Palladium-catalyzed nucleophilic allylic substitution of Morita–Baylis–Hillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds

Article abstract of DOI:10.1016/j.crci.2016.11.011

An efficient nucleophilic allylic substitution of a variety of Morita–Baylis–Hillman adducts with enamines catalyzed by Pd(OAc)₂ in the presence of ZnBr₂ as a promoter is described in the present study. The reaction gives S_N2-type 1,5-dicarbonyl compounds that may subsequently undergo an intramolecular conjugate addition onto the enone moiety affording the corresponding 1,4-adducts. All the synthesized compounds have been isolated in moderate to good yields and fully characterized.

Full text of DOI:10.1016/j.crci.2016.11.011

C. R. Chimie xxx (2017) 1e8
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Full paper/Memoire
Palladium-catalyzed nucleophilic allylic substitution of
MoritaeBayliseHillman adducts with enamines: Synthesis of
1,5-dicarbonyl compounds
,
Ghalia Bouhalleb a *, Jalloul Bouajila b, Farhat Rezgui a
a
ꢀ
ꢀ
Universite de Tunis EL Manar, Faculte des sciences, Laboratoire de chimie organique structurale, Campus universitaire, 2092 Tunis,
Tunisia
b
ꢀ
ꢀ
ꢀ
Universite de Toulouse-3, Universite Paul-Sabatier, Faculte des sciences pharmaceutiques, Laboratoire des IMRCP, UMR CNRS 5623, 35,
chemin des Maraichers, 31062 Toulouse cedex 09, France
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient nucleophilic allylic substitution of a variety of MoritaeBayliseHillman adducts
with enamines catalyzed by Pd(OAc)2 in the presence of ZnBr2 as a promoter is described
in the present study. The reaction gives SN2-type 1,5-dicarbonyl compounds that may
subsequently undergo an intramolecular conjugate addition onto the enone moiety
affording the corresponding 1,4-adducts. All the synthesized compounds have been iso-
lated in moderate to good yields and fully characterized.
Received 2 August 2016
Accepted 8 November 2016
Available online xxxx
Keywords:
Allylic substitution
Palladium
© 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Enamine
1,5-Dicarbonyl compounds
MoritaeBayliseHillman
Conjugate addition
1. Introduction
also be prepared by a cross-coupling reaction of aryl methyl
ketones with either aromatic aldehydes [14] or acetohy-
1,5-Diketones are useful precursors to various substituted
anilines [1] and heterocyclic compounds including pyridine
derivatives [2e5], dihydropyridines [5,6], and pyrazolo[1,5-
a] pyrimidines [7]. Moreover, 1,5-diketones with abstract-
drazones [15], as well as by dimerization of a,b-enones in
the presence of a quaternary ammonium salt as a phase-
transfer catalyst [16]. In addition, the cross-metathesis of
olefins was found to be a rapid access to such dicarbonyl
derivatives [1,3]. In another synthetic protocol, Zard et al.
reported a free radical approach for the synthesis of 1,5-
diketones from alkenylacylphosphonates and keto-
xanthates [2].
On the other hand, during the last decades, the nucle-
ophilic behavior of enamines has been explored in
palladium-catalyzed nucleophilic substitution of allylic
compounds. Indeed, the reaction of allylic acetates with
enamines worked well in the presence of Pd(II)/
metallocene-based ligands, affording the corresponding
allylation products [17]. Such a nucleophilic allylic substi-
able g-hydrogen atoms were shown to be highly photoactive
cage molecules for the release of fragrances [8]. These
dicarbonyl compounds were also used for the synthesis of
bicyclic ethers via their annulation reaction with bis (tri-
methylsilyl) enol ethers [9] and pinacol coupling through
their reductive dimerization [10].
Michael addition of ketone enolates or their surrogates
onto
a,b-enones is one of the common methods for the
synthesis of 1,5-diketones [11e13]. These compounds can
tution was used to prepare
g,d-unsaturated ketones
* Corresponding author.
through the reaction of allylic benzotriazoles with
E-mail address: ghaliabhbh@hotmail.com (G. Bouhalleb).
http://dx.doi.org/10.1016/j.crci.2016.11.011
1631-0748/© 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: G. Bouhalleb, et al., Palladium-catalyzed nucleophilic allylic substitution of MoritaeBaylis
eHillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds, Comptes Rendus Chimie (2017), http://dx.doi.org/
10.1016/j.crci.2016.11.011

2
G. Bouhalleb et al. / C. R. Chimie xxx (2017) 1e8
Table 2
enamines under the action of Pd(0)/PPh3 in the presence of
ZnBr2 [18].
Furthermore, it was shown that the one-pot reaction of
functionalized acyclic MoritaeBayliseHillman (MBH) ace-
Optimization of the reaction conditions for the synthesis of 4a from the
reaction of 2a with 3a.a
Entry
1
T (ꢀC)
Solvent
None
Time (h)
48
Yield 4ab (%)
tates with various enamino b-ketoesters in the presence of
rt
e
e
e
NaH afforded a series of trisubstituted 2-pyridones [19,20].
Nevertheless, it is worth noting that up to now, no Pd-
catalyzed nucleophilic reaction of enamines with acyclic
or cyclic MBH adducts has been reported. In our previous
studies on the MBH chemistry, we have reported a Pd-free
Tsuji-Trostetype reaction of MBH alcohols or acetates with
2
3
rt
Toluene
Toluene
72
72
110
4
5
rt
40
CH2Cl2
CH2Cl2
72
72
30
30
a
The reaction was performed using the acetate 3a (1 equiv) and
enamine 2a (5 equiv) in CH2Cl2.
b
-dicarbonyl compounds, affording g,d-unsaturated 1,5-
b
diketones [21,22]. In continuation of our interest in the
allylic substitution of MBH derivatives with various nucle-
ophiles [23,24], we report herein the first examples of a Pd-
catalyzed allylic nucleophilic substitution of both cyclic and
acyclic MBH adducts, as functionalized allylic substrates,
with ketoenamines, providing a new series of saturated and
Isolated yield.
solvent in the same reaction at rt or at reflux for 72 h (Table
2, entries 2 and 3). Interestingly, in dichloromethane at rt,
the 1,5-dicarbonyl compound 4a was obtained, within 72 h,
but in only 30% yield (Scheme 1, Table 2, entry 4). To
improve the reaction yield and reduce the reaction time,
our subsequent experiment was conducted in refluxing
dichloromethane. Under these conditions, the 1,5-keto
ester 4a was produced in the same yield within 72 h
(Scheme 1, Table 2, entry 5).
Taking into account the low yields of the compound 4a
and long reaction times recorded in the previous pre-
liminary attempts, we therefore decided to explore a new
synthetic approach for 4a under catalytic conditions. In this
context, we reacted, under the established conditions, the
enamine 2a (5 equiv) with the MBH acetate 3a (1 equiv) in
the presence of Pd(OAc)2 (0.04 equiv)/PPh3 (0.16 equiv) and
ZnBr2 (2.66 equiv) as a Lewis acid in refluxing dichloro-
methane. The conversion of the substrate 3a was complete
within 6 h, yielding exclusively, after hydrolysis of the re-
action mixture, the unsaturated 1,5-keto ester 4a in 70%
yield (Scheme 1, Table 3, entry 1). Under the same condi-
tions, the allylic nucleophilic substitution of the substrate
3a was also successfully performed with enamines 2b and
2c, affording similarly the corresponding SN2 and/or SN20-
type products 4b and 4c in 80 and 68% yield, respectively
(Scheme 1, Table 3, entries 2 and 3).
g,d-unsaturated 1,5-dicarbonyl compounds.
2. Results and discussion
For this purpose, we have initially prepared the en-
amines 2aec in 60e70% yields (Table 1) from the reaction
of cyclic ketones 1aec with morpholine using conventional
reaction conditions [25].
Next, upon treatment of the enamine 2a with the MBH
acetate 3a [21], at room temperature (rt), under solvent-
free conditions, and without any additive, the starting
materials were recovered within 48 h (Table 2, entry 1). The
same result was also obtained when toluene was used as a
Table 1
Synthesis of enamines 2aec from the reaction of ketones 1aec with
morpholine.a
Next, to establish the substrate scope, we selected the
cyclic MBH derivatives 3bed bearing three different leav-
ing groups (LG ¼ OAc, OMe, OEt), and we explored their
behavior toward the nucleophilic enamines 2. First, upon
treatment of allylic acetate 3b or allylic ethers 3c and 3d
with enamine 2a, under the previous conditions (MBH
adduct (1 equiv), ketoenamine (5 equiv), Pd(OAc)2 (0.04
equiv), PPh3 (0.16 equiv), and ZnBr2 (2.66 equiv) in CH2Cl2),
the reaction worked well. Nevertheless, the expected SN2-
type product 4d was not isolated but we exclusively ob-
tained the same compound 5d, in 75e80% yields (entries 4
e6). This derivative was presumably formed through an in
situ intramolecular Michael addition on the enone moiety
of its precursor 4d (Scheme 2, Table 3, entries 4e6). The
best yield (80%) and the shorter reaction time (24 h) were
achieved with the allylic acetate 3b that was found to be
the most reactive.
Entry Enamine 2
Reaction
time (days)
Yield 2 (%)b
60
1
2
2a
2b
2c
3
4
1
70
65
3
It is noteworthy that the monitoring of the reaction
progress by thin layer chromatography, from the beginning
of our experiment, showed only the formation of the
compound 5d with no trace of its precursor 4d (Table 3,
a
The reaction was performed using ketones 1aec (1 equiv), morpho-
line (1.5 equiv), p-toluenesulfonic acid (2 equiv) in toluene.
b
Isolated yield.
Please cite this article in press as: G. Bouhalleb, et al., Palladium-catalyzed nucleophilic allylic substitution of MoritaeBaylis
eHillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds, Comptes Rendus Chimie (2017), http://dx.doi.org/
10.1016/j.crci.2016.11.011

G. Bouhalleb et al. / C. R. Chimie xxx (2017) 1e8
3
Scheme 1. Synthesis of ketoesters 4aec from acyclic MBH 3a and enamines 2aec.
Table 3
Synthesis of 1,5-dicarbonyl compounds 4 and 5 through the reaction of substrates 3aee with enamines 2aec.a
Entry
1
3
2
Time (h)
6
Product 4 and/or 5b
Ratio 4:5
3a
2a
4a/5a ¼ 100:0
4a, 70%
2
3a
2b
4
4b/5b ¼ 100:0
4b, 80%
3
3a
2c
4
4c/5c ¼ 100:0
4c, 68%
5d, 80%
5d, 75%
5d, 75%
4
5
6
3b
3c
3d
2a
2a
2a
24
48
24
4d/5d ¼ 0:100
4d/5d ¼ 0:100
4d/5d ¼ 0:100
(continued on next page)
Please cite this article in press as: G. Bouhalleb, et al., Palladium-catalyzed nucleophilic allylic substitution of MoritaeBaylis
eHillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds, Comptes Rendus Chimie (2017), http://dx.doi.org/
10.1016/j.crci.2016.11.011

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G. Bouhalleb et al. / C. R. Chimie xxx (2017) 1e8
Product 4 and/or 5b
Table 3 (continued)
Entry
7
3
2
Time (h)
37
Ratio 4:5
3e
2a
4e/5e ¼ 0:100
5e, 60%
5f, 64%
8
3e
3e
3b
2b
2c
2b
32
40
7
4f/5f ¼ 0:100
4g/5g ¼ 0:100
4h/5h ¼ 31:69
9
5g, 57%
10
4h, 27%
5h, 60%
11
12
13
3c
3d
3b
2b
2b
2c
28
12
24
4h/5h ¼ 29:71
4h/5h ¼ 38:62
4i/5i ¼ 40:60
4h, 26%
5h, 63%
4h, 35%
5h, 57%
5i, 54%
4i, 37%
4i, 28%
4i, 27%
14
15
3c
2c
2c
28
24
4i/5i ¼ 30:70
5i, 65%
3d
4i/5i ¼ 30:70
5i, 64%
a
The reaction was performed using MBH adducts 3 (1 equiv), ketoenamine 2 (5 equiv), Pd(OAc)2 (0.04 equiv), PPh3 (0.16 equiv), and ZnBr2 (2.66 equiv) in
refluxing CH2Cl2.
b
Isolated yield.
Please cite this article in press as: G. Bouhalleb, et al., Palladium-catalyzed nucleophilic allylic substitution of MoritaeBaylis
eHillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds, Comptes Rendus Chimie (2017), http://dx.doi.org/
10.1016/j.crci.2016.11.011

G. Bouhalleb et al. / C. R. Chimie xxx (2017) 1e8
5
Scheme 2. Allylic substitution of MBH adducts 3bee with enamines 2aec.
entries 4e6), suggesting that the conversion of this inter-
mediate into 5d was kinetically faster than that of sub-
strates 3bed into the intermediate 4d.
and enamines 2aec. We believe that this allylic substitu-
tion is under thermodynamic control, affording exclusively
the
a-products [27,28].
Correlatively, an interesting example on MichaeleStork
addition of enamine 2a to allenyl ketones and esters was
previously reported by Lepore et al. [26]. They showed that
a Michael addition onto the title substrates provided an
iminium ion intermediate, which could further undergo
hydrolysis to afford the 1,4-adducts 6. Alternatively, the
corresponding enamines can undergo an intramolecular
cyclization to yield the bicyclic compounds 7 (Scheme 3).
Furthermore, we explored the scope of this allylic
nucleophilic substitution reaction involving the five-
membered MBH acetate 3e with enamines 2aec. Under
the previous conditions (Pd(OAc)2/ZnBr2), adducts 5eeg
were exclusively obtained in 57e64% yields (Scheme 2,
Table 3, entries 7e9).
To explain the formation of the 1,5-dicarbonyl com-
pounds 4 and 5, we propose an initial departure of the
leaving group on adducts 3, which would be assisted by the
Lewis acid ZnBr2 [29e31]. Indeed, the resulting interme-
diate 7 undergoes an oxidative addition to Pd(0) to form a
cationic
Peallyl Pd(II) complex 8 (i) that is further attacked
by the enamines 2, yielding an iminium intermediate 9 (ii).
After that, there is either the hydrolysis of the intermediate
9 to give the d-diketones 4 (iii), or alternatively the carb-
anion derived from the tautomeric form 90 of 9 undergoes
an intramolecular Michael addition on the enone moiety to
finally provide, after hydrolysis, the
d-diketones 5 (iv)
(Scheme 4).
Finally, the nucleophilic allylic substitution of substrates
3bed with six-membered enamines 2b and 2c has been
investigated (Scheme 2, Table 3, entries 10e15). We
observed that these substrates did not have the same
behavior toward the five-membered enamine 2a (vide
supra) and the six-membered enamines 2b and 2c (Scheme
2, Table 3, entries 10e15). Indeed, the reaction with
enamine 2a gave exclusively the adduct 5d (Scheme 2,
Table 3, entries 4e6), whereas the use of 2b and 2c gave
predominantly adducts 5h and 5i along with their corre-
sponding precursors 4h and 4i (Scheme 2, Table 3, entries
10e15) in high overall yields.
3. Conclusion
We have reported the first examples of an efficient
ZnBr2-promoted Pd-catalyzed allylic substitution reactions
of cyclic and acyclic MBH adducts with cyclic ketoenamines
in refluxing dichloromethane. These reactions afford a se-
ries of SN2-type unsaturated 1,5-dicarbonyl compounds,
which can further undergo an intramolecular Michael
addition on the enone moiety, yielding the corresponding
1,4-adducts. All the newly synthesized compounds were
isolated in moderate to good yields and fully characterized.
Compounds 5h and 5i and the corresponding precursors
4h and 4i were easily separated by column chromatography
(petroleum ether/ether ¼ 60:40) and fully characterized.
Polycyclic compounds 5dei were unequivocally elucidated
by 1H NMR and high-resolution mass spectra (HRMS).
It is notable that, under the catalysis of both Pd(0) and
ZnBr2, we did not observe any SN20 product along with the
SN2-type products 4dei using cyclic MBH adducts 3bee
4. Experimental section
4.1. General comments
1H NMR and 13C NMR spectra were recorded either on a
300 MHz Bruker for 1H or 75 MHz in CDCl3, using tetra-
methylsilane as an internal standard (chemical shifts in
Scheme 3. MichaeleStork addition of an enamine to allenyl ketones and esters.
Please cite this article in press as: G. Bouhalleb, et al., Palladium-catalyzed nucleophilic allylic substitution of MoritaeBaylis
eHillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds, Comptes Rendus Chimie (2017), http://dx.doi.org/
10.1016/j.crci.2016.11.011

6
G. Bouhalleb et al. / C. R. Chimie xxx (2017) 1e8
Scheme 4. Proposed reaction mechanism for 1,5-dicarbonyl compounds 4 and 5.
d
values and J in Hz). HRMS were recorded as ESI-HRMS on
1.99e1.86 (m, 1H), 1.54e1.50 (m, 1H), 1.32 (t, J ¼ 7.5 Hz, 3H).
13C NMR (CDCl3, 75 MHz):
219.5, 166.9, 138.9, 126.1, 60.7,
an Auto Spec Ultima/micromass mass spectrometer. Mass
spectra (EI) were obtained at 70 eV on a HewlettePackard
HP-5890. Analytical thin layer chromatography was per-
formed using Fluka Kieselgel 60 F254 precoated silica gel
plates. Visualization was achieved by UV light (254 nm).
Flash chromatography was performed using silica gel 60
and a gradient solvent system (petroleum ether/ether).
Compounds 3 and enamines 2 were prepared according to
the literature methods [21,25].
d
48.1, 37.8, 32.1, 29.7, 20.6,14.2. MS (m/z), 55 (53), 68 (50), 96
(100), 151 (21), 168 (51), 196 (Mþ, 39); HRMS calcd for
C
11H16Oþ3 [MꢂH]þ 195.1021, found 195.1020.
4.4. Ethyl 2-((2-oxocyclohexyl)methyl)acrylate (4b)
Yield 80%; colorless oil. 1H NMR (CDCl3, 300 MHz):
d 6.19
(d, J ¼ 3 Hz, 1H), 5.57 (d, J ¼ 3 Hz, 1H), 4.20 (q, J ¼ 7.5 Hz,
2H), 2.36e2.32 (m, 4H), 2.12e2.08 (m, 2H), 1.89e1.85 (m,
4H), 1.74e1.68 (m, 1H), 1.30 (t, J ¼ 7.5 Hz, 3H). 13C NMR
4.2. General procedure for the synthesis of 1,5-dicarbonyl
compounds 4aei and 5aei
(CDCl3, 75 MHz): d 212.1, 166.9, 138.4, 126.6, 60.5, 49.1, 41.8,
33.5, 31.8, 27.9, 26.9,14.0. MS (m/z), 55 (39), 67 (34), 97 (41),
136 (100), 165 (32), 210 (Mþ, 8); HRMS calcd for C12H18Oþ3
[MþH]þ 211.1327, found 211.1325.
Under nitrogen, a mixture of MBH acetate 3 (1.5 mmol),
Pd(OAc)2 (13 mg, 0.06 mmol), PPh3 (63 mg, 0.24 mmol),
and ZnBr2 (0.90 g, 4 mmol) was refluxed in CH2Cl2 (10 mL)
for 15 min. Then the solution of enamine 2 (7.5 mmol) in
CH2Cl2 (5 mL) was added, and the reaction mixture was
refluxed for 4e48 h. After evaporation of CH2Cl2, water
(10 mL) was added with NaOH (1 M, 30 mL), and the
mixture was extracted with CH2Cl2 (3 ꢁ 30 mL). The
organic phase was washed with a saturated solution of
ammonium chloride (10 mL) and dried over magnesium
sulfate. After removal of the solvent, the residue was sub-
jected to column chromatography (petroleum ether/
ether ¼ 60:40) to produce pure unsaturated 1,5-dicarbonyl
compounds 4aei and 5aei.
4.5. Ethyl 2-((5-methyl-2-oxocyclohexyl)methyl)acrylate (4c)
Yield 68%; colorless oil. 1H NMR (CDCl3, 300 MHz):
d
6.20 (s, 1H), 5.56 (d, J ¼ 3 Hz, 1H), 4.20 (q, J ¼ 8 Hz, 2H),
2.87e2.80 (m, 1H), 2.71e2.67 (m, 1H), 2.42e2.27 (m, 3H),
2.14e2.04 (m, 2H), 1.70 (t, J ¼ 6 Hz, 2H), 1.65e1.55 (m, 1H),
1.30 (t, J ¼ 8 Hz, 3H), 1.08 (d, J ¼ 6 Hz, 3H). 13C NMR (CDCl3,
75 MHz):
d 213.3, 166.8, 138.3, 126.4, 60.7, 46.5, 39.3, 37.9,
34.2, 32.9, 26.6, 19.5, 14.1. MS (m/z), 55 (89), 67 (42), 136
(28), 151 (100), 179 (62), 224 (Mþ, 10); HRMS calcd for
C
13H20Oþ3 [MþH]þ 225.1484, found 225.1486.
4.3. Ethyl 2-((2-oxocyclopentyl)methyl)acrylate (4a)
4.6. Decahydro-1H-5,8-methanobenzo[7]annulene-1,10-
dione (5d)
Yield 70%; colorless oil. 1H NMR (CDCl3, 300 MHz):
d 6.19
(d, J ¼ 3 Hz,1H), 5.59 (d, J ¼ 3 Hz,1H), 4.21 (q, J ¼ 7.5 Hz, 2H),
Yield 80% from (6-oxocyclohex-1-en-1-yl)methyl ace-
tate 3b, 75% from 2-(methoxymethyl)cyclohex-2-enone 3c,
2.91e2.85 (m, 1H), 2.38e2.34 (m, 2H), 2.33e2.21 (m, 4H),
Please cite this article in press as: G. Bouhalleb, et al., Palladium-catalyzed nucleophilic allylic substitution of MoritaeBaylis
eHillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds, Comptes Rendus Chimie (2017), http://dx.doi.org/
10.1016/j.crci.2016.11.011

G. Bouhalleb et al. / C. R. Chimie xxx (2017) 1e8
7
and 75% from 2-(ethoxymethyl)cyclohex-2-enone 3d;
white solid; mp 128e130 ꢀC. 1H NMR (CDCl3, 300 MHz):
d
3.44e3.35 (m, 1H), 2.58e2.53 (m, 2H), 2.46e2.22 (m, 4H),
2.15e1.98 (m, 7H), 1.74e1.54 (m, 4H). 13C NMR (CDCl3,
75 MHz): 219.2, 213.0, 51.8, 47.8, 47.5, 46.8, 37.9, 34.5, 34.1,
d
2.66e2.57 (m, 1H), 2.40e2.32 (m, 3H), 2.19e1.92 (m, 7H),
180e1.60 (m, 4H), 1.25e1.16 (m, 1H). 13C NMR (CDCl3,
75 MHz): 219.4, 210.6, 51.4, 49.2, 47.1, 43.4, 41.3, 34.7, 29.7,
d
33.6, 27.9, 24.5, 20.0. MS (m/z): 55 (77), 95 (52), 110 (34),
150 (34), 178 (21), 206 (Mþ, 100); HRMS calcd for C13H18O2þ
[MþH]þ 207.1385, found 207.1383.
d
26.0, 23.1, 18.5. MS (m/z), 96 (48), 110 (40), 164 (31), 192
(Mþ, 100); HRMS calcd for C12H16Oþ2 [MþH]þ 193.1229,
found 193.1230.
4.12. 2-((5-Methyl-2-oxocyclohexyl)methyl)cyclohex-2-
enone (4i)
4.7. Octahydro-4,7-methanoazulene-1,9(2H)-dione (5e)
Yield 60%; white solid; mp 122e126 ꢀC. 1H NMR (CDCl3,
Yield 37% from (6-oxocyclohex-1-en-1-yl)methyl ace-
tate 3b, 28% from 2-(methoxymethyl)cyclohex-2-enone 3c,
and 27% from 2-(ethoxymethyl)cyclohex-2-enone 3d;
300 MHz):
d 2.37e2.00 (m, 4H), 1.81e1.43 (m, 4H), 1.39
e1.23 (m, 4H), 0.91e0.83 (m, 2H). 13C NMR (CDCl3,
colorless oil. 1H NMR (CDCl3, 300 MHz):
d
6.80 (t, J ¼ 4.5 Hz,
75 MHz):
d 220.8, 220.7, 47.1, 46.8, 38.0, 30.2, 30.1, 29.9,
1H), 2.77e2.37 (m, 2H), 2.34e2.31 (m, 6H), 2.02e1.92 (m,
7H), 1.90e1.28 (m, 1H), 0.96 (d, J ¼ 6 Hz, 3H). 13C NMR
29.7, 29.6, 20.7. MS (m/z), 150 (100), 178 (Mþ, 60); HRMS
calcd for C11H14Oþ2 [MþH]þ 179.1072, found 179.1071.
(CDCl3, 75 MHz): d 220.9, 199.7, 147.8, 137.5, 47.9, 42.1, 41.6,
38.5, 36.1, 31.9, 30.2, 26.2, 23.0, 21.2. MS (m/z), 55 (79), 110
(47), 203 (88), 220 (Mþ, 100); HRMS calcd for C14H20O2þ
[MþH]þ 221.1542, found 221.1544.
4.8. Decahydro-1H-4,8-methanocyclopenta[8]annulene-1,10-
dione (5f)
Yield 64%; white solid; mp 119e121 ꢀC. 1H NMR (CDCl3,
4.13. 7-Methyldecahydro-5,9-methanobenzo[8]annulene-
1,11(2H)-dione (5i)
300 MHz):
e2.31 (m, 3H), 2.19e2.05 (m, 9H), 1.77e1.63 (m, 2H). 13C
NMR (CDCl3, 75 MHz): 219.3, 219.2, 50.3, 47.4, 45.7, 45.2,
d 3.04e2.95 (m, 1H), 2.82e2.74 (m, 1H), 2.43
d
Yield 54% from (6-oxocyclohex-1-en-1-yl)methyl ace-
tate 3b, 65% from 2-(methoxymethyl)cyclohex-2-enone 3c,
and 64% from 2-(ethoxymethyl)cyclohex-2-enone 3d;
white solid; mp 106e108 ꢀC. 1H NMR (CDCl3, 300 MHz):
36.9, 35.1, 34.3, 32.2, 27.0, 20.1. MS (m/z), 96 (48), 110 (40),
164 (31), 192 (Mþ, 100); HRMS calcd for C12H16Oþ2 [MþH]þ
193.1229, found 193.1241.
d
3.46e3.38 (m, 1H), 2.56e2.23 (m, 7H), 2.18e2.12 (m, 4H),
1.69e1.40 (m, 4H), 1.35e1.17 (m, 1H), 0.89 (d, J ¼ 6 Hz, 3H).
13C NMR (CDCl3, 75 MHz):
219.4, 212.9, 51.9, 48.4, 47.8,
4.9. 6-Methyldecahydro-1H-4,8-methanocyclopenta[8]
annulene-1,10-dione (5g)
d
45.8, 43.2, 42.8, 37.4, 33.6, 27.6, 26.4, 24.4, 22.4. MS (m/z),
Yield 57%; white solid; mp 120e123 ꢀC. 1H NMR (CDCl3,
55 (100), 110 (77), 163 (42), 220 (Mþ, 59); HRMS calcd for
300 MHz):
d 2.47e2.42 (m, 1H), 2.26e1.96 (m, 4H), 1.94
C
14H20Oþ2 [MþH]þ 221.1542, found 221.1546.
e1.83 (m, 4H), 1.76e1.27 (m, 6H), 0.96 (d, J ¼ 9 Hz, 3H). 13
C
NMR (CDCl3, 75 MHz):
d 219.2, 213.0, 51.8, 47.8, 47.5, 46.8,
Appendix A. Supplementary data
37.9, 34.5, 34.1, 33.6, 27.9, 24.5, 20.0. MS (m/z) 96 (90), 110
(88), 164 (89), 206 (Mþ, 98); HRMS calcd for C13H18O2þ
[MþH]þ 207.1385, found 207.1389.
Supplementary data related to this article can be found
at http://dx.doi.org/10.1016/j.crci.2016.11.011.
4.10. 2-((2-Oxocyclohexyl)methyl)cyclohex-2-enone (4h)
References
Yield 27% from (6-oxocyclohex-1-en-1-yl)methyl ace-
tate 3b, 26% from 2-(methoxymethyl)cyclohex-2-enone 3c,
and 35% from 2-(ethoxymethyl)cyclohex-2-enone 3d;
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eHillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds, Comptes Rendus Chimie (2017), http://dx.doi.org/
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Please cite this article in press as: G. Bouhalleb, et al., Palladium-catalyzed nucleophilic allylic substitution of MoritaeBaylis
eHillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds, Comptes Rendus Chimie (2017), http://dx.doi.org/
10.1016/j.crci.2016.11.011