Homocoupling of 3-Halooxindole via Visible-Light Photocatalysis: A Mild Access to 3,3′-Bioxindoles

Article abstract of DOI:10.1021/acs.joc.6b01045

This paper introduces a simple way to the homocoupling of tertiary halides induced by photocatalysis. This method features mild reaction conditions, excellent functional group tolerance, high yields, low photocatalyst loading and successful application to the highly sterically hindered systems. On the basis of the reaction results, a novel stable-radical-induced homocoupling reaction mechanism has been proposed.

Full text of DOI:10.1021/acs.joc.6b01045

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Article
Homocoupling of 3-Halooxindole via Visible-Light
Photocatalysis: A Mild Access to 3,3#-Bioxindoles
Wen-Liang Jia, Jian He, Jia-Jing Yang, Xue-Wang Gao, Qiang Liu, and Li-Zhu Wu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01045 • Publication Date (Web): 27 Jun 2016
Downloaded from http://pubs.acs.org on June 28, 2016
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Homocoupling of 3-Halooxindole via Visible-Light Photocatalysis: A Mild
Access to 3,3′-Bioxindoles
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Wen-Liang Jia†, Jian He†, Jia-Jing Yang†, Xue-Wang Gao‡, Qiang Liu*†, Li-Zhu Wu*‡
†State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou, Gansu 730000, China
‡Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of
Physics and Chemistry, the Chinese Academy of Sciences, Beijing 100190, P. R. China
ABSTRACT
This paper introduced a simple way to the homocoupling of tertiary halides induced by
photocatalysis. This method features mild reaction conditions, excellent functional group
tolerance, high yields, low photocatalyst loading and successful application to the highly
sterically hindered systems. Based on the reaction results, a novel stable-radical-induced
homocoupling reaction mechanism was proposed.
INTRODUCTION
The coupling reactions of halogen compounds to form carbon-carbon bonds are among central methods
of connecting two simpler molecules to generate a more complex one. The initial discovery by Wurtz et
al. used alkali metal, such as sodium metal to reduce alkyl or benzyl halides, resulting in the
homocoupling of two sp3-carbon centers1, whereas the classic Ullmann reaction uses Copper to induce
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homocoupling of aryl halides2. Because the synthetic applications of both the Wurtz coupling and classic
Ullmann reaction are fairly limited, numerous reducing systems have thereafter been developed for the
transformation, especially the transition metal-catalyzed coupling reactions of halides which have
advanced rapidly both in cross-electrophile coupling3 and homocoupling. For example, Ni4, Ti5 and Rh6-
catalyzed reductive homocoupling of alkyl halides have been developed for the formation of
C(sp3)−C(sp3) bonds by using Zn, Et2Zn or Mn as the reductant. More excitedly, this method has served
as key steps for the total syntheses of many natural products. For example, the Movassaghi group has
many excellent works on natural products syntheses by applying the Co-mediated homocoupling of C3-
halogenated diketopiperazine as key step7. Overall, however, in most cases, metal-based reductants are
essential for an efficient coupling of alkyl halides, and the reductive coupling of tertiary alkyl chlorides is
still a challenge due to the associated difficulty in the formation of a C−C bond containing a vicinal all-
carbon quaternary center.
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The dimerization of indole and oxindole precursors, especially at C-3 position, has been always an
attractive but challenging procedure8. Serving as key intermediates for the total syntheses of many natural
products8,9, such as folicanthine, chimonanthine, calycanthine etc, the synthesis of 3,3’–bioxindoles
rapidly caught organic chemists’ attention. Maybe because of the highly steric hindrance, the initial
attempts had low efficiency9a,10. Until 1994, the Rodrigo group obtained the dehydrogenative (±)dl–dimer
(yield: 49-57%) and meso–dimer (yield: 8%) of ethyl 2-(1-methyl-2-oxoindolin-3-yl)acetate at C-3
position and applied the former to achieve the total synthesis of (±) folicanthine successfully8. Even so,
the harsh conditions, very long reaction time and many byproducts made it unfavorable. After that,
several means to 3,3’ –bioxindoles were reported, among which, either multiple procedures or excessive
oxidants represented respective drawbacks9b-f.
Visible light photoredox chemistry is emerging as a powerful synthetic methodology owing to its
attractive features such as mild and green conditions, excellent functional group tolerance, and high
reactivity11. Recently, the group of Xiao described a visible-light-induced photocatalytic formyloxylation
reaction of 3-alkyl-3-bromooxindole with water and DMF, in which the key intermediate 3-alkyl-2-
oxoindolin-3-yl radical were generated by the electron transfer from the excited photocatalyst to 3-alkyl-
3-bromooxindole12. In continuation of our interest in utilizing visible light to drive useful organic
reactions13, we are intrigued by the structure of the 3-alkyl-2-oxoindolin-3-yl radical because this tertiary
radical is stabilized by synergistic effect of electron-withdrawing carbonyl group and electron-donating
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aminophenyl group. The captodative stabilization and steric effect extend their life time and make
homocoupling of 3-alkyl-2-oxoindolin-3-yl radical possible if other radical approaches are suppressed
under proper photocatalytic conditions. Although several reports about dehalogenation-homocoupling
induced by visible light were available14, the homocoupling of tertiary halides hasn’t been researched
before (Scheme 1). Herein, we report the first example of visible-light-driven construction of vicinal all-
carbon quaternary center by homocoupling of 3-chloroxindole, which provide a mild and simple approach
to 3,3’-substituted bioxindoles.
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Scheme 1
Scheme 1: Visible light induced homocoupling of halides, Hantzsch ester = diethyl 1,4-dihydro-2,6-
dimethylpyridine-3,5-dicarboxylate, DBU = 1,8-diazabicyclo[5,4,0]undec-7-ene.
RESULTS AND DISSCUSSION
We initiated our investigations with 1a (1.0 equiv) as the model substrate and DBU (1.0 equiv) as the
electron donor. After 12 h of irradiation (blue LEDs, λ = 450 nm) in dry THF (0.06 M) with the loading
of 0.5 mmol% fac-Ir(ppy)3 as photocatalyst at room temperature, excitedly, 1b was obtained in 57%
isolated yield ((±), dl:meso = 1:2). After scrupulous evaluation of several solvents (Entries 2-5, Table 1),
acetonitrile was found superior to others with 1b yielding 82% (1.1:1). However, Attention must be paid
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when DMF was used, we got the same product as the Xiao group’s report without 1b being obtained12.
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We then replaced DBU with other commonly used electron donors. DBN had a slightly lower efficiency
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Table 1: Optimization of reaction conditions
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Entrya
1
Solvent
THF
DCM
Electron donor
DBU
DBU
DBU
DBU
DBU
DBN
DABCO
Et3N
Catalyst
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
Ru(bpy)3Cl2
Eosin Y
Yield(%)b,c
57 (1:2)
76 (1:1)
82 (1.1:1)
34 (1:1)
No detect
76 (1.2:1)
39 (1:2.5)
27 (1:1)
Trace
82 (1:1)
80 (1:1)
44 (1:1)
Trace
51 (1:1.2)
Trace
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7
Acetonitrile
Acetone
DMF
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
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9d
-
10e
11f
12g
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17h
18
19
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
-
Eosin B
FIrPic
fac-Ir(ppy)3
fac-Ir(ppy)3
-
75 (1.1:1)
Trace
Trace
DBU
Trace
a Reaction conditions: 1a (0.15 mmol, 1.0 equiv), electron donor (0.15 mmol, 1.0 equiv) and photocatalyst
(0.00075 mmol, 0.5 mol%) in dry solvent (2.5 ml) was irradiated with two 3W blue LEDs lamp for 15h. b
Yield of the isolated product (averages of at least two separate runs). c The ratios in parentheses represent
(±)dl: meso. d 1.0 equiv of K2CO3 was used. e 2.0 equiv of DBU was used. f 3.0 equiv of DBU was used.
g 0.5 equiv of DBU was used. h No irradiation. DBN = 1,5-diazabicyclo[4.3.0]non-5-ene, DABCO = 1,4-
diazabicyclo[2.2.2]octane, ppy = 2-phenylpyridine, Eosin Y = 2,4,5,7-tetrabromofluorescein sodium salt,
Eosin B = 4,5-dibromo-2,7-dinitro fluorescein sodium salt,
fluorophenyl)-pyridinato-N,C2′]picolinate.
FIrPic = iridium(III)-bis[4,6-(di-
than DBU, and we got 1b in 76% (1.2:1) yield (Entry 6, Table 1). Other electron donors weren’t suitable
for this transformation for lower yields (Entries 7-8, Table 1). The use of K2CO3 instead of DBU resulted
in a trace amount of the desired product (Entry 9, Table 1), indicating that DBU merely act as an electron
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donor rather than a base. Next, enhancing the amount of DBU didn’t increase the yield of 1b
(Entries
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10-11, Table 1), and 0.5 equiv of DBU reduced the yield nearly by half (Entry 12, Table 1). In addition
,
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several typical photocatalysts were studied for their efficiency (Entries 13-16, Table 1). Ru(bpy)3Cl2 and
Eosin B turned out to be useless to catalyze the reaction and Eosin Y and FIrPic were inferior to fac-
Ir(ppy)3, albeit obtaining 1b in 51% and 75% yields respectively. Moreover, control experiments
established the importance of visible light, the electron donor and the photocatalyst, as no desired reaction
was observed in the absence of light, DBU or fac-Ir(ppy)3 (Entries 17-19, Table 1).
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With the optimized conditions in hand, we next examined the generality of various substituted 3-
halooxindoles in this visible-light-induced homocoupling protocol (Table 2). It was glad to see that the
homocoupling of 1a proceeded very well on a gram scale. The yield was similar to that obtained under
standard reaction conditions, demonstrating the practicability of this visible-light driven photocatalytic
process. When 3-bromoxindole 20a was used instead of 1a, the yield of 2b was increased to 92%.
Because alkyl chlorides are less reactive and more atom-efficient alternatives to alkyl bromides, 3-
chloroxindoles were employed as the substrates for further studies. As shown in Table 2, 3-
chloroxindoles with various substituents at C-5 and C-7 position of the benzene ring were found to
undergo the desired homocoupling smoothly under the standard reaction conditions, affording the
corresponding target products in 71–93% yields (Products 2b to 8b, 10b, Table 2). In particular, halogen
atoms in benzene ring are retained, thus providing an additional handle for further manipulation. Multi-
substituted oxindole 8a is also an excellent precursor, affording product 8b in 90% yield. Next, various
N-protected 3-chloroxindoles were tested, most of which can give satisfactory results (Products 9b to 13b,
Table 2). The substrates protected by benzyl were also compatible with this new visible-light-driven
homocoupling approach, although the reaction proceeded less efficiently. In contrast, unprotected and t-
butyloxy carbonyl (Boc) protected 3-chloroxindoles failed to give the desired product. Finally, we
examined 3-chloroxindoles with different substituents at C-3 position. In the case of 3-ethyl-3-
chloroxindole, the two diastereoisomers of product 16b were determined by X-ray crystallographic
analysis. Notably, a number of key intermediates for the syntheses of natural products were obtained by
altering substituents at C-3 position. For example, product 15b has been employed to construct
cyclotryptamine alkaloids9e by Trost et al. and product 17b has been used to synthesize meso- and (-)-
Chimonanthine and (+)-Calycanthine9b by Overman et al. In addition, the reaction of 3-cyclopropyl-3-
chloroxindole produced 19b without ring opening of the cyclopropane, which adds proof for our
hypothesis that the 3-alkyl-2-oxoindolin-3-yl radical intermediate is stable15.
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Table 2: Scope of homocoupling of 3-halooxindolesa, b
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a
Reaction conditions: a (0.15 mmol, 1.0 equiv), DBU (0.15 mmol, 1.0 equiv) and fac-Ir(ppy)3 (0.00075
mmol, 0.5 mol%) in dry CH3CN (2.5 mL) was irradiated with two 3W blue LED lamps for 15h. b Yield of
the isolated product (averages of at least two separate runs). The ratios in parentheses represent (±)dl:
c
d
meso. 1.0 g of 3-chloro-1,3-dimethylindolin-2-one was used. 3-bromo-1,3-dimethylindolin-2-one 20a
e
f
was used as the substrate. Reactions were performed at -30 °C. To achieve full conversion , the
reaction time was prolonged to 24h. g The ellipsoid contour percent probability level is 30%.
The photoluminescence of fac-Ir(ppy)3 was quenched by 3-chloro-1,3-dimethylindolin-2-one 1a with a
rate constant of 87.7 L·mol−1. In contrast, no significant quenching of fac-Ir(ppy)3 took place in the
presence of DBU (see Figure S2). This result indicated that the photoreaction is mainly initiated by the
interaction between the excited fac-Ir(ppy)3 and 3-chloro-1,3-dimethylindolin-2-one 1a. Based on the
results, a possible mechanism is proposed (Scheme 2). After absorbing a photon, [IrIII] turns into excited
[IrIII]*. It is a strong reductant which can be oxidized to [IrIV] by 3-halooxindole via a single electron
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transfer (SET) process12. At the same time, 3-halooxindole was transferred to its radical anion, which can
generate 3-alkyl-2-oxoindolin-3-yl radical after losing halide anion spontaneously. Successive SET
between [IrIV] and DBU regenerates the photocatalyst and populates DBU radical cation. Further
deprotonation of DBU radical cation can produce DBU radical, which should be oxidized to
corresponding iminium ion16. Finally, the homocoupling of 3-alkyl-2-oxoindolin-3-yl radical affords the
desired product b. Although Hashmi and co-workers have shown that the cross-coupling reaction can
occur efficiently between α-aminoalkyl radical and alkynyl radical17, we only observed homocoupling
reaction of 3-alkyl-2-oxoindolin-3-yl radical in the present case, and no cross-coupling reaction between
DBU radical and 3-alkyl-2-oxoindolin-3-yl radical took place. The selectivity for the preferred
homocoupling 3-alkyl-2-oxoindolin-3-yl radical may be attributed to the lower deprotonation rate of
DBU radical cation, the higher steric hindrance of DBU radical and the less eletrophilicity of 3-alkyl-2-
oxoindolin-3-yl radicals, which inhibit the cross-coupling process18.
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Scheme 2. Proposed reaction mechanism
CONCLUSIONS
In summary, we have developed a concise way to achieve homocoupling of tertiary halides in the
presence of 0.5 mol % of the commercially available photocatalyst fac-Ir(ppy)3, DBU, and visible light.
With this method, a number of 3,3’-substituted bioxindoles including several key intermediates for the
total syntheses of natural products were produced in good to excellent yields. The capacity to form vicinal
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all-carbon quaternary center readily demonstrates the inherent value of visible-light driven radical−radical
couplings as a route to traditionally difficult bond constructions19.
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EXPERIMENTAL SECTION
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General Information
For product purification by flash column chromatography, silica gel (200~300 mesh) and light
petroleum ether (PE) (bp. 60~90 °C) are used. All solvents were purified and dried by standard
techniques, and distilled prior to use. Preparative TLC purification was performed on silica gel GF254
TLC plates (20 cm × 20 cm, 0.5−1.0 mm). Experiments were conducted under an argon or nitrogen
atmosphere, unless otherwise specified. NMR spectra were measured on 400 MHz instruments at room
temperature. All new products were further characterized by HRMS (high-resolution mass spectrometry).
HRMS spectra were obtained on a micrOTOF-Q instrument equipped with an ESI source or on a TOF
instrument equipped with an EI source.
Preparation of 3-(2-acetoxyethyl)indole20:
Tryptophol (2.418 g, 15.0 mmol) was dissolved in 30 mL pyridine and 2.0 mL (21.00 mmol) acetic
anhydride was added dropwise. After the mixture was allowed to stir for 15 h at room temperature, the
solution was poured into 120 mL H2O and stirred for another 20 min. The heterogeneous mixture was
separated and the aqueous layer was extracted with CH2Cl2 (30 mL × 4). The combined organic layers
were washed with brine (30 mL), dried (Na2SO4), filtered through celite and concentrated under reduced
pressure. Purification by flash chromatography on silica gel using EtOAc-hexanes for elution provided
the title compound as colourless oil.
Preparation of N-benzyl-3-(2-((tert-butyldimethylsilyl)oxy)ethyl) indole21:
Step 1: tert-Butyldimethylsilylchloride (1.66 g, 11.0 mmol, 1.1 equiv) was added to a solution of
tryptophol (1.61g, 10.0 mmol, 1.0 equiv) and imidazole (1.36 g, 20.0 mmol, 2.0 equiv) in DMF (50 mL)
at 0 °C. The ice bath was then removed and the reaction mixture was stirred at room temperature for 3 h.
The mixture was quenched with water (40 mL) and extracted with EtOAc (30 mL × 3), then the
combined organic layers were washed with water (30 mL × 3), brine (30 mL), separated and dried over
Na2SO4, then filtered and concentrated under reduced pressure. The residue was used directly for the next
step without further purification.
Step 2: To a solution of the above TBS-tryptophol in DMF (50 mL) was added NaH (400.0 mg, 10.0
mmol, 1.0 equiv, 60% dispersion in mineral oil) at 0 °C. After stirring at 0 ℃ fo15 min and then at room
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temperature for 1 h, the reaction mixture was cooled to 0 °C, treated with BnBr (1.88 g, 11.0 mmol, 1.1
equiv) and then allowed to stir at room temperature for 12 h. After the reaction was complete (monitored
by TLC), aqueous saturated NaHCO3 (30 mL) was added slowly. The organic layer was separated and the
aqueous layer was extracted with EtOAc (30 mL × 3). The combined organic layers were washed with
water (30 mL × 3), brine (30 mL), separated, dried over Na2SO4, filtered and concentrated under reduced
pressure. Purification by flash chromatography on silica gel using EtOAc-hexanes for elution provided
the title compound as pale yellow oil.
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Preparation of 3-halooxindoles
General procedure A:
Step 1: Preparation of N-substituted isatins22:
Substituted isatin (20.0 mmol) was dissolved in anhydrous DMF (80 mL), and the resultant solution
was cooled to 0 °C, whereupon sodium hydride (0.95 g, 24.0 mmol, 60% dispersion in mineral oil,) was
added in one portion and stirred for 10 minutes. Halide (30.0 mmol) was added slowly and the reaction
mixture was stirred at 0 °C for 30 min before stirring overnight at room temperature. The reaction mixture
was then poured into saturated aqueous NH4Cl and extracted with EtOAc (30 mL × 4). The combined
organic layers were washed with water (15 mL × 3) and brine (20 mL), then dried over Na2SO4, filtered,
and concentrated to give the crude N-substituted isatin product. Careful purification by column
chromatography on silica gel affords the pure product.
Step 2: Preparation of 3-hydroxyoxindoles22d, 23
:
The obove N-substituted isatin (34 mmol, 1.0 equiv) was dissolved in dry THF (200 mL) and the
solution was cooled (-78 °C or 0 °C). Newly purchased Grignard reagent (51 mmol, 1.5 equiv) was added
dropwise via a syringe to the solution. After that, the solution was warmed to room temperature slowly
and continued to stir for another several hours. Saturated aqueous NH4Cl (50 mL) was added and the
mixture was extracted with CH2Cl2 (50 mL × 3). The combined organic layers were washed with brine
(50 mL), dried with Na2SO4 and concentrated under reduced pressure to yield the crude product. Careful
purification by column chromatography on silica gel offords 3-hydroxyoxindole.
Step 3: Preparation of 3-chlorooxindole24:
A solution of 3-hydroxyoxindole (28.1 mmol, 1.0 equiv) and pyridine (281.0 mmol, 10.0 equiv) in
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CH2Cl2 (200 mL) was stirred at 0 °C under Ar atmosphere for 15min. Thionyl chloride (112.0 mmol, 4.0
equiv) was added dropwise and the solution was stirred at room temperature for several hours. Water (50
mL) was added and the mixture extracted with CH2Cl2 (50 mL × 3). The combined organic layers were
washed with water (50 mL × 2), saturated aqueous NaHCO3 (60 mL), brine (50 mL), dried with Na2SO4
and concentrated under reduced pressure to yield the crude product. The crude product was purified by
column chromatography on silica gel.
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General procedure B:
Step 1: General synthesis of N-methylindole25:
To a stirred solution of indole (17.1 mmol) in dry DMF (25 mL), NaH (820 mg, 20.5 mmol 60%
suspension in mineral oil) was added in portions under N2 atmosphere at 0 °C. The reaction mixture was
then warmed to room temperature and stirred for 30 min. After cooling to 0 °C again, MeI (1.28 mL, 20.5
mmol) was added dropwise. The reaction mixture was warmed to room temperature again and stirred
overnight. The mixture was quenched with water and the aqueous layer was extracted with ether (50 mL
× 3). The combined organic layer was washed with water (60 mL × 3), brine (50 mL), dried with Na2SO4
and concentrated under vacuum. The residue was purified by column chromatography on silica gel.
Step 2: Preparation of 3-chlorooxindole26:
Substituted indole (15.25 mmol, 1.0 equiv) was dissolved in a mixture of THF (10 mL), t-BuOH (100
mL) and H2O (1 mL). N–bromosuccinimide (NBS) or N–chlorosuccinimide (NCS) (30.49 mmol, 2.0
equiv) dissolved in cooled THF (100 mL) was added dropwise to this vigorously stirred reaction system
over a period of at least 1h. Then the mixture was leaved to warm to ambient temperature and stirred for
another several hours. Evaporating the solvents under reduced pressure, the resulting residue was purified
by column chromatography on silica gel.
The preparation of 17a:
Step 1: preparation of 1-benzyl-3-(2-((tert-butyldimethylsilyl)oxy)ethyl)-3-chloroindolin-2-one26:
1-benzyl-3-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-indole (15.25 mmol, 1.0 equiv) was dissolved in
a mixture of THF (10 mL), t-BuOH (100 mL), Et3N (31.5 mmol, 2.0 equiv) and H2O (1 mL). N–
chlorosuccinimide (NCS) (30.49 mmol, 2.0 equiv) dissolved in cooled THF (100 mL) was added
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dropwise to this vigorously stirred reaction system over a period of at least 1h. Then the mixture was
leaved to warm to ambient temperature and stirred for 5 hours. Evaporating the solvents under reduced
pressure, the resulting residue was purified by column chromatography on silica gel.
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Step 2: preparation of 17a21:
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The above product (10.0 mmol, 1.0 equiv) was treated with treated with tetra-N-butylammonium fluoride
(TBAF) (15.0 mmol, 1.5 equiv) in dry THF. After 24 h, the mixture was worked up and purified by
column chromatography on silica gel to afford the desired product 17a.
3-chloro-1,3-dimethylindolin-2-one (1a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H NMR (400MHz, CDCl3) δ 7.44 (d, J=7.2Hz, 1H), 7.38-7.34 (m, 1H),
7.15-7.12 (m, 1H), 6.86 (d, J=8.0Hz, 1H), 3.25 (s, 3H), 1.91 (s, 3H); 13C-NMR (100MHz, CDCl3) δ
174.4, 142.1, 131.1, 130.1, 123.8, 123.4, 108.7, 61.8, 26.6, 25.9. MS (ESI) Calculated m/z for [M+Na]+=
218.1. Experimental m/z for [M+Na]+= 218.7. Characterization data obtained for 1a matched those
previously reported in the literature27.
3-chloro-5-fluoro-1,3-dimethylindolin-2-one (2a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.19-7.16 (m, 1H), 7.08-7.03 (m, 1H), 6.79
(dd, J=8.6, 4.0Hz, 1H), 3.24, (s, 3H), 1.89 (s, 3H). 13C-NMR (100MHz, CDCl3) δ 174.1, 159.5 (d,
J=241Hz), 138.0 (d, J=2Hz), 132.4 (d, J=9Hz), 116.5 (d, J=24Hz), 111.9 (d, J=25Hz), 109.4 (d, J=8Hz),
61.4, 26.7, 25.8. MS (ESI) Calculated m/z for [M+Na]+ = 236.0. Experimental m/z for [M+Na]+= 235.9.
HRMS (ESI, m/z): Calculated for [C10H10ClFNO] [M+H]+ 214.0435, found 214.0429.
3,5-dichloro-1,3-dimethylindolin-2-one (3a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.41 (d, J=2.0Hz, 1H), 7.35-7.32 (m, 1H),
6.80 (d, J=8.4Hz, 1H), 3.24 (s, 3H), 1.90 (s, 3H). 13C-NMR (100MHz, CDCl3) δ 173.9, 140.6, 132.5,
130.1, 128.8, 124.4, 109.7, 61.2, 26.8, 25.8. MS (ESI) Calculated m/z for [M+Na]+ = 252.0. Experimental
m/z for [M+Na]+= 252.2. Characterization data obtained for 3a matched those previously reported in the
literature27.
5-bromo-3-chloro-1,3-dimethylindolin-2-one (4a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.52 (d, J=1.6Hz, 1H), 7.47-7.44 (m, 1H),
6.74 (d, J=8.4Hz, 1H), 3.21 (s, 3H), 1.87 (s, 3H). 13C-NMR (100MHz, CDCl3) δ 173.7, 141.0, 132.9,
132.7, 127.0, 115.8, 110.2, 61.1, 26.7, 25.7. MS (ESI) Calculated m/z for [M+NH4]+ = 293.0.
Experimental m/z for [M+NH4]+= 293.4. HRMS (ESI, m/z): Calculated for [C10H10BrClNO] [M+H]+
273.9634, found 273.9629.
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3-chloro-1,3,5-trimethylindolin-2-one (5a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
provided the title compound. 1H-NMR (400MHz, CDCl3) δ 7.25 (s, 1H), 7.14 (d, J=8.0Hz, 1H), 6.75 (d,
J=8.0Hz, 1H), 3.22 (s, 3H), 2.36 (s, 3H), 1.88 (s, 3H). 13C-NMR (100MHz, CDCl3) δ 174.3, 139. 6, 133.1,
130.9, 130.4, 124.5, 108.4, 62.0, 26.6, 25.9, 21.0. MS (ESI) Calculated m/z for [M+H]+ = 210.1.
Experimental m/z for [+M+H]+= 210.3. Characterization data obtained for 5a matched those previously
reported in the literature27.
3-chloro-5-methoxy-1,3-dimethylindolin-2-one (6a): The general method A was followed. After fast
chromatography with EtOAc/PE (75%), further purification by chromatography (14.3% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.04 (d, J=2.4Hz, 1H), 6.89-6.86 (m, 1H),
6.77 (d, J=8.4Hz, 1H), 3.83 (s, 3H), 3.23 (s, 3H), 1.89 (s, 3H); 13C-NMR (100MHz, CDCl3) δ 174.1,
156.6, 135.4, 132.1, 114.7, 110.8, 109.2, 62.1, 55.9, 26.7, 26.0; MS (ESI) Calculated m/z for [M+H]+ =
226.1. Experimental m/z for [M+H]+= 226.6. HRMS (ESI, m/z): Calculated for [C11H13ClNO2] [M+H]+
226.0635, found 226.0629.
3-chloro-7-fluoro-1,3-dimethylindolin-2-one (7a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.24-7.21 (m, 1H), 7.11-7.03 (m, 2H), 3.47
(d, J=2.8Hz, 3H), 1.90 (s, 3H). 13C-NMR (100MHz, CDCl3) δ 174.0, 147.7 (d, J=243Hz), 133.7, 124.0 (d,
J=6Hz), 119.7 (d, J=3Hz), 118.1 (d, J=19Hz), 117.9, 61.4, 29.7 (d, J=5Hz), 26.1. MS (ESI) Calculated
m/z for [M+Na]+ = 236.0. Experimental m/z for [M+Na]+= 236.0. HRMS (EI, m/z): Calculated for
[C10H9FNOCl] [M]+ 213.0357, found 213.0354.
3-chloro-1,3,5,7-tetramethylindolin-2-one (8a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
provided the title compound. 1H-NMR (400MHz, CDCl3) δ 7.09 (s, 1H), 6.88 (s, 1H), 3.50 (s, 3H), 2.53
(s, 3H), 2.31 (s, 3H), 1.87 (s, 3H); 13C-NMR (100MHz, CDCl3) δ 175.1, 137.3, 134.3, 133.0, 131.7,
122.4, 120.1, 61.7, 30.0, 26.2, 20.7, 18.7. MS (ESI) Calculated m/z for [M+H]+ = 224.1. Experimental
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m/z for [M+H]+= 224.5. HRMS (ESI, m/z): Calculated for [C12H15ClNO] [M+H]+ 224.0842, found
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3-chloro-1-ethyl-3-methylindolin-2-one (9a): The general method A was followed. After fast
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chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.43 (d, J=7.2Hz, 1H), 7.36-7.32 (m, 1H),
7.13-7.09 (m, 1H), 6.88 (d, J=8.0Hz, 1H), 3.78 (q, J=7.2Hz, 2H), 1.89 (s, 3H), 1,29 (t, J=7.2Hz, 3H). 13C-
NMR (100MHz, CDCl3) δ 173.9, 141.1, 131.1, 130.0, 123.9, 123.1, 108.8, 61.8, 35.1, 25.8, 12.4. MS
(ESI) Calculated m/z for [M+H]+ = 210.1. Experimental m/z for [M+H]+= 210.4. Characterization data
obtained for 9a matched those previously reported in the literature27.
3-chloro-3-ethyl-1-methyl-7-(trifluoromethyl)indolin-2-one (10a): The general method A was
followed. After fast chromatography with EtOAc/PE (50%), further purification by chromatography
(11.1% EtOAc/PE) provided the title compound. 1H-NMR (400MHz, CDCl3) δ 7.64 (d, J=8.0Hz, 1H), 7.
56 (d, J=7.2Hz, 1H), 7.23-7.18 (m, 1H), 3.44 (q, J=2.4Hz, 3H), 2.41-2.23 (m, 2H) 0.78 (t, J=7.2Hz, 3H).
13C-NMR (100MHz, CDCl3) δ 174.6, 140.8, 131.7, 127.9 (q, J=6Hz), 127.7, 123.2 (q, J=270Hz), 122.7,
113.0 (q, J=33Hz), 63.3, 32.8, 29.2 (q, J=7Hz), 8.6. MS (ESI) Calculated m/z for [M+NH4]+ = 295.1.
Experimental m/z for [M+NH4]+= 259.4. HRMS (ESI, m/z): Calculated for [C12H12ClF3NO] [M+H]+
278.0559, found 278.0554.
1-allyl-3-chloro-3-methylindolin-2-one (11a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.44-7.42 (m, 1H), 7.33-7.27 (m, 1H), 7.13-
7.09 (m, 1H), 6.85 (d, J=8.0Hz, 1H), 5.89-5.79 (m, 1H), 5.25 (d, J=1.2Hz, 1H), 5.22-5.21 (m, 1H), 4.41-
4.29 (m, 2H), 1.91 (s, 3H). 13C-NMR (100MHz, CDCl3) δ 174.0, 141.1, 130.8, 130.6, 130.0, 123.7, 123.3,
117.7, 109.5, 61.7, 42.4, 25.8. MS (ESI) Calculated m/z for [M+H]+ = 222.1. Experimental m/z for
[M+H]+= 222.3. HRMS (ESI, m/z): Calculated for [C12H13ClNO] [M+H]+ 222.0685, found 222.0680.
3-chloro-3-ethyl-1-(prop-2-yn-1-yl)indolin-2-one (12a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (10% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.42-7.36 (m, 2H), 7.19-7.15 (m, 1H), 7.08
(d, J=8.0Hz), 4. 64 (dd, J=17.6, 2. 4Hz, 1H), 4.42 (dd, J=17.6, 2.4Hz, 1H), 2.39-2.25 (m, 3H), 0.81 (t, J=7.
6Hz, 3H). 13C-NMR (100MHz, CDCl3) δ 173.0, 140.8, 130.0, 129.0, 124.2, 123.7, 109.6, 76.2, 72.7, 65.4,
32.8, 29.6, 8.7. MS (ESI) Calculated m/z for [M+Na]+ = 256.1. Experimental m/z for [M+Na]+= 256.0.
HRMS (ESI, m/z): Calculated for [C13H13ClNO] [M+H]+ 234.0685, found 234.0680.
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1-benzyl-3-chloro-3-methylindolin-2-one (13a): The general method A was followed. After fast
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.46-7.44 (m, 1H), 7.36-7.28 (m, 5H), 7.25-
7.21 (m, 1H), 7.12-7.08 (m, 1H), 6.73 (d, J=7.6 Hz, 1H), 4.99 (d, J=16.0Hz, 1H), 4.90 (d, J=16.0Hz, 1H),
1.97 (s, 3H); 13C-NMR (100MHz, CDCl3) δ 174.6, 141.2, 135.1, 131.0, 130.0, 128.9, 127.8, 127.1, 123.8,
123.4, 109.7, 61.8, 44.0, 25.9. MS (ESI) Calculated m/z for [M+H]+ = 272.1. Experimental m/z for
[M+H]+= 272.5. Characterization data obtained for 13a matched those previously reported in the
literature28.
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3-allyl-3-chloro-1-methylindolin-2-one (14a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (10% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.41 (d, J=7.2Hz, 1H), 7.38-7.33 (m, 1H),
7.14-7.10 (m, 1H), 6.85 (d, J=8.0Hz, 1H), 5.60-5.50 (m, 1H), 5.13-5.06 (m, 2H), 3.23 (s, 3H), 3.03 (m,
1H), 2.93 (m, 1H). 13C-NMR (100MHz, CDCl3) δ 173.5, 142.6, 130.1, 130.1, 129.0, 124.5, 123.2, 120.9,
108.6, 63.9, 43.1, 26.6. MS (ESI) Calculated m/z for [M+Na]+ = 244.1. Experimental m/z for [M+Na]+=
244.3. HRMS (ESI, m/z): Calculated for [C12H13ClNO] [M+H]+ 222.0685, found 222.0680.
3-allyl-1-benzyl-3-chloroindolin-2-one (15a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (7.7% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.44-7.42 (m, 1H), 7.35-7.26 (m, 5H), 7.25-
7.20 (m, 1H), 7.11-7.07 (m, 1H), 6.71 (d, J=8.0 Hz, 1H), 5.59-5.49 (m, 1H), 5.168 (dd, J=17.2, 1.2 Hz,
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1H), 5.10 (dd, J=10.2, 0.7Hz, 1H), 5.01 (d, J=15.6 Hz), 4.85 (d, J=16 Hz), 3.14-3.02 (m, 2H). C-NMR
(100MHz, CDCl3) δ 173.7, 141.8, 135.1, 130.2, 130.1, 128.9, 127.8, 127.2, 124.5, 123.2, 121.2, 109.7,
63.9, 44.0, 43.2. MS (ESI) Calculated m/z for [M+H]+ = 298.1. Experimental m/z for [M+H]+= 298.7.
HRMS (EI, m/z): Calculated for [C18H16ClNO] [M]+ 297.0920, found 297.0928.
3-chloro-3-ethyl-1-methylindolin-2-one (16a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.39-7.33 (m, 2H), 7.14-7.10 (m, 1H), 6.86
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(d, J=8.0Hz, 1H), 3,23 (s, 3H), 2.29 (qd, J=7.2, 2.4Hz, 2H), 0.81 (t, J=7. 6Hz, 3H); C-NMR (100MHz,
CDCl3) δ 173.9, 142.8, 130.0, 129.2, 124.1, 123.3, 108.5, 65.6, 32.5, 26.5, 8.8. MS (ESI) Calculated m/z
for [M+Na]+ = 232.1. Experimental m/z for [M+Na]+= 232.4. HRMS (EI, m/z): Calculated for
[C11H12ClNO] [M]+ 209.0607, found 209.0609.
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1-benzyl-3-chloro-3-(2-hydroxyethyl)indolin-2-one (17a): After fast chromatography with EtOAc,
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further purification by chromatography (20% EtOAc/PE) provided the title compound. H-NMR
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(400MHz, CDCl3) δ 7.39 (d, J=7.6 Hz, 1H), 7.36-7.22 (m, 6H), 7.13-7.09 (m, 1H), 6.74 (d, 8.0Hz, 1H),
4.94 (s, 2H), 4.06-3.99 (m, 1H), 3.70-3.62 (m, 1H), 2.70-2.63 (m, 1H), 2.50-2.41 (m, 1H); 13C-NMR
(100MHz, CDCl3) δ 175.1, 141.6, 134.9, 130.3, 129.5, 128.9, 127.9, 127.2, 124.1, 123.6, 110.0, 64.4,
59.0, 44.2, 41.2. MS (ESI) Calculated m/z for [M+H]+ = 302.1. Experimental m/z for [M+H]+= 302.9.
HRMS (EI, m/z): Calculated for [C17H16ClNO2] [M]+ 301.0870, found 301.0872.
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2-(1-benzyl-3-chloro-2-oxoindolin-3-yl)ethyl acetate (18a): The general method B was followed. After
fast chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.411 (d, J=7.2 Hz, 1H), 7.36-7.28 (m, 5H),
7.26-7.22 (m, 1H), 7.12-7.08 (m, 1H), 6.73 (d, J=8.0 Hz), 5.00 (d, J=15.6 Hz, 1H), 4.90 (d, J=15.6 Hz,
1H), 4.24-4.18 (m, 1H), 3.98-3.92 (m, 1H), 2.83-2.76 (m, 1H), 2.74-2.67 (m, 1H), 1.78 (s, 3H). 13C-NMR
(100MHz, CDCl3) δ 173.5, 170.4, 141.9, 135.0, 130.4, 128.9, 128.7, 127.8, 127.1, 124.4, 123.4, 109.9,
63.0, 60.0, 44.1, 37.6, 20.4. MS (ESI) Calculated m/z for [M+NH4]+ = 361.1. Experimental m/z for
[M+NH4]+= 361.4. HRMS (EI, m/z): Calculated for [C19H18ClNO3] [M]+ 343.0975, found 343.0987.
3-chloro-3-cyclopropyl-1-methylindolin-2-one (19a): The general method A was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (11.1% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, DMSO-d6) δ 7.47-7.45 (m, 1H), 7.43-7.39 (m, 1H),
7.14-7.08 (m, 1H), 3.17 (s, 3H), 1.72-1.65 (m, 1H), 0.73-0.64 (m, 2H), 0.62-0.55 (m, 1H), 0.38-0.32 (m,
1H); 13C-NMR (100MHz, DMSO-d6) δ 172.0, 142.2, 130.4, 127.8, 124.2, 123.0, 109.4, 66.8, 26.4, 18.1,
3.0, 2.7. MS (ESI) Calculated m/z for [M+H]+ = 222.1. Experimental m/z for [M+H]+= 222.8. HRMS
(ESI, m/z): Calculated for [C12H12NO] [M-Cl]+ 186.0919, found 186.0913.
3-bromo-1,3-dimethylindolin-2-one (20a): The general method B was followed. After fast
chromatography with EtOAc/PE (50%), further purification by chromatography (7.7% EtOAc/PE)
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provided the title compound. H-NMR (400MHz, CDCl3) δ 7.45 (d, J=7.2Hz, 1H), 7.36-7.32 (m, 1H),
7.15-7.11 (m, 1H), 6.85 (d, J=8.0Hz, 1H), 3.25 (s, 3H), 2.04 (s, 3H); 13C-NMR (100MHz, CDCl3) δ
174.7, 141.8, 131.6, 130.1, 124.1, 123.4, 108.7, 52.4, 26.7, 26.4. MS (ESI) Calculated m/z for [M+H]+ =
240.0. Experimental m/z for [M+H]+= 240.3. Characterization data obtained for 20a matched those
previously reported in the literature12.
General procedure for the visible light induced homocoupling of 3-halooxindole:
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In a 10 mL snap-cap vial equipped with a magnetic stirring bar and fitted with a septum, a (0.15 mmol,
1.0 equiv), DBU (0.15 mmol, 1.0 equiv), fac-Ir(ppy)3 (0.00075 mmol, 0.5 mol%) were dissolved in
CH3CN (0.06 M). The mixture was bubbled with a stream of argon for 30 min through a syringe needle.
The vial was then irradiated by using two 450 nm blue LED lamps for 15h. Upon removal of solvent
under vacuum, the residue was purified by flash chromatography on silica gel to afford pure (±)dl b and
crude meso b. The meso b can be purified by preparative TLC.
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1,1',3,3'-tetramethyl-[3,3'-biindoline]-2,2'-dione (1b) ((±)dl): In a 100 mL round-bottom flask
equipped with a magnetic stirring bar and fitted with a septum, a (1.00 g, 3.12 mmol), DBU (475 mg,
3.12 mmol), fac-Ir(ppy)3 (10.5 mg, 0.016 mmol) were dissolved in 50 mL CH3CN. The mixture was
bubbled with a stream of argon for 30 min through a syringe needle. The vial was then irradiated by using
three 450 nm blue LED lamps for 15h. Upon removal of solvent under vacuum, the residue was purified
by chromatography (14% EtOAc/PE) provided pure (±)dl 1b (375 mg, 45.8%) and crude meso 1b. The
crude meso 1b was further purified by preparative TLC with EtOAc/PE (16.7%) as solvent (288 mg,
35.2%). 1H-NMR (400MHz, CDCl3) δ 7.07 (d, J=7.2Hz, 2H), 7.05-7.00 (m, 2H), 6.85-6.81 (m, 2H), 6.45
(d, J=7.6Hz, 2H), 3.10 (s, 3H), 1.76 (s, 3H); 13C-NMR (100MHz, CDCl3) δ 178.1, 142.6, 131.1, 128.0,
122.8, 121.7, 107.3, 51.1, 25.7, 16.0. MS (ESI) Calculated m/z for [M+H]+ = 321.2. Experimental m/z for
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[M+H]+= 321.3. (meso): H-NMR (400MHz, CDCl3) δ 7.25-7.23 (m, 2H), 6.89-6.85 (m, 2H), 6.72 (d,
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J=8.0Hz, 2H), 6.62 (m, J=6.4Hz, 2H), 2.98 (s, 6H), 1.68 (s, 6H); C-NMR (100MHz, CDCl3) δ 177.6,
143.7, 131.1, 128.5, 123.6, 121.6, 107.9, 51.6, 25.9, 17.3. MS (ESI) Calculated m/z for [M+H]+ = 321.2.
Experimental m/z for [M+H]+= 321.5. Characterization data obtained for 1b matched those previously
reported in the literature9f.
5,5'-difluoro-1,1',3,3'-tetramethyl-[3,3'-biindoline]-2,2'-dione (2b) ((±)dl): The general method was
followed. Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 2b (10.4 mg, 39.6%) and
crude meso 2b. The crude meso 2b was further purified by preparative TLC with EtOAc/PE (16.7%) as
solvent (13.5 mg, 51.4%). 1H-NMR (400MHz, CDCl3) δ 6.86-6.83 (m, 2H), 6.79-6.74 (m, 2H), 6.45-6.42
(m, 2H), 3.13 (s, 6H), 1.75 (s, 6H); 13C-NMR (100MHz, CDCl3) δ 177.5, 158.9 (d, J=239Hz), 138.4,
132.5 (d, J=9Hz), 114.4 (d, J=23Hz), 111.2 (d, J=25Hz), 107.9 (d, J=8Hz), 51.3, 25.9, 16.1. HRMS (ESI,
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m/z): Calculated for [C20H19F2N2O2] (M+H)+ 357.1414, found 357.1403. (meso): H-NMR (400MHz,
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CDCl3) δ 7.02-6.97 (m, 2H), 6.69-6.66 (m, 2H), 6.41 (d, J=7.2Hz, 2H), 3.00 (s, 6H), 1.67 (s, 6H); C-
NMR (100MHz, CDCl3) δ 177.0, 158.5 (d, J=239Hz), 139.7, 132.2 (d, J=8Hz), 114.9 (d, J=23Hz), 11.8
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(d, J=25Hz), 108.4 (d, J=8Hz), 51.8, 26.1, 17.3. HRMS (ESI, m/z): Calculated for [C20H19F2N2O2]
(M+H)+ 357.1414, found 357.1404.
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5,5'-dichloro-1,1',3,3'-tetramethyl-[3,3'-biindoline]-2,2'-dione (3b) ((±)dl): The general method was
followed. Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 3b (11.7 mg, 40.1%) and
crude meso 3b. The crude meso 3b was further purified by preparative TLC with EtOAc/PE (16.7%) as
solvent (9.0 mg, 31%). 1H-NMR (400MHz, CDCl3) δ 7.05-7.01 (m, 4H), 6.43 (d, J=8.4Hz, 2H), 3.12 (s,
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6H), 1.73 (s, 6H). C-NMR (100MHz, CDCl3) δ 177.3, 141.1, 132.3, 128.1, 127.4, 123.5, 108.4, 51.3,
25.9, 15.6. MS (ESI) Calculated m/z for [M+H]+ = 389.1. Experimental m/z for [M+H]+= 389.2. (meso):
1H-NMR (400MHz, CDCl3) δ 7.28-7.26 (m, 2H), 6.69 (d, J=8.4Hz, 2H), 6.61 (m, 2H), 2.98 (s, 6H), 1.66
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(s, 6H). C-NMR (100MHz, CDCl3) δ 176.8, 142.3, 132.2, 128.6, 127.1, 124.1, 108.9, 51.8, 26.1, 17.1.
MS (ESI) Calculated m/z for [M+H]+ = 389.1. Experimental m/z for [M+H]+= 389.4. Characterization
data obtained for 3b matched those previously reported in the literature29.
5,5'-dibromo-1,1',3,3'-tetramethyl-[3,3'-biindoline]-2,2'-dione (4b) ((±)dl): The general method was
followed. Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 4b (13.2 mg, 36.8%) and
crude meso 4b. The crude meso 4b was further purified by preparative TLC with EtOAc/PE (16.7%) as
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solvent (19.8 mg, 55.2%). H-NMR (400MHz, CDCl3) δ 7.19-7.17 (m, 4H), 6.39-6.37 (m, 2H), 3.12 (s,
6H), 1.73 (s, 6H); 13C-NMR (100MHz, CDCl3) δ 177.2, 141.6, 132.5, 131.0, 126.2, 114.6, 109.0, 51.3,
25.8, 15.4. HRMS (ESI, m/z): Calculated for [C20H19Br2N2O2] (M+H)+ 476.9808, found 476.9814.
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(meso): H-NMR (400MHz, CDCl3) δ 7.43-7.41 (m, 2H), 6.73 (m, 2H), 6.65 (d, J=8.4Hz, 2H), 2.97 (s,
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6H), 1.65 (s, 6H); C-NMR (100MHz, CDCl3) δ 176.7, 142.8, 132.5, 131.6, 126.8, 114.3, 109.4, 51.8,
26.1, 17.0. HRMS (ESI, m/z): Calculated for [C20H19Br2N2O2] (M+H)+ 476.9808, found 476.9802.
1,1',3,3',5,5'-hexamethyl-[3,3'-biindoline]-2,2'-dione (5b) ((±)dl): The general method was followed.
Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 5b (11.2 mg, 42.9%) and crude
meso 5b. The crude meso 5b was further purified by preparative TLC with EtOAc/PE (16.7%) as solvent
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(12.6 mg, 48.1%). H-NMR (400MHz, CDCl3) δ 6.90 (s, 2H), 6.83 (dd, J=7.9, 0.8Hz, 2H), 6.34 (d,
J=8.0Hz, 2H), 3.08 (s, 6H), 2.21 (s, 6H), 1.74 (s, 6H); 13C-NMR (100MHz, CDCl3) δ 178.1, 140.2, 131.2,
131.2, 128.1, 123.8, 106.9, 51.1, 25.7, 21.0, 16.0. HRMS (ESI, m/z): Calculated for [C22H25N2O2]
(M+H)+ 349.1911, found 349.1915. (meso): 1H-NMR (400MHz, CDCl3) δ 7.05 (d, J=7.6Hz, 2H), 6.60 (d,
J=8.0Hz, 2H), 6.40 (m, 6H), 2.94 (s, 6H), 2.22 (s, 6H), 1.66 (s, 6H); 13C-NMR (100MHz, CDCl3) δ 177.6,
141.4, 131.1, 130.8, 128.5, 124.6, 107.3, 51.7, 25.9, 21.1, 17.2. HRMS (ESI, m/z): Calculated for
[C22H25N2O2] (M+H)+ 349.1911, found 349.1904.
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5,5'-dimethoxy-1,1',3,3'-tetramethyl-[3,3'-biindoline]-2,2'-dione (6b) ((±)dl): The general method was
followed. Purification by chromatography (20% EtOAc/PE) provided pure (±)dl 6b (9.6 mg, 34%) and
crude meso 6b. The crude meso 6b was further purified by preparative TLC with EtOAc/PE (25%) as
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solvent (10.6 mg, 37.2%). H-NMR (400MHz, CDCl3) δ 6.742-6.736 (m, 2H), 6.60-6.58 (m, 2H), 6.41-
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6.39 (m, 2H), 3.70 (s, 6H), 3.11 (s, 6H), 1.75 (s, 6H); 13C-NMR (100MHz, CDCl3) δ 177.8, 155.6, 136.0,
132.4, 112.9, 110.0, 107.7, 55.8, 51.3, 25.9, 16.5. MS (ESI) Calculated m/z for [M+H]+ = 381.2.
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Experimental m/z for [M+H]+= 381.3. (meso): H-NMR (400MHz, CDCl3) δ 6.80-6.78 (m, 2H), 6.65-
6.63 (m, 2H), 6.30 (m, 2H), 3.66 (s, 6H), 2.97 (s, 6H), 1.67 (s, 6H); 13C-NMR (100MHz, CDCl3) δ 177.2,
155.1, 137.4, 132.3, 113.0, 111.2, 108.1, 55.8, 51.9, 26.0, 17.4. MS (ESI) Calculated m/z for [M+H]+ =
381.2. Experimental m/z for [M+H]+= 381.5. Characterization data obtained for 3b matched those
previously reported in the literature30.
7,7'-difluoro-1,1',3,3'-tetramethyl-[3,3'-biindoline]-2,2'-dione (7b) ((±)dl): The general method was
followed. Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 7b (11.5 mg, 43.0%) and
crude meso 7b. The crude meso 7b was further purified by preparative TLC with EtOAc/PE (16.7%) as
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solvent (10.4 mg, 39.0%). H-NMR (400MHz, CDCl3) δ 6.89-6.84 (m, 2H), 6.82-6.77 (m, 4H), 3.32 (d,
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J=2.8Hz, 6H), 1.74 (s, 6H); C-NMR (100MHz, CDCl3) δ 177.5, 147.1 (d, J=242Hz), 133.8, 129.3 (d,
J=9Hz), 122.5 (d, J=7Hz), 118.8 (d, J=3Hz), 116.2 (d, J=19Hz), 51.4, 28.2 (d, J=6Hz), 16.3. HRMS (ESI,
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m/z): Calculated for [C20H19F2N2O2] (M+H)+ 357.1409, found 357.1405. (meso): H-NMR (400MHz,
CDCl3) δ 7.03-6.97 (m, 2H), 6.86-6.81 (m, 2H), 6.44-6.42 (m, 2H), 3.21 (d, J=2.8Hz, 6H), 1.66 (s, 6H);
13C-NMR (100MHz, CDCl3) δ 177.1, 147.5 (d, J=242Hz), 133.6, 130.5, 122.1 (d, J=7Hz), 119.4 (d,
J=4Hz), 116.6 (d, J=19Hz), 51.9, 28.4 (d, J=6Hz), 17.5. HRMS (ESI, m/z): Calculated for [C20H19F2N2O2]
(M+H)+ 357.1409, found 357.1414.
1,1',3,3',5,5',7,7'-octamethyl-[3,3'-biindoline]-2,2'-dione (8b) ((±)dl): The general method was
followed. Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 8b (13.3 mg, 47.1%) and
crude meso 8b. The crude meso 8b was further purified by preparative TLC with EtOAc/PE (16.7%) as
solvent (12.1 mg, 42.9%). 1H-NMR (400MHz, CDCl3) δ 6.72 (s, 2H), 6.57 (s, 2H), 3.36 (s, 6H), 2.27 (s,
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6H), 2.18 (s, 6H), 1.59 (s, 6H). C-NMR (100MHz, CDCl3) δ 178.8, 137.9, 132.0, 131.9, 130.8, 121.5,
118.3, 50.7, 29.0, 20.6, 18.7, 16.2. HRMS (ESI, m/z): Calculated for [C24H29N2O2] (M+H)+ 377.2224,
found 377.2216. (meso): 1H-NMR (400MHz, CDCl3) δ 6.78 (s, 1H), 6.19 (s, 1H), 3.19 (m, 3H), 2.43 (s,
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3H), 2.12 (s, 3H), 1.60 (s, 3H). C-NMR (100MHz, CDCl3) δ 178.4, 139.1, 132.3, 131.6, 130.4, 112.4,
118.7, 51.3, 29.2, 20.7, 18.8, 17.1. HRMS (ESI, m/z): Calculated for [C24H29N2O2] (M+H)+ 377.2224,
found 377.2217.
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1,1'-diethyl-3,3'-dimethyl-[3,3'-biindoline]-2,2'-dione (9b) ((±)dl): The general method was followed.
Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 9b (12.6 mg, 48.2%) and crude
meso 9b. The crude meso 9b was further purified by preparative TLC with EtOAc/PE (16.7%) as solvent
(11.4 mg, 43.8%). 1H-NMR (400MHz, CDCl3) δ 7.15 (d, J=7.6Hz, 2H), 7.05-7.01 (m, 2H), 6.82-6.79 (m,
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2H), 6.52 (d, J=7.6Hz, 2H), 3.82-3.73 (m, 2H), 3.61 (m, 2H), 1.76 (s, 6H), 1.21 (t, J=7.2Hz, 6H); C-
NMR (100MHz, CDCl3) δ 177.9, 141.7, 131.4, 127.9, 123.7, 121.6, 107.5, 50.5, 30.5, 16.9, 12.5. MS
(ESI) Calculated m/z for [M+H]+ = 349.2. Experimental m/z for [M+H]+= 349.4. (meso): H-NMR
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(400MHz, CDCl3) δ 7.25-7.21 (m, 2H), 6.86-6.83 (m, 2H), 6.72 (d, J=7.6Hz, 2H), 6.61 (m, 2H), 3.73 (m,
2H), 3.40 (m, 2H), 1.67 (s, 6H), 0.90 (m, 6H); 13C-NMR (100MHz, CDCl3) δ 177.1, 142.9, 131.3, 128.3,
123.9, 121.4, 107.8, 51.3, 34.2, 17.3, 11.9. MS (ESI) Calculated m/z for [M+H]+ = 349.2. Experimental
m/z for [M+H]+= 349.4. Characterization data obtained for 9b matched those previously reported in the
literature31.
3,3'-diethyl-1,1'-dimethyl-7,7'-bis(trifluoromethyl)-[3,3'-biindoline]-2,2'-dione (10b) ((±)dl): The
general method was followed. Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 10b
(17.0 mg, 46.8%) and crude meso 10b. The crude meso 10b was further purified by preparative TLC with
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EtOAc/PE (16.7%) as solvent (16.8 mg, 46.2%). H-NMR (400MHz, CDCl3) δ 7.32 (d, J=8.0Hz, 2H),
7.12 (d, J=7.2Hz, 2H), 6.95-6.91 (m, 2H), 3.28 (t, J=2.4Hz, 6H), 2.80-2.71 (m, 2H), 2.41-2.33 (m, 2H),
0.42 (t, J=7.4Hz, 6H); 13C-NMR (100MHz, CDCl3) δ 177.9, 141.2, 130.6, 126.2 (q, J=6.0Hz), 126.1,
123.2 (q, J=270.0Hz), 121.0, 111.8 (q, J=33.0Hz), 56.3, 28.2 (q, J=7.0Hz), 21.2, 8.8. HRMS (ESI, m/z):
Calculated for [C24H23F6N2O2] (M+H)+ 485.1641, found 485.1649. (meso): 1H-NMR (400MHz, CDCl3)
δ 7.57 (d, J=8.0Hz, 2H), 6.98-6.95 (m, 2H), 6.68 (m, 2H), 3.13 (d, J=2.0Hz, 6H), 2.75 (m, 2H), 2.05 (m,
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2H), 0.44 (m, 6H); C-NMR (100MHz, CDCl3) δ 177.1, 142.8, 130.7, 126.9 , 126.7(q, J=6.0Hz), 123.4
(q, J=294.7Hz), 120.8, 112.2 (q, J=33Hz), 56.7, 28.5 (q, J=6.0Hz), 22.7, 8.6. HRMS (ESI, m/z):
Calculated for [C24H23F6N2O2] (M+H)+ 485.1641, found 485.1650.
1,1'-diallyl-3,3'-dimethyl-[3,3'-biindoline]-2,2'-dione (11b) ((±)dl): The general method was followed.
Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 11b (10.4 mg, 37.2%) and crude
meso 11b. The crude meso 11b was further purified by preparative TLC with EtOAc/PE (16.7%) as
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solvent (9.5 mg, 34%). H-NMR (400MHz, CDCl3) δ 7.14 (d, J=7.2Hz, 2H), 7.03-7.00 (m, 2H), 6.84-
6.80 (m,2H), 6.53 (d, J=8.0Hz, 2H), 5.79-5.69 (m, 2H), 5.20-5.13 (m, 2H), 4.37-4.32 (m, 4H), 4.26-4.20
(m, 2H), 1.78 (s, 6H); 13C-NMR (100MHz, CDCl3) δ 177.9, 141.9, 131.3, 131.2, 128.0, 123.7, 121.9,
118.0, 108.4, 50.6, 42.3, 17.2. HRMS (ESI, m/z): Calculated for [C24H25N2O2] (M+H)+ 373.1916, found
373.1902. (meso): 1H-NMR (400MHz, CDCl3) δ 7.23-7.20 (m, 2H), 6.88-6.85 (m, 2H), 6.72 (d, J=7.6Hz,
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2H), 6.64 (m, 2H), 5.47-5.35 (m, 2H), 5.05-4.97 (m, 4H), 4.35-4.29 (m, 2H), 4.00 (dd, J=16.3, 5.8Hz, 2H),
1.71 (s, 6H); 13C-NMR (100MHz, CDCl3) δ 177.3, 143.0, 131.6, 131.2, 128.3, 123.8, 121.7, 117.2, 108.8,
51.4, 42.2, 17.7. HRMS (ESI, m/z): Calculated for [C24H25N2O2] (M+H)+ 373.1916, found 373.1905.
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3,3'-diethyl-1,1'-di(prop-2-yn-1-yl)-[3,3'-biindoline]-2,2'-dione (12b) ((±)dl): The general method was
followed. Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 12b (11.2 mg, 37.8%)
and crude meso 12b. The crude meso 12b was further purified by preparative TLC with EtOAc/PE
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(16.7%) as solvent (7.4 mg, 25%). H-NMR (400MHz, CDCl3) δ 7.08-7.02 (m, 4H), 6.87-6.83 (m, 2H),
6.67 (d, J=7.6Hz, 2H), 4.51 (dd, J=17.6, 2.4Hz, 2H), 4.38 (dd, J=17.6, 2.8Hz, 2H), 2.82 (m, 2H), 2.37 (m,
2H), 2.18 (t, J=2.4Hz, 2H), 0.40 (t, J=7.4Hz, 6H); 13C-NMR (100MHz, CDCl3) δ 176.6, 141.6, 128.4,
127.9, 123.5, 122.6, 108.0, 76.6, 72.1, 56.9, 28.8, 22.3, 8.6. HRMS (ESI, m/z): Calculated for
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[C26H25N2O2] (M+H)+ 397.1911, found 397.1904. (meso): H-NMR (400MHz, CDCl3) δ 7.29-7.24 (m,
2H), 6.92-6.89 (m, 4H), 6.59 (d, J=5.6Hz), 4.45 (dd, J=17.6, 2.0Hz, 2H), 4.12 (dd, J=17.6, 2.4Hz, 2H),
2.78 (m, 2H), 2.11 (m, 2H), 0.46 (m, 6H); 13C-NMR (100MHz, CDCl3) δ 176.6, 141.5, 128.4, 127.9,
123.5, 122.6, 108.0, 76.6, 72.1, 57.0, 28.8, 22.3, 8.6. HRMS (ESI, m/z): Calculated for [C26H25N2O2]
(M+H)+ 397.1911, found 397.1903.
1,1'-dibenzyl-3,3'-dimethyl-[3,3'-biindoline]-2,2'-dione (13b) ((±)dl): The general method was
followed. Purification by chromatography (11.1% EtOAc/PE) provided pure (±)dl 13b (11.3 mg, 32%)
and crude meso 13b. The crude meso 13b was further purified by preparative TLC with EtOAc/PE
(12.5%) as solvent (11.7 mg, 33%). 1H-NMR (400MHz, CDCl3) δ 7.24-7.14 (m, 10H), 7.09 (d, J=8.0Hz,
2H), 6.98-6.95 (m, 2H), 6.71-6.67 (m, 2H), 6.49 (d, J=8.0Hz, 2H), 5.04 (d, J=16.0Hz, 2H), 4.71 (d,
J=16.0Hz, 2H), 1.87 (s, 6H); 13C-NMR (100MHz, CDCl3) δ 178.4, 141.8, 135.6, 131.3, 128.7, 128.4,
127.9, 127.6, 123.5, 122.1, 108.5, 50.7, 43.7, 17.7. HRMS (EI, m/z): Calculated for [C32H28N2O2] [M]+
472.2151, found 472.2154. (meso): 1H-NMR (400MHz, CDCl3) δ 7.18-7.13 (m, 8H), 6.97 (m, 4H), 6.84-
6.80 (m, 2H), 6.70 (m, 2H), 6.59 (d, J=8.0Hz, 2H), 4.94 (d, J=15.6Hz, 2H), 4.66 (d, J=15.6Hz, 2H), 1.81
(s, 6H); 13C-NMR (100MHz, CDCl3) δ 178.0, 142.9, 135.8, 131.4, 128.6, 128.4, 127.1(127.14),
127.1(127.05), 123.9, 122.0, 109.2, 51.3, 43.8, 18.6. HRMS (EI, m/z): Calculated for [C32H28N2O2] [M]+
472.2151, found 472.2155.
3,3'-diallyl-1,1'-dimethyl-[3,3'-biindoline]-2,2'-dione (14b) ((±)dl): The general method was followed.
Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 14b (8.1 mg, 29%) and crude
meso 14b. The crude meso 14b was further purified by preparative TLC with EtOAc/PE (16.7%) as
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solvent (5.6 mg, 20%). H-NMR (400MHz, CDCl3) δ 7.06-6.99 (m, 4H), 6.85-6.81 (m, 2H), 6.417 (d,
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J=7.6Hz, 2H), 5.10-4.97 (m, 4H), 4.77-4.74 (m, 2H), 3.67-3.62 (m, 2H), 3.07-3.01 (m, 8H). C-NMR
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(100MHz, CDCl3) δ 176.9, 143.3, 132.5, 128.2, 128.1, 123.4, 121.6, 118.8, 107.2, 55.9, 33.2, 25.6. MS
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(ESI) Calculated m/z for [M+H]+= 373.3. Experimental m/z for [M+H]+= 373.5. (meso): H-NMR
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(400MHz, CDCl3) δ 7.26-7.22 (m, 2H), 6.89-6.85 (m, 2H), 6.69 (d, J=8.0Hz, 2H), 6.61 (d, J=8.0Hz, 2H),
5.15-5.05 (m, 2H), 4.97-4.93 (m, 2H), 4.77 (dd, J=11.6, 1.6Hz, 2H), 3.48 (dd, J=12.0, 7.6Hz, 2H), 2.94 (s,
6H), 2.89 (dd, J=13.2, 6.8Hz, 2H). 13C-NMR (100MHz, CDCl3) δ 176.0, 144.6, 132.0, 128.5, 128.4,
124.1, 121.5, 119.2, 107.8, 56.5, 34.7, 25.8. MS (ESI) Calculated m/z for [M+H]+ = 373.3. Experimental
m/z for [M+H]+= 373.3. Characterization data obtained for 14b matched those previously reported in the
literature32.
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3,3'-diallyl-1,1'-dibenzyl-[3,3'-biindoline]-2,2'-dione (15b) ((±)dl): The general method was followed.
Purification by chromatography (9.1% EtOAc/PE) provided pure (±)dl 15b (6.3 mg, 16%) and crude
meso 15b. The crude meso 15b was further purified by preparative TLC with EtOAc/PE (11.1%) as
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solvent (9.4 mg, 24%). H-NMR (400MHz, CDCl3) δ 7.37-7.22 (m, 14H), 7.18 (d, J=8.0Hz, 2H), 6.94-
6.91 (m, 2H), 6.73-6.70 (m, 2H), 6.36 (d, J=7.6Hz, 2H), 5.13 (d, J=15.6Hz, 2H), 5.09-5.05 (m, 4H), 4.82-
4.79 (m, 2H), 4.48 (d, J=15.6Hz, 2H), 3.76 (dd, J=14.6, 3.4Hz, 2H), 3.12 (td, J=8.0, 4.0Hz, 2H). 13C-
NMR (100MHz, CDCl3) δ 177.1, 142.8, 135.5, 132.5, 128.6, 128.2, 128.0, 127.6, 127.5, 124.0, 121.9,
119.2, 108.4, 55.7, 43.7, 34.1. MS (ESI) Calculated m/z for [M+Na]+ = 547.3. Experimental m/z for
[M+Na]+= 547.7. (meso): 1H-NMR (400MHz, CDCl3) δ 7.19-7.12 (m, 4H), 6.98 (m, 2H), 6.86-6.82 (m,
1H), 6.69 (m, 1H), 6.54 (d, J=7.8Hz, 1H), 5.19-5.09 (m, 1H), 5.02 (dd, J=17.0, 2.0Hz, 1H), 4.83 (dd,
J=9.8, 2.2Hz, 1H), 4.80-4.71 (m, 2H), 3.65-3.60 (dd, J=12.4, 7.6Hz, 1H), 3.01-2.96 (dd, J=13.2, 10.0Hz,
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1H). C-NMR (100MHz, CDCl3) δ 176.3, 143.9, 135.7, 131.8, 128.6, 128.5 (128.54), 128.5 (128.48),
127.1, 124.3, 121.8, 119.6, 109.1, 56.3, 43.8, 35.5, 29.7. MS (ESI) Calculated m/z for [M+Na]+ = 547.3.
Experimental m/z for [M+Na]+= 547.4. Characterization data obtained for 15b matched those previously
reported in the literature32.
3,3'-diethyl-1,1'-dimethyl-[3,3'-biindoline]-2,2'-dione (16b) ((±)dl): The general method was followed.
Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 16b (10.2 mg, 39.0%) and crude
meso 16b. The crude meso 16b was further purified by preparative TLC with EtOAc/PE (16.7%) as
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solvent (9.9 mg, 38%). H-NMR (400MHz, CDCl3) δ 7.03-7.00 (m, 4H), 6.85-6.81 (m, 2H), 6.43-6.41
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(m, 2H), 3.08 (s, 6H), 2.85-2.76 (m, 2H), 2.40-2.31 (m, 2H), 0.41 (t, J=7.2Hz, 6H); 13C-NMR (100MHz,
CDCl3) δ 177.5, 143.6, 128.7, 127.9, 123.1, 121.6, 107.1, 57.4, 25.5, 21.5, 8.9. HRMS (ESI, m/z):
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Calculated for [C22H25N2O2] (M+H)+ 349.1911, found 349.1914. (meso): H-NMR (400MHz, CDCl3) δ
7.26-7.22 (m, 2H), 6.88-6.84 (m, 2H), 6.70 (d, J=8.0Hz, 2H), 6.55 (m, 2H), 2.96 (s, 6H), 2.81-2.72 (m,
2H), 2.15-2.06 (m, 2H), 0.44 (t, J=7.8Hz, 6H); 13C-NMR (100MHz, CDCl3) δ 176.7, 144.8, 128.8, 128.3,
123.9, 121.4, 107.6, 57.9, 25.7, 23.0, 8.6. HRMS (ESI, m/z): Calculated for [C22H25N2O2] (M+H)+
349.1911, found 349.1912.
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1,1'-dibenzyl-3,3'-bis(2-hydroxyethyl)-[3,3'-biindoline]-2,2'-dione (17b) ((±)dl): The general method
was followed. Purification by chromatography (33% EtOAc/CH2Cl2) provided pure (±)dl 17b (10.0 mg,
25.0%) and crude meso 17b. The crude meso 17b was further purified by preparative TLC with
EtOAc/CH2Cl2 (33%) as solvent (8.0 mg, 20%). 1H-NMR (400MHz, d6) δ 7.32-7.23 (m, 10H), 6.95-6.91
(m, 2H), 6.90-6.88 (m, 2H), 6.71-6.67 (m, 2H), 6.52 (d, J=8.0Hz, 2H), 5.15 (d, J=16.0Hz, 2H), 4.45-4.41
(m, 4H), 3.08-3.01 (m, 2H), 2.85-2.81 (m, 4H), 2.44-2.37 (m, 2H). 13C-NMR (100MHz, CDCl3) δ 178.2,
142.9, 135.6, 128.6, 128.3, 127.7, 127.6, 127.2, 124.1, 121.7, 108.7, 59.6, 54.2, 44.1, 32.0. MS (ESI)
Calculated m/z for [M+H]+ = 533.3. Experimental m/z for [M+H]+= 533.2. (meso): 1H-NMR (400MHz,
d6) δ 7.22-7.17 (m, 8H), 7.00 (m, 4H), 6.84 (m, 2H), 6.67-6.45 (m, 4H), 4.70-4.63 (m, 4H), 4.48-4.45 (m,
2H), 3.00-2.92 (m, 4H), 2.73-2.68 (m, 2H), 2.40-2.31 (m, 2H). 13C-NMR (100MHz, CDCl3) δ 177.1,
143.9, 135.7, 128.9, 128.6, 128.1, 127.3, 127.1, 124.3, 122.0, 109.4, 59.3, 44.2, 34.0, 29.7. MS (ESI)
Calculated m/z for [M+H]+ = 533.3. Experimental m/z for [M+H]+= 533.4. Characterization data
obtained for 17b matched those previously reported in the literature9b,32
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(1,1'-dibenzyl-2,2'-dioxo-[3,3'-biindoline]-3,3'-diyl)bis(ethane-2,1-diyl) diacetate (18b) ((±)dl): The
general method was followed. Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 18b
(12.5 mg, 27.0%) and crude meso 18b. The crude meso 18b was further purified by preparative TLC with
EtOAc/PE (16.7%) as solvent (12.1 mg, 26.2%). 1H-NMR (400MHz, CDCl3) δ 7.35-7.26 (m, 10H), 7.01-
6.94 (m, 4H), 6.68-6.64 (m, 2H), 6.43 (d, J=8.0Hz, 2H), 5.01 (d, J=15.6Hz, 2H), 4.61 (d, J=15.6Hz, 2H),
3.89 (d, J=12.0, 6.0Hz, 2H), 3.51 (td, J=11.2, 6.0Hz, 2H), 3.39-3.32 (m, 2H), 2.78-2.71 (m, 2H), 1.77 (s,
6H). 13C-NMR (100MHz, CDCl3) δ 177.0, 170.5, 142.8, 135.3, 128.7, 128.5, 127.72, 127.69, 126.9,
124.1, 122.1, 108.7, 6.9, 54.0, 44.1, 28.1, 20.1. HRMS (ESI, m/z): Calculated for [C38H37N2O6] (M+H)+
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617.2646, found 617.2636. (meso): H-NMR (400MHz, CDCl3) δ 7.19-7.13 (m, 4H), 6.99 (m, 2H), 6.83
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(m, 1H), 6.66-6.56 (m, 2H), 4.86 (d, J=15.7Hz, 1H), 4.69 (m, 1H), 3.81-3.72 (m, 2H), 3.22 (m, 1H), 2.65-
2.58 (m, 1H), 1.68 (s, 3H). 13C-NMR (100MHz, CDCl3) δ 175.9, 170.5, 143.8, 135.5, 128.9, 128.6, 127.9,
127.3, 127.0, 124.3, 122.1, 109.5, 60.7, 54.6, 44.1, 29.6, 20.4. HRMS (ESI, m/z): Calculated for
[C38H37N2O6] (M+H)+ 617.2646, found 617.2632.
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3,3'-dicyclopropyl-1,1'-dimethyl-[3,3'-biindoline]-2,2'-dione (19b) ((±)dl): The general method was
followed. Purification by chromatography (14% EtOAc/PE) provided pure (±)dl 19b (12.0 mg, 43.0%)
and crude meso 19b. The crude meso 19b was further purified by preparative TLC with EtOAc/PE
(16.7%) as solvent (10.0 mg, 35.8%). 1H-NMR (400MHz, CDCl3) δ 7.07 (d, J=7.2Hz, 2H), 7.04-7.00 (m,
2H), 6.83-6.79 (m, 2H), 6.45 (d, J=8.0Hz, 2H), 3.07 (s, 6H), 2.34-2.27 (m, 2H), 0.810-0.746 (m, 2H),
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0.66-0.59 (m, 2H), 0.53-0.45 (m, 2H). C-NMR (100MHz, CDCl3) δ 175.6, 142.9, 129.3, 127.9, 123.4,
121.6, 107.2, 55.8, 25.6, 11.5, 2.01, 2.05. HRMS (ESI, m/z): Calculated for [C24H25N2O2] (M+H)+
373.1911, found 373.1904. (meso): 1H-NMR (400MHz, CDCl3) δ 7.26-7.22 (m, 1H), 6.81-6.78 (m, 1H),
6.70 (d, J=7.6Hz, 1H), 6.59 (m, 1H), 3.01 (s, 3H), 2.38-2.31 (m, 1H), 0.80-0.73 (m, 1H), 0.57-0.51 (m,
1H), 0.39-0.32 (m, 1H), (-0.42)-(-0.48) (m, 1H). 13C-NMR (100MHz, CDCl3) δ 177.5, 145.2, 128.9,
125.9, 125.7, 121.1, 107.9, 56.4, 26.1, 11.3, 4.3, -0.5. HRMS (ESI, m/z): Calculated for [C24H25N2O2]
(M+H)+ 373.1911, found 373.1904.
ASSOCIATED CONTENT
Supporting Information
Characterization data, spectral data, and crystal data for 16b (PDF)
X-ray data for 16b (CIF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: liuqiang@lzu.edu.cn
*E-mail: lzwu@mail.ipc.ac.cn.
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
We are grateful for financial support from the Ministry of Science and Technology of China
(2013CB834804), NSFC (21572090 and 21172102), and the fundamental research funds for the central
universities (lzujbky-2015-49).
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