Enantioselective synthesis of indanone spiro-isochromanone derivativesviaa dinuclear zinc-catalyzed Michael/transesterification tandem reaction

Article abstract of DOI:10.1039/d0ob00541j

An enantioselective Michael/transesterification tandem reaction of a-hydroxy indanones withortho-ester chalcones was realized using dinuclear zinc catalysts. A series of enantiomerically pure spiro[indanone-2,3'-isochromane-1-one] derivatives were obtained in good yields with excellent stereoselectivities (up to >20:1 dr, up to >99% ee). This protocol could be conducted on a gram scale without affecting its stereoselectivities. In addition, the absolute stereochemistry of the products was determined by X-ray crystallographic analysis of3ac, and a positive nonlinear effect was observed. Finally, a possible catalytic cycle was proposed to explain the origin of the enantioselectivity.

Full text of DOI:10.1039/d0ob00541j

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DOI: 10.1039/D0OB00541J
ARTICLE
Enantioselective Synthesis of Indanone Spiro-Isochromanone
Derivatives via Dinuclear Zinc-Catalyzed
Michael/Transesterification Tandem Reaction
Received 00th January 20xx,
Accepted 00th January 20xx
Xiao-Chao Yang, Meng Xu, Jin-Bao Wang, Meng-Meng Liu, François Mathey, Yuan-Zhao Hua,* and
Min-Can Wang*
DOI: 10.1039/x0xx00000x
An enantioselective Michael/transesterification tandem reaction of α-hydroxy indanones with ortho-ester chalcones was
realized by dinuclear zinc catalysts. A series of enantiomerically pure spiro[indanone-2,3’-isochromane-1-one] derivatives
were obtained in good yields with excellent stereoselectivities (up to >20:1 dr, up to >99% ee). This protocol could be run
on a gram scale without affecting its stereoselectivities. In addition, the absolute stereochemistry of the products was
determined by X-ray crystallographic analysis of 3ac, and a positive nonlinear effect was observed. Finally, a possible
catalytic cycle was proposed to explain the origin of the enantioselectivity.
their catalytic asymmetric synthesis by using enzyme,5a
organocatalysts,5b-g and metal catalysts,5h-j up to now, only one
example is reported for the enantioselective synthesis of
spiroisochromanones which may have larger steric hindrance
compared to isochromanones. In 2008, Tanaka and co-workers
reported a rhodium-catalyzed enantioselective intermolecular [4+2]
annulation of 2-alkynylbenzaldehydes with isatin derivatives or
Introduction
Isochromanone motifs are found in a large number of natural
molecules.1
products and pharmaceutical Meanwhile,
isochromanone derivatives, especially the optically pure
isochromanone compounds, possess a wide spectrum of important
bioactivities. For examples, AI-77-B (A) shows anti-inflammatory
activity,2a compound B has been investigated as an aldosterone
synthase inhibitor,1e and compound C shows aromatase inhibitory
activity (Fig. 1).2b Moreover, isochromanones are also valuable
building blocks for a number of complex heterocyclic compounds.1a
acenaphthenequinone,
which
led
to
enantioenriched
spirooxindoles-isochromanones (Scheme 1a).6 As a consequence, it
is highly desirable to develop a novel and efficient method for the
enantioselective construction of spiroisochromanone scaffolds.
a) Only one example reported by Tanaka
O
O
O
O
O
O
H
[Rh((R,R)-walphos)]BF4
O
O
R2
X
*
OH
O
O
O
+
X
R2
[4+2] annulation
O
O
O
H
OH NH3
CO2
R1
H
R1
H
N
H3CO
N
O
b) This work
O
OH
O
O
N
O
R'
COOPh
O
dinuclear zinc catalyst
tandem
Michael/transesterification
B
C
)
A
(
)
(
(
) AI-77-B
+
R
OH
an aldosterone
synthase inhibitor
aromatase inhibitory activity
anti-inflammatory activity
O
R'
R
new substrate combination to obtain spiro isochromanones
novel structure of spiro[indanone-2,3'-isochromane-1-one] derivatives
two adjacent stereocenters
Fig. 1 Some biologically important isochromanones.
excellent stereoselectivities (up to >20:1 dr, >99% ee)
Owing to their significant bioactivities and synthetic applications,
the synthesis of isochromanones and their analogues has attracted
great attention of organic chemists. A variety of synthetic methods
have been developed to build this type of isochromanone
Scheme 1 Strategies for the synthesis of spiroisochromanones.
During the past few years, our group has developed some
compounds.3-5 Although there are also some elegant methods for catalytic asymmetric reactions.7 It is found that α-hydroxy ketones
can be well activated by dinuclear zinc catalytic system which
provides an ideal active site architecture.8,9 However, α-hydroxy
College of Chemistry and Institute of Green catalysis, Zhengzhou University; No.
100, Science Road, Zhengzhou, Henan province, 450000, P. R. China. E-mail:
indanones with a cyclic backbone has been rarely reported.10 It is
probably owing to the large steric hindrance of α-hydroxy
indanones compared to α-hydroxyacetophenone.10a Very recently,
we reported a dinuclear zinc-catalyzed enantioselective synthesis of
hyzh@gs.zzu.edu.cn; wangmincan@zzu.edu.cn
Electronic Supplementary Information
10.1039/x0xx00000x
(ESI)
available:
See
DOI:
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ARTICLE
Journal Name
spirocyclic γ-butyrolactones from α,β-unsaturated esters.10c Based
on the strategies of the dinuclear zinc-catalyzed cascade reactions,
we assumed that the spiro isochromanones could be synthesized by
designing the suitable substrates. Herein, we report an efficient
method for the diastereo- and enantioselective construction of
spiro[indanone-2,3’-isochromane-1-one] through dinuclear zinc-
catalyzed tandem Michael/transesterification of α-hydroxy
indanones with ortho-ester chalcones (Scheme 1b).
b
c
d
oC. Isolated yield. Determined by chiral HPLC. Determined by
View Article Online
chiral HPLC. e 5 mol% of L2b and 10 mol% of Et2Zn was used. 2 mol%
of L2b and 4 mol % of Et2Zn was used. g The reaction was conducted
f
DOI: 10.1039/D0OB00541J
at
30
oC.
With the promising result in hand, extensive ligands L1 containing
prolinol moieties and ligands L2 containing chiral azetidine moieties
were screened, and the results were depicted in Table 1 (entries 2-
8). Ligand L2b was discovered to be optimal, which gave the
product 3aa in 92% yield with excellent diastereoselectivity and
enantioselectivity (> 99:1 dr, > 99% ee) (Table 1, entry 7).
In this work, changing the solvents resulted in a slight decline in
yields and seteroselectivies (Table 1, entries 7 vs 9-14). Next,
catalyst loading was also explored (Table 1, entries 15-16). Changing
the loading of L2b from 10 mol% to 5 mol% did not affect the yield
and stereoselectivies of product 3aa (Table 1, entries 7 vs 15).
However, the loading of 2 mol% L2b led to a dramatic decrease in
yield (Table 1, entry 16). Thus, optimization of temperature was
carried out by using a 5 mol% catalyst loading. Lowering the
Results and discussion
Initially, we performed the reaction of α-hydroxy indanone 1a with
ortho-ester chalcone 2a by using dinuclear zinc catalysts. To our
delight, in the presence of 10 mol% ligand L1a and 20 mol % Et2Zn,
the reaction was accomplished in THF at 40 oC in 3.5 h, and afforded
the desired product 3aa in 97% yield with excellent
diastereoselectivity and good enantioselectivity (>20:1 dr, 88% ee)
(Table 1, entry 1).
Table 1 Optimization of the reaction conditionsa
o
o
O
temperature from 40 C to 30 C reduced the yield, and prolonged
the reaction time (Table 1, entries 15 vs 17).
L
O
: 10 mol%
Et2Zn: 20 mol%
O
COOPh
O
+
Ph
OH
solvent, 40 o
C
Table 2 Substrate Scope of α-Hydroxy Indanonesa
O
O
1a
2a
3aa
Ar2
Ar2
Ph
O
Ar1
Ar2
Ar2
OH
Ar1
Ar1
O
L2b
: 5 mol%
Et2Zn: 10 mol%
O
HO
N
COOPh
OH
HO
OH
O
Ar1
+
R'
OH
R
THF, 40 o
C
: Ar1 = C6H5
N
N
OH
N
L1a
L1b
L1c
L1d
L1e
n
n
: Ar1 = p-CH3C6H4
: Ar1 = p-CF3C6H4
: Ar1 = p-ClC6H4
: Ar1 = 2-naphthyl
O
O
: Ar2 = C6H5
: Ar2 = p-CH3C6H4
: Ar2 = p-CF3C6H4
L2a
2a
2d
2e
: R = C6H5
: R = 4-BrC6H4
: R = 4-MeC6H4
1a-1g
1h
(n = 1)
(n = 2)
R'
R
L2b
L2c
3
Entry 1; R’
2
3
yieldb (%)
92
drc
eed (%)
>99
>99
>99
99
Time Yieldb
Entry Ligand Solvent
drc
eed (%)
(h)
3.5
12
12
12
12
4
(%)
97
96
79
92
89
97
92
84
79
1
2
3
4
5
6
7
8
9
1a; H
2a
2a
2a
2a
2a
2a
2a
2d
2e
2a
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ed
3ee
3ha
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
-
1b; 5-F
1c; 5-Cl
1d; 5-Br
68
1
2
3
4
5
6
7
8
9
L1a
L1b
L1c
L1d
L1e
L2a
L2b
L2c
L2b
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
26:1
42:1
39:1
35:1
27:1
88
92
16
68
61
75
73
1e; 5-MeO
1f; 4-Br
69
98
68
>99
96
1g; 6-Br
59
>99:1 98
1e; 5-MeO
1e; 5-MeO
1h; H
73
97
6
>99:1 >99
69
NRe
97
12
10
70:1
81
10
-
>20:1 97
a
Reaction conditions: unless otherwise noted, all reactions were
conducted with 1 (0.2 mmol), 2a (0.21 mmol), 5 mol% of L2b, 10
mol% of ZnEt2 (1 M in hexanes) in THF (1.5 mL) under nitrogen at 40
oC. b Isolated yield. c Determined by 1H NMR. d Determined by chiral
1,4-
dioxane
10
L2b
9
87
>99:1 99
11
12
13
14
15e
16f
L2b
L2b
L2b
L2b
L2b
L2b
L2b
toluene
CH2Cl2
CHCl3
CH3CN
THF
9
80
80
72
88
92
46
66
28:1
11:1
19:1
52:1
96
94
96
98
e
22
22
22
6
HPLC. No reaction, and more than 90% of raw materials was
recovered,
respectively.
>99:1 >99
>99:1 >99
>99:1 >99
With the optimal conditions in hand, a series of α-hydroxy
indanones 1b-1g participated in the tandem
THF
28
22
Michael/transesterification reaction to afford the corresponding
products 3ba-3ga with excellent diastereoselectivities and
enantioselectivities (Table 2, entries 2-7). 5-Methoxy α-hydroxy 1-
indanone could also reacted with 4-Br or 4-Me substituted ortho-
ester chalcones 2d and 2e under the optimal conditions (Table 2,
17e,g
THF
a
Reaction conditions: unless otherwise noted, all reactions were
conducted with 1a (0.2 mmol), 2a (0.21 mmol), 10 mol% of L, 20
mol% of ZnEt2 (1 M in hexanes) in THF (1.5 mL) under nitrogen at 40
2 | J. Name., 2012, 00, 1-3
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ARTICLE
>20:1 >99
17
2r; 2-naphthyl
2s; Me
3ar
3as
77
NRe
entries 8 and 9). The corresponding products were achieved in good
yields with >20:1 dr and 97% ee, respectively. The results showed
that the electronic nature and position of the substituents on the
aromatic rings of α-hydroxy indanones had little effect on the
stereoselectivities. However, using α-hydroxy tetralone 1h as a
nucleophile, no reactions were observed, and more than 90% of
raw materials was recovered, respectively (Table 2, entry 10). The
reason might owe to the larger steric hindrance of α-hydroxy
tetralone.
View Article Online
DOI: 10.1039/D0OB00541J
18
a
—
—
Reaction conditions: unless otherwise noted, all reactions were
conducted with 1a (0.2 mmol), 2 (0.21 mmol), 5 mol% of L2b, 10
mol% of ZnEt2 (1 M in hexanes) in THF (1.5 mL) under nitrogen at 40
oC. b Isolated yield. c Determined by 1H NMR. d Determined by chiral
e
HPLC.
No
reaction.
L2b
: 5 mol%
Et2Zn: 10 mol%
COOPh
Subsequently, to broaden the substrate scope of this tandem
reaction, a diversity of ortho-ester chalcones 2 were investigated
under the optimal conditions. The results were summarized in Table
3. The reaction of α-hydroxy indanone 1a with diverse aryl-
substituted ortho-ester chalcones 2b-2m proceeded efficiently to
give the desired products 3ab-3am in good yields (71-89%) with
excellent diastereoselectivities (up to >20:1 dr) and
enantioselectivities (up to 99% ee) (Table 3, entries 1-12).
Additionally, disubstituted and trisubstituted aromatic rings
substrates 2n-2p were also well-tolerated (Table 3, entries, 13-15).
Furthermore, ortho-ester chalcones 2q-2r bearing a 2-thienyl or 2-
naphthyl group were also proved to be suitable substrates in this
tandem reaction, giving 3aq in 78% yield with 99% ee and 3ar in 77%
yield with 99% ee, respectively (Table 3, entries 16 and 17). Notably,
nearly a single diastereoisomer of the product was achieved in
almost all these cases. However, when substituent R was Me, no
obvious reaction occurred (Table 3, entry 18). The possible reason
was that the reactivities of the aliphatic enone was lower than that
of the aromatic enones. The absolute configuration of the product
3ac was determined according to X-ray crystal structural analysis
(Fig. 2).
O
OH
No Reaction
+
Ph
THF, 40 o
C
(a)
(b)
O
1i
1j
2a
O
O
L2b
: 5 mol%
Et2Zn: 10 mol%
COOPh
O
O
OH
+
Ph
O
Ph
THF, 40 o
C
Ph
O
Ph
2a
3ja
, yield: 82%
dr: 2:1, ee: 3/16%
Scheme 2 Dinuclear zinc-catalyzed tandem reaction of ortho-ester
chalcone 2a with hydroxyacetone 1i and α-hydroxyacetophenone 1j.
Two other kinds of α-hydroxy ketones 1i and 1j were examined.
No reaction occurred when hydroxyacetone 1i was investigated
(Scheme 2, a). In addition, when α-hydroxyacetophenone 1j reacted
with ortho-ester chalcone 2a under the optimal conditions, the
corresponding product 3ja was obtained in 82% yield with 2:1 dr,
but the ee value of the major isomer is only 3% (Scheme 2, b).
Table 3 Substrate scope of ortho-ester chalconesa
O
O
O
L2b
: 5 mol%
Et2Zn: 10 mol%
COOPh
O
+
R
OH
THF, 40 o
C
O
O
1a
2b-2r
3
R
Yieldb
eed
(%)
Entry
2; R
3
drc
(%)
86
88
85
87
87
89
86
80
85
84
71
1
2b; 4-FC6H4
2c; 4-ClC6H4
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>99
99
99
99
99
99
98
98
99
>99
99
98
98
97
96
99
2
3
2d; 4-BrC6H4
2e; 4-MeC6H4
4
5
2f; 4-MeOC6H4
2g; 3-FC6H4
6
Fig. 2 X-ray crystal structure of product 3ac (CCDC: 1921049).
7
2h; 3-ClC6H4
To test the synthetic value of this method, a large-scale
experiment was carried out under the optimal conditions (Scheme
3). The tandem reaction of 1a and 2a was performed successfully to
provide the product 3aa in 88% yield with >20:1 dr and 99% ee. The
further derivation experiments revealed that the oximation reaction
had high regioselectivity. Treatment of 3aa with hydroxylamine
hydrochloride provided an oxime product 4 in 91% yield with 98%
8
2i; 3-BrC6H4
9
2j; 3-MeOC6H4
2k; 2-ClC6H4
3aj
10
11
12
13
14
15
16
3ak
3al
2l; 2-BrC6H4
2m; 2-MeOC6H4
2n; 2,4-Cl2C6H3
2o; 3,4-Cl2C6H3
2p; 2,4-Cl2-5-FC6H2
2q; 2-thienyl
3am 81
3an
3ao
3ap
3aq
81
85
82
78
1
ee. The two-dimensional H detected heteronuclear multiple bond
correlation (HMBC) showed that oxime 4 retained carbonyl group of
indanone (see the Supporting Information for details).
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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O
3aa and gave the zinc phenoxide species Ⅳ . With another α-
View Article Online
O
L2b
: 5 mol%
Et2Zn: 10 mol%
O
COOPh
O
hydroxy indanone 1a deprotonated, thDeOIc:a1t0a.1ly0t3i9c/Dc0yOcBle005w4a1Js
+
Ph
OH
THF, 40 o
C
restarted.
O
O
Ph
3aa,
1a
2a
1.01 g
0.444 g
1.04 g
88% yield, >20:1 dr, 99% ee
N
O
O
O
Ar
Ar
N
O
O
O
Zn
Et
O
Ar
Ar
O
Ar
Ar
O
O
N
Ar
Ar
O
Zn
Et
Ar
2.0 eq.
Et2Zn
Zn
.
.
Zn
O
O
NaOAc
NH2OH HCl,
3H2O
n
Zn
O
N
Ar
Ar
Et
N
N
O
Zn
MeOH, reflux
Ar
HO
L2b
N
O
Ph
Ph
3aa
3.0 eq.
ethane
4
91% yield, >20:1 dr, 98% ee
Zn2EtL2b
(Zn2EtL2b)n
Ph
O
O
Scheme 3 Gram-scale reaction and synthetic transformation of 3aa.
O
O
Ar
O
Ar
O
N
(R)
Ar
Ar
Zn
(S)
Zn
O
In addition, a nonlinear effect11 was investigated in this catalytic
asymmetric reaction. The correlation of ee values of product 3aa
and the ee values of ligand L2b was examined carefully, and a
positive nonlinear effect was observed in the mode reaction (Fig. 3).
This observation could be explained by the formation of the
oligomeric aggregates (Zn2EtL2b)n containing two or more
monomeric species Zn2EtL2b when one equivalent of ligand L2b
and two equivalent of Et2Zn were put together.12 These complex
could generated the real catalytically active species by the
deprotonation of nucleophiles (such as α-hydroxy indanone 1 in this
reaction, Scheme 3), which led to the observed nonlinear effect.
1a
N
O
O
OH
ethane
3aa
1a
Ph
IV
OH
Ar
Ar
O O
Zn
Ar
Ar
O
O
Zn
N
O
N
O
Ph
OPh
O
Ar
Ar
O
Ar
O
O
Zn
Zn
Ar
N
O
N
I
COOPh
O
Ph
OPh
Ar
Ph
OH
Zn
O
O
2a
III
Ar
Ar
O
O
O
Ar
Zn
N
O
N
II
Scheme
4
Proposed
catalytic
cycle
for
the
Michael/transesterification.
Conclusions
In conclusion, we have successfully developed an asymmetric
Michael/transesterification of α-hydroxy indanones with ortho-
ester chalcones by using a dinuclear zinc catalyst. A series of chiral
spiro[indanone-2,3’-isochromane-1-one] derivatives bearing two
adjacent stereocenters are obtained under mild reaction conditions
in up to 92% yields with up to >20:1 dr and >99% ee. The mode of
the dinuclear zinc cooperative catalysis accounts for the realization
of the asymmetric process. This work is also a successful application
of the dinuclear zinc synergetic catalytic stragety for the
enantioselective synthesis of compounds bearing potential
bioactivities. Currently, we are focusing on the asymmetric
reactions involving α-hydroxy indanones by using dinuclear zinc
catalysts.
Fig. 3 Correlation between the ee values of the ligand L2b and the
ee of product 3aa.
Based on the experimental results and previous reports on the
mechanism of dinuclear zinc catalysis,10,12,13 a possible catalytic
cycle was proposed (Scheme 4). Treatment of ligand L2b with ZnEt2
(2 equiv) afforded the dinuclear zinc complex (Zn2EtL2b)n and
Zn2EtL2b. Next, α-hydroxy indanone 1a was deprotonated to give
real catalytically active species Ⅰ. Then, ortho-ester chalcones 2a
coordinated to both zinc atoms from the less hindered face to
afford Ⅱ. The C-C bond formation through Michael addition gave
Ⅲ. We could not separate the intermediate Ⅲ from the reaction
system, so we designed an intramolecular Michael addition reaction
to verify the reaction sequence.14 Subsequently, complex Ⅲ
underwent an intramolecular transesterification to release product
Experimental
General information
All of the solvents were dried with standard methods and freshly
distilled prior to use if needed. All of the reactions sensitive to air or
4 | J. Name., 2012, 00, 1-3
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moisture were carried out under nitrogen using standard Schlenk 2922, 2853, 1721, 1683, 1616, 1592, 1482, 1448, 1294, 1253, 1123,
View Article Online
+
and vacuum line techniques. 1H NMR and 13C NMR spectra were 1076, 983 cm-1; HRMS (ESI-TOF) m/z: [M + DHO]+I:C1a0l.c1d03f9o/rD0CO25BH0108F5O414J
recorded on a 400 MHz (1H NMR) and 100 MHz (13C NMR) 401.1184; Found 401.1182.
spectrometer using CDCl3 as solvent and TMS as internal standard. (2R,4'S)-5-Chloro-4'-(2-oxo-2-phenylethyl)spiro[indene-2,3'-
Optical rotation values were measured with instruments operating isochromane]-1,1'(3H)-dione (3ca). White solid; yield 75% (62.5
at λ = 589 nm, corresponding to the sodium D line at 20 °C. High- mg); mp 66.6-67.2 oC. >99% ee, >20:1 dr; [α]D20 = +284.7 (CHCl3, c =
resolution mass spectra (HRMS) were performed on a Q-TOF Micro 1.066); the ee value was determined by HPLC (Chiral IC cloumn, i-
LC/MS System ESI spectrometer. The enantiomeric excesses (ee) PrOH/n-Hexane = 20/80, Flow rate: 1.0 mL/min, λ = 254 nm), t
were determined by HPLC (chiral column; mobile phase n-hexane/i- (minor) = 18.21 min, t (major) = 21.73 min. 1H NMR (400 MHz, CDCl3)
PrOH). Compounds 1a-1h were synthesized according to the δ 8.16-8.14 (m, 1H), 7.89-7.86 (m, 2H), 7.71 (d, J = 8.2 Hz, 1H), 7.62-
literature.10a Compound 1i and 1j was used as purchased.
7.52 (m, 2H), 7.49-7.40 (m, 4H), 7.37-7.35 (m, 2H), 4.21 (dd, J = 6.6,
18.5 Hz, 1H), 4.00-3.97 (m, 1H), 3.32 (s, 2H), 3.04 (dd, J = 5.1, 18.6
Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 197.2, 196.9, 163.7, 150.4,
142.9, 142.1, 136.3, 134.9, 134.5, 132.6, 130.7, 129.6, 128.6, 128.5,
128.2, 128.1, 126.7, 126.5, 123.9, 86.3, 41.1, 39.8, 39.2. IR (neat) v
2922, 2849, 1723, 1682, 1599, 1578, 1448, 1421, 1296, 1269, 1241,
1124, 1066, 983 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C25H18ClO4+ 417.0888; Found 417.0886.
General procedure for dinuclear zinc-catalyzed asymmetric
Michael/transesterification of α-hydroxy indanones 1 with ortho-
ester chalcones 2. In a flame-dried Schlenk tube, a solution of
diethylzinc (20 µL, 1.0 mol/L in hexane, 0.02 mmol, 10 mol%) was
added to a solution of the chiral ligand L2b (6.7 mg, 0.01 mmol, 5
mol%) in dry THF (1.0 mL) under nitrogen. The mixture was stirred
at room temperature for 30 min. Then a solution of α-hydroxy
indanones 1 (0.2 mmol, 1.0 equiv) and substrates 2 (0.21 mmol,
1.05 equiv) in dry THF (0.5 mL) was added to the mixture at 40 oC in
oil bath. The solution stirred at 40 oC for the necessary reaction
time, and then quenched with aqueous NH4Cl (2 mL), extracted
three times with DCM (3 × 6 mL). The combined organics were
washed with brine before being dried over MgSO4, filtered and
concentrated in vacuo. The crude product was purified by flash
column chromatography (EtOAc:petroleum ether = 1:2) to give the
corresponding product 3.
(2R,4'S)-5-Bromo-4'-(2-oxo-2-phenylethyl)spiro[indene-2,3'-
isochromane]-1,1'(3H)-dione (3da). White solid; yield 73% (67.3
o
20
mg); mp 78.6-79.4 C. 99% ee, >20:1 dr; [α]D = +262.3 (CHCl3, c =
1.26); the ee value was determined by HPLC (Chiral IC cloumn, i-
PrOH/n-Hexane = 20/80, Flow rate: 1.0 mL/min, λ = 254 nm), t
(minor) = 40.99 min, t (major) = 49.29 min. 1H NMR (400 MHz, CDCl3)
δ 8.16-8.14 (m, 1H), 7.89-7.86 (m, 2H), 7.65-7.52 (m, 5H), 7.49-7.40
(m, 3H), 7.36 (d, J = 7.6 Hz, 1H), 4.21 (dd, J = 6.6, 18.5 Hz, 1H), 4.00-
3.97 (m, 1H), 3.33 (s, 2H), 3.04 (dd, J = 5.1, 18.5 Hz, 1H). 13C NMR
(100 MHz, CDCl3) δ 197.4, 196.9, 163.6, 150.4, 142.0, 136.3, 134.9,
133.5, 133.0, 132.4, 131.8, 130.7, 129.8, 128.6, 128.5, 128.2, 128.1,
126.5, 123.9, 86.3, 41.0, 39.8, 39.2. IR (neat) v 2925, 2849, 1720,
1682, 1595, 1448, 1414, 1355, 1296, 1269, 1120, 1083, 982 cm-1;
(2R,4'S)-4'-(2-Oxo-2-phenylethyl)spiro[indene-2,3'-isochromane]-
1,1'(3H)-dione (3aa). White solid; yield 92% (70 mg); mp 52.4-53.6
20
oC. >99% ee, >20:1 dr; [α]D = +203.9 (CHCl3, c = 1.414); the ee
+
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H18BrO4 461.0383;
value was determined by HPLC (Chiral IF cloumn, i-PrOH/n-Hexane
= 40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t (minor) = 27.15 min,
t (major) = 37.78 min; 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 7.7 Hz,
1H), 7.91-7.88 (m, 2H), 7.79 (d, J = 7.7 Hz, 1H), 7.69-7.64 (m, 1H),
7.61-7.52 (m, 2H), 7.48-7.41 (m, 4H), 7.38-7.34 (m, 2H), 4.23 (dd, J =
6.0, 18.5 Hz, 1H), 4.00 (t, J = 5.9 Hz, 1H), 3.35 (s, 2H), 3.09 (dd, J =
5.8, 18.5 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.6, 197.0, 163.9,
149.1, 142.3, 136.4, 134.7, 134.1, 133.4, 130.6, 128.7, 128.6, 128.3,
128.2, 128.1, 126.5, 125.4, 124.0, 86.4, 41.4, 39.7, 39.2. IR (neat) v
2920, 2849, 1719, 1682, 1603, 1448, 1295, 1124, 1080, 982 cm-1;
Found 461.0385.
(2R,4'S)-5-Methoxy-4'-(2-oxo-2-phenylethyl)spiro[indene-2,3'-
isochromane]-1,1'(3H)-dione (3ea). White solid; yield 69% (56.9
o
20
mg); mp 74.5-75.2 C. 98% ee, >20:1 dr; [α]D = +280.9 (CHCl3, c =
0.84); the ee value was determined by HPLC (Chiral IC cloumn, i-
PrOH/n-Hexane = 40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t
(minor) = 33.08 min, t (major) = 40.90 min. 1H NMR (400 MHz, CDCl3)
δ 8.15 (d, J = 7.7 Hz, 1H), 7.89 (d, J = 7.6 Hz, 2H), 7.72 (d, J = 8.6 Hz,
1H), 7.59-7.51 (m, 2H), 7.46-7.36 (m, 4H), 6.98-6.94 (m, 1H), 6.76 (d,
J = 1.8 Hz, 1H), 4.25 (dd, J = 5.7, 18.5 Hz, 1H), 4.00 (t, J = 5.9 Hz, 1H),
3.87 (s, 3H), 3.28 (s, 2H), 3.09 (dd, J = 6.1, 18.5 Hz, 1H). 13C NMR
(100 MHz, CDCl3) δ 197.0, 196.4, 166.6, 164.1, 152.1, 142.4, 136.5,
134.6, 133.4, 130.6, 128.6, 128.2, 128.1, 127.23, 127.19, 124.1,
116.6, 86.5, 55.8, 41.5, 39.7, 39.3. IR (neat) v 2918, 2843, 1719,
1679, 1597, 1448, 1295, 1263, 1122, 1080, 982 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C26H21O5+ 413.1384; Found 413.1382.
+
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H18NaO4 405.1097;
Found 405.1098.
(2R,4'S)-5-Fluoro-4'-(2-oxo-2-phenylethyl)spiro[indene-2,3'-
isochromane]-1,1'(3H)-dione (3ba). White solid; yield 68% (54.5
mg); mp 79.5-80.5 oC. >99% ee, >20:1 dr; [α]D20 = +225.2 (CHCl3, c =
0.72); the ee value was determined by HPLC (Chiral IC cloumn, i-
PrOH/n-Hexane = 40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t
(minor) = 14.63 min, t (major) = 19.46 min. 1H NMR (400 MHz, CDCl3)
δ 8.16 (d, J = 7.8 Hz, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.83-7.79 (m, 1H),
7.62-7.53 (m, 2H), 7.49-7.36 (m, 4H), 7.18-7.13 (m, 1H), 7.03 (d, J =
8.2 Hz, 1H), 4.24 (dd, J = 6.4, 18.6 Hz, 1H), 4.02-3.98 (m, 1H), 3.34 (s,
2H), 3.05 (dd, J = 5.3, 18.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
196.9, 196.6, 168.0 (d, J = 257.5 Hz), 163.7, 152.0 (d, J = 10.4 Hz),
142.1, 136.4, 134.8, 133.5, 130.7, 130.5 (d, J = 1.9 Hz), 128.6, 128.4,
128.2, 128.1, 128.0 (d, J = 10.5 Hz), 123.9, 117.1 (d, J = 23.7 Hz),
113.3 (d, J = 22.6 Hz), 86.3, 41.3 (d, J = 1.4 Hz), 39.8, 39.2. IR (neat) v
(2R,4'S)-4-Bromo-4'-(2-oxo-2-phenylethyl)spiro[indene-2,3'-
isochromane]-1,1'(3H)-dione (3fa). White solid; yield 68% (62.7 mg);
o
20
mp 164.8-165.5 C. >99% ee, >20:1 dr; [α]D = +224.3 (CHCl3, c =
1.04); the ee value was determined by HPLC (Chiral IC cloumn, i-
PrOH/n-Hexane = 40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t
(minor) = 15.74 min, t (major) = 20.49 min. 1H NMR (400 MHz, CDCl3)
δ 8.19-8.16 (m, 1H), 7.90-7.87 (m, 2H), 7.84-7.81 (m, 1H), 7.74 (d, J
= 7.3 Hz, 1H), 7.64-7.59 (m, 1H), 7.57-7.52 (m, 1H), 7.51-7.47 (m,
1H), 7.45-7.41 (m, 2H), 7.39-7.34 (m, 2H), 4.25 (dd, J = 6.8, 18.6 Hz,
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1H), 4.03-3.99 (m, 1H), 3.26 (dd, J = 17.5, 30.5 Hz, 2H), 3.04 (dd, J = HPLC (Chiral IC cloumn, i-PrOH/n-Hexane = 20/80, Flow rate: 1.0
View Article Online
4.9, 18.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.0, 196.9, 163.6, mL/min, λ = 254 nm), t (minor) = 41.03 min, t (major) = 28.01 min.
DOI: 10.1039/D0OB00541J
148.9, 142.0, 139.0, 136.3, 136.2, 135.0, 133.5, 130.7, 130.4, 128.7, 1H NMR (400 MHz, CDCl3) δ 8.30-8.28 (m, 1.28H), 8.20-8.13 (m, 1H),
128.5, 128.2, 128.1, 124.2, 123.9, 121.9, 86.0, 42.5, 39.8, 39.1. IR 8.15-8.13 (m, 0.33H), 8.01-7.96 (m, 2H), 7.82-7.80 (m, 0.66H), 7.67-
(neat) v 2922, 1722, 1677, 1598, 1459, 1407, 1358, 1296, 1267, 7.60 (m, 1.7H), 7.59-7.55 (m, 1.76H), 7.52-7.47 (m, 3H), 7.46-7.38
1120, 1082, 981 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for (m, 2H), 7.08-7.06 (m, 0.64H), 6.23 (d, J = 0.8 Hz, 0.66H), 6.08 (d, J =
C25H18BrO4+ 461.0383; Found 461.0382.
2.8Hz, 0.34H), 4.34-4.30 (m, 0.33H), 4.10 (dd, J = 2.6, 10.8 Hz,
0.67H), 3.93-3.86 (m, 0.67H), 3.56 (dd, J = 4.6, 18.0 Hz, 0.34H), 3.29-
(2R,4'S)-6-Bromo-4'-(2-oxo-2-phenylethyl)spiro[indene-2,3'-
isochromane]-1,1'(3H)-dione (3ga). White solid; yield 59% (54.4 3.18 (m, 1H) 13C NMR (100 MHz, CDCl3) δ 197.7, 196.5, 194.3, 193.1,
o
20
mg); mp 145.5-146.3 C. 96% ee, >20:1 dr; [α]D = +164 (CHCl3, c = 164.3, 164.2, 142.6, 138.1, 136.2, 136.0, 134.6, 134.4, 134.35,
0.22); the ee value was determined by HPLC (Chiral IC cloumn, i- 134.28, 134.1, 134.0, 133.5, 132.9, 130.8, 130.0, 129.2, 129.1, 129.0,
PrOH/n-Hexane = 20/80, Flow rate: 1.0 mL/min, λ = 254 nm), t 128.9, 128.8, 128.7, 128.6, 128.5, 128.2, 128.1, 127.9, 127.0, 127.0,
(minor) = 14.59 min, t (major) = 19.66 min. 1H NMR (400 MHz, CDCl3) 125.2, 124.0, 80.7, 80.5, 43.5, 38.8, 36.3, 35.1. IR (neat) v 3065,
δ 8.16 (d, J = 7.9 Hz, 1H), 7.92 (m, 3H), 7.76 (m, 1H), 7.62 -7.53 (m, 2955, 1729, 1679, 1594, 1578, 1449, 1289, 1218, 1202, 971, 753,
+
2H), 7.49-7.42 (m, 3H), 7.36 (d, J = 7.6 Hz, 1H), 7.26-7.24 (m, 2H), 688 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C24H18NaO4
4.21 (dd, J = 6.7, 18.6 Hz, 1H), 4.01-3.98 (m, 1H), 3.34-3.24 (m, 2H), 393.1097; Found 393.1100.
3.04 (dd, J = 5.0, 18.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 197.3, (2R,4'S)-4'-(2-(4-Fluorophenyl)-2-oxoethyl)spiro[indene-2,3'-
196.9, 163.6, 147.5, 142.1, 139.2, 136.3, 135.9, 134.9, 133.5, 130.7, isochromane]-1,1'(3H)-dione (3ab). white solid; yield 86% (68.9
128.7, 128.5, 128.22, 128.16, 128.1, 128.0, 123.9, 122.8, 86.5, 41.1, mg); mp 167.5-168.3 oC. >99% ee, >20:1 dr; [α]D20 = +243.1 (CHCl3, c
39.7, 39.2. IR (neat) v 2923, 2853, 1724, 1680, 1600, 1450, 1403, = 1.308); the ee value was determined by HPLC (Chiral IF cloumn, i-
1297, 1272, 1243, 1130, 1089, 982 cm-1; HRMS (ESI-TOF) m/z: [M + PrOH/n-Hexane = 20/80, Flow rate: 1.0 mL/min, λ = 254 nm), t
H]+ Calcd for C25H18BrO4+ 461.0383; Found 461.0381.
(2R,4'S)-4'-(2-(4-bromophenyl)-2-oxoethyl)-5-
(minor) = 39.91 min, t (major) = 74.18 min. 1H NMR (400 MHz, CDCl3)
δ 8.17-8.14 (m, 1H), 7.95-7.91 (m, 2H), 7.78 (d, J = 7.7 Hz, 1H), 7.69-
(3ed). 7.64 (m, 1H), 7.62-7.57 (m, 1H), 7.49-7.43 (m, 2H), 7.38-7.35 (m, 2H),
methoxyspiro[indene-2,3'-isochromane]-1,1'(3H)-dione
White solid; yield 73% (71.5mg); mp 89.5-90.1 oC. 97% ee, >20:1 dr; 7.12-7.07 (m, 2H), 4.23 (dd, J = 6.4, 18.4 Hz, 1H), 4.00-3.97 (m, 1H),
[α]D = +213.2 (CHCl3, c = 1.230); the ee value was determined by 3.34 (s, 2H), 3.02 (dd, J = 5.4, 18.4 Hz, 1H). 13C NMR (100 MHz, CDCl3)
20
HPLC (Chiral IC column, i-PrOH/n-Hexane = 40/60, Flow rate: 1.0 δ 198.6, 195.4, 165.9 (d, J = 253.6 Hz), 163.9, 149.1, 142.2, 136.5,
mL/min, λ = 254 nm), t (minor) = 32.94 min, t (major) = 51.50 min. 134.8, 134.1, 132.8 (d, J = 3.0 Hz), 130.8 (d, J = 9.3 Hz), 130.6, 128.7,
1H NMR (400 MHz, CDCl3) δ 8.15-8.13 (m, 1H), 7.76 (d, J = 8.6 Hz, 128.4, 128.2, 126.5, 125.4, 124.0, 115.7 (d, J = 21.8 Hz), 86.3, 41.4,
2H), 7.70 (d, J = 8.6 Hz, 1H), 7.60-7.54 (m, 3H), 7.47-7.43 (m, 1H), 39.7, 39.2. IR (neat) v 2925, 2887, 1722, 1679, 1594, 1504, 1455,
7.36 (d, J = 7.5 Hz, 1H), 6.97-6.94 (m, 1H), 6.75 (d, J = 1.9 Hz, 1H), 1431, 1292, 1270, 1219, 1152, 1087, 983 cm-1; HRMS (ESI-TOF) m/z:
4.26 (dd, J = 6.2, 18.5 Hz, 1H), 3.96 (t, J = 5.8 Hz, 1H), 3.87 (s, 3H), [M + Na]+ Calcd for C25H17FNaO4+ 423.1003; Found 423.1004.
3.27 (s, 2H), 2.98 (dd, J = 5.6, 18.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) (2R,4'S)-4'-(2-(4-Chlorophenyl)-2-oxoethyl)spiro[indene-2,3'-
δ 196.4, 196.1, 166.7, 164.0, 152.1, 142.3, 135.2, 134.7, 131.9, isochromane]-1,1'(3H)-dione (3ac). white solid; yield 88% (73.4 mg);
20
130.6, 129.7, 128.6, 128.4, 128.2, 127.2, 127.1, 124.0, 116.6, 109.7, mp 172.9-174.1 oC. 99% ee, >20:1 dr; [α]D = +254.0 (CHCl3, c =
86.3, 55.8, 41.5, 39.8, 39.3. IR (neat) v 3065, 2945, 1713, 1598, 1489, 1.12); the ee value was determined by HPLC (Chiral IC cloumn, i-
1261, 1071, 823, 756, cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for PrOH/n-Hexane = 20/80, Flow rate: 1.0 mL/min, λ = 254 nm), t
C26H20BrO5+ 491.0489; Found 491.0488.
(2R,4'S)-5-methoxy-4'-(2-oxo-2-(p-tolyl)ethyl)spiro[indene-2,3'-
(minor) = 33.70 min, t (major) = 49.11 min. 1H NMR (400 MHz, CDCl3)
δ 8.15 (d, J = 7.7 Hz, 1H), 7.83 (d, J = 8.6 Hz, 2H), 7.77 (d, J = 7.6 Hz,
isochromane]-1,1'(3H)-dione (3ee). White solid; yield 69% (58.8 1H), 7.69-7.64 (m, 1H), 7.62-7.57 (m, 1H), 7.48-7.44 (m, 2H), 7.40-
o
20
mg); mp 177.5-178.0 C. 97% ee, >20:1 dr; [α]D = +243.4 (CHCl3, c 7.34 (m, 4H), 4.24 (dd, J = 6.6, 18.5 Hz, 1H), 3.99-3.96 (m, 1H), 3.34
= 0.946); the ee value was determined by HPLC (Chiral IC column, i- (s, 2H), 3.00 (dd, J = 5.2, 18.5 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
PrOH/n-Hexane = 40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t 198.7, 195.8, 163.9, 149.1, 142.1, 139.9, 136.5, 134.8, 134.7, 134.0,
(minor) = 33.61 min, t (major) = 61.31 min. 1H NMR (400 MHz, CDCl3) 130.6, 129.6, 129.5, 129.0, 128.7, 128.4, 128.2, 126.5, 125.4, 124.0,
δ 8.13 (d, J = 7.5 Hz, 1H), 7.79 (d, 8.2 Hz, 2H), 7.71 (d, J = 8.6Hz, 1H), 115.4, 86.3, 41.4, 39.7, 39.2. IR (neat) v 2925, 2853, 1721, 1682,
7.57-7.53 (m, 1H), 7.44-7.40 (m, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.21 (d, 1587, 1455, 1397, 1292, 1270, 1241, 1219, 1153, 1125, 1087, 982
+
J = 8.3 Hz, 2H), 6.96-6.93 (m, 1H), 6.75 (d, J = 1.9 Hz, 1H), 4.20 (dd, J cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H17ClNaO4
= 5.6, 18.4 Hz, 1H), 3.99 (t, J = 5.9 Hz, 1H), 3.86 (s, 3H), 3.28 (s, 2H), 439.0708; Found 439.0709.
3.08 (dd, J = 6.2, 18.4 Hz, 1H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) (2R,4'S)-4'-(2-(4-Bromophenyl)-2-oxoethyl)spiro[indene-2,3'-
δ 196.6, 196.4, 166.6, 164.1, 152.1, 144.2, 142.5, 134.6, 134.0, isochromane]-1,1'(3H)-dione (3ad). white solid; yield 85% (78.4
o
20
130.5, 129.3, 128.26, 128.18, 127.22, 127.18, 124.0, 116.6, 109.7, mg); mp 171.2-171.8 C. 99% ee, >20:1 dr; [α]D = +130 (CHCl3, c =
86.6, 55.8, 41.5, 39.5, 39.3, 21.7. IR (neat) v 2975, 2948, 1715, 1679, 0.74); the ee value was determined by HPLC (Chiral IC cloumn, i-
1597, 1488, 1296, 1262, 1081, 984, 757 cm-1; HRMS (ESI-TOF) m/z: PrOH/n-Hexane = 30/70, Flow rate: 1.0 mL/min, λ = 254 nm), t
[M + H]+ Calcd for C27H23O5+ 427.1540; Found 427.1542.
(minor) = 24.28 min, t (major) = 35.18 min. 1H NMR (400 MHz, CDCl3)
(3R,4S)-3-benzoyl-4-(2-oxo-2-phenylethyl)isochroman-1-one (3ja). δ 8.15 (d, J = 7.8 Hz, 1H), 7.78-7.74 (m, 3H), 7.69-7.64 (m, 1H), 7.61-
o
white solid; yield 82% (60.7 mg); mp 182.5-183.1 C. 3% ee, 2:1 dr; 7.55 (m, 3H), 7.48-7.43 (m, 2H), 7.38-7.34 (m, 2H), 4.24 (dd, J = 6.6,
20
[α]D = +15.4 (CHCl3, c = 0.74); the ee value was determined by 18.5 Hz, 1H), 3.99-3.96 (m, 1H), 3.34 (s, 2H), 2.99 (dd, J = 5.2, 18.5
6 | J. Name., 2012, 00, 1-3
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Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.6, 196.0, 163.9, 149.1, 1.10); the ee value was determined by HPLC (ChiralViIeCw cArltoiculemOnn,linie-
DOI: 10.1039/D0OB00541J
142.1, 136.5, 135.1, 134.8, 134.0, 131.9, 130.7, 129.7, 128.7, 128.6, PrOH/n-Hexane = 25/75, Flow rate: 1.0 mL/min, λ = 254 nm), t
128.4, 128.2, 126.5, 125.4, 124.0, 86.2, 41.4, 39.7, 39.2. IR (neat) v (minor) = 22.94 min, t (major) = 32.16 min. 1H NMR (400 MHz, CDCl3)
2954, 2920, 2850, 1721, 1682, 1584, 1457, 1377, 1293, 1218, 1069, δ 8.17-8.14 (m, 1H), 7.87-7.86 (m, 1H), 7.79-7.76 (m, 2H), 7.69-7.65
+
981 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H17BrNaO4
(m, 1H), 7.63-7.58 (m, 1H), 7.52-7.43 (m, 3H), 7.39-7.35 (m, 3H),
483.0202; Found 483.0204.
4.26 (dd, J = 6.7, 18.6 Hz, 1H), 3.99-3.96 (m, 1H), 3.34 (s, 2H), 3.00
(2R,4'S)-4'-(2-Oxo-2-(p-tolyl)ethyl)spiro[indene-2,3'-isochromane]- (dd, J = 5.1, 18.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.7, 195.8,
1,1'(3H)-dione (3ae). white solid; yield 87% (69.0 mg); mp 66.5-67.4 163.9, 149.1, 142.1, 137.9, 136.5, 135.0, 134.9, 134.0, 133.3, 130.7,
20
oC. 99% ee, >20:1 dr; [α]D = +257.0 (CHCl3, c = 1.15); the ee value 130.0, 128.7, 128.5, 128.2, 126.5, 126.3, 125.4, 124.0, 86.2, 41.4,
was determined by HPLC (Chiral IC cloumn, i-PrOH/n-Hexane = 39.9, 39.1. IR (neat) v 2918, 2849, 1718, 1686, 1604, 1458, 1428,
40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t (minor) = 19.57 min, t 1295, 1278, 1266, 1243, 1124, 1078, 908 cm-1; HRMS (ESI-TOF) m/z:
(major) = 34.27 min. 1H NMR (400 MHz, CDCl3) δ 8.16-8.13 (m, 1H), [M + Na]+ Calcd for C25H17ClNaO4+ 439.0708; Found 439.0707.
7.80-7.77 (m, 3H), 7.68-7.63 (m, 1H), 7.59-7.55 (m, 1H), 7.47-7.42 (2R,4'S)-4'-(2-(3-Bromophenyl)-2-oxoethyl)spiro[indene-2,3'-
(m, 2H), 7.37-7.34 (m, 2H), 7.21 (d, J = 8.0 Hz, 2H), 4.16 (dd, J = 6.0, isochromane]-1,1'(3H)-dione (3ai). white solid; yield 80% (73.8 mg);
o
20
18.4 Hz, 1H), 4.01-3.98 (m, 1H), 3.34 (s, 2H), 3.07 (dd, J = 5.8, 18.4 mp 71.6-73.5 C. 98% ee, >20:1 dr; [α]D = +179 (CHCl3, c = 1.600);
Hz, 1H), 2.38 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 198.6, 196.5, the ee value was determined by HPLC (Chiral IC cloumn, i-PrOH/n-
164.0, 149.1, 144.3, 142.4, 136.4, 134.7, 134.1, 133.9, 130.6, 129.3, Hexane = 25/75, Flow rate: 1.0 mL/min, λ = 254 nm), t (minor) =
1
128.7, 128.3, 128.2, 126.5, 125.4, 124.0, 86.5, 41.4, 39.6, 39.2, 21.7. 24.41 min, t (major) = 34.59 min. H NMR (400 MHz, CDCl3) δ 8.17-
IR (neat) v 2920, 1719, 1678, 1605, 1458, 1406, 1355, 1294, 1243, 8.14 (m, 1H), 8.02 (t, J = 1.2 Hz, 1H), 7.83-7.77 (m, 2H), 7.69-7.65 (m,
1219, 1180, 981 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for 2H), 7.62-7.58 (m, 1H), 7.49-7.43 (m, 2H), 7.38-7.27 (m, 3H), 4.24
C26H20NaO4+ 419.1254; Found 419.1257.
(2R,4'S)-4'-(2-(4-Methoxyphenyl)-2-oxoethyl)spiro[indene-2,3'-
(dd, J = 6.6, 18.6 Hz, 1H), 3.99-3.95 (m, 1H), 3.34 (s, 2H), 3.00 (dd, J
= 5.1, 18.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.7, 195.7, 163.8,
isochromane]-1,1'(3H)-dione (3af). white solid; yield 87% (71.8 mg); 149.1, 142.1, 138.1, 136.5, 136.2, 134.9, 134.0, 131.1, 130.6, 130.2,
20
mp 152.3-152.6 oC. 99% ee, >20:1 dr; [α]D = +214.9 (CHCl3, c = 128.7, 128.5, 128.2, 126.7, 126.5, 125.4, 124.0, 123.0, 86.2, 41.4,
1.372); the ee value was determined by HPLC (Chiral IC cloumn, i- 39.9, 39.1. IR (neat) v 2921, 2853, 1717, 1688, 1604, 1566, 1458,
PrOH/n-Hexane = 40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t 1420, 1295, 1241, 1203, 1124, 1079, 994 cm-1; HRMS (ESI-TOF) m/z:
(minor) = 31.00 min, t (major) = 49.36 min. 1H NMR (400 MHz, CDCl3) [M + Na]+ Calcd for C25H17BrNaO4+ 483.0202; Found 483.0206.
δ 8.16-8.13 (m, 1H), 7.88-7.84 (m, 2H), 7.78 (d, J = 7.7 Hz, 1H), 7.68- (2R,4'S)-4'-(2-(3-Methoxyphenyl)-2-oxoethyl)spiro[indene-2,3'-
7.63 (m, 1H), 7.59-7.54 (m, 1H), 7.46-7.42 (m, 2H), 7.37-7.34 (m, 2H), isochromane]-1,1'(3H)-dione (3aj). white solid; yield 85% (70.1 mg);
6.90-6.86 (m, 2H), 4.12 (dd, J = 5.9, 18.5 Hz, 1H), 4.02-3.98 (m, 1H), mp 64.5-65.1 oC. 99% ee, >20:1 dr; [α]D20 = +212.8 (CHCl3, c = 1.156);
3.84 (s, 3H), 3.34 (s, 2H), 3.06 (dd, J = 5.9, 18.2 Hz, 1H). 13C NMR the ee value was determined by HPLC (Chiral IC cloumn, i-PrOH/n-
(100 MHz, CDCl3) δ 198.6, 195.3, 164.0, 163.7, 149.1, 142.4, 136.4, Hexane = 25/75, Flow rate: 1.0 mL/min, λ = 254 nm), t (minor) =
1
134.7, 134.1, 130.5, 130.4, 129.4, 128.7, 128.29, 128.26, 126.5, 46.41 min, t (major) = 57.40 min. H NMR (400 MHz, CDCl3) δ 8.17-
125.3, 124.0, 113.8, 86.6, 55.5, 41.4, 39.25, 39.24. IR (neat) v 2922, 8.14 (m, 1H), 7.79 (d, J = 7.7 Hz, 1H), 7.69-7.64 (m, 1H), 7.61-7.56 (m,
2853, 1724, 1672, 1597, 1574, 1509, 1455, 1418, 1293, 1258, 1242, 1H), 7.49-7.43 (m, 3H), 7.40-7.32 (m, 4H), 7.10-7.07 (m, 1H), 4.20
1167, 1125, 1086, 982 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd (dd, J = 6.1, 18.5 Hz, 1H), 4.00-3.97 (m, 1H), 3.83 (s, 3H), 3.35 (s, 2H),
for C26H20NaO5+ 435.1203; Found 435.1207.
3.08 (dd, J = 5.7, 18.5 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.6,
(2R,4'S)-4'-(2-(3-Fluorophenyl)-2-oxoethyl)spiro[indene-2,3'-
196.8, 164.0, 159.8, 149.1, 142.3, 137.7, 136.4, 134.7, 134.1, 130.6,
isochromane]-1,1'(3H)-dione (3ag). white solid; yield 89% (71.3 mg); 129.7, 128.7, 128.3, 128.2, 126.5, 125.4, 124.0, 120.8, 120.0, 112.2,
mp 71.2-72.1 oC. 99% ee, >20:1 dr; [α]D20 = +216.2 (CHCl3, c = 1.09); 86.4, 55.5, 41.4, 39.8, 39.2. IR (neat) v 2921, 2849, 1721, 1682, 1601,
the ee value was determined by HPLC (Chiral IC cloumn, i-PrOH/n- 1583, 1456, 1429, 1294, 1271, 1254, 1124, 1079, 860 cm-1; HRMS
+
Hexane = 20/80, Flow rate: 1.0 mL/min, λ = 254 nm), t (minor) = (ESI-TOF) m/z: [M + Na]+ Calcd for C26H20NaO5 435.1203; Found
1
23.11 min, t (major) = 28.82 min. H NMR (400 MHz, CDCl3) δ 8.16 435.1208.
(d, J = 7.8 Hz, 1H), 7.79 (d, J = 7.7 Hz, 1H), 7.69-7.65 (m, 2H), 7.62- (2R,4'S)-4'-(2-(2-Chlorophenyl)-2-oxoethyl)spiro[indene-2,3'-
7.56 (m, 2H), 7.62-7.56 (m, 2H), 7.49-7.35 (m, 5H), 7.27-7.22 (m, 1H), isochromane]-1,1'(3H)-dione (3ak). white solid; yield 84% (70.0 mg);
4.26 (dd, J = 6.7, 18.6 Hz, 1H), 3.99-3.96 (m, 1H), 3.34 (s, 2H), 3.02 mp 56.2-56.8 oC. >99% ee, >20:1 dr; [α]D20 = +118.7 (CHCl3, c = 1.63);
(dd, J = 5.3, 18.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.6, 195.8 the ee value was determined by HPLC (Chiral IC cloumn, i-PrOH/n-
(d, J = 2.0 Hz), 163.8, 162.8 (d, J = 246.7 Hz), 149.1, 142.1, 138.5 (d, J Hexane = 20/80, Flow rate: 1.0 mL/min, λ = 254 nm), t (minor) =
1
= 6.3 Hz), 136.5, 134.8, 134.1, 130.7, 130.4 (d, J = 7.5 Hz), 128.7, 22.79 min, t (major) = 27.37 min. H NMR (400 MHz, CDCl3) δ 8.16-
128.4, 128.2, 126.5, 125.4, 124.0, 123.95 (d, J = 2.9 Hz), 120.4 (d, J = 8.13 (m, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.69-7.57 (m, 3H), 7.49-7.44 (m,
21.3 Hz), 114.8 (d, J = 22.4 Hz), 86.2, 41.4, 40.0, 39.2. IR (neat) v 2H), 7.39-7.30 (m, 5H), 4.09 (dd, J = 7.0, 18.8 Hz, 1H), 3.97-3.93 (m,
2918, 1719, 1687, 1587, 1442, 1296, 1248, 1152, 1124, 1078, 871, 1H), 3.34 (s, 2H), 3.08 (dd, J = 5.0, 18.8 Hz, 1H). 13C NMR (100 MHz,
+
cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H17FNaO4
423.1003; Found 423.1004.
(2R,4'S)-4'-(2-(3-Chlorophenyl)-2-oxoethyl)spiro[indene-2,3'-
CDCl3) δ 199.7, 198.7, 163.8, 149.1, 141.8, 138.3, 136.5, 134.9,
134.1, 132.0, 130.8, 130.6, 130.5, 129.4, 128.7, 128.5, 128.2, 127.0,
126.5, 125.4, 124.0, 86.2, 44.0, 41.4, 39.3. IR (neat) v 2920, 2851,
isochromane]-1,1'(3H)-dione (3ah). white solid; yield 86% (71.7 1717, 1604, 1588, 1458, 1432, 1355, 1294, 1124, 1068, 983 cm-1;
mg); mp 80.5-81.0 C. 98% ee, >20:1 dr; [α]D = +222.2 (CHCl3, c =
o
20
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
+
13
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H17ClNaO4 439.0708; 3.95-3.92 (m, 1H), 3.34 (s, 2H), 3.02 (dd, J = 4.5, 18.8 Hz, 1H).
Found 439.0710.
C
View Article Online
DOI: 10.1039/D0OB00541J
NMR (100 MHz, CDCl3) δ 198.8, 198.4, 163.7, 149.1, 141.8, 137.7,
(2R,4'S)-4'-(2-(2-Bromophenyl)-2-oxoethyl)spiro[indene-2,3'-
136.6, 136.5, 134.9, 134.0, 132.0, 130.70, 130.67, 130.4, 128.8,
isochromane]-1,1'(3H)-dione (3al). white solid; yield 71% (65.5 mg); 128.6, 128.1, 127.4, 126.5, 125.4, 124.0, 86.0, 44.0, 41.4, 39.3. IR
mp 58.6-59.2 oC. 99% ee, >20:1 dr; [α]D20 = +133.4 (CHCl3, c = 0.35); (neat) v 2922, 2849, 1721, 1605, 1581, 1458, 1295, 1219, 1124,
the ee value was determined by HPLC (Chiral IC cloumn, i-PrOH/n- 1079, 984 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
Hexane = 30/70, Flow rate: 1.0 mL/min, λ = 254 nm), t (minor) = C25H16Cl2NaO4+ 473.0318; Found 473.0322.
1
18.47 min, t (major) = 25.03 min. H NMR (400 MHz, CDCl3) δ 8.16- (2R,4'S)-4'-(2-(2,4-Dichloro-5-fluorophenyl)-2-
8.13 (m, 1H), 7.83 (d, J = 7.7 Hz, 1H), 7.70-7.60 (m, 2H), 7.57-7.53 (m, oxoethyl)spiro[indene-2,3'-isochromane]-1,1'(3H)-dione
(3ap).
2H), 7.50-7.44 (m, 2H), 7.41-7.35 (m, 3H), 7.29-7.25 (m, 1H), 4.08 white solid; yield 82% (77.0 mg); mp 69.7-70.2 oC. 96% ee, >20:1 dr;
20
(dd, J = 6.9, 19.0 Hz, 1H), 3.96-3.92 (m, 1H), 3.35 (s, 2H), 3.07 (dd, J [α]D = +164.7 (CHCl3, c = 0.702); the ee value was determined by
= 5.0, 19.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 200.5, 198.7, 163.8, HPLC (Chiral IC cloumn, i-PrOH/n-Hexane = 40/60, Flow rate: 1.0
149.1, 141.8, 140.4, 136.5, 134.9, 134.1, 133.7, 131.9, 130.6, 129.0, mL/min, λ = 254 nm), t (minor) = 18.30 min, t (major) = 16.36 min.
128.7, 128.5, 128.2, 126.5, 125.5, 124.0, 118.6, 86.2, 43.8, 41.4, 1H NMR (400 MHz, CDCl3) δ 8.16-8.14 (m, 1H), 7.81 (d, J = 7.7 Hz,
39.1. IR (neat) v 2920, 2849, 1716, 1604, 1588, 1458, 1428, 1295, 1H), 7.70-7.62 (m, 2H), 7.52-7.43 (m, 4H), 7.37 (d, J = 7.7 Hz, 2H),
1219, 1123, 1078, 983 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd 4.12 (dd, J = 7.9, 18.9 Hz, 1H), 3.94-3.91 (m, 1H), 3.34 (s, 2H), 3.00
for C25H17BrNaO4+ 483.0202; Found 483.0203.
(2R,4'S)-4'-(2-(2-Methoxyphenyl)-2-oxoethyl)spiro[indene-2,3'-
(dd, J = 4.1, 18.9 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.8, 197.3,
163.6, 156.8 (d, J = 250.6 Hz), 149.2, 141.6, 137.8 (d, J = 5.2 Hz),
isochromane]-1,1'(3H)-dione (3am). white solid; yield 81% (66.8 136.7, 135.0, 134.0, 132.2, 130.7, 128.8, 128.6, 128.0, 126.5, 126.4
o
20
mg); mp 60.5-61.3 C. 98% ee, >20:1 dr; [α]D = +160 (CHCl3, c = (d, J = 3.8 Hz), 125.5, 124.9 (d, J = 19.0 Hz), 124.0, 117.6 (d, J = 23.7
0.30); the ee value was determined by HPLC (Chiral IC cloumn, i- Hz), 85.8, 44.0, 41.4, 39.3. IR (neat) v 2922, 2853, 1717, 1604, 1568,
PrOH/n-Hexane = 40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t 1467, 1379, 1294, 1267, 1253, 1219, 1125, 1082, 1061, 928 cm-1;
(minor) = 27.22 min, t (major) = 40.88 min. 1H NMR (400 MHz, CDCl3) HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H15Cl2FNaO4+ 491.0224;
δ 8.16-8.13 (m, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.69-7.63 (m, 2H), 7.59- Found 491.0227.
7.55 (m, 1H), 7.48-7.41 (m, 3H), 7.36 (d, J = 7.6 Hz, 1H), 7.31 (d, J = (2R,4'S)-4'-(2-Oxo-2-(thiophen-2-yl)ethyl)spiro[indene-2,3'-
7.7 Hz, 1H), 7.00-6.95 (m, 1H), 6.89 (d, J = 8.4 Hz, 1H), 4.02-3.87 (m, isochromane]-1,1'(3H)-dione (3aq). white solid; yield 78% (60.6
o
20
2H), 3.74 (s, 3H), 3.34 (s, 2H), 3.24 (dd, J = 5.8, 18.0 Hz, 1H). 13C mg); mp 72.1-73.0 C. 99% ee, >20:1 dr; [α]D = +267.9 (CHCl3, c =
NMR (100 MHz, CDCl3) δ 199.1, 198.6, 164.2, 158.7, 149.0, 136.3, 0.352); the ee value was determined by HPLC (Chiral IC cloumn, i-
134.5, 134.3, 134.0, 130.5, 130.4, 128.6, 128.2, 128.1, 127.5, 126.4, PrOH/n-Hexane = 20/80, Flow rate: 1.0 mL/min, λ = 254 nm), t
125.3, 124.2, 120.6, 111.5, 86.8, 55.4, 44.5, 41.4, 39.7. IR (neat) v (minor) = 55.46 min, t (major) = 60.47 min. 1H NMR (400 MHz, CDCl3)
2924, 2849, 1719, 1668, 1596, 1484, 1458, 1435, 1295, 1242, 1162, δ 8.15 (d, J = 7.7 Hz, 1H), 7.81 (d, J = 7.7 Hz, 1H), 7.69-7.55 (m, 4H),
1083, 1020, 987 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for 7.46 (t, J = 7.6 Hz, 2H), 7.38-7.34 (m, 2H), 7.10-7.07 (m, 1H), 4.08
C26H20NaO5+ 435.1203; Found 435.1205.
(2R,4'S)-4'-(2-(2,4-Dichlorophenyl)-2-oxoethyl)spiro[indene-2,3'-
(dd, J = 5.6, 17.9 Hz, 1H), 3.95-3.91 (m, 1H), 3.34 (s, 2H), 3.12 (s, 2H),
3.12 (dd, J = 6.4, 17.9 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.4,
isochromane]-1,1'(3H)-dione (3an). white solid; yield 81% (73.1 189.8, 163.9, 149.1, 143.4, 141.9, 136.5, 134.7, 134.1, 134.0, 132.5,
o
20
mg); mp 180.1-180.9 C. 98% ee, >20:1 dr; [α]D = +254.8 (CHCl3, c 130.7, 128.7, 128.42, 128.36, 128.3, 126.5, 125.4, 123.9, 86.4, 41.4,
= 0.668); the ee value was determined by HPLC (Chiral IF cloumn, i- 40.2, 39.2. IR (neat) v 2920, 2853, 1717, 1660, 1604, 1518, 1458,
PrOH/n-Hexane = 30/70, Flow rate: 1.0 mL/min, λ = 254 nm), t 1415, 1295, 1244, 1219, 1124, 1078, 939 cm-1; HRMS (ESI-TOF) m/z:
(minor) = 17.18 min, t (major) = 28.11 min. 1H NMR (400 MHz, CDCl3) [M + Na]+ Calcd for C23H16NaO4S+ 411.0662; Found 411.0664.
δ 8.17-8.15 (m, 1H), 7.98 (d, J = 2.0 Hz, 1H), 7.79-7.72 (m, 2H), 7.69- (2R,4'S)-4'-(2-(Naphthalen-2-yl)-2-oxoethyl)spiro[indene-2,3'-
7.65 (m, 1H), 7.64-7.59 (m, 1H), 7.53-7.44 (m, 3H), 7.36 (d, J = 7.7 Hz, isochromane]-1,1'(3H)-dione (3ar). white solid; yield 77% (66.6 mg);
20
2H), 4.26 (dd, J = 6.9, 18.6 Hz, 1H), 3.98-3.95 (m, 1H), 3.34 (s, 2H), mp 89.5-90.0 oC. >99% ee, >20:1 dr; [α]D = +335.6 (CHCl3, c =
2.94 (dd, J = 4.8, 18.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.7, 0.562); the ee value was determined by HPLC (Chiral IC cloumn, i-
194.9, 163.8, 149.1, 142.0, 138.0, 136.6, 135.9, 134.9, 134.0, 133.4, PrOH/n-Hexane = 40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t
130.8, 130.7, 130.1, 128.8, 128.6, 128.1, 127.2, 126.5, 125.4, 124.0, (minor) = 26.90 min, t (major) = 38.26 min. 1H NMR (400 MHz, CDCl3)
86.0, 41.4, 39.9, 39.1. IR (neat) v 2922, 2853, 1721, 1686, 1604, δ 8.43 (s, 1H), 8.19-8.16 (m, 1H), 7.96-7.92 (m, 2H), 7.86-7.79 (m,
1581, 1454, 1386, 1293, 1271, 1219, 1197, 1153, 1086, 1052, 963 3H), 7.69-7.65 (m, 1H), 7.61-7.51 (m, 3H), 7.48-7.40 (m, 3H), 7.36 (d,
+
cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H16Cl2NaO4
473.0318; Found 473.0317.
(2R,4'S)-4'-(2-(3,4-Dichlorophenyl)-2-oxoethyl)spiro[indene-2,3'-
J = 7.7 Hz, 1H), 4.37 (dd, J = 6.0, 18.4 Hz, 1H), 4.06 (t, J = 5.9 Hz, 1H),
3.37 (s, 2H), 3.24 (dd, J = 5.8, 18.4 Hz, 1H). 13C NMR (100 MHz, CDCl3)
δ 198.7, 196.8, 164.0, 149.1, 142.4, 136.5, 135.7, 134.8, 134.1,
isochromane]-1,1'(3H)-dione (3ao). white solid; yield 85% (76.7 133.7, 132.4, 130.7, 130.1, 129.7, 128.7, 128.6, 128.5, 128.4, 128.3,
o
20
mg); mp 46.7-47.3 C. 97% ee, >20:1 dr; [α]D = +165.8 (CHCl3, c = 127.7, 126.9, 126.5, 125.4, 124.0, 123.7, 86.6, 41.4, 39.8, 39.3. IR
0.654); the ee value was determined by HPLC (Chiral IC cloumn, i- (neat) v 2925, 2853, 1718, 1618, 1604, 1467, 1459, 1361, 1295,
PrOH/n-Hexane = 20/80, Flow rate: 1.0 mL/min, λ = 254 nm), t 1278, 1219, 1184, 1124, 1079, 942, 910 cm-1; HRMS (ESI-TOF) m/z:
(minor) = 33.91 min, t (major) = 46.62 min. 1H NMR (400 MHz, CDCl3) [M + Na]+ Calcd for C29H20NaO4+ 455.1254; Found 455.1258.
δ 8.15 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 7.7 Hz, 1H), 7.70-7.58 (m, 3H), General Procedure for the Preparation of Compound 4. In an oven-
7.51-7.44 (m, 2H), 7.39-7.31 (m, 4H), 4.11 (dd, J = 7.5, 18.8 Hz, 1H), dried 50 mL round-bottom flask, compound 3aa (102 mg, 0.28
8 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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Kurahashi and S. Matsubara, Chem. Lett., 2011, 40, 322; (f)
mmol), hydroxylamine hydrochloride (386 mg, 5.6 mmol, 20.0 equiv)
and sodium acetate trihydrate (571 mg, 15.0 equiv) were taken, and
then MeOH (15 mL) was added. The reaction mixture was refluxed
in heating mantle for 3 hours, and then quenched with aqueous
NaHCO3, extracted three times with CH2Cl2. The combined organics
were washed with brine before being dried over Na2SO4, filtered
and concentrated in vacuo. The crude product was purified by flash
View Article Online
W. Xia, Y. Shao, W. Gui and C. Yang, Chem. Commun., 2011,
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D. Vankar, Org. Biomol. Chem., 2018, 16, 8258.
4
For selected examples of chiral isochromanones starting
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column chromatography (acetone:CH2Cl2
= 1:30) to give the
corresponding product 4.
(2R,4'S)-4'-(-2-(hydroxyimino)-2-phenylethyl)spiro[indene-2,3'-
isochromane]-1,1'(3H)-dione (4). White solid; yield 91% (96.4 mg);
mp 88.5-89.1 oC. 98% ee, >20:1 dr; [α]D20 = +254.7 (CHCl3, c = 1.426);
the ee value was determined by HPLC (Chiral IC cloumn, i-PrOH/n-
Hexane = 40/60, Flow rate: 1.0 mL/min, λ = 254 nm), t (minor) =
1
11.72 min, t (major) = 18.41 min. H NMR (400 MHz, CDCl3) δ 8.94
5
(brs, 1H), 8.05-8.03 (m, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.67-7.62 (m,
1H), 7.45 (t, J = 7.5 Hz, 1H), 7.36-7.28 (m, 3H), 7.22-7.17 (m, 1H),
7.14-7.05 (m, 4H), 6.98-6.96 (m, 1H), 3.57-3.51 (m, 2H), 3.34-3.20
(m, 3H). 13C NMR (100 MHz, CDCl3) δ 198.2, 163.9, 156.9, 149.2,
140.4, 136.4, 135.1, 134.0, 133.9, 130.5, 129.2, 128.7, 128.6, 128.4,
126.6, 125.4, 123.9, 87.1, 41.3, 40.7, 28.0. IR (neat) v 3057, 2922,
1715, 1605, 1459, 1282, 1238, 1030, 961, 695 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C25H20NO4+ 398.1387; Found 398.1390.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (NNSFC: 21871237).
6
7
D. Hojo, K. Noguchi, M. Hirano and K. Tanaka, Angew. Chem.
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Notes and references
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Journal Name
Liu, X.-C. Yang, Y.-Z. Hua, J.-B. Chang and M.-C. Wang, Org.
Lett., 2019, 21, 7089.
View Article Online
DOI: 10.1039/D0OB00541J
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14 For details see Supporting Information.
10 | J. Name., 2012, 00, 1-3
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