Article

Cite This: J. Org. Chem. 2019, 84, 8984−8997 pubs.acs.org/joc

Diastereoselective Construction of 2‑Aminoindanones via an

In(OTf)3‑Catalyzed Domino Reaction
Siyang Xing,* Hanyu Xia, Junshuo Guo, Chenchen Zou, Tingxuan Gao, Kui Wang,* Bolin Zhu,*
Meiqi Pei, and Mengpei Bai
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Key Laboratory of Inorganic−Organic Hybrid
Functional Material Chemistry, Ministry of Education (Tianjin Normal University), College of Chemistry, Tianjin Normal
University, Tianjin 300387, People’s Republic of China
*
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ABSTRACT: An In(OTf)3-catalyzed domino reaction involving

sequential oxidative ring opening of aziridines by using the solvent
dimethyl sulfoxide and intramolecular Michael addition has been
developed for the modular synthesis of 2-aminoindanone compounds
by the formation of one new CO bond and one new C−C bond. The
notable feature of this strategy includes broad substrate scope, excellent
trans-diastereoselectivities, highly functionalized products, and mild
conditions. The catalyst In(OTf)3 plays an important role in the
formation of the indanone ring.

■ INTRODUCTION
Indanones are structural motifs of many natural products and
reported a palladium(II)-catalyzed domino reaction of ortho-
electron-deficient alkynyl-substituted aryl aldehydes with
biologically relevant molecules displaying a remarkable variety indoles for the synthesis of 3-indole-substituted indanones.7b
of activities1 (Scheme 1). The development of synthetic Despite these notable advances, as an important kind of
indanone compounds, modular approaches for the synthesis of
Scheme 1. Representative Indanone Compounds 2-aminoindanones are few in the literature. Successful
examples mainly include N-heterocyclic carbene-catalyzed [4
+ 1] annulations involving aza-benzoin reactions8 and
rhodium-catalyzed domino cyclizations based on ring opening
of N-sulfonyl 1,2,3-triazoles.9 Considering the importance of
indanone compounds in the field of organic synthetic
chemistry and medical chemistry, developing efficient and
general methodologies to access 2-aminoindanones remained
to be particularly useful.
N-activated aziridines,10 as valuable building blocks, are
ready to react with various nucleophiles to afford ring opening
products. In addition, Michael addition11 of electron-deficient
alkenes with nucleophiles is a powerful strategy for the
formation of carbon−carbon and carbon−heteroatom bonds.
Based on the ring opening of aziridines12 and Michael addition
of electron-deficient alkenes,13 a lot of domino reactions have
methodologies toward these highly useful heterocyclic been developed for the construction of cyclic compounds with
compounds has drawn much attention from synthetic organic molecular complexity and structural diversity, respectively.
chemists. Typical methods for the synthesis of indanone However, domino reactions that simultaneously involves ring
compounds include Friedel−Crafts acylation,2 Nazarov cycli- opening of aziridines and Michael addition were rarely
zation,3 Dieckmann condensation,4 hydroacylation of o-alkenyl reported in the literature.14 In 2016, we designed and
aromatic aldehydes,5 and carbonylative cyclization of o- synthesized a type of substrates containing aziridines and
halogenstyrenes,6 and so forth. Besides, a lot of elegant electron-deficient alkenes.15 Secondary amines and primary
domino reactions have been developed for the efficient amines were first selected as nucleophiles to initiate domino
construction of indanone skeletons in recent years.7 For reactions of this kind of substrates under the catalysis of
example, Xi et al. achieved an efficient synthesis of 2,3-
disubstituted indanones through MeOTf-catalyzed domino Received: March 28, 2019
annulation of aldehydes and arylalkynes.7a Lu and Han et al. Published: June 28, 2019

© 2019 American Chemical Society 8984 DOI: 10.1021/acs.joc.9b00876

J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

AgOTf.15a For secondary amines, the domino reaction Scheme 3. Synthesis of Aziridine 3a
followed path 1 to provide tetrahydroisoquinoline products
in good yields with good diastereoelectivities (Scheme 2, eq 1).

Scheme 2. Domino Reactions Involving Aziridines and

Electron-Deficient Alkenes

for 5 h. To our delight, indanone product 4a was obtained in

65% yield with good trans-diastereoselectivity (6:1 dr), along
with 4-isoquinolone product 5a in less than 5% yield (Table 1,

Table 1. Optimization of the Reaction Conditionsa

entry catalyst 4a yield/%b drb 5a yield/%b

d
1 In(OTf)3 65 6:1 <5
2 In(OTf)3 74 6:1 n.d.c
3 InCl3 n.d. n.d.
4 In(OAc)3 n.d. n.d.
5 Al(OTf)3 n.d. 62
6 Ga(OTf)3 n.d. 48
7 Sn(OTf)2 n.d. 34
8 Bi(OTf)3 10 6:1 30
9 Sc(OTf)3 n.d. 51
10 Yb(OTf)3 n.d. 52
When primary amines were subjected to the domino reaction,
11 Fe(OTf)3 n.d. 48
isoindoline products were obtained in good yields with good
12 Ni(ClO4)2 n.d. 43
diastereoelectivities by following path 2 (Scheme 2, eq 2).
13 Cu(OTf)2 n.d. 45
Subsequently, we found that the solvent dimethyl sulfoxide
14 AgOTf n.d. 60
(DMSO) could be also used as the nucleophile to initiate the
15 Zn(OTf)2 n.d. 39
domino reaction under the catalysis of AgOTf.15c Following a
16 BF3·OEt2 n.d. 44
similar path with path 1, sequential oxidative ring opening of
17 TMSOTf n.d. 35
aziridines by DMSO and aza-Michael addition took place to
18 n.d. 50
generate a series of 4-isoquinolone products (Scheme 2, eq 3).
19e In(OTf)3 70 6:1 n.d.
Recently, when we used In(OTf)316 to catalyze the domino
20f In(OTf)3 30 6:1 6
reaction of aziridines-bearing electron-deficient alkenes with a
DMSO instead of AgOTf, a dramatic catalyst effect was Reaction conditions: 3a (1 equiv, 0.05 mmol), the catalyst (20 mol
observed. The use of In(OTf)3 changed the reaction pathway %, 0.001 mmol), 1 mL DMSO, in the open air, 90 °C, 2 h.
b
Determined by 1H NMR using 1-chloro-2,4-dinitrobenzene as the
of the domino reaction. After oxidative ring opening of internal standard. cNot detected. dThe reaction was run at 70 °C for 5
aziridines, Michael addition selectively took place to provide a h. eA DMSO−DCE mixed solvent was used (DMSO−DCE = 1:1).
series of 2-aminoindanones in acceptable to good yields with f
DMSO (20 equiv, 1 mmol) was used in DCE (1 mL).
excellent trans-diastereoselectivities (Scheme 2, eq 4). Differ-
ent from all of our previous results about domino reactions
involving ring opening of aziridines and Michael addition, two entry 1). Increasing the reaction temperature to 90 °C was
carbons in the aziridine ring were utilized as the formation of beneficial for improving the yield of the indanone product
the new ring in the current domino reaction. It represented a (entry 2). Product 4a was obtained in 74% yield without the
new cyclization mode, further enriching the diversity of decrease of diastereoselectivity. Then, several other indium
domino products. Herein, we would like to report detailed salts including InCl3 and In(OAc)3 were used to catalyze the
results on the In(OTf)3-catalyzed domino reaction.

■
domino reaction instead of In(OTf)3 (entries 3 and 4). It was
found that the anions of indium salts had an obvious influence
RESULTS AND DISCUSSION on the formation of the indanone product. The domino
Aziridine 3a was synthesized in two steps without using reaction failed to provide either product 4a or product 5a
protecting groups according to our previously reported under the catalysis of these two indium salts. Subsequently, we
method15a (Scheme 3). Kenovengel condensation of aldehyde turned to screen a series of metal salts containing different
1a with dimethyl malonate generated diene 2a in 76% yield. metal ions to optimize the reaction conditions (entries 5−15).
Then, it was further converted to 3a in 66% yield via a copper- In most cases, product 5a was obtained in moderate to good
catalyzed aziridination. yields without the generation of product 4a. As an exception,
Our initial trial was conducted by the treatment of aziridine Bi(OTf)3 provided product 4a in low yield with good
3a in DMSO in the presence of In(OTf)3 (20 mol %) at 70 °C diastereoselectivity, along with the predominant formation of
8985 DOI: 10.1021/acs.joc.9b00876
J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

product 5a. Next, BF3·OEt2 and TMSOTf, as two kinds of the best result of domino reactions and product 4c was
nonmetallic Lewis acids, were also attempted to catalyze the obtained in 70% yield with excellent diastereoselectivities
domino reaction (entries 16 and 17). It was found that product (>20:1 dr). This finding impelled us to select the n-propyl
5a was obtained in 44 and 35% yields without the generation group as the ester group of aziridines 3 in the next
of product 4a. Moreover, the domino reaction was run in the investigation. Subsequently, aziridines 3h−3k were subjected
absence of metal salts (entry 18). The result showed that to domino reactions under the optimized reaction conditions
product 4a was not detected and product 5a was obtained in to examine the influence of the protecting groups of the N-
50% yield. When the domino reaction was conducted in a atoms of the aziridine ring on the domino reaction. It was
DMSO−DCE mixed solvent (DMSO−DCE = 1:1), product found that the enhancement of electron-withdrawing proper-
4a could be obtained in a slightly decreased yield with good ties on the aromatic ring of the protecting group is unfavorable
diastereoselectivity and without the generation of product 5a for the formation of the indanone products. Indanone products
(entry 19). At last, we attempted to run the domino reaction 4h−4k were obtained in moderate to good yields (45−66%)
using 20 equiv of DMSO in DCE (entry 20). It was found that with excellent diastereoselectivities (>20:1 dr), along with
it had an obvious harmful influence on the formation of products 5h−5k in 15−20% yields (entries 8−10). Among
product 4a. The domino reaction gave rise to product 4a in them, the relative configuration of 4i was unambiguously
30% yield along with product 5a in 6% yield. confirmed by X-ray crystal structure analysis.17
Based on the optimized reaction conditions, a systematic We then moved on to investigate the scope of the domino
investigation of the scope of the domino reaction was reaction with respect to different substituents on the aromatic
conducted by synthesizing a series of aziridines 3a−3k with ring. The results of these reactions are shown in Table 3. In
different substituents on the electron-deficient alkenes and
aziridine. The results are summarized in Table 2. Aziridines Table 3. Testing the Electronic Effect on the Aromatic
Ringa
Table 2. Examining the Substituent Effect on the Electron-
Deficient Alkenes and Aziridinesa

entry 3 R1/R2 4 yield/%b drc 5 yield/%c

1 3a Me/Me 4a 74 6:1 5a <5
2 3b Et/Me 4b 72 9:1 5b <5
3 3c n-Pr/Me 4c 70 >20:1 5c <5
4 3d i-Pr/Me 4d 65 >20:1 5d <5
5 3e n-Bu/Me 4e 62 >20:1 5e <5
6 3f Bn/Me 4f 65 >20:1 5f <5
7 3g t-Bu/Me 4g <5 >20:1 5g <5
8 3h n-Pr/t-Bu 4h 63 >20:1 5h <5
9 3i n-Pr/H 4i 66 >20:1 5i 15
10 3j n-Pr/Br 4j 62 >20:1 5j 20
11 3k n-Pr/NO2 4k 45 >20:1 5k 18
a a
Reaction conditions: 3 (1 equiv, 0.2 mmol), In(OTf)3 (20 mol %, Reaction conditions: 3 (1 equiv, 0.2 mmol), In(OTf)3 (20 mol %,
0.04 mmol), 4 mL DMSO, 90 °C, 2 h, in open air. bIsolated yields. 0.04 mmol), 4 mL DMSO, 90 °C, 2 h, in open air. bIsolated yields.
c c
Determined by 1H NMR using 1-chloro-2,4-dinitrobenzene as the Determined by 1H NMR using 1-chloro-2,4-dinitrobenzene as the
internal standard. internal standard. dProduct was isolated as a mixture of diastereomers
(dr = 7:1). eProduct was isolated as a mixture of diastereomers (dr =
3a−3g bearing different ester groups on the electron-deficient 3.5:1).
alkene were first subjected to domino reactions to react with
the solvent DMSO under the optimized reaction conditions
(entries 1−7). It was found that indanone products 4a−4f general, electron-donating and electron-accepting substituents
were furnished in acceptable yields with good trans- such as Me, Ph, OMe, F, and Cl residing at different positions
diastereoselectivities, along with 4-isoquinolone products 5a− on the aromatic ring were compatible, providing the
5f in less than 5% yield. As an exception, aziridine 3g with the corresponding indanone products 4 in acceptable to good
t-butyl ester group on the electron-deficient alkene provided yields with excellent trans-diastereoselectivities, along with a
the corresponding indanone product 4g in less than 5% yield, small quantity of 4-isoquinolone products 5. However,
along with the decomposition of aziridine 3g. A remarkably substrates 3 with strong electron-accepting substituents such
enhanced diastereoslectivity and a slightly decreased yield were as CN and NO2 failed to provide indanone products 4 in
observed with the increase of the bulkiness of the ester group separable yields. First, aziridines 3l and 3m with R 1
from the methyl group to the ethyl, n-propyl, i-propyl, n-butyl, substituents on the aromatic ring were selected to react with
and benzyl groups. It should be noted that aziridine 3c gave DMSO under optimized reaction conditions. The correspond-
8986 DOI: 10.1021/acs.joc.9b00876
J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

ing products 4l and 4m were furnished in 62 and 58% yields happened to afford intermediate C, which was further
with excellent diastereoselectivities, respectively (entries 1 and transformed into intermediate D via enolization reaction
2). It should be noted that slight epimerization was observed in with the assistance of In(OTf)3.19 Next, metal chalation of
the processing of isolating product 4m. Product 4m was intermediate D with In(OTf)320 provided a stable five-
actually obtained with a decreased diastereoselectivity (7:1 dr). membered indium complex E. Instead of previous generation
Then, domino reactions of aziridines 3n−3s bearing R2 of 4-isoquinolone products via aza-Michael addition,15c
substituents on the aromatic ring were carried out (entries intramolecular Michael addition of complex E finally took
3−8). It can be seen that electronic properties of R2 place to provide product 4a in good yield with excellent trans-
substituents have an obvious influence on the yields of domino diastereoselectivity. A reasonable explanation for the gener-
reactions. Electron-donating R2 groups were more favorable for ation of excellent diastereoselectivity is that trans-4a might be
the formation of indanone products than electron-accepting R2 thermodynamically more stable, in which two bulky sub-
groups. Aziridines 3n−3r reacted with DMSO soomthly to stituents on the five-membered ring of indanones avoid
provide indanone products 4n−4r in 40−70% yields with unfavorable interaction. It should be noted that 4-isoquinolone
excellent trans-diastereoselectivities. As an expection, the byproducts 5 were obviously observed with the increase of
domino reaction of aziriidne 3s with the CN group on the electron-withdrawing properties of substitutions at the nitro-
aromatic ring led to indanone product 4s in less than 10% yield gen atom of aziridine or the substitutions on the aromatic ring.
along with 4-isoquinolone product 5s in less than 5% yield. The reason for this might be that these electron-withdrawing
Next, aziridines 3t−3x having R3 substituents on the aromatic substitutions reduced the electron cloud density of the
ring were subjected to the domino reaction under the nitrogen atom or the oxygen atom which coordinated with
optimized reaction conditions (entries 9−13). It was found In(OTf)3. It caused the metal chalation of intermediate D with
that aziridines 3t−3w reacted with DMSO well to provide the In(OTf)3 to become weaker to provide less-stable five-
corresponding product 4t−4w in 60−64% yields with excellent membered indium complex E.
trans-diastereoselectivities. Similar to product 4m, epimeriza- In order to demonstrate the synthetic utility of the domino
tion also occurred when we attempted to isolate product 4u reaction, further chemical transformations of product 4c were
and 4w. These two products were actually obtained with conducted (Scheme 6). The ketone carbonyl group of product
markedly decreased diastereoselectivities (3.5:1 dr). It seems 4c could be easily reduced by NaBH4 at room temperature.
that the NO2 group had harmful influence on the domino The corresponding product 6 was isolated in 56% yield with
reaction like the CN group. Under the optimized reaction good diastereoselectivity. The relative configuration of 6 was
conditions, aziridine 3x reacted with DMSO to provide established by the NOESY experiment. Moreover, the
indanone 4x in less than 5% yield, along with 4-isoquinolone alkylation reaction of product 4c with benzyl bromide was
product 5v in less than 10% yield. In addition, domino carried out under basic conditions. N-alkylation product 7 was
reactions of aziridines 3y and 3z with R4 substituents obtained as the major product, the structure of which was
possessing OMe and Cl groups afforded indanone products confirmed by the 2D NMR experiment.

■
4y and 4z in 38 and 20% yields, respectively, with excellent
diastereoselectivities (entries 14 and 15). At last, the CONCLUSIONS
naphthalene-containing aziridine 3aa was used in the domino
reaction as well (entry 16). The domino reaction could In conclusion, an In(OTf)3-catalyzed domino reaction of
successfully take place to provide indanone product 4aa in 64% dialkyl 2-(2-(1-tosylaziridin-2-yl)benzylidene)malonates with
yield with excellent diastereoselectivity. the solvent DMSO has been accomplished. Compared with
After successful construction of a series of indanone our previous formation of 4-isoquinolones under the catalysis
compounds 4, the control experiment was conducted in of AgOTf, a dramatic catalyst effect was observed. The present
order to understand the mechanism of the domino reaction domino reaction underwent sequential oxidative ring opening
(Scheme 4). 4-Isoquinolone 5a was treated with In(OTf)3 at of aziridines and Michael addition to afford a series of 2-
aminoindanone products in acceptable to good yields with
Scheme 4. Convertion from 4-Isoquinolone 5a to Indanone excellent trans-diastereoselectivities. We believe that the
4a remarkable catalyst effect of In(OTf)3 along with interesting
structural features of the domino products would draw much
attention from synthetic organic chemists. Further studies on
the selective synthesis of distinct types of complicated cyclic
compounds based on the ring opening of aziridines are in
progress.

90 °C in DMSO for 2 h. It was found that 4-isoquinolone 5a

■ EXPERIMENTAL SECTION
General Experimental Methods. 1H NMR and 13C{1H} NMR
was almost completely recovered without the generation of were recorded with Bruker 400 MHz spectrometer instruments in
indanone 4a. It indicated that 4-isoquinolone 5a was not the CDCl3. The chemical shifts (δ) were measured in ppm and with the
intermediate of the domino reaction generating indanone 4a. solvents as references (for CDCl3, 1H: δ 7.26 ppm, 13C{1H}: δ 77.00
According to the literature and our previous work,15c,18 a ppm). All solvents were obtained from commercial sources and were
purified according to standard procedures. Purification of products
possible mechanism is proposed in Scheme 5. The initial ring was accomplished by flash chromatography using silica gel (200−300
opening of aziridine 3a with DMSO under the catalysis of mesh). Thin-layer chromatography was performed on Merck silica gel
In(OTf)3 gave intermediate A, which underwent hydrogen GF254 plates and visualized by UV-light (254 nm). Melting points
migration in a six-membered transition state to provide were obtained on a Yanaco-241 apparatus and are uncorrected. IR
intermediate B. Then, tautomerization of intermediate B spectra were recorded on a MAGNA-560 spectrometer made by

8987 DOI: 10.1021/acs.joc.9b00876

J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

Scheme 5. Possible Mechanism of the Domino Reaction

Scheme 6. Further Transformation of 4c 1.76 (h, J = 7.2 Hz, 2H), 1.57 (h, J = 7.1 Hz, 2H), 1.01 (t, J = 7.2 Hz,
3H), 0.80 (t, J = 7.4 Hz, 3H).
Dipropyl 2-(3-Methyl-2-vinylbenzylidene)malonate 2l. Following
the general procedure, 2l was synthesized from 1l.15c It is obtained as
yellow oil (3.92 g, 62% yield); 1H NMR (400 MHz, CDCl3): δ 7.97
(s, 1H), 7.30−7.22 (m, 1H), 7.19 (d, J = 7.2 Hz, 1H), 7.12 (t, J = 7.6
Hz, 1H), 6.79 (dd, J = 17.6, 11.3 Hz, 1H), 5.66 (dd, J = 11.3, 1.2 Hz,
1H), 5.28 (dd, J = 17.6, 1.2 Hz, 1H), 4.19 (t, J = 6.6 Hz, 2H), 4.10 (t,
J = 6.5 Hz, 2H), 2.30 (s, 3H), 1.72 (h, J = 7.2 Hz, 2H), 1.57 (h, J =
7.1 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H), 0.77 (t, J = 7.4 Hz, 3H).
Dipropyl 2-(3-Fluoro-2-vinylbenzylidene)malonate 2m. Follow-
ing the general procedure, 2m was synthesized from 1m.21b It is
obtained as yellow oil (4.99 g, 78% yield); 1H NMR (400 MHz,
CDCl3): δ 7.84 (s, 1H), 7.14−7.05 (m, 2H), 6.98 (ddd, J = 9.7, 7.6,
Nicolet Company. HRMS were acquired in the ESI mode (positive 1.8 Hz, 1H), 6.69 (dd, J = 17.7, 11.6 Hz, 1H), 5.56 (dd, J = 20.7, 14.7
ion) with the use of TOF mass analyzer. Hz, 2H), 4.13 (t, J = 6.6 Hz, 2H), 4.00 (t, J = 6.6 Hz, 2H), 1.64 (h, J =
General Procedure for the Preparation of Aziridines 3. Step 7.2 Hz, 2H), 1.46 (h, J = 7.2 Hz, 2H), 0.89 (t, J = 7.4 Hz, 3H), 0.69
1: piperidine (1 mL) and 4 Å MS (8 g) were added to the solution of (t, J = 7.4 Hz, 3H).
aldehyde 1 (20 mmol) and malonic ester (26 mmol) in toluene (20 Dipropyl 2-(4-Methyl-2-vinylbenzylidene)malonate 2n. Follow-
mL) at room temperature. Then, the mixture was heated in an oil
ing the general procedure, 2n was synthesized from 1n.21b It is
bath (65 °C) for 8 h. After filtration, the mixture was extracted with
obtained as yellow oil (3.29 g, 52% yield); 1H NMR (400 MHz,
EtOAc (100 mL) and dried over Na2SO4. The solvent was evaporated
CDCl3): δ 8.02 (s, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.16−7.14 (m, 2H),
under reduced pressure. The residue was purified by flash column
6.86 (dd, J = 17.3, 11.0 Hz, 1H), 5.59 (dd, J = 17.3, 0.7 Hz, 1H), 5.36
chromatography on silica gel (petroleum ether/ethyl acetate, 25:1) to
afford product 2. (dd, J = 11.0, 0.7 Hz, 1H), 4.21 (t, J = 6.6 Hz, 2H), 4.09 (t, J = 6.5
Dienes 2a−2b and 2d−2g have been prepared in our previous Hz, 2H), 2.30 (s, 3H), 1.73 (h, J = 7.2 Hz, 2H), 1.56 (h, J = 7.1 Hz,
work15c,21a according to the general procedure. Dienes 2c and 2l−2aa 2H), 0.98 (t, J = 7.4 Hz, 3H), 0.78 (t, J = 7.4 Hz, 3H).
were newly prepared according to the general procedure. As synthetic Dipropyl 2-((3-Vinyl-[1,1′-biphenyl]-4-yl)methylene)malonate
intermediates of substrates 3, the yields and 1H NMR data of dienes 2o. Following the general procedure, 2o was synthesized from
2c and 2l−2aa were provided. 1o.15c It is obtained as yellow oil (6.05 g, 80% yield); 1H NMR (400
Step 2: under an argon atmosphere, CuCl (0.75 mmol, 15% cat.) MHz, CDCl3): δ 8.06 (s, 1H), 7.70 (s, 1H), 7.65−7.55 (m, 2H),
was added to a suspension of alkene 2 (5 mmol), PhINSO2Ar (7.5 7.51−7.40 (m, 4H), 7.37 (t, J = 7.3 Hz, 1H), 6.97 (dd, J = 17.3, 11.0
mmol) in MeCN (50 mL) at room temperature. The reaction mixture Hz, 1H), 5.70 (d, J = 17.3 Hz, 1H), 5.47 (d, J = 11.0 Hz, 1H), 4.23 (t,
was stirred overnight, diluted with ethyl acetate (300 mL), washed J = 6.6 Hz, 2H), 4.13 (t, J = 6.7 Hz, 2H), 1.73 (h, J = 7.2 Hz, 2H),
with brine (100 mL), dried over Na2SO4, and evaporated under 1.58 (h, J = 6.8 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H), 0.79 (t, J = 7.4 Hz,
reduced pressure. The residue was purified by flash column 3H).
chromatography on silica gel (petroleum ether/ethyl acetate, 5:1) Dipropyl 2-(4-Methoxy-2-vinylbenzylidene)malonate 2p. Follow-
to afford aziridine 3. Aziridines 3a, 3b, 3d, and 3f have been prepared ing the general procedure, 2p was synthesized from 1p.21c It is
in our previous work15c according to the general procedure. obtained as yellow oil (5.38 g, 81% yield); 1H NMR (400 MHz,
Dipropyl 2-(2-Vinylbenzylidene)malonate 2c. Following the CDCl3): δ 7.98 (s, 1H), 7.34 (d, J = 8.7 Hz, 1H), 6.98 (d, J = 2.6 Hz,
general procedure, 2c was synthesized from 1a.21b It is obtained as 1H), 6.92 (dd, J = 17.3, 11.0 Hz, 1H), 6.78 (dd, J = 8.7, 2.6 Hz, 1H),
yellow oil (4.95 g, 82% yield); 1H NMR (400 MHz, CDCl3): δ 8.06 5.62 (d, J = 17.3 Hz, 1H), 5.44 (d, J = 11.1 Hz, 1H), 4.20 (t, J = 6.6
(s, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.41−7.34 (m, 2H), 7.32−7.24 (m, Hz, 2H), 4.13 (t, J = 6.6 Hz, 2H), 3.83 (s, 3H), 1.72 (h, J = 7.2 Hz,
1H), 6.93 (dd, J = 17.3, 11.0 Hz, 1H), 5.67 (d, J = 17.3 Hz, 1H), 5.45 2H), 1.61 (h, J = 7.1 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H), 0.84 (t, J = 7.4
(d, J = 11.0 Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 4.11 (t, J = 6.4 Hz, 2H), Hz, 3H).

8988 DOI: 10.1021/acs.joc.9b00876

J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

Dipropyl 2-(4-Fluoro-2-vinylbenzylidene)malonate 2q. Following 3.77 (s, 3H), 1.74 (h, J = 7.1 Hz, 2H), 1.45 (h, J = 7.0 Hz, 2H), 0.99
the general procedure, 2q was synthesized from 1q.21b It is obtained (t, J = 7.4 Hz, 3H), 0.73 (t, J = 7.4 Hz, 3H).
as yellow oil (4.48 g, 70% yield); 1H NMR (400 MHz, CDCl3): δ Dipropyl 2-(2-Chloro-6-vinylbenzylidene)malonate 2z. Following
7.93 (s, 1H), 7.33 (dd, J = 8.6, 5.7 Hz, 1H), 7.17 (dd, J = 9.8, 2.5 Hz, the general procedure, 2z was synthesized from 1z.21h It is obtained as
1H), 6.92 (td, J = 8.4, 2.5 Hz, 1H), 6.85 (dd, J = 17.3, 11.0 Hz, 1H), yellow oil (4.57 g, 68% yield); 1H NMR (400 MHz, CDCl3): δ 7.78
5.65 (d, J = 17.3 Hz, 1H), 5.46 (d, J = 11.0 Hz, 1H), 4.21 (t, J = 6.6 (s, 1H), 7.38 (d, J = 7.5 Hz, 1H), 7.24 (d, J = 7.0 Hz, 1H), 7.20−7.14
Hz, 2H), 4.08 (t, J = 5.9 Hz, 2H), 1.72 (h, J = 7.2 Hz, 2H), 1.56 (h, J (m, 1H), 6.64 (dd, J = 17.3, 11.0 Hz, 1H), 5.62 (d, J = 17.3 Hz, 1H),
= 7.2 Hz, 2H), 0.97 (t, J = 6.7 Hz, 3H), 0.79 (t, J = 7.4 Hz, 3H). 5.25 (d, J = 11.0 Hz, 1H), 4.17 (t, J = 6.7 Hz, 2H), 3.85 (t, J = 6.6 Hz,
Dipropyl 2-(4-Chloro-2-vinylbenzylidene)malonate 2r. Following 2H), 1.68 (h, J = 7.2 Hz, 2H), 1.30 (h, J = 7.2 Hz, 2H), 0.92 (t, J = 7.4
the general procedure, 2r was synthesized from 1r.21d It is obtained as Hz, 3H), 0.64 (t, J = 7.4 Hz, 3H).
yellow oil (4.37 g, 65% yield); 1H NMR (400 MHz, CDCl3): δ 7.93 Dipropyl 2-((1-Vinylnaphthalen-2-yl)methylene)malonate 2aa.
(s, 1H), 7.47 (d, J = 2.1 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 7.21 (dd, J Following the general procedure, 2aa was synthesized from 1aa.21i It
= 8.4, 2.1 Hz, 1H), 6.83 (dd, J = 17.3, 11.0 Hz, 1H), 5.67 (dd, J = is obtained as yellow oil (4.29 g, 61% yield); 1H NMR (400 MHz,
17.3, 0.5 Hz, 1H), 5.48 (dd, J = 11.0, 0.5 Hz, 1H), 4.22 (t, J = 6.6 Hz, CDCl3): δ 8.18 (s, 1H), 8.14−8.08 (m, 1H), 7.85−7.79 (m, 1H), 7.72
2H), 4.10 (t, J = 6.6 Hz, 2H), 1.73 (h, J = 7.5 Hz, 2H), 1.57 (h, J = 7.4 (d, J = 8.7 Hz, 1H), 7.57−7.46 (m, 3H), 7.27 (dd, J = 17.6, 11.3 Hz,
Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H), 0.81 (t, J = 7.4 Hz, 3H). 1H), 5.92 (d, J = 11.3 Hz, 1H), 5.48 (d, J = 17.5 Hz, 1H), 4.23 (t, J =
Dipropyl 2-(4-Cyano-2-vinylbenzylidene)malonate 2s. Following 6.6 Hz, 2H), 4.14 (t, J = 6.7 Hz, 2H), 1.74 (h, J = 7.0 Hz, 2H), 1.57
the general procedure, 2s was synthesized from 1s.21e It is obtained as (h, J = 7.2 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H), 0.77 (t, J = 7.4 Hz, 3H).
yellow oil (5.23 g, 80% yield); 1H NMR (400 MHz, CDCl3): δ 7.90 Dipropyl 2-(2-(1-Tosylaziridin-2-yl)benzylidene)malonate 3c.
(s, 1H), 7.75 (d, J = 1.6 Hz, 1H), 7.49 (dd, J = 8.0, 1.6 Hz, 1H), 7.40 Following the general procedure, 3c was synthesized from 2c. It is
(d, J = 8.0 Hz, 1H), 6.81 (dd, J = 17.3, 11.0 Hz, 1H), 5.72 (d, J = 17.4 obtained as yellow oil (1.48 g, 63% yield); 1H NMR (400 MHz,
Hz, 1H), 5.53 (d, J = 10.8 Hz, 1H), 4.21 (t, J = 6.7 Hz, 2H), 4.04 (t, J CDCl3): δ 8.01 (s, 1H), 7.87 (d, J = 8.2 Hz, 2H), 7.33 (d, J = 8.0 Hz,
= 6.4 Hz, 2H), 1.72 (h, J = 7.2 Hz, 2H), 1.52 (h, J = 7.2 Hz, 2H), 0.96 2H), 7.28 (d, J = 7.1 Hz, 1H), 7.26−7.18 (m, 3H), 4.22 (t, J = 6.4 Hz,
(t, J = 7.2 Hz, 3H), 0.76 (t, J = 7.4 Hz, 3H). 2H), 4.04 (t, J = 6.6 Hz, 2H), 3.83 (dd, J = 7.0, 4.5 Hz, 1H), 2.98 (d, J
Dipropyl 2-(5-Methyl-2-vinylbenzylidene)malonate 2t. Following = 7.2 Hz, 1H), 2.42 (s, 3H), 2.29 (d, J = 4.4 Hz, 1H), 1.73 (h, J = 6.7
the general procedure, 2t was synthesized from 1t.21f It is obtained as Hz, 2H), 1.48 (h, J = 7.0 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H), 0.72 (t, J =
yellow oil (3.73 g, 59% yield); 1H NMR (400 MHz, CDCl3): δ 8.02 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.8, 163.6,
(s, 1H), 7.34−7.27 (m, 2H), 7.05 (d, J = 7.8 Hz, 1H), 6.91 (dd, J = 144.9, 139.9, 134.6, 134.1, 133.0, 130.0, 129.8, 129.8, 128.2, 128.1,
17.4, 11.0 Hz, 1H), 5.63 (dd, J = 17.3, 1.0 Hz, 1H), 5.42 (dd, J = 11.0, 127.8, 126.7, 67.4, 67.2, 38.8, 35.6, 21.9, 21.7, 21.6, 10.4, 10.2; HRMS
1.0 Hz, 1H), 4.22 (t, J = 6.6 Hz, 2H), 4.12 (t, J = 6.6 Hz, 2H), 2.36 (s, (ESI): calcd for C25H30NO6S (M + H)+, 472.1788; found, 472.1791;
3H), 1.74 (h, J = 7.1 Hz, 2H), 1.59 (h, J = 7.3 Hz, 2H), 0.99 (t, J = 7.4 IR (neat) ν: 540, 858, 980, 1075, 1206, 1260, 1330, 1730, 2966, 3364
Hz, 3H), 0.82 (t, J = 7.4 Hz, 3H). cm−1.
Dipropyl 2-((4-Vinyl-[1,1′-biphenyl]-3-yl)methylene)malonate Dibutyl 2-(2-(1-Tosylaziridin-2-yl)benzylidene)malonate 3e. Fol-
2u. Following the general procedure, 2u was synthesized from lowing the general procedure, 3e was synthesized from 2e. It is
1u.15c It is obtained as yellow oil (6.28 g, 83% yield); 1H NMR (400 obtained as yellow oil (1.32 g, 53% yield); 1H NMR (400 MHz,
MHz, CDCl3): δ 8.08 (s, 1H), 7.62−7.52 (m, 5H), 7.42 (t, J = 7.5 Hz, CDCl3): δ 8.03 (s, 1H), 7.90 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 7.9 Hz,
2H), 7.34 (t, J = 7.3 Hz, 1H), 6.92 (dd, J = 17.4, 11.0 Hz, 1H), 5.69 2H), 7.32−7.23 (m, 4H), 4.29 (t, J = 6.6 Hz, 2H), 4.10 (t, J = 6.5 Hz,
(d, J = 17.3 Hz, 1H), 5.43 (d, J = 11.0 Hz, 1H), 4.23 (t, J = 6.6 Hz, 2H), 3.86 (dd, J = 6.9, 4.6 Hz, 1H), 3.00 (d, J = 7.2 Hz, 1H), 2.44 (s,
2H), 4.05 (t, J = 6.6 Hz, 2H), 1.73 (h, J = 6.9 Hz, 2H), 1.47 (h, J = 7.2 3H), 2.30 (d, J = 4.4 Hz, 1H), 1.74−1.68 (m, 2H), 1.50−1.37 (m,
Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H), 0.68 (t, J = 7.4 Hz, 3H). 4H), 1.15 (h, J = 7.4 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H), 0.80 (t, J = 7.4
Dipropyl 2-(5-Fluoro-2-vinylbenzylidene)malonate 2v. Following Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.7, 163.5, 144.8,
the general procedure, 2v was synthesized from 1v.21b It is obtained as 139.8, 134.5, 133.9, 132.9, 129.9, 129.7, 128.1, 128.0, 127.7, 126.6,
yellow oil (5.31 g, 83% yield); 1H NMR (400 MHz, CDCl3): δ 7.93 65.6, 65.2, 38.7, 35.4, 30.4, 30.1, 21.5, 19.0, 18.7, 13.6, 13.4; HRMS
(s, 1H), 7.46 (dd, J = 8.3, 5.6 Hz, 1H), 7.10−7.02 (m, 2H), 6.83 (dd, (ESI): calcd for C27H34NO6S (M + H)+, 500.2101; found, 500.2102;
J = 17.3, 11.0 Hz, 1H), 5.58 (d, J = 17.3 Hz, 1H), 5.40 (d, J = 11.0 IR (neat) ν: 570, 719, 766, 915, 1069, 1162, 1206, 1259, 1330, 1389,
Hz, 1H), 4.22 (t, J = 6.6 Hz, 2H), 4.12 (t, J = 6.5 Hz, 2H), 1.73 (h, J = 1458, 1729, 2960 cm−1.
7.2 Hz, 2H), 1.59 (h, J = 7.3 Hz, 2H), 0.98 (t, J = 6.9 Hz, 3H), 0.82 Di-tert-butyl 2-(2-(1-Tosylaziridin-2-yl)benzylidene)malonate
(t, J = 7.4 Hz, 3H). 3g. Following the general procedure, 3g was synthesized from 2g.
Dipropyl 2-(5-Chloro-2-vinylbenzylidene)malonate 2w. Follow- It is obtained as yellow oil (0.70 g, 63% yield); 1H NMR (400 MHz,
ing the general procedure, 2w was synthesized from 1w.21b It is CDCl3): δ 7.91−7.86 (m, 2H), 7.80 (s, 1H), 7.34 (t, J = 7.6 Hz, 3H),
obtained as yellow oil (4.30 g, 64% yield); 1H NMR (400 MHz, 7.25−7.18 (m, 3H), 3.83 (dd, J = 6.6, 4.9 Hz, 1H), 2.97 (dd, J = 7.2,
CDCl3): δ 7.91 (s, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.33−7.29 (m, 2H), 1.5 Hz, 1H), 2.42 (s, 3H), 2.27 (d, J = 4.4 Hz, 1H), 1.54 (s, 9H), 1.35
6.82 (dd, J = 17.3, 11.0 Hz, 1H), 5.63 (dd, J = 17.3, 0.8 Hz, 1H), 5.43 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 164.8, 162.7, 144.7,
(dd, J = 11.0, 0.8 Hz, 1H), 4.22 (t, J = 6.6 Hz, 2H), 4.13 (t, J = 6.6 137.4, 134.5, 133.8, 133.2, 132.5, 129.7, 129.5, 128.0, 128.0, 127.8,
Hz, 2H), 1.73 (h, J = 7.3 Hz, 2H), 1.59 (h, J = 7.1 Hz, 2H), 0.98 (t, J 126.4, 82.2, 82.2, 38.8, 35.4, 27.9, 27.6, 21.5; HRMS (ESI): calcd for
= 7.4 Hz, 3H), 0.81 (t, J = 7.4 Hz, 3H). C27H34NO6S (M + H)+, 500.2101; found, 500.2103; IR (neat) ν: 459,
Dipropyl 2-(5-Nitro-2-vinylbenzylidene)malonate 2x. Following 566, 1071, 1162, 1205, 1259, 1327, 1388, 1626, 1726, 2961, 3418
the general procedure, 2x was synthesized from 1x.21b It is obtained as cm−1.
yellow oil (3.47 g, 64% yield); 1H NMR (400 MHz, chloroform-d): δ Dipropyl 2-(2-(1-((4-(tert-Butyl)phenyl)sulfonyl)aziridin-2-yl)-
8.25 (d, J = 2.4 Hz, 1H), 8.19 (dd, J = 8.6, 2.4 Hz, 1H), 7.92 (s, 1H), benzylidene)malonate 3h. Following the general procedure, 3h
7.66 (d, J = 8.6 Hz, 1H), 6.92 (dd, J = 17.3, 11.0 Hz, 1H), 5.84 (d, J = was synthesized from 2c. It is obtained as yellow oil (1.39 g, 54%
17.4 Hz, 1H), 5.64 (d, J = 11.2 Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 4.16 yield); 1H NMR (400 MHz, CDCl3): δ 8.04 (s, 1H), 7.97−7.91 (m,
(t, J = 6.7 Hz, 2H), 1.74 (h, J = 7.2 Hz, 2H), 1.64 (h, J = 7.2 Hz, 2H), 2H), 7.59−7.56 (m, 2H), 7.32−7.23 (m, 4H), 4.25 (td, J = 6.7, 1.2
0.99 (t, J = 7.4 Hz, 3H), 0.86 (t, J = 7.4 Hz, 3H). Hz, 2H), 4.06 (t, J = 6.6 Hz, 2H), 3.89 (dd, J = 7.1, 4.5 Hz, 1H), 3.00
Dipropyl 2-(2-Methoxy-6-vinylbenzylidene)malonate 2y. Follow- (d, J = 7.2 Hz, 1H), 2.31 (d, J = 4.4 Hz, 1H), 1.76 (q, J = 6.9 Hz, 2H),
ing the general procedure, 2y was synthesized from 1y.21g It is 1.50 (p, J = 7.0 Hz, 2H), 1.35 (s, 9H), 1.00 (t, J = 7.4 Hz, 3H), 0.75
obtained as yellow oil (5.25 g, 79% yield); 1H NMR (400 MHz, (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.8,
CDCl3): δ 7.89 (s, 1H), 7.28 (t, J = 8.0 Hz, 1H), 7.13 (d, J = 7.8 Hz, 163.5, 157.7, 139.9, 134.4, 134.0, 132.9, 129.9, 129.7, 128.1, 127.9,
1H), 6.79 (dd, J = 18.2, 10.1 Hz, 2H), 5.66 (d, J = 17.3 Hz, 1H), 5.34 127.7, 126.7, 126.2, 67.3, 67.1, 38.6, 35.6, 35.2, 30.9, 21.8, 21.5, 10.3,
(d, J = 11.0 Hz, 1H), 4.22 (t, J = 6.7 Hz, 2H), 3.97 (t, J = 6.6 Hz, 2H), 10.1; HRMS (ESI): calcd for C28H36NO6S (M + H)+, 514.2258;

8989 DOI: 10.1021/acs.joc.9b00876

J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

found, 514.2256; IR (neat) ν: 540, 621, 695, 765, 862, 951, 987, J = 3.4 Hz), 134.4, 129.7 (d, J = 8.7 Hz), 129.6, 129.6, 128.2, 124.2
1067, 1207, 1262, 1331, 1392, 1463, 1597, 1633, 1730, 2025, 2069, (d, J = 3.4 Hz), 120.7 (d, J = 13.0 Hz), 116.6 (d, J = 22.3 Hz), 67.2,
2369, 2967, 3376 cm−1. 67.0, 34.7 (d, J = 4.4 Hz), 34.0 (d, J = 4.0 Hz), 21.8, 21.6, 21.5, 10.3,
Dipropyl 2-(2-(1-(Phenylsulfonyl)aziridin-2-yl)benzylidene)- 10.1; HRMS (ESI): calcd for C25H29FNO6S (M + H)+, 490.1694;
malonate 3i. Following the general procedure, 3i was synthesized found, 490.1697; IR (neat) ν: 557, 663, 717, 816, 916, 1074, 1163,
from 2c. It is obtained as yellow oil (1.37 g, 60% yield); 1H NMR 1232, 1331, 1393, 1462, 1619, 1730, 2368, 2968, 3417 cm−1.
(400 MHz, CDCl3): δ 8.03 (dd, J = 5.7, 2.9 Hz, 3H), 7.65 (dd, J = Dipropyl 2-(4-Methyl-2-(1-tosylaziridin-2-yl)benzylidene)-
4.9, 3.7 Hz, 1H), 7.57 (t, J = 7.6 Hz, 2H), 7.32−7.21 (m, 4H), 4.25 malonate 3n. Following the general procedure, 3n was synthesized
(td, J = 6.7, 1.1 Hz, 2H), 4.06 (t, J = 6.6 Hz, 2H), 3.90 (dd, J = 7.1, from 2n. It is obtained as yellow oil (1.94 g, 80% yield); 1H NMR
4.5 Hz, 1H), 3.04 (d, J = 7.2 Hz, 1H), 2.33 (d, J = 4.5 Hz, 1H), 1.76 (400 MHz, CDCl3): δ 7.99 (s, 1H), 7.89 (d, J = 8.3 Hz, 2H), 7.35 (d,
(h, J = 7.3 Hz, 2H), 1.51 (h, J = 7.3 Hz, 2H), 1.00 (t, J = 7.4 Hz, 3H), J = 8.1 Hz, 2H), 7.21 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 5.8 Hz, 2H),
0.74 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.8, 4.29−4.16 (m, 2H), 4.08 (t, J = 6.6 Hz, 2H), 3.84 (dd, J = 7.1, 4.5 Hz,
163.6, 139.8, 137.7, 133.9, 133.8, 133.0, 130.0, 129.8, 129.2, 128.2, 1H), 2.97 (d, J = 7.2 Hz, 1H), 2.44 (s, 3H), 2.28 (d, J = 4.4 Hz, 1H),
128.0, 127.8, 126.6, 67.4, 67.2, 38.9, 35.6, 21.9, 21.6, 10.3, 10.1; 2.26 (s, 3H), 1.74 (h, J = 7.2 Hz, 2H), 1.55 (h, J = 7.1 Hz, 2H), 0.98
HRMS (ESI): calcd for C24H28NO6S (M + H)+, 458.1632; found, (t, J = 7.4 Hz, 3H), 0.78 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100
458.1633; IR (neat) ν: 544, 604, 692, 742, 857, 915, 980, 1069, 1164, MHz, CDCl3): δ 166.1, 163.7, 144.8, 140.5, 139.6, 134.5, 134.0,
1208, 1260, 1329, 1388, 1452, 1631, 1730, 2969, 3386 cm−1. 129.9, 129.8, 128.9, 128.7, 128.1, 127.8, 127.4, 67.2, 67.1, 38.7, 35.6,
Dipropyl 2-(2-(1-((4-Bromophenyl)sulfonyl)aziridin-2-yl)- 21.9, 21.6, 21.6, 21.3, 10.3, 10.1; HRMS (ESI): calcd for C26H32NO6S
benzylidene)malonate 3j. Following the general procedure, 3j was (M + H)+, 486.1945; found, 486.1949; IR (neat) ν: 541, 667, 718,
synthesized from 2c. It is obtained as yellow oil (1.23 g, 46% yield); 856, 941, 980, 1070, 1161, 1208, 1262, 1330, 1388, 1460, 1606, 1729,
1
H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 5.7 Hz, 3H), 7.58 (t, J = 2425, 2970, 3377 cm−1.
7.4 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.24−7.13 (m, 3H), 4.17 (t, J = Dipropyl 2-((3-(1-Tosylaziridin-2-yl)-[1,1′-biphenyl]-4-yl)-
6.5 Hz, 2H), 3.98 (t, J = 6.6 Hz, 2H), 3.82 (dd, J = 6.9, 4.5 Hz, 1H), methylene)malonate 3o. Following the general procedure, 3o was
2.96 (d, J = 7.2 Hz, 1H), 2.25 (d, J = 4.4 Hz, 1H), 1.68 (h, J = 7.2 Hz, synthesized from 2o. It is obtained as yellow oil (1.75 g, 64% yield);
2H), 1.43 (h, J = 7.1 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H), 0.67 (t, J = 7.4
1
H NMR (400 MHz, CDCl3): δ 8.05 (s, 1H), 7.93 (d, J = 8.3 Hz,
Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.7, 163.5, 139.8, 2H), 7.48−7.34 (m, 10H), 4.29−4.21 (m, 2H), 4.11 (t, J = 6.6 Hz,
137.7, 133.9, 133.8, 133.0, 130.0, 129.8, 129.2, 128.2, 128.0, 127.8, 2H), 3.89 (dd, J = 7.1, 4.5 Hz, 1H), 3.07 (d, J = 7.2 Hz, 1H), 2.44 (s,
126.6, 67.3, 67.1, 38.9, 35.6, 21.9, 21.5, 10.3, 10.1; HRMS (ESI): 3H), 2.38 (d, J = 4.4 Hz, 1H), 1.76 (h, J = 7.3 Hz, 2H), 1.56 (h, J =
calcd for C24H27BrNO6S (M + H)+, 536.0737; found, 536.0739; IR 7.2 Hz, 2H), 1.00 (t, J = 7.4 Hz, 3H), 0.77 (t, J = 7.4 Hz, 3H);
(neat) ν: 543, 604, 691, 743, 855, 915, 980, 1068, 1163, 1209, 1261, 13
C{1H} NMR (100 MHz, CDCl3): δ 166.0, 163.6, 144.9, 142.8,
1330, 1387, 1452, 1630, 1730, 2883, 2969, 3068, 3287 cm−1. 139.5, 139.1, 134.7, 134.6, 131.5, 129.8, 129.3, 128.8, 128.3, 128.1,
Dipropyl 2-(2-(1-((4-Nitrophenyl)sulfonyl)aziridin-2-yl)- 128.0, 126.9, 126.6, 125.5, 67.3, 67.2, 39.0, 35.3, 21.9, 21.6, 21.6, 10.3,
benzylidene)malonate 3k. Following the general procedure, 3k 10.1; HRMS (ESI): calcd for C31H34NO6S (M + H)+, 548.2101;
was synthesized from 2c. It is obtained as yellow oil (0.78 g, 31% found, 548.2103; IR (neat) ν: 561, 668, 698, 718, 763, 815, 869, 926,
yield); 1H NMR (400 MHz, CDCl3): δ 8.38 (d, J = 8.8 Hz, 2H), 8.21 980, 1066, 1160, 1211, 1330, 1393, 1459, 1602, 1629, 1729, 2882,
(d, J = 8.8 Hz, 2H), 8.01 (s, 1H), 7.33−7.26 (m, 3H), 7.19 (d, J = 7.6 2968 cm−1.
Hz, 1H), 4.23 (t, J = 6.7 Hz, 2H), 4.04 (t, J = 6.6 Hz, 2H), 3.99 (dd, J Dipropyl 2-(4-Methoxy-2-(1-tosylaziridin-2-yl)benzylidene)-
= 7.1, 4.6 Hz, 1H), 3.11 (d, J = 7.2 Hz, 1H), 2.44 (d, J = 4.6 Hz, 1H), malonate 3p. Following the general procedure, 3p was synthesized
1.76 (h, J = 7.3 Hz, 2H), 1.52 (h, J = 7.3 Hz, 2H), 0.98 (t, J = 7.4 Hz, from 2p. It is obtained as yellow oil (1.33 g, 53% yield); 1H NMR
3H), 0.74 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ (400 MHz, CDCl3): δ 7.95 (s, 1H), 7.91 (d, J = 8.1 Hz, 2H), 7.36 (d,
165.6, 163.5, 150.7, 143.6, 139.7, 133.2, 133.1, 130.2, 130.1, 129.4, J = 8.0 Hz, 2H), 7.31 (d, J = 8.3 Hz, 1H), 6.74 (d, J = 8.3 Hz, 2H),
128.6, 128.0, 126.3, 124.4, 67.4, 67.2, 39.6, 36.1, 21.9, 21.6, 10.3, 10.1; 4.23 (t, J = 6.1 Hz, 2H), 4.12 (t, J = 6.8 Hz, 2H), 3.85 (dd, J = 7.2, 4.4
HRMS (ESI): calcd for C24H27N2O8S (M + H)+, 503.1483; found, Hz, 1H), 3.71 (s, 3H), 3.04 (d, J = 7.2 Hz, 1H), 2.45 (s, 3H), 2.30 (d,
503.1486; IR (neat) ν: 463, 559, 625, 696, 747, 856, 914, 1067, 1092, J = 4.4 Hz, 1H), 1.74 (h, J = 7.1 Hz, 2H), 1.60 (h, J = 7.1 Hz, 2H),
1166, 1210, 1261, 1309, 1348, 1461, 1532, 1607, 1729, 2882, 2969, 0.99 (t, J = 7.4 Hz, 3H), 0.83 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100
3106, 3285 cm−1. MHz, CDCl3): δ 166.5, 163.9, 161.1, 144.9, 138.7, 136.5, 134.5,
Dipropyl 2-(3-Methyl-2-(1-tosylaziridin-2-yl)benzylidene)- 129.8, 129.6, 128.1, 127.3, 124.8, 114.0, 112.1, 67.2, 55.3, 38.9, 35.6,
malonate 3l. Following the general procedure, 3l was synthesized 21.9, 21.6, 10.3, 10.2; HRMS (ESI): calcd for C26H32NO7S (M + H)+,
from 2l. It is obtained as yellow oil (1.70 g, 70% yield); 1H NMR 502.1894; found, 502.1897; IR (neat) ν: 540, 616, 855, 985, 1088,
(400 MHz, CDCl3): δ 8.19 (s, 1H), 7.86 (d, J = 8.2 Hz, 2H), 7.34 (d, 1387, 1462, 1600, 1731, 2367, 2969, 3384 cm−1.
J = 8.0 Hz, 2H), 7.17−7.11 (m, 2H), 7.08−7.03 (m, 1H), 4.27−4.19 Dipropyl 2-(4-Fluoro-2-(1-tosylaziridin-2-yl)benzylidene)-
(m, 2H), 3.96 (dt, J = 10.1, 5.3 Hz, 3H), 2.86 (d, J = 7.2 Hz, 1H), malonate 3q. Following the general procedure, 3q was synthesized
2.44 (s, 3H), 2.42 (s, 3H), 2.20 (d, J = 4.5 Hz, 1H), 1.73 (h, J = 7.3 from 2q. It is obtained as yellow oil (1.52 g, 62% yield); 1H NMR
Hz, 2H), 1.45 (h, J = 7.3 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H), 0.72 (t, J = (400 MHz, CDCl3): δ 7.92 (s, 1H), 7.86 (d, J = 8.2 Hz, 2H), 7.34 (d,
7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.9, 163.8, J = 8.2 Hz, 2H), 7.29 (dd, J = 8.4, 5.5 Hz, 1H), 6.92 (ddd, J = 15.3,
144.8, 143.7, 138.4, 134.7, 133.9, 131.7, 131.4, 129.7, 128.2, 128.2, 8.8, 2.6 Hz, 2H), 3.81 (dd, J = 7.1, 4.3 Hz, 1H), 2.99 (d, J = 7.2 Hz,
128.0, 126.3, 67.1, 66.9, 38.5, 35.1, 21.9, 21.6, 21.5, 20.0, 10.3, 10.1; 1H), 2.42 (s, 3H), 2.25 (d, J = 4.3 Hz, 1H), 1.72 (h, J = 7.2 Hz, 2H),
HRMS (ESI): calcd for C26H32NO6S (M + H)+, 486.1945; found, 1.52 (h, J = 7.2 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H), 0.76 (t, J = 7.4 Hz,
486.1948; IR (neat) ν: 546, 660, 719, 856, 916, 980, 1069, 1161, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.6, 163.4 (d, J = 251.4
1220, 1329, 1389, 1463, 1596, 1631, 1730, 2969, 3402 cm−1. Hz), 163.3, 145.0, 138.4, 137.1 (d, J = 8.1 Hz), 134.3, 129.9 (d, J =
Dipropyl 2-(3-Fluoro-2-(1-tosylaziridin-2-yl)benzylidene)- 8.7 Hz), 129.8, 129.7, 128.8 (d, J = 3.1 Hz), 127.9, 115.2 (d, J = 21.9
malonate 3m. Following the general procedure, 3m was synthesized Hz), 113.8 (d, J = 23.8 Hz), 67.3, 67.1, 38.0, 35.7, 21.8, 21.5, 21.5,
from 2m. It is obtained as yellow oil (1.71 g, 70% yield); 1H NMR 10.2, 10.0; HRMS (ESI): calcd for C25H29FNO6S (M + H)+,
(400 MHz, CDCl3): δ 8.17 (s, 1H), 7.86 (d, J = 8.1 Hz, 2H), 7.32 (d, 490.1694; found, 490.1697; IR (neat) ν: 540, 613, 668, 719, 853, 886,
J = 8.0 Hz, 2H), 7.24−7.16 (m, 1H), 7.00 (d, J = 7.8 Hz, 2H), 4.21 (t, 946, 1087, 1162, 1214, 1332, 1389, 1461, 1492, 1604, 1730, 2434,
J = 6.6 Hz, 2H), 3.98 (t, J = 6.5 Hz, 2H), 3.94−3.85 (m, 1H), 2.90 (d, 2970, 3413 cm−1.
J = 7.2 Hz, 1H), 2.47 (d, J = 4.1 Hz, 1H), 2.42 (s, 3H), 1.73 (h, J = Dipropyl 2-(4-Chloro-2-(1-tosylaziridin-2-yl)benzylidene)-
7.1 Hz, 2H), 1.45 (h, J = 7.0 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H), 0.73 malonate 3r. Following the general procedure, 3r was synthesized
(t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.4, from 2r. It is obtained as yellow oil (1.77 g, 70% yield); 1H NMR
163.4, 161.5 (d, J = 249.9 Hz), 144.7, 141.1 (d, J = 2.9 Hz), 136.0 (d, (400 MHz, CDCl3): δ 7.91 (s, 1H), 7.86 (d, J = 8.0 Hz, 2H), 7.34 (d,

8990 DOI: 10.1021/acs.joc.9b00876

J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

J = 8.0 Hz, 2H), 7.20 (q, J = 8.4 Hz, 3H), 4.21 (t, J = 6.6 Hz, 2H), 490.1694; found, 490.1696; IR (neat) ν: 542, 665, 720, 859, 983,
4.04 (t, J = 6.6 Hz, 2H), 3.79 (dd, J = 7.0, 4.4 Hz, 1H), 2.96 (d, J = 1070, 1161, 1215, 1331, 1386, 1461, 1494, 1599, 1730, 2427, 2971,
7.2 Hz, 1H), 2.41 (s, 3H), 2.25 (d, J = 4.3 Hz, 1H), 1.71 (h, J = 7.0 3380 cm−1.
Hz, 2H), 1.51 (h, J = 7.0 Hz, 2H), 0.95 (t, J = 7.4 Hz, 3H), 0.75 (t, J = Dipropyl 2-(5-Chloro-2-(1-tosylaziridin-2-yl)benzylidene)-
7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.4, 163.2, malonate 3w. Following the general procedure, 3w was synthesized
144.9, 138.3, 136.0, 134.2, 131.2, 130.1, 129.7, 129.0, 128.2, 127.9, from 2w. It is obtained as yellow oil (1.82 g, 72% yield); 1H NMR
126.8, 67.3, 67.1, 37.8, 35.6, 21.7, 21.5, 21.4, 10.2, 10.0; HRMS (ESI): (400 MHz, CDCl3): δ 7.94 (s, 1H), 7.88 (d, J = 8.1 Hz, 2H), 7.36 (d,
calcd for C25H29ClNO6S (M + H)+, 506.1399; found, 506.1402; IR J = 7.9 Hz, 2H), 7.30 (d, J = 3.3 Hz, 1H), 7.25 (d, J = 8.4 Hz, 1H),
(neat) ν: 539, 667, 718, 861, 926, 982, 1070, 1162, 1208, 1260, 1332, 7.18 (d, J = 8.4 Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 4.11 (t, J = 6.6 Hz,
1391, 1463, 1596, 1633, 1729, 2425, 2970, 3373 cm−1. 2H), 3.80 (dd, J = 6.7, 4.6 Hz, 1H), 2.99 (d, J = 7.1 Hz, 1H), 2.44 (s,
Dipropyl 2-(4-Cyano-2-(1-tosylaziridin-2-yl)benzylidene)- 3H), 2.29 (d, J = 4.3 Hz, 1H), 1.76 (h, J = 7.0 Hz, 2H), 1.57 (h, J =
malonate 3s. Following the general procedure, 3s was synthesized 7.0 Hz, 2H), 1.00 (t, J = 7.4 Hz, 3H), 0.79 (t, J = 7.4 Hz, 3H);
from 2s. It is obtained as yellow oil (1.29 g, 52% yield); 1H NMR 13
C{1H} NMR (100 MHz, CDCl3): δ 165.1, 163.0, 144.8, 138.1,
(400 MHz, CDCl3): δ 7.94 (s, 1H), 7.90 (d, J = 8.3 Hz, 2H), 7.53 (dt, 134.4, 134.3, 133.9, 132.5, 130.7, 129.7, 128.0, 127.9, 127.5, 67.3,
J = 3.7, 2.2 Hz, 2H), 7.39 (d, J = 8.2 Hz, 3H), 4.26 (td, J = 6.7, 1.4 Hz, 67.2, 38.0, 35.4, 21.7, 21.5, 10.2, 10.0; HRMS (ESI): calcd for
2H), 4.05 (td, J = 6.7, 1.4 Hz, 2H), 3.83 (dd, J = 7.1, 4.3 Hz, 1H), C25H29ClNO6S (M + H)+, 506.1399; found, 506.1403; IR (neat) ν:
3.02 (d, J = 7.2 Hz, 1H), 2.47 (s, 3H), 2.25 (d, J = 4.3 Hz, 1H), 1.75 542, 616, 669, 720, 854, 983, 1070, 1162, 1207, 1262, 1331, 1389,
(h, J = 7.1 Hz, 2H), 1.51 (h, J = 7.1 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H), 1461, 1598, 1633, 1730, 2435, 2970, 3382 cm−1.
0.76 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 164.9, Dipropyl 2-(5-Nitro-2-(1-tosylaziridin-2-yl)benzylidene)-
163.0, 145.3, 137.8, 137.7, 135.7, 134.2, 132.1, 131.6, 130.3, 130.0, malonate 3x. Following the general procedure, 3x was synthesized
128.6, 128.1, 117.8, 113.6, 67.7, 67.5, 37.6, 35.9, 21.8, 21.7, 21.6, 10.3, from 2x. It is obtained as yellow oil (1.57 g, 61% yield); 1H NMR
10.1; HRMS (ESI): calcd for C26H29N2O6S (M + H)+, 497.1741; (400 MHz, CDCl3): δ 8.20 (d, J = 2.3 Hz, 1H), 8.12 (dd, J = 8.6, 2.3
found, 497.1742; IR (neat) ν: 538, 617, 718, 862, 951, 987, 1067, Hz, 1H), 7.94 (s, 1H), 7.89 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.6 Hz,
1262, 1332, 1386, 1653, 1727, 2025, 2070, 2442, 3378 cm−1. 1H), 7.38 (d, J = 7.9 Hz, 2H), 4.27 (t, J = 6.3 Hz, 2H), 4.14 (t, J = 6.7
Dipropyl 2-(5-Methyl-2-(1-tosylaziridin-2-yl)benzylidene)- Hz, 2H), 3.88 (dd, J = 7.2, 4.3 Hz, 1H), 3.07 (d, J = 7.2 Hz, 1H), 2.46
malonate 3t. Following the general procedure, 3t was synthesized (s, 3H), 2.30 (d, J = 4.2 Hz, 1H), 1.77 (h, J = 7.4 Hz, 2H), 1.67−1.58
from 2t. It is obtained as yellow oil (1.29 g, 53% yield); 1H NMR (m, 2H), 1.00 (t, J = 7.4 Hz, 3H), 0.85 (t, J = 7.4 Hz, 3H); 13C{1H}
(400 MHz, CDCl3): δ 8.00 (s, 1H), 7.88 (d, J = 8.3 Hz, 2H), 7.34 (d, NMR (100 MHz, CDCl3): δ 164.9, 163.0, 147.5, 145.4, 141.1, 136.9,
J = 8.1 Hz, 2H), 7.09 (q, J = 4.1 Hz, 3H), 4.24 (t, J = 6.5 Hz, 2H), 134.3, 134.1, 132.2, 130.0, 128.1, 128.0, 124.5, 122.9, 67.8, 67.7, 38.0,
4.06 (t, J = 6.6 Hz, 2H), 3.81 (dd, J = 7.1, 4.5 Hz, 1H), 2.97 (d, J = 35.9, 21.9, 21.7, 21.6, 10.3, 10.2; HRMS (ESI): calcd for
7.2 Hz, 1H), 2.43 (s, 3H), 2.28 (d, J = 4.4 Hz, 1H), 2.26 (s, 3H), 1.75 C25H29N2O8S (M + H)+, 517.1639; found, 517.1642; IR (neat) ν:
(h, J = 7.2 Hz, 2H), 1.52 (h, J = 7.2 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H), 538, 617, 720, 862, 953, 988, 1068, 1207, 1262, 1349, 1385, 1462,
0.75 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.9, 1528, 1639, 1727, 2070, 2371, 3376 cm−1.
163.6, 144.7, 140.0, 138.0, 134.6, 132.8, 131.1, 130.7, 129.8, 129.4, Dipropyl 2-(2-Methoxy-6-(1-tosylaziridin-2-yl)benzylidene)-
128.3, 128.0, 126.6, 67.3, 67.1, 38.7, 35.4, 21.9, 21.6, 21.6, 20.9, 10.3, malonate 3y. Following the general procedure, 3y was synthesized
10.2; HRMS (ESI): calcd for C26H32NO6S (M + H)+, 486.1945; from 2y. It is obtained as yellow oil (1.50 g, 60% yield); 1H NMR
found, 486.1946; IR (neat) ν: 547, 665, 720, 820, 911, 982, 1069, (400 MHz, CDCl3): δ 7.86 (d, J = 8.2 Hz, 2H), 7.81 (s, 1H), 7.32 (d,
1161, 1222, 1329, 1388, 1460, 1496, 1600, 1631, 1730, 2883, 2969, J = 8.2 Hz, 2H), 7.19 (t, J = 8.1 Hz, 1H), 6.78 (dd, J = 14.1, 8.0 Hz,
3421 cm−1. 2H), 4.22 (t, J = 6.7 Hz, 2H), 3.95 (t, J = 6.6 Hz, 2H), 3.75 (dd, J =
Dipropyl 2-((4-(1-Tosylaziridin-2-yl)-[1,1′-biphenyl]-3-yl)- 7.1, 4.5 Hz, 1H), 3.72 (s, 3H), 2.93 (d, J = 7.2 Hz, 1H), 2.42 (s, 3H),
methylene)malonate 3u. Following the general procedure, 3u was 2.24 (d, J = 4.4 Hz, 1H), 1.75 (q, J = 7.1 Hz, 2H), 1.42 (dt, J = 14.2,
synthesized from 2u. It is obtained as yellow oil (1.81 g, 66% yield); 7.1 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H), 0.69 (t, J = 7.4 Hz, 3H);
1
H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.91 (d, J = 8.3 Hz, 13
C{1H} NMR (100 MHz, CDCl3): δ 164.9, 164.1, 156.2, 144.7,
2H), 7.55 (d, J = 1.6 Hz, 1H), 7.50 (dd, J = 11.7, 4.5 Hz, 3H), 7.41 138.6, 134.8, 134.5, 130.9, 130.3, 129.7, 128.0, 122.5, 118.2, 110.2,
(dd, J = 10.1, 4.8 Hz, 2H), 7.38−7.32 (m, 3H), 7.29 (d, J = 8.1 Hz, 67.1, 66.5, 55.3, 38.9, 35.7, 21.8, 21.6, 21.5, 10.3, 10.1; HRMS (ESI):
1H), 4.26 (t, J = 6.5 Hz, 2H), 4.04 (t, J = 6.6 Hz, 2H), 3.89 (dd, J = calcd for C26H32NO7S (M + H)+, 502.1894; found, 502.1895; IR
7.1, 4.4 Hz, 1H), 3.04 (d, J = 7.2 Hz, 1H), 2.44 (s, 3H), 2.35 (d, J = (neat) ν: 557, 669, 722, 791, 873, 937, 985, 1072, 1161, 1211, 1267,
4.4 Hz, 1H), 1.77 (h, J = 7.2 Hz, 2H), 1.44 (h, J = 7.2 Hz, 2H), 1.00 1329, 1376, 1467, 1597, 1631, 1727, 2883, 2968 cm−1.
(t, J = 7.4 Hz, 3H), 0.66 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 Dipropyl 2-(2-Chloro-6-(1-tosylaziridin-2-yl)benzylidene)-
MHz, CDCl3): δ 165.8, 163.5, 144.8, 141.1, 139.9, 139.5, 134.5, malonate 3z. Following the general procedure, 3z was synthesized
133.4, 132.8, 130.1, 129.8, 128.8, 128.4, 128.0, 127.8, 127.1, 126.8, from 2z. It is obtained as yellow oil (1.87 g, 74% yield); 1H NMR
126.5, 67.3, 67.2, 38.6, 35.5, 21.9, 21.6, 21.5, 10.3, 10.0; HRMS (ESI): (400 MHz, CDCl3): δ 7.83 (d, J = 8.2 Hz, 2H), 7.79 (s, 1H), 7.31 (d,
calcd for C31H34NO6S (M + H)+, 548.2101; found, 548.2104; IR J = 8.1 Hz, 2H), 7.29−7.26 (m, 1H), 7.19−7.09 (m, 2H), 4.24 (t, J =
(neat) ν: 551, 665, 718, 764, 815, 846, 915, 979, 1069, 1161, 1207, 6.6 Hz, 2H), 3.91 (t, J = 6.5 Hz, 2H), 3.73 (dd, J = 7.0, 4.4 Hz, 1H),
1249, 1329, 1391, 1459, 1599, 1631, 1730, 2882, 2968, 3033, 3444 2.87 (d, J = 7.2 Hz, 1H), 2.40 (s, 3H), 2.21 (d, J = 4.3 Hz, 1H), 1.75
cm−1. (p, J = 7.1 Hz, 2H), 1.33 (h, J = 7.1 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H),
Dipropyl 2-(5-Fluoro-2-(1-tosylaziridin-2-yl)benzylidene)- 0.67 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 163.8,
malonate 3v. Following the general procedure, 3v was synthesized 162.9, 144.7, 139.9, 134.9, 134.1, 132.7, 132.5, 132.1, 129.6, 129.5,
from 2v. It is obtained as yellow oil (1.32 g, 54% yield); 1H NMR 128.6, 127.9, 124.2, 67.2, 66.7, 38.5, 35.9, 21.6, 21.4, 21.3, 10.1, 9.9;
(400 MHz, CDCl3): δ 7.93 (s, 1H), 7.85 (d, J = 8.2 Hz, 2H), 7.33 (d, HRMS (ESI): calcd for C25H29ClNO6S (M + H)+, 506.1399; found,
J = 8.2 Hz, 2H), 7.19 (dd, J = 8.6, 5.6 Hz, 1H), 7.00 (dd, J = 9.2, 2.5 506.1402; IR (neat) ν: 541, 616, 721, 855, 983, 1077, 1260, 1333,
Hz, 1H), 6.94 (td, J = 8.3, 2.6 Hz, 1H), 4.22 (t, J = 6.6 Hz, 2H), 4.07 1387, 1452, 1599, 1730, 2369, 2970, 3380 cm−1.
(t, J = 6.6 Hz, 2H), 3.78 (dd, J = 7.0, 4.4 Hz, 1H), 2.95 (d, J = 7.1 Hz, Dipropyl 2-((1-(1-Tosylaziridin-2-yl)naphthalen-2-yl)methylene)-
1H), 2.41 (s, 3H), 2.26 (d, J = 4.4 Hz, 1H), 1.73 (h, J = 7.2 Hz, 2H), malonate 3aa. Following the general procedure, 3aa was synthesized
1.53 (h, J = 7.2 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H), 0.76 (t, J = 7.4 Hz, from 2aa. It is obtained as yellow oil (1.48 g, 57% yield); 1H NMR
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.2, 163.1, 161.9 (d, J = (400 MHz, CDCl3): δ 8.45 (d, J = 9.3 Hz, 2H), 7.92 (d, J = 8.2 Hz,
247.3 Hz), 144.9, 138.2, 134.7 (d, J = 8.2 Hz), 134.4, 130.6, 129.9 (d, 2H), 7.81 (d, J = 7.5 Hz, 1H), 7.75 (d, J = 8.6 Hz, 1H), 7.58−7.50
J = 3.1 Hz), 129.7, 128.7 (d, J = 8.5 Hz), 127.9, 116.7 (d, J = 21.4 (m, 2H), 7.35 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 8.5 Hz, 1H), 4.37 (dd,
Hz), 114.7 (d, J = 23.4 Hz), 67.4, 67.2, 38.1, 35.4, 21.7, 21.5, 21.5, J = 6.7, 4.8 Hz, 1H), 4.29−4.22 (m, 2H), 4.00 (tt, J = 6.5, 3.5 Hz,
10.2, 10.0; HRMS (ESI): calcd for C25H29FNO6S (M + H)+, 2H), 3.07 (d, J = 7.2 Hz, 1H), 2.44 (s, 3H), 2.32 (d, J = 4.5 Hz, 1H),

8991 DOI: 10.1021/acs.joc.9b00876

J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

1.77 (h, J = 7.1 Hz, 2H), 1.44 (h, J = 7.3 Hz, 2H), 1.00 (t, J = 7.4 Hz, C25H30NO7S (M + H)+, 488.1737; found, 488.1736; IR (neat) ν: 541,
3H), 0.67 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 617, 662, 755, 853, 990, 1102, 1261, 1340, 1379, 1462, 1604, 1726,
165.8, 163.9, 144.9, 143.4, 134.5, 133.5, 131.6, 131.4, 129.7, 129.5, 2447, 2924, 2982, 3266 cm−1.
128.8, 128.8, 128.4, 128.3, 127.1, 126.9, 125.3, 124.5, 67.2, 66.9, 37.9, rel-Dibutyl 2-((1R,2S)-2-(4-Methylphenylsulfonamido)-3-oxo-
35.5, 21.8, 21.6, 21.5, 10.3, 10.0; HRMS (ESI): calcd for C29H32NO6S 2,3-dihydro-1H-inden-1-yl)malonate 4e. It is obtained as yellow
(M + H)+, 522.1945; found, 522.1946; IR (neat) ν: 552, 719, 820, oil (64 mg, 62% yield, dr > 20:1); 1H NMR (400 MHz, CDCl3): δ
861, 913, 978, 1070, 1161, 1214, 1329, 1392, 1462, 1628, 1730, 2883, 7.84 (d, J = 7.9 Hz, 2H), 7.71−7.55 (m, 3H), 7.42−7.28 (m, 3H),
2969, 3376 cm−1. 5.38 (d, J = 5.3 Hz, 1H), 4.64 (s, 1H), 4.35 (t, J = 5.5 Hz, 1H), 4.31−
General Procedure for the Preparation of 2-Aminoinda- 4.25 (m, 1H), 4.24−4.16 (m, 1H), 3.93−3.89 (m, 3H), 2.42 (s, 3H),
nones 4. In open air, In(OTf)3 (0.04 mmol, 20% cat.) was added to 1.71−1.62 (m, 2H), 1.43−1.36 (m, 2H), 1.36−1.29 (m, 2H), 1.16−
a solution of aziridine 3 (0.2 mmol) in DMSO (4 mL) at room 1.10 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H), 0.78 (t, J = 7.3 Hz, 3H);
temperature. The reaction mixture was heated in an oil bath (90 °C) 13
C{1H} NMR (100 MHz, CDCl3): δ 199.5, 169.2, 167.8, 150.3,
for 2 h. Then, the reaction mixture was cooled to room temperature 143.9, 136.0, 136.0, 133.9, 129.7, 128.6, 127.5, 126.7, 124.0, 65.8,
and poured into water (20 mL) and extracted with ethyl acetate (5 × 65.4, 62.4, 51.5, 46.1, 30.4, 30.2, 21.6, 19.0, 18.9, 13.6, 13.5; HRMS
10 mL). The combined organic extract was washed with brine (20 (ESI): calcd for C27H34NO7S (M + H)+, 516.2050; found, 516.2053;
mL), dried over Na2SO4, and evaporated under reduced pressure. The IR (neat) ν: 540, 617, 855, 993, 1113, 1385, 1462, 1603, 1734, 2449,
residue was purified by flash column chromatography on silica gel 2961, 3373 cm−1.
(petroleum ether/ethyl acetate/acetic acid, 100:20:0.5) to afford rel-Dibenzyl 2-((1R,2S)-2-(4-Methylphenylsulfonamido)-3-oxo-
product 4. 2,3-dihydro-1H-inden-1-yl)malonate 4f. It is obtained as yellow oil
rel-Dimethyl 2-((1R,2S)-2-(4-Methylphenylsulfonamido)-3-oxo- (76 mg, 65% yield, dr > 20:1); 1H NMR (400 MHz, CDCl3): δ 7.76
2,3-dihydro-1H-inden-1-yl)malonate 4a. It is obtained as yellow (d, J = 8.2 Hz, 2H), 7.59 (d, J = 7.6 Hz, 1H), 7.52−7.44 (m, 2H),
oil (64 mg, 74% yield, dr = 6:1); 1H NMR (400 MHz, CDCl3): δ 7.85 7.41−7.27 (m, 7H), 7.23 (dd, J = 11.9, 4.2 Hz, 4H), 7.02 (d, J = 7.1
(d, J = 8.2 Hz, 2.32H), 7.70−7.58 (m, 3.48H), 7.43−7.31 (m, 3.48H), Hz, 2H), 5.32−5.20 (m, 3H), 4.94 (s, 2H), 4.76 (d, J = 2.4 Hz, 1H),
5.54 (d, J = 6.5 Hz, 1H), 5.29 (d, J = 5.2 Hz, 1H), 4.68 (d, J = 2.5 Hz, 4.31 (t, J = 5.5 Hz, 1H), 3.96 (dd, J = 5.6, 2.2 Hz, 1H), 2.40 (s, 3H);
1H), 4.46 (dd, J = 8.0, 2.9 Hz, 0.16H), 4.33 (t, J = 5.5 Hz, 1H), 4.26− 13
C{1H} NMR (100 MHz, CDCl3): δ 199.2, 168.8, 167.4, 149.9,
4.21 (m, 0.32H), 3.95 (dd, J = 5.5, 2.3 Hz, 1H), 3.84 (s, 3H), 3.71 (s,
143.9, 136.0, 135.8, 135.0, 134.6, 133.8, 129.8, 128.6, 128.6, 128.5,
0.48H), 3.57 (s, 3H), 3.48 (s, 0.48H), 2.42 (d, J = 3.9 Hz, 3.48H);
128.5, 128.4, 128.4, 128.4, 127.5, 126.6, 124.0, 67.8, 67.4, 62.3, 51.4,
13
C{1H} NMR (100 MHz, CDCl3): δ 199.4, 169.4, 168.2, 150.1,
46.2, 21.6; HRMS (ESI): calcd for C33H30NO7S (M + H)+, 584.1737;
144.1, 136.1, 135.8, 133.8, 129.8, 128.7, 127.5, 126.4, 124.1, 62.3,
found, 584.1740; IR (neat) ν: 554, 1092, 1161, 1261, 1340, 1386,
52.9, 52.6, 51.1, 46.1, 21.6; HRMS (ESI): calcd for C21H22NO7S (M
1458, 1605, 1729, 2925, 3443 cm−1.
+ H)+, 432.1111; found, 432.1113; IR (neat) ν: 556, 662, 814, 1025,
Dipropyl 2-(2-(4-(tert-Butyl)phenylsulfonamido)-3-oxo-2,3-dihy-
1091, 1159, 1337, 1438, 1603, 1729, 2924, 2955, 3281 cm−1. dro-1H-inden-1-yl)malonate 4h. It is obtained as yellow oil (67 mg,
rel-Diethyl 2-((1R,2S)-2-(4-Methylphenylsulfonamido)-3-oxo-2,3-
dihydro-1H-inden-1-yl)malonate 4b. It is obtained as yellow oil (66 63% yield, dr > 20:1); 1H NMR (400 MHz, CDCl3): δ 7.89 (d, J =
mg, 72% yield, dr = 9:1); 1H NMR (400 MHz, CDCl3): δ 7.85 (dd, J 8.6 Hz, 2H), 7.71−7.59 (m, 3H), 7.54 (d, J = 8.6 Hz, 2H), 7.39 (t, J =
= 8.4, 1.9 Hz, 2H), 7.67−7.59 (m, 3H), 7.39 (dd, J = 7.7, 6.9 Hz, 1H), 7.3 Hz, 1H), 5.35 (d, J = 5.0 Hz, 1H), 4.70 (d, J = 2.3 Hz, 1H), 4.35
7.33 (d, J = 8.0 Hz, 2H), 5.29 (d, J = 5.3 Hz, 1H), 4.64 (d, J = 2.4 Hz, (t, J = 5.3 Hz, 1H), 4.28−4.14 (m, 2H), 4.01−3.94 (m, 1H), 3.90−
1H), 4.41−4.22 (m, 3H), 4.04−3.94 (m, 3H), 2.43 (s, 3H), 1.33 (t, J 3.79 (m, 2H), 1.73 (dt, J = 14.2, 7.1 Hz, 2H), 1.39 (dq, J = 9.6, 3.4,
= 7.1 Hz, 3H), 0.99 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, 2.5 Hz, 2H), 1.34 (s, 9H), 0.98 (t, J = 7.4 Hz, 3H), 0.73 (t, J = 7.4 Hz,
CDCl3): δ 199.5, 169.1, 167.8, 150.3, 144.0, 136.0, 133.9, 129.8, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 199.5, 169.2, 167.9,
128.6, 127.5, 127.4, 126.8, 124.0, 62.4, 61.9, 61.6, 51.5, 46.1, 21.6, 156.9, 150.4, 136.0, 135.8, 133.9, 128.6, 127.3, 126.7, 126.2, 124.0,
14.0, 13.8; HRMS (ESI): calcd for C23H26NO7S (M + H)+, 460.1424; 67.6, 67.2, 62.4, 51.6, 46.2, 35.2, 31.0, 21.8, 21.6, 10.4, 10.2; HRMS
found, 460.1426; IR (neat) ν: 540, 617, 856, 991, 1115, 1381, 1604, (ESI): calcd for C28H36NO7S (M + H)+, 530.2207; found, 530.2209;
1727, 2458, 2924, 3365 cm−1. IR (neat) ν: 538, 620, 760, 862, 988, 1068, 1263, 1387, 1655, 1723,
rel-Dipropyl 2-((1R,2S)-2-(4-Methylphenylsulfonamido)-3-oxo- 2025, 2070, 2441, 3376 cm−1.
2,3-dihydro-1H-inden-1-yl)malonate 4c. It is obtained as yellow rel-Dipropyl 2-((1R,2S)-3-oxo-2-(Phenylsulfonamido)-2,3-dihy-
oil (68 mg, 70% yield, dr > 20:1); 1H NMR (400 MHz, CDCl3): δ dro-1H-inden-1-yl)malonate 4i. It is obtained as white solid (62
7.85 (d, J = 8.2 Hz, 2H), 7.63 (dd, J = 13.9, 7.7 Hz, 3H), 7.39 (t, J = mg, 66% yield, dr > 20:1); mp 90−93 °C; 1H NMR (400 MHz,
7.3 Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H), 5.34 (d, J = 5.4 Hz, 1H), 4.66 CDCl3): δ 7.97 (d, J = 7.6 Hz, 2H), 7.58 (ddd, J = 28.4, 13.5, 7.6 Hz,
(d, J = 2.3 Hz, 1H), 4.36 (t, J = 5.6 Hz, 1H), 4.27−4.22 (m, 1H), 4.16 6H), 7.37 (t, J = 7.2 Hz, 1H), 5.47 (s, 1H), 4.62 (s, 1H), 4.41 (t, J =
(dd, J = 6.6, 4.0 Hz, 1H), 3.96−3.92 (m, 1H), 3.88 (t, J = 6.6 Hz, 5.7 Hz, 1H), 4.23 (dd, J = 11.9, 5.3 Hz, 1H), 4.16 (dd, J = 11.9, 5.3
2H), 2.42 (s, 4H), 1.72 (h, J = 7.2 Hz, 2H), 1.45−1.37 (m, 2H), 0.97 Hz, 1H), 3.93 (d, J = 5.0 Hz, 1H), 3.88 (t, J = 6.6 Hz, 2H), 1.71 (h, J
(t, J = 7.4 Hz, 3H), 0.75 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 = 7.0 Hz, 2H), 1.44−1.36 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H), 0.74 (t, J
MHz, CDCl3): δ 199.5, 169.2, 167.9, 150.3, 144.0, 136.0, 133.9, = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 199.4, 169.1,
129.8, 128.6, 127.5, 126.7, 124.0, 67.6, 67.2, 62.4, 51.5, 46.1, 21.8, 167.8, 150.2, 139.2, 136.0, 133.9, 133.1, 129.1, 128.6, 127.4, 126.6,
21.6, 10.4, 10.2; HRMS (ESI): calcd for C25H30NO7S (M + H)+, 124.0, 67.5, 67.2, 62.4, 51.4, 46.0, 21.8, 21.5, 10.3, 10.2; HRMS (ESI):
488.1737; found, 488.1739; IR (neat) ν: 557, 664, 1059, 1094, 1161, calcd for C24H28NO7S (M + H)+, 474.1581; found, 474.1582; IR
1338, 1395, 1464, 1604, 1731, 2969, 3444 cm−1. (neat) ν: 551, 616, 667, 752, 815, 930, 1057, 1092, 1159, 1327, 1394,
rel-Diisopropyl 2-((1R,2S)-2-(4-Methylphenylsulfonamido)-3- 1461, 1626, 1732, 2372, 2928, 2965, 3447 cm−1.
oxo-2,3-dihydro-1H-inden-1-yl)malonate 4d. It is obtained as rel-Dipropyl 2-((1R,2S)-2-(4-Bromophenylsulfonamido)-3-oxo-
yellow oil (63 mg, 65% yield, dr > 20:1); 1H NMR (400 MHz, 2,3-dihydro-1H-inden-1-yl)malonate 4j. It is obtained as yellow oil
CDCl3): δ 7.86 (d, J = 8.3 Hz, 2H), 7.70 (dd, J = 7.9, 0.7 Hz, 1H), (68 mg, 62% yield, dr > 20:1); 1H NMR (400 MHz, CDCl3): δ 7.88−
7.67−7.58 (m, 2H), 7.38 (t, J = 7.5 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.79 (m, 2H), 7.72−7.58 (m, 5H), 7.43−7.35 (m, 1H), 5.53 (d, J =
5.32 (d, J = 5.4 Hz, 1H), 5.17 (dt, J = 12.5, 6.3 Hz, 1H), 4.83 (dt, J = 6.3 Hz, 1H), 4.54 (d, J = 2.6 Hz, 1H), 4.45 (t, J = 6.0 Hz, 1H), 4.21
12.5, 6.3 Hz, 1H), 4.58 (d, J = 2.2 Hz, 1H), 4.37 (t, J = 5.5 Hz, 1H), (dt, J = 10.8, 6.7 Hz, 1H), 4.18−4.10 (m, 1H), 3.97−3.87 (m, 3H),
3.93 (d, J = 4.6 Hz, 1H), 2.42 (s, 3H), 1.33 (d, J = 3.1 Hz, 3H), 1.31 1.69 (h, J = 7.2 Hz, 2H), 1.46−1.39 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H),
(d, J = 3.2 Hz, 3H), 1.01 (d, J = 6.3 Hz, 3H), 0.88 (d, J = 6.2 Hz, 3H); 0.77 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 199.4,
13
C{1H} NMR (100 MHz, CDCl3): δ 199.6, 168.7, 167.3, 150.4, 168.9, 167.8, 150.1, 138.6, 136.0, 133.9, 132.3, 129.0, 128.7, 128.1,
144.0, 135.9, 135.9, 134.0, 129.8, 128.6, 127.5, 127.3, 123.9, 69.7, 126.5, 124.0, 67.6, 67.4, 62.3, 51.4, 45.9, 21.8, 21.6, 10.3, 10.2; HRMS
69.3, 62.5, 51.7, 46.0, 21.7, 21.6, 21.4, 21.2; HRMS (ESI): calcd for (ESI): calcd for C24H27BrNO7S (M + H)+, 552.0686; found,

8992 DOI: 10.1021/acs.joc.9b00876

J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

552.0685; IR (neat) ν: 550, 608, 74 614, 738, 857, 1091, 1163, 1313, (m, 2H), 7.46−7.41 (m, 2H), 7.39−7.31 (m, 3H), 5.43 (d, J = 5.6 Hz,
1350, 1464, 1531, 1614, 1730, 2926, 2964, 3415 cm−1. 1H), 4.68 (d, J = 2.4 Hz, 1H), 4.42 (t, J = 5.6 Hz, 1H), 4.26 (dt, J =
rel-Dipropyl 2-((1R,2S)-2-(4-Nitrophenylsulfonamido)-3-oxo-2,3- 10.7, 6.7 Hz, 1H), 4.18 (dt, J = 10.7, 6.7 Hz, 1H), 3.97 (dd, J = 5.5,
dihydro-1H-inden-1-yl)malonate 4k. It is obtained as yellow oil (47 1.8 Hz, 1H), 3.92 (t, J = 6.6 Hz, 2H), 2.42 (s, 3H), 1.74 (h, J = 7.3
mg, 45% yield, dr > 20:1); 1H NMR (400 MHz, CDCl3): δ 8.38 (d, J Hz, 2H), 1.48−1.38 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H), 0.77 (t, J = 7.4
= 8.7 Hz, 2H), 8.17 (d, J = 8.7 Hz, 2H), 7.63 (dd, J = 18.1, 7.6 Hz, Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 199.5, 169.2, 167.9,
3H), 7.41 (t, J = 7.2 Hz, 1H), 5.64 (d, J = 6.9 Hz, 1H), 4.62 (t, J = 6.3 149.1, 144.0, 141.8, 139.2, 136.0, 134.9, 134.5, 129.8, 129.0, 128.0,
Hz, 1H), 4.48 (d, J = 2.9 Hz, 1H), 4.18 (dt, J = 10.8, 6.7 Hz, 1H), 127.5, 127.0, 122.0, 67.6, 67.3, 62.7, 51.4, 45.9, 21.8, 21.60, 21.6, 10.4,
4.11 (dd, J = 11.9, 5.3 Hz, 1H), 3.98 (ddd, J = 8.8, 7.0, 2.5 Hz, 3H), 10.2; HRMS (ESI): calcd for C31H34NO7S (M + H)+, 564.2050;
1.70−1.63 (m, 2H), 1.53−1.47 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H), found, 564.2051; IR (neat) ν: 550, 664, 697, 762, 812, 1059, 1093,
0.83 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 199.2, 1160, 1262, 1339, 1379, 1461, 1616, 1728, 2922, 2957, 3417 cm−1.
168.6, 167.9, 150.2, 149.9, 145.7, 136.2, 133.9, 128.9, 128.7, 126.2, rel-Dipropyl 2-((1R,2S)-5-Methoxy-2-(4-methylphenylsulfonami-
124.3, 124.2, 67.6, 62.3, 51.5, 45.8, 21.8, 21.6, 10.3, 10.2; HRMS do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4p. It is obtained as
(ESI): calcd for C24H27N2O9S (M + H)+, 519.1432; found, 519.1434; yellow oil (73 mg, 70% yield, dr > 20:1); 1H NMR (400 MHz,
IR (neat) ν: 546, 823, 1010, 1064, 1093, 1163, 1266, 1341, 1390, CDCl3): δ 7.83 (d, J = 7.8 Hz, 2H), 7.52 (d, J = 8.6 Hz, 1H), 7.31 (d,
1466, 1576, 1611, 1728, 2968, 3415 cm−1. J = 8.0 Hz, 2H), 7.19−7.11 (m, 1H), 7.03 (d, J = 2.0 Hz, 1H), 5.47
rel-Dipropyl 2-((1R,2S)-4-Methyl-2-(4-methylphenylsulfonami- (d, J = 5.8 Hz, 1H), 4.57 (s, 1H), 4.37 (t, J = 5.5 Hz, 1H), 4.26−4.19
do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4l. It is obtained (m, 1H), 4.17−4.11 (m, 1H), 3.86 (dd, J = 12.9, 6.2 Hz, 3H), 3.76 (s,
as yellow oil (62 mg, 62% yield, dr > 20:1); 1H NMR (400 MHz, 3H), 2.41 (s, 3H), 1.71 (h, J = 6.8 Hz, 2H), 1.49−1.34 (m, 2H), 0.96
CDCl3): δ 7.85 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 4.7 Hz, 2H), 7.32 (d, (t, J = 7.4 Hz, 3H), 0.75 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100
J = 8.0 Hz, 2H), 7.12 (t, J = 4.2 Hz, 1H), 5.32 (d, J = 5.0 Hz, 1H), MHz, CDCl3): δ 199.5, 169.3, 167.9, 160.0, 144.0, 143.1, 136.0,
4.68 (d, J = 2.3 Hz, 1H), 4.30−4.13 (m, 3H), 3.89 (t, J = 6.6 Hz, 3H), 135.2, 129.8, 127.8, 127.5, 125.0, 105.2, 67.5, 67.2, 62.7, 55.6, 51.5,
2.51 (s, 3H), 2.42 (s, 3H), 1.79−1.67 (m, 2H), 1.48−1.34 (m, 2H), 45.5, 21.8, 21.6, 10.4, 10.2; HRMS (ESI): calcd for C26H32NO8S (M
0.97 (t, J = 7.4 Hz, 3H), 0.76 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 + H)+, 518.1843; found, 518.1842; IR (neat) ν: 551, 664, 1064, 1161,
MHz, CDCl3): δ 199.9, 169.3, 168.0, 150.9, 143.9, 139.0, 135.8, 1621, 1726, 2367, 2923, 3421 cm−1.
135.2, 131.5, 130.3, 129.8, 127.5, 123.8, 67.5, 67.1, 62.5, 51.4, 45.7, rel-Dipropyl 2-((1R,2S)-5-Fluoro-2-(4-methylphenylsulfonami-
21.8, 21.6, 18.4, 10.4, 10.2; HRMS (ESI): calcd for C26H32NO7S (M do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4q. It is obtained
+ H)+, 502.1894; found, 502.1896; IR (neat) ν: 554, 664, 814, 940, as yellow oil (41 mg, 40% yield, dr > 20:1); 1H NMR (400 MHz,
1058, 1092, 1162, 1265, 1337, 1392, 1462, 1595, 1724, 2928, 2965, CDCl3): δ 7.84 (d, J = 8.2 Hz, 2H), 7.67 (dd, J = 8.4, 4.5 Hz, 1H),
3416 cm−1. 7.31 (m, 4H), 5.29 (s, 1H), 4.64 (d, J = 2.2 Hz, 1H), 4.40 (t, J = 5.5
rel-Dipropyl 2-((1R,2S)-4-Fluoro-2-(4-methylphenylsulfonami- Hz, 1H), 4.25 (m, 1H), 4.17 (m, 1H), 3.90 (t, J = 6.6 Hz, 3H), 2.43
do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4m. It is obtained
(s, 3H), 1.72 (h, J = 7.2 Hz, 2H), 1.46−1.40 (m, 2H), 0.98 (t, J = 7.4
as yellow oil (59 mg, 58% yield, dr = 7:1); 1H NMR (400 MHz,
Hz, 3H), 0.78 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3): δ 7.84 (d, J = 8.3 Hz, 2.28H), 7.63−7.55 (m, 1.14H), 7.50
CDCl3): δ 198.6, 169.2, 167.8, 162.7 (d, J = 250.7 Hz), 145.9 (d, J =
(d, J = 7.7 Hz, 0.14H), 7.43 (d, J = 7.8 Hz, 1H), 7.32 (d, J = 8.1 Hz,
2.0 Hz), 144.1, 135.9, 135.8 (d, J = 7.5 Hz), 129.8, 128.8 (d, J = 8.0
2.28H), 7.01 (q, J = 8.1 Hz, 1.14H), 5.53 (d, J = 6.4 Hz, 0.14H), 5.36
Hz), 127.5, 123.5 (d, J = 23.4 Hz), 109.9 (d, J = 22.3 Hz), 67.7, 67.3,
(d, J = 5.7 Hz, 1H), 4.67 (d, J = 2.3 Hz, 1H), 4.43 (dd, J = 8.1, 3.0 Hz,
62.9, 51.4, 45.7, 21.8, 21.6, 21.6, 10.3, 10.2; HRMS (ESI): calcd for
0.14H), 4.37 (t, J = 5.8 Hz, 1H), 4.27−4.06 (m, 2.56H), 3.97−3.83
C25H29FNO7S (M + H)+, 506.1643; found, 506.1645; IR (neat) ν:
(m, 3.28H), 2.42−2.41 (m, 3.42H), 1.77−1.68 (m, 2H), 1.62−1.58
(m, 0.28H), 1.51−1.39 (m, 2.28H), 0.97 (t, J = 7.4 Hz, 3H), 0.88 (t, J 560, 667, 813, 958, 1058, 1093, 1172, 1261, 1340, 1394, 1444, 1757,
= 7.4 Hz, 0.42H), 0.83−0.75 (m, 3.42H); 13C{1H} NMR (100 MHz, 1785, 2937, 2975, 3438 cm−1.
CDCl3): δ 195.6, 195.3, 169.1, 168.7, 167.7, 167.5, 158.3 (dd, J = rel-Dipropyl 2-((1R,2S)-5-Chloro-2-(4-methylphenylsulfonami-
do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4r. It is obtained
265.1 Hz), 158.2 (dd, J = 264.6 Hz), 151.8 (d, J = 1.7 Hz), 151.1 (d, J
as yellow oil (52 mg, 50% yield, dr > 20:1); 1H NMR (400 MHz,
= 2.0 Hz), 144.1, 144.0, 137.8 (d, J = 8.4 Hz), 137.4 (d, J = 8.3 Hz),
CDCl3): δ 7.83 (d, J = 8.2 Hz, 2H), 7.65−7.53 (m, 3H), 7.33 (d, J =
136.0, 135.7, 129.8, 127.5, 127.4, 123.5 (d, J = 3.9 Hz), 122.5 (d, J =
8.0 Hz, 2H), 5.31 (d, J = 4.4 Hz, 1H), 4.63 (d, J = 1.9 Hz, 1H), 4.38
4.0 Hz), 122.2 (d, J = 13.5 Hz), 121.9 (d, J = 13.3 Hz), 116.0 (d, J =
(t, J = 5.2 Hz, 1H), 4.27−4.22 (m, 1H), 4.16 (dt, J = 10.7, 6.7 Hz,
19.0 Hz), 115.4 (d, J = 18.6 Hz), 67.7, 67.5, 67.5, 67.3, 62.7, 60.8,
1H), 3.88 (dt, J = 17.5, 6.2 Hz, 3H), 2.43 (s, 3H), 1.72 (h, J = 7.2 Hz,
51.3, 51.1, 45.9 (d, J = 1.2 Hz), 42.2 (d, J = 1.3 Hz), 21.8, 21.7, 21.6,
21.6, 21.4, 10.4, 10.2, 10.1; HRMS (ESI): calcd for C25H29FNO7S (M 2H), 1.48−1.42 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H), 0.79 (t, J = 7.4 Hz,
+ H)+, 506.1643; found, 506.1645; IR (neat) ν: 559, 664, 811, 958, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 198.3, 169.1, 167.7,
1058, 1093, 1161, 1261, 1339, 1394, 1474, 1617, 1735, 2927, 2965, 148.5, 144.1, 136.0, 135.8, 135.4, 135.1, 129.8, 128.2, 127.5, 123.7,
3418 cm−1. 67.7, 67.4, 62.7, 51.3, 45.8, 21.8, 21.7, 10.3, 10.2; HRMS (ESI): calcd
rel-Dipropyl 2-((1R,2S)-5-Methyl-2-(4-methylphenylsulfonami- for C25H29ClNO7S (M + H)+, 522.1348; found, 522.1349; IR (neat)
do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4n. It is obtained ν: 557, 666, 1062, 1093, 1162, 1265, 1334, 1394, 1465, 1600, 1732,
as yellow oil (66 mg, 66% yield, dr > 20:1); 1H NMR (400 MHz, 2969, 3302 cm−1.
CDCl3): δ 7.84 (d, J = 8.2 Hz, 2H), 7.52 (d, J = 7.9 Hz, 1H), 7.47− rel-Dipropyl 2-((1R,2S)-6-Methyl-2-(4-methylphenylsulfonami-
7.38 (m, 2H), 7.32 (d, J = 8.1 Hz, 2H), 5.31 (s, 1H), 4.63 (d, J = 2.1 do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4t. It is obtained
Hz, 1H), 4.32 (t, J = 5.4 Hz, 1H), 4.24 (dt, J = 10.6, 6.7 Hz, 1H), as yellow oil (62 mg, 62% yield, dr > 20:1); 1H NMR (400 MHz,
4.20−4.13 (m, 1H), 3.88 (t, J = 6.5 Hz, 3H), 2.42 (s, 3H), 2.35 (s, CDCl3): δ 7.85 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 7.9 Hz, 1H), 7.43 (s,
3H), 1.72 (h, J = 7.2 Hz, 2H), 1.45−1.39 (m, 2H), 0.97 (t, J = 7.4 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 7.9 Hz, 1H), 5.28 (d, J =
3H), 0.76 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 5.0 Hz, 1H), 4.65 (d, J = 2.3 Hz, 1H), 4.32 (t, J = 5.4 Hz, 1H), 4.28−
199.5, 169.2, 167.9, 147.7, 143.9, 138.7, 137.2, 136.0, 134.0, 129.7, 4.21 (m, 1H), 4.18 (dd, J = 6.6, 4.0 Hz, 1H), 3.89 (td, J = 6.6, 2.7 Hz,
127.5, 126.4, 123.9, 67.5, 67.2, 62.6, 51.5, 45.9, 21.8, 21.6, 21.6, 21.0, 3H), 2.42 (d, J = 3.9 Hz, 3H), 2.41 (s, 3H), 1.73 (h, J = 7.3 Hz, 2H),
10.4, 10.2; HRMS (ESI): calcd for C26H32NO7S (M + H)+, 502.1894; 1.46−1.33 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H), 0.76 (t, J = 7.4 Hz, 3H);
found, 502.1896; IR (neat) ν: 551, 664, 814, 1059, 1094, 1161, 1337,
13
C{1H} NMR (100 MHz, CDCl3): δ 198.9, 169.2, 167.9, 150.8,
1394, 1460, 1619, 1728, 2928, 2967, 3446 cm−1. 147.6, 144.0, 136.0, 131.6, 129.8, 129.8, 127.5, 127.0, 123.9, 67.5,
rel-Dipropyl 2-((1R,2S)-2-(4-Methylphenylsulfonamido)-3-oxo-5- 67.2, 62.5, 51.6, 46.0, 22.4, 21.9, 21.6, 21.6, 10.4, 10.2; HRMS (ESI):
phenyl-2,3-dihydro-1H-inden-1-yl)malonate 4o. It is obtained as calcd for C26H32NO7S (M + H)+, 502.1894; found, 502.1897; IR
yellow oil (77 mg, 68% yield, dr > 20:1); 1H NMR (400 MHz, (neat) ν: 559, 672, 810, 1060, 1093, 1161, 1264, 1335, 1387, 1460,
CDCl3): δ 7.89−7.81 (m, 4H), 7.71 (d, J = 7.9 Hz, 1H), 7.55−7.51 1609, 1726, 2924, 2961, 3447 cm−1.

8993 DOI: 10.1021/acs.joc.9b00876

J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

rel-Dipropyl 2-((1R,2S)-2-(4-Methylphenylsulfonamido)-3-oxo-6- CDCl3): δ 7.78 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 7.5 Hz, 1H), 7.61 (d,
phenyl-2,3-dihydro-1H-inden-1-yl)malonate 4u. It is obtained as J = 7.8 Hz, 1H), 7.40 (t, J = 7.7 Hz, 1H), 7.31 (d, J = 8.2 Hz, 2H),
yellow oil (72 mg, 64% yield, dr = 3.5:1); 1H NMR (400 MHz, 5.09 (d, J = 5.5 Hz, 1H), 4.79 (d, J = 3.7 Hz, 1H), 4.61 (dd, J = 5.5,
CDCl3): δ 7.97−7.82 (m, 3.9H), 7.71 (dd, J = 8.0, 3.1 Hz, 1.3H), 2.7 Hz, 1H), 4.30−4.21 (m, 3H), 3.82 (dd, J = 12.7, 6.4 Hz, 2H), 2.43
7.59 (ddd, J = 17.8, 8.7, 1.2 Hz, 3.9H), 7.49−7.38 (m, 3.9H), 7.37− (s, 3H), 1.77−1.72 (m, 2H), 1.42−1.35 (m, 2H), 0.98 (d, J = 7.4 Hz,
7.29 (m, 2.9H), 5.62 (d, J = 6.7 Hz, 0.3H), 5.38 (d, J = 5.4 Hz, 1H), 3H), 0.74 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
4.69 (d, J = 2.3 Hz, 1H), 4.50 (dd, J = 8.0, 3.0 Hz, 0.3H), 4.41 (t, J = 199.1, 168.5, 167.4, 147.6, 143.7, 138.1, 137.7, 136.1, 132.3, 130.3,
5.5 Hz, 1H), 4.32−4.14 (m, 2.6H), 4.07 (td, J = 6.7, 2.8 Hz, 0.6H), 129.6, 127.3, 122.9, 68.0, 67.2, 60.4, 50.6, 46.0, 21.8, 21.6, 21.5, 10.3,
4.00 (dd, J = 3.3, 2.2 Hz, 1H), 3.88 (t, J = 6.6 Hz, 2H), 3.84 (td, J = 10.0; HRMS (ESI): calcd for C25H29ClNO7S (M + H)+, 522.1348;
6.8, 2.7 Hz, 0.6H), 2.43 (s, 3H), 2.42 (s, 0.9H), 1.72 (h, J = 7.3 Hz, found, 522.1351; IR (neat) ν: 541, 616, 795, 856, 985, 1071, 1210,
2H), 1.61−1.55 (m, 0.6H), 1.46−1.30 (m, 2.6H), 0.96 (t, J = 7.4 Hz, 1260, 1388, 1461, 1601, 1734, 2439, 2969, 3418 cm−1.
3H), 0.84 (t, J = 7.4 Hz, 0.9H), 0.77 (t, J = 7.4 Hz, 0.9H), 0.68 (t, J = rel-Dipropyl 2-((2S,3R)-2-(4-Methylphenylsulfonamido)-1-oxo-
7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 199.0, 198.8, 2,3-dihydro-1H-cyclopenta[a]naphthalene-3-yl)malonate 4aa. It
169.2, 168.9, 167.9, 167.7, 151.0, 150.0, 149.0, 148.5, 144.0, 143.8, is obtained as yellow oil (69 mg, 64% yield, dr > 20:1); 1H NMR (400
139.7, 139.7, 136.4, 136.0, 133.0, 132.7, 129.8, 129.7, 129.0, 129.0, MHz, CDCl3): δ 8.83 (d, J = 8.3 Hz, 1H), 8.03 (d, J = 8.6 Hz, 1H),
128.6, 128.2, 127.8, 127.5, 127.5, 127.4, 126.1, 125.2, 124.4, 124.1, 7.89 (d, J = 8.3 Hz, 2H), 7.85 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.6 Hz,
67.6, 67.4, 67.2, 62.7, 60.9, 51.6, 51.5, 46.2, 42.5, 21.8, 21.7, 21.6, 1H), 7.65−7.59 (m, 1H), 7.59−7.53 (m, 1H), 7.34 (d, J = 8.0 Hz,
21.6, 21.4, 10.3, 10.2, 10.1; HRMS (ESI): calcd for C31H34NO7S (M 2H), 5.44 (d, J = 5.0 Hz, 1H), 4.75 (d, J = 2.3 Hz, 1H), 4.35 (t, J = 5.0
+ H)+, 564.2050; found, 564.2052; IR (neat) ν: 762, 812, 858, 1092, Hz, 1H), 4.28 (dt, J = 10.7, 6.7 Hz, 1H), 4.20 (dt, J = 10.7, 6.7 Hz,
1161, 1386, 1461, 1609, 1728, 2925, 2961, 3416 cm−1. 1H), 4.08 (dd, J = 4.9, 2.2 Hz, 1H), 3.84 (td, J = 6.6, 2.4 Hz, 2H),
rel-Dipropyl 2-((1R,2S)-6-Fluoro-2-(4-methylphenylsulfonami- 2.43 (s, 3H), 1.74 (h, J = 7.3 Hz, 2H), 1.45−1.32 (m, 2H), 0.99 (t, J =
do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4v. It is obtained 7.4 Hz, 3H), 0.73 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
as yellow oil (64 mg, 63% yield, dr > 20:1); 1H NMR (400 MHz, 199.4, 169.3, 167.9, 153.6, 144.0, 136.9, 135.8, 132.8, 129.8, 129.3,
CDCl3): δ 7.84 (d, J = 8.2 Hz, 2H), 7.67 (dd, J = 8.4, 5.4 Hz, 1H), 128.6, 128.5, 128.2, 127.6, 127.3, 124.1, 123.4, 67.6, 67.2, 62.6, 51.5,
7.38 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 8.1 Hz, 2H), 7.12−7.06 (m, 46.3, 21.9, 21.6, 10.4, 10.2; HRMS (ESI): calcd for C29H32NO7S (M
1H), 5.34 (d, J = 5.3 Hz, 1H), 4.65 (d, J = 2.1 Hz, 1H), 4.34 (t, J = 5.5 + H)+, 538.1894; found, 538.1897; IR (neat) ν: 557, 663, 1089, 1160,
Hz, 1H), 4.29−4.23 (m, 1H), 4.21−4.15 (m, 1H), 3.91 (t, J = 6.6 Hz, 1265, 1332, 1379, 1460, 1623, 1717, 2924, 2959, 3415 cm−1.
3H), 2.43 (s, 3H), 1.76−1.70 (m, 2H), 1.47−1.41 (m, 2H), 0.99 (t, J Convertion from 4-Isoquinolone 5a to Indanone 4a. In open
= 7.4 Hz, 3H), 0.78 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, air, In(OTf)3 (0.04 mmol, 20% cat.) was added to a solution of 4-
CDCl3): δ 197.6, 169.1, 167.7 (d, J = 258.5 Hz), 167.7, 153.5 (d, J = isoquinolone 5a (86.2 mg, 0.2 mmol) in DMSO (4 mL) at room
10.1 Hz), 144.1, 135.9, 130.4, 129.8, 127.5, 126.5 (d, J = 10.7 Hz), temperature. The reaction mixture was heated in an oil bath (90 °C)
117.0 (d, J = 23.8 Hz), 114.1 (d, J = 23.9 Hz), 67.7, 67.4, 62.5, 51.3, for 2 h. Then, the reaction mixture was cooled to room temperature,
46.1, 21.8, 21.6, 21.6, 10.3, 10.2; HRMS (ESI): calcd for poured into water (20 mL), and extracted with ethyl acetate (5 × 10
C25H29FNO7S (M + H)+, 506.1643; found, 506.1646; IR (neat) ν: mL). The combined organic extract was washed with brine (20 mL),
562, 668, 814, 1093, 1162, 1263, 1340, 1696, 1700, 1729, 1734, 1772, dried over Na2SO4, and evaporated under reduced pressure. The
1792, 1830, 3650 cm−1. residue was purified by flash column chromatography on silica gel
rel-Dipropyl 2-((1R,2S)-6-Chloro-2-(4-methylphenylsulfonami- (petroleum ether/ethyl acetate, 5:1) to afford the recovered material
do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4w. It is obtained 5a (93%, 80 mg). 1H NMR (400 MHz, CDCl3): δ 7.60 (dd, J = 7.8,
as yellow oil (63 mg, 60% yield, dr = 3.5:1); 1H NMR (400 MHz, 1.4 Hz, 1H), 7.45−7.41 (m, 1H), 7.37 (dt, J = 7.4, 2.1 Hz, 3H), 7.25
CDCl3): δ 7.84 (d, J = 8.2 Hz, 3H), 7.74 (s, 1H), 7.67 (s, 1H), 7.58 (td, J = 7.5, 1.4 Hz, 1H), 6.94 (d, J = 8.0 Hz, 2H), 5.93 (d, J = 9.8 Hz,
(dd, J = 8.2, 2.3 Hz, 1H), 7.38−7.31 (m, 4H), 5.56 (d, J = 6.6 Hz, 1H), 4.53 (d, J = 20.1 Hz, 1H), 4.31 (d, J = 20.1 Hz, 1H), 3.92 (d, J =
0.3H), 5.36 (d, J = 5.5 Hz, 1H), 4.63 (d, J = 2.3 Hz, 1H), 4.36 (t, J = 9.8 Hz, 1H), 3.84 (s, 3H), 3.62 (s, 3H), 2.23 (s, 3H). The analytical
5.6 Hz, 1.3H), 4.29−4.07 (m, 3.6H), 3.95−3.88 (m, 2.6H), 3.81 (t, J data were in accordance with those reported in our previous work.15c
= 6.8 Hz, 0.6H), 2.42 (s, 3H), 2.42 (s, 0.9H), 1.73 (h, J = 7.2 Hz, Synthesis of Compound 6. To a solution of ketone 4c (146 mg,
2H), 1.68−1.57 (m, 0.6H), 1.50−1.41 (m, 2.6H), 0.98 (t, J = 7.4 Hz, 0.3 mmol) in MeOH (4 mL) was added sodium borohydride (11.4
3H), 0.89 (t, J = 7.4 Hz, 0.9H), 0.80 (td, J = 7.4, 3.6 Hz, 3.9H); mg, 0.3 mmol) in small portions with stirring and external cooling.
13
C{1H} NMR (100 MHz, CDCl3): δ 198.1, 197.9, 169.0, 168.7, When the addition was complete, stirring was continued for 2 h at
167.6, 167.5, 151.8, 150.9, 144.1, 144.0, 142.7, 142.0, 136.3, 136.0, room temperature. The solution was poured into 20 mL of water and
132.8, 132.4, 129.8, 129.4, 128.2, 127.5, 127.4, 127.2, 125.1, 124.8, stirred for 2 h. The solid formed was filtered and extracted with
67.7, 67.5, 67.4, 67.4, 62.4, 60.8, 51.4, 51.2, 46.0, 42.2, 21.8, 21.7, EtOAc (40 mL × 2). The combined organic extract was washed with
21.6, 21.6, 21.5, 21.4, 10.3, 10.2, 10.1; HRMS (ESI): calcd for brine (10 mL), dried over Na2SO4, and evaporated under reduced
C25H29ClNO7S (M + H)+, 522.1348; found, 522.1352; IR (neat) ν: pressure. The residue was purified by flash column chromatography
557, 666, 814, 910, 963, 1058, 1091, 1163, 1265, 1338, 1393, 1462, on silica gel (petroleum ether/ethyl acetate, 3:1) to afford product 6
1599, 1732, 2930, 2967, 3283 cm−1. (56%, 0.168 mmol, 82 mg) as a yellow oil. 1H NMR (400 MHz,
rel-Dipropyl 2-((1R,2S)-7-Methoxy-2-(4-methylphenylsulfonami- CDCl3): δ 7.89−7.74 (m, 2H), 7.41 (d, J = 7.4 Hz, 1H), 7.29 (t, J =
do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4y. It is obtained as 6.9 Hz, 3H), 7.24 (d, J = 7.3 Hz, 1H), 7.11 (d, J = 7.4 Hz, 1H), 6.49
yellow oil (39 mg, 38% yield, dr > 20:1); 1H NMR (400 MHz, (s, 1H), 5.26 (s, 1H), 4.08−4.00 (m, 3H), 3.98 (d, J = 3.8 Hz, 1H),
CDCl3): δ 7.81 (d, J = 8.3 Hz, 2H), 7.34 (ddd, J = 12.0, 11.1, 5.5 Hz, 3.71 (t, J = 6.7 Hz, 2H), 3.68−3.60 (m, 2H), 2.42 (s, 3H), 1.60−1.54
4H), 7.07 (d, J = 7.7 Hz, 1H), 5.19 (d, J = 5.8 Hz, 1H), 4.75 (d, J = (m, 2H), 1.32 (h, J = 7.1 Hz, 2H), 0.89 (t, J = 7.4 Hz, 3H), 0.68 (t, J =
3.7 Hz, 1H), 4.51 (dd, J = 5.9, 4.0 Hz, 1H), 4.20 (dd, J = 10.6, 3.7 Hz, 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 169.5, 167.3,
1H), 4.17−4.15 (m, 1H), 3.94−3.83 (m, 6H), 2.42 (s, 3H), 1.73− 143.6, 141.5, 136.9, 136.0, 129.6, 128.4, 128.4, 127.7, 124.6, 123.2,
1.67 (m, 2H), 1.48−1.39 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H), 0.78 (t, J 80.3, 67.8, 67.2, 66.4, 53.4, 46.4, 21.7, 21.5, 10.2, 10.0; HRMS (ESI):
= 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 200.1, 168.7, calcd for C25H32NO7S (M + H)+, 490.1894; found, 490.1897; IR
167.9, 156.9, 138.8, 137.7, 136.5, 130.2, 129.5, 127.4, 127.3, 116.6, (neat) ν: 552, 667, 748, 815, 926, 1056, 1092, 1158, 1326, 1394,
116.0, 67.6, 66.9, 61.2, 55.5, 50.7, 44.6, 21.8, 21.6, 21.6, 10.3, 10.2; 1461, 1735, 2968, 3286, 3502 cm−1.
HRMS (ESI): calcd for C26H32NO8S (M + H)+, 518.1843; found, Synthesis of Compound 7. A round-bottom flask was charged
518.1842; IR (neat) ν: 669, 1112, 1620, 2363, 2925, 3416 cm−1. with (13.2 mg, 0.33 mmol) sodium hydride and 6 mL of DMF. The
rel-Dipropyl 2-((1R,2S)-7-Chloro-2-(4-methylphenylsulfonami- suspension was cooled to 0 °C and compound 4c (146 mg, 0.3
do)-3-oxo-2,3-dihydro-1H-inden-1-yl)malonate 4z. It is obtained mmol) was added. Then, the reaction mixture was warmed to room
as yellow oil (21 mg, 20% yield, dr > 20:1); 1H NMR (400 MHz, temperature and stirred for 0.5 h. Following complete gas evolution,

8994 DOI: 10.1021/acs.joc.9b00876

J. Org. Chem. 2019, 84, 8984−8997
The Journal of Organic Chemistry Article

benzyl bromide (507 mg, 3 mmol) was added. The reaction was then from the Stem Bark of Vatica pauciflora. J. Nat. Prod. 2004, 67, 932.
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cm−1.

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Catalytic Intramolecular Friedel-Crafts Reaction. J. Org. Chem. 2005,
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ASSOCIATED CONTENT Synthesis of 1-Indanones by Intramolecular Friedel-Crafts Reaction of
* Supporting Information
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■ AUTHOR INFORMATION
Corresponding Authors
(b) Frontier, A. J.; Collison, C. The Nazarov Cyclization in Organic
Synthesis. Recent Advances. Tetrahedron 2005, 61, 7577. ; selected
examples for the synthesis of indanones: (c) Zhou, X.; Zhao, Y.; Cao,
Y.; He, L. Catalytic Efficient Nazarov Reaction of Unactivated Aryl
*E-mail: hxxyxsy@tjnu.edu.cn (S.X.).
Vinyl Ketones via a Bidentate Diiron Lewis Acid Activation Strategy.
*E-mail: hxxywk@tjnu.edu.cn (K.W.). Adv. Synth. Catal. 2017, 359, 3325. (d) Tang, M.-L.; Peng, P.; Liu, Z.-
*E-mail: hxxyzbl@gmail.com (B.Z.). Y.; Zhang, J.; Yu, J.-M.; Sun, X. Sulfoxide-Based Enantioselective
ORCID Nazarov Cyclization: Divergent Syntheses of (+)-Isopaucifloral F,
Siyang Xing: 0000-0002-6240-0363 (+)-Quadrangularin A and (+)-Pallidol. Chem.Eur. J. 2016, 22,
Kui Wang: 0000-0002-0379-3865 14535. (e) Xi, Z.-G.; Zhu, L.; Luo, S.; Cheng, J.-P. Catalytic Nazarov
Reaction of Aryl Vinyl Ketones via Binary Acid Strategy. J. Org. Chem.
Bolin Zhu: 0000-0002-6846-566X 2013, 78, 606. (f) Vaidya, T.; Atesin, A. C.; Herrick, I. R.; Frontier, A.
Notes J.; Eisenberg, R. A Highly Reactive Dicationic Iridium(III) Catalyst
The authors declare no competing financial interest.

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for the Polarized Nazarov Cyclization Reaction. Angew. Chem., Int. Ed.
2010, 49, 3363. (g) Lawrence, N. J.; Armitage, E. S. M.; Greedy, B.;
ACKNOWLEDGMENTS Cook, D.; Ducki, S.; McGown, A. T. The Synthesis of Indanones
We thank the National Natural Science Foundation of China Related to Combretastatin A-4 via Microwave-Assisted Nazarov
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