5
L5
L5
L5
L1
L2
L3
L4
L6
L5
L5
L5
L5
80
99
89
99
43
70
84
65
77
54
39
64
77
75
73
84
71
73
63
73
82
66
30
35
62
82
86
86
90
92
3
O
4
AgOAc
R1
Cu(CH3CN)4BF4
(3 mol%)
L5 (3.3 mol%)
5
AgOTf
1
6
AgNTf2
R1
CO2Me
+
NaH2PO4 (2.0 equiv)
THF, –20 °C
7
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
Cu(CH3CN)4BF4
O
Ph
Ph
N
CO2Me
N
8
2a
H
9
3
10
11
12d
13e
14e,f
15e,g
Entry
R1
Ph (1a)
Yield (%)b
ee (%)c
1
2
73 (3aa)
75 (3ba)
72 (3ca)
79 (3da)
74 (3ea)
81 (3fa)
73 (3ga)
77 (3ha)
92 (3ia)
87 (3ja)
91 (3ka)
85 (3la)
78 (3ma)
88 (3na)
79 (3oa)
74 (3pa)
92
87
91
83
93
90
88
87
93
87
90
90
97
94
97
90
2-MeC6H4 (1b)
3-MeC6H4 (1c)
4-MeC6H4 (1d)
3-FC6H4 (1e)
3
4
a Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), catalyst (5 mol%),
GanPhos (6 mol%), NaH2PO4 (20 mol%), rt, 12 h.
b Isolated yield of 3aa. The diastereomeric ratio (d.r.) was >20:1.
c The ee value was determined by HPLC analysis on a chiral stationary
phase.
5
6
4-FC6H4 (1f)
7
2-ClC6H4 (1g)
2-BrC6H4 (1h)
3-BrC6H4 (1i)
4-BrC6H4 (1j)
2-Br-4-FC6H3 (1k)
1-naphthyl (1l)
2-furyl (1m)
d Cu(CH3CN)4BF4 (2.5 mol%) and GanPhos (2.75 mol%) were used.
e Cu(CH3CN)4BF4 (3 mol%) and GanPhos (3.3 mol%) were used.
f Reaction temperature: 0 °C.
8
9
g Reaction temperature: –20 °C.
10
11
12
13
14
15
16
participated in the [3+2] cycloaddition to afford the corre-
sponding product 3al in 83% yield and 80% ee (Table 3, en-
try 11). The structures and stereochemistries of products 3
were characterized by a combination of NMR, HPLC, HRMS,
and single-crystal X-ray analysis (3oa) (see the Supporting
Information).15
To explore the synthetic potential of this reaction, a
large-scale synthesis of 3aa was carried out. When (E)-2-
benzylidene-3,4-dihydronaphthalen-1(2H)-one (1a) and
aldimino ester 2a were used in the presence of
2-thiophenyl (1n)
3-thiophenyl (1o)
Cy (1p)
a Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), Cu(CH3CN)4BF4 (3
mol%), GanPhos (3.3 mol%), NaH2PO4 (20 mol%), –20 °C, 12 h.
b Isolated yield of 3. The diastereomeric ratio (d.r.) was >20:1.
c The ee value was determined by HPLC analysis on a chiral stationary
phase.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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Z. Gan et al.
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Synthesis
Table 3 Substrates Scope of Various Aldimino Estersa
All reactions were performed under nitrogen using solvents dried by
standard methods. All commercially available reagents were used
without further purification. All known compounds were synthesized
according to literature procedures.17 Qingdao Ocean silica gel (200–
300 mesh) was used for chromatographic separations. Melting points
were recorded using a SGW X-4B apparatus (heating rate: 4 °C/min)
and are uncorrected. NMR spectra were obtained using a Bruker
AV300 spectrometer. Chemical shifts are expressed in parts per mil-
lion (ppm) downfield from TMS as the internal standard. HRMS
spectra were obtained on an Agilent 1290-6540 UHPLC Q-Tof HR-MS
spectrometer. X-ray crystallographic analyses were performed on an
Oxford Diffraction Gemini E diffractometer. Enantiomeric excesses
were determined by chiral HPLC analysis using Chiralcel IA/AD col-
umns and by comparison with authentic racemates. Chiral HPLC anal-
yses were recorded on Thermoscientific Dionex Ultimate 3000 and
Agilent Technologies 1260 Infinity instruments.
O
Ph
Cu(CH3CN)4BF4
(3 mol%)
1a
L5 (3.3 mol%)
Ph
CO2Me
+
NaH2PO4 (2.0 equiv)
THF, –20 °C
O
R2
N
CO2Me
R2
N
H
2
3
Entry
R2
3-MeC6H4 (2b)
Yield (%)b
ee (%)c
1
85 (3ab)
80
83
85
96
98
83
94
83
91
83
80
2
3-MeOC6H4 (2c) 79 (3ac)
4-MeOC6H4 (2d) 83 (3ad)
3
4
2-FC6H4 (2e)
3-FC6H4 (2f)
2-ClC6H4 (2g)
3-ClC6H4 (2h)
4-ClC6H4 (2i)
4-BrC6H4 (2j)
3-F3CC6H4 (2k)
Cy (2l)
90 (3ae)
71 (3af)
90 (3ag)
83 (3ah)
84 (3ai)
75 (3aj)
83 (3ak)
83 (3al)
5
1,3-Dipolar [3+2] Cycloaddition; General Procedure
6
GanPhos (L5) (6.0 mg, 0.0066 mmol, 3.3 mol%) and Cu(CH3CN)4BF4
(3.14 mg, 0.006 mmol, 3 mol%) were dissolved in THF (2.0 mL) in a
Schlenk tube under N2. After stirring at room temperature for 1 h, 2-
alkylidene-cycloketone 1 (0.2 mmol) and aldimino ester 2 (0.4 mmol)
were added, followed by NaH2PO4 (48 mg, 0.4 mmol). The resulting
mixture was then stirred at –20 °C until the 2-alkylidene-cycloketone
had been totally consumed. The reaction mixture was directly puri-
fied by flash column chromatography (petroleum ether/ethyl acetate,
5:1) to afford the corresponding product 3.
7
8
9
10
11
a Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmol), Cu(CH3CN)4BF4 (3
mol%), GanPhos (3.3 mol%), NaH2PO4 (20 mol%), –20 °C, 12 h.
b Isolated yield of 3. The diastereomeric ratio (d.r.) was >20:1.
c The ee value was determined by HPLC analysis on a chiral stationary
phase.
Methyl (2R,2′R,4′R,5′R)-1-Oxo-2′,4′-diphenyl-3,4-dihydro-1H-
spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate (3aa)
Yield: 60.2 mg (73%); white solid; mp 194–195 °C; []D +69 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.70–1.80 (m, 1 H), 1.90–1.98 (m, 1 H),
2.23 (s, 1 H), 2.70–2.78 (m, 1 H), 3.07–3.18 (m, 1 H), 3.77 (s, 3 H), 4.37
(d, J = 8.8 Hz, 1 H), 4.55 (d, J = 8.8 Hz, 1 H), 4.64 (s, 1 H), 6.96 (d, J = 7.8
Hz, 1 H), 7.05–7.10 (m, 4 H), 7.16–7.19 (m, 2 H), 7.24–7.27 (m, 2 H),
7.32–7.38 (m, 4 H), 7.61–7.64 (m, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.4, 30.6, 52.4, 55.5, 61.4, 64.3,
71.0, 126.3, 127.1, 127.5, 127.8, 127.95, 128.01, 128.28, 129.31, 132.9,
132.9, 138.2, 139.3, 142.0, 173.9, 198.4.
According to previous literature,16 a reaction pathway
has been proposed (Scheme 3). The P-stereogenic ligand
and in situ formed azomethine ylide coordinate to the Cu(I)
center, leading to a tetracoordinated species, which facili-
tated the deprotonation by NaH2PO4 to generate the well-
organized, enantioenriched, N-metalated azomethine ylide
A. Conjugate addition of the enolate to (E)-2-benzylidene-
3,4-dihydronaphthalen-1(2H)-one (1a) gave the zwitter-
ionic intermediate C. Subsequent intramolecular cyclization
then produced the intermediate D. Finally, protonation gave
the product 3aa and regenerated the catalyst.
HRMS (ESI): m/z [M + H]+ calcd for C27H26NO3: 412.1907; found:
412.1908.
HPLC: 92% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 21.12 and 25.01 min.
In summary, we have accomplished a highly effective,
diastereo- and enantioselective 1,3-dipolar cycloaddition
using 2-arylidene-3,4-dihydronaphthalen-1(2H)-ones and
aldimino esters. This methodology provides efficient and
economic access to a series of optically active spiro[dihy-
dronaphthalene-2,3′-pyrrolidine]s, bearing one spiro qua-
ternary and three tertiary stereogenic centers, in good
yields and with high ee values. Remarkably, an aliphatic al-
dimino ester also participated in the [3+2] cycloaddition to
afford the corresponding product 3al in high yield and en-
antioselectivity. Further studies on the exploration of other
types of catalytic asymmetric transformations are under
way in our laboratory.
Methyl (2R,2′R,4′R,5′R)-1-Oxo-2′-phenyl-4′-(o-tolyl)-3,4-dihydro-
1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate (3ba)
Yield: 63.9 mg (75%); white solid; mp 141–142 °C; []D +80 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.74–1.81 (m, 2 H), 2.27 (s, 3 H), 2.43–
2.52 (m, 1 H), 2.76–2.87 (m, 1 H), 3.15 (s, 1 H), 3.85 (s, 3 H), 4.28 (d, J =
5.9 Hz, 1 H), 4.55 (s, 1 H), 4.65 (d, J = 5.9 Hz, 1 H), 6.83 (d, J = 7.5 Hz, 1
H), 7.04–7.15 (m, 4 H), 7.18–7.25 (m, 4 H), 7.28–7.34 (m, 2 H), 7.50–
7.53 (m, 1 H), 7.85–7.88 (m, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 20.7, 25.7, 31.0, 52.4, 52.6, 60.2,
67.5, 74.6, 126.3, 126.9, 127.5, 127.9, 127.97, 128.03, 128.3, 128.4,
130.7, 132.7, 133.1, 137.3, 137.9, 139.0, 142.6, 174.0, 200.6.
HRMS (ESI): m/z [M + H]+ calcd for C27H28NO3: 426.2064; found:
426.2065.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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Z. Gan et al.
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Synthesis
Ph
N
CO2Me
3aa + base
CuL*
2a
base
BH+
P
O
Ph
Ph
Cu
P
N
O
Ph
N
Ph
A
O
HN
MeO
S
L* =
L*Cu
O
O
Ph
O
Ph
OMe
D
1a
intramolecular
cyclization
P
O
Ph
Cu
N
O
O
Ph
N
MeO
Ph
O
*LCu
O
Ph
B
OMe
C
Scheme 3 A proposed reaction mechanism
HPLC: 87% ee (Chiralpak IA-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 11.35 and 12.47 min.
1H NMR (300 MHz, CDCl3):  = 1.73–1.98 (m, 2 H), 2.32 (s, 3 H), 2.71–
2.98 (m, 2 H), 3.06–3.18 (m, 1 H), 3.76 (s, 3 H), 4.36 (d, J = 8.8 Hz, 1 H),
4.54 (d, J = 8.8 Hz, 1 H), 4.63 (s, 1 H), 6.96 (d, J = 7.6 Hz, 1 H), 7.04–7.14
(m, 6 H), 7.17–7.20 (m, 2 H), 7.24–7.27 (m, 3 H), 7.64 (d, J = 7.7 Hz, 1
H).
Methyl (2R,2′R,4′R,5′R)-1-Oxo-2′-phenyl-4′-(m-tolyl)-3,4-dihydro-
1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate (3ca)
13C{1H} NMR (75 MHz, CDCl3):  = 21.1, 25.4, 30.5, 52.4, 55.2, 61.4,
64.3, 70.9, 126.3, 127.5, 127.8, 127.95, 127.98, 128.1, 129.0, 129.2,
132.9, 133.0, 135.1, 136.6, 139.5, 142.1, 174.0, 198.5.
HRMS (ESI): m/z [M + H]+ calcd for C27H28NO3: 426.2064; found:
426.2066.
Yield: 61.4 mg (72%); white solid; mp 144–145 °C; []D +103 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.72–1.82 (m, 1 H), 1.88–1.95 (m, 1 H),
2.34 (s, 3 H), 2.70–2.76 (m, 1 H), 3.04–3.15 (m, 2 H), 3.78 (s, 3 H), 4.49
(d, J = 8.4 Hz, 1 H), 4.61 (s, 1 H), 6.95 (d, J = 7.7 Hz, 1 H), 7.05–7.07 (m,
4 H), 7.16–7.27 (m, 7 H), 7.65 (d, J = 7.9 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 21.5, 25.4, 30.6, 52.4, 55.7, 61.2,
64.5, 71.2, 126.2, 126.3, 127.5, 127.82, 127.84, 127.9, 128.0, 128.1,
130.2, 132.9, 133.0, 137.9, 138.3, 139.2, 142.1, 173.9, 198.7.
HPLC: 83% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 25.66 and 34.45 min.
Methyl (2R,2′R,4′R,5′R)-4′-(3-Fluorophenyl)-1-oxo-2′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3ea)
HRMS (ESI): m/z [M + H]+ calcd for C27H28NO3: 426.2064; found:
426.2065.
Yield: 63.7 mg (74%); white solid; mp 145–146 °C; []D +77 (c 0.1,
CH2Cl2, 21 °C).
HPLC: 91% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 13.28 and 13.36 min.
1H NMR (300 MHz, CDCl3):  = 1.69–1.80 (m, 1 H), 1.94–2.01 (m, 1 H),
2.72–2.82 (m, 2 H), 3.13–3.24 (m, 1 H), 3.77 (s, 3 H), 4.33 (d, J = 9.0 Hz,
1 H), 4.55 (d, J = 9.0 Hz, 1 H), 4.65 (s, 1 H), 6.98 (d, J = 7.6 Hz, 1 H),
7.05–7.15 (m, 6 H), 7.22–7.36 (m, 5 H), 7.57–7.61 (m, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.3, 30.5, 52.5, 54.7, 61.4, 63.8,
70.5, 127.3, 127.6, 127.9, 128.0, 128.1, 129.4, 129.5, 132.8, 133.1,
134.2, 139.2, 140.1, 141.9, 173.5, 197.9.
Methyl (2R,2′R,4′R,5′R)-1-Oxo-2′-phenyl-4′-(p-tolyl)-3,4-dihydro-
1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate (3da)
Yield: 67.3 mg (79%); white solid; mp 76–77 °C; []D +107 (c 0.1,
CH2Cl2, 21 °C).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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Z. Gan et al.
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Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C27H25FNO3: 430.1813; found:
430.1814.
HPLC: 87% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 18.08 and 25.16 min.
HPLC: 93% ee (Chiralpak IA-H, n-hexane/i-PrOH = 95:5, flow rate = 1.0
mL/min,  = 254 nm); tR = 26.10 and 27.59 min.
Methyl (2R,2′R,4′R,5′R)-4′-(3-Bromophenyl)-1-oxo-2′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3ia)
Methyl (2R,2′R,4′R,5′R)-4′-(4-Fluorophenyl)-1-oxo-2′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3fa)
Yield: 90.2 mg (92%); white solid; mp 76–77 °C; []D +61 (c 0.1,
CH2Cl2, 21 °C).
Yield: 69.7 mg (81%); white solid; mp 143–144 °C; []D +83 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.68–1.79 (m, 1 H), 1.93–2.00 (m, 1 H),
2.74–2.81 (m, 2 H), 3.12–3.23 (m, 1 H), 3.76 (s, 3 H), 4.32 (d, J = 9.1 Hz,
1 H), 4.54 (d, J = 9.1 Hz, 1 H), 4.64 (s, 1 H), 6.96–6.99 (m, 1 H), 7.04–
7.08 (m, 4 H), 7.13–7.20 (m, 3 H), 7.24–7.27 (m, 1 H), 7.29–7.31 (m, 1
H), 7.36–7.39 (m, 1 H), 7.52–7.60 (m, 2 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.3, 30.5, 52.5, 54.7, 61.4, 63.8,
70.5, 122.5, 126.4, 127.6, 127.9, 128.0, 128.06, 128.08, 129.8, 130.3,
132.3, 132.8, 133.1, 139.3, 140.5, 141.9, 173.6, 197.9.
1H NMR (300 MHz, CDCl3):  = 1.68–1.78 (m, 1 H), 1.96–2.00 (m, 1 H),
2.77–2.91 (m, 2 H), 3.15–3.26 (m, 1 H), 3.76 (s, 3 H), 4.32 (d, J = 9.4 Hz,
1 H), 4.56–4.65 (m, 2 H), 6.97–7.15 (m, 8 H), 7.25–7.35 (m, 4 H), 7.58
(d, J = 7.7 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.3 (s), 30.4, 52.4, 54.3, 61.5, 63.8,
70.2, 115.1 (d, J = 21.1 Hz), 126.4, 127.5, 127.8, 127.9, 128.0, 128.1,
130.8 (d, J = 7.8 Hz), 132.9, 133.0, 133.4 (d, J = 3.3 Hz), 139.6, 141.9,
161.9 (d, J = 245.7 Hz), 173.7, 198.0.
HRMS (ESI): m/z [M + H]+ calcd for C27H25BrNO3: 490.1012; found:
490.1014.
HRMS (ESI): m/z [M + H]+ calcd for C27H25FNO3: 430.1813; found:
430.1815.
HPLC: 93% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 13.25 and 23.55 min.
HPLC: 90% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 22.71 and 31.04 min.
Methyl (2R,2′R,4′R,5′R)-4′-(4-Bromophenyl)-1-oxo-2′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3ja)
Methyl (2R,2′R,4′S,5′R)-4′-(2-Chlorophenyl)-1-oxo-2′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3ga)
Yield: 85.7 mg (87%); white solid; mp 123–124 °C; []D +54 (c 0.1,
CH2Cl2, 21 °C).
Yield: 65.1 mg (73%); white solid; mp 88–89 °C; []D +47 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.67–1.77 (m, 1 H), 1.94–2.00 (m, 1 H),
2.75–2.83 (m, 2 H), 3.16–3.26 (m, 1 H), 3.75 (s, 3 H), 4.32 (d, J = 9.5 Hz,
1 H), 4.55 (d, J = 9.5 Hz, 1 H), 4.64 (s, 1 H), 6.98–7.16 (m, 7 H), 7.22–
7.28 (m, 3 H), 7.42–7.44 (m, 2 H), 7.56–7.58 (m, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.3, 30.4, 52.5, 54.4, 61.5, 63.6,
70.2, 121.1, 126.4, 127.6, 127.9, 128.0, 128.1, 131.1, 131.4, 132.8,
133.1, 136.8, 139.5, 141.9, 173.6, 197.8).
1H NMR (300 MHz, CDCl3):  = 1.59–1.63 (m, 1 H), 1.90–2.04 (m, 1 H),
2.42–2.59 (m, 1 H), 2.68– 2.79 (m, 1 H), 3.16 (s, 1 H), 3.90 (s, 3 H), 4.24
(d, J = 4.1 Hz, 1 H), 4.48 (s, 1 H), 4.93 (d, J = 4.5 Hz, 1 H), 6.78 (d, J = 7.4
Hz, 1 H), 7.01–7.03 (m, 2 H), 7.09–7.25 (m, 4 H), 7.27–7.28 (m, 1 H),
7.37–7.42 (m, 3 H), 7.63–7.65 (m, 1 H), 7.90–7.92 (m, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.7, 30.3, 52.6, 53.6, 59.8, 67.2,
74.8, 126.3, 127.4, 127.9, 128.0, 128.2, 128.4, 128.5, 129.6, 129.8,
132.7, 133.0, 135.1, 137.5, 139.1, 142.6, 174.0, 200.4.
HRMS (ESI): m/z [M + H]+ calcd for C27H25BrNO3: 490.1012; found:
490.1012.
HPLC: 87% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 26.96 and 24.65 min.
HRMS (ESI): m/z [M + H]+ calcd for C27H25ClNO3: 446.1517; found:
446.1519.
Methyl (2R,2′R,4′S,5′R)-4′-(2-Bromo-4-fluorophenyl)-1-oxo-
2′-phenyl-3,4-dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-
5′-carboxylate (3ka)
HPLC: 88% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 18.00 and 26.54 min.
Yield: 91.5 mg (90%); white solid; mp124–125 °C; []D +90 (c 0.1,
CH2Cl2, 21 °C).
Methyl (2R,2′R,4′S,5′R)-4′-(2-Bromophenyl)-1-oxo-2′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3ha)
1H NMR (300 MHz, CDCl3):  = 1.57–1.62 (m, 1 H), 1.91–2.01 (m, 1 H),
2.45–2.53 (m, 1 H), 2.70–2.80 (m, 1 H), 3.20 (s, 1 H), 3.93 (s, 3 H), 4.14
(d, J = 4.2 Hz, 1 H), 4.45 (s, 1 H), 4.88 (d, J = 4.4 Hz, 1 H), 6.78–6.81 (m,
1 H), 7.02–7.04 (m, 3 H), 7.10–7.27 (m, 5 H), 7.34–7.38 (m, 1 H), 7.59–
7.64 (m, 1 H), 7.89–7.92 (m, 1 H).
13C NMR (75 MHz, CDCl3):  = 25.2, 30.6, 52.7, 55.6, 59.6, 67.8, 74.8,
115.3 (d, J = 20.9 Hz), 120.2 (d, J = 23.9 Hz), 126.4, 127.4, 127.9, 128.0,
128.2, 128.4, 130.4 (d, J = 8.7 Hz), 132.7, 133.1, 137.0 (d, J = 3.6 Hz),
137.4, 142.5, 161.1 (d, J = 251.0 Hz), 173.9, 200.3).
Yield: 75.5 mg (77%); white solid; mp 92–93 °C; []D +73 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.57–1.61 (m, 1 H), 1.94–2.04 (m, 1 H),
2.43–2.52 (m, 1 H), 2.67–2.78 (m, 1 H), 3.22 (s, 1 H), 3.93 (s, 3 H), 4.21
(d, J = 4.0 Hz, 1 H), 4.48 (s, 1 H), 4.92 (d, J = 4.3 Hz, 1 H), 6.79 (d, J = 7.5
Hz, 1 H), 7.02–7.04 (m, 3 H), 7.11–7.26 (m, 4 H), 7.27–7.28 (m, 1 H),
7.43–7.47 (m, 1 H), 7.60–7.65 (m, 2 H), 7.91–7.93 (m, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.7, 30.5, 52.6, 56.4, 59.7, 67.7,
74.9, 126.3, 126.5, 127.4, 127.9, 128.0, 128.1, 128.2, 128.5, 128.6,
129.6, 132.7, 133.0, 133.2, 137.5, 141.0, 142.6, 174.0, 200.5.
HRMS (ESI): m/z [M + H]+ calcd for C27H24BrFNO3: 508.0918; found:
508.0920.
HRMS (ESI): m/z [M + H]+ calcd for C27H25BrNO3: 490.1012; found:
490.1013.
HPLC: 90% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 21.43 and 44.18 min.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

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Z. Gan et al.
Paper
Synthesis
Methyl (2R,2′R,4′R,5′R)-4′-(Naphthalen-1-yl)-1-oxo-2′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3la)
1H NMR (300 MHz, CDCl3):  = 1.72–1.83 (m, 1 H), 1.98–2.05 (m, 1 H),
2.62–2.88 (m, 2 H), 3.19–3.30 (m, 1 H), 3.78 (s, 3 H), 4.32 (d, J = 9.8 Hz,
1 H), 4.67–4.71 (m, 2 H), 7.03–7.14 (m, 8 H), 7.17–7.18 (m, 1 H), 7.23–
7.31 (m, 2 H), 7.55–7.58 (m, 1 H).
Yield: 78.6 mg (85%); white solid; mp 101–102 °C; []D +53 (c 0.1,
13C{1H} NMR (75 MHz, CDCl3):  = 25.3, 29.8, 50.4, 52.5, 61.6, 63.9,
69.3, 122.8, 125.2, 126.4, 127.6, 127.7, 127.8, 128.0, 128.2, 128.3,
133.0, 138.0, 139.9, 142.0, 173.9, 197.8.
HRMS (ESI): m/z [M + H]+ calcd for C25H24NO3S: 418.1471; found:
418.1472.
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.68–1.71 (m, 2 H), 2.31–2.37 (m, 1 H),
2.74–2.85 (m, 1 H), 3.05 (s, 1 H), 3.83 (s, 3 H), 4.50 (d, J = 5.7 Hz, 1 H),
4.62 (s, 1 H), 5.40 (d, J = 5.6 Hz, 1 H), 6.74 (d, J = 7.3 Hz, 1 H), 7.04–7.18
(m, 5 H), 7.27–7.31 (m, 2 H), 7.45–7.48 (m, 2 H), 7.58–7.63 (m, 1 H),
7.77–7.94 (m, 4 H), 8.11–8.14 (m, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.6, 31.1, 51.2, 52.5, 60.5, 67.3,
74.6, 124.0, 125.4, 125.7, 125.9, 126.3, 126.5, 127.5, 127.8, 127.9,
128.0, 128.1, 128.5, 128.9, 132.90, 132.94, 133.0, 133.9, 136.9, 138.0,
142.6, 174.2, 200.6.
HPLC: 97% ee (Chiralpak IA-H, n-hexane/i-PrOH = 95:5, flow rate = 1.0
mL/min,  = 254 nm); tR = 31.01 and 33.11 min.
Methyl (2R,2′R,4′R,5′R)-4′-Cyclohexyl-1-oxo-2′-phenyl-3,4-dihy-
dro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate (3pa)
HRMS (ESI): m/z [M + H]+ calcd for C31H28NO3: 462.2064; found:
462.2066.
Yield: 61.9 mg (74%); white solid; mp 133–134 °C; []D +60 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 0.57–0.80 (m, 2 H), 0.84–1.03 (m, 3 H),
1.21–1.45 (m, 6 H), 2.34–2.42 (m, 3 H), 3.02–3.07 (m, 1 H), 3.19–3.25
(m, 1 H), 3.30–3.34 (m, 1 H), 3.38 (s, 3 H), 4.06–4.12 (m, 2 H), 7.29–
7.42 (m, 5 H), 7.51 (t, J = 7.1 Hz, 1 H), 7.65 (d, J = 7.3 Hz, 2 H), 8.06 (d,
J = 7.7 Hz, 1 H).
HPLC: 90% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 20.14 and 29.91 min.
Methyl (2R,2′R,4′R,5′R)-4′-(Furan-2-yl)-1-oxo-2′-phenyl-3,4-dihy-
dro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate (3ma)
13C{1H} NMR (75 MHz, CDCl3):  = 26.1, 26.22, 26.24, 26.5, 32.6, 33.7,
34.1, 39.8, 52.2, 60.8, 61.9, 65.2, 76.4, 126.4, 126.6, 128.1, 128.2,
133.2, 134.0, 137.3, 142.9, 176.1, 200.0.
HRMS (ESI): m/z [M + H]+ calcd for C27H32NO3: 418.2377; found:
418.2378.
Yield: 62.7 mg (78%); white solid; mp 175–176 °C; []D +87 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.96–2.05 (m, 1 H), 2.37–2.45 (m, 1 H),
2.66–2.82 (m, 2 H), 3.14–3.19 (m, 1 H), 3.41 (s, 3 H), 4.18 (s, 1 H), 4.35
(d, J = 11.0 Hz, 1 H), 4.63 (d, J = 11.0 Hz, 1 H), 5.99–6.18 (m, 2 H), 7.19–
7.34 (m, 6 H), 7.45–7.54 (m, 3 H), 8.06 (d, J = 7.7 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.4, 29.7, 49.7, 52.5, 61.6, 62.9,
71.0, 108.6, 110.3, 126.4, 127.5, 127.87, 127.90, 127.95, 128.1, 132.9,
133.1, 138.8, 142.1, 142.4, 152.5, 173.4, 198.4.
HPLC: 90% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 16.58 and 18.52 min.
Methyl (2R,2′R,4′R,5′R)-1-Oxo-4′-phenyl-2′-(m-tolyl)-3,4-dihydro-
1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate (3ab)
HRMS (ESI): m/z [M + H]+ calcd for C25H24NO4: 402.1700; found:
402.1701.
Yield: 72.5 mg (85%); white solid; mp 149–150 °C; []D +107 (c 0.1,
CH2Cl2, 21 °C).
HPLC: 97% ee (Chiralpak IA-H, n-hexane/i-PrOH = 95:5, flow rate = 1.0
mL/min,  = 254 nm); tR = 31.01 and 33.11 min.
1H NMR (300 MHz, CDCl3):  = 1.69–1.79 (m, 1 H), 1.88–1.95 (m, 1 H),
2.12 (s, 3 H), 2.68–2.92 (m, 2 H), 3.06–3.16 (m, 1 H), 3.76 (s, 3 H), 4.37
(d, J = 8.7 Hz, 1 H), 4.54 (d, J = 8.7 Hz, 1 H), 4.59 (s, 1 H), 6.85–7.10 (m,
6 H), 7.23–7.38 (m, 6 H), 7.65 (dd, J = 7.9, 0.9 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 21.2, 25.4, 30.5, 52.4, 55.5, 61.3,
64.3, 71.0, 125.1, 126.2, 127.0, 127.4, 127.9, 128.0, 128.3, 128.5, 128.7,
129.3, 132.9, 133.2, 137.5, 138.3, 139.1, 142.1, 173.9, 198.6.
Methyl (2R,2′R,4′R,5′R)-1-Oxo-2′-phenyl-4′-(thiophen-2-yl)-3,4-di-
hydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3na)
Yield: 73.6 mg (88%); white solid; mp 160–161 °C; []D +83 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 2.01–2.11 (m, 1 H), 2.30–2.35 (m, 1 H),
2.82–2.88 (m, 2 H), 3.24–3.34 (m, 1 H), 3.42 (s, 3 H), 4.25 (s, 1 H), 4.54
(d, J = 11.3 Hz, 1 H), 4.73 (d, J = 11.3 Hz, 1 H), 6.78–6.82 (m, 2 H), 7.06
(d, J = 4.5 Hz, 1 H), 7.20–7.27 (m, 2 H), 7.32–7.37 (m, 3 H), 7.45–7.50
(m, 1 H), 7.62–7.65 (m, 2 H), 8.07 (d, J = 7.6 Hz, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C28H28NO3: 426.2064; found:
426.2066.
HPLC: 80% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 16.15 and 24.62 min.
13C{1H} NMR (75 MHz, CDCl3):  = 25.2, 29.5, 51.9, 53.5, 61.7, 66.6,
66.7, 124.2, 126.4, 126.7, 126.8, 127.7, 127.9, 128.1, 128.6, 128.7,
132.6, 133.5, 139.0, 139.8, 143.3, 172.9, 197.6.
HRMS (ESI): m/z [M + H]+ calcd for C25H24NO3S: 418.1471; found:
418.1473.
Methyl (2R,2′R,4′R,5′R)-2′-(3-Methoxyphenyl)-1-oxo-4′-phenyl-
3,4-dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxyl-
ate (3ac)
Yield: 69.9 mg (79%); white solid; mp 157–158 °C; []D +57 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.72–1.80 (m, 1 H), 1.94–1.98 (m, 1 H),
2.73–3.21 (m, 3 H), 3.63 (s, 3 H), 3.76 (s, 3 H), 4.39 (d, J = 8.6 Hz, 1 H),
4.54–4.63 (m, 2 H), 6.61–6.80 (m, 3 H), 7.00–7.13 (m, 3 H), 7.27–7.35
(m, 6 H), 7.67 (d, J = 7.4 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.4, 30.4, 52.4, 55.1, 55.2, 61.5,
64.1, 70.6, 113.1, 114.0, 120.3, 126.4, 127.1, 127.5, 128.1, 128.3, 129.0,
129.4, 133.0, 133.1, 138.0, 141.2, 142.1, 159.1, 174.0, 198.2.
HPLC: 94% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 36.92 and 38.10 min.
Methyl (2R,2′R,4′S,5′R)-1-Oxo-2′-phenyl-4′-(thiophen-3-yl)-3,4-di-
hydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3oa)
Yield: 66.1 mg (79%); white solid; mp 170–171 °C; []D +71 (c 0.1,
CH2Cl2, 21 °C).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

H
Z. Gan et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C28H28NO4: 442.2013; found:
HRMS (ESI): m/z [M + H]+ calcd for C27H25FNO3: 430.1813; found:
442.2016.
430.1815.
HPLC: 83% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 44.72 and 57.05 min.
HPLC: 98% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 23.73 and 25.80 min.
Methyl (2R,2′R,4′R,5′R)-2′-(4-Methoxyphenyl)-1-oxo-4′-phenyl-
3,4-dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxyl-
ate (3ad)
Methyl (2R,2′S,4′R,5′R)-2′-(2-Chlorophenyl)-1-oxo-4′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3ag)
Yield: 73.4 mg (83%); white solid; mp 160–161 °C; []D +66 (c 0.1,
Yield: 80.3 mg (90%); white solid; mp 145–146 °C; []D +59 (c 0.1,
CH2Cl2, 21 °C).
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.68–1.78 (m, 1 H), 1.87–1.94 (m, 1 H),
2.56–2.76 (m, 2 H), 3.04–3.15 (m, 1 H), 3.67 (s, 3 H), 3.76 (s, 3 H), 4.34
(d, J = 8.7 Hz, 1 H), 4.50–4.59 (m, 2 H), 6.58–6.61 (m, 2 H), 6.96 (d, J =
7.6 Hz, 1 H), 7.10–7.06 (m, 3 H), 7.24–7.36 (m, 6 H), 7.66 (d, J = 7.7 Hz,
1 H).
1H NMR (300 MHz, CDCl3):  = 1.76–1.86 (m, 1 H), 1.98–2.05 (m, 1 H),
2.71–2.80 (m, 1 H), 2.92 (s, 1 H), 3.23–3.34 (m, 1 H), 3.76 (s, 3 H), 4.44
(d, J = 9.2 Hz, 1 H), 4.58 (d, J = 9.2 Hz, 1 H), 5.30 (s, 1 H), 6.97–7.06 (m,
3 H), 7.09–7.27 (m, 3 H), 7.24–7.26 (m, 1 H), 7.29–7.36 (m, 4 H), 7.57–
7.67 (m, 2 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.4, 30.6, 52.4, 55.1, 55.6, 61.1,
64.2, 70.5, 113.3, 126.3, 127.0, 128.0, 128.3, 129.1, 129.3, 131.3, 132.9,
138.3, 142.1, 159.0, 174.0, 198.7.
13C NMR (75 MHz, CDCl3):  = 25.5, 30.1, 52.4, 55.4, 61.9, 63.8, 64.8,
126.3, 126.9, 127.1, 127.4, 128.1, 128.3, 128.7, 129.1, 129.4, 130.0,
132.7, 133.1, 133.3, 137.5, 137.7, 143.0, 174.0, 198.1.
HRMS (ESI): m/z [M + H]+ calcd for C28H28NO4: 442.2013; found:
HRMS (ESI): m/z [M + H]+ calcd for C27H25ClNO3: 446.1517; found:
442.2014.
446.1518.
HPLC: 85% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 42.61 and 49.11 min.
HPLC: 83% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 23.01 and 33.40 min.
Methyl (2R,2′S,4′R,5′R)-2′-(2-Fluorophenyl)-1-oxo-4′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3ae)
Methyl (2R,2′R,4′R,5′R)-2′-(3-Chlorophenyl)-1-oxo-4′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3ah)
Yield: 77.4 mg (90%); white solid; mp 158–159 °C; []D +48 (c 0.1,
Yield: 74.1 mg (83%); white solid; mp 146–147 °C; []D +101 (c 0.1,
CH2Cl2, 21 °C).
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.70–1.81 (m, 1 H), 1.97–2.02 (m, 1 H),
2.62–2.77 (m, 2 H), 3.15–3.25 (m, 1 H), 3.74 (s, 3 H), 4.40 (d, J = 9.5 Hz,
1 H), 4.59 (d, J = 9.5 Hz, 1 H), 5.09 (s, 1 H), 6.65–6.72 (m, 1 H), 6.99–
7.08 (m, 4 H), 7.23–7.35 (m, 6 H), 7.47–7.53 (m, 1 H), 7.63 (d, J = 7.8
Hz, 1 H).
13C NMR (75 MHz, CDCl3):  = 30.2, 52.4, 55.2, 61.2, 61.3, 61.7, 63.6,
114.7 (d, J = 22.9 Hz), 124.2 (d, J = 3.4 Hz), 126.2, 126.9 (d, J = 12.0 Hz),
127.1, 127.4, 128.1, 128.3, 129.1 (d, J = 8.8 Hz), 129.35, 129.44 (d, J =
3.2 Hz), 132.6, 133.0, 137.6, 142.7, 159.9 (d, J = 245.7 Hz), 173.8,
198.0.
1H NMR (300 MHz, CDCl3):  = 1.72–1.82 (m, 1 H), 1.94–1.98 (m, 1 H),
2.68 (s, 1 H), 2.76–2.82 (m, 1 H), 3.05–3.17 (m, 1 H), 3.77 (s, 3 H), 4.39
(d, J = 9.0 Hz, 1 H), 4.54–4.61 (m, 2 H), 7.00–7.04 (m, 3 H), 7.09–7.15
(m, 3 H), 7.27–7.36 (m, 6 H), 7.65 (d, J = 7.6 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.3, 30.1, 52.4, 54.6, 61.4, 63.9,
69.6, 126.1, 126.6, 127.2, 127.6, 127.8, 128.2, 128.3, 129.2, 129.4,
132.9, 133.2, 133.7, 137.7, 141.8, 142.0, 173.8, 197.9.
HRMS (ESI): m/z [M + H]+ calcd for C27H25ClNO3: 446.1517; found:
446.1520.
HPLC: 94% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 20.29 and 26.45 min.
HRMS (ESI): m/z [M + H]+ calcd for C27H25FNO3: 430.1813; found:
430.1814.
HPLC: 96% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 21.18 and 28.47 min.
Methyl (2R,2′R,4′R,5′R)-2′-(4-Chlorophenyl)-1-oxo-4′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3ai)
Methyl (2R,2′R,4′R,5′R)-2′-(3-Fluorophenyl)-1-oxo-4′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3af)
Yield: 74.9 mg (84%); white solid; mp 149–150 °C; []D +94 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.71–1.81 (m, 1 H), 1.92–1.99 (m, 1 H),
2.73–2.87 (m, 2 H), 3.04–3.15 (m, 1 H), 3.75 (s, 3 H), 4.38 (d, J = 9.0 Hz,
1 H), 4.54 (d, J = 9.0 Hz, 1 H), 4.62 (s, 1 H), 6.98–7.13 (m, 6 H), 7.24–
7.35 (m, 6 H), 7.64 (d, J = 7.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3):  = 25.3, 30.2, 52.4, 54.9, 61.3, 63.9, 69.8,
126.6, 127.2, 127.6, 128.1, 128.2, 128.3, 129.3, 132.8, 133.2, 133.4,
137.7, 138.3, 141.9, 173.9, 198.0.
Yield: 61.1 mg (71%); white solid; mp 153–154 °C; []D +79 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.72–1.83 (m, 1 H), 1.93–2.00 (m, 1 H),
2.65 (s, 1 H), 2.74–2.83 (m, 1 H), 3.07–3.23 (m, 1 H), 3.76 (s, 3 H), 4.39
(d, J = 8.6 Hz, 1 H), 4.56 (d, J = 9.1 Hz, 1 H), 4.64 (s, 1 H), 6.73–6.79 (m,
1 H), 6.91–7.13 (m, 5 H), 7.24–7.36 (m, 6 H), 7.65 (d, J = 7.3 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.3, 30.2, 52.4, 54.8, 61.4, 63.9,
69.8, 114.6 (d, J = 21.4 Hz), 115.1 (d, J = 22.4 Hz), 123.6 (d, J = 2.3 Hz),
126.5, 127.2, 127.6, 128.2, 128.3, 129.36, 129.47 (d, J = 8.5 Hz), 133.2,
137.7, 141.9, 142.5 (dd, J = 6.6, 1.9 Hz), 173.8, 175.1 (d, J = 12.2 Hz),
197.7.
HRMS (ESI): m/z [M + H]+ calcd for C27H25ClNO3: 446.1517; found:
446.1518.
HPLC: 83% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 34.96 and 42.47 min.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

I
Z. Gan et al.
Paper
Synthesis
Methyl (2R,2′R,4′R,5′R)-2′-(4-Bromophenyl)-1-oxo-4′-phenyl-3,4-
dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate
(3aj)
(2017M610458 and 2018T110737) and Henan University of Engi-
neering of China for financial support of this research.NationalNatural
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Yield: 73.5 mg (75%); white solid; mp 148–149 °C; []D +79 (c 0.1,
CH2Cl2, 21 °C).
Supporting Information
1H NMR (300 MHz, CDCl3):  = 1.71–1.82 (m, 1 H), 1.93–1.98 (m, 1 H),
2.59–2.88 (m, 2 H), 3.04–3.15 (m, 1 H), 3.75 (s, 3 H), 4.37–4.40 (m, 1
H), 4.53–4.61 (m, 2 H), 6.99–7.14 (m, 4 H), 7.19–7.35 (m, 8 H), 7.64 (d,
J = 7.7 Hz, 1 H).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1706599. Su
p
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Su
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ortingInformatio
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13C{1H} NMR (75 MHz, CDCl3):  = 25.3, 30.2, 52.4, 54.9, 61.3, 63.9,
69.7, 121.7, 126.6, 127.2, 127.6, 128.2, 128.3, 129.3, 129.7, 131.0,
132.8, 133.3, 137.7, 138.7, 141.9, 173.9, 198.0.
HRMS (ESI): m/z [M + H]+ calcd for C27H25BrNO3: 490.1012; found:
490.1013.
References
(1) For selected examples, see: (a) Galliford, C. V.; Scheidt, K. A.
Angew. Chem. Int. Ed. 2007, 46, 8748. (b) Harvey, A. L. Drug Dis-
covery Today 2008, 13, 894. (c) Li, J. W. H.; Vederas, J. C. Science
2009, 325, 161.
HPLC: 91% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 23.87 and 32.29 min.
(2) (a) Obniska, J.; Byrtus, H.; Kamiński, K.; Pawłowski, M.;
Szczesio, M.; Karolak-Wojciechowska, J. Bioorg. Med. Chem.
2010, 18, 6134. (b) Obniska, J.; Kołaczkowski, M.; Bojarski, A.;
Duszyńska, B. Eur. J. Med. Chem. 2006, 41, 874.
(3) Jiang, B.; Xu, M. Angew. Chem. Int. Ed. 2004, 43, 2543.
(4) Tomita, M.; Okamoto, Y.; Kikuchi, T.; Osaki, K.; Nishikawa, M.;
Kamiya, K.; Sasaki, Y.; Matoba, K.; Goto, K. Chem. Pharm. Bull.
1971, 19, 770.
Methyl (2R,2′R,4′R,5′R)-1-Oxo-4′-phenyl-2′-[4-(trifluorometh-
yl)phenyl]-3,4-dihydro-1H-spiro[naphthalene-2,3′-pyrrolidine]-
5′-carboxylate (3ak)
Yield: 79.7 mg (83%); white solid; mp 165–166 °C; []D +113 (c 0.1,
CH2Cl2, 21 °C).
(5) For selected examples, see: (a) Wei, L.; Chang, X.; Wang, C.-J.
Acc. Chem. Res. 2020, 53, 1084. (b) Maroto, E. E.; Izquierdo, M.;
Reboredo, S.; Marco-Martínez, J.; Filippone, S.; Martín, N. Acc.
Chem. Res. 2014, 47, 2660. (c) Hashimoto, T.; Maruoka, K. Chem.
Rev. 2015, 115, 5366. (d) Bdiri, B.; Zhao, B.-J.; Zhou, Z.-M. Tetra-
hedron: Asymmetry 2017, 28, 876. (e) Adrio, J.; Carretero, J. C.
Chem. Commun. 2014, 50, 12434. (f) Fang, X.; Wang, C.-J. Org.
Biomol. Chem. 2018, 16, 2591. (g) Adrio, J.; Carretero, J. C. Chem.
Commun. 2019, 55, 11979. (h) Han, R.; Ding, Y.; Jin, X.; Li, E.-Q.
Org. Biomol. Chem. 2020, 18, 646. (i) Cui, H.; Li, K.; Wang, Y.;
Song, M.; Wang, C.; Wei, D.; Li, E.-Q.; Duan, Z.; Mathey, F. Org.
Biomol. Chem. 2020, 18, 3740. (j) Liu, T.-L.; Xue, Z.-Y.; Tao, H.-Y.;
Wang, C.-J. Org. Biomol. Chem. 2011, 9, 1980. (k) Liu, T.-L.; He,
Z.-L.; Li, Q.-H.; Tao, H.-Y.; Wang, C.-J. Adv. Synth. Catal. 2011,
353, 1713. (l) Li, Q.-H.; Liu, T.-L.; Wei, L.; Tao, H.-Y.; Wang, C.-J.
Chem. Commun. 2013, 49, 9642. (m) Meng, X.; Du, Y.; Zhang, Q.;
Yu, A.; Zhang, Y.; Jia, J.; Liu, X. Asian J. Org. Chem. 2017, 6, 1719.
(6) Allway, P.; Grigg, R. Tetrahedron Lett. 1991, 32, 5817.
(7) Liu, Y.; Li, W.; Zhang, J. Natl. Sci. Rev. 2017, 4, 326.
(8) For selected examples, see: (a) Antonchick, A. P.; Gerding-
Reimers, C.; Catarinella, M.; Schürmann, M.; Preut, H.; Ziegler,
S.; Rauh, D.; Waldmann, H. Nat. Chem. 2010, 2, 735.
(b) Takayama, H.; Jia, Z.-J.; Kremer, L.; Bauer, J. O.; Strohmann,
C.; Ziegler, S.; Antonchick, A. P.; Waldmann, H. Angew. Chem. Int.
Ed. 2013, 52, 12404.
(9) For selected examples, see: (a) Liu, T.-L.; He, Z.-L.; Wang, C.-J.
Chem. Commun. 2011, 47, 9600. (b) Teng, H.-L.; Huang, H.;
Wang, C.-J. Chem. Eur. J. 2012, 18, 12614. (c) Liu, H.-C.; Liu, K.;
Xue, Z.-Y.; He, Z.-L.; Wang, C.-J. Org. Lett. 2015, 17, 5440. (d) Liu,
H.-C.; Tao, H.-Y.; Cong, H.; Wang, C.-J. J. Org. Chem. 2016, 81,
3752. (e) Shen, C.; Yang, Y.; Wei, L.; Dong, W.-W.; Chung, L. W.;
Wang, C.-J. iScience 2019, 11, 146.
1H NMR (300 MHz, CDCl3):  = 1.73–1.83 (m, 1 H), 2.01–2.06 (m, 1 H),
2.80–3.19 (m, 3 H), 3.77 (s, 3 H), 4.42 (d, J = 9.2 Hz, 1 H), 4.60 (d, J = 9.2
Hz, 1 H), 4.71 (s, 1 H), 6.99–7.11 (m, 2 H), 7.22–7.34 (m, 8 H), 7.49–
7.59 (m, 3 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.2, 20.0, 52.4, 54.2, 61.4, 63.7,
69.4, 124.5 (d, J = 3.7 Hz), 124.9 (d, J = 3.9 Hz), 126.6, 127.2, 127.5,
128.2, 128.3, 128.5, 129.4, 131.2, 132.8, 133.3, 137.4, 141.1, 141.6,
173.8, 197.7.
HRMS (ESI): m/z [M + H]+ calcd for C28H25F3NO3: 480.1781; found:
480.1783.
HPLC: 83% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 25.05 and 27.44 min.
Methyl (2R,2′R,4′R,5′R)-2′-Cyclohexyl-1-oxo-4′-phenyl-3,4-dihy-
dro-1H-spiro[naphthalene-2,3′-pyrrolidine]-5′-carboxylate (3al)
Yield: 69.4 mg (83%); white solid; mp 134–135 °C; []D +44 (c 0.1,
CH2Cl2, 21 °C).
1H NMR (300 MHz, CDCl3):  = 1.05–1.13 (m, 3 H), 1.39–1.55 (m, 5 H),
1.66–1.79 (m, 3 H), 1.86–1.98 (m, 2 H), 2.41–2.55 (m, 2 H), 2.70–2.81
(m, 1 H), 3.13 (d, J = 5.0 Hz, 1 H), 3.63 (s, 3 H), 4.14 (dd, J = 30.6, 9.9 Hz,
2 H), 7.07–7.09 (m, 1 H), 7.15–7.24 (m, 4 H), 7.27–7.31 (m, 2 H), 7.41
(t, J = 8.0 Hz, 1 H), 8.02 (d, J = 7.3 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3):  = 25.4, 26.15, 26.21, 26.5, 29.0, 31.5,
33.3, 39.9, 52.1, 58.5, 59.5, 64.0, 74.8, 126.8, 127.1, 127.5, 128.2,
128.4, 129.1, 133.29, 133.32, 137.9, 142.9, 173.2, 200.2.
HRMS (ESI): m/z [M + H]+ calcd for C27H31NO3: 418.2377; found:
418.2379.
HPLC: 80% ee (Chiralpak AD-H, n-hexane/i-PrOH = 90:10, flow rate =
1.0 mL/min,  = 254 nm); tR = 8.90 and 21.16 min.
(10) For selected examples, see: (a) Zhang, Z.-M.; Xu, B.; Xu, S.; Wu,
H.-H.; Zhang, J. Angew. Chem. Int. Ed. 2016, 55, 6324. (b) Xu, B.;
Zhang, Z.-M.; Xu, S.; Liu, B.; Xiao, Y.; Zhang, J. ACS Catal. 2017, 7,
210. (c) Liu, B.; Zhang, Z.-M.; Xu, B.; Xu, S.; Wu, H.-H.; Zhang, J.
Adv. Synth. Catal. 2018, 360, 2144. (d) Wang, L.; Chen, M.; Zhang,
J. Org. Chem. Front. 2019, 6, 694.
Funding Information
We are grateful to the National Natural Science Foundation of China
(21702189), the Key Scientific and Technological Project of Henan
Province (202102310004), the China Postdoctoral Science Foundation
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

J
Z. Gan et al.
Paper
Synthesis
(11) For selected examples, see: (a) Liu, Y.-Z.; Shang, S.-J.; Yang, W.-
L.; Luo, X.; Deng, W.-P. J. Org. Chem. 2017, 82, 11141. (b) Liu, Y.-
Z.; Shang, S.-J.; Zhu, J.-Y.; Yang, W.-L.; Deng, W.-P. Adv. Synth.
Catal. 2018, 360, 2191. (c) Deng, H.; Jia, R.; Yang, W.-L.; Yu, X.;
Deng, W.-P. Chem. Commun. 2019, 55, 7346. (d) Zou, X.-J.; Yang,
W.-L.; Zhu, J.-Y.; Deng, W.-P. Chin. J. Chem. 2020, 38, 435.
(12) For other ligands used for 1,3-dipolar cycloadditions of azome-
thine ylides, see: (a) Awata, A.; Arai, T. Chem. Eur. J. 2012, 18,
8278. (b) Arai, T.; Ogawa, H.; Awata, A.; Sato, M.; Watabe, M.;
Yamanaka, M. Angew. Chem. Int. Ed. 2015, 54, 1595. (c) Deng, H.;
He, F.-S.; Li, C.-S.; Yang, W.-L.; Deng, W.-P. Org. Chem. Front.
2017, 4, 2343. (d) Zhu, J.-Y.; Yang, W.-L.; Liu, Y.-Z.; Shang, S.-J.;
Deng, W.-P. Org. Chem. Front. 2018, 5, 70. (e) Xu, S.; Zhang, Z.-
M.; Xu, B.; Liu, B.; Liu, Y.; Zhang, J. J. Am. Chem. Soc. 2018, 140,
2272. (f) Cheng, F.; Kalita, S. J.; Zhao, Z.-N.; Yang, X.; Zhao, Y.;
Schneider, U.; Shibata, N.; Huang, Y.-Y. Angew. Chem. Int. Ed.
2019, 58, 16637.
(14) (a) Xi, Q.-Z.; Gan, Z.-J.; Li, E.-Q.; Duan, Z. Eur. J. Org. Chem. 2018,
4917. (b) Li, E.; Jin, H.; Huang, Y. ChemistrySelect 2018, 3, 12007.
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