Amberlyst-15 catalyzed Michael addition of β-dicarbonyl compounds to the enones and unexpected ring closure products

Article abstract of DOI:10.1016/j.tet.2017.05.092

Conjugate addition reactions of 2,4-pentandione, dibenzoylmethane and ethylacetoacetate to enones have been investigated using Amberlyst-15 or Amberlyst-15-DMAP acetate system as catalysts. When 2,4-pentandione reactions were carried out in the presence o

Full text of DOI:10.1016/j.tet.2017.05.092

Tetrahedron 73 (2017) 4335e4340
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Tetrahedron
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Amberlyst-15 catalyzed Michael addition of
b-dicarbonyl compounds
to the enones and unexpected ring closure products
Hande Gunduz, Hamdiye Ece, Armagan Atsay, Volkan Kumbaraci*, Naciye Talinli**
Istanbul Technical University, Department of Chemistry, Maslak, Istanbul, 34469, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
Conjugate addition reactions of 2,4-pentandione, dibenzoylmethane and ethylacetoacetate to enones
have been investigated using Amberlyst-15 or Amberlyst-15-DMAP acetate system as catalysts. When
2,4-pentandione reactions were carried out in the presence of Amberlyst-15, conjugate addition and/or
conjugate-addition initiated ring closure products were obtained depending on the reaction conditions.
However, unlike 2,4-pentandione, dibenzoylmethane gave only conjugate addition products with
Amberlyst-15. When Amberlyst-15-DMAP acetate system was used, always only conjugate addition
Received 16 January 2017
Received in revised form
15 May 2017
Accepted 30 May 2017
Available online 1 June 2017
products were obtained with
b
-dicarbonyl compounds independent of the reaction conditions.
Keywords:
Amberlyst-15
DMAP acetate
© 2017 Elsevier Ltd. All rights reserved.
b
-Dicarbonyl compounds
Ring closure
Michael addition
1. Introduction
heterogenous catalyst systems such as acid-functionalized ionic
liquids,11 dicationic ammonium salts,12 and K10 montmorillonite13
Carbon-carbon bond formation is a very important method for
the preparation of complex structures. Alkylation of 1,3-dicarbonyl
compounds is one of the most important CeC bond construction
methodology in organic synthesis. The basic method for alkylation
are also used for conjugate addition of
enones.
b-dicarbonyl compounds to
The aim of the present study is to develop a new alternative
heterogenous catalyst system without using toxic and corrosive
metallic compounds. For this purpose, we examined an inexpen-
sive, reusable, non-toxic heterogenous catalyst, Amberlyst-15,
which was also easy to remove from the reaction mixture. 2,4-
Pentandione, dibenzoylmethane and ethylacetoacetate (ethyl-3-
oxobutanoate) were chosen as Michael donors and 2-
cyclohexene-1-one, 2-cyclopenten-1-one, and benzalacetone
were used as representative Michael acceptors, as shown in Fig. 1.
These Michael donors were chosen for two reasons: (a) there were
several studies on 2,4-pentandione (1a) and ethylacetoacetate
(ethyl-3-oxobutanoate) (2a) as Michael donors, with yields varying
between 66 and 90%, using a wide variety of catalysts such as Lewis
acids (e.g. Cu(OTf)3, Yb(OTf)3, CeCl3), or phase transfer cata-
lyst.2e4,9e12,14,15 Therefore, it would be possible to compare the
conjugate addition reactions with Amberlyst-15 to other catalyst
systems and verify its feasibility; (b) Michael addition reactions
using dibenzoylmethane (1b) was very limited and the yields of
desired products were low or moderate.10
of b-dicarbonyl compounds is performed with alkyl halides in the
presence of stoichiometric amount of a base. However, there are
some disadvantages of this methodology such as, toxicity of halo-
genated reagents, usage of strong bases etc. In recent years, new
methodologies have been developed using alcohols,1,2 alkenes3,4 or
benzylic/allylic sp3 CeH bonds5e7 as alkylation reagents. Conjugate
addition of
b-dicarbonyl compounds to enones is also another
important CeC bond construction route in organic synthesis.
Different from the classical methods including deprotonation with
strong bases in conjugate addition, important developments have
been made using transition-metal catalysts. Reactions were per-
formed using Cu(OTf)2,8,9 microsized cerium chloride,10 iron, in-
dium, zinc, bismuth, and scandium salts8 as acidic catalysts.
Unfortunately, these metal-catalyzed conjugate additions still have
some problems. In order to overcome these problems alternative
* Corresponding author.
** Corresponding author.
E-mail addresses: kumbaracii@itu.edu.tr (V. Kumbaraci), talinlin@itu.edu.tr
(N. Talinli).
http://dx.doi.org/10.1016/j.tet.2017.05.092
0040-4020/© 2017 Elsevier Ltd. All rights reserved.

4336
H. Gunduz et al. / Tetrahedron 73 (2017) 4335e4340
and 2,4-pentandione reactions were repeated under the same re-
action conditions but for a longer reaction time of 48 h. At the end
of the reaction time, ring closure product was observed with a yield
25%. Second approach was to start with alkylation product 9 and
use a solvent with a higher boiling point, dichloroethane (DCE), for
16 h. After this reaction, it has been detected by GC-MS analysis
that, alkylation product was transformed to compound 10 with a
higher yield of 30% (Scheme 3). This experiment confirmed the two
steps reaction mechanism. Similarly, compound 6 was heated with
Amberlyst-15 in DCE for 16 h and analysis revealed that 35% of
compound 6 was transformed to compound 7 (Scheme 3). The rest
of the mixture was by-products.
The relatively unreactive Michael acceptor, benzalacetone, (1,3-
diphenylpropane-1,3-dione) was reacted with 2,4-pentandione
with Amberlyst-15 as the catalyst and provided two products
with an overall yield of 25% (Table 1). From the chromatographic
and spectroscopic analysis, the products were found to be, again,
Michael addition product 11 and ring closure product 12. Although
compound 11 was a known product,15 there was no information on
compound 12 in the literature in this reaction system. Compound
12 was detected from the GC-MS analysis but we could not afford to
separate it from the reaction mixture because of the low conversion
of starting compounds leading to poor yield for by-products.
Fig. 1. Acceptors and donors used in the Michael reaction.
2. Results and discussion
Initially, we performed the reaction of 2,4-pentandione with 2-
cyclohexen-1-one in the presence of Amberlyst-15 in dichloro-
methane. Unexpectedly, three reaction products 6, 7 and 8 were
observed in chromatographic analysis (Table 1, entry 1). The com-
pound 68 was the expected Michael addition product obtained with
a yield of 56%. The compounds 7 and 8, interestingly, were the new
products formed via ring closure reactions. Jung and Maderna14
reported one pot formation of compound 7 as the main product
with 40% yield starting from 2,4-pentandione and cyclohexenone
under microwave conditions using triflouromethanesulfonic acid
and P4O10. However, there was no spectroscopic data to confirm the
structure of 7 and they claimed that the by-products of this reaction
were mostly higher oligomers. Different from Maderna's work, we
obtained compound 6 as the major product among the three
compounds. We could also isolate by-products 7 and 8 and their
structures were fully characterized by IR, MS, 1H-NMR, 13C-NMR,
HSQC, 1,1-ADEQUATE and superimposed HSQC-1,1-ADEQUATE
given in supplementary material.
NMR analysis of 8 showed that there were two stereoisomers in
ratio 70:30. However, because of the low yield, stereoisomers could
not be separated properly and analysis were performed as mixture.
The structure of compound 8 was confirmed by the bridgehead
methine protons -nearby carbonyl group-of two isomers at 2.93
and 2.55 ppm respectively. Moreover, in 13C-NMR spectrum there
were six peaks between 73.5 and 59.6 ppm for two stereoisomers
coming from three carbons of cyclobutane skeleton and four peaks
for carbonyl groups. All the other resonance signals were in
agreement with designated structure.
Jung and Maderna proposed a reaction mechanism which was
called “Bridged Robinson Annulation” for the formation of com-
pound 7. In compliance with this mechanism, reaction took place in
two steps and the ring closure products 7 and 8 were formed from
the alkylation product 6 depending on the two enolic isomers of
cyclohexanone (Scheme 1).
For further study, 2-cyclopenten-1-one was reacted with 2,4-
pentandione to examine the utility and reproducibility of the
catalyst activity of Amberlyst-15. Similarly, Michael addition
product 98 was obtained with a yield of 67%. In addition, ring
closure product 10 was obtained with low yield, 15%, probably due
to the strained ring system formation from intramolecular aldol
reaction (Table 1, entry 2). Different from compound 7, enolic
structure of cyclopentanone could not give bicyclic cyclobutane
derivative probably due to ring strain (Scheme 2).
In order to examine the procedure on
b-ketoesters, dime-
thylmalonate and ethylacetoacetate were reacted with cyclo-
hexene-2-one. In case of ethylacetoacetate, the major product was
the alkylation product 1612 as expected, and ring closure product 17
was detected and isolated in enol form as single stereoisomer with
low yield, 6%. (Table 1, entry 7). Compound 17 was synthesized
before16 using solid lithium S-(-) prolinate under microwave con-
ditions in the yield 75%. However, different from our proposed
structure, they showed the compound as diketone form. The
structure of 17 was confirmed by spectroscopic analysis. In partic-
ular, the geminal hydrogens bonded to carbon on the
a position of
carbonyl group, was detected at 2.53 ppm and 2.44 ppm as two
doublets with J ¼ 18.86 Hz. The methyl group was not observed on
the spectrum because of ring closure formation via enolic structure
of donor group. Unfortunately, dimethylmalonate gave neither
alkylation nor ring closure products.
The feasibility of our method was examined by reacting diben-
zoylmethane as the Michael donor. When the reaction was per-
formed with 2-cyclohexene-1-one in the presence of Amberlyst-15,
contrary to expectations, only Michael addition product was ob-
tained with a yield of 45% without getting any ring closure prod-
ucts. In order to improve the yield, we carried out the reaction in an
ionic liquid, dimethylaminopyridine (DMAP) acetate, based on the
work by Bhanage and co-workers which reported that Amberlyst-
15-[Bmim][PF6] is an efficient reusable catalyst1 for the benzylation
and hydroalkylation of b-dicarbonyl compounds. The reaction was
repeated with Amberlyst-15-DMAP acetate system with the same
molar ratio of dibenzoylmethane/2-cyclohexene-1-one (1:2) at
80 ꢀC for 2 h. Isolated yield was increased to 75% (Table 2). The
influence of substrates' mol ratio, reaction time and reaction tem-
perature were examined. The reaction was carried out at various
temperatures to find that it cannot be efficiently carried out at
temperatures below 80 ꢀC. Increasing the reaction time did not
appreciably change the yield, but decreasing the reaction time
decreased the yield. This result encouraged us to react dibenzoyl-
methane with 2-cyclohexene-1-one, 2-cyclopentene-1-one, and
benzalacetone under the same reaction conditions and the desired
products 13, 14, 154,12,17e19 were obtained (Table 2) with the yields
which were compatible with the yield reported by Tan17 et al.
(yields 61e99%). However, different from our work, they carried out
the reaction in basic conditions using chiral bicyclic guanidine as
catalyst and it was mediated by Et3N.
In order to increase the yield of the ring closure products and
also to confirm the reaction mechanism, two experimental ap-
proaches were applied. In the first attempt, the cyclopentene-2-one

H. Gunduz et al. / Tetrahedron 73 (2017) 4335e4340
4337
Table 1
Amberlyst-15 catalyzed Michael addition reactions of 1,3-diketones with enones.
Entry
1
Donor
Acceptor
Time (h)
16
Product(s) and Yielda (%)
1a
3
2
1a
4
16
3
1a
5
16
4
5
1b
1b
3
4
5
5
6
7
1b
2a
5
3
16
16
Reaction conditions: Donor (5 mmol) and acceptors (10 mmol) were dissolved in DCM (15 mL) and Amberlyst-15 (10% in w/w) was added to the mixture. The reaction
mixture was refluxed for 5e16 h depending on substrates. a: isolated yield by column chromatography. b: the yield obtained by GC analysis. c: Compound 16 was isolated as a
diastereomeric mixture (1:1).
Unlike 2-cyclohexene-1-one and 2-cyclopent-1-one, benzala-
cetone did not give an efficient reaction yield (20%) (Table 2, entry
6) when compared with the values reported before. The report
written by Kotrusz and Toma, the yield of benzalacetone and
dibenzoyl methane reaction was given as 34% using L-proline
catalyzed Michael addition in ionic liquids.19
Finally, to investigate the effect of DMAP acetate on the Michael
addition reactions of 2,4-pentandione, 2,4-pentandione was
exposed with enones using Amberlyst-15-DMAP acetate as catalyst
under identical reaction conditions used before. Surprisingly,
Amberlyst-15-DMAP acetate system resulted with only alkylation
products but with lower yields (Table 2, entries; 1, 2, 3),

4338
H. Gunduz et al. / Tetrahedron 73 (2017) 4335e4340
Scheme 1. Reaction mechanism for the formation of compounds 7 and 8.
depending on the reaction time or reaction temperature whereas
only Michael addition products were synthesized when same re-
actions were carried out with Amberlyst-15-DMAP acetate catalyst
system. However, dibenzoylmethane always gave only Michael
addition products independent from the catalyst system and re-
action conditions. Ethylacetoacetate also gave corresponding
compounds under similar conditions.
4. Experimental
Scheme 2. The formation of compound 10.
Unless otherwise noted, commercially available materials which
were received from Aldrich, Alfa Aesar, Acros Merck and TCI used
without further purification. All solvents were of HPLC or ACS
grade. MgSO4 anhydrous (99.0%, Aldrich) and 4 Å molecular sieves
were used for drying agents.
Purifications via column chromatography were performed with
silica gel 60 (Merck, 0.040e0.063 mm) which have 230e400 mesh
ASTM and Celite®. Analytical thin layer chromatography (TLC) was
performed on Merck labelled silica gel (60 HF254, 90% < 55 mm)
plates (0.25 mm) precoated with a fluorescent indicator, and pre-
parative plate chromatography purifications were performed on
silica gel plates (750.0 mm) precoated with a fluorescent indicator.
Visualization was affected with 254 nm ultraviolet light and iodine
on silica.
Proton nuclear magnetic resonance (1H-NMR) measurements
were recorded in Merck d-CDCl3 which had deuteration degree
99.8% with Si(CH3)4 as internal standard, using a Agilent VNMRS
(500 MHz) instrument. The carbon nuclear magnetic resonance
(
13C-NMR) spectra were recorded at Agilent VNMRS 125 MHz. Gas
chromatography, which was equipped with mass spectrometry,
(GC-MS) measurements were performed by using Thermo Finnigan
Trace DSQ instrument equipped with TR-5MS capillary GC column
Scheme 3. Transformation of alkylation products to bicyclic compounds.
interestingly, none of the ring closure products were detected. In
order to improve the yields, reactions were performed for different
reaction times and reaction temperatures. The best results were
obtained at 80 ꢀC and for 4 h. However, yields were still lower than
that of the yields obtained using Amberlyst-15 in DCM.
(5% Phenyl Polysilphenylene-siloxane) with following parameters:
ꢀ
initial temperature: 100 C, heating rate: 15 ꢀC/min, final temper-
ature: 300 ꢀC.
4.1. General procedure A
3. Conclusion
To a round-bottomed flask, b-dicarbonyl compounds com-
pounds (1 equiv.) and enone derivatives (2 equiv.) were dissolved in
DCM and Amberlyst-15 (10% in w/w) was added to the mixture. The
reaction mixture was refluxed for 5e16 h. After the reaction was
cooled to the room temperature, Amberlyst-15 was filtered of from
the crude mixture and solvent was evaporated under reduced
pressure and the products were purified by chromatographic
methods.
The conjugate addition of b-dicarbonyl compounds to enones
have been studied using Amberlyst-15 or Amberlyst-15-DMAP ac-
etate system as catalysts. It has been revealed that, 2,4-pentandione
gave Michael addition and/or ring closure products depending on
reaction conditions and catalyst system as follows: alkylation and/
or only ring closure products were obtained with Amberlyst-15

H. Gunduz et al. / Tetrahedron 73 (2017) 4335e4340
4339
Table 2
Amberlyst-15-DMAP.OAc catalyzed Michael additions reactions.
products were purified by chromatographic methods.
4.2.1. 3-(3-Oxocyclohexyl)pentan-2,4-dione (6)
Colorless oil: nmax (liquid film) 2929, 2866, 1692, 1420, 1358,
1248, 1151 cmꢂ1; Rf (20% EtOAc/hexane) 0.11; 1H-NMR (CDCl3,
Yielda (%)
45
500 MHz)
d
3.62 (d, CH, J ¼ 10.5 Hz, 1H), 2.69e2.61 (m, CH, 1H),
Entry
1
Donor
Acceptor
Time (h)
4
Product
2.40e2.35 (m, CH2, 1H), 2.30e2.26 (m, CH2, 1H), 2.25e2.20 (m, CH2,
1H), 2.16 (s, CH3, 3H), 2.14 (s, CH3, 3H), 2.05e1.98 (m, CH2, 2H),
1.81e1.75 (m, CH2, 1H), 1.72e1.63 (m, CH2, 1H), 1.39e1.32 (m, CH2,
1a
3
1H); 13C-NMR (CDCl3, 126 MHz)
d 209.1, 202.9, 202.7, 74.8, 45.2,
41.0, 38.4, 29.8, 29.7, 28.8, 24.4. GS-MS (EI): calc. C11H16O3: 196.11.
Found: 196.24 (Mþ), m/e 196.24, 178.22, 153.15, 136.18, 125.15,
111.14, 97.11, 96.15, 85.11, 68.10, 55.00.
2
1a
4
4
52
4.2.2. 5-Acetyl-6-methyl-bicyclo[2.2.2]oct-5-ene-2-one (7)
Colorless oil: nmax (liquid film) 2933, 1703, 1420, 1259,
1013 cmꢂ1
500 MHz)
;
Rf (30% acetone/hexane) 0.49; 1H-NMR (CDCl3,
3.48 (m, 1H), 3.06 (t, CH, J ¼ 3.0 Hz, 1H), 2.30 (s, COCH3,
d
3H), 2.15 (s, CH3, 3H), 2.04e2.02 (dd, COCH2, J ¼ 5.0, 2.5 Hz, 2H),
3
4
1a
1b
5
3
4
2
12
75
1.90e1.84 (m, CH, 1H), 1.74e1.68 (m, CH, 1H), 1.66e1.59 (m, CH, 1H),
1.56e1.50 (m, CH, 1H); 13C-NMR (CDCl3, 126 MHz)
d
211.0, 197.3,
147.0, 140.7, 57.7, 40.3, 33.3, 30.1, 24.7, 22.1, 19.9. GS-MS (EI): calc.
11H14O2: 178.10. Found: 178.05 (Mþ), m/e 178.05, 136.10, 121.03,
C
107.09, 93.08, 77.02, 65.06.
4.2.3. 7-Acetyl-8-hydroxy-8-methyl bicyclo [4.2.0] octan-2-one (8)
White solid: nmax (neat) 3392, 2918, 1700 (br), 1293, 1110 cmꢂ1
;
Rf (30% acetone/hexane) 0.47; 1H-NMR (CDCl3, 500 MHz) Stereo-
isomer 1:
d
2.93 (br. s., CH, 1H), 2.81 (dt, CH2, J ¼ 19.5, 2.5 Hz, 1H),
2.34 (m, CH, 1H), 2.33 (s, CH3, 3H), 2.19 (m, CH, 1H), 2.09 (ddd, CH2,
5
6
1b
1b
4
5
2
4
60
20
J ¼ 19.5, 3.0, 2.0 Hz, 1H), 1.82e1.45 (m, CH2, 4H), 1.20 (s, CH3, 3H);
13C-NMR (CDCl3, 126 MHz)
27.01, 26.09, 19.7, 17.8.
d 214.2, 209.7, 72.1, 59.6, 59.2, 39.9, 29.7,
1H-NMR (CDCl3, 500 MHz) Stereoisomer 2:
d 2.72 (dt, CH2,
J ¼ 20.0, 2.5 Hz,1H), 2.58 (m, CH,1H), 2.55 (m, CH,1H), 2.34 (m, CH2,
1H), 2.33 (s, CH3, 3H), 2.28 (m, CH,1H), 2.15 (dt, CH2, J ¼ 20.0, 2.0 Hz,
1H), 1.82e1.45 (m, CH2, 4H), 1.59 (s, CH3, 3H); 13C-NMR (CDCl3,
126 MHz)
d 213.6, 209.4, 73.5, 58.4, 56.8, 40.4, 31.2, 30.9, 28.4, 17.7,
17.8. GS-MS (EI): calc. C11H16O3: 196.11. Found: 196.09 (Mþ), m/e
196.09, 178.08, 153.09, 138.08, 111.06, 96.06, 84.08, 69.05.
4.2.4. 3-(3-oxocyclopentyl)pentane-2,4-dione (9)
7
2a
3
4
40
Yellow oil: nmax (liquid film) 2959, 1736, 1692, 1405, 1356, 1192,
1159 cmꢂ1; Rf (20% EtOAc/hexane) 0.10; 1H-NMR (CDCl3, 500 MHz)
d
3.60 (d, CH, J ¼ 11.0 Hz, 1H), 2.94e2.85 (m, CH, 1H), 2.37e2.32 (dd,
CH2, J ¼ 18.0, 7.5 Hz, 1H), 2.29e2.23 (m, CH2, 1H), 2.18 (s, CH3, 3H),
2.14 (s, CH3, 3H), 2.17e2.07 (m, CH2, 2H), 1.77e1.70 (ddd, CH2,
J ¼ 18.0, 11.0, 1.5 Hz, 1H), 1.51e1.42 (m, CH2, 1H); 13C-NMR (CDCl3,
126 MHz) d 216.4, 202.7, 202.5, 74.7, 42.6, 37.9, 36.1, 29.6, 29.3, 27.4.
Reaction conditions: Donor (4 equiv.), acceptors, (1 equiv.) DMAP.OAc (4 equiv.)
and Amberlyst-15 (10% in w/w) were added sequentially in round-bottomed flask
and heated to 80 ꢀ C for 2e4 h depending on substrates.
GS-MS (EI): calc. C10H14O3: 182.09. Found: 182.15 (Mþ), m/e 182.15,
164.14, 139.14,125.11, 111.50,100.06, 97.09, 83.10, 82.10, 69.10, 55.10.
a
Isolated yield by column chromatography.
4.2.5. 4-Acetyl-1-hydroxy-bicyclo[3.2.1]octan-3-one (10)
4.2. General procedure B
Yellow oil: nmax (liquid film) 3451 (br), 2967, 1733, 1692, 1401,
1356, 1159 cmꢂ1; Rf (20% CH3CN/toluene) 0.36; 1H-NMR (CDCl3,
DMAP.OAc ionic liquid was added to a round-bottomed flask
with b-dicarbonyl compound (4 equiv.), enone derivative (1 equiv.)
and Amberlyst-15 (10% in w/w) were added sequentially in order to
form reaction mixture. Then, the mixture was heated to 80 C and
stirred for 2e4 h. After reaction cooled to the room temperature,
Amberlyst-15 was decanted from the crude mixture and residue
was poured to water, extracted with diethyl ether (ꢁ3), dried with
MgSO4 and solvent was evaporated under reduced pressure. The
500 MHz)
d
15.77 (s, OH, 1H), 2.95 (t, CH, J ¼ 5.0 Hz, 1H), 2.79e2.75
(dt, CH2, J ¼ 18.0, 2.0 Hz, 1H), 2.64e2.60 (dd, CH2, J ¼ 18.0, 2.5 Hz,
1H), 2.13 (s, COCH3, 3H), 2.18e2.11 (m, CH2, 1H), 1.94e1.91 (m, CH2,
1H), 1.87e1.83 (m, CH2, 1H), 1.69e1.61 (m, CH2, 2H); 13C-NMR
ꢀ
(CDCl3, 126 MHz)
d 192.1, 185.8, 114.5, 76.8, 50.3, 43.8, 37.0, 35.1,
33.9, 23.4. GS-MS (EI): calc. C10H14O3: 182.09. Found: 182.14 (Mþ),
m/e 182.14, 164.15, 153.09, 139.13, 121.09, 111.09, 97.11, 83.11, 69.49,
52.09.

4340
H. Gunduz et al. / Tetrahedron 73 (2017) 4335e4340
4.2.6. 3-Acetyl-4-phenylheptane-2,6-dione (11)
J ¼ 7.5 Hz, 4H), 3.35 (d, 2xCH, J ¼ 9.5 Hz, 2H), 2.58e2.50 (m, 2xCH,
2H), 2.40e2.28 (m, 2xCOCH2, 4H), 2.25e2.21 (dd, CH2, J ¼ 14.0,
6.5 Hz, 2H), 2.19 (s, CH3, 3H), 2.18 (s, CH3, 3H), 2.14e2.09 (dd, CH2,
J ¼ 14.0, 6.5 Hz, 2H), 2.05e1.98 (m, CH2, 2H),1.88e1.77 (m, CH2, 2H),
1.70e1.61 (m, CH2, 2H), 1.57e1.50 (m, CH2, 1H), 1.44e1.37 (m, CH2,
1H), 1.26e1.21 (m, 2xOCH2CH3, 6H); 13C-NMR (CDCl3, 125 MHz)
Pale yellow solid: nmax (neat) 3034, 2948, 1703, 1658, 1621, 1494,
1435, 1334, 1244, 1069 cmꢂ1; Rf (20% EtOAc/hexane) 0.17; 1H-NMR
(CDCl3, 500 MHz)
d
7.33 (t, Ar, J ¼ 7.34 Hz, 1H), 7.28 (t, Ar, J ¼ 7.0 Hz,
2H), 7.21 (d, Ar, J ¼ 7.0 Hz, 2H), 4.19 (d, CH, J ¼ 11.5 Hz, 1H),
4.03e3.99 (m, CH, 1H), 2.79e2.74 (dd, CH2, J ¼ 16.0, 9.5 Hz, 1H),
2.66e2.62 (dd, CH2, J ¼ 17.0, 4.5 Hz, 1H), 2.23 (s, CH3, 3H), 1.97 (s,
d
211.2, 209.5, 201.6, 201.5, 168.2, 168.0, 65.0, 64.6, 61.6, 61.5, 46.3,
CH3, 3H), 1.86 (s, CH3, 3H); 13C-NMR (CDCl3, 126 MHz)
d
206.5,
45.3, 45.0, 41.0, 40.9, 38.7, 37.7, 37.5, 30.5, 29.0, 25.0, 22.7, 14.1, 14.0.
GS-MS (EI): calc. C12H18O4: 226.12. Found: 226.08 (Mþ), m/e 226.08,
198.12, 183.03, 153.12, 137.00, 130.02, 110.09, 97.08, 68.07.
203.1, 203.1, 140.3, 128.5, 128.0, 127.1, 74.0, 47.1, 41.1, 30.0, 29.3. GS-
MS (EI): calc. C15H18O3: 246.143. Found: 246.29 (Mþ), m/e 246.29,
202.85, 185.06, 161.05, 147.11, 129.13, 119.50, 103.11, 91.09, 77.09,
65.09, 51.09.
4.2.11. Ethyl 3,5-dihydroxybicyclo[3.3.1]non-2-ene-2-carboxylate
(17)
4.2.7. 2-(3-Oxocyclohexyl)-1,3-diphenylpropane-1,3-dione (13)
Pale yellow solid: nmax (neat) 3051, 2930, 1700, 1694, 1657, 1585,
1450, 1382 cmꢂ1; Rf (20% EtOAc/hexane) 0.11; 1H-NMR (CDCl3,
Pale yellow oil: nmax (liquid film) 3427 (br), 2930, 1731, 1688,
1450, 1352, 1126 cmꢂ1; Rf (20% EtOAc/hexane) 0.34; 1H-NMR
(CDCl3, 500 MHz)
d 12.22 (br. s, OH enolic, 1H), 4.22 (q, OCH2,
500 MHz)
d
7.98 (d, Ar, 2H), 7.95 (d, Ar, J ¼ 8.0 Hz, 2H), 7.57e7.52 (m,
J ¼ 7.5 Hz, 2H), 2.53 (d, CH2, J ¼ 18.0 Hz, 1H), 2.44 (d, CH2,
J ¼ 18.0 Hz, 1H), 2.24e2.21 (m, bridgehead CH, 1H), 1.82e1.77 (m,
CH2, 2H), 1.72e1.66 (m, CH2, 2H), 1.65e1.57 (m, CH2, 2H), 1.53e1.46
(m, CH2, 2H), 1.3 (t, OCH2CH3, J ¼ 7.5 Hz, 3H); 13C-NMR (CDCl3,
Ar, 2H), 0.45e7.39 (m, Ar, 4H) 5.29 (d, CH, J ¼ 8.5 Hz, 1H), 3.05e2.97
(m, CH, 1H), 2.44e2.35 (m, CH2, 2H), 2.29e2.21 (m, CH2, 2H),
2.03e1.99 (m, CH2, 1H), 1.92 (d, CH2, J ¼ 13.0 Hz, 1H), 1.69e1.62 (m,
CH2, 1H), 1.59e1.52 (m, CH2, 1H); 13C-NMR (CDCl3, 125 MHz)
125 MHz)
d 171.9, 171.5, 100.0, 69.0, 60.2, 43.7, 41.4, 40.9, 29.7, 28.6,
d
200.6, 194.6, 194.4, 136.6, 133.5, 129.0, 128.7, 128.5, 62.6, 45.9, 41.2,
19.4, 14.3. GS-MS (EI): calc. C12H18O4: 226.12. Found: 226.08 (Mþ),
m/e 226.16, 192.00, 175.13, 164.13, 149.12, 136.11, 121.09, 108.09,
91.01, 79.07.
39.5, 29.5. GS-MS (EI): calc. C21H20O3: 320.14. Found: 320.31 (Mþ)
m/e 320.31, 302.17, 224.15, 215.17, 147.10, 105.06, 77.08, 51.07.
4.2.8. 2-(3-oxocyclopentyl)-1,3-diphenylpropane-1,3-dione (14)
White solid: nmax (neat) 3056, 2922, 2855, 1736, 1692, 1662,
1595, 1446, 1267, 998 cmꢂ1; Rf (20% EtOAc/hexane) 0.16; 1H-NMR
Acknowledgment
We are grateful to Istanbul Technical University research fund
for financial support.
(CDCl3, 500 MHz)
d
8.02 (dd, Ar, J ¼ 8.5, 1.5 Hz, 2H), 7.98 (dd, Ar,
J ¼ 8.5, 1.5 Hz, 2H), 7.60e7.55 (m, Ar, 2H), 7.46 (t, Ar, J ¼ 8.5 Hz, 2H),
7.44 (t, Ar, J ¼ 8.5 Hz, 2H), 5.21 (d, CH, J ¼ 9.5 Hz, 1H), 3.34e3.25 (m,
CH, 1H), 2.52e2.47 (dd, CH2, J ¼ 18.5, 7.5 Hz, 1H), 2.35e2.30 (dd,
CH2, J ¼ 16.0, 8.0 Hz, 1H), 2.23e2.15 (m, CH2, 2H), 2.0e1.94 (ddd,
CH2, J ¼ 18.5, 11.5, 1.0 Hz, 1H), 1.71e1.62 (m, CH2, 1H); 13C-NMR
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2017.05.092.
(CDCl3, 125 MHz)
d 217.1, 194.8, 194.7, 136.3, 136.2, 133.9, 133.8,
129.1, 129.0,128.7, 128.6, 62.8, 43.4, 38.2, 37.8, 28.1. GS-MS (EI): calc.
C
20H18O3: 306.13. Found: 306.23 (Mþ), m/e 306.23, 224.20, 201.20,
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186.16, 158.17, 147.50, 115.12, 104.96, 82.11, 78.11, 77.05, 76.11, 51.08.
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206.9, 195.0, 194.7, 140.7, 136.7, 136.5, 133.7, 133.3, 128.8e127.0,
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368.60 (Mþ), m/e 368.60, 265.16, 247.17, 223.12, 147.09, 131.09,
105.07, 78.09, 77.07, 51.06.
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Colorless oil: nmax (liquid film) 2950, 2857,1741,1702,1450,1360,
1257, 1235, 1142 cmꢂ1; Rf (20% EtOAc/hexane) 0.30; Diastereomeric
ratio ¼ 1:1; 1H-NMR (CDCl3, 500 MHz)
d 4.20e4.13 (q, 2xOCH2,