Facile Synthesis of Spiro[cyclohexane-1,3'-indoline]-2,2'-diones

Article abstract of DOI:10.1515/hc-2019-0022

Spiro[cyclohexane-1,3'-indoline]-2,2'-diones were easily prepared in good to high yields by the oxidation of N-aryl-N-methyl-2-oxocyclohexane-1-carboxamides in one pot with a short reaction time. The spiroindolinediones could be important for the total synthesis of natural products.

Full text of DOI:10.1515/hc-2019-0022

Heterocycl. Commun. 2019; 25: 157–161
Preliminary Communication
Open Access
Shin-taro Katayama and Hiroshi Nishino*
Facile Synthesis of Spiro[cyclohexane-
1
,3’-indoline]-2,2’-diones
https://doi.org/10.1515/hc-2019-0022
conditions and techniques. In the course of these studies,
we envisioned that the oxidation of N-aryl-2-oxocyclohe-
xane-1-carboxamide might give spiro[cyclohexane-1,3’-
indoline]-2,2’-diones via the formal 5-exo-trig cyclization.
In order to confirm the hypothesis, N-methyl-2-oxo-N-
phenylcyclohexane-1-carboxamide (1a) was prepared by
the direct condensation of N-methylaniline with ethyl
Received January 22, 2019; accepted June 03, 2019.
Abstract: Spiro[cyclohexane-1,3’-indoline]-2,2’-diones were
easily prepared in good to high yields by the oxidation
of N-aryl-N-methyl-2-oxocyclohexane-1-carboxamides in
one pot with a short reaction time. The spiroindolinedio-
nes could be important for the total synthesis of natural
products.
2
-oxocyclohexane-1-carboxylate and subjected to the
Mn(III)-based oxidation.
The reaction was carried out in AcOH at room tem-
perature using a stoichiometric amount of Mn(OAc)3.
Although the oxidant was consumed for 2 days, the
desired product 2a was obtained as a racemic mixture
Keywords: spiro[cyclohexane-1,3’-indoline]-2,2’-diones; oxi-
dative cyclization; 5-exo cyclization; radicals; heterocycles.
Carbon-carbon and carbon-heteroatom bond forma- in a low yield from the reaction mixture (Scheme 1 and
tions are some of the most important goals in organic Table 1, Entry 1). A typical methine peak at δ 3.23 (1H,
synthesis [1], and the second is cyclization from the point dd, J = 11.6, 5.8 Hz, H-1) and one of the ortho aromatic
1
of kinetic and thermodynamic control [2]. Especially, protons at δ 7.17 (2H, dd, J = 8.5, 1.4 Hz) in the H NMR
these ingenious techniques are sometimes needed for the spectrum of 1a disappeared in that of 2a. In addition, a
1
3
total synthesis of both simple and complex natural pro- typical methine carbon at δ 54.9 in the C NMR spectrum
ducts [3,4]. For example, the C-C bond formation using of 1a became a spiro quaternary carbon at δ 63.4, and
boronic acid esters is well-known as a typical Suzuki- furthermore, five aromatic C-H carbons of 1a reduced
Miyaura cross-coupling reaction [5-9], and the cycliza- to four in that of 2a. These spectroscopic data clearly
tion using Grubbs reagents as a ring-closing metathesis showed that the desired cyclization took place, that is,
(
RCM) [10-12]. However, these reactions are needed to set the product 2a should be 1’-methylspiro[cyclohexane-
the complicated stage for the coupling and cyclization, 1,3’-indoline]-2,2’-dione [15,16]. Very recently, the same
and sometimes under special conditions. Recently, we spirocyclic oxindole obtained by Cu(II)-mediated radical
reported the synthesis of 3,4-dihydro-2(1H)-quinolinoes cross-dehydrogenative coupling using 1a was reported
by the Mn(III)-based oxidative 6-endo-trig cyclization of by Taylor et al. [17] and the spectroscopic data of 2a was
2
-[2-(N-arylamino)-2-oxoethyl]malonates [13], and 3-ace- in complete accordance with that of the reported com-
tylindolin-2-ones by the oxidative 5-exo-trig cyclization pound. We were encouraged by the result, and optimized
of N-arylbutanamides [14]. Both reactions are fully satis- the Mn(III)-based reaction under various conditions
fied as the goal in organic synthesis, in addition, they (Entries 2-6). As a result, when the reaction was conduc-
are simple and convenient synthetic methods suitable ted using Mn(OAc) (2.5 eq.) in boiling AcOH, the reaction
3
for substituted quinolines and indoles without special finished within only 4 min and the spiroindolinedione
2
a was produced in 69% maximum yield (Entry 5) which
is similar to that of Taylor et al. (65% yield) in boiling
toluene for 1.5 h. In order to apply the cyclization to other
substituted oxocyclohexanecarboxamides, we examined
the reactions of 1b-j [18] under the optimized conditions.
Gratifyingly, the results were very good as expected,
giving 75-96% isolated yields of the corresponding new
spiroindolinediones 2b-j (Entries 7-15).
*
Corresponding author: Hiroshi Nishino, Department of Chemistry,
Graduate School of Science, Kumamoto University, Kurokami 2-39-1,
Chûou-Ku, Kumamoto 860-8555, Japan
Fax: +81-96-342-3374; e-mail: nishino@kumamoto-u.ac.jp
Shin-taro Katayama, Department of Chemistry, Graduate School of
Science and Technology, Kumamoto University, Kurokami 2-39-1,
Chûou-Ku, Kumamoto 860-8555, Japan
Open Access. © 2019 Katayama and Nishino, published by De Gruyter.ꢀ
Attribution alone 4.0 License.
ꢀThis work is licensed under the Creative Commons
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ꢁ
S. Katayama and H. Nishino: Facile Synthesis of Spiro[cyclohexane-1,3’-indoline]-2,2’-diones
158ꢁ
In conclusion, a simple and convenient one-pot synthe- spectra were measured in CHCl or KBr using a Shimadzu
3
−1
sis of spiro[cyclohexane-1,3’-indoline]-2,2’-diones 2a-j was 8400 FT IR spectrometer and expressed in cm . The NMR
demonstrated. The spiro compounds would be important for spectra were recorded using a JNM ECX 500 spectrometer
1
13
the total synthesis of several natural products as the starting at 500 MHz for the H and at 125 MHz for C, with tetra-
material [19-22]. The scope of the reaction using the N-aryl- methylsilane as the internal standard. The chemical shifts
-oxocycloalkane-1-carboxamides and synthetic applica- are reported as δ values (ppm) and the coupling cons-
2
tions using the spiro compounds are currently underway.
tants in Hz. The following abbreviations are used for the
multiplicities: s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet; and brs, broad singlet for the NMR spectra.
The high-resolution mass spectra using a JEOL JMS-700
MStation were obtained at the Instrumental Analysis
Experimental
Melting points were taken using a MP-J3 Yanagimoto Center, Kumamoto University, Kumamoto, Japan.
micromelting point apparatus and are uncorrected. The IR
Preparation of Materials
A mixture of N-methylaniline (0.650 mL) and ethyl 2-oxo-
cyclohexane-1-carboxylate (0.170 g) was heated under
reflux for 24 h, and the crude products were separated
by silica gel column chromatography eluting with EtOAc/
hexane/acetone (2:7:1 v/v), giving N-methyl-2-oxo-N-phe-
nylcyclohexane-1-carboxamide (1a) (0.126 g; 54% yield).
Other 2-oxocyclohexane-1-carboxamides 1b-j were pre-
pared according to a procedure similar to that described
above. Manganese(III) acetate dihydrate, Mn(OAc) •2H O,
3
2
Scheme 1ꢀ
was synthesized according to our modified method [14].
a
Table 1ꢂOxidation of N-Methyl-2-oxocyclohexane-1-carboxamides 1a-j with Mn(OAc)3
Entry
ꢃ
Carboxamide ꢁ/
ꢁ:Mn(OAc) b
Temp/°C
rt
Time/min
Product yield/%c
ꢃa (ꢃꢇ)
ꢃa (ꢅꢇ)
ꢃa (ꢆꢊ)
ꢃa (ꢋꢉ)
ꢃa (ꢋꢌ)
ꢃa (ꢇꢇ)
ꢃb (ꢊꢆ)
ꢃc (ꢊꢋ)
ꢃd (ꢈꢇ)
ꢃe (ꢌꢉ)
ꢃf (ꢌꢋ)
ꢂ
ꢃ
ꢄ
ꢅ
ꢆ
ꢁa : R = R = R = R = H
ꢃ:ꢄ
ꢃ:ꢄ
ꢄ d
ꢈꢉ
ꢈ
ꢃ
ꢄ
ꢅ
ꢆ
ꢄ
ꢁa : R = R = R = R = H
ꢈꢉ
ꢃ
ꢄ
ꢅ
ꢆ
ꢅ
ꢁa : R = R = R = R = H
ꢃ:ꢄ
ꢃꢉꢉ
ꢃ
ꢄ
ꢅ
ꢆ
ꢆ
ꢁa : R = R = R = R = H
ꢃ:ꢄ
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
ꢄ
ꢃ
ꢄ
ꢅ
ꢆ
ꢇ
ꢁa : R = R = R = R = H
ꢃ:ꢄ.ꢇ
ꢃ:ꢅ
ꢆ
ꢃ
ꢄ
ꢅ
ꢆ
ꢋ
ꢁa : R = R = R = R = H
ꢇ
ꢃ
ꢄ
ꢆ
ꢅ
ꢈ
ꢁb : R = R = R = H, R = Me
ꢃ:ꢄ
ꢃ
ꢃ
ꢄ
ꢆ
ꢅ
ꢊ
ꢁc : R = R = R = H, R = OMe
ꢃ:ꢄ
ꢃ
ꢃ
ꢄ
ꢆ
ꢅ
ꢌ
ꢁd : R = R = R = H, R = Cl
ꢃ:ꢄ.ꢇ
ꢃ:ꢄ.ꢇ
ꢃ:ꢄ
ꢃ
ꢃ
ꢄ
ꢆ
ꢅ
ꢃꢉ
ꢃꢃ
ꢃꢄ
ꢃꢅ
ꢃꢆ
ꢃꢇ
ꢁe : R = R = R = H, R = F
ꢃ
ꢃ
ꢄ
ꢅ
ꢆ
ꢁf : R = Me, R = R = R = H
ꢉ.ꢇ
ꢃ
ꢃ
ꢄ
ꢅ
ꢆ
ꢁg : R = OMe, R = R = R = H
ꢃ:ꢄ.ꢇ
ꢃ:ꢄ.ꢇ
ꢃ:ꢄ.ꢇ
ꢃ:ꢄ.ꢇ
ꢃg (ꢊꢊ)
ꢃh (ꢌꢅ)
ꢃi (ꢌꢇ)
ꢃ
ꢄ
ꢅ
ꢆ
ꢁh: R = Cl, R = R = R = H
ꢉ.ꢇ
ꢃ
ꢃ
ꢄ
ꢅ
ꢆ
ꢁi : R = R = Me, R = R = H
ꢃ
ꢅ
ꢄ
ꢆ
ꢁj : R = R = H, R = R = Me
ꢃ
ꢃj (ꢊꢊ)
a
b
c
The reaction of the carboxamide ꢁ (ꢉ.ꢇ mmol) was carried out in AcOH (ꢃꢇ mL).
Molar ratio.
Isolated yield.
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S. Katayama and H. Nishino: Facile Synthesis of Spiro[cyclohexane-1,3’-indoline]-2,2’-dionesꢁ
ꢁ159
1
Oxidation of 2-Oxocyclohexane-1-carboxamides 1a-j
(-N-C=O); H NMR (500 MHz, CDCl ): δ 6.89 (1H, d,
3
J = 2.4 Hz, arom H), 6.83 (1H, dd, J = 8.5, 2.4 Hz, arom H),
The general procedure for the reactions of the 2-oxocyc- 6.74 (1H, d, J = 8.5 Hz, arom H), 3.80 (3H, s, MeO), 3.17 (3H,
lohexane-1-carboxamides 1a-j with Mn(OAc) •2H O was s, =N-Me), 3.08 (1H, ddd, J = 16.0, 11.0, 6.0 Hz, H-CH), 2.57
3
2
as follows. To a cyclohexanecarboxamide 1 (0.5 mmol) (1H, dt, J = 14.0, 5.0 Hz, H-CH), 2.49-2.40 (1H, m, H-CH),
dissolved in glacial AcOH (15 mL) was added 2.25-2.17 (2H, m, CH ), 2.08 (1H, ddd, J = 14.5, 11.0, 4.0 Hz,
2
Mn(OAc) •2H O (1 mmol), and the mixture was quickly H-CH), 2.01-1.92 (1H, m, H-CH), 1.87-1.81 (1H, m, H-CH);
3
2
1
3
heated under reflux using a pre-heated oil bath at 140 °C
C NMR (125 MHz, CDCl ): δ 205.1 (C=O), 173.8 (-N-C=O),
3
until the brown color of Mn(III) turned transparent. 155.9 (C-5’), 136.7 (C-7’a), 130.6 (C-3’a), 112.6, 112.3, 108.6
After the Mn(III) oxidant was completely consumed, if (arom CH), 64.0 (C-1), 55.8 (MeO), 39.7, 37.5, 26.9 (CH ), 26.5
2
needed the existence of the Mn(III) could be monitored (=N-Me), 20.3 (CH ). FAB HRMS (acetone-NBA) calcd for
2
by iodine-starch paper, the solvent was removed under C H NO : 260.1287 (M+H). Found: 260.1296.
1
5
18
3
reduced pressure. Each reaction time is listed in Table 1.
5’-Chloro-1’-methylspiro[cyclohexane-1,3’-
The residue was triturated with 2M HCl (15 mL) and the indoline]-2,2’-dione (2d) Yield 75%; Colorless micro-
aqueous mixture was extracted three times with CHCl3 crystals (from EtOH-hexane): mp 89-91 °C; IR: ν = 1694
1
(
20 mL × 3). The combined extracts were washed with a (-N-C=O); H NMR (500 MHz, CDCl ): δ 7.29 (1H, dd, J = 8.3,
3
saturated aqueous solution of NaHCO and water, dried 2.0 Hz, arom H), 7.25 (1H, d, J = 2.0 Hz, arom H), 6.76 (1H,
3
over anhydrous MgSO , then concentrated to dryness. The d, J = 8.3 Hz, arom H), 3.18 (3H, s, =N-Me), 3.10 (1H, ddd,
4
obtained residue was separated by silica gel column chro- J = 16.5, 11.5, 6.0 Hz, H-CH), 2.57 (1H, dt, J = 14.0, 5.0 Hz,
matography eluting with EtOAc–hexane (3:7 v/v), giving H-CH), 2.50-2.42 (1H, m, H-CH), 2.25-2.19 (2H, m, CH ), 2.08
2
the desired spiro[cyclohexane-1,3’-indoline]-2,2’-diones (1H, ddd, J = 15.0, 11.5, 4.0 Hz, H-CH), 2.00-1.91 (1H, m,
1
3
2
a-j (Table 1).
H-CH), 1.86-1.80 (1H, m, H-CH); C NMR (125 MHz, CDCl ):
3
1
’-Methylspiro[cyclohexane-1,3’-indoline]-2,2’- δ 204.4 (C=O), 173.6 (-N-C=O), 141.7 (C-7’a), 130.9 (C-3’a),
1
dione (2a) [17] Yield 69%; H NMR (500 MHz, CDCl ): 128.5 (arom CH), 128.0 (C-5’), 125.2, 109.2 (arom CH), 63.7
3
δ 7.31-7.28 (2H, m, arom H), 7.09 (1H, dt, J = 7.6, 1.0 Hz, (C-1), 39.6, 37.5, 26.9 (CH ), 26.6 (=N-Me), 20.1 (CH ). FAB
2
2
arom H), 6.84 (1H, dd, J = 8.0, 0.8 Hz, arom H), 3.18 (3H, HRMS (acetone-NBA) calcd for C H ClNO : 264.0791
14
15
2
s, =N-Me), 3.05 (1H, ddd, J = 14.3, 10.4, 5.6 Hz, H-CH), 2.59 (M+H). Found: 264.0784.
1H, dt, J = 14.3, 5.6 Hz, H-CH), 2.45-2.37 (1H, m, H-CH), 5’-Fluoro-1’-methylspiro[cyclohexane-1,3’-
.26-2.21 (1H, m, H-CH), 2.20-2.13 (1H, m, H-CH), 2.09 (1H, indoline]-2,2’-dione (2e) Yield 90%; Colorless micro-
ddd, J = 14.1, 10.3, 4.1 Hz, H-CH), 2.02-1.94 (1H, m, H-CH), crystals (from EtOH-hexane): mp 76-78 °C; IR: ν = 1697
(
2
1
3
1
1
.89-1.82 (1H, m, H-CH); C NMR (125 MHz, CDCl ): δ 204.9 (-N-C=O); H NMR (500 MHz, CDCl ): δ 7.04-6.99 (2H, m,
3
3
(
C=O), 174.0 (-N-C=O), 143.0 (C-7’a), 129.2 (C-3’a), 128.4, arom H), 6.77-6.75 (1H, m, arom H), 3.18 (3H, s, =N-Me),
24.3, 122.4, 108.2 (arom CH), 63.4 (C-1), 39.5, 37.0, 26.7 3.12 (1H, ddd, J = 17.0, 11.5, 5.5 Hz, H-CH), 2.56 (1H, dt,
J = 13.5, 4.5 Hz, H-CH), 2.52-2.43 (1H, m, H-CH), 2.25-2.19
1
(
CH ), 26.2 (=N-Me), 20.1 (CH ).
2
2
1
’,5’-Dimethylspiro[cyclohexane-1,3’-indoline]- (2H, m, CH ), 2.08 (1H, ddd, J = 15.5, 11.5, 4.0 Hz, H-CH),
2
1
3
2
,2’-dione (2b) Yield 84%; Colorless microcrystals (from 2.00-1.91 (1H, m, H-CH), 1.85-1.79 (1H, m, H-CH); C NMR
1
EtOH-hexane): mp 125-127 °C; IR: ν = 1690 (-N-C=O); H (125 MHz, CDCl ): δ 204.5 (C=O), 173.7 (-N-C=O), 159.0
3
NMR (500 MHz, CDCl ): δ 7.12-7.10 (2H, m, arom H), 6.73 (d, J = 239 Hz, C-5’), 139.0 (d, J = 3 Hz, C-7’a), 130.7 (d,
3
(
1H, d, J = 8.0 Hz, arom H), 3.18 (3H, s, =N-Me), 3.07 (1H, J = 9 Hz, C-3’a), 114.7 (d, J = 23 Hz, C-6’), 112.8 (d, J = 23 Hz,
ddd, J = 16.0, 11.0, 6.0 Hz, H-CH), 2.59 (1H, dt, J = 14.0, C-4’), 108.6 (d, J = 9 Hz, C-7’), 63.8 (d, J = 1 Hz, C-1), 39.5,
5
2
.0 Hz, H-CH), 2.44-2.40 (1H, m, H-CH), 2.36 (3H, s, Me), 37.5, 26.9 (CH ), 26.5 (=N-Me), 20.0 (CH ). FAB HRMS (ace-
2
2
.25-2.27 (2H, m, H-CH), 2.08 (1H, ddd, J = 13.5, 10.5, 4.0 Hz, tone-NBA) calcd for C H FNO : 248.1087 (M+H). Found:
14 15 2
H-CH), 2.01-1.93 (1H, m, H-CH), 1.89-1.82 (1H, m, H-CH); 248.1091.
C NMR (125 MHz, CDCl ): δ 205.3 (C=O), 174.1 (-N-C=O),
13
1’,7’-Dimethylspiro[cyclohexane-1,3’-indoline]-
3
1
40.8 (C-7’a), 132.1 (C-5’), 129.4 (C-3’a), 128.9, 125.4, 108.1 2,2’-dione (2f) Yield 96%; Colorless microcrystals (from
(
arom CH), 63.7 (C-1), 39.8, 37.3, 26.9 (CH ), 26.4 (=N-Me), EtOH-hexane): mp 128-130 °C; IR: ν = 1684 (-N-C=O);
2
1
2
1.2 (Me), 20.3 (CH ). FAB HRMS (acetone-NBA) calcd for H NMR (500 MHz, CDCl ): δ 7.09 (1H, d, J = 7.2 Hz arom
2
3
C H NO : 244.1338 (M+H). Found: 244.1321.
H), 7.03 (1H, d, J = 7.6 Hz, arom H), 6.99 (1H, t, J = 7.6 Hz,
15
18
2
5
’-Methoxy-1’-methylspiro[cyclohexane-1,3’- arom H), 3.47 (3H, s, =N-Me), 3.08 (1H, ddd, J = 16.5, 11.5,
indoline]-2,2’-dione (2c) Yield 86%; Colorless microc- 5.5 Hz, H-CH), 2.59-2.57 (1H, m, H-CH), 2.56 (3H, s, Me),
rystals (from EtOH-hexane): mp 111-113 °C; IR: ν = 1684 2.48-2.41 (1H, m, H-CH), 2.21-2.18 (2H, m, CH ), 2.07 (1H,
2
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ꢁ
S. Katayama and H. Nishino: Facile Synthesis of Spiro[cyclohexane-1,3’-indoline]-2,2’-diones
1
60ꢁ
ddd, J = 14.0, 10.5, 4.0 Hz, H-CH), 1.99-1.90 (1H, m, H-CH),
1’,4’,6’-Trimethylspiro[cyclohexane-1, 3’-
1
3
1
.86-1.81 (1H, m, H-CH); C NMR (125 MHz, CDCl ): δ 205.4 indoline]-2,2’-dione (2j) Yield 88%; Colorless microc-
3
(
C=O), 174.8 (-N-C=O), 140.9 (C-7’a), 132.3 (arom CH), 130.0 rystals (from EtOH-hexane): mp 164-166 °C; IR: ν = 1686
1
(C-3’a), 122.5 (2C, arom CH), 119.9 (C-7’), 63.0 (C-1), 39.7, (-N-C=O); H NMR (500 MHz, CDCl ): δ 6.72 (1H, s,
3
3
7.7 (CH ), 29.8 (=N-Me), 26.9, 20.3 (CH ), 19.1 (Me). FAB arom H), 6.49 (1H, s, arom H), 3.19-3.15 (1H, m, H-CH),
2
2
HRMS (acetone-NBA) calcd for C H NO : 244.1338 (M+H). 3.13 (3H, s, =N-Me), 2.64-2.54 (2H, m, CH ), 2.38 (1H, dt,
1
5
18
2
2
Found: 244.1326.
J = 13.8, 4.5 Hz, H-CH), 2.33 (3H, s, Me-C-6’), 2.27-2.22 (1H,
7
’-Methoxy-1’-methylspiro[cyclohexane-1,3’- m, H-CH), 2.17 (3H, s, Me-C-4’), 2.05-2.01 (1H, m, H-CH),
13
indoline]-2,2’-dione (2g) Yield 88%; Colorless micro- 1.87-1.79 (1H, m, H-CH), 1.78-1.74 (1H, m, H-CH); C NMR
crystals (from EtOH-hexane): mp 94-96 °C; IR: ν = 1684 (125 MHz, CDCl ): δ 204.6 (C=O), 173.8 (-N-C=O), 143.4
3
1
(
-N-C=O); H NMR (500 MHz, CDCl ): δ 7.04 (1H, t, J = 7.9 Hz, (C-7’a), 138.6 (C-6’), 134.6 (C-4’), 125.9 (arom C), 124.7 (C-3’a),
3
arom H), 6.88 (1H, s, arom H), 6.88 (1H, d, J = 8.0 Hz, arom 125.9 (arom C), 63.3 (C-1), 40.3, 34.8, 26.4 (CH ), 26.3 (=N-
2
H), 3.84 (3H, s, MeO), 3.46 (3H, s, =N-Me), 3.10 (1H, ddd, Me), 21.5 (Me-C-6’), 20.0 (CH ), 19.0 (Me-C-4’). FAB HRMS
2
J = 16.5, 11.0, 6.0 Hz, H-CH), 2.56 (1H, dt, J = 13.5, 4.8 Hz, (acetone-NBA) calcd for C H NO Na: 280.1313 (M+Na).
1
6
19
2
H-CH), 2.50-2.41 (1H, m, H-CH), 2.23-2.19 (2H, m, CH ), 2.07 Found: 280.1315.
2
(
1H, ddd, J = 14.0, 10.0, 4.0 Hz, H-CH), 1.98-1.89 (1H, m,
13
H-CH), 1.85-1.80 (1H, m, H-CH); C NMR (125 MHz, CDCl ): Acknowledgments: This research was supported by a
3
δ 205.4 (C=O), 174.2 (-N-C=O), 145.3 (C-7’a), 131.1 (C-3’a), Grant-in-Aid for Scientific Research (C), No. 25410049,
1
30.9 (C-7’), 123.1, 117.2, 112.4 (arom CH), 63.6 (C-1), 55.9 from the Japan Society for the Promotion of Science.
(
MeO), 39.6, 37.6 (CH ), 29.7 (=N-Me), 26.8, 20.1 (CH ). FAB We also acknowledge the Nissan Chemical Corporation
2
2
HRMS (acetone-NBA) calcd for C H NO : 260.1287 (M+H). for the financial support. HN thanks Mr. Daichi Hirata,
15
18
3
Found: 260.1277.
Department of Science, Faculty of Science, Kumamoto
7
’-Chloro-1’-methylspiro[cyclohexane-1,3’- University, Japan, for his technical assistance.
indoline]-2,2’-dione (2h) Yield 93%; Yellow oil; IR:
ν = 1699 (-N-C=O); H NMR (500 MHz, CDCl ): δ 7.23 (1H,
1
3
dd, J = 8.2, 1.1 Hz, arom H), 7.12 (1H, dd, J = 7.4, 1.1 Hz, arom
H), 7.01 (1H, t, J = 7.5 Hz, arom H), 3.56 (3H, s, =N-Me), 3.13
References
(
1H, ddd, J = 18.0, 12.5, 6.0 Hz, H-CH), 2.55 (1H, dt, J = 13.5,
.3 Hz, H-CH), 2.52-2.45 (1H, m, H-CH), 2.25-2.18 (2H, m,
CH ), 2.08 (1H, ddd, J = 15.5, 11.5, 4.0 Hz, H-CH), 1.97-1.88
[
1] Smith, M. B. Organic Synthesis; McGraw-Hill, Inc: New York,
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[
2] Illuminati, G; Mandolini, L. Ring Closure Reactions of
2
1
3
Bifunctional Chain Molecules. Acc. Chem. Res. 1981, 14,
(
1H, m, H-CH), 1.84-1.78 (1H, m, H-CH); C NMR (125 MHz,
95-102.
CDCl ): δ 204.5 (C=O), 174.1 (-N-C=O), 139.0 (C-7’a), 131.9
3
[
3] Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis;
Wiley: New York, 1989.
(
C-3’a), 130.8, 123.4, 123.2 (arom CH), 115.5 (C-7’), 63.2 (C-1),
3
9.5, 37.9 (CH ), 29.8 (=N-Me), 26.9, 20.0 (CH ). FAB HRMS
[4] Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis;
VCH: New York, 1996.
2
2
(
acetone-NBA) calcd for C H ClNO : 264.0791 (M+H).
14 15 2
[
5] Miyaura, N.; Suzuki, A. Stereoselective Synthesis of Arylated
E)-Alkenes by the Reaction of Alk-1-enylboranes with Aryl
Found: 264.0777.
(
1
’,6’,7’-Trimethylspiro[cyclohexane-1, 3’-
Halides in the Presence of Palladium Catalyst. J. Chem. Soc.,
Chem. Commun. 1979, 866-867.
indoline]-2,2’-dione (2i) Yield 95%; Colorless microc-
rystals (from EtOH-hexane): mp 132-134 °C; IR: ν = 1684
[
6] Miyaura, N.; Yanagi, T.; Suzuki, A. The palladium-catalyzed
cross-coupling reaction of phenylboronic acid with haloarenes
in the presence of bases. Synth. Commun. 1981, 11(7), 513-19.
1
(
-N-C=O); H NMR (500 MHz, CDCl ): δ 6.99 (1H, d,
3
J = 7.5 Hz, arom H), 6.92 (1H, d, J = 7.5 Hz, arom H), 3.49
3H, s, =N-Me), 3.07 (1H, ddd, J = 16.5, 11.0, 5.5 Hz, H-CH),
[
7] Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling
(
Reactions of Organoboron Compounds. Chem. Rev. 1995, 95(7),
2
2
.56 (1H, dt, J = 14.5, 5.0 Hz, H-CH), 2.47 (3H, s, Me-C-7’),
.45-2.38 (1H, m, H-CH), 2.30 (3H, s, Me-C-6’), 2.21-2.17 (2H,
2
457-2483.
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8] Martin, R.; Buchwald, S. L. Palladium-Catalyzed Suzuki-
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m, CH ), 2.11-2.02 (1H, m, H-CH), 1.98-1.89 (1H, m, H-CH),
2
13
1
.86-1.79 (1H, m, H-CH); C NMR (125 MHz, CDCl ): δ 205.5
3
[
9] Lennox, A. J. J.; Lloyd-Jones, G. C. Selection of boron reagents
(
C=O), 175.2 (-N-C=O), 141.2 (C-7’a), 138.4 (C-6’), 127.9 (C-3’a),
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1
3
24.2, 121.7 (arom C), 119.1 (C-7’), 62.7 (C-1), 39.6, 37.6 (CH ),
2
412-443.
0.6 (=N-Me), 26.8 (CH ), 20.8 (Me-C-7’a), 20.3 (CH ), 14.1
2
2
[10] Trnka, T. M.; Grubbs, R. H. The Development of L2X2RudCHR
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(Me-C-6’a). FAB HRMS (acetone-NBA) calcd for C H NO :
16 20 2
2
58.1494 (M+H). Found: 258.1505.
Unauthenticated
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S. Katayama and H. Nishino: Facile Synthesis of Spiro[cyclohexane-1,3’-indoline]-2,2’-dionesꢁ
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3
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Unauthenticated
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