Ir-catalyzed asymmetric hydrogenation of 3-arylindenones for the synthesis of chiral 3-arylindanones

Article abstract of DOI:10.1016/j.tet.2021.132003

An efficient synthesis of chiral 3-arylindanones via iridium-catalyzed asymmetric hydrogenation of 3-arylindenones has been developed. The reaction showed good compatibility with various functional groups, delivering a variety of 3-arylindanones in excellent yields and with good enantioselectivities. The reaction was also carried out on a gram-scale, delivering the product in quantitative yield. In addition, the products can be easily derivatized and transformed into natural products and pharmaceutical agents.

Full text of DOI:10.1016/j.tet.2021.132003

Tetrahedron 84 (2021) 132003
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ir-catalyzed asymmetric hydrogenation of 3-arylindenones for the
synthesis of chiral 3-arylindanones
Jun Yan, Yu Nie, Feng Gao, Qianjia Yuan, Fang Xie**, Wanbin Zhang*
Shanghai Key Laboratory of Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and
Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient synthesis of chiral 3-arylindanones via iridium-catalyzed asymmetric hydrogenation of 3-
arylindenones has been developed. The reaction showed good compatibility with various functional
groups, delivering a variety of 3-arylindanones in excellent yields and with good enantioselectivities. The
reaction was also carried out on a gram-scale, delivering the product in quantitative yield. In addition, the
products can be easily derivatized and transformed into natural products and pharmaceutical agents.
© 2021 Elsevier Ltd. All rights reserved.
Received 30 December 2020
Received in revised form
2 February 2021
Accepted 3 February 2021
Available online 15 February 2021
Keywords:
Iridium
Asymmetric hydrogenation
Chiral 3-arylindanone
Axis-unfixed
Phosphine-oxazoline
1. Introduction
axis-unfixed biphenylphosphine-oxazoline/iridium catalysts could
provide efficient access to chiral indanones (Scheme 1c).
In drug discovery, indanones are considered to be privileged
structures as these are present in numerous pharmaceuticals [1].
Among them, optically active 3-arylindanones are a core structural
motif of many bioactive molecules and natural products, and are
also very useful building blocks with applications in the pharma-
ceutical industry [2]. For example, (þ)-isopaucifloral F, (ꢀ)-ampe-
lopsin D, (þ)-pallidol and (þ)-laetevirenol A are resveratrol-
derived natural products [3]; (þ)-Brazilane and (þ)-haematox-
ylane are used in traditional Chinese medicine for the treatment of
convulsion, menstrual disorders and straumatic disease [4]; and
(þ)-indatraline is a famous pharmaceutical used for the treatment
of depression (Fig. 1) [5]. Although the chiral 3-arylindanone motif
is important, the methods for obtaining such structures are limited
[6], and the reported strategies predominantly focus on the
transition-metal catalyzed enantioselective intramolecular hydro-
acylation of 2-vinyl benzaldehydes (Scheme 1a) [7] and reductive
Heck cyclization reactions of enones (Scheme 1b) [8]. Given the
importance of this molecular structure, we postulated that the
asymmetric hydrogenation of 3-arylindenones using our developed
Transition-metal catalyzed asymmetric hydrogenation reaction
is a popular method for obtaining chiral molecules, as it is opera-
tionally simple and requires only low catalyst loadings [9]. How-
ever, to the best of our knowledge, there are no reports concerning
transition-metal catalyzed asymmetric hydrogenation reactions for
the synthesis of chiral 3-arylindanones. Our group developed an
axis-unfixed biphenylphosphine-oxazoline/iridium catalyst which
showed excellent reactivity and enantioselectivity for the asym-
metric hydrogenation of a few types of C]C bonds [10,11], espe-
cially for the hydrogenation of five-membered exo-a,b-unsaturated
compounds [11]. The carbonyl group is used as a coordinating
functional group in the reaction and delivers the corresponding
products bearing an
contrast to our previous work, 3-arylindenones are endo-
saturated compounds, and possess a substituent group at the
a
-chiral carbon to the carbonyl group [11]. In
a,b
-un-
b-
position. For such structures, maybe the carbonyl group could not
be used as the coordinating functional group due to the rigidity of
the system. Additionally, the C]C bond in such structures is
electron-deficient, so the compound may not readily bind with the
catalyst. To date, no catalytic system for the asymmetric hydroge-
nation of 3-arylindenones has been reported. The synthesis of 3-
arylindanones with excellent enantioselectivities and yields via
transition-metal catalyzed asymmetric hydrogenation is
* Corresponding author.
** Corresponding author.
E-mail addresses: xiefang@sjtu.edu.cn (F. Xie), wanbin@sjtu.edu.cn (W. Zhang).
https://doi.org/10.1016/j.tet.2021.132003
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

J. Yan, Y. Nie, F. Gao et al.
Tetrahedron 84 (2021) 132003
Fig. 1. Selected examples of natural products and pharmaceuticals bearing 3-arylindanones.
Table 1
Optimization of reaction conditionsa.
Entry
Catalyst
Solvent
Conv (%)b
Erc
1
2
3
4
5
6
C1
C1
C1
C1
C1
C1
C1
C1
C2
C3
C3
Toluene
DCM
DCE
THF
MeOH
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
o-xylene
99
99
99
50
14
99
47
64
99
99
51
90:10
91:9
88:12
86:14
91:9
92:8
92:8
91:9
78:22
93:7
Scheme 1. Different methods for obtaining the chiral 3-aryl-indanones.
challenging.
7d
8e
9
2. Results and discussion
Based on our previous results [10,11], catalyst C1 was selected
and evaluated under asymmetric hydrogenation conditions for the
reaction of 3-phenylindenone 1a (Table 1). First, the solvent for the
reaction was examined (entries 1e6). To our delight, the reaction
proceeded very well when using toluene, dichloromethane, 1,2-
dichloroethane or o-xylene as the reaction solvents, delivering
the product 2a in quantitative yields and with good enantiose-
lectivities (entries 1e3 and 6). To improve the enantioselectivity of
the product, various types of acids and bases were employed as
additives and screened for the reaction, however better results
were not obtained (entries 7e8). Next, the catalysts for the reaction
were screened using o-xylene as the reaction solvent. Catalysts C2
and C3 provided the product 2a with 78:22 and 93:7 er values,
respectively (entries 9e10). 51% Conversion was obtained, when
the hydrogen pressure was reduced to 30 bar (entry 11). The reac-
tion solvent and temperature were also screened using C3 as the
10
11f
93:7
a
Reaction conditions: 3-phenylindenone 1a (0.2 mmol) and catalyst (1 mol %)
were stirred under H2 (50 bar) in solvent (2 mL) in an autoclave at 30 ꢁC for 48 h.
b
Determined by 1H NMR of the crude product.
Determined by HPLC analysis on chiral stationary phases.
CH3COONa was used as the additive.
CH3COOH was used as the additive.
c
d
e
f
The pressure of hydrogen was 30 bar.
catalyst, however no better results was obtained.
With the optimized reaction conditions in hand (Table 1, entry
10), we next examined the substrate scope of this asymmetric hy-
drogenation reaction (Table 2). First, 3-phenylindenones bearing
different substituted groups on the indenone ring were tested. 3-
2

J. Yan, Y. Nie, F. Gao et al.
Tetrahedron 84 (2021) 132003
Table 2
Substrate scopea,b
.
Phenylindenones bearing an electron-withdrawing or electron-
donating group at various positions of the indenones delivered
the corresponding products with excellent yields and high enan-
tioselectivities (2b-2g). Interestingly, methoxy substitution at the
4-position on the 3-phenylindenone gave the desired product 2b in
97% yield, albeit with diminished enantioselectivity (79:21 er). It
should be noted that the substrate bearing 5,6-dimethoxy groups
on the 3-phenylindenone gave no product, and the starting mate-
rial was recovered in quantitative yield. This may be ascribed to the
two oxygens in the substrate coordinating to the catalyst, deacti-
vating it. Next, the compatibility of 3-aryl substitutions for the
synthesis of various 3-arylated indanones was examined. The
transformation performs well with an electron-donating group at
the para- or meta-position of the 3-phenyl ring, delivering the
3

J. Yan, Y. Nie, F. Gao et al.
Tetrahedron 84 (2021) 132003
Fig. 2. Stereochemical model for the asymmetric hydrogenation of 3-arylindenones.
desired products in excellent yields and enantioselectivities (2h-
2k). A substrate bearing a methoxy group at the ortho-position of 3-
phenyl ring gave the product 2l in 98% yield with a lower enan-
tioselectivity (88:12 er). A variety of electron-withdrawing groups
on the 3-phenyl ring were well tolerated under the reaction con-
ditions, including fluoro, chloro, bromo, trifluoromethyl and phenyl
groups, affording the corresponding products in excellent yields
and good enantioselectivities (2m-2s). Similar to the results ob-
tained for product 2l, a substrate bearing a chloro substituent at the
ortho-position of the 3-phenyl ring delivered the desired product 2t
in excellent yield but with a lower enantioselectivity (85:15 er),
most likely due to the steric hindrance of the substrates. 2-
Naphthyl substituted indenone afforded product 2u in 98% yield
and with 95:5 er. A heteroaryl ring 2-furyl substituted indenone
delivered the desired product 2v with moderate enantioselectivity.
An alkyl-substituted indenone gave the product 2w in 98% yield
with 88:12 er. In addition, 2-methyl-3-phenylindenone was also
synthesized, and tested under the reaction conditions, however, no
reduced product was obtained. The absolute configuration of
product 2a was determined to be (S) by comparing the optical
rotation value with previously reported data [8a]. The remainder of
the products were assigned by analogy with product 2a.
The observed stereochemical outcome of the reaction with the
axis-unfixed biphenylphosphine-oxazoline/iridium catalyst can be
rationalized based on favored and disfavored intermediates shown
in Fig. 2 [11]. In the favored intermediate A, the R-group oriented
upward, away from the phenyl group of the catalyst, thus leading to
products with the S-configuration.
The asymmetric hydrogenation reaction can be performed on a
gram-scale, delivering the corresponding product 2a in quantita-
tive yield with little erosion in enantioselectivity (Scheme 2a). The
enantiomerically enriched 3-arylindanones can be derivatized into
a variety of synthetically useful building blocks. For example, the
carbonyl group in the product 2a can be transformed into alkenyl
and hydroxyl groups via a Wittig reaction and reduction reaction,
delivering the corresponding product 3 and 4 in excellent yields,
respectively. In addition, the product 2a can also be transformed
into lactone 5 in 76% yield with 89:11 er (Scheme 2b).
Scheme 2. Gram-scale reaction, product derivatization and formal synthesis of (S)-
tolterodine and (þ)-indatraline.
method for the synthesis of enantiomerically enriched 3-
arylindanones in excellent yields and good enantioselectivitites
using an iridium-catalyzed asymmetric hydrogenation reaction
employing our developed axis-unfixed biphenylphosphine-oxazo-
line ligand. The reaction shows excellent compatibility with various
functional groups, and the reaction can be carried out on gram-
scale with the product being easily derivatized. In addition, (S)-
tolterodine and (þ)-indatraline can be formally synthesized from
the reduced products 2e and 2r, respectively.
4. Experimental sections
4.1. General experimental
(S)-Tolterodine possesses spasmolytic activity against urinary
disorders and intestinal spasms caused by various non-cholinergic
mechanisms or where anti-muscarinc effects are not acceptable; its
synthesis has attracted much attention [12,2b]. This new method
provides an efficient formal synthesis of (S)-tolterodine, starting
from the reduced product 2e (Scheme 2c) [2b]. In addition,
(þ)-indatraline is a long-acting monoamine reuptake inhibitor and
it has been subjected to several stereoselective synthesis [13]. The
product 2r was obtained in 95:5 er using our asymmetric hydro-
genation conditions, which can be employed in the synthesis of
(þ)-indatraline via a reported method (Scheme 2c) [8c].
All commercially available reagents were used as received. All
asymmetric hydrogenation reactions were performed in autoclave
under an atmosphere of hydrogen and the solvents were dried and
distilled by standard procedures. 1H, 13C, and 19F NMR spectra were
obtained using Bruker Avance III HD 400 MHz NMR or Bruker
Avance III HD 500 MHz NMR Spectrometer with TMS as an internal
standard. Melting points were measured with SGW X-4 micro
melting point apparatus. Enantioselectivities were determined by
high performance liquid chromatography (HPLC) using Daicel
CHIRALPAK OD-H and OJ-H columns with hexane/iPrOH as eluent.
Optical rotations were measured on a Rudolph Research Analytical
Autopol VI automatic polarimeter using a 50 mm path-length cell at
589 nm. High Resolution Mass Spectrometry (HRMS) analysis was
carried out using an electrospray spectrometer Waters Micromass
Q-TOF Premier Mass Spectrometer.
3. Conclusions
In summary, we have successfully developed an efficient
4

J. Yan, Y. Nie, F. Gao et al.
Tetrahedron 84 (2021) 132003
4.2. General procedure for the asymmetric hydrogenation of 3-
arylindenones 1
d
7.70 (d, J ¼ 8.0 Hz, 1H), 7.32 (t, J ¼ 7.5 Hz, 2H), 7.28e7.19 (m, 2H),
7.13 (d, J ¼ 7.5 Hz, 2H), 7.05 (s, 1H), 4.51 (dd, J ¼ 8.0, 4.0 Hz, 1H), 3.21
(dd, J ¼ 19.0, 8.0 Hz, 1H), 2.68 (dd, J ¼ 19.5, 4.0 Hz, 1H), 2.37 (s, 3H).
The catalyst C3 (1 mol %), 3-arylindenone (1, 0.2 mmol) and
anhydrous o-xylene (2 mL) were added to the hydrogenation tube
and then the hydrogenation tube was charged in an autoclave. The
autoclave was sealed and purged three times with hydrogen. The
autoclave was charged with hydrogen to 50 bar, and the reaction
mixture was stirred at 30 ꢁC for 48 h. After releasing the hydrogen
and removing the solvent, the mixture was purified by preparative
TLC on silica gel to afford the pure product. The er values was
determined by chiral HPLC.
13C NMR (125 MHz, CDCl3)
d 205.6, 158.5, 146.4, 143.8, 134.5, 129.2,
128.9, 127.6, 127.1, 126.9, 123.2, 47.0, 44.3, 22.1. HPLC [DAICEL
CHIRALPAK OD-H, hexane/iPrOH ¼ 95/5, 254 nm, 0.5 mL/min,
25 ꢁC. tR1 ¼16.9 min (major), tR2 ¼ 18.6 min (minor)]; 93:7 er.
[
a
]25D ¼ þ20.3 (c ¼ 0.1, CH2Cl2).
4.3.6. (S)-6-Chloro-3-phenyl-2,3-dihydro-1H-inden-1-one (2f) [14]
Colorless oil (47.6 mg, 98% yield). 1H NMR (400 MHz, CDCl3)
7.79e7.74 (m, 1H), 7.55e7.50 (m, 1H), 7.36e7.30 (m, 2H),
d
7.29e7.27 (m, 1H), 7.22 (d, J ¼ 8.4 Hz, 1H), 7.14e7.08 (m, 2H), 4.55
4.3. Characterization data of products 2
(dd, J ¼ 8.0, 4.0 Hz, 1H), 3.27 (dd, J ¼ 19.2, 8.0 Hz, 1H), 2.73 (dd,
J ¼ 19.6, 4.0 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d 204.6, 156.1, 143.2,
4.3.1. (S)-3-Phenyl-2,3-dihydro-1H-inden-1-one (2a) [8a]
138.3, 135.2, 134.5, 129.1, 128.3, 127.7, 127.3, 123.3, 47.3, 44.2. HPLC
[DAICEL CHIRALPAK OD-H, hexane/iPrOH ¼ 95/5, 254 nm, 0.5 mL/
min, 25 ꢁC. tR1 ¼18.8 min (major), tR2 ¼ 24.0 min (minor)]; 91:9 er.
Colorless solid (41.2 mg, 99% yield). 1H NMR (500 MHz, CDCl3)
d
7.85e7.78 (m, 1H), 7.55 (td, J ¼ 7.5, 1.5 Hz, 1H), 7.40 (t, J ¼ 7.5 Hz,
1H), 7.33e7.28 (m, 2H), 7.27e7.21 (m, 2H), 7.16e7.08 (m, 2H), 4.56
(dd, J ¼ 8.0, 4.0 Hz, 1H), 3.22 (dd, J ¼ 19.0, 8.0 Hz, 1H), 2.68 (dd,
[
a
]25D ¼ þ55.6 (c ¼ 0.2, CH2Cl2).
J ¼ 19.5, 4.0 Hz, 1H). 13C NMR (125 MHz, CDCl3)
d
206.0, 158.0, 143.7,
4.3.7. (S)-5-Chloro-3-phenyl-2,3-dihydro-1H-inden-1-one (2g)
[14]
136.8, 135.1, 128.9, 127.9, 127.7, 127.0, 126.9, 123.4, 46.9, 44.5. HPLC
[DAICEL CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/
min, 25 ꢁC. tR1 ¼11.9 min (minor), tR2 ¼ 15.2 min (major)]; 93:7 er.
White solid (47.6 mg, 98% yield). 1H NMR (400 MHz, CDCl3)
d
7.75e7.70 (m, 1H), 7.40e7.36 (m, 1H), 7.36e7.30 (m, 2H),
[
a
]25D ¼ þ64.9 (c ¼ 0.4, CH2Cl2).
7.29e7.26 (m, 1H), 7.24 (s, 1H), 7.13e7.08 (m, 2H), 4.53 (dd, J ¼ 8.0,
3.6 Hz, 1H), 3.23 (dd, J ¼ 19.6, 8.4 Hz, 1H), 2.71 (dd, J ¼ 19.2, 4.0 Hz,
4.3.2. (S)-4-Methoxy-3-phenyl-2,3-dihydro-1H-inden-1-one (2b)
[8a]
1H). 13C NMR (100 MHz, CDCl3)
d 204.5, 159.5, 142.9, 141.7, 135.2,
129.2, 128.9, 127.7, 127.4, 127.1, 124.7, 46.9, 44.3. HPLC [DAICEL
CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/min, 25 ꢁC.
tR1 ¼11.8 min (minor), tR2 ¼ 14.7 min (major)]; 92:8 er.
Brown solid (46.2 mg, 97% yield). 1H NMR (500 MHz, CDCl3)
d
7.43e7.40 (m, 2H), 7.26e7.22 (m, 2H), 7.21e7.16 (m,1H), 7.08e7.05
(m, 2H), 7.04 (dd, J ¼ 6.0, 2.5 Hz, 1H), 4.65 (dd, J ¼ 8.0, 2.5 Hz, 1H),
[
a
]25D ¼ ꢀ12.8 (c ¼ 0.1, CH2Cl2).
3.69 (s, 3H), 3.21 (dd, J ¼ 19.5, 8.5 Hz, 1H), 2.63 (dd, J ¼ 19.0, 2.5 Hz,
1H). 13C NMR (125 MHz, CDCl3)
d
206.5, 157.3, 145.7, 143.7, 138.5,
4.3.8. (S)-3-(p-Tolyl)-2,3-dihydro-1H-inden-1-one (2h) [14]
129.8, 128.4, 127.2, 126.4, 116.1, 115.1, 55.6, 47.3, 41.7. HPLC [DAICEL
CHIRALPAK OD-H, hexane/iPrOH ¼ 95/5, 254 nm, 0.5 mL/min,
25 ꢁC. tR1 ¼15.4 min (major), tR2 ¼ 19.6 min (minor)]; 79:21 er.
Yellow oil (43.6 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
d 7.80
(d, J ¼ 8.0 Hz, 1H), 7.56 (t, J ¼ 7.0 Hz, 1H), 7.41 (t, J ¼ 7.5 Hz, 1H),
7.29e7.23 (m, 1H), 7.15e7.08 (m, 2H), 7.04e7.00 (m, 2H), 4.54 (dd,
J ¼ 8.0, 3.5 Hz, 1H), 3.22 (dd, J ¼ 19.0, 8.0 Hz, 1H), 2.67 (dd, J ¼ 19.0,
[
a
]25D ¼ ꢀ7.5 (c ¼ 0.2, CH2Cl2).
3.5 Hz, 1H), 2.33 (s, 3H). 13C NMR (125 MHz, CDCl3)
d 206.2, 158.1,
4.3.3. (S)-5-Methoxy-3-phenyl-2,3-dihydro-1H-inden-1-one (2c)
[8a]
140.6, 136.6, 136.5, 135.0, 129.5, 127.7, 127.4, 126.8, 123.3, 46.9, 44.0,
21.0. HPLC [DAICEL CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm,
1.0 mL/min, 25 ꢁC. tR1 ¼10.7 min (minor), tR2 ¼ 17.3 min (major)];
White solid (46.7 mg, 98% yield). 1H NMR (400 MHz, CDCl3)
d
7.74 (d, J ¼ 8.4 Hz, 1H), 7.36e7.28 (m, 2H), 7.28e7.23 (m, 1H),
92:8 er. [
a
]25D ¼ þ109.0 (c ¼ 0.2, CH2Cl2).
7.16e7.09 (m, 2H), 6.94 (dd, J ¼ 8.4, 2.0 Hz, 1H), 6.66 (d, J ¼ 1.6 Hz,
1H), 4.50 (dd, J ¼ 8.0, 3.6 Hz, 1H), 3.79 (s, 3H), 3.21 (dd, J ¼ 19.2,
8.0 Hz,1H), 2.66 (dd, J ¼ 18.8, 3.6 Hz,1H). 13C NMR (100 MHz, CDCl3)
4.3.9. (S)-3-(tert-Butyl)phenyl)-2,3-dihydro-1H-inden-1-one (2i)
[15]
d
204.2, 165.6, 160.9, 143.7, 130.2, 128.9, 127.7, 127.0, 125.1, 116.0,
Yellow solid (51.3 mg, 97% yield). 1H NMR (500 MHz, CDCl3)
109.8, 55.7, 47.1, 44.5. HPLC [DAICEL CHIRALPAK OJ-H, hexane/
d
7.81 (d, J ¼ 7.5 Hz,1H), 7.57 (t, J ¼ 7.5 Hz,1H), 7.41 (t, J ¼ 7.5 Hz,1H),
iPrOH ¼ 95/5, 254 nm, 1.0 mL/min, 25 ꢁC. tR1 ¼ 22.8 min (minor),
7.34e7.29 (m, 3H), 7.06 (d, J ¼ 8.5 Hz, 2H), 4.56 (dd, J ¼ 8.0, 3.5 Hz,
1H), 3.22 (dd, J ¼ 19.0, 8.0 Hz,1H), 2.70 (dd, J ¼ 19.0, 4.0 Hz,1H),1.31
tR2 ¼ 24.7 min (major)]; 92:8 er. [ ]25D ¼ ꢀ10.0 (c ¼ 0.2, CH2Cl2).
a
(s, 9H). 13C NMR (125 MHz, CDCl3)
d 206.2, 158.1, 149.8, 140.5, 136.7,
4.3.4. (S)-6-Methoxy-3-phenyl-2,3-dihydro-1H-inden-1-one (2d)
[14]
135.0, 127.7, 127.2, 126.9, 125.7, 123.3, 46.8, 43.9, 34.4, 31.3. HPLC
[DAICEL CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/
min, 25 ꢁC. tR1 ¼6.9 min (minor), tR2 ¼ 8.8 min (major)]; 91:9 er.
White solid (46.7 mg, 98% yield). 1H NMR (400 MHz, CDCl3)
d
7.34e7.28 (m, 2H), 7.27e7.26 (m, 1H), 7.25e7.23 (m, 1H), 7.19e7.13
[
a
]25D ¼ þ35.6 (c ¼ 0.6, CH2Cl2).
(m, 2H), 7.14e7.10 (m, 2H), 4.50 (dd, J ¼ 8.0, 3.6 Hz, 1H), 3.79 (s, 3H),
3.21 (dd, J ¼ 19.2, 8.0 Hz, 1H), 2.66 (dd, J ¼ 18.8, 3.6 Hz, 1H). 13C NMR
4.3.10. (S)-3-(4-Methoxyphenyl)-2,3-dihydro-1H-inden-1-one (2j)
[8a]
(100 MHz, CDCl3)
d 206.0, 159.8, 150.9, 143.9, 138.0, 128.9, 127.6,
127.5, 126.9, 124.5, 104.4, 55.7, 47.6, 43.8. HPLC [DAICEL CHIRALPAK
OJ-H, 254 nm, 1.0 mL/min,
hexane/iPrOH ¼ 95/5,
25 ꢁC.
tR1 ¼19.8 min (minor), tR2 ¼ 24.8 min (major)]; 89:11 er.
]25D ¼ þ43.4 (c ¼ 0.2, CH2Cl2).
Yellow solid (46.2 mg, 97% yield). 1H NMR (500 MHz, CDCl3)
d
7.80 (d, J ¼ 7.5 Hz,1H), 7.56 (t, J ¼ 7.5 Hz,1H), 7.41 (t, J ¼ 7.5 Hz,1H),
7.27 (d, J ¼ 6.0 Hz, 1H), 7.04 (d, J ¼ 8.5 Hz, 2H), 6.85 (d, J ¼ 9.0 Hz,
2H), 4.53 (dd, J ¼ 8.0, 4.0 Hz, 1H), 3.79 (s, 3H), 3.21 (dd, J ¼ 19.0,
8.0 Hz,1H), 2.65 (dd, J ¼ 19.5, 4.0 Hz,1H). 13C NMR (125 MHz, CDCl3)
[
a
4.3.5. (S)-5-Methyl-3-phenyl-2,3-dihydro-1H-inden-1-one (2e)
[14]
d 206.4, 158.8, 158.5, 136.9, 136.0, 135.3, 128.8, 128.0, 127.0, 123.5,
114.5, 55.5, 47.2, 43.9. HPLC [DAICEL CHIRALPAK OJ-H, hexane/
Yellow solid (43.6 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
iPrOH ¼ 95/5, 254 nm, 1.0 mL/min, 25 ꢁC. tR1 ¼ 21.8 min (minor),
5

J. Yan, Y. Nie, F. Gao et al.
Tetrahedron 84 (2021) 132003
tR2 ¼ 34.2 min (major)]; 92:8 er. [
a
]25D ¼ þ59.1 (c ¼ 0.6, CH2Cl2).
4.3.16. (S)-3-(4-(Trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-
one (2p) [16]
4.3.11. (S)-3-(3-Methoxyphenyl)-2,3-dihydro-1H-inden-1-one (2k)
White solid (54.1 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
[15]
d
7.84 (d, J ¼ 7.5 Hz, 1H), 7.63e7.52 (m, 3H), 7.50e7.41 (m, 1H),
Yellow oil (46.7 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
d
7.81
7.29e7.21 (m, 3H), 4.66 (dd, J ¼ 8.0, 4.0 Hz, 1H), 3.27 (dd, J ¼ 19.0,
(d, J ¼ 8.0 Hz, 1H), 7.57 (t, J ¼ 7.5 Hz, 1H), 7.42 (t, J ¼ 7.5 Hz, 1H), 7.29
(d, J ¼ 7.5 Hz, 1H), 7.23 (t, J ¼ 7.5 Hz, 1H), 6.79 (dd, J ¼ 8.0, 2.5 Hz,
1H), 6.72 (d, J ¼ 8.0 Hz,1H), 6.66 (s,1H), 4.55 (dd, J ¼ 8.0, 4.0 Hz,1H),
3.76 (s, 3H), 3.22 (dd, J ¼ 19.5, 8.0 Hz, 1H), 2.70 (dd, J ¼ 19.5, 4.0 Hz,
8.0 Hz,1H), 2.67 (dd, J ¼ 19.0, 4.0 Hz,1H). 13C NMR (125 MHz, CDCl3)
d
205.1, 156.8, 147.7, 136.7, 135.2, 129.3 (q, J ¼ 32.5 Hz), 128.2, 128.0,
126.7, 125.8 (q, J ¼ 3.8 Hz), 124.0 (q, J ¼ 272.5 Hz), 123.6, 46.5, 44.1.
19F NMR (471 MHz, CDCl3)
d - 62.5. HPLC [DAICEL CHIRALPAK OD-H,
1H). 13C NMR (125 MHz, CDCl3)
d
206.2, 160.2, 158.0, 145.5, 137.0,
hexane/iPrOH ¼ 95/5, 254 nm, 0.5 mL/min, 25 ꢁC. tR1 ¼16.8 min
135.3, 130.2, 128.1, 127.1, 123.6, 120.2, 113.9, 112.2, 55.4, 46.9, 44.7.
HPLC [DAICEL CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm,
1.0 mL/min, 25 ꢁC. tR1 ¼19.5 min (minor), tR2 ¼ 24.6 min (major)];
(major), tR2 ¼ 20.8 min (minor)]; 94:6 er. [ ]25D ¼ þ32.0 (c ¼ 0.6,
a
CH2Cl2).
91.5:8.5 er. [
a]25D ¼ þ51.6 (c ¼ 0.5, CH2Cl2).
4.3.17. (S)-3-([1,10-Biphenyl]-4-yl)-2,3-dihydro-1H-inden-1-one
(2q) [15]
4.3.12. (R)-3-(2-Methoxyphenyl)-2,3-dihydro-1H-inden-1-one (2l)
White solid (55.7 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
[15]
d
7.82 (d, J ¼ 7.5 Hz, 1H), 7.61e7.48 (m, 5H), 7.46e7.38 (m, 3H),
Brown oil (46.7 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
d
7.80
7.36e7.28 (m, 2H), 7.18 (d, J ¼ 8.0 Hz, 2H), 4.61 (dd, J ¼ 8.0, 4.0 Hz,
(d, J ¼ 7.5 Hz, 1H), 7.55 (t, J ¼ 7.5 Hz, 1H), 7.43e7.34 (m, 1H), 7.29 (d,
J ¼ 7.5 Hz, 1H), 7.25e7.20 (m, 1H), 6.97e6.93 (m, 1H), 6.90e6.84 (m,
2H), 4.94e4.81 (m, 1H), 3.74 (s, 3H), 3.17 (dd, J ¼ 19.0, 8.0 Hz, 1H),
1H), 3.25 (dd, J ¼ 19.5, 8.5 Hz, 1H), 2.72 (dd, J ¼ 19.5, 4.0 Hz, 1H). 13
C
NMR (125 MHz, CDCl3)
d 206.2, 158.1, 142.9, 140.8, 140.2, 137.0,
135.4, 129.0, 128.3, 128.2, 127.9, 127.6, 127.2, 127.1, 123.7, 47.1, 44.4.
HPLC [DAICEL CHIRALPAK OD-H, hexane/iPrOH ¼ 95/5, 254 nm,
1.0 mL/min, 25 ꢁC. tR1 ¼ 20.6 min (minor), tR2 ¼ 24.5 min (major)];
2.69 (dd, J ¼ 19.0, 3.5 Hz, 1H). 13C NMR (125 MHz, CDCl3)
d 206.7,
157.8, 157.2, 137.0, 134.6, 131.5, 128.3, 128.0, 127.4, 126.5, 123.2,
120.6, 110.8, 55.3, 45.1, 39.0. HPLC [DAICEL CHIRALPAK OJ-H, hex-
ane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/min, 25 ꢁC. tR1 ¼13.9 min (ma-
94:6 er. [
a
]25D ¼ þ56.2 (c ¼ 0.3, CH2Cl2).
jor), tR2 ¼ 16.9 min (minor)]; 88:12 er. [
a
]25D ¼ þ29.1 (c ¼ 0.5,
4.3.18. (S)-3-(3,4-Dichlorophenyl)-2,3-dihydro-1H-inden-1-one
(2r) [16]
CH2Cl2).
Yellow solid (54.3 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
4.3.13. (S)-3-(4-Fluorophenyl)-2,3-dihydro-1H-inden-1-one (2m)
[8a]
d
7.83 (d, J ¼ 7.5 Hz,1H), 7.61 (t, J ¼ 7.5 Hz,1H), 7.46 (t, J ¼ 7.0 Hz,1H),
7.38 (d, J ¼ 8.0 Hz, 1H), 7.30e7.20 (m, 2H), 6.95 (dd, J ¼ 8.5, 2.0 Hz,
1H), 4.55 (dd, J ¼ 8.0, 4.0 Hz, 1H), 3.23 (dd, J ¼ 19.5, 8.5 Hz, 1H), 2.62
White solid (44.3 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
d
7.81 (d, J ¼ 8.0 Hz, 1H), 7.59 (t, J ¼ 7.5 Hz, 1H), 7.43 (t, J ¼ 7.5 Hz,
(dd, J ¼ 19.0, 4.0 Hz, 1H). 13C NMR (125 MHz, CDCl3)
d 205.2, 156.8,
1H), 7.30e7.20 (m, 1H), 7.12e7.04 (m, 2H), 7.04e6.94 (m, 2H), 4.58
(dd, J ¼ 8.0, 4.0 Hz, 1H), 3.23 (dd, J ¼ 19.5, 8.0 Hz, 1H), 2.64 (dd,
144.2,137.0,135.6,133.2,131.3,131.1,129.9,128.6,127.2,126.9,123.9,
46.7, 43.8. HPLC [DAICEL CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5,
254 nm, 1.0 mL/min, 25 ꢁC. tR1 ¼16.5 min (major), tR2 ¼ 18.1 min
J ¼ 19.5, 4.0 Hz, 1H). 13C NMR (125 MHz, CDCl3)
d 205.9, 162.0, (d,
J ¼ 244.1 Hz), 157.9, 139.7 (d, J ¼ 2.9 Hz), 136.9, 135.4, 129.3 (d,
(minor)]; 95:5 er. [
a
]25D ¼ þ38.2 (c ¼ 0.5, CH2Cl2).
J ¼ 7.9 Hz), 128.3, 127.0, 123.7, 116.0 (d, J ¼ 21.2 Hz), 47.1, 43.9. 19F
NMR (471 MHz, CDCl3)
d
ꢀ115.7. HPLC [DAICEL CHIRALPAK OJ-H,
4.3.19. (S)-3-(3-Chlorophenyl)-2,3-dihydro-1H-inden-1-one (2s)
[17]
hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/min, 25 ꢁC. tR1 ¼14.3 min
(minor), tR2 ¼ 16.8 min (major)]; 95:5 er. [
a
]25D ¼ þ37.9 (c ¼ 0.3,
White solid (47.6 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
7.82 (d, J ¼ 8.0 Hz, 1H), 7.59 (t, J ¼ 7.5 Hz, 1H), 7.44 (t, J ¼ 7.5 Hz,
CH2Cl2).
d
1H), 7.31e7.20 (m, 3H), 7.12 (s, 1H), 7.04e6.97 (m, 1H), 4.56 (dd,
J ¼ 8.0, 4.0 Hz, 1H), 3.23 (dd, J ¼ 19.5, 8.0 Hz, 1H), 2.66 (dd, J ¼ 19.0,
4.3.14. (S)-3-(4-Chlorophenyl)-2,3-dihydro-1H-inden-1-one (2n)
[8a]
4.0 Hz, 1H). 13C NMR (125 MHz, CDCl3)
d 205.3, 156.9, 145.7, 136.7,
White solid (48.1 mg, 99% yield). 1H NMR (500 MHz, CDCl3)
135.2, 134.6, 130.1, 128.1, 127.7, 127.2, 126.7, 125.8, 123.5, 46.5, 44.0.
HPLC [DAICEL CHIRALPAK OD-H, hexane/iPrOH ¼ 95/5, 254 nm,
0.5 mL/min, 25 ꢁC. tR1 ¼18.4 min (major), tR2 ¼ 23.0 min (minor)];
d
7.82 (d, J ¼ 8.0 Hz, 1H), 7.61e7.54 (m, 1H), 7.44 (t, J ¼ 7.5 Hz, 1H),
7.31e7.21 (m, 3H), 7.06 (d, J ¼ 8.4 Hz, 2H), 4.56 (dd, J ¼ 8.0, 3.5 Hz,
1H), 3.23 (dd, J ¼ 19.5, 8.5 Hz, 1H), 2.63 (dd, J ¼ 19.0, 4.0 Hz, 1H). 13
C
92:8 er. [
a
]25D ¼ þ41.4 (c ¼ 0.6, CH2Cl2).
NMR (125 MHz, CDCl3)
d 206.1, 157.9, 142.8, 137.3, 135.8, 133.4,
129.6, 129.5,128.7, 127.3, 124.1, 47.3, 44.4. HPLC [DAICEL CHIRALPAK
OJ-H, 254 nm, 1.0 mL/min,
hexane/iPrOH ¼ 95/5,
25 ꢁC.
tR1 ¼16.4 min (minor), tR2 ¼ 18.0 min (major)]; 95:5 er.
]25D ¼ þ48.5 (c ¼ 0.4, CH2Cl2).
4.3.20. (R)-3-(2-Chlorophenyl)-2,3-dihydro-1H-inden-1-one (2t)
[17]
Yellow solid (47.6 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
[
a
d
7.83 (d, J ¼ 7.5 Hz, 1H), 7.61 (t, J ¼ 8.5 Hz, 1H), 7.48e7.40 (m, 2H),
7.38e7.31 (m, 1H), 7.23e7.11 (m, 2H), 6.87 (s, 1H), 5.12 (s, 1H), 3.31
4.3.15. (S)-3-(4-Bromophenyl)-2,3-dihydro-1H-inden-1-one (2o)
[16]
(dd, J ¼ 19.5, 8.5 Hz, 1H), 2.61 (d, J ¼ 18.5 Hz, 1H). 13C NMR
(125 MHz, CDCl3)
d 205.5, 156.5, 141.1, 137.2, 135.0, 134.0, 129.8,
White solid (56.3 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
128.4, 128.2, 128.0, 127.3, 126.8, 123.6, 45.3, 29.7. HPLC [DAICEL
CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/min, 25 ꢁC.
tR1 ¼9.3min (major), tR2 ¼ 10.7 min (minor)]; 85:15 er.
d
7.81 (d, J ¼ 7.5 Hz, 1H), 7.59 (t, J ¼ 7.5 Hz, 1H), 7.50e7.37 (m, 3H),
7.31e7.15 (m, 1H), 7.00 (d, J ¼ 8.0 Hz, 2H), 4.55 (dd, J ¼ 8.0, 4.0 Hz,
1H), 3.23 (dd, J ¼ 19.5, 8.0 Hz, 1H), 2.63 (dd, J ¼ 19.5, 4.0 Hz, 1H). 13
C
[
a
]25D ¼ ꢀ36.0 (c ¼ 0.4, CH2Cl2).
NMR (125 MHz, CDCl3)
d 205.4, 157.2, 142.7, 136.7, 135.2, 132.0,
129.3, 128.1, 126.7, 123.5, 120.8, 46.6, 43.8. HPLC [DAICEL CHIR-
ALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/min, 25 ꢁC.
tR1 ¼18.7 min (minor), tR2 ¼ 20.6 min (major)]; 95:5 er.
4.3.21. (S)-3-(Naphthalen-2-yl)-2,3-dihydro-1H-inden-1-one (2u)
[8a]
Yellow solid (54.3 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
[
a
]25D ¼ þ44.0 (c ¼ 0.4, CH2Cl2).
d
7.85 (d, J ¼ 7.5 Hz, 1H), 7.82e7.74 (m, 3H), 7.66 (s, 1H), 7.56 (t,
6

J. Yan, Y. Nie, F. Gao et al.
Tetrahedron 84 (2021) 132003
J ¼ 7.5 Hz,1H), 7.51e7.39 (m, 3H), 7.31e7.24 (m,1H), 7.13 (dd, J ¼ 8.5,
1.5 Hz, 1H), 4.74 (dd, J ¼ 8.0, 3.5 Hz, 1H), 3.29 (dd, J ¼ 19.0, 8.0 Hz,
1H), 2.78 (dd, J ¼ 19.0, 3.5 Hz, 1H). 13C NMR (125 MHz, CDCl3)
purified by flash column chromatography on silica gel (2:1 hex-
anes/EA) to afford the product 4 (63.3 mg, 86% yield; >20:1 dr) as a
white solid. 1H NMR (500 MHz, CDCl3)
d
7.49 (d, J ¼ 7.5 Hz, 1H),
d
206.2, 158.1, 141.1, 137.1, 135.4, 133.7, 132.7, 129.2, 128.2, 127.9,
7.35e7.28 (m, 3H), 7.27e7.22 (m, 4H), 6.95 (d, J ¼ 7.5 Hz,1H), 5.30 (t,
127.8, 127.2, 126.65, 126.63, 126.1, 125.7, 123.7, 46.9, 44.8. HPLC
[DAICEL CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/
min, 25 ꢁC. tR1 ¼32.4 min (minor), tR2 ¼ 45.2 min (major)]; 95:5 er.
J ¼ 7.5 Hz, 1H), 4.19 (t, J ¼ 8.5 Hz, 1H), 3.07e2.99 (m, 1H), 1.99e1.90
(m, 2H). 13C NMR (125 MHz, CDCl3)
d 145.8, 145.4, 144.4, 128.8,
128.6,128.5,127.4, 126.8,125.3,123.9, 75.4, 48.5, 47.4. HPLC [DAICEL
CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/min, 25 ꢁC.
tR1 ¼14.4 min (minor), tR2 ¼ 17.9 min (major)]; 93:7 er.
[
a
]25D ¼ þ95.3 (c ¼ 0.3, CH2Cl2).
4.3.22. (S)-3-(furan-2-yl)-2,3-dihydro-1H-inden-1-one (2v) [18]
Yellow oil (38.8 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
7.80
[
a
]25D ¼ þ16.1 (c ¼ 0.1, CH2Cl2).
d
(d, J ¼ 7.5 Hz, 1H), 7.62 (td, J ¼ 8.0, 1.5 Hz, 1H), 7.53 (dd, J ¼ 8.0,
1.0 Hz, 1H), 7.44 (t, J ¼ 7.0 Hz, 1H), 7.35 (dd, J ¼ 2.0, 1.0 Hz, 1H), 6.32
(dd, J ¼ 3.0, 2.0 Hz, 1H), 6.12 (d, J ¼ 3.0 Hz, 1H), 4.69 (dd, J ¼ 8.5,
4.0 Hz, 1H), 3.13 (dd, J ¼ 19.0, 8.0 Hz, 1H), 2.88 (dd, J ¼ 19.0, 4.0 Hz,
4.4.3. (S)-4-phenylchroman-2-one (5) [8a]
m-CPBA (200.0 mg, 1.34 mmol) and p-TsOH$H2O (13.0 mg,
0.068 mmol) were added to a solution of 2a (70 mg, 0.34 mmol) in
CH2Cl2 (5 mL), and the mixture was stirred for 24 h under reflux.
After cooling to room temperature, the reaction mixture was
quenched with saturated aqueous NaHCO3 (5 mL) and Na2S2O3
(5 mL). The aqueous layer was extracted with EtOAc (10 mL ꢂ 2),
the combined organic layers was dried over Na2SO4, filtered and
concentrated under reduced pressure. The residue was purified by
flash column chromatography on silica gel (10:1 hexanes/EA) to
1H). 13C NMR (125 MHz, CDCl3)
d 205.1, 155.4, 154.9, 142.4, 136.6,
135.2, 128.5, 126.8, 123.9, 110.5, 106.0, 43.0, 37.9. HPLC [DAICEL
CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/min, 25 ꢁC,
tR1 ¼11.1 min (major), tR2 ¼ 13.0 min (minor)]; 71:29 er.
[
a
]25D ¼ ꢀ7.4 (c ¼ 0.3, CHCl3).
afford the product 5 (57.9 mg, 76% yield) as a pale yellow solid; 1
NMR (500 MHz, CDCl3) 7.38e7.27 (m, 4H), 7.19e7.11 (m, 3H), 7.09
(td, J ¼ 7.5, 1.5 Hz, 1H), 6.98 (d, J ¼ 8.0 Hz, 1H), 4.39e4.27 (m, 1H),
3.12e2.99 (m, 2H). 13C NMR (125 MHz, CDCl3)
167.6, 151.6, 140.2,
H
4.3.23. (R)-3-ethyl-2,3-dihydro-1H-inden-1-one (2w) [19]
Yellow oil (31.4 mg, 98% yield). 1H NMR (500 MHz, CDCl3)
d 7.74
d
(d, J ¼ 8.0 Hz, 1H), 7.61 (td, J ¼ 7.5, 1.5 Hz, 1H), 7.52 (dd, J ¼ 8.0,
1.0 Hz, 1H), 7.38 (t, J ¼ 7.5 Hz, 1H), 3.39e3.25 (m, 1H), 2.86 (dd,
J ¼ 19.0, 7.5 Hz, 1H), 2.38 (dd, J ¼ 19.0, 3.0 Hz, 1H), 2.03e1.92 (m,
1H), 1.62e1.47 (m, 1H), 0.99 (t, J ¼ 7.0 Hz, 3H). 13C NMR (125 MHz,
d
129.1, 128.7, 128.3, 127.6, 127.5, 125.7, 124.6, 117.1, 40.6, 37.0. HPLC
[DAICEL CHIRALPAK OJ-H, hexane/iPrOH ¼ 95/5, 254 nm, 1.0 mL/
min, 25 ꢁC. tR1 ¼11.7 min (minor), tR2 ¼ 15.0 min (major)]; 89:11 er;
CDCl3)
d 206.5, 158.6, 136.8, 134.5, 127.4, 125.5, 123.4, 42.5, 39.5,
28.6, 11.5. HPLC [DAICEL CHIRALPAK OD-H, hexane/iPrOH ¼ 95/5,
[
a
]25D ¼ þ55.7 (c ¼ 0.5, CH2Cl2).
254 nm, 0.5 mL/min, 25 ꢁC, tR1 ¼11.0 min (minor), tR2 ¼ 11.6 min
(major)]; 88:12 er. [
a
]25D ¼ ꢀ8.3 (c ¼ 0.1, CH2Cl2).
Declaration of competing interest
4.4. Derivatization of the product
The authors declare that they have no known competing finical
interests or personal relationships that could have appeared to
influence the work reported in this paper.
4.4.1. (S,E)-1-benzylidene-3-phenyl-2,3-dihydro-1H-indene (3)
[20]
n-BuLi (0.4 mL, 1.6 M in hexane) was added dropwise to a sus-
pension of benzyltriphenylphosphonium bromide (430.0 mg,
1.11 mmol) in anhydrous THF (20 mL). After the mixture was stirred
at room temperature for 2 h, indanone (2a, 110.0 mg, 0.53 mmol) in
THF (5 mL) was added. The reaction mixture was stirred at reflux
for 24 h, then cooled to room temperature, quenched with water
(5 mL), and extracted with n-hexane (30 mL ꢂ 4). The organic layers
were combined, washed with water, dried (Na2SO4) and filtered.
The filtrate was concentrated under reduced pressure. The residue
was purified by flash column chromatography on silica gel (n-
hexane) to give the corresponding product 3 (130.0 mg, 92% yield;
Acknowledgments
The authors would like to thank National Natural Science
Foundation of China (Nos. 21991112, 22001164) and Shanghai
Pujiang Program (20PJ1406400) for financial support. We thank the
Instrumental Analysis Center of SJTU for characterization.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.132003.
92:8 er) as a yellow solid; 1H NMR (500 MHz, CDCl3)
d 7.47e7.41 (m,
2H), 7.41e7.36 (m, 2H), 7.35e7.31 (m, 2H), 7.31e7.23 (m, 5H),
7.17e7.11 (m, 1H), 7.04e6.97 (m, 2H), 6.67 (s, 1H), 4.50e4.34 (m,
1H), 3.40 (ddd, J ¼ 15.5, 8.0, 1.5 Hz, 1H), 2.96 (ddd, J ¼ 15.5, 6.0,
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7

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