Double methylenecyclopentane annulation of succinimides: Easy access to 3,7-dioxobicyclo[3.3.0]octane-1,5-dicarboximides

Article abstract of DOI:10.1002/ejoc.200900273

N-Alkylsuccinimides reacted with excess of LHMDS and 3chloro-2- (chloromethyl)-l.-p:ropene to give in medium, yields N-alkyl-3,7-dim.ethylen. ebicyclo[3.3.0]octane-l.,5-dicarboximides, which were ozonized to the corresponding 3,7-dioxobicyclo[3.3.0]octane

Full text of DOI:10.1002/ejoc.200900273

FULL PAPER
DOI: 10.1002/ejoc.200900273
Double Methylenecyclopentane Annulation of Succinimides: Easy Access to
3,7-Dioxobicyclo[3.3.0]octane-1,5-dicarboximides
Pelayo Camps,*[a] José A. Fernández,[a] Jordi Rull,[a] and Santiago Vázquez[a]
Dedicated to Prof. Dr. Armin de Meijere on the occasion of his 70th birthday
Keywords: Alkylation / Annulation / Carbocycles / Lithiation / Ozonolysis
N-Alkylsuccinimides reacted with excess of LHMDS and 3-
chloro-2-(chloromethyl)-1-propene to give in medium yields
N-alkyl-3,7-dimethylenebicyclo[3.3.0]octane-1,5-dicarbox-
imides, which were ozonized to the corresponding 3,7-di-
alkyl-4-methylenecyclopentane-1,2-dicarboximides
mainly obtained, in spite of using excess of both base and
alkylating agent.
were
oxobicyclo[3.3.0]octane-1,5-dicarboximides. When these al- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
kylations were carried out by using LDA as the base, cis-N-
Germany, 2009)
Weiss–Cook reaction is dimethyl cis-3,7-dioxobicyclo[3.3.0]-
octane-1,5-dicarboxylate (2), which was prepared several
years ago by our research group.[3] Disodium dihydroxytar-
trate was esterified with MeOH/HCl, the crude dimethyl
2,3-dioxobutanedioate or derivative thereof thus obtained
was condensed with dimethyl acetonedicarboxylate and the
mixture of condensation products was directly submitted to
methoxydecarboxylation under the Krapcho conditions[4]
to give 2 in only 18% yield. Deslongchamps et al.[5] found
that this is an unusual Bertz–Weiss–Cook condensation in
which an oxabicyclic intermediate instead of the expected
carbobicyclic diketo ester is formed. Demethoxycarboxyla-
tion of this oxabicyclic intermediate under the Krapcho
conditions gives 2, probably via the usual carbobicyclic di-
keto ester.
Introduction
Many cis-bicyclo[3.3.0]octane-3,7-diones mono- or di-
substituted at the bridgehead positions 1 (Figure 1) are
readily available compounds through the Bertz–Weiss–
Cook reaction.[1] These compounds have been used for the
synthesis of many polyquinenes, such as staurane-2,5,8,11-
tetraene, modhephene, triquinacene, polyquinane natural
products, such as gymnomitrol, quadrone, isocomene,
pentalenene, and non-natural products, such as semibullval-
enes, [5]peristylane, among others.[2]
This research group transformed compound 2 in three
steps into compound 3a, as a key intermediate for the prep-
aration of a novel scaffold for the modular assembly of re-
Figure 1. Diketones from the Bertz–Weiss–Cook reaction and de-
rivative thereof.
To the best of our knowledge, the only described cis-bicy-
clo[3.3.0]octane-3,7-dione having two carbonyl substituents
at the bridgehead positions directly obtained via the Bertz–
[a] Laboratori de Química Farmacèutica (Unitat Associada al
CSIC), Facultat de Farmàcia, and Institute of Biomedicine
(IBUB), Universitat de Barcelona,
Av. Diagonal 643, 08028 Barcelona, Spain
Fax: +34-93-4035941
E-mail: camps@ub.edu
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900273.
Scheme 1. Mono- and bis-annulations of succinimides 4.
Eur. J. Org. Chem. 2009, 3081–3087
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3081

P. Camps, J. A. Fernández, J. Rull, S. Vázquez
FULL PAPER
ceptor models (Figure 1).[6] However, the preparation of 3a showing that LDA is an adequate base to prepare double-
is lengthy and low-yielding. Other transformations from 2 annulated products (7) from monoannulated ones (6). Reac-
were also carried out by the same group.[7]
tion of succinimide 4a with 5 using lithium 2,2,6,6-tet-
Our continued interest on diones 1 as starting com- ramethylpiperidide (LTMP) as the base under standard
pounds to prepare functionalized tricyclo[3.3.0.03,7]octane conditions (great excess of base and 5) gave mainly
derivatives,[8] led us to plan an alternative and shorter pro- monoannulated product 6a and traces of diannulated prod-
cedure to prepare compound 3a and related compounds uct 7a (Entry 3). As before, reaction of 6a with 5 using
from readily available starting materials, as shown in LTMP as the base gave 7a although in only 24% yield.
Scheme 1.
These results might be partly understood on the basis of
steric effects, the less bulky base (LDA) acting as a nucleo-
phile might participate in side reactions whether with the
alkylating agent or the succinimide in a greater extent, while
the more bulky base (LTMP) might be not so adequate for
Results and Discussion
It is known that diethyl trans-4-methylenecyclopentane- the alkylation of the monoannulated products 6.
1,2-dicarboxylate can be obtained from succinic acid by (i)
conversion into a bis-oxazoline derivative by reaction with
Table 1. Conditions, products and yields from the reaction of suc-
cinimides 4 and 6a with 5.
2-amino-2,2-dimethylethanol, (ii) alkylation of the corre-
sponding dianion, generated by reaction with nBuLi, with
3-chloro-2-(chloromethyl)-1-propene (5) and (iii) etha-
nolysis.[9] Also, diastereo-enriched di-(–)-menthyl trans-4-
methylenecyclopentane-1,2-dicarboxylate has been ob-
tained by reaction of the dianion of di-(–)-menthyl succi-
nate with the above dialkylating agent 5 using 2,2,6,6-tet-
ramethylpiperidide as the base.[10] Moreover, we had experi-
ence in the formation of cyclopentane derivatives by alky-
lation of a dianion derived from an N-aryl-α,αЈ-disubsti-
tuted succinimide with 1,3-dibromopropane using LDA as
the base,[11] following a known procedure.[12]
Consequently, we imagined that reaction of N-substi-
tuted succinimides 4 with an excess of a base, such as LDA,
and an excess of the alkylating agent 5 might give imides 6
which could be further alkylated to give finally imides 7
(Scheme 1).
Entry
Compd.
5 (equiv.) Base (equiv.)
Product
6 (%)
7 (%)
1
2
3
4
5
6
7
8
4a
4a
4a
6a
6a
4b
4b
4b
4c
4c
4d
4d
4e
4e
4.0
4.0
4.0
2.0
2.0
2.4
4.3
4.3
3.9
4.0
4.0
4.0
2.4
2.4
LDA (6.0)
65
–
24
–
–
79
3
54
24
23
–
36
–
47
–
69
–
LHMDS (6.0)
LTMP (6.0)
LDA (3.0)
LTMP (3.0)
LDA (4.5)
LDA (6.0)
LHMDS (6.0)
LDA (6.0)
LHMDS (6.1)
LDA (6.0)
LHMDS (6.0)
LDA (5.0)
–
34
49
–
53
–
50
–
–
9
10
11
12
13
14
LHMDS (5.0)
–
–
Succinimide 4a was prepared by a known procedure,[13]
succinimide 4b is commercially available, succinimide 4c[14]
was prepared in good yield by the same procedure described
for 4a,[13] and succinimide 4d[14] was obtained by a known
procedure.[15] Results of the alkylation of different suc-
cinimides 4 with 5 are collected in Table 1. Worthy of note,
using lithium diisopropylamide (LDA) as the base,
monoannulated products 6 were usually isolated in medium
(49–65%) yields as the only defined reaction products, in
spite of using a great excess of base and alkylating agent
(Entries 1, 7, 9 and 11). The rest of material could not be
identified. Only in one case (Entry 5) starting from 4b and
using lower excesses of base (4.5 equiv.) and alkylating
agent (2.4 equiv.), monoannulated and diannulated prod-
ucts 6b (34%) and 7b (23%), respectively, were isolated.
Contrarily, using lithium hexamethyldisilazide (LHMDS)
as the base, under similar reaction conditions, diannulated
products 7 were obtained in 36–79% yield (Entries 2, 4, 8,
10 and 12), monannulated products 6 being not detected.
The best yield was obtained for the N-(p-methoxybenzyl)
derivative 7a (79%, Entry 2) and then for the tert-butyl de-
rivative 7d (69%, Entry 12). However, the yield of the N-
methyl derivative 7b was low (36%, Entry 8). Reaction of
Curiously, no mono- or bis-annelated products were ever
isolated starting from N-phenylsuccinimide 4e using either
LDA or LHMDS as the base. This result is in striking con-
trast with a parallel transformation performed by the group
starting from the N-phenylsuccinimide derivative 8, which
gave the annulated product 9 in 65% yield (Scheme 2).
Scheme 2. Successful annulation of the N-phenylimide 8.
The p-methoxybenzyl group of imide 7a could be cleaved
by treatment with Cerium(IV) ammonium nitrate (CAN) in
the usual way[16] to give the corresponding deprotected
imide 7f in 67% yield.
The new mono- and bis-annulated products 6a–d/7a–d
compound 6a with LDA (3 equiv.) and 5 (2 equiv.) under were submitted to ozonization leading, after hydrogenation
the usual conditions gave 7a in 54% yield (Entry 4), thus of the ozonide, to the corresponding mono- or di-ketones
3082
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Eur. J. Org. Chem. 2009, 3081–3087

Double Methylenecyclopentane Annulation of Succinimides
(10 or 3) in high yields (Scheme 3).[17] Other oxidation
A compound 6 (R = H), has been used as an intermedi-
methods based on ruthenium or osmiun tetraoxide and ate in the preparation of SC-52491 and SC-52490, two az-
NaIO4/KMnO4 failed to give the desired ketones.[18–20] Ex- anoradamantane benzamide derivatives which exhibit very
cept dioxoimide 3a[6] and oxoimide 10b,[21] the rest of com- potent affinity for both the serotonin 5-HT4 and 5-HT3 re-
pounds 3, 6, 7, 9 and 10 described herein are novel and ceptors.[23,24] We are currently pursuing the application of
have been fully characterized through their spectroscopic ketones 3 and 10 or diene 7 for the preparation of new
data as well as elemental analysis and/or HRMS. Several of functionalized cage compounds related to those previously
the prepared compounds, especially those containing more prepared by the group,[8] as scaffolds for potentially active
carbonyl functions, retain molecules of water in spite of be- compounds.[25,26]
ing carefully dried under high vacuum. It is known that
inclusion of water in organic crystals is very common due
Conclusions
to the small size of the water molecule and its excellent
hydrogen bonding ability. As stated by G. R. Desiraju,[22]
“the proportion of non-ionic, metal-free, organic com-
pounds that crystallize as hydrates increases, within the
class, with an increase in the number of hydrogen-bond ac-
ceptor groups with respect to the donor groups”.
We have developed a two-step synthesis of diketoimides
3, that can be readily performed on gram scale now. The
key-step consists of a double methylenecyclopentane annu-
lation of N-substituted succimides by alkylation with 3-
chloro-2-(chloromethyl)-1-propene (5). The preparation of
the known 3a in 64% yield greatly improves the previous
preparation from diketone 2, obtained through the Bertz–
Weiss–Cook reaction. Similarly, ketoimides 10 have been
obtained which, together with the corresponding alkene
precursors 7 and 6, constitute a series of interesting syn-
thetic intermediates.
Experimental Section
General Methods: Melting points were determined in open capillary
tubes. Unless otherwise stated, NMR spectra were recorded at
25 °C in CDCl3: 1H NMR (400 MHz), 13C NMR (100.6 MHz).
Chemical shifts (δ) are reported in ppm related to internal standard
(CHCl3 at δH = 7.26 ppm, δC = 77.0 ppm). Assignments given for
the NMR spectra are based on DEPT sequence, 1H/1H COSY, 1H/
Scheme 3. Oxidation of alkenes 6/7 to the corresponding ketones
10/3.
1
13C HETCOR (HSQC sequence) and H/1H NOESY experiments
According to a referee, the presence of water in one of
these compounds (6a) was established by H NMR, as fol-
for selected compounds. Unless otherwise stated, IR spectra were
performed with the attenuated total reflection (ATR) technique
and the absorption values are given as wavenumbers (cm–1). Ele-
mental analyses were done at the Microanalysis Service of the
IIQAB (CSIC, Barcelona, Spain). Column chromatography was
performed on silica gel 60 A C.C. (35–70 mesh). For the thin-layer
chromatography (TLC), aluminum-backed sheets with silica gel 60
F254 were used and spots were visualized with UV light and/or 1%
aqueous KMnO4.
1
lows: (a) First, we obtained the spectrum of the solvent
(CDCl3) containing tetramethylsilane (TMS) as internal
reference, collecting 32 scans with a delay of 25 s to facili-
tate relaxation of all kind of protons, (b) solid compound
6a was then added to the NMR tube and once dissolved
the sample, a new spectrum was collected under the same
conditions (See Supporting Information). The ratio of the
integral of the TMS and the signal of water at δ = 1.53 ppm
was 100:79.4 in the spectrum of the solvent alone and
100:91.6 in the spectrum of the solvent plus 6a. Taking into
account the values for the integral of two protons of 6a
in all the signals except the one overlapping with CHCl3
N-(p-Methoxybenzyl)-4-methylene-cis-cyclopentane-1,2-dicarbox-
imide (6a): A solution of nBuLi in hexanes (44.0 mL, 2.50 ,
110 mmol) was added to a cold (0 °C) solution of anhydrous diiso-
propylamine (15.4 mL, 110 mmol) in anhydrous THF (100 mL),
and the mixture was allowed to react for 1 h at this temperature.
Then, a solution of succinimide 4a (4.00 g, 18.2 mmol) in anhy-
(minimum value: 90.1; maximum value: 92.7; average value: drous THF (65 mL) was added, the solution was stirred for 15 min
at –78 °C and then it was warmed to 0 °C in 1 h. The solution
was cooled to –78 °C and dichloride 5 (8.50 mL, 73.4 mmol) in
anhydrous THF (40 mL) was added dropwise. The mixture was
warmed to room temperature and stirred for 3 d at this tempera-
ture. The mixture was made acidic with aqueous 2  HCl (125 mL)
and extracted with Et2O (3ϫ150 mL). The combined organic ex-
tracts were dried (MgSO4), concentrated in vacuo, and the residue
(7.66 g) was subjected to column chromatography [silica gel (154 g),
hexane/AcOEt, 1:1] to yield alkene 6a (3.22 g, 65% yield) as a pale
yellow solid. The analytical sample was obtained as a white solid
by crystallization from AcOEt/hexane, 8:5, m.p. 106–107 °C; Rf =
91.6), a molar ratio water/6a = 0.13 was calculated, in good
concordance with the elemental analysis which agrees with
a molar ratio water/6a = 0.15. A similar experiment carried
out with compound 10c showed also the presence of water,
although calculations could not be so clearly performed due
to overlapping of the signals of water and the methyl groups
from the isopropyl substituent. For similar reasons, this
kind of experiment was not performed for the rest of com-
pounds (3d, 6c and 7c) whose elemental analyses also sug-
gest the presence of water.
Eur. J. Org. Chem. 2009, 3081–3087
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3083

P. Camps, J. A. Fernández, J. Rull, S. Vázquez
FULL PAPER
0.54 (hexane/AcOEt, 2:1). IR (KBr): ν = 3019, 2971, 2959, 2936,
N-(p-Methoxybenzyl)-3,7-dimethylene-cis-bicyclo[3.3.0]octane-1,5-
dicarboximide (7a) from 4a: A solution of nBuLi in hexanes
(44.0 mL, 2.50 , 110 mmol) was added to a cold (–78 °C) solution
˜
2906, 2839, 1766, 1707, 1694, 1611, 1514, 1461, 1431, 1400, 1365,
1350, 1244, 1178, 1028, 926, 914, 816 cm–1. 1H NMR: δ = 2.60 [br.
d, J = 16.4 Hz, 2 H, 3(5)-Hcis], 2.65–2.74 [ddm, J = 16.4, JЈ = of HMDS (23.0 mL, 110 mmol) in anhydrous THF (100 mL), and
9.6 Hz, 2 H, 3(5)-Htrans], 3.21 [m, 2 H, 1(2)-H], 3.77 (s, 3 H, OCH3), the mixture was allowed to react for 1 h at this temperature. Then,
4.56 (s, 2 H, N-CH2), 4.87 (br. s, 2 H, C4=CH2), 6.81 [dm, J = a solution of succinimide 4a (4.00 g, 18.2 mmol) in anhydrous THF
9.2 Hz, 2 H, Ar-3(5)-H], 7.25 [overlapped dm, 2 H, Ar-2(6)-H]
(50 mL) was added, the solution was stirred for 15 min at –78 °C
and then it was warmed to 0 °C in 1 h. The solution was cooled to
ppm. 13C NMR: δ = 36.1 [CH2, C-3(5)], 41.9 (CH2, N-CH2), 44.3
[CH, C-1(2)], 55.2 (CH3, OCH3), 109.6 (CH2, C-4=CH2), 113.9 –78 °C and dichloride 5 (8.40 mL, 72.6 mmol) in anhydrous THF
[CH, Ar-C-3(5)], 128.0 (C, Ar-C-1), 129.8 [CH, Ar-C-2(6)], 145.7 (100 mL) was added dropwise. The mixture was warmed to room
(C, C-4), 159.2 (C, Ar-C-4), 179.5 (C, CON) ppm. HRMS (ES+): temperature and stirred for 4 d at this temperature. The mixture
c a l c d . f o r [ M + N a ] + 2 9 4 . 1 1 0 1 ; f o u n d 2 9 4 . 1 0 9 9 .
was made acidic with aqueous 1  HCl (150 mL) and extracted
C16H17NO3·0.15H2O (274.02): calcd. C 70.13, H 6.36, N 5.11; with Et2O (3ϫ250 mL). The combined organic extracts were dried
found C 69.81, H 6.27, N 4.82.
(MgSO4), concentrated in vacuo and the residue (8.00 g) was sub-
jected to column chromatography [silica gel (160 g), hexane/AcOEt,
1:1] yielding diene 7a (4.64 g, 79% yield) as a yellow solid. The
analytical sample was obtained as a white solid by crystallization
from hexane, m.p. 102–103 °C; Rf = 0.29 (hexane/AcOEt, 2:1). IR
N-Methyl-4-methylene-cis-cyclopentane-1,2-dicarboximide (6b):
This compound was prepared in a similar manner to that described
before for 6a. From 4b (1.00 g, 8.84 mmol), 6b (710 mg, 49%) was
obtained. The analytical sample was prepared as a white solid by
crystallization from hexane, m.p. 84–86 °C, Rf 0.52 (hexane/AcOEt,
(KBr): ν = 2956, 2899, 2834, 1769, 1690, 1611, 1509, 1432, 1390,
˜
1341, 1305, 1291, 1244, 1175, 1153, 1032, 984, 906, 810, 729, 651,
1:1). IR: ν = 2952, 2909, 2842, 1766, 1686, 1429, 1380, 1312, 1281,
˜
1
640, 614 cm–1. H NMR: δ = 2.43 (d, J = 16.0 Hz, 4 H) and 2.75
1186, 1156, 1090, 1054, 1000, 964, 916, 872, 763, 676, 622 cm–1. 1H
NMR (300 MHz): δ = 2.62 [br. d, J = 16.2 Hz, 2 H, 3(5)-Hcis],
2.66–2.78 [m, 2 H, 3(5)-Htrans], 2.96 (s, 3 H, N-CH3), 3.21–3.28 [m,
2 H, 1(2)-H], 4.91 (br. s, 2 H, C4=CH2) ppm. 13 C NMR
(75.4 MHz): δ = 25.0 (CH3, N-CH3), 36.0 [CH2, C-3(5)], 44.3 [CH,
C-1(2)], 109.6 (CH2, C-4=CH2), 145.6 (C, C-4), 179.8 (C, CON)
ppm. HRMS (ES+): calcd. for [M + H]+ 166.0863; found 166.0861.
C9H11NO2 (165.19): calcd. C 65.44, H 6.71, N 8.48; found C 65.26,
H 6.67, N 8.28.
(d, J = 16.0 Hz, 4 H, 2(4,6,8)-Hexo and 2(4,6,8)-Hendo), 3.77 (s, 3
H, OCH3), 4.54 (s, 2 H, N-CH2), 4.82 [br. s, 4 H, C-3(7) = CH2],
6.79 [d, J = 9.0 Hz, 2 H, Ar-3(5)-H], 7.18 [d, J = 9.0 Hz, 2 H, Ar-
2(6)-H] ppm. 13C NMR: δ = 41.9 (CH2, N-CH2), 42.6 [CH2, C-
2(4,6,8)], 55.2 (CH3, OCH3), 60.4 [C, C-1(5)], 109.5 [CH2, C-3(7)
= CH2], 113.8 [CH, Ar-C-3(5)], 128.0 (C, Ar-C-1), 129.2 [CH, Ar-
C-2(6)], 147.4 [C, C-3(7)], 159.0 (C, Ar-C-4), 180.8 (C, CON) ppm.
HRMS (APCI): calcd. for [M + H]+ 324.1594; found 324.1595.
C
20H21NO3 (323.39): calcd. C 74.28, H 6.55, N 4.33; found C
74.10, H 6.65, N 4.28.
N-Isopropyl-4-methylene-cis-cyclopentane-1,2-dicarboximide (6c):
This compound was prepared in a similar manner to that described
before for 6a. From 4c (500 mg, 3.54 mmol), 6c (310 mg, 45 %
yield) was isolated as a pale yellow oil. An analytical sample of 6c
was obtained as colorless oil by microdistillation at 200 °C/2 Torr
in a rotary microdistillation equipment. Rf 0.64 (hexane/AcOEt,
7a from 6a: This compound was prepared in a similar manner to
that described before for 6a. From 6a (250 mg, 0.92 mmol), LDA
[from nBuLi in hexanes (1.10 mL, 2.50 , 2.75 mmol) and diisopro-
pylamine (390 µL, 2.75 mmol)] and 5 (210 µL, 1.84 mmol), 7a
(160 mg, 54% yield) was isolated as a pale yellow solid after col-
umn chromatography.
3:1). IR: ν = 2973, 2935, 1768, 1686, 1431, 1395, 1382, 1364, 1309,
˜
1284, 1225, 1176, 1134, 1098, 1052, 1033, 1014, 897, 884, 853, 664
cm–1. H NMR: δ = 1.32 [d, J = 7.2 Hz, 6 H, N-CH(CH3)2], 2.58 N-Methyl-3,7-dimethylene-cis-bicyclo[3.3.0]octane-1,5-dicarbox-
1
[br. d, J = 16.0 Hz, 2 H, 3(5)-Hcis], 2.67 [ddm, J = 16.0, JЈ = 7.6 Hz,
2 H, 3(5)-Htrans], 3.12 [m, 2 H, 1(2)-H], 4.30 [hept, J = 7.2 Hz, 1
H, N-CH(CH3)2], 4.88 (br. s, 2 H, C4=CH2) ppm. 13C NMR δ =
imide (7b): This compound was prepared in a similar manner to
that described for 7a. From 4b (1.00 g, 8.84 mmol), 7b (700 mg,
36% yield) was obtained. The analytical sample was prepared as a
19.2 [CH3, N-CH(CH3)2], 36.2 [CH2, C-3(5)], 43.79 [CH, C-1(2)], white solid by crystallization from AcOEt/hexane, m.p. 90–92 °C,
43.84 [CH, N-CH(CH3)2], 109.3 (CH2, C-4=CH2), 145.6 (C, C-4), R = 0.39 (hexane/AcOEt, 1:1). IR: ν = 2987, 2949, 2914, 2847,
˜
f
179.8 (C, CON) ppm. HRMS (APCI): calcd. for [M + H]+
194.1176; found 194.1167. C11H15NO2·0.1H2O (195.05): calcd. C
67.74, H 7.85, N 7.18; found C 67.46, H 7.68, N 6.85.
1769, 1697, 1439, 1426, 1376, 1322, 1275, 1127, 1091, 1023, 998,
907, 887, 730, 662, 654 cm–1. H NMR: δ = 2.45 (d, J = 16.0 Hz,
1
4 H) and 2.78 (d, J = 16.0 Hz, 4 H, 2(4,6,8)-Hexo and 2(4,6,8)-
Hendo), 2.95 (s, 3 H, N-CH3), 4.86 [br. s, 4 H, C-3(7) = CH2] ppm.
13C NMR (75.4 MHz): δ = 25.2 (CH3, N-CH3), 42.7 [CH2, C-
2(4,6,8)], 60.6 [C, C-1(5)], 109.6 [CH2, C-3(7) = CH2], 147.4 [C, C-
3(7)], 181.2 (C, CON) ppm. HRMS (APCI): calcd. for [M + H]+
218.1176; found 218.1168. C13H15NO2 (217.27): calcd. C 71.87, H
6.96, N 6.45; found C 71.67, H 7.03, N 6.20.
N-tert-Butyl-4-methylene-cis-cyclopentane-1,2-dicarboximide (6d):
This compound was prepared in a similar manner to that described
before for 6a. From 4d (3.00 g, 19.3 mmol), 6d (2.00 mg, 50% yield)
was obtained. The analytical sample of 6d was prepared as a white
solid by crystallization from AcOEt/hexane, 1:1, m.p. 104–105 °C,
R 0.75 (hexane/AcOEt, 5:1). IR: ν = 2977, 2962, 2925, 1780, 1693,
˜
f
1433, 1365, 1338, 1306, 1296, 1262, 1206, 1181, 1117, 1061, 1011,
N-Isopropyl-3,7-dimethylene-cis-bicyclo[3.3.0]octane-1,5-dicarbox-
imide (7c): This compound was prepared in a similar manner to
that described for 7a. From 4c (2.00 g, 14.2 mmol), 7c (1.65 g, 47%
1
912, 881, 733, 653 cm–1. H NMR: δ = 1.54 [s, 9 H, N-C(CH3)3],
2.59 [br. d, J = 16.0 Hz, 2 H, 3(5)-Hcis], 2.69 [ddm, J = 16.0, JЈ =
7.6 Hz, 2 H, 3(5)-Htrans], 3.06 [m, 2 H, 1(2)-H], 4.90 (br. s, 2 H, C- yield) was obtained. The analytical sample was prepared as a white
4=CH2) ppm. 13C NMR: δ = 28.3 [CH3, N-C(CH3)3], 36.6 [CH2,
solid by crystallization from hexane, m.p. 49.8–50.4 °C, Rf = 0.61
C-3(5)], 44.0 [CH, C-1(2)], 58.3 [C, N-C(CH3)3], 109.1 (CH2, C- (hexane/AcOEt, 1:1). IR (ATR): ν = 2968, 2914, 1759, 1693, 1435,
˜
4=CH2), 145.9 (C, C-4), 180.9 (C, CON) ppm. HRMS (APCI):
calcd. for [M + H]+ 208.1332; found 208.1326. C12H17NO2
(207.27): calcd. C 69.54, H 8.27, N 6.76; found C 69.47, H 8.37, N
6.65.
1390, 1382, 1363, 1315, 1297, 1269, 1213, 1121, 1093, 1049, 904,
891, 730, 655 cm–1. 1H NMR: δ = 1.32 [d, J = 6.8 Hz, 6 H, N-
CH(CH3)2], 2.42 (d, J = 16.0 Hz, 4 H) and 2.76 (d, J = 16.0 Hz, 4
H, 2(4,6,8)-Hexo and 2(4,6,8)-Hendo), 4.29 [hept, J = 6.8 Hz, 1 H,
3084
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3081–3087

Double Methylenecyclopentane Annulation of Succinimides
N-CH(CH3)2], 4.84 [s, 4 H, C3(7)=CH2] ppm. 13C NMR: δ = 19.3 (60 mL) was added dropwise. The mixture was warmed to room
[CH3, N-CH(CH3)2], 42.8 [CH2, C-2(4,6,8)], 44.0 [CH, N-CH- temperature and stirred for 60 h at this temperature. The mixture
(CH3)2], 59.8 [C, C-1(5)], 109.3 [CH2, C-3(7) = CH2], 147.6 [C, C-
3(7)], 181.3 (C, CON) ppm. HRMS (APCI): calcd. for [M + H]+
246.1489; found 246.1484. C15H19NO2·0.2H2O (248.92): calcd. C
72.38, H 7.86, N 5.63; found C 72.14, H 7.73, N 5.41.
was made acidic with 1  HCl (50 mL), diluted with water (50 mL)
and extracted with Et2O (3ϫ75 mL). The combined organic ex-
tracts were dried (Na2SO4), concentrated in vacuo and the residue
(3.40 g) was submitted to column chromatography [silica gel
(100 g), hexane/AcOEt, 95:5] yielding 9 (1.90 g, 65% yield) as a
white solid. The analytical sample was obtained by crystallization
N-tert-Butyl-3,7-dimethylene-cis-bicyclo[3.3.0]octane-1,5-dicarbox-
imide (7d): This compound was prepared in a similar manner to
that described for 7a. From 4d (5.00 g, 32.2 mmol), 7d (5.73 g, 69%
yield) was obtained. The analytical sample of 7d was prepared as
a white solid by crystallization from AcOEt/pentane, 5:3, m.p. 92–
from Et O, m.p. 107–108 °C. IR (KBr): ν = 3078, 2977, 2944, 2883,
˜
2
1771, 1708, 1591, 1499, 1487, 1433, 1376, 1301, 1284, 1171, 1146,
1
915, 891, 736, 691, 617 cm–1. H NMR (300 MHz): δ = 1.44 [m, 2
H, 8(9)-Hβ], 1.56 (dt, J = 10.8, JЈ = 1.5 Hz, 1 H, 10-Hanti), 1.69 [m,
2 H, 8(9)-Hα], 1.96 (dm, J = 10.8 Hz, 1 H, 10-Hsyn), 2.46 [dt, J =
16.8, JЈ = 2.4 Hz, 2 H, 3(5)-Hβ], 2.63 [m, 2 H 1(7)-H], 2.93 [dm, J
= 16.8 Hz, 2 H, 3(5)-Hα], 4.91 (m, 2 H, C4=CH2), 7.20 (m, 2 H,
Ar-Hortho), 7.38 (m, 1 H, Ar-Hpara), 7.44 (m, 2 H, Ar-Hmeta) ppm.
13C NMR (75.4 MHz): δ = 25.0 [CH2, C-8(9)], 37.7 (CH2, C-10),
41.8 [CH2, C-3(5)], 44.0 [CH, C-1(7)], 63.4 [C, C-2(6)], 109.3 (CH2,
C-4=CH2), 126.7 (CH, Ar-Cortho), 128.7 (CH, Ar-Cpara), 129.1 (CH,
Ar-Cmeta), 131.8 (C, Ar-Cipso), 146.8 (C, C-4), 179.9 (C, CON) ppm.
C19H19NO2 (293.37): calcd. C 77.79, H 6.53, N 4.77; found C
77.69, H 6.54, N 4.69.
93 °C, R 0.41 (hexane/AcOEt, 1:1). IR (KBr): ν = 3081, 3014,
˜
f
2976, 2962, 2915, 2846, 1766, 1698, 1686, 1481, 1465, 1438, 1398,
1369, 1337, 1312, 1295, 1269, 1262, 1239, 1201, 1144, 1023, 896,
887, 732, 646 cm–1. 1H NMR (300 MHz): δ = 1.51 [s, 9 H, N-
C(CH3)3], 2.41 (dm, J = 16.0 Hz, 4 H) and 2.74 (dm, J = 16.0 Hz,
4 H, 2(4,6,8)-Hexo and 2(4,6,8)-Hendo), 4.83 [pseudo quint, J =
1.7 Hz, 4 H, C3(7)=CH2] ppm. 13C NMR (75.4 MHz): δ = 28.4
[CH3, N-C(CH3)3], 43.2 [CH2, C-2(4,6,8)], 58.4 [C, N-C(CH3)3],
59.6 [C, C-1(5)], 108.9 [CH2, C-3(7) = CH2], 147.6 [C, C-3(7)], 182.1
(C, CON) ppm. HRMS (APCI): calcd. for [M + H]+ 264.1230;
found 264.1222. C16H21NO2 (259.35): calcd. C 74.10, H 8.16, N
5.40; found C 73.69, H 8.27, N 5.20.
N-(p-Methoxybenzyl)-3,7-dioxo-cis-bicyclo[3.3.0]octane-1,5-dicarb-
oximide (3a): Through a cold (–78 °C) solution of 7a (1.03 g,
3.19 mmol) in AcOEt (50 mL) a stream of ozone in oxygen (Flow
1.67 L/min, about 1.1 mmol O3/min) was bubbled for 45 min,
whereby the solution took an intense blue color. The solution was
warmed to room temperature, 5% Pd/C (850 mg) was added and
the mixture was subjected to hydrogenation at 1 atm and room tem-
perature overnight. When hydrogen absorption ceased, the mixture
was filtered through Celite®, washed with AcOEt (25 mL) and con-
centrated in vacuo to give a residue (1.15 g) which was subjected
to column chromatography [silica gel (60 g), hexane/AcOEt mix-
tures]. On elution with hexane/AcOEt, 1:1, the known[6] 3a
(846 mg, 81% yield) was isolated as a yellow solid. The analytical
sample was obtained as a white solid by crystallization from Ac-
3,7-Dimethylene-cis-bicyclo[3.3.0]octane-1,5-dicarboximide (7f): A
solution of cerium(IV) ammonium nitrate (CAN, 3.50 g,
6.38 mmol) in water (8 mL) was added dropwise to a solution of
7a (500 mg, 1.55 mmol) in ACN (8 mL), and the mixture was
stirred for 2.5 h at room temperature till no more starting com-
pound (TLC) was observed. The mixture was diluted with water
(30 mL) and extracted with AcOEt (3ϫ50 mL). The combined or-
ganic extracts were dried (MgSO4) and concentrated under reduced
pressure. The residue (557 mg) was taken in abs EtOH (25 mL),
aqueous NH3 (20 %, 13 mL) was added, and the mixture was
heated in a closed reactor at 100 °C for 2 h. The mixture was cooled
to room temperature, the volatile materials were eliminated in
vacuo and the solid residue was extracted with hot AcOEt
(2ϫ30 mL). The combined organic extracts were concentrated in
vacuo and the residue (389 mg) was subjected to column
chromatography [silica gel (39 g), hexane/AcOEt mixtures]. On elu-
tion with hexane/AcOEt, 9:1, 7f (210 mg, 67% yield) was obtained
as a pale yellow solid. The analytical sample was obtained as a
white solid by crystallization from hexane/AcOEt, 3:1, m.p. 149–
OEt, m.p. 177.0–177.5 °C; R = 0.79 (hexane/AcOEt, 1:1). IR: ν =
˜
f
1741, 1697, 1510, 1395, 1340, 1248, 1198, 1173, 1157, 1029, 792
1
cm–1. H NMR: δ = 2.61 (d, J = 20.0 Hz, 4 H) and 2.95 (d, J =
20.0 Hz, 4 H, 2(4,6,8)-Hexo and 2(4,6,8)-Hendo), 3.79 (s, 3 H,
OCH3), 4.62 (s, 2 H, N-CH2), 6.84 [d, J = 8.4 Hz, 2 H, Ar-3(5)-H],
7.27 [d, J = 8.4 Hz, 2 H, Ar-2(6)-H] ppm. 13C NMR: δ = 42.8
(CH2, N-CH2), 47.0 [CH2, C-2(4,6,8)], 53.6 [C, C-1(5)], 55.3 (CH3,
OCH3), 114.3 [CH, Ar-C-3(5)], 127.1 (C, Ar-C-1), 130.0 [CH, Ar-
C-2(6)], 159.6 (C, Ar-C-4), 178.0 (C, CON), 210.5 [C, C-3(7)] ppm.
HRMS (APCI): calcd. for [M + H]+ 327.1101; found 327.1106.
C18H17NO5 (327.34): calcd. C 66.05, H 5.23, N 4.28; found C
65.81, H 5.22, N 4.24.
150 °C. IR (KBr): ν = 3188, 3072, 2991, 2964, 1771, 1704, 1432,
˜
1384, 1350, 1319, 1185, 1138, 1099, 899, 838 cm–1 1H NMR
.
(300 MHz): δ = 2.44 (br. d, J = 16.0 Hz, 4 H) and 2.83 (br. d, J =
16.0 Hz, 4 H, 2(4,6,8)-Hexo and 2(4,6,8)-Hendo), 4.90 [m, 4 H, C-
3(7) = CH2], 8.60 (br. s, 1 H, NH) ppm. 13C NMR (75.4 MHz): δ
= 42.6 [CH2, C-2(4,6,8)], 61.8 [C, C-1(5)], 109.7 [CH2, C-3(7) =
CH2], 147.2 [C, C-3(7)], 181.6 (C, CON) ppm. HRMS (APCI):
calcd. for [M + H]+ 204.1019; found 204.0946. C12H13NO2
(203.24): calcd. C 70.92, H 6.45, N 6.89; found C 71.05, H 6.70, N
6.99.
N-Methyl-3,7-dioxo-cis-bicyclo[3.3.0]octane-1,5-dicarboximide (3b):
This compound was prepared in a similar manner to that described
for 3a. From 7b (680 mg, 3.13 mmol), 3b (530 mg, 77% yield) was
obtained as a white solid after crystallization from AcOEt, m.p.
243–244 °C, R = 0.36 (hexane/AcOEt, 1:3). IR: ν = 2930, 1770,
˜
f
4-Methylene-N-phenyltricyclo[5.2.1.02,6]decane-2β,6β-dicarboximide
(9): A solution of nBuLi in hexanes (9.6 mL, 2.5 , 24.0 mmol)
was added to a cold (0 °C) solution of anhydrous diisopropylamine
(3.4 mL, 24.0 mmol) in anhydrous THF (30 mL), and the mixture
was reacted for 10 min at this temperature. Then, the mixture was
cooled to –95 °C and a solution of N-phenylbicyclo[2.2.1]heptane-
2β,3β-dicarboximide 8 (2.41 g, 10.0 mmol) in anhydrous THF
(65 mL) was added, the solution was stirred for 15 min at –95 °C
and then it was warmed to 0 °C in 1 h. The solution was cooled to
–95 °C and dichloride 5 (1.5 mL, 12.0 mmol) in anhydrous THF
1741, 1698, 1687, 1442, 1403, 1387, 1325, 1278, 1261, 1190, 1083,
1006, 815, 797, 628 cm–1. 1H NMR: δ = 2.67 (d, J = 20.4 Hz, 4 H)
and 3.04 (d, J = 20.4 Hz, 4 H, 2(4,6,8)-Hexo and 2(4,6,8)-Hendo),
3.08 (s, 3 H, N-CH3) ppm. 13C NMR δ = 25.5 (CH3, N-CH3), 47.4
[CH2, C-2(4,6,8)], 53.6 [C, C-1(5)], 180.0 (C, CON), 213.8 [C, C-
3(7)] ppm. HRMS (APCI): calcd. for [M + H]+ 222.0761; found
222.0761. C11H11NO4 (221.21): calcd. C 59.73, H 5.01, N 6.33;
found C 59.42, H 5.11, N 6.17.
N-Isopropyl-3,7-dioxo-cis-bicyclo[3.3.0]octane-1,5-dicarboximide
(3c): This compound was prepared in a similar manner to that de-
Eur. J. Org. Chem. 2009, 3081–3087
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3085

P. Camps, J. A. Fernández, J. Rull, S. Vázquez
FULL PAPER
scribed for 3a. From 7c (400 mg, 1.63 mmol), 3c (300 mg, 74 %
was isolated as a pale yellow oil after column chromatography and
yield) was obtained as a white solid, after crystallization from Ac-
microdistillation at 200 °C/2 Torr in a rotary microdistillation
OEt, m.p. 228–230 °C, R = 0.43 (hexane/AcOEt, 1:1). IR: ν =
equipment. R = 0.28 (AcOEt). IR: ν = 2978, 2935, 1744, 1687,
˜
˜
f
f
2967, 2930, 1739, 1682, 1396, 1383, 1365, 1315, 1205, 1185, 1081,
964, 821, 631 cm–1. 1H NMR: δ = 1.39 [d, J = 7.2 Hz, 6 H, N-
CH(CH3)2], 2.63 (d, J = 20.0 Hz, 4 H) and 2.98 (d, J = 20.0 Hz, 4
H, 2(4,6,8)-Hexo and 2(4,6,8)-Hendo), 4.37 [hept, J = 7.2 Hz, 1 H,
1459, 1396, 1383, 1363, 1310, 1224, 1173, 1164, 1137, 1090, 1044,
1
1021, 959, 951, 855, 837, 769 cm–1. H NMR (300 MHz): δ = 1.39
[d, J = 6.9 Hz, 6 H, N-CH(CH3)2], 2.56 [dm, J = 20.0 Hz, 2 H,
3(5)-Hcis], 2.78 [ddm, J = 20.0, JЈ = 11.4 Hz, 2 H, 3(5)-Htrans], 3.47
N-CH(CH3)2] ppm. 13C NMR: δ = 19.1 [CH3, N-CH(CH3)2], 44.7 [m, 2 H, 1(2)-H], 4.38 [hept, J = 6.9 Hz, 1 H, N-CH(CH3)2] ppm.
[CH, N-CH(CH3)2], 47.1 [CH2, C-2(4,6,8)], 53.3 [C, C-1(5)], 178.3 13C NMR (75.4 MHz): δ = 19.1 [CH3, N-CH(CH3)2], 39.3 [CH2,
(C, CON), 210.8 [C, C-3(7)] ppm. HRMS (APCI): calcd. for [M +
C-3(5)], 40.5 [CH, C-1(2)], 44.2 [CH, N-CH(CH3)2], 178.1 (C,
H]+ 250.1074; found 250.1075. C13H15NO4 (249.27): calcd. C 62.64, CON), 212.9 (C, C-4) ppm. HRMS (APCI): calcd. for [M + H]+
H 6.07, N 5.62; found C 62.77, H 6.09, N 5.53.
196.0968; found 196.0960. C10H13NO3·0.25H2O (199.72): calcd. C
60.14, H 6.81, N 7.01; found C 60.07, H 6.63, N 6.82.
N-tert-Butyl-3,7-dioxo-cis-bicyclo[3.3.0]octane-1,5-dicarboximide
(3d): This compound was prepared in a similar manner to that
described for 3a. From 7d (400 mg, 1.54 mmol), 3d (250 mg, 62%
yield) was obtained as a white solid. The analytical sample was
prepared by crystallization from Et2O/hexane, 1:1, m.p. 215–
N-tert-Butyl-4-oxo-cis-cyclopentane-1,2-dicarboximide (10d): This
compound was prepared in a similar manner to that described be-
fore for 3a. From 6d (525 mg, 2.53 mmol), 10d (325 mg, 61% yield)
was obtained as a pale yellow solid. The analytical sample of 10d
217 °C, R 0.18 (Et O/AcOEt, 1:1). IR: ν = 2972, 2930, 1742, 1696, was prepared as a white solid by crystallization from AcOEt/hex-
˜
f
2
1457, 1400, 1367, 1340, 1307, 1262, 1184, 1137, 1046, 1017, 982,
ane, 1:4, m.p. 110–111 °C, Rf = 0.69 (AcOEt). IR (KBr): ν˜ = 2976,
1
924, 826, 797, 632 cm–1. H NMR: δ = 1.59 [s, 9 H, N-C(CH3)3],
2928, 1741, 1693, 1484, 1456, 1398, 1368, 1339, 1310, 1262, 1232,
1
2.61 (dm, J = 20.0 Hz, 4 H) and 2.98 (dm, J = 20.0 Hz, 4 H,
1178, 1105, 1013, 961, 828, 801, 765 cm–1. H NMR: δ = 1.58 [s, 9
2(4,6,8)-Hexo and 2(4,6,8)-Hendo) ppm. 13C NMR: δ = 27.1 [CH3, H, N-C(CH3)3], 2.56 [br. d, J = 20.0 Hz, 2 H, 3(5)-Hcis], 2.75 [ddm,
N-C(CH3)3], 46.3 [CH2, C-2(4,6,8)], 52.4 [C, C-1(5)], 58.3 [C, N-
C(CH3)3], 178.3 (C, CON), 210.1 [C, C-3(7)] ppm. HRMS (APCI):
c a l c d . f o r [ M + H ] + 2 6 0 . 1 6 4 5 ; f o u n d 2 6 0 . 1 6 4 7 .
J = 20.0, JЈ = 11.2 Hz, 2 H, 3(5)-Htrans], 3.40 [m, 2 H, 1(2)-H] ppm.
13C NMR δ = 28.2 [CH3, N-C(CH3)3], 39.6 [CH2, C-3(5)], 40.8
[CH, C-1(2)], 58.7 [C, N-C(CH3)3], 179.1 (C, CON), 213.3 (C, C-
C
14H17NO4·0.25H2O (267.80): calcd. C 62.79, H 6.59, N 5.23; 4) ppm. HRMS (APCI): calcd. for [M + H]+ 210.1125; found
found C 62.93, H 6.53, N 5.01.
210.1120. C11H15NO3 (209.25): C, 63.14; H, 7.23; N, 6.69. Found:
C, 63.17; H, 7.20; N, 6.58.
N-(p-Methoxybenzyl)-4-oxo-cis-cyclopentane-1,2-dicarboximide
(10a): This compound was prepared in a similar manner to that
described before for 3a. From 6a (299 mg, 1.10 mmol), 10a
(195 mg, 65% yield) was obtained as a pale yellow solid. The ana-
lytical sample was obtained as a white solid by crystallization from
AcOEt/hexane, 5:1, m.p. 110–111 °C, Rf = 0.55 (AcOEt). IR (KBr):
Supporting Information (see also the footnote on the first page of
this article): 1H NMR spectrum of CDCl3 containing TMS and
1H NMR spectrum of 6a in the same solvent and under the same
conditions.
ν = 3009, 2930, 2904, 2832, 1743, 1710, 1614, 1587, 1511, 1463,
˜
Acknowledgments
1432, 1394, 1359, 1341, 1299, 1249, 1199, 1174, 1158, 1117, 1108,
1
1030, 1011, 982, 915, 825, 793, 635 cm–1. H NMR: δ = 2.47 [dm,
Financial support from Ministerio de Educación y Ciencia (MEC)
(CTQ2008-03768) and Comissionat per a Universitats i Recerca
(2005-SGR-00180) is gratefully acknowledged. J. R. thanks the
MEC for support (FPU Program).
J = 20.0 Hz, 2 H, 3(5)-Hcis], 2.69 [ddm, J = 20.0, JЈ = 8.4 Hz, 2 H,
3(5)-Htrans], 3.43–3.46 [m, 2 H, 1(2)-H], 3.71 (s, 3 H, OCH3), 4.53
(s, 2 H, N-CH2), 6.76 [dm, J = 8.6 Hz, 2 H, Ar-3(5)-H], 7.24 [dm,
J = 8.6 Hz, 2 H, Ar-2(6)-H] ppm. 13C NMR: δ = 39.1 [CH2, C-
3(5)], 40.7 [CH, C-1(2)], 42.3 (CH2, N-CH2), 55.2 (CH3, OCH3),
114.1 [CH, Ar-C-3(5)], 127.6 (C, Ar-C-1), 130.3 [CH, Ar-C-2(6)],
159.4 (C, Ar-C-4), 177.8 (C, CON), 212.8 (C, C-4) ppm.
C15H15NO4 (273.29): calcd. C 65.92, H 5.53, N 5.13; found C
65.83, H 5.50, N 5.16.
[1] S. H. Bertz, J. M. Cook, A. Gawish, U. Weiss, in: Org. Synth.,
Coll. Vol. VII, John Wiley & Sons, New York, 1990, pp. 50–
56.
[2] a) A. K. Gupta, X. Fu, J. P. Snyder, J. M. Cook, Tetrahedron
1991, 47, 3665–3710; b) X. Fu, G. Kubiak, W. Zhang, W. Han,
A. K. Gupta, J. M. Cook, Tetrahedron 1993, 49, 1511–1524.
[3] P. Camps, M. Figueredo, Can. J. Chem. 1984, 62, 1184–1193.
[4] A. P. Krapcho, A. J. Lovey, Tetrahedron Lett. 1973, 14, 957–
960.
N-Methyl-4-oxo-cis-cyclopentane-1,2-dicarboximide (10b): This
compound was prepared in a similar manner to that described be-
fore for 3a. From 6b (535 mg, 3.24 mmol), 10b (375 mg, 69% yield)
was obtained as a pale yellow solid. The analytical sample was
prepared as a white solid by crystallization from AcOEt/pentane,
[5] G. Deslongchamps, D. Mink, P. D. Boyle, N. Singh, Can. J.
Chem. 1994, 72, 1162–1164.
2:1, m.p. 115–117 °C, R = 0.52 (AcOEt). IR: ν = 2956, 2925, 1748,
˜
f
[6] D. Mink, G. Deslongchamps, Tetrahedron Lett. 1996, 37, 7035–
1687, 1682, 1434, 1397, 1382, 1317, 1282, 1264, 1168, 1085, 1062,
1010, 960, 836, 777, 619, 602 cm–1. 1H NMR: δ = 2.59 [dm, J =
20.2 Hz, 2 H, 3(5)-Hcis], 2.80 [ddm, J = 20.2, JЈ = 11.4 Hz, 2 H,
3(5)-Htrans], 3.03 (s, 3 H, N-CH3), 3.55–3.59 [m, 2 H, 1(2)-H] ppm.
13C NMR: δ = 25.3 (CH3, N-CH3), 39.2 [CH2, C-3(5)], 40.6 [CH,
C-1(2)], 178.2 (C, CON), 212.7 (C, C-4) ppm. HRMS (APCI):
calcd. for [M + H]+ 168.0655; found 168.0655. C8H9NO3 (167.16):
calcd. C 57.48, H 5.43, N 8.38; found C 57.48, H 5.50, N 8.14.
7038.
[7] D. Mink, G. Deslongchamps, Synlett 1996, 875–876.
[8] a) For a review, see: S. Vázquez, P. Camps, Tetrahedron 2005,
61, 5147–5208; b) C. Ayats, P. Camps, M. Font-Bardia, M. R.
Muñoz, X. Solans, S. Vázquez, Tetrahedron 2006, 62, 7436–
7444; c) P. Camps, M. R. Muñoz, S. Vázquez, Tetrahedron
2006, 62, 7645–7652; d) C. Ayats, P. Camps, J. A. Fernández,
S. Vázquez, Chem. Eur. J. 2007, 13, 1522–1532; e) C. Ayats, P.
Camps, M. Font-Bardia, X. Solans, S. Vázquez, Tetrahedron
2007, 63, 8027–8036.
N-Isopropyl-4-oxo-cis-cyclopentane-1,2-dicarboximide (10c): This
compound was prepared in a similar manner to that described be-
fore for 3a. From 6c (250 mg, 1.29 mmol), 10c (160 mg, 63% yield)
[9] K. Furuta, N. Ikeda, H. Yamamoto, Tetrahedron Lett. 1984,
25, 675–678.
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Received: April 2, 2009
Published Online: May 4, 2009
Eur. J. Org. Chem. 2009, 3081–3087
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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