Iodine-Catalyzed Aerobic Oxidation of Spirovinylcyclopropyl Oxindoles to Form Spiro-1,2-dioxolanes Diastereoselectively

Article abstract of DOI:10.1021/acs.joc.0c00652

A novel method of iodine-catalyzed aerobic oxidation with spirovinylcyclopropyl oxindoles under mild conditions has been described. A series of spiro-1,2-dioxolanes were prepared in good to excellent yields and considerable diastereoselectivities. The new approach is operationally simple, scalable, and tolerant of various functional groups.

Full text of DOI:10.1021/acs.joc.0c00652

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Note
Iodine-Catalyzed Aerobic Oxidation of Spirovinylcyclopropyl
Oxindoles to Form Spiro-1,2-dioxolanes Diastereoselectively
Cheng Xiong, Kunpeng Cheng, Jiahua Wang, Fulai Yang, Jinrong Lu, and Qingfa Zhou
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00652 • Publication Date (Web): 12 Jun 2020
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Cheng Xiong, Kunpeng Cheng, Jiahua Wang, Fulai Yang, Jinrong Lu*, and Qingfa Zhou*
State Key Laboratory of Natural Medicines, Department of Organic Chemistry, China Pharmaceutical University, Nanjing,
210009, P. R. China.
ABSTRACT: A novel method of iodine-catalyzed aerobic oxidation with spirovinylcyclopropyl oxindoles under mild conditions
had been described. A series of spiro-1,2-dioxolanes were prepared in good to excellent yields and considerable diastereoselectivities.
The new approach is operationally simple, scalable and tolerant of various functional groups.
1,2-Dioxolanes can be easily found in biologically active natu-
ral products and synthetic molecules (Figure 1).1 For example,
the mixture of plakortinic acids A and B isolated from the
sponge-sponge symbiotic association shows cytotoxic activity
on A2058 melanoma and DU-145 prostate cancer cells.2a 3-
Alkoxy-1,2-dioxolanes exhibits promising levels of antimalar-
ial activity against Plasmodium falciparum2b and endoperoxide
triterpene derived from 11-keto-β-boswellic acid shows potent
antitumor activity.2c Meanwhile, 1,2-dioxolane derivatives are
also key building blocks in the synthesis of structurally complex
targets, such as plakortone B3a and andavadoic acid.3b
electrolysis conditions, several cyclopropanes with a strong
electron-donating group combined with oxygen to furnish 1,2-
dioxolanes.8 Most of methods have modest stereoselectivity or
poor stability of products, which severely restricts application
in organic and pharmaceutical synthesis.9 Besides, spirooxin-
dole is a key structural motif in a broad range of natural alka-
loids and biologically active molecules.10 Therefore, a general
protocol to synthesize stereoselective spiro-1,2-dioxolanes, es-
pecially the parallel combinations of 1,2-dioxolane and indo-
lone motifs, would be highly desirable from the medicinal point
of view. And molecular iodine11 has emerged as an excellent
catalyst, because of its high solubility in the reaction media,
easy handling, low cost, and environmentally friendly nature in
comparison to heavy metals. Heroin, we report a molecular io-
dine-catalyzed aerobic oxidation of spirovinylcyclopropyl ox-
indole for the synthesis of 5'-vinylspiro[indoline-3,3'-[1,2]diox-
olane]-2-ones with exclusive stereoselectivity in high yields un-
der mild conditions.
Recently, the aerobic oxidation of donor–acceptor cyclopro-
panes, which have become important building blocks for con-
structing a wide range of carbo- and heterocyclic compounds,4a
have been popular in the synthesis of 1,2-dioxolanes (Scheme
1). 4b-4e The Mizuno’s group reported that the photooxygenation
of electron-rich 1,2-diarylcyclopropanes in the presence of
9,10-dicyanoanthracene (DCA) as a sensitizer in acetonitrile
could afford cis- and trans-3,5-diaryl-l,2-dioxolanes in high
yields.5 And Shim’s group showed that 2,2-diphenyl-2-vinyl-
cyclopropane could yield 3,3-diphenyl-5-vinyl-l,2-dioxolane
and benzophenone as the major products on the similarly co-
sensitized photooxygenation.6a Feldman and co-workers widely
explored the radical-mediated reaction of vinylcyclopropanes6b
with oxygen in the presence of Ph2Se2 and AIBN to give l,2-
dioxolanes in good yield and acceptable diastereoselectivity. 6c-
6g Then, Zhao and other researchers achieved the total synthesis
of pharmaceutically active compounds via an asymmetric rad-
ical-mediated intermolecular Feldman oxygenation of vinylcy-
clopropanes.7 In addition, Kulinkovich, Nguyen, Barnier and
other researchers described that under UV irradiation or
Figure 1. 1, 2-dioxolanes found in natural products and syn-
thetic molecules
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Table 1. Survey on Conditions for Formation of 2aa
Scheme 1. Formal [3+2] Cycloaddition of Cyclopropanes
1
with Oxygen
2
3
4
5
6
7
8
catalyst
yield
entry
catalyst
solvent
time
drb
amount
%
(%)
9
1
I2
5
Toluene
Toluene
Toluene
Toluene
Toluene
DMF
2 h
30
>95 :5
>95 :5
>95 :5
>95 :5
>95 :5
--
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2
I2
20
10
1
1 h
28
3
I2
1.5 h
3.5 h
7 d
37
4
I2
50
5
I2
0.1
1
23
6
I2
7 d
NRf
NRf
trace
46
7
I2
1
DMSO
C2H5OH
DCM
7 d
--
8
I2
1
3 d
--
We initiated our investigation by subjecting N-benzyl spirovi-
nylcyclopropyl oxindole 1a with 5 mol % I2 in toluene at room
temperature under air atmosphere. The desired spiro-1,2-diox-
olane 2a could be obtained in a good diastereoselectivity while
the yield was just 30% (Table 1, entry 1). The structure and ste-
reochemistry of compound 2a were characterized by a combi-
nation of NMR spectroscopy, high-resolution mass spectrome-
try (HRMS), and single-crystal X-ray diffraction.15 To obtain
satisfying yield of our desired compound, we then screened var-
ious amounts of this catalyst and solvents. The result indicated
the amount of iodine had no apparent impact on diastereoselec-
tivity but yield (entries 2-5). Among tested solvents, acetonitrile
proved to be the best reaction solvent, giving 2a in 91% yield
with excellent diastereoselectivity (entries 6-14). Subsequently,
we tried other iodine-containing catalysts. It showed that the
corresponding product 2a could be obtained only when adding
100% mol of SmI2, but the reaction was hardly performed even
if one of the above amounts (1%, 5%, 10% and 20%) of catalyst
or 100% mol TEAI (tetra ethylammonium iodide) was added.
(entries 15 and 16). In addition, when the reaction was run at
0 ℃, the target compound 2a could be obtained in a favorable
diastereoselectivity while the yield was just 39% (entry 17).
However, the target product was not observed when the reac-
tion was performed at reflux temperature (entry 18). Therefore,
the reaction conditions identified in entry 14 were chosen as the
standard conditions for further investigations.
9
I2
1
3.5 h
3 d
>95 :5
NDg
10
11
12
13
14
15
16
17c
18d
I2
1
Et2O
11
I2
1
THF
3 d
22
NDg
I2
1
Acetone
CH3NO2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
3.5 h
3.5 h
3.5 h
7 d
41
>95 :5
>95 :5
>95 :5
--
I2
1
38
I2
1
91
TEAIe
SmI2
I2
100
100
1
NRf
47
5 h
>95 :5
>95 :5
--
5 h
39
I2
1
1 h
trace
aTypical conditions: 1a (0.1 mmol), solvent (1.0 mL), rt, 1h-7d.
bDetermined through H NMR spectroscopic analysis. The reac-
tion was performed at 0 oC. dThe reaction was performed at reflux.
eTEAI = Tetraethylammonium iodide. fNR = No Reaction. gND =
not determined.
1
c
substituents of spirovinylcyclopropyl oxindoles on the present
reaction were examined. As shown in entries 2f-2j, halogen
substituents in C-4 and C-5 position could give excellent dia-
seteroselectivities (90:10 to >95:5 dr) and acceptable yields
(62%-73%). And products 2k and 2l could be generated in rel-
atively satisfying diaseteroselectivities (86:14 dr and 66:34 dr)
and yields (65% and 80%).In addition, electron-donating
groups located in C-5 position on benzene ring, such as methyl
and methoxy, could give the desired products in satisfactory
yields while a longer reaction time and 5 mol % loading of I2
were required (2m, 2n). It is worthy to note that the aerobic ox-
idation product 2o could also be effectively formed using 1'-
benzyl-2-methyl-2-vinylspiro[cyclopropane-1,3'-indolin]-2'-
one as reactant partner. When R4 was a phenyl group, the reac-
tion became badly and a complex mixture was observed (2p).
It indicated that the phenyl carried at the end of the double bond
With the optimal conditions in hand, we first studied the effect
of substituents of nitrogen in spirovinylcyclopropyl oxindoles
on the aerobic oxidation (Scheme 2). The introduction of alkyl
substituents or phenyl at nitrogen position was tolerated and
gave the corresponding products in good to excellent yield
yields. However, the diastereoselectivities could be affected
greatly, such as N-phenyl spirovinylcyclopropyl oxindole gave
the target product in 75% yield and 70:30 diastereoselectivity.
It is worth mentioning that, the target product 2e could also be
obtained in 65% yield and a good diastereoselectivity (>95:5
dr), while the amount of catalyst was increased to 5% and the
reaction time was slightly prolonged, which showed that the
process was compatible for the containing carbon-carbon dou-
ble bond substrates. Subsequently, the effects of aromatic ring
2
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Scheme 3. Proposed Mechanism for the Formation of 2a
Scheme 2. Substrate Scopea
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Conditiona
Time
30 h
Yield
30%
88%
Dark
Irradiation
3.5 h
aGeneral conditions: at room temperature, to a stirred solution of
1a (0.1 mmol) in CH3CN (1.0 mL) was added 1 mol % I2.
Scheme 4. Scale-up Preparation and Synthetic Transfor-
mations of 2a
aTypical conditions: at room temperature, to a stirred solution of 1
(0.1 mmol) in CH3CN (1.0 mL) was added 1 mol % I2. bDetermined
1
through H NMR spectroscopic analysis. cThe amount of I2 was 5
mol %.
might cause free radical transfer and destroy the stability of free
radical intermediate C (Scheme 3). And we also tried spiro-
coumaranone to perform under the same condition, but the cor-
responding compound 2q was not also obtained because of a
complex mixture, suggesting that the cyclopropane with elec-
tron-donating group might hardly conduct this reaction. Besides,
to compare the results against previous work, we also used to
serveral simple vinyl cyclopropanes, such as (3-vinylcyclopro-
pane-1,2-diyl)bis(phenylmethanone) but there was no reaction,
which might indicate that spirovinylcyclopropyl oxindoles have
a desirable activity on this reaction under the condition.
1,5-radical cation B and then undergoes a single-electron trans-
fer from I-. Finally, the corresponding compound 2a and it’s di-
astereomer 2a’ could be obtained from free radical intermediate
C (via path a and b). Besides, the result of control experiments
under dark condition and with irradiation indicated iodine radi-
cal production rate might have influence on the reaction.
To demonstrate the synthetic potential of this catalytic system,
the gram-scale preparation of highly functionalized 2a was in-
vestigated. The reaction of 4 mmol of the starting material (1a)
proceeded smoothly, delivering the corresponding product 2a
(1.04 g) in a yield of 85%, showing the reaction to be a practical
tool for the synthesis of highly functionalized 1,2- dioxolanes
(Scheme 4). When 1,2-dioxolane 2a was treated with zinc metal
in acetic acid, the O-O bond underwent reductive cleavage in
high yield (95%) to afford 1,3-diol 3a, which retained its origi-
nal stereocenters set in the oxygenation reaction.14a,14b And hex-
5-ene-1,3-diol fragment of 3a has been reported to be used as
intermediate directly during the synthesis of rugulactone, which
can inhibit constitutive nuclear factor tor NF-κB activity in hu-
man lymphoma cell lines.14c In Addition, when 2a was placed
in the solvent of MeOH at reflux temperature, 1,2-dioxolane of
To understand this unique reaction pattern, we initially per-
formed the reaction using the stereoisomer of 1a (1a’) in place
of 1a and the target product 2a was formed in 83% yield and
excellent diastereoselectivity (1). Then the reaction was added
butylated hydroxytoluene under the standard condition and
found that it inhibited the progression of reaction completely
(2).According to references and the above results, we proposed
the reaction could proceed via a free radical process (Scheme
3).12 Firstly, iodine radical13 is generated in the solvent of ace-
tonitrile and then produced the radical cation of A via a single-
electron transfer step from 1a to I-. Subsequently, the attack of
molecular dioxygen on the 1,3-radical cation A generates the
3
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2a could be destroyed completely to convert back into 4 1-ben-
zylindoline-2,3-dione.
by infrared lamp to obtain crude product which was directly
put to the next step without further purification.
1
2
3
4
5
6
7
8
9
In conclusion, we have developed the first molecular iodine-
catalyzed aerobic oxidation of spirovinylcyclopropyl oxindole.
Various functional groups were well tolerated in the reaction
affording the corresponding products in moderate to excellent
yields and considerable diastereoselectivities (66:34 dr to >95:5
dr). More importantly, only a small amount of catalyst is re-
quired for this reaction to proceed smoothly, which means the
less pollution to environment. In addition, the reaction could be
scaled up without significant loss of yield, and the synthesized
functionalized spiro-1,2-dioxolane could be further trans-
formed into other promising diol compounds.
1-Benzyl isatin derive: To a solution of N-benzyl isatin derive
(30 mmol) in DMF (120 ml) was added K2CO3 (72 mmol) and
benzyl bromide (4.28 ml). The resulting mixture was stirred at
room temperature overnight. After isatin derive was consumed
thoroughly, reaction mixture was poured into 60 ml ice water
and desired precipitate appeared. Filtration under reduced pres-
sure, residue washed by water and dried by infrared lamp to
obtain crude product N-protected isatin derive which was di-
rectly put to the next step without further purification.
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Step2: General Procedure for Spirovinylcyclopropyl Oxindoles.
N-protected isatin derive (21 mmol) and hydrazine hydrate (30
ml) were added to a round bottomed flask in oil bath. Then, the
resulting mixture was heated to reflux for 3 h, cooled to room
temperature, extracted with EtOAc, combined organic layer
dried over anhydrous MgSO4, filtered, filtrate concentrated in
vacuo and recrystallized from ethanol/water to obtain N-pro-
tected lindolin-2-one in 71% yield. Subsequently, to a solution
of N-protected lindolin-2-one (15 mmol) in acetone (45 ml) was
added 1,4-dibromobut-2-ene (4.51g, 21 mmol) and K2CO3
(6.22 g, 45 mmol) in oil bath. The resulting mixture was heated
to reflux until the complete consumption of N-protected lin-
dolin-2-one, cooled to room temperature, filtered, residue
washed by ethyl acetate and combined organic layer washed by
water and brine in sequence, dried over anhydrous Na2SO4, fil-
tered, filtrate concentrated in vacuo and purified by flash chro-
matography on silica gel (eluent: petroleum ether - ethyl acetate
= 30 : 1) to afford spirovinylcyclopropyl oxindole 1.
General information. All reactions were performed in dry sol-
vents and anhydrous conditions. DCM, THF, DMSO and
MeCN etc. were freshly distilled over CaH2 prior to use. All
other reagents were used as received from commercial sources.
Reactions were monitored through thin layer chromatography
(TLC) on 0.25mm SiliCycle silica gel plates and visualized un-
der UV light. NMR spectra of the new product were recorded
on Bruker Avance instrument (300 MHz, 400 MHz or 500
MHz for 1H, 75 MHz, 101 MHz or 126 MHz for 13C), calibrated
to CD(H)Cl3 as the internal reference (7.26 and 77.0 ppm for 1H
and 13C NMR spectra respectively), calibrated to DMSO-d6 as
the internal reference (2.50 and 39.5 ppm for 1H and 13C NMR
1
spectra respectively). H NMR spectral data are reported in
terms of chemical shift (δ, ppm), multiplicity, coupling constant
(Hz), and integration. 13C NMR spectral data are reported in
terms of chemical shift (δ, ppm) and multiplicity. The following
abbreviations indicate the multiplicities: s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet. Mass spectra were taken on a
Finnigan TSQ Quantum-MS instrument in the electron spray
ionization (ESI). All of the spirovinylcyclopropanyl oxindoles
(1a, 1c, 1f, 1g, 1h, 1l, 1m, 1n and 1o) were prepared according
to literature procedures.16 The rest of chemical reagents were
obtained from commercial suppliers.
(1S,2S)-1'-phenyl-2-vinylspiro[cyclopropane-1,3'-indolin]-2'-
1
one (1b). 1.02 g, 26% yield. H NMR (500 MHz, Chloroform-
d) δ 7.61 – 7.54 (m, 2H), 7.54 – 7.49 (m, 2H), 7.48 – 7.42 (m,
1H), 7.24 (td, J = 7.7, 1.3 Hz, 1H), 7.13 (td, J = 7.5, 1.1 Hz, 1H),
7.00 – 6.94 (m, 2H), 6.36 (ddd, J = 17.2, 10.4, 9.3 Hz, 1H), 5.35
(dd, J = 17.2, 1.8 Hz, 1H), 5.21 (dd, J = 10.4, 1.7 Hz, 1H), 2.65
(q, J = 8.6 Hz, 1H), 2.13 (dd, J = 7.9, 4.7 Hz, 1H), 2.08 (dd, J =
8.8, 4.7 Hz, 1H). 13C{1H} NMR (126 MHz, Chloroform-d) δ
174.1, 143.2, 135.0, 134.0, 130.3, 129.5, 127.8, 126.7, 126.6,
122.6, 118.2, 117.0, 109.2, 38.0, 33.8, 25.3. HRMS (ESI) m/z:
[M + H]+ Calcd for C18H16NO 262.1154; found 262.1157.
General Procedure for the substrates. (1b, 1d, 1e, 1i-1k)
(1S,2R)-1'-trityl-2-vinylspiro[cyclopropane-1,3'-indolin]-2'-
one (1d). 1.67 g, 26% yield. 1H NMR (300 MHz, Chloroform-
d) δ 7.52 – 7.42 (m, 6H), 7.32 – 7.23 (m, 9H), 6.94 – 6.82 (m,
3H), 6.39 – 6.30 (m, 1H), 5.89 (ddd, J = 16.9, 10.3, 7.8 Hz, 1H),
5.40 (dt, J = 17.1, 1.3 Hz, 1H), 5.28 (dd, J = 10.3, 1.6 Hz, 1H),
2.62 (q, J = 8.0 Hz, 1H), 2.02 (dd, J = 9.0, 4.4 Hz, 1H), 1.60 (d,
J = 3.1 Hz, 1H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 174.9,
148.3, 142.7, 134.6, 130.9, 129.2, 128.1, 127.1, 125.6, 122.0,
119.0, 117.3, 114.8, 74.2, 37.9, 34.4, 23.6. HRMS (ESI) m/z:
[M + H]+ Calcd for C31H26NO 428.1936; found 428.1940.
Step 1: Experimental Procedure for the Synthesis of N-pro-
tected isatin derives.
1-Phenylindoline-2,3-dione: To a solution of isatin (4.41 g, 30
mmol) in DCE (150 ml) was added phenylboronic acid (5.49 g,
45 mmol), copper acetate (5.99 g, 30 mmol) and triethylamine
(8.35 ml). The resulting mixture was stirred at room tempera-
ture for 1.5 h. After isatin was consumed thoroughly, reaction
mixture was poured into water, extracted with EtOAc, washed
by brine, combined organic layer dried over anhydrous MgSO4,
filtered, filtrate concentrated in vacuo to obtain crude product
which was directly put to the next step without further purifica-
tion.
(1S,2S)-1'-((E)-4-bromobut-2-en-1-yl)-2-vinylspiro[cyclopro-
pane-1,3'-indolin]-2'-one (1e). According to the step 2, isatin
(4.41 g, 30 mmol) and hydrazine hydrate (42 ml) were added to
a round-bottomed flask in oil bath under reflux temperature for
3 h. After work-up, indolin-2-one was obtained to the further
step. Then, the solution of indolin-2-one (4.0 g, 30 mmol) in
acetone (90 ml) was added 1,4-dibromobut-2-ene (19.25 g, 90
mmol) and K2CO3 (18.66 g, 135 mmol) to a round-bottomed
flask in oil bath under reflux temperature until the complete
consumption ofsubstrates. After work-up, the crude product
was purified by flash chromatography on silica gel (eluent: pe-
1-Tritylindoline-2,3-dione:To a solution of isatin (4.41 g, 30
mmol) in DMF (150 ml) was added NaH (864 mg, 36 mmol,
60% dispersed in mineral oil) portion-wise during half hour at
room temperature, stirred for 30 min, and triphenylmethyl bro-
mide (11.64 g, 36 mmol) was added subsequently. The resulting
mixture was stirred at room temperature for 2.5 h. After isatin
was consumed thoroughly, reaction mixture was poured into so-
dium chloride solution, and yellow precipitate appeared. Filtra-
tion under reduced pressure, residue washed by water and dried
1
troleum ether - ethyl acetate = 30 : 1). 1.53 g, 16% yield. H
NMR (300 MHz, Chloroform-d) δ 7.25 (td, J = 7.7, 1.2 Hz, 1H),
4
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7.06 (td, J = 7.5, 1.0 Hz, 1H), 6.93 – 6.84 (m, 2H), 6.26 (ddd, J
(3S,5'S)-1-phenyl-5'-vinylspiro[indoline-3,3'-[1,2]dioxolan]-
2-one (2b) 24 h. 22.0 mg, 75% yield. Yellow oil. IR (KBr, cm−1)
3043, 2939, 2860, 1735, 1609, 1503, 1465, 1369, 1201, 757,
1
2
3
4
5
6
7
8
= 17.2, 10.3, 9.4 Hz, 1H), 6.02 – 5.75 (m, 2H), 5.27 (dd, J =
17.2, 1.7 Hz, 1H), 5.15 (dd, J = 10.4, 1.7 Hz, 1H), 4.45 (dd, J =
5.2, 1.2 Hz, 2H), 3.98 – 3.90 (m, 2H), 2.54 (td, J = 9.0, 7.8 Hz,
1H), 2.06 – 1.92 (m, 2H). 13C{1H} NMR (126 MHz, Chloro-
form-d) δ 174.4, 142.2, 133.9, 130.4, 129.3, 129.0, 126.8, 122.1,
118.1, 116.9, 108.6, 41.2, 37.4, 33.6, 31.4, 24.9. HRMS (ESI)
m/z: [M + H]+ Calcd for C16H17BrNO 318.0415; found
318.0420.
1
697. H NMR (300 MHz, Chloroform-d): δ 7.55 (t, J = 6.7 Hz,
3H), 7.44 (d, J = 7.2 Hz, 3H), 7.38 – 7.26 (m, 1H), 7.17 (t, J =
7.6 Hz, 1H), 6.85 (t, J = 6.6 Hz, 1H), 6.21 – 5.95 (m, 1H), 5.56
(dd, J = 17.2 Hz, 5.9 Hz, 1H), 5.44 (t, J = 9.6 Hz, 1H), 5.18 (q,
J = 7.5 Hz, 1H), 3.44 – 2.74 (m, 2H); 13C{1H} NMR (126 MHz,
Chloroform-d): δ 173.5, 144.2, 133.9, 133.0, 130.7, 129.7,
128.3, 126.3, 124.9, 123.9, 121.0, 120.6, 110.0, 84.2, 83.2,
50.00. HRMS (ESI) m/z: [M + H]+ Calcd for C18H16NO3
294.1052; found 294.1057.
(1S,2R)-1'-benzyl-4'-chloro-2-vinylspiro[cyclopropane-1,3'-in-
9
1
dolin]-2'-one (1i). 1.12 g, 24% yield. H NMR (500 MHz,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
DMSO-d6) δ 7.37 – 7.32 (m, 2H), 7.32 – 7.25 (m, 3H), 7.20 (t,
J = 8.0 Hz, 1H), 7.00 (dd, J = 10.9, 8.0 Hz, 2H), 6.23 (dt, J =
17.2, 9.9 Hz, 1H), 5.40 (dd, J = 17.3, 1.8 Hz, 1H), 5.17 (dd, J =
10.4, 1.8 Hz, 1H), 4.99 (s, 2H), 3.31 (d, J = 8.7 Hz, 1H), 2.68
(dd, J = 8.8, 4.7 Hz, 1H), 1.87 (dd, J = 7.9, 4.7 Hz, 1H). 13C{1H}
NMR (126 MHz, DMSO-d6) δ 173.4, 144.5, 136.7, 133.9, 129.1,
128.7, 128.0, 127.6, 126.6, 124.6, 123.4, 118.4, 108.7, 43.6,
34.7, 32.0, 21.4. HRMS (ESI) m/z: [M + H]+ Calcd for
C19H17ClNO 310.0920; found 310.0925.
(3S,5'S)-1-methyl-5'-vinylspiro[indoline-3,3'-[1,2]dioxolan]-
2-one (2c) 3 h. 18.9 mg, 82% yield. Yellow oil. IR (KBr, cm−1)
3046, 2947, 2931, 2850, 1733, 1610, 1502, 1464, 1451, 1379,
1278, 1080, 754, 703. 1H NMR (500 MHz, Chloroform-d): δ
7.47 (d, J = 7.4 Hz, 1H), 7.43 – 7.36 (m, 1H), 7.14 (t, J = 7.6
Hz, 1H), 6.86 (d, J = 7.8 Hz, 1H), 6.16 – 6.09 (m, 1H), 5.53 (d,
J = 17.2 Hz, 1H), 5.42 (d, J = 10.3 Hz, 1H), 5.13 (q, J = 7.5 Hz,
1H), 3.23 (s, 3H), 2.99 (qd, J = 12.4 Hz, 7.3 Hz, 2H); 13C{1H}
NMR (126 MHz, Chloroform-d): δ 174.0, 144.1, 133.1, 130.8,
126.4, 124.4, 123.4, 120.9, 120.5, 108.6, 84.0, 49.8, 26.4.
HRMS (ESI) m/z: [M + H]+ Calcd for C13H14NO3 232.0895;
found 232.0899.
(1S,2R)-1'-benzyl-4'-bromo-2-vinylspiro[cyclopropane-1,3'-in-
dolin]-2'-one (1j). 1.54 g, 29% yield. 1H NMR (500 MHz,
DMSO-d6) δ 7.34 (t, J = 7.5 Hz, 2H), 7.31 – 7.25 (m, 3H), 7.14
(dt, J = 15.7, 8.0 Hz, 2H), 7.02 (d, J = 7.5 Hz, 1H), 6.24 (dt, J
= 17.2, 9.9 Hz, 1H), 5.40 (dd, J = 17.3, 1.8 Hz, 1H), 5.18 (dd, J
= 10.3, 1.8 Hz, 1H), 4.99 (d, J = 2.1 Hz, 2H), 3.37 (d, J = 9.0
Hz, 1H), 2.75 (dd, J = 8.9, 4.7 Hz, 1H), 1.83 (dd, J = 8.0, 4.7
Hz, 1H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 173.4, 144.6,
136.7, 133.8, 129.2, 129.0, 127.9, 127.6, 126.6, 125.8, 118.5,
114.6, 109.2, 43.5, 35.3, 31.8, 21.2. HRMS (ESI) m/z: [M + H]+
Calcd for C19H17BrNO 354.0415; found 354.0419.
(3S,5'S)-1-trityl-5'-vinylspiro[indoline-3,3'-[1,2]dioxolan]-2-
one (2d) 3 h. 34.0 mg, 74% yield. Yellow oil. IR (KBr, cm−1)
3055, 2954, 2853, 1736, 1612, 1466, 1312, 1188, 748, 702. 1H
NMR (400 MHz, Chloroform-d): δ 7.52 – 7.46 (m, 6H), 7.44 –
7.40 (m, 1H), 7.32 – 7.23 (m, 9H), 7.03 – 6.96 (m, 2H), 6.33 –
6.28 (m, 1H), 6.10 – 5.98 (m, 1H), 5.50 (d, J = 17.2 Hz, 1H),
5.37 (d, J = 10.2 Hz, 1H), 5.11 (q, J = 7.5 Hz, 1H), 2.94 (d, J =
7.3 Hz, 2H). 13C{1H} NMR (126 MHz, Chloroform-d): δ 174.8,
144.3, 141.8, 133.1, 129.3, 127.8, 127.0, 127.0, 124.1, 122.7,
120.9, 120.3, 116.2, 84.4, 83.4, 49.7, 48.8. HRMS (ESI) m/z:
[M + H]+ Calcd for C31H26NO3 460.1834; found 460.1836.
(1S,2R)-1'-benzyl-7'-fluoro-2-vinylspiro[cyclopropane-1,3'-in-
dolin]-2'-one (1k). 1.89 g, 43% yield. 1H NMR (300 MHz,
Chloroform-d) δ 7.34 (ddt, J = 18.6, 9.1, 4.8 Hz, 5H), 6.95 (dt,
J = 8.2, 2.2 Hz, 2H), 6.74 (dt, J = 5.5, 2.4 Hz, 1H), 5.85 (dt, J =
17.8, 9.1 Hz, 1H), 5.41 (d, J = 16.8 Hz, 1H), 5.30 (d, J = 10.2
Hz, 1H), 5.25 – 5.09 (m, 2H), 2.75 (q, J = 8.2 Hz, 1H), 2.19 (dt,
J = 6.6, 3.2 Hz, 1H), 1.75 (dt, J = 6.7, 3.0 Hz, 1H). 13C{1H}
NMR (126 MHz, Chloroform-d) δ 176.0, 148.7, 146.8, 137.5,
133.0, 128.6, 127.6, 127.5, 122.2, 119.4, 116.9, 115.0, 114.9,
45.8, 36.4, 33.6, 23.9. HRMS (ESI) m/z: [M + H]+ Calcd for
C19H17FNO 294.1216; found 294.1219.
(3S,5'S)-1-((E)-4-bromobut-2-en-1-yl)-5'-vinylspiro[indoline-
3,3'-[1,2]dioxolan]-2-one (2e) 7.5 h. 22.8 mg, 65% yield. Yel-
low oil. 1H NMR (500 MHz, Chloroform-d): δ 7.47 (d, J = 7.4
Hz, 1H), 7.41 – 7.33 (m, 1H), 7.14 (t, J = 7.6 Hz, 1H), 6.84 (d,
J = 7.9 Hz, 1H), 6.16 – 6.04 (m, 1H), 6.00 – 5.89 (m, 1H), 5.79
(dt, J = 15.4 Hz, 5.5 Hz, 1H), 5.54 (dd, J = 17.1 Hz, 5.2 Hz, 1H),
5.43 (dd, J = 10.3 Hz, 4.0 Hz, 1H), 5.21 (q, J = 6.8 Hz, 1H),
4.36 (d, J = 5.5 Hz, 2H), 3.94 (d, J = 7.2 Hz, 2H), 3.30 – 2.70
(m, 2H); 13C{1H} NMR (126 MHz, Chloroform-d): δ 173.8,
143.1, 133.0, 130.8, 130.0, 127.9, 126.1, 124.7, 123.5, 121.0,
120.5, 109.4, 84.1, 49.7, 41.2, 31.0. HRMS (ESI) m/z: [M + H]+
Calcd for C16H17BrNO3 350.0314; found 350.0318.
General Procedure for Synthesis of spiro-1,2-dioxolane. A
mixture of 2-vinylspiro[cyclopropane-1,3'-indolin]-2'-one 1a
(0.1 mmol) and 1 mol % I2 (0.254 mg) in CH3CN (1 mL) was
placed in an oven-dried 25 mL eggplant type flask containing a
magnetic stirrer (400 rpm/min) at room temperature for 10 h.
Then, the solvent was removed, the product was purified
through silica gel chromatography, eluting with petroleum
ether/ethyl acetate (15:2~5:1) to give the desired products 2a.
(3S,5'S)-1-benzyl-5-fluoro-5'-vinylspiro[indoline-3,3'
[1,2]dioxolan]-2-one (2f) 5 h. 20.5 mg, 63% yield. Yellow oil.
1H NMR (500 MHz, Chloroform-d): δ 7.40 – 7.31 (m, 2H), 7.35
– 7.26 (m, 3H), 7.21 (dd, J = 7.5 Hz, 2.6 Hz, 1H), 6.96 (td, J =
8.8 Hz, 2.6 Hz, 1H), 6.65 (dd, J = 8.5 Hz, 4.0 Hz, 1H), 6.18 –
6.09 (m, 1H), 5.55 (dd, J = 16.4 Hz, 1.6 Hz, 1H), 5.44 (dt, J =
10.4 Hz, 0.8 Hz, 1H), 5.13 (q, J = 7.3 Hz, 1H), 4.98 – 4.82 (m,
2H), 3.05 (d, J = 7.1 Hz, 2H); 13C{1H} NMR (126 MHz, Chlo-
roform-d): δ 173.8, 160.5, 158.5, 134.9, 133.1, 129.0, 128.0,
127.3, 121.0, 117.0, 116.9, 112.7, 112.5, 110.4, 83.9, 50.0, 44.2.
HRMS (ESI) m/z: [M + H]+ Calcd for C19H17FNO3 326.1114;
found 326.1117.
(3S,5'S)-1-benzyl-5'-vinylspiro[indoline-3,3'-[1,2]dioxolan]-2-
one (2a) 10 h. 27.9 mg, 91% yield. Yellow oil. IR (KBr, cm−1)
3055, 2931, 2862, 1728, 1612, 1489, 1466, 1366, 1195, 949,
756, 733, 694. 1H NMR (300 MHz, Chloroform-d) : δ 7.46 (dd,
J = 7.4 Hz, 1.3 Hz, 1H), 7.36 – 7.22 (m, 6H), 7.09 (td, J = 7.6,
1.0 Hz, 1H), 6.74 (d, J = 7.8 Hz, 1H), 6.21 – 6.05 (m, 1H), 5.55
(dt, J = 17.1, 1.0 Hz, 1H), 5.43 (dd, J = 10.3, 1.1 Hz, 1H), 5.16
(q, J = 7.4 Hz, 1H), 4.99 – 4.82 (dd, 2H), 3.04 (dd, J = 7.3, 1.6
Hz, 2H). 13C{1H} NMR (101 MHz, Chloroform-d): δ 174.1,
144.1, 133.0, 130.8, 126.3, 124.4, 123.4, 121.1, 108.7, 84.4,
84.1, 49.7, 26.4. HRMS (ESI) m/z: [M + H]+ Calcd for
C19H18NO3 308.1208; found 308.1210.
(3S,5'S)-1-benzyl-5-chloro-5'-vinylspiro[indoline-3,3'-[1,2]di-
oxolan]-2-one (2g) 5 h. 23.3 mg, 68% yield. Yellow oil. IR
(KBr, cm−1) 3086, 2924, 2854, 1728, 1612, 1481, 1435, 1342,
1
1265, 1172, 1072, 980, 935, 810, 740. H NMR (500 MHz,
5
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Page 6 of 9
Chloroform-d): δ 7.47 (d, J = 2.2 Hz, 1H), 7.40 – 7.34 (m, 2H),
83.9, 47.4, 44.1. HRMS (ESI) m/z: [M + H]+ Calcd for
C19H17ClNO3 342.0819; found 342.0823.
1
2
3
4
5
6
7
8
7.34 – 7.29 (m, 3H), 7.25 (dd, J = 8.3 Hz, 2.2 Hz, 1H), 6.67 (d,
J = 8.3 Hz, 1H), 6.19 – 6.12 (m, 1H), 5.57 (d, J = 17.1 Hz, 1H),
5.46 (d, J = 10.3 Hz, 1H), 5.16 (q, J = 7.3 Hz, 1H), 4.91 (q, J =
15.7 Hz, 2H), 3.06 (d, J = 7.1 Hz, 2H); 13C{1H} NMR (126
MHz, Chloroform-d): δ 173.6, 141.6, 134.8, 133.0, 130.5, 129.0,
128.9, 128.2, 128.0, 127.3, 125.1, 121.0, 110.8, 84.2, 84.0, 49.9,
44.2. HRMS (ESI) m/z: [M + H]+ Calcd for C19H17ClNO3
342.0819; found 342.0821.
(3S,5'S)-1-benzyl-5-methyl-5'-vinylspiro[indoline-3,3'-[1,2]di-
oxolan]-2-one (2m) 24 h. 26.6 mg, 83% yield. Yellow oil. 1H
NMR (300 MHz, Chloroform-d): δ 7.32 (d, J = 5.7 Hz, 6H),
7.05 (d, J = 8.0 Hz, 1H), 6.62 (dd, J = 8.0 Hz, 2.1 Hz, 1H), 6.20
– 6.07 (m, 1H), 5.55 (d, J = 17.2 Hz, 1H), 5.43 (d, J = 10.3 Hz,
1H), 5.15 (q, J = 7.4 Hz, 1H), 4.97 – 4.81 (m, 2H), 3.10 – 2.96
(m, 2H), 2.33 (d, J = 2.2 Hz, 3H); 13C{1H} NMR (126 MHz,
Chloroform-d): δ 174.2, 140.8, 135.4, 133.2, 133.1, 131.0,
128.9, 127.8, 127.3, 126.3, 125.3, 120.9, 109.5, 84.6, 84.1, 49.8,
44.0, 21.0. HRMS (ESI) m/z: [M + H]+ Calcd for C20H20NO3
322.1365; found 322.1368.
(3S,5'S)-1-benzyl-5-bromo-5'-vinylspiro[indoline-3,3'-[1,2]di-
9
1
oxolan]-2-one (2h) 5 h. 28.2 mg, 73% yield. Yellow oil. H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR (300 MHz, Chloroform-d): δ 7.58 (d, J = 2.1 Hz, 1H),
7.39 – 7.26 (m, 6H), 6.60 (dd, J = 8.3 Hz, 2.2 Hz, 1H), 6.18 –
6.06 (m, 1H), 5.55 (d, J = 17.1 Hz, 1H), 5.44 (d, J = 10.0 Hz,
1H), 5.14 (q, J = 7.8 Hz, 1H), 5.00 – 4.77 (m, 2H), 3.04 (d, J =
7.6 Hz, 2H); 13C{1H} NMR (126 MHz, Chloroform-d): δ 173.5,
142.1, 134.7, 133.4, 133.0, 129.0, 128.6, 128.0, 127.8, 127.3,
121.1, 116.0, 111.2, 84.1, 84.0, 49.9, 44.2. HRMS (ESI) m/z:
[M + H]+ Calcd for C19H17BrNO3 386.0314; found 386.0319.
(3S,5'S)-1-benzyl-5-methoxy-5'-vinylspiro[indoline-3,3'-
[1,2]dioxolan]-2-one (2n) 48 h. 24.6 mg, 73% yield. Yellow oil.
1H NMR (500 MHz, Chloroform-d): δ 7.37 – 7.29 (m, 5H), 7.10
(dd, J = 9.4, 2.6 Hz, 1H), 6.79 (ddd, J = 8.6, 4.1, 2.6 Hz, 1H),
6.64 (dd, J = 8.6, 3.3 Hz, 1H), 6.09 (dddd, J = 71.9, 17.2, 10.3,
7.3 Hz, 1H), 5.57 (ddt, J = 17.1, 15.9, 1.1 Hz, 1H), 5.49 – 5.41
(m, 1H), 5.25 (dq, J = 96.4, 7.2 Hz, 1H), 4.97 – 4.83 (m, 2H),
3.81 (s, 3H), 3.35 – 2.74 (m, 2H). 13C{1H} NMR (126 MHz,
Chloroform-d): δ 174.0, 156.6, 136.4, 135.3, 133.2, 133.0,
128.9, 127.8, 127.3, 120.9, 115.2, 111.7, 110.2, 84.0, 83.2, 55.9,
50.0, 44.1. HRMS (ESI) m/z: [M + H]+ Calcd for C20H20NO4
338.1314；found 338.1317.
(3S,5'R)-1-benzyl-4-chloro-5'-vinylspiro[indoline-3,3'-[1,2]di-
oxolan]-2-one (2i) 4.5 h. 21.2 mg, 62% yield. Yellow oil. IR
(KBr, cm−1) 3055, 2939, 2856, 1720, 1612, 1496, 1465, 1373,
1350, 1265, 1087, 948, 756, 686. 1H NMR (400 MHz, Chloro-
form-d): δ 7.39 – 7.26 (m, 5H), 7.18 (t, J = 8.0 Hz, 1H), 7.04
(dd, J = 8.3, 0.8 Hz, 1H), 6.64 (dd, J = 7.9, 0.9 Hz, 1H), 6.01
(ddd, J = 17.2, 10.2, 7.7 Hz, 1H), 5.58 (dt, J = 17.1, 1.0 Hz, 1H),
5.47 – 5.37 (m, 2H), 4.89 (s, 2H), 3.34 (dd, J = 12.3, 9.3 Hz,
1H), 3.03 (dd, J = 12.3, 5.9 Hz, 1H). 13C{1H} NMR (75 MHz,
Chloroform-d): δ 173.9, 144.9, 134.8, 132.0, 131.9, 131.8,
129.0, 128.0, 127.3, 124.7, 122.0, 121.7, 108.3, 85.3, 83.9, 47.4,
44.1. HRMS (ESI) m/z: [M + H]+ Calcd for C19H17ClNO3
342.0819; found 342.0820.
(3S,5'S)-1-benzyl-5'-methyl-5'-vinylspiro[indoline-3,3'-
[1,2]dioxolan]-2-one (2o) 24 h. 28.2 mg, 88% yield. Yellow oil.
1H NMR (300 MHz, Chloroform-d): δ 7.48 (dd, J = 18.4, 7.4
Hz, 1H), 7.36 – 7.21 (m, 6H), 7.08 (dt, J = 12.9, 7.5 Hz, 1H),
6.72 (t, J = 6.9 Hz, 1H), 6.29 (ddd, J = 34.2, 17.8, 11.1 Hz, 1H),
5.52 (dd, J = 17.5, 3.1 Hz, 1H), 5.41 – 5.29 (m, 1H), 5.00 – 4.78
(m, 2H), 3.16 (dd, J = 40.1, 12.5 Hz, 1H), 2.86 (dd, J = 47.5,
12.9 Hz, 1H), 1.74 (d, J = 10.5 Hz, 3H). 13C{1H} NMR (101
MHz, DMSO-d6): δ 174.0, 143.4, 140.9, 139.6, 136.4, 131.2,
129.2, 127.7, 126.6, 125.5, 123.6, 115.6, 110.2, 87.3, 85.0, 54.0,
43.3, 23.1. HRMS (ESI) m/z: [M + H]+ Calcd for C20H20NO3
322.1365; found 322.1368.
(3S,5'R)-1-benzyl-4-bromo-5'-vinylspiro[indoline-3,3'-[1,2]di-
1
oxolan]-2-one (2j) 1 h. 27.0 mg, 70% yield. Yellow oil. H
NMR (500 MHz, Chloroform-d): δ 7.38 – 7.26 (m, 5H), 7.22
(dd, J = 8.2 Hz, 0.9 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 6.68 (dd,
J = 7.9 Hz, 0.9 Hz, 1H), 6.06 – 5.98 (m, 1H), 5.59 (dt, J = 17.3
Hz, 1.0 Hz, 1H), 5.50 – 5.41 (m, 2H), 4.89 (d, J = 2.4 Hz, 2H),
3.41 (dd, J = 12.3 Hz, 9.6 Hz, 1H), 2.97 (dd, J = 12.3 Hz, 5.7
Hz, 1H); 13C{1H} NMR (126 MHz, Chloroform-d): δ 173.5,
142.1, 134.7, 133.5, 132.9, 129.0, 128.6, 128.0, 127.8, 127.3,
121.1, 116.0, 111.21, 84.1, 84.0, 49.9, 44.2. HRMS (ESI) m/z:
[M + H]+ Calcd for C19H17BrNO3 386.0314; found 386.0318.
Control Experiment. To a mixture of 1'-benzyl-2-vinyl-
spiro[cyclopropane-1,3'-indolin]-2'-one 1a’ (27.54 mg, 0.1
mmol) in CH3CN (1 mL) was added 1 mol % I2 (0.254 mg). The
resulting solution was stirred at room temperature until the
complete consumption of 1a’. After removal of solvent, the
product was purified through silica gel to give the desired prod-
ucts 2a in 89% yield. To a mixture of 1'-benzyl-2-vinylspiro[cy-
clopropane-1,3'-indolin]-2'-one 1a (27.54 mg, 0.1 mmol) in
CH3CN (1 mL) was added by 1 mol % I2 (0.254 mg) and BHT
(44.1 mg, 2 e.q.). The resulting solution was stirred at room
temperature. No desired product was obtained.
(3S,5'S)-1-benzyl-7-fluoro-5'-vinylspiro[indoline-3,3'-[1,2]di-
1
oxolan]-2-one (2k) 4 h. 21.1 mg, 65% yield. Yellow oil. H
NMR (500 MHz, Chloroform-d): δ 7.40 – 7.34 (m, 5H), 7.28
(dd, J = 5.4 Hz, 3.2 Hz, 1H), 7.09 – 7.06 (m, 2H), 6.19 – 6.12
(m, 1H), 5.56 (dt, J = 17.1 Hz, 1.0 Hz, 1H), 5.45 (d, J = 10.3
Hz, 1H), 5.15 (q, J = 7.3 Hz, 1H), 5.10 – 5.04 (m, 2H), 3.04 (d,
J = 7.1 Hz, 2H); 13C{1H} NMR (126 MHz, Chloroform-d): δ
173.8, 160.5, 158.5, 134.9, 133.1, 129.0, 128.0, 127.3, 121.0,
117.0, 116.8, 112.8, 112.5, 110.4, 83.9, 50.0, 44.2. HRMS (ESI)
m/z: [M + H]+ Calcd for C19H17FNO3 326.1114; found
326.1116.
To a mixture of 1'-benzyl-2-vinylspiro[cyclopropane-1,3'-in-
dolin]-2'-one 1a (27.54 mg, 0.1 mmol) in CH3CN (1 mL) was
added 1 mol % I2 (0.254 mg) under dark condition and with
irradiation for 30 h and 3.5 h respectively. Then, the solvent was
removed, the product was purified through silica gel chroma-
tography, eluting with petroleum ether/ethyl acetate (15:2~5:1)
to give the desired products 2a in 30% and 88% yield respec-
tively.
(3S,5'S)-1-benzyl-6-chloro-5'-vinylspiro[indoline-3,3'-[1,2]di-
1
oxolan]-2-one (2l) 4 h. 27.4 mg, 80% yield. Yellow oil. H
NMR (500 MHz, Chloroform-d): δ 7.39 (td, J = 7.9 Hz, 6.2 Hz,
3H), 7.33 (tt, J = 6.9 Hz, 2.8 Hz, 3H), 7.09 (dt, J = 7.9 Hz, 1.6
Hz, 1H), 6.75 (dd, J = 3.3 Hz, 1.8 Hz, 1H), 6.04 – 5.97 (m, 1H),
5.61 – 5.53 (m, 1H), 5.49 – 5.44 (m, 1H), 5.24 (q, J = 7.2 Hz,
1H), 4.96 – 4.84 (m, 2H), 3.36 – 2.67 (m, 2H); 13C{1H} NMR
(75 MHz, Chloroform-d): δ 173.9, 144.9, 134.8, 132.0, 131.9,
131.8, 129.0, 128.0, 127.3, 124.7, 122.0, 121.7, 108.3, 85.3,
Scale-up Experiment. A mixture of 2-vinylspiro[cyclopro-
pane-1,3'-indolin]-2'-one 1a (4 mmol) and 1 mol % I2 (10.16
mg) in CH3CN (40 mL) was placed in an oven-dried 100 mL
eggplant type flask containing a magnetic stirrer (500 rpm/min)
at room temperature for 4 h. Then, the solvent was removed, the
product was purified through silica gel chromatography, eluting
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1
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3
4
5
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sired products 2a (1.04 g, 85%).
Synthetic Transformations of 2a. To a mixture of (3S,5'S)-1-
benzyl-5'-vinylspiro[indoline-3,3'-[1,2]dioxolan]-2-one
2a
(30.74 mg, 0.1 mmol) in MeOH (1 mL) was added sizeable stir-
rer. The resulting mixture was heated to reflux for 1 h. After
removal of solvent, the product was purified through silica gel
chromatography (eluent: petroleum ether - ethyl acetate = 5 : 1)
to give the 4 1-benzylindoline-2,3-dione in 86% yield.
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To a mixture of (3S,5'S)-1-benzyl-5'-vinylspiro[indoline-3,3'-
[1,2]dioxolan]-2-one 2a (30.74 mg, 0.1 mmol) in CH2Cl2 (2 mL)
was added zinc powder (325 mg). The resulting mixture was
o
cooled to 0 C and acetic acid (1 ml) was added dropwise
slowly. Then this mixture was stirred at room temperature for
1.5 h. Filtration under reduced pressure, residue washed by
CH2Cl2, combined organic layer dried over anhydrous Na2SO4,
filtered, filtrate concentrated in vacuo and purified by flash
chromatography on silica gel (eluent: petroleum ether - ethyl
acetate = 3 : 1) to afford 3a in 95% yield.
(S)-1-benzyl-3-hydroxy-3-((S)-2-hydroxybut-3-en-1-yl)indolin-
2-one (3a) 29.4 mg, 95% yield. Colorless oil. H NMR (300
1
MHz, Chloroform-d): δ 7.52 (dd, J = 7.4 Hz, 1.3 Hz, 1H), 7.36
– 7.24 (m, 6H), 7.11 (td, J = 7.6 Hz, 1.0 Hz, 1H), 6.77 (d, J =
7.8 Hz, 1H), 5.96 – 5.84 (m, 1H), 5.29 (dt, J = 17.2 Hz, 1.4 Hz,
1H), 5.14 (dt, J = 10.4 Hz, 1.3 Hz, 1H), 5.00 (d, J = 15.6 Hz,
1H), 4.81 (d, J = 15.6 Hz, 1H), 4.77 – 4.71 (m, 1H), 2.25 (dd, J
= 14.7 Hz, 10.2 Hz, 1H), 1.97 (dd, J = 14.7 Hz, 2.9 Hz, 1H);
13C{1H} NMR (75 MHz, Chloroform-d): δ 178.0, 142.0, 140.0,
135.3, 130.5, 129.8, 128.9, 127.8, 127.3, 124.3, 123.3, 115.3,
109.8, 76.0, 69.6, 43.9, 43.5.
The Supporting Information is available free of charge on the ACS
Publications website at DOI:
1H and 13C NMR spectra of substrates and products (PDF); Crys-
tallographic data for compound 2a (CIF)
*E-mail: zhouqingfa@cpu.edu.cn
Qingfa Zhou: 0000-0001-6360-2285
Fulai Yang: 0000-0002-1136-0867
The authors declare no competing financial interest.
This work was financially supported by the National Natural Sci-
ence Foundation of China (Grant Nos. 21572271 and 21102179),
Qing Lan Project of Jiangsu Province, and National Science Fund
for Fostering Talents in Basic Science (Grant No. J1030830), Post-
graduate Scientific Research Innovation Projects of Jiangsu Prov-
ince (KYCX17_0664).
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