Three types of products obtained unexpectedly from the reaction of dimedone with chalcones

Article abstract of DOI:10.1002/ejoc.201100374

The apparently simple Michael reaction of dimedone with chalcones afforded three types of products. The reaction of dimedone with chalcones in water at reflux, mediated by cetyltrimethylammonium bromide, gave the expected Michael adducts in good to excell

Full text of DOI:10.1002/ejoc.201100374

FULL PAPER
DOI: 10.1002/ejoc.201100374
Three Types of Products Obtained Unexpectedly from the Reaction of
Dimedone with Chalcones
Guan-Wu Wang,*[a] Qing-Quan Lu,[a] and Jing-Jing Xia*[a,b]
Keywords: Michael addition / Autoxidation / Chalcones / Dimedone / Structure elucidation
The apparently simple Michael reaction of dimedone with
chalcones afforded three types of products. The reaction of
dimedone with chalcones in water at reflux, mediated by
cetyltrimethylammonium bromide, gave the expected
Michael adducts in good to excellent yields after purification
by column chromatography. The attempted purification of
the Michael adducts by recrystallization from ethanol in air
unexpectedly generated hydroperoxidated and hydroxylated
Michael adducts in low yields. The efficient synthesis of hy-
droperoxidated Michael adducts could be achieved in nearly
quantitative yields by autoxidation of the Michael adducts in
1,2-dichloroethane at room temperature under aerobic con-
ditions. The conversion of the hydroperoxidated Michael ad-
ducts to hydroxylated Michael adducts was facilitated by re-
duction with triphenylphosphane in excellent yields. Some
of the reported Michael adducts in the literature need to be
reassigned. Particular caution must be exerted to assign the
Michael products generated from cyclic β-diketones, such as
dimedone, because different purification processes may give
different types of products.
sults and further manipulation of the Michael adducts for
the efficient synthesis of hydroperoxidated and hydroxyl-
ated Michael adducts.
Introduction
The Michael reaction stands as one of the most impor-
tant processes for the formation of C–C bonds in organic
synthesis, because the formed Michael adducts are versatile
precursors for many biologically active compounds.[1]
A
Results and Discussion
survey of the literature indicated that, among the numerous
reported Michael reactions, the addition of cyclic β-di-
ketones to α,β-conjugated compounds has been relatively
scarce,[2,3] because the reaction tends to continue to subse-
quent cyclization steps in most cases.[2]
On the other hand, water in place of harmful organic
solvents as the environmentally friendly and benign reac-
tion medium has gained increasing popularity in organic
synthesis.[4] As a continuation of our interest in aqueous
organic reactions,[2c,5] we recently investigated the Michael
reaction of 5,5-dimethylcyclohexane-1,3-dione (dimedone,
1) with 1,3-diaryl-2-propen-1-ones (chalcones, 2) with water
as the reaction medium. We unexpectedly isolated three
types of products during the workup processes, which were
identified as simple Michael adducts, hydroperoxidated and
hydroxylated Michael adducts. Herein, we disclose these re-
In an attempt to extend the methodology of synthesizing
1,4-dihydropyridine derivatives with water as the reaction
medium,[6] we recently explored the reaction of dimedone
with chalcones and ammonium acetate in refluxing water.
The expected products should be 1,4-dihydropyridine deriv-
atives formed through Michael addition followed by cycli-
zation.[6] However, we found that ammonium acetate was
not involved, and the reaction could not proceed beyond
the Michael addition step. We thus focused on the aqueous
Michael addition. The Michael addition of 1 to the simplest
chalcone, namely, 1,3-diphenyl-2-propen-1-one (2a), was
chosen as the model reaction for investigation. The Michael
reaction is conventionally catalyzed by strong bases, such
as NaOH, KOH, and NaOEt, which often lead to undesir-
able side reactions, such as bis(addition) and subsequent
condensation. We intended to use mild conditions to avoid
such side reactions. At the onset, the reaction of 1 with 2a
[a] Hefei National Laboratory for Physical Sciences at Microscale,
CAS Key Laboratory of Soft Matter Chemistry, Joint Laboratory in water at reflux (120 °C in an oil bath) for 3 h gave
of Green Synthetic Chemistry, and Department of Chemistry,
Michael adduct 3a in 28% yield (Table 1, Entry 1). Benzyl
University of Science and Technology of China,
triethylammonium chloride (BTEAC) as a phase-transfer
catalyst (PTC) was previously applied by us to the aqueous
aminochlorination of chalcones.[5] We found that BTEAC
could increase the product yield to 49% (Table 1, Entry 2),
and tetrabutylammonium bromide (TBAB) further im-
proved the product yield to 72% (Table 1, Entry 3). Cetyl-
trimethylammonium bromide (CTAB) was superior to
Hefei, Anhui 230026, P. R. China
Fax: +86-551-360-7864
E-mail: gwang@ustc.edu.cn
[b] School of Materials and Chemical Engineering, Anhui University
of Architecture,
Hefei, Anhui 230601, P. R. China
E-mail: xiajj@mail.ustc.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100374.
Eur. J. Org. Chem. 2011, 4429–4438
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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G.-W. Wang, Q.-Q. Lu, J.-J. Xia
FULL PAPER
other ammonium salts and afforded 3a in 76% yield Table 2. Aqueous Michael reaction of 1 with 2 mediated by
CTAB.[a]
(Table 1, Entry 4). Decreasing the temperature of the oil
bath from 120 to 110 °C reduced the yield to 70% (Table 1,
Entry 5). Prolonging the reaction time from 3 to 5 h en-
hanced the yield to 89% (Table 1, Entry 6). However, an-
ionic surfactants, such as sodium dodecyl sulfate (SDS) and
sodium dodecylbenzenesulfonate (ABS-Na), reduced the
formation of 3a, giving yields even lower than that without
any additive (Table 1, Entries 7 and 8 vs. Entry 1). There-
fore, equimolar amounts of 1 and 2a with 10 mol-% of
CTAB were selected as the optimal conditions for the aque-
ous Michael reaction of 1 and 2a.
Entry Substrate
R
RЈ
Time Product Yield
[h]
[%][b]
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
H
H
H
H
H
H
H
5
5
5
5
5
7
7
7
7
3a
3b
3c
3d
3e
3f
3g
3h
3i
89
84
74
89
85
93
87
75
84
4-H3C
4-H3CO
4-Cl
3,4-Cl2
3-O2N
4-O2N
4-Cl
Table 1. Optimization of reaction conditions for the aqueous
Michael reaction of 1 with chalcone 2a.[a]
4-H3CO
4-Cl
4-Cl
[a] All reactions were performed with 1 (0.2 mmol), 2 (0.2 mmol),
and CTAB (10 mol-%) in water (2 mL) at 120 °C (oil bath tempera-
ture). [b] Isolated yield after chromatographic purification.
Entry
Additive
Time [h]
Temp. [°C][b]
Yield [%][c]
1
2
3
4
5
6
7
8
none
BTEAC
TBAB
CTAB
CTAB
CTAB
SDS
3
3
3
3
3
5
3
3
120
120
120
120
110
120
120
120
28
49
72
76
70
89
17
24
either phenyl ring performed well and afforded Michael ad-
ducts 3a–i in good to excellent yields (Table 2, Entries 1–9).
Michael adducts 3a–i were fully characterized by HRMS,
1
as well as by H and 13C NMR and FTIR spectroscopy.
The HR mass spectra of products 3a–i gave the correct mo-
lecular ion masses. The 1H NMR spectra in [D6]DMSO
showed the expected signals from the chalcone moiety, in-
cluding two doublets and one pseudo-triplet for the newly
formed –CHCH2– fragment, as well as signals of the dime-
done moiety. The 13C NMR spectra of 3a–i displayed sig-
nals for the two phenyl rings; one coincidently overlapped
ABS-Na
[a] All reactions were performed with 1 (0.2 mmol), chalcone 2a
(0.2 mmol), and additive (10 mol-%) in water (2 mL). [b] Tempera-
ture of the oil bath. [c] Isolated yield after chromatographic purifi-
cation.
With the optimized conditions in hands, we then ex- the signal at δ ≈ 199 ppm for the carbonyl groups, one signal
tended the substrate to other chalcones. A variety of chal- at δ ≈ 115 ppm, and four signals in the range of δ = 28–
cones with electron-withdrawing or -donating groups on 41 ppm for aliphatic carbon atoms. The dimedone moiety
Figure 1. HMQC spectrum of 3a. Inset: partial assignment of 3a.
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Eur. J. Org. Chem. 2011, 4429–4438

Products from the Reaction of Dimedone with Chalcones
should exist in an enol form, since one broad signal at δ = During the NMR spectroscopy experiments, we found that
10.42–10.86 ppm due to the enolic hydroxy group and a adducts 3 were stable in [D6]DMSO and [D6]acetone, but
signal at δ = 114.6–115.7 ppm for the enolic carbon atom unstable in CDCl3. We then screened different solvents with
were observed in the 1H and 13C NMR spectra, respectively. or without an additive for the efficient conversion of 3a. We
The dimedone moiety as an enol form was also observed found that Michael adduct 3a was converted to hydroperox-
previously by us in the nonreductive addition products from ide 5a in low yields at room temperature in air for 4 h when
the manganese(III) acetate mediated reaction of 1,3-cyclo- toluene, ethanol, or N,N-dimethylformamide (DMF) were
hexanediones with imines.[7] Surprisingly, in the 13C NMR employed as the solvents (Table 3, Entries 1–3). When chlo-
spectra of 3, only four signals for the seven sp3-carbon roform was used, a moderate yield could be obtained
atoms were observed. Among the four signals, one over- (Table 3, Entry 4). The yield was significantly increased to
lapped signal at δ = 27.7–27.9 ppm corresponds to two car- 88% when the reaction was performed in dichloromethane
bon atoms, leaving two of the seven sp3-carbon atoms for (Table 3, Entry 5). Further improvement of the yield to
which no 13C NMR signals could be identified. The hetero- 91% was attained if 1,2-dichloroethane (DCE) was utilized
nuclear multiple quantum correlation (HMQC) spectrum as the solvent (Table 3, Entry 6). However, when acetic acid
of 3a (Figure 1) was measured to help assign its molecular was added, the yield decreased from 91 to 68% (Table 3,
structure. Two protons [signals at δ = 3.65 (dd, J = 16.8, Entry 6 vs. 7). Nearly quantitative yields were achieved
6.8 Hz) and 3.87 (dd, J = 16.8, 8.4 Hz) ppm] are attached when the reaction in DCE was conducted under 1 atm of
to the same carbon atom (signal at δ = 40.9 ppm), whereas O2 or prolonged from 4 to 6 h (Table 3, Entries 8 and 9),
one proton [signal at δ = 4.78 (t, J = 7.5 Hz) ppm] is bonded indicating that this transformation involved oxygen.
to the carbon atom with signal at δ = 34.4 ppm. Unexpec-
Table 3. Solvent screening for the conversion of Michael adduct 3a
tedly, the broad signal for the methylene protons of the di-
medone moiety showed no cross-peak in the HMQC spec-
into hydroperoxide 5a.[a]
trum, indicating that fast ring flipping of the dimedone
fragment resulted in the signal disappearance of the methyl-
ene carbon atoms in the 13C NMR spectrum of 3a. The
same effect was responsible for the occurrence of only one
signal at δ = 199.2 ppm for the two carbonyl carbon atoms
and one signal at δ = 27.8 ppm for the two methyl carbon
Entry
Solvent
Time [h]
Additive
Yield [%][b]
atoms of the dimedone moiety.
To further confirm that the integrity of the dimedone
fragment was preserved in the Michael adduct, compound
3a was treated with acetyl chloride in the presence of trieth-
ylamine at room temperature for 40 min, and acetoxylated
product 4a was obtained in 89% yield (Scheme 1).
1
2
3
4
5
6
7
8
9
toluene
ethanol
DMF
CHCl3
CH2Cl2
DCE
DCE
DCE
DCE
4
4
4
4
4
4
4
4
6
–
–
–
–
–
–
16
12[c]
15
44
88
91
68
98
97
AcOH[d]
[e]
O2
–
[a] Michael adduct 3a (0.2 mmol), solvent (2 mL), and additive
were stirred in the presence of air at room temperature for the indi-
cated time. [b] Isolated yield after chromatographic purification. [c]
Mixture of 5a and 6a (see below) in a ratio of 1:1. [d] AcOH
(0.2 mL) as the additive. [e] Under 1 atm of O2.
Scheme 1. Acetoxylation of Michael adduct 3a.
It is more convenient to operate in air than under oxy-
The HR mass spectrum of 4a gave a signal at m/z = gen. Therefore, the conversion of Michael adducts 3b–i to
1
390.1829, corresponding to the molecular ion. The H and hydroperoxides 5b–i was performed in air at room tempera-
13C NMR spectra showed all expected signals, including ture with DCE as the solvent. The results are shown in
those at δ = 42.8, 51.8, and 167.5 ppm, which correspond Table 4 and demonstrate that autoxidation of 3a–i in DCE
to two methylene carbon atoms and one enolic carbon atom is very efficient and affords 5a–i in 95–98% yields.
in the dimedone moiety, but were absent in the 13C NMR
In attempts to purify products 5 by recrystallization from
spectrum of 3a. The broad signals at δ = 2.02 and 2.29 ppm ethanol, a third type of products, 6, was identified. Products
1
1
for the two CH2 groups in the H NMR spectrum of 3a 6 showed similar H and 13C NMR spectra to those of hy-
became a singlet at δ = 2.24 ppm and two doublets at δ = droperoxides 5 with the same numbers of protons and car-
2.42 and 2.53 ppm with a coupling constant of 17.7 Hz in bon atoms (see below). This puzzle was eventually solved
1
the H NMR spectrum of 4a.
by obtaining the single-crystal X-ray structure of 6d (see
In initial attempts to purify Michael adducts 3, the prod- below). The third type of products was identified as the
ucts were recrystallized from ethanol. Some other products, hydroxylated Michael adducts, which were likely to be gen-
including those identified later as hydroperoxides 5 and hy- erated by the reduction of hydroperoxides 5 with ethanol.
droxylated Michael adducts 6, were obtained in low yields. The yield from 5 to 6 by recrystallization from ethanol was
Eur. J. Org. Chem. 2011, 4429–4438
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G.-W. Wang, Q.-Q. Lu, J.-J. Xia
FULL PAPER
Table 4. Autoxidation of Michael adducts 3 to hydroperoxides 5.[a] the hydroperoxides could easily lose an oxygen atom during
mass spectrometry. While different from Michael adducts 3,
1
products 5 and 6 displayed similar H and 13C NMR spec-
tra, and showed the expected signals for all protons and
carbon atoms. The only significant differences in the NMR
spectra of 5 and 6 were the signal shifts from δ = 9.38–
9.46 ppm for the –OOH group to δ = 4.04–4.13 ppm for
the –OH group and from δ = 99.5–100.7 to 91.2–91.9 ppm
for the carbon atoms connected to the –OOH and –OH
groups, respectively. The broad signal(s) for the two CH2
Entry Substrate
R
RЈ
Time Product Yield
[h]
[%][b]
1
groups of the dimedone moiety in the H NMR spectra of
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
H
H
H
H
H
6
7
5a
5b
5c
5d
5e
5f
5g
5h
5i
97
96
96
95
95
97
96
98
97
1
4-H3C
4-H3CO
4-Cl
3,4-Cl2
3-O2N
4-O2N
4-Cl
3 became two doublets and two double doublets in the H
14
13
12
18
17
13
15
NMR spectra of both 5 and 6. In addition, the missing
signals for the two CH2 groups of the dimedone moiety in
the 13C NMR spectra of 3 could be observed at δ = 52.4–
52.6 and 53.3–53.5 ppm for 5, and δ = 51.6–51.7 and 51.7–
51.9 ppm for 6. Furthermore, the identity of product 6d was
unequivocally established by its single-crystal X-ray struc-
ture, which is shown in Figure 2.
4-H3CO
4-Cl
4-Cl
[a] All reactions were performed by stirring 3 (0.2 mmol) in DCE
(2 mL) in air at room temperature for the indicated time. [b] Iso-
lated yield after chromatographic purification.
low to moderate. Therefore, triphenylphosphane was added
to reduce the –OOH group to the –OH group.[8] We found
that after the conversion of Michael adducts 3 into hydro-
peroxides 5 was complete in air at room temperature, subse-
quent treatment of the reaction mixture with Ph3P
(1 equiv.) gave hydroxylated products 6 in 90–95% yields
(Table 5).
Table 5. One-pot conversion of Michael adducts 3 into hydroxyl-
ated products 6.[a]
Figure 2. Single-crystal X-ray structure of 6d. Ellipsoids are drawn
at the 40% probability level.
The α-hydroxylation of β-dicarbonyl compounds by
using various oxidants, such as peracids, dimethyldioxirane,
or molecular oxygen, has been reported.[9] Oxidation by O2
of compounds containing a tertiary carbon atom to give
hydroperoxides is known in the literature. For example, the
autoxidation of cyclic β-diketones with a tertiary α-C atom
to give hydroperoxides was described over 50 years ago.[10]
A large number of Michael adducts have been synthe-
sized.[1] Nevertheless, there has been no report on the per-
oxidation of Michael adducts from dimedone and chal-
Entry Substrate
R
RЈ
Time Product Yield
[h]
[%][b]
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
H
H
H
H
H
6
7
6a
6b
6c
6d
6e
6f
6g
6h
6i
92
94
91
90
93
90
93
95
94
4-H3C
4-H3CO
4-Cl
3,4-Cl2
3-O2N
4-O2N
4-Cl
14
13
12
18
17
13
15
4-H3CO
4-Cl
4-Cl
[a] The reaction conditions for the first step were the same as those cones.[3] By comparing the spectroscopic data in ref.[3a] with
given in Table 4. After the completion of the first step, Ph3P
ours, we found that the reported spectroscopic data of 3a,
(0.2 mmol) was added to the reaction mixture, which was then
3d, and 3f in ref.[3a] match more closely with those of 6a,
stirred at 60 °C for 30 min. [b] Isolated yield after chromatographic
5d, and 6f, respectively. Therefore, the assumed Michael ad-
purification.
ducts in ref.[3a] should be corrected and reassigned. We re-
Hydroperoxides 5a–i and hydroxylated products 6a–i peated the KF/Al2O3-catalyzed reaction of dimedone and
were characterized by HRMS, as well as 1H and 13C NMR chalcones in DMF at 80 °C,[3a] and indeed obtained the ex-
and FTIR spectroscopy. The HR mass spectra of 5 exhib- pected Michael adducts with the same workup procedure
ited mass signals that correspond to [M–O], indicating that for our aqueous Michael reaction. The hydroperoxidated
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Products from the Reaction of Dimedone with Chalcones
sities in the 13C NMR spectroscopic data are 1 C, except where
indicated. Single-crystal X-ray analysis was carried out with an Ox-
ford Diffraction Xcalibur diffractometer equipped with a Sapphire
3 CCD detector and graphite-monochromated Mo-Kα radiation (λ
= 0.71073 Å).
Michael adduct (5d) and hydroxylated Michael adducts (6a
and 6f) in ref.[3a] should result from further transformation
of the Michael adducts during recrystallization from eth-
anol. This is consistent with our observation that both hy-
droperoxidated and hydroxylated Michael adducts could be
generated by the treatment of 3 in ethanol (see above). De-
duced from the reported spectroscopic data, it is likely that
all of the reported Michael adducts in ref.[3a] are in fact
either the corresponding hydroperoxidated or hydroxylated
products after treatment with ethanol. It is taken for
granted that only Michael products can be isolated from
the addition of β-diketones to α,β-conjugated com-
pounds.[3a] In our case, three types of products were ob-
tained from the Michael reaction of dimedone with chal-
cones, depending on the purification processes. The present
work clearly demonstrates that special caution must be ex-
erted for the purification procedure and product assignment
of Michael adducts from cyclic β-diketones, such as 1.
General Procedure A. Michael Addition of Dimedone 1 to Chalcones
2: To a mixture of dimedone (1; 28.0 mg, 0.2 mmol), chalcone 2a
(2b–i, 0.2 mmol), and CTAB (7.3 mg, 0.02 mmol) in a 25 mL
round-bottomed flask was added H2O (2 mL). This reaction mix-
ture was stirred vigorously in an oil bath preheated at 120 °C for
the desired time (monitored by TLC). The residue remaining after
concentration was separated by column chromatography on silica
gel with petroleum ether/ethyl acetate (3:1) as the eluent to give
Michael product 3a (3b–i).
3-Hydroxy-5,5-dimethyl-2-(3-oxo-1,3-diphenylpropyl)cyclohex-2-en-
one (3a): According to general procedure A, chalcone 2a (41.6 mg,
0.2 mmol) was employed. Column chromatography gave 3a as a
1
white solid (62.0 mg, 89%). H NMR (300 MHz, [D6]DMSO): δ =
0.90 (s, 6 H, CH3), 2.02 (br. s, 2 H, CH2), 2.29 (br. s, 2 H, CH2),
3.65 (dd, J = 16.8, 6.8 Hz, 1 H, CH2), 3.87 (dd, J = 16.8, 8.4 Hz,
1 H, CH2), 4.78 (t, J = 7.5 Hz, 1 H, CH), 7.08 (t, J = 7.2 Hz, 1 H,
ArH), 7.19 (t, J = 7.5 Hz, 2 H, ArH), 7.26 (d, J = 7.5 Hz, 2 H,
ArH), 7.50 (t, J = 7.4 Hz, 2 H, ArH), 7.61 (t, J = 7.3 Hz, 1 H,
ArH), 7.90 (d, J = 7.4 Hz, 2 H, ArH), 10.48 (br. s, 1 H, OH) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 199.2 (2 C), 144.7, 137.1,
132.8, 128.6 (2 C), 127.8 (2 C), 127.7 (2 C), 127.5 (2 C), 125.2,
Conclusions
Three types of products, that is, Michael adducts (3), hy-
droperoxidated (5) and hydroxylated (6) Michael adducts,
were unexpectedly obtained from the reaction of 1 with 2
depending on different purification processes. The reaction
of 1 with 2 in water at reflux mediated by CTAB gave the
expected Michael adducts 3 in good to excellent yields (74–
93%) after purification by column chromatography. When
our Michael adducts 3 were treated in ethanol both hydro-
peroxidated (5) and hydroxylated (6) Michael adducts were
generated in low yields. Hydroxylated Michael adducts 6
could also be formed by recrystallization of 5 from ethanol
in low to moderate yields. Gratifyingly, hydroperoxidated
Michael adducts 5 were easily produced in nearly quantita-
tive yields (95–98%) by autoxidation of 3 in 1,2-dichlor-
ethane at room temperature under aerobic conditions. The
conversion of hydroperoxidated Michael adducts 5 to hy-
115.4, 40.9, 34.4, 31.5, 27.8 (2 C) ppm. FTIR (KBr): ν = 3426,
˜
2957, 1685, 1599, 1493, 1449, 1378, 1253, 1210, 1151, 1076, 1008,
752, 696 cm–1. HRMS (EI-TOF): calcd. for C23H24O3 [M]+
348.1725; found 348.1732.
3-Hydroxy-5,5-dimethyl-2-(3-oxo-3-phenyl-1-p-tolylpropyl)cyclo-
hex-2-enone (3b): According to general procedure A, chalcone 2b
(44.5 mg, 0.2 mmol) was employed. Column chromatography gave
3b as a white solid (61.0 mg, 84 %). 1H NMR (300 MHz, [D6]-
DMSO): δ = 0.90 (s, 6 H, CH3), 1.99–2.35 (m, 4 H, CH2), 2.21 (s,
3 H, CH3), 3.62 (dd, J = 16.6, 6.9 Hz, 1 H, CH2), 3.83 (dd, J =
16.6, 8.3 Hz, 1 H, CH2), 4.73 (t, J = 7.5 Hz, 1 H, CH), 6.99 (d, J
= 7.8 Hz, 2 H, ArH), 7.13 (d, J = 7.8 Hz, 2 H, ArH), 7.50 (t, J =
7.5 Hz, 2 H, ArH), 7.60 (t, J = 7.3 Hz, 1 H, ArH), 7.89 (d, J =
8.0 Hz, 2 H, ArH), 10.42 (br. s, 1 H, OH) ppm. 13C NMR
droxylated Michael adducts 6 could be facilitated by re- (75 MHz, [D6]DMSO): δ = 199.2 (2 C), 141.7, 137.1, 134.0, 132.8,
128.6 (2 C), 128.3 (2 C), 127.7 (2 C), 127.4 (2 C), 115.6, 40.9, 34.0,
duction with triphenylphosphane in Ͼ90% yields. Some of
the reported Michael adducts in the literature may need to
be revised. Particular care must be exerted to determine
what type of product is generated from cyclic β-diketones,
such as 1, because purification processes have substantial
effects on the type of products.
31.5, 27.8 (2 C), 20.5 ppm. FTIR (KBr): ν = 3428, 2957, 2924,
˜
1686, 1597, 1513, 1449, 1378, 1314, 1254, 1210, 1151, 1057, 1008,
814, 765, 691 cm–1. HRMS (EI-TOF): calcd. for C24H26O3 [M]+
362.1882; found 362.1879.
3-Hydroxy-2-[1-(4-methoxyphenyl)-3-oxo-3-phenylpropyl]-5,5-di-
methylcyclohex-2-enone (3c): According to general procedure A,
chalcone 2c (47.7 mg, 0.2 mmol) was employed. Column
chromatography gave 3c as a white solid (56.0 mg, 74%). 1H NMR
(300 MHz, [D6]DMSO): δ = 0.90 (s, 6 H, CH3), 2.00 (br. s, 2 H,
CH2), 2.28 (br. s, 2 H, CH2), 3.64 (dd, J = 16.7, 6.9 Hz, 1 H, CH2),
3.68 (s, 3 H, OCH3), 3.84 (dd, J = 16.7, 8.4 Hz, 1 H, CH2), 4.72
(t, J = 7.5 Hz, 1 H, CH), 6.76 (d, J = 8.6 Hz, 2 H, ArH), 7.17 (d,
J = 8.6 Hz, 2 H, ArH), 7.50 (t, J = 7.3 Hz, 2 H, ArH), 7.61 (t, J
= 7.3 Hz, 1 H, ArH), 7.89 (d, J = 7.3 Hz, 2 H, ArH), 10.46 (br. s,
1 H, OH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 199.3 (2 C),
157.0, 137.1, 136.7, 132.8, 128.6 (2 C), 128.4 (2 C), 127.7 (2 C),
115.7, 113.1 (2 C), 54.9, 41.2, 33.7, 31.5, 27.8 (2 C) ppm. FTIR
Experimental Section
General Methods: Flash chromatographic purification of products
was performed on silica gel (200–300 mesh). Thin-layer chromatog-
raphy was visualized with a UV light (254 and 365 nm). IR spectra
were recorded with a Bruker Vector-22 spectrometer as KBr pellets
and are reported in cm–1. 1H NMR spectra were recorded at
300 MHz with a Bruker Avance-300 spectrometer in CDCl3 with
chemical shifts (δ) given in ppm relative to TMS as an internal
standard. 13C NMR spectra were recorded with a Bruker Avance-
300 (75.5 MHz) spectrometer with complete proton decoupling;
chemical shifts are reported in ppm relative to the solvent reso-
nance as the internal standard (CDCl3: δ = 77.16 ppm). All inten-
(KBr): ν = 3437, 2956, 2927, 1684, 1607, 1511, 1450, 1378, 1308,
˜
1248, 1178, 1035, 830, 765, 691 cm–1. HRMS (EI-TOF): calcd. for
C24H26O4 [M]+, 378.1831; found 378.1840.
Eur. J. Org. Chem. 2011, 4429–4438
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4433

G.-W. Wang, Q.-Q. Lu, J.-J. Xia
2-[1-(4-Chlorophenyl)-3-oxo-3-phenylpropyl]-3-hydroxy-5,5-dimeth- cedure A, chalcone 2h (54.6 mg, 0.2 mmol) was employed. Column
FULL PAPER
ylcyclohex-2-enone (3d): According to general procedure A, chalc-
one 2d (48.6 mg, 0.2 mmol) was employed. Column chromatog-
raphy gave 3d as a white solid (68.2 mg, 89%). 1H NMR (300 MHz,
[D6]DMSO): δ = 0.90 (s, 6 H, CH3), 2.03 (br. s, 2 H, CH2), 2.30
(br. s, 2 H, CH2), 3.68 (dd, J = 17.0, 7.1 Hz, 1 H, CH2), 3.83 (dd,
J = 17.0, 8.0 Hz, 1 H, CH2), 4.77 (t, J = 7.5 Hz, 1 H, CH), 7.26 (s,
4 H, ArH), 7.50 (t, J = 7.5 Hz, 2 H, ArH), 7.61 (t, J = 7.2 Hz, 1
chromatography gave 3h as a white solid (62.0 mg, 75%). 1H NMR
(400 MHz, [D6]DMSO): δ = 0.88 (s, 6 H, CH3), 2.15 (br. s, 4 H,
CH2), 3.61 (dd, J = 16.7, 7.2 Hz, 1 H, CH2), 3.71 (dd, J = 16.7,
7.9 Hz, 1 H, CH2), 3.81 (s, 3 H, OCH3), 4.76 (t, J = 7.6 Hz, 1 H,
CH), 7.00 (d, J = 8.9 Hz, 2 H, ArH), 7.22 (d, J = 9.0 Hz, 2 H,
ArH), 7.25 (d, J = 9.0 Hz, 2 H, ArH), 7.87 (d, J = 8.9 Hz, 2 H,
ArH), 10.85 (br. s, 1 H, OH) ppm. 13C NMR (100 MHz, [D6]-
H, ArH), 7.90 (d, J = 7.6 Hz, 2 H, ArH), 10.63 (br. s, 1 H, OH) DMSO): δ = 197.6 (2 C), 163.1, 143.9, 130.2 (2 C), 130.0, 129.9,
ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 199.0 (2 C), 143.7, 129.4 (2 C), 127.7 (2 C), 115.4, 114.0 (2 C), 55.6, 40.3, 34.0, 31.6,
137.0, 132.9, 129.8, 129.3 (2 C), 128.6 (2 C), 127.7 (2 C), 127.6 (2
27.9 (2 C) ppm. FTIR (KBr): ν = 3079, 2957, 2928, 1676, 1600,
˜
C), 115.2, 40.6, 33.8, 31.5, 27.7 (2 C) ppm. FTIR (KBr): ν = 3064,
1575, 1509, 1491, 1376, 1313, 1256, 1169, 1091, 1056, 1014,
˜
2957, 1687, 1596, 1580, 1491, 1449, 1377, 1315, 1254, 1211, 1150,
833 cm–1. HRMS (EI-TOF): calcd. for C24H25O435Cl [M]+
1092, 1056, 1014, 825, 760, 690 cm–1. HRMS (EI-TOF): calcd. for 412.1441; found 412.1450.
C23H23O337Cl [M]+ 384.1306; found 384.1299.
2-[1,3-Bis(4-chlorophenyl)-3-oxopropyl]-3-hydroxy-5,5-dimethyl-
2-[1-(3,4-Dichlorophenyl)-3-oxo-3-phenylpropyl]-3-hydroxy-5,5-di-
methylcyclohex-2-enone (3e): According to general procedure A,
chalcone 2e (55.4 mg, 0.2 mmol) was employed. Column
chromatography gave 3e as a white solid (70.9 mg, 85%). 1H NMR
(300 MHz, [D6]DMSO): δ = 0.90 (s, 6 H, CH3), 1.99–2.35 (br., 4
H, CH2), 3.71 (dd, J = 17.3, 7.1 Hz, 1 H, CH2), 3.85 (dd, J = 17.3,
8.0 Hz, 1 H, CH2), 4.76 (t, J = 7.4 Hz, 1 H, CH), 7.23 (d, J =
8.4 Hz, 1 H, ArH), 7.46 (s, 1 H, ArH), 7.46–7.53 (m, 3 H, ArH),
7.62 (t, J = 7.3 Hz, 1 H, ArH), 7.92 (d, J = 8.2 Hz, 2 H, ArH),
10.77 (br. s, 1 H, OH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
198.7 (2 C), 146.0, 136.9, 133.0, 130.2, 129.9, 129.4, 128.7 (2 C),
128.0, 127.8 (2 C), 127.7, 114.7, 40.4, 33.7, 31.5, 27.7 (2 C) ppm.
cyclohex-2-enone (3i): According to general procedure A, chalcone
2i (55.4 mg, 0.2 mmol) was employed. Column chromatography
gave 3i as a white solid (70.1 mg, 84 %, white solid). 1H NMR
(400 MHz, [D6]DMSO): δ = 0.88 (s, 6 H, CH3), 2.15 (br. s, 4 H,
CH2), 3.65 (dd, J = 16.9, 6.9 Hz, 1 H, CH2), 3.82 (dd, J = 16.9,
8.4 Hz, 1 H, CH2), 4.74 (t, J = 7.6 Hz, 1 H, CH), 7.23 (d, J =
8.9 Hz, 2 H, ArH), 7.26 (d, J = 8.9 Hz, 2 H, ArH), 7.55 (d, J =
8.5 Hz, 2 H, ArH), 7.90 (d, J = 8.5 Hz, 2 H, ArH), 10.57 (br. s, 1
H, OH) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 198.2 (2 C),
143.6, 138.0, 135.7, 130.0, 129.8 (2 C), 129.4 (2 C), 128.9 (2 C),
127.7 (2 C), 115.1, 40.8, 33.9, 31.6, 27.8 (2 C) ppm. FTIR (KBr):
ν = 3087, 2958, 2928, 1687, 1589, 1490, 1377, 1314, 1254, 1092,
˜
1150, 1011, 1055, 890, 823 cm–1. HRMS (EI–TOF): calcd. for
C23H22O335Cl2 [M]+ 416.0946; found 416.0955.
FTIR (KBr): ν = 3083, 2958, 1686, 1596, 1580, 1470, 1449, 1375,
˜
1252, 1211, 1149, 1057, 1029, 818, 761, 689 cm–1. HRMS (EI-
TOF): calcd. for C23H22O335Cl2 [M]+ 416.0946; found 416.0932.
Procedure for the Acetoxylation of Michael Adduct 3a To Give 5,5-
Dimethyl-3-oxo-2-(3-oxo-1,3-diphenylpropyl)cyclohex-1-enyl Acet-
ate (4a): Triethylamine (117 μL, 0.84 mmol) was added dropwise at
room temperature to a solution of Michael adduct 3a (104.4 mg,
0.30 mmol) in dichloromethane (3 mL). After stirring for 10 min,
acetyl chloride (53.1 μL, 0.75 mmol) was added, and stirring was
maintained for 40 min. The crude product obtained was separated
by chromatography on silica gel with petroleum ether/acetyl acetate
(4:1) as the eluent to give 4a (104.0 mg, 89%). 1H NMR (300 MHz,
CDCl3): δ = 1.01 (s, 3 H, CH3), 1.03 (s, 3 H, CH3), 2.16 (s, 3 H,
CH3), 2.24 (s, 2 H, CH2), 2.42 (d, J = 17.7 Hz, 1 H, CH2), 2.53 (d,
J = 17.7 Hz, 1 H, CH2), 3.74 (dd, J = 17.1, 6.9 Hz, 1 H, CH2),
3.82 (dd, J = 17.1, 8.1 Hz, 1 H, CH2) 4.79 (t, J = 7.4 Hz, 1 H, CH),
7.12–7.18 (m, 1 H, ArH), 7.21–7.29 (m, 4 H, ArH), 7.44 (t, J =
7.5 Hz, 2 H, ArH), 7.54 (t, J = 7.4 Hz, 1 H, ArH), 7.87 (d, J =
7.5 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 198.9,
198.8, 167.5, 164.0, 142.2, 137.0, 133.1, 129.1, 128.6 (2 C), 128.3 (2
C), 128.2 (2 C), 127.6 (2 C), 126.3, 51.8, 42.8, 40.9, 35.9, 32.7, 28.0
3-Hydroxy-5,5-dimethyl-2-[1-(3-nitrophenyl)-3-oxo-3-phenyl-
propyl]cyclohex-2-enone (3f): According to general procedure A,
chalcone 2f (50.7 mg, 0.2 mmol) was employed. Column
chromatography gave 3f as a yellow solid (73.2 mg, 93%). 1H NMR
(300 MHz, [D6]DMSO): δ = 0.91 (s, 6 H, CH3), 2.07 (br. s, 2 H,
CH2), 2.30 (br. s, 2 H, CH2), 3.81 (dd, J = 17.4, 7.4 Hz, 1 H, CH2),
3.90 (dd, J = 17.4, 7.9 Hz, 1 H, CH2), 4.90 (t, J = 7.4 Hz, 1 H,
CH), 7.49–7.55 (m, 3 H, ArH), 7.63 (t, J = 7.3 Hz, 1 H, ArH), 7.73
(d, J = 7.7 Hz, 1 H, ArH), 7.94 (d, J = 8.2 Hz, 2 H, ArH), 7.99 (d,
J = 8.1 Hz, 1 H, ArH), 8.11 (s, 1 H, ArH), 10.86 (br. s, 1 H, OH)
ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 198.7 (2 C), 147.5,
147.0, 136.9, 134.5, 133.0, 129.2, 128.7 (2 C), 127.8 (2 C), 122.0,
120.5, 114.7, 40.4, 34.1, 31.6, 27.7 (2 C) ppm. FTIR (KBr): ν =
˜
3425, 2958, 2925, 1686, 1598, 1527, 1449, 1378, 1349, 1255, 1213,
1150, 1081, 1011, 805, 748, 690 cm–1. HRMS (EI-TOF): calcd. for
C23H23NO5 [M]+ 393.1576; found 393.1595.
3-Hydroxy-5,5-dimethyl-2-[1-(4-nitrophenyl)-3-oxo-3-phenyl-
propyl]cyclohex-2-enone (3g): According to general procedure A,
chalcone 2g (50.7 mg, 0.2 mmol) was employed. Column
chromatography gave 3g as a yellow solid (68.5 mg, 87 %). 1H
NMR (300 MHz, [D6]DMSO): δ = 0.91 (s, 6 H, CH3), 2.05 (br. s,
2 H, CH2), 2.31 (br. s, 2 H, CH2), 3.83 (d, J = 7.5 Hz, 2 H, CH2),
4.91 (t, J = 7.5 Hz, 1 H, CH), 7.51 (d, J = 8.7 Hz, 2 H, ArH), 7.51
(t, J = 7.5 Hz, 2 H, ArH), 7.63 (t, J = 7.2 Hz, 1 H, ArH), 7.93 (d,
J = 7.2 Hz, 2 H, ArH), 8.09 (d, J = 8.7 Hz, 2 H, ArH), 10.79 (br.
s, 1 H, OH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 198.6 (2
C), 153.0, 145.4, 136.8, 133.0, 128.6 (4 C), 127.8 (2 C), 122.9 (2 C),
(2 C), 21.0 ppm. FTIR (KBr): ν = 2960, 1768, 1684, 1598, 1494,
˜
1450, 1358, 1272, 1183, 1142, 1078, 1015, 850, 753, 699 cm–1
.
HRMS (EI–TOF): calcd. for C25H26O4 [M]+ 390.1831; found
390.1829.
General Procedure B. Conversion of Michael Adducts 3 to Hydroper-
oxides 5: Michael adduct 3a (3b–i, 0.2 mmol) was stirred in DCE
(2 mL) in air at room temperature for the indicated time (moni-
tored by TLC). The reaction mixture was separated on a silica gel
column (pretreated with AcOH) with petroleum ether/ethyl acetate
(3:1) as the eluent to afford hydroperoxide 5a (5b–i).
114.6, 39.6, 34.3, 31.5, 27.7 (2 C) ppm. FTIR (KBr): ν = 3424,
˜
3180, 2957, 2923, 1677, 1602, 1507, 1449, 1378, 1346, 1313, 1270,
1152, 1109, 1057, 1011, 855, 753, 698 cm–1. HRMS (EI-TOF):
calcd. for C23H23NO5 [M]+ 393.1576; found 393.1566.
2-Hydroperoxy-5,5-dimethyl-2-(3-oxo-1,3-diphenylpropyl)cyclo-
hexane-1,3-dione (5a): According to general procedure B, Michael
adduct 3a (69.7 mg, 0.2 mmol) was employed. Column chromatog-
raphy gave 5a as a white solid (73.8 mg, 97%). 1H NMR (300 MHz,
CDCl3): δ = 0.87 (s, 3 H, CH3), 1.24 (s, 3 H, CH3), 2.42 (dd, J =
2-[3-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-oxopropyl]-3-hydroxy-
5,5-dimethylcyclohex-2-enone (3h): According to general pro-
4434
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4429–4438

Products from the Reaction of Dimedone with Chalcones
14.1, 3.0 Hz, 1 H, CH2), 2.56 (dd, J = 15.3, 3.0 Hz, 1 H, CH2), 134.1, 133.7, 130.6 (2 C), 128.9 (2 C), 128.7 (2 C), 128.1 (2 C),
2.92 (d, J = 14.1 Hz, 1 H, CH2), 3.17 (d, J = 15.3 Hz, 1 H, CH2),
100.1, 53.3, 52.4, 44.9, 38.9, 30.7, 30.5, 26.0 ppm. FTIR (KBr): ν
˜
3.37 (dd, J = 18.8, 7.3 Hz, 1 H, CH2), 3.66 (dd, J = 18.8, 4.5 Hz, = 3403, 2957, 1735, 1704, 1595, 1491, 1449, 1417, 1358, 1237, 1204,
1 H, CH2), 4.39 (dd, J = 7.3, 4.5 Hz, 1 H, CH), 7.22–7.29 (m, 3 H,
1093, 1074, 1014, 754, 690, 618 cm–1. HRMS (EI-TOF): calcd. for
ArH), 7.34 (d, J = 6.3 Hz, 2 H, ArH), 7.41 (t, J = 7.5 Hz, 2 H, C23H23O435Cl [M – O]+ 398.1285; found 398.1290.
ArH), 7.54 (t, J = 7.5 Hz, 1 H, ArH), 7.87 (d, J = 7.5 Hz, 2 H,
2-[1-(3,4-Dichlorophenyl)-3-oxo-3-phenylpropyl]-2-hydroperoxy-
ArH), 9.43 (s, 1 H, OOH) ppm. 13C NMR (75 MHz, CDCl3): δ =
5,5-dimethylcyclohexane-1,3-dione (5e): According to general pro-
204.0, 202.9, 197.2, 137.1, 136.4, 133.6, 129.3 (2 C), 128.8 (2 C),
cedure B, Michael adduct 3e (83.5 mg, 0.2 mmol) was employed.
128.7 (2 C), 128.3 (3 C), 100.5, 53.5, 52.6, 45.8, 39.1, 30.8, 30.7,
Column chromatography gave 5e as a white solid (85.4 mg, 95%).
26.2 ppm. FTIR (KBr): ν = 3334, 3064, 2966, 2927, 1731, 1703,
˜
1H NMR (300 MHz, CDCl3): δ = 0.88 (s, 3 H, CH3), 1.26 (s, 3 H,
CH3), 2.47 (dd, J = 14.0, 3.3 Hz, 1 H, CH2), 2.58 (dd, J = 15.3,
3.3 Hz, 1 H, CH2), 2.85 (d, J = 14.0 Hz, 1 H, CH2), 3.14 (d, J =
15.3 Hz, 1 H, CH2), 3.29 (dd, J = 18.9, 7.5 Hz, 1 H, CH2), 3.63
(dd, J = 18.9, 4.2 Hz, 1 H, CH2), 4.34 (dd, J = 7.5, 4.2 Hz, 1 H,
CH), 7.22 (dd, J = 8.4, 2.1 Hz, 1 H, ArH), 7.34 (d, J = 8.3 Hz, 1
H, ArH), 7.43 (d, J = 7.5 Hz, 2 H, ArH), 7.44 (d, J = 2.1 Hz, 1 H,
ArH), 7.56 (t, J = 7.4 Hz, 1 H, ArH), 7.87 (d, J = 7.5 Hz, 2 H,
ArH), 9.42 (s, 1 H, OOH) ppm. 13C NMR (75 MHz, CDCl3): δ =
203.3, 202.5, 196.7, 137.4, 136.0, 133.9, 132.8, 132.6, 131.3, 130.8,
128.9 (2 C), 128.8, 128.3 (2 C), 99.9, 53.5, 52.6, 44.6, 39.0, 30.8,
1449, 1357, 1239, 1086, 1010, 748, 703, 634 cm–1 HRMS (EI-TOF):
calcd. for C23H24O4 [M – O]+ 364.1675; found 364.1670.
2-Hydroperoxy-5,5-dimethyl-2-(3-oxo-3-phenyl-1-p-tolylpropyl)-
cyclohexane-1,3-dione (5b): According to general procedure B,
Michael adduct 3b (72.5 mg, 0.2 mmol) was employed. Column
chromatography gave 5b as a white solid (75.7 mg, 96%). 1H NMR
(300 MHz, CDCl3): δ = 0.86 (s, 3 H, CH3), 1.24 (s, 3 H, CH3), 2.27
(s, 3 H, CH3), 2.41 (dd, J = 14.0, 3.2 Hz, 1 H, CH2), 2.55 (dd, J =
15.3, 3.2 Hz, 1 H, CH2), 2.92 (d, J = 14.0 Hz, 1 H, CH2), 3.16 (d,
J = 15.3 Hz, 1 H, CH2), 3.35 (dd, J = 18.7, 7.4 Hz, 1 H, CH2),
3.62 (dd, J = 18.7, 4.4 Hz, 1 H, CH2), 4.35 (dd, J = 7.4, 4.4 Hz, 1
H, CH), 7.06 (d, J = 8.0 Hz, 2 H, ArH), 7.21 (d, J = 8.0 Hz, 2 H,
ArH), 7.41 (t, J = 7.6 Hz, 2 H, ArH), 7.52 (t, J = 7.4 Hz, 1 H,
ArH), 7.87 (d, J = 7.6 Hz, 2 H, ArH), 9.38 (s, 1 H, OOH) ppm.
13C NMR (75 MHz, CDCl3): δ = 204.1, 203.0, 197.2, 137.9, 136.4,
134.0, 133.5, 129.5 (2 C), 129.1 (2 C), 128.7 (2 C), 128.2 (2 C),
100.6, 53.5, 52.6, 45.5, 39.1, 30.7, 30.6, 26.2, 21.2 ppm. FTIR
30.6, 26.2 ppm. FTIR (KBr): ν = 3414, 2957, 1737, 1707, 1686,
˜
1597, 1471, 1449, 1359, 1236, 1209, 1134, 1076, 1031, 1003, 758,
688, 634 cm–1. HRMS (EI-TOF): calcd. for C23H22O435Cl2
[M – O]+ 432.0895; found 432.0890.
2-Hydroperoxy-5,5-dimethyl-2-[1-(3-nitrophenyl)-3-oxo-3-phenyl-
propyl]cyclohexane-1,3-dione (5f): According to general pro-
cedure B, Michael adduct 3f (78.7 mg, 0.2 mmol) was employed.
Column chromatography gave 5f as a yellow solid (82.5 mg, 97%).
1H NMR (300 MHz, CDCl3): δ = 0.89 (s, 3 H, CH3), 1.27 (s, 3 H,
CH3), 2.47 (dd, J = 14.1, 3.3 Hz, 1 H, CH2), 2.62 (dd, J = 15.3,
3.3 Hz, 1 H, CH2), 2.88 (d, J = 14.1 Hz, 1 H, CH2), 3.17 (d, J =
15.3 Hz, 1 H, CH2), 3.37 (dd, J = 18.9, 7.5 Hz, 1 H, CH2), 3.71
(dd, J = 18.9, 4.4 Hz, 1 H, CH2), 4.49 (dd, J = 7.5, 4.4 Hz, 1 H,
CH), 7.41–7.49 (m, 3 H, ArH), 7.56 (t, J = 7.5 Hz, 1 H, ArH), 7.73
(d, J = 7.8 Hz, 1 H, ArH), 7.88 (d, J = 7.3 Hz, 2 H, ArH), 8.11 (d,
J = 7.8 Hz, 1 H, ArH), 8.23 (s, 1 H, ArH), 9.39 (s, 1 H, OOH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 203.4, 202.6, 196.5, 148.3,
139.2, 135.9, 135.5, 133.9, 129.7, 128.8 (2 C), 128.3 (2 C), 124.3,
123.2, 99.5, 53.4, 52.5, 44.9, 38.9, 30.8, 30.4, 26.1 ppm. FTIR
(KBr): ν = 3420, 2955, 1736, 1705, 1449, 1360, 1240, 761, 687,
˜
623 cm–1. HRMS (EI-TOF): calcd. for C24H26O4 [M – O]+
378.1831; found 378.1827.
2-Hydroperoxy-2-[1-(4-methoxyphenyl)-3-oxo-3-phenylpropyl]-5,5-
dimethylcyclohexane-1,3-dione (5c): According to general pro-
cedure B, Michael adduct 3c (75.7 mg, 0.2 mmol) was employed.
Column chromatography gave 5c as a white solid (78.8 mg, 96%).
1H NMR (300 MHz, CDCl3): δ = 0.87 (s, 3 H, CH3), 1.24 (s, 3 H,
CH3), 2.41 (dd, J = 13.9, 3.2 Hz, 1 H, CH2), 2.55 (dd, J = 15.3,
3.2 Hz, 1 H, CH2), 2.90 (d, J = 13.9 Hz, 1 H, CH2), 3.15 (d, J =
15.3 Hz, 1 H, CH2), 3.35 (dd, J = 18.7, 7.6 Hz, 1 H, CH2), 3.59
(dd, J = 18.7, 4.3 Hz, 1 H, CH2), 3.74 (s, 3 H, OCH3), 4.35 (dd, J
= 7.6, 4.3 Hz, 1 H, CH), 6.78 (d, J = 8.7 Hz, 2 H, ArH), 7.25 (d,
J = 8.7 Hz, 2 H, ArH), 7.41 (t, J = 7.6 Hz, 2 H, ArH), 7.53 (t, J
= 7.4 Hz, 1 H, ArH), 7.87 (d, J = 7.6 Hz, 2 H, ArH), 9.45 (s, 1 H,
OOH) ppm. 13C NMR (75 MHz, CDCl3): δ = 204.0, 202.9, 197.3,
159.3, 136.4, 133.6, 130.4 (2 C), 129.0, 128.7 (2 C), 128.2 (2 C),
114.2 (2 C), 100.7, 55.2, 53.5, 52.6, 45.2, 39.2, 30.7, 30.6, 26.2 ppm.
(KBr): ν = 3413, 2956, 1739, 1710, 1682, 1597, 1525, 1447, 1352,
˜
1257, 1208, 1074, 1004, 744, 698, 685 cm–1. HRMS (EI-TOF):
calcd. for C23H23NO6 [M – O]+ 409.1525; found 409.1523.
2-Hydroperoxy-5,5-dimethyl-2-[1-(4-nitrophenyl)-3-oxo-3-phenyl-
propyl]cyclohexane-1,3-dione (5g): According to general pro-
cedure B, Michael adduct 3g (78.7 mg, 0.2 mmol) was employed.
Column chromatography gave 5g as a yellow solid (81.7 mg, 96%).
1H NMR (300 MHz, CDCl3): δ = 0.89 (s, 3 H, CH3), 1.26 (s, 3 H,
CH3), 2.47 (dd, J = 14.1, 3.0 Hz, 1 H, CH2), 2.62 (dd, J = 15.3,
3.0 Hz, 1 H, CH2), 2.85 (d, J = 14.1 Hz, 1 H, CH2), 3.16 (d, J =
15.3 Hz, 1 H, CH2), 3.36 (dd, J = 18.9, 7.8 Hz, 1 H, CH2), 3.68
(dd, J = 18.9, 4.2 Hz, 1 H, CH2), 4.48 (dd, J = 7.8, 4.2 Hz, 1 H,
CH), 7.43 (t, J = 7.8 Hz, 2 H, ArH), 7.53–7.58 (m, 3 H, ArH), 7.87
(d, J = 7.2 Hz, 2 H, ArH), 8.13 (d, J = 8.7 Hz, 2 H, ArH), 9.43 (s,
1 H, OOH) ppm. 13C NMR (75 MHz, CDCl3): δ = 203.3, 202.4,
196.5, 147.7, 144.4, 135.9, 134.0, 130.4 (2 C), 128.9 (2 C), 128.2 (2
C), 123.9 (2 C), 99.5, 53.4, 52.5, 45.0, 38.8, 30.8, 30.5, 26.1 ppm.
FTIR (KBr): ν = 3400, 2957, 1737, 1704, 1686, 1611, 1514, 1449,
˜
1371, 1298, 1249, 1181, 1072, 1033, 836, 762, 735, 690, 623 cm–1.
HRMS (EI-TOF): calcd. for C24H26O5 [M – O]+ 394.1780; found
394.1791.
2-[1-(4-Chlorophenyl)-3-oxo-3-phenylpropyl]-2-hydroperoxy-5,5-
dimethylcyclohexane-1,3-dione (5d): According to general pro-
cedure B, Michael adduct 3d (76.6 mg, 0.2 mmol) was employed.
Column chromatography gave 5d as a white solid (78.9 mg, 95%).
1H NMR (400 MHz, CDCl3): δ = 0.87 (s, 3 H, CH3), 1.24 (s, 3 H,
CH3), 2.43 (dd, J = 14.0, 3.3 Hz, 1 H, CH2), 2.57 (dd, J = 15.3,
3.3 Hz, 1 H, CH2), 2.86 (d, J = 14.0 Hz, 1 H, CH2), 3.15 (d, J =
15.3 Hz, 1 H, CH2), 3.33 (dd, J = 18.8, 7.6 Hz, 1 H, CH2), 3.62
(dd, J = 18.8, 4.3 Hz, 1 H, CH2), 4.36 (dd, J = 7.6, 4.3 Hz, 1 H,
CH), 7.23 (d, J = 8.7 Hz, 2 H, ArH), 7.29 (d, J = 8.7 Hz, 2 H,
ArH), 7.42 (t, J = 7.7 Hz, 2 H, ArH), 7.54 (t, J = 7.4 Hz, 1 H,
ArH), 7.86 (dd, J = 8.4 Hz, 2 H, ArH), 9.46 (s, 1 H, OOH) ppm.
FTIR (KBr): ν = 3405, 2955, 1735, 1707, 1680, 1598, 1515, 1450,
˜
1349, 1236, 1211, 1111, 1074, 1003, 857, 754, 706, 690 cm–1. HRMS
(EI-TOF): calcd. for C23H23NO6 [M – O]+ 409.1525; found
409.1530.
2-[3-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-oxopropyl]-2-hydro-
13C NMR (100 MHz, CDCl3): δ = 203.5, 202.5, 196.8, 136.0, 135.5, peroxy-5,5-dimethylcyclohexane-1,3-dione (5h): According to gene-
Eur. J. Org. Chem. 2011, 4429–4438
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4435

G.-W. Wang, Q.-Q. Lu, J.-J. Xia
FULL PAPER
ral procedure B, Michael adduct 3h (82.6 mg, 0.2 mmol) was em-
raphy gave 6b as a white solid (71.2 mg, 94%). 1H NMR (300 MHz,
CDCl3): δ = 0.77 (s, 3 H, CH3), 1.31 (s, 3 H, CH3), 2.27 (s, 3 H,
ployed. Column chromatography gave 5h as a white solid (87.2 mg,
1
98%). H NMR (300 MHz, CDCl3): δ = 0.87 (s, 3 H, CH3), 1.24 CH3), 2.40 (d, J = 13.4 Hz, 1 H, CH2), 2.52 (d, J = 14.5 Hz, 1 H,
(s, 3 H, CH3), 2.42 (dd, J = 13.8, 3.0 Hz, 1 H, CH2), 2.56 (dd, J =
15.3, 3.0 Hz, 1 H, CH2), 2.86 (d, J = 13.8 Hz, 1 H, CH2), 3.16 (d,
CH2), 3.09 (d, J = 13.4 Hz, 1 H, CH2), 3.40 (dd, J = 18.7, 6.4 Hz,
1 H, CH2), 3.43 (d, J = 14.5 Hz, 1 H, CH2), 3.54 (dd, J = 18.7,
J = 15.3 Hz, 1 H, CH2), 3.28 (dd, J = 18.6, 7.5 Hz, 1 H, CH2), 5.4 Hz, 1 H, CH2), 4.04 (s, 1 H, OH), 4.35 (t, J = 5.8 Hz, 1 H,
3.53 (dd, J = 18.6, 4.2 Hz, 1 H, CH2), 3.85 (s, 3 H, OCH3), 4.37
(dd, J = 7.5, 4.2 Hz, 1 H, CH), 6.88 (d, J = 8.9 Hz, 2 H, ArH),
7.23 (d, J = 8.6 Hz, 2 H, ArH), 7.28 (d, J = 8.6 Hz, 2 H, ArH),
7.85 (d, J = 8.9 Hz, 2 H, ArH), 9.40 (s, 1 H, OOH) ppm. 13C NMR
CH), 7.07 (d, J = 7.7 Hz, 2 H, ArH), 7.25 (d, J = 7.7 Hz, 2 H,
ArH), 7.41 (t, J = 7.4 Hz, 2 H, ArH), 7.53 (t, J = 7.3 Hz, 1 H,
ArH), 7.88 (d, J = 7.2 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 205.7, 204.7, 197.9, 137.8, 136.6, 135.1, 133.5, 129.6
(75 MHz, CDCl3): δ = 203.6, 202.7, 195.3, 164.1, 135.7, 134.1, (2 C), 128.7 (2 C), 128.5 (2 C), 128.2 (2 C), 91.9, 51.82, 51.79, 47.0,
130.7 (2 C), 130.6 (2 C), 129.2, 129.0 (2 C), 113.9 (2 C), 100.4, 55.6,
40.2, 31.6, 30.8, 26.5, 21.2 ppm. FTIR (KBr): ν = 3491, 2957, 2924,
˜
53.4, 52.5, 45.2, 38.6, 30.8, 30.6, 26.2 ppm. FTIR (KBr): ν = 3417,
1734, 1694, 1515, 1450, 1365, 1238, 1142, 1079, 1000, 814, 764,
689, 529 cm–1. HRMS (EI-TOF): calcd. for C24H26O4 [M]+
378.1831; found 378.1815.
˜
2959, 2925, 1733, 1704, 1688, 1603, 1574, 1510, 1492, 1420, 1358,
1241, 1170, 1093, 1031, 1014, 838, 822, 600 cm–1. HRMS (EI-
TOF): calcd. for C24H23O535Cl [M – H2O]+ 426.1234; found
426.1237.
2-Hydroxy-2-[1-(4-methoxyphenyl)-3-oxo-3-phenylpropyl]-5,5-
dimethylcyclohexane-1,3-dione (6c): According to general pro-
cedure C, Michael adduct 3c (75.7 mg, 0.2 mmol) was employed.
Column chromatography gave 6c as a white solid (71.8 mg, 91%).
1H NMR (400 MHz, CDCl3): δ = 0.77 (s, 3 H, CH3), 1.30 (s, 3 H,
CH3), 2.39 (dd, J = 13.5, 2.8 Hz, 1 H, CH2), 2.52 (dd, J = 14.4,
2.8 Hz, 1 H, CH2), 3.07 (d, J = 13.5 Hz, 1 H, CH2), 3.40 (dd, J =
18.6, 6.7 Hz, 1 H, CH2), 3.42 (d, J = 14.4 Hz, 1 H, CH2), 3.50 (dd,
J = 18.6, 5.0 Hz, 1 H, CH2), 3.74 (s, 3 H, OCH3), 4.05 (s, 1 H,
OH), 4.35 (t, J = 6.0 Hz, 1 H, CH), 6.79 (d, J = 8.7 Hz, 2 H, ArH),
7.30 (d, J = 8.7 Hz, 2 H, ArH), 7.41 (t, J = 7.7 Hz, 2 H, ArH),
7.53 (t, J = 7.4 Hz, 1 H, ArH), 7.88 (d, J = 7.2 Hz, 2 H, ArH)
ppm. 13C NMR (100 MHz, CDCl3): δ = 205.7, 204.6, 198.0, 159.2,
136.5, 133.5, 130.1, 129.6 (2 C), 128.7 (2 C), 128.2 (2 C), 114.2 (2
C), 91.9, 55.2, 51.7 (2 C), 46.6, 40.2, 31.5, 30.8, 26.5 ppm. FTIR
2-[1,3-Bis(4-chlorophenyl)-3-oxopropyl]-2-hydroperoxy-5,5-dimeth-
ylcyclohexane-1,3-dione (5i): According to general procedure B,
Michael adduct 3i (83.5 mg, 0.2 mmol) was employed. Column
chromatography gave 5i as a white solid (87.2 mg, 97%). 1H NMR
(300 MHz, CDCl3): δ = 0.87 (s, 3 H, CH3), 1.25 (s, 3 H, CH3), 2.44
(dd, J = 13.5, 3.2 Hz, 1 H, CH2), 2.57 (dd, J = 15.3, 3.2 Hz, 1 H,
CH2), 2.84 (d, J = 13.5 Hz, 1 H, CH2), 3.13 (d, J = 15.3 Hz, 1 H,
CH2), 3.25 (dd, J = 18.8, 7.2 Hz, 1 H, CH2), 3.59 (dd, J = 18.8,
4.5 Hz, 1 H, CH2), 4.33 (dd, J = 7.2, 4.5 Hz, 1 H, CH), 7.26–7.33
(m, 4 H, ArH), 7.40 (d, J = 8.4 Hz, 2 H, ArH), 7.80 (d, J = 8.4 Hz,
2 H, ArH), 9.38 (s, 1 H, OOH) ppm. 13C NMR (100 MHz, CDCl3):
δ = 203.7, 202.6, 195.8, 140.3, 135.4, 134.3, 134.1, 130.6 (2 C), 129.7
(2 C), 129.1 (2 C), 129.0 (2 C), 100.0, 53.4, 52.6, 45.0, 39.0, 30.8,
30.6, 26.1 ppm. FTIR (KBr): ν = 3412, 2958, 2920, 1737, 1705,
˜
(KBr): ν = 3462, 2951, 2936, 1728, 1698, 1611, 1514, 1448, 1358,
˜
1688, 1590, 1491, 1400, 1237, 1093, 1013, 831, 778, 724 cm–1
.
1299, 1251, 1179, 1141, 1078, 1032, 820, 764, 733, 690 cm–1. HRMS
(EI-TOF): calcd. for C24H26O5 [M]+ 394.1780; found 394.1775.
HRMS (EI-TOF): calcd. for C23H22O435Cl2 [M – O]+ 432.0895;
found 432.0899.
2-[1-(4-Chlorophenyl)-3-oxo-3-phenylpropyl]-2-hydroxy-5,5-di-
methylcyclohexane-1,3-dione (6d): According to general pro-
cedure C, Michael adduct 3d (76.6 mg, 0.2 mmol) was employed.
Column chromatography gave 6d as a white solid (71.8 mg, 90%).
1H NMR (300 MHz, CDCl3): δ = 0.78 (s, 3 H, CH3), 1.32 (s, 3 H,
CH3), 2.41 (dd, J = 13.5, 2.6 Hz, 1 H, CH2), 2.54 (dd, J = 14.4,
2.6 Hz, 1 H, CH2), 3.03 (d, J = 13.5 Hz, 1 H, CH2), 3.35–3.43 (m,
2 H, CH2), 3.50 (dd, J = 18.6, 5.4 Hz, 1 H, CH2), 4.07 (s, 1 H,
OH), 4.36 (t, J = 5.9 Hz, 1 H, CH), 7.24 (d, J = 8.4 Hz, 2 H, ArH),
7.34 (d, J = 8.4 Hz, 2 H, ArH), 7.43 (t, J = 7.5 Hz, 2 H, ArH),
7.55 (t, J = 7.5 Hz, 1 H, ArH), 7.88 (d, J = 7.5 Hz, 2 H, ArH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 205.5, 204.3, 197.6, 136.7,
136.4, 134.1, 133.7, 130.0 (2 C), 129.1 (2 C), 128.8 (2 C), 128.2 (2
C), 91.6, 51.8, 51.7, 46.6, 40.0, 31.6, 30.8, 26.5 ppm. FTIR (KBr):
General Procedure C. One-Pot Conversion of Michael Adducts 3 to
Products 6: Michael adduct 3a (3b–i, 0.2 mmol) was stirred in DCE
(2 mL) in air at room temperature for the desired time until the
starting Michael adduct had disappeared (monitored by TLC).
Then, Ph3P (0.2 mmol) was added to the reaction mixture, which
was stirred at 60 °C for 30 min. The reaction mixture was separated
on a silica gel column with petroleum ether/ethyl acetate (3:1) as
the eluent to give product 6a (6b–i).
2-Hydroxy-5,5-dimethyl-2-(3-oxo-1,3-diphenylpropyl)cyclohexane-
1,3-dione (6a): According to general procedure C, Michael adduct
3a (69.7 mg, 0.2 mmol) was employed. Column chromatography
gave 6a as a white solid (67.0 mg, 92%, white solid). 1H NMR
(300 MHz, CDCl3): δ = 0.77 (s, 3 H, CH3), 1.31 (s, 3 H, CH3), 2.40
(dd, J = 13.6, 2.7 Hz, 1 H, CH2), 2.53 (dd, J = 14.5, 2.7 Hz, 1 H,
CH2), 3.09 (d, J = 13.6 Hz, 1 H, CH2), 3.42 (dd, J = 18.7, 6.4 Hz,
1 H, CH2), 3.46 (d, J = 14.5 Hz, 1 H, CH2), 3.58 (dd, J = 18.7,
5.5 Hz, 1 H, CH2), 4.06 (s, 1 H, OH), 4.39 (t, J = 5.9 Hz, 1 H,
CH), 7.22–7.29 (m, 3 H, ArH), 7.37–7.44 (m, 4 H, ArH), 7.54 (t,
J = 7.2 Hz, 1 H, ArH), 7.89 (d, J = 7.4 Hz, 2 H, ArH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 205.7, 204.6, 197.9, 138.2, 136.5,
133.6, 128.9 (2 C), 128.74 (2 C), 128.68 (2 C), 128.3 (2 C), 128.1,
ν = 3447, 2959, 2923, 1733, 1693, 1597, 1491, 1449, 1237, 1142,
˜
1080, 1016, 822, 753, 689 cm–1. HRMS (EI-TOF): calcd. for
C23H23O4Cl [M]+ 398.1285; found 398.1286.
2-[1-(3,4-Dichlorophenyl)-3-oxo-3-phenylpropyl]-2-hydroxy-5,5-
dimethylcyclohexane-1,3-dione (6e): According to general pro-
cedure C, Michael adduct 3e (83.5 mg, 0.2 mmol) was employed.
Column chromatography gave 6e as a white solid (80.6 mg, 93%).
1H NMR (300 MHz, CDCl3): δ = 0.78 (s, 3 H, CH3), 1.32 (s, 3 H,
CH3), 2.44 (dd, J = 13.5, 2.9 Hz, 1 H, CH2), 2.54 (dd, J = 14.4,
2.9 Hz, 1 H, CH2), 3.00 (d, J = 13.5 Hz, 1 H, CH2), 3.36 (dd, J =
18.8, 6.6 Hz, 1 H, CH2), 3.37 (d, J = 14.4 Hz, 1 H, CH2), 3.50 (dd,
J = 18.8, 5.3 Hz, 1 H, CH2), 4.08 (s, 1 H, OH), 4.34 (t, J = 6.0 Hz,
1 H, CH), 7.27 (dd, J = 8.4, 2.0 Hz, 1 H, ArH), 7.35 (d, J = 8.4 Hz,
1 H, ArH), 7.43 (t, J = 7.7 Hz, 2 H, ArH), 7.50 (d, J = 2.0 Hz, 1
H, ArH), 7.56 (t, J = 7.5 Hz, 1 H, ArH), 7.88 (d, J = 7.2 Hz, 2 H,
91.8, 51.84, 51.80, 47.3, 40.2, 31.6, 30.9, 26.5 ppm. FTIR (KBr): ν
˜
= 3460, 3062, 2951, 1730, 1698, 1595, 1450, 1354, 1323, 1238, 1141,
1079, 1003, 748, 703, 686, 633, 600 cm–1. HRMS (EI-TOF): calcd.
for C23H24O4 [M]+ 364.1675; found 364.1680.
2-Hydroxy-5,5-dimethyl-2-(3-oxo-3-phenyl-1-p-tolylpropyl)cyclohex-
ane-1,3-dione (6b): According to general procedure C, Michael ad-
duct 3b (72.5 mg, 0.2 mmol) was employed. Column chromatog-
4436
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4429–4438

Products from the Reaction of Dimedone with Chalcones
ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.2, 204.2, 197.2, Michael adduct 3i (83.5 mg, 0.2 mmol) was employed. Column
138.4, 136.2, 133.8, 132.9, 132.4, 130.8, 130.6, 128.8 (2 C), 128.2 (2
C), 128.0, 91.3, 51.8, 51.6, 46.2, 39.9, 31.7, 30.8, 26.4 ppm. FTIR
chromatography gave 6i as a white solid (81.5 mg, 94%). 1H NMR
(300 MHz, CDCl3): δ = 0.77 (s, 3 H, CH3), 1.31 (s, 3 H, CH3), 2.41
(KBr): ν = 3492, 2960, 1738, 1700, 1597, 1471, 1450, 1358, 1237, (dd, J = 13.5, 2.9 Hz, 1 H, CH2), 2.53 (dd, J = 14.4, 2.9 Hz, 1 H,
˜
1143, 1080, 1030, 1002, 829, 757, 688, 629 cm–1. HRMS (EI-TOF): CH2), 3.00 (d, J = 13.5 Hz, 1 H, CH2), 3.32 (dd, J = 18.6, 6.6 Hz,
calcd. for C23H22O435Cl2 [M]+ 432.0895; found 432.0890.
1 H, CH2), 3.37 (d, J = 14.4 Hz, 1 H, CH2), 3.49 (dd, J = 18.6,
5.4 Hz, 1 H, CH2), 4.05 (s, 1 H, OOH), 4.33 (t, J = 6.0 Hz, 1 H,
CH), 7.24 (d, J = 8.4 Hz, 2 H, ArH), 7.32 (d, J = 8.4 Hz, 2 H,
ArH), 7.40 (d, J = 8.7 Hz, 2 H, ArH), 7.82 (d, J = 8.7 Hz, 2 H,
ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.5, 204.3, 196.4,
140.3, 136.5, 134.6, 134.1, 129.9 (2 C), 129.6 (2 C), 129.1 (4C), 91.4,
2-Hydroxy-5,5-dimethyl-2-[1-(3-nitrophenyl)-3-oxo-3-phenyl-
propyl]cyclohexane-1,3-dione (6f): According to general pro-
cedure C, Michael adduct 3f (78.7 mg, 0.2 mmol) was employed.
Column chromatography gave 6f as a yellow solid (73.7 mg, 90%).
1H NMR (300 MHz, CDCl3): δ = 0.78 (s, 3 H, CH3), 1.34 (s, 3 H,
CH3), 2.44 (dd, J = 13.6, 2.8 Hz, 1 H, CH2), 2.57 (dd, J = 14.5,
2.8 Hz, 1 H, CH2), 3.06 (d, J = 13.6 Hz, 1 H, CH2), 3.40 (d, J =
14.5 Hz, 1 H, CH2), 3.45 (dd, J = 18.7, 6.9 Hz, 1 H, CH2), 3.56
(dd, J = 18.7, 5.2 Hz, 1 H, CH2), 4.13 (s, 1 H, OH), 4.51 (t, J =
6.0 Hz, 1 H, CH), 7.41–7.50 (m, 3 H, ArH), 7.56 (t, J = 7.4 Hz, 1
H, ArH), 7.79 (d, J = 7.7 Hz, 1 H, ArH), 7.89 (d, J = 7.3 Hz, 2 H,
51.8, 51.7, 46.5, 40.0, 31.6, 30.8, 26.5 ppm. FTIR (KBr): ν = 3500,
˜
2962, 2948, 1734, 1692, 1590, 1491, 1404, 1357, 1342, 1236, 1203,
1173, 1144, 1095, 1080, 1016, 999, 970, 830, 760, 674, 621,
520 cm–1. HRMS (EI-TOF): calcd. for C23H22O435Cl2 [M]+
432.0866; found 432.0890.
X-ray Crystallographic Analysis of 6d:[11–13] Compound 6d was
crystallized as white crystals from EtOAc with the diffusion of pe-
troleum ether at 0 °C in a refrigerator for two weeks. C23H22Cl2O4,
ArH), 8.10 (d, J = 8.1 Hz, 1 H, ArH), 8.28 (s, 1 H, ArH) ppm. 13
NMR (75 MHz, CDCl3): δ = 205.1, 204.2, 197.0, 148.4, 140.2,
136.1, 134.8, 133.9, 129.8, 128.9 (2 C), 128.3 (2 C), 123.8, 123.2,
91.2, 51.9, 51.6, 46.7, 39.8, 31.7, 30.8, 26.4 ppm. FTIR (KBr): ν =
3481, 3431, 2957, 2917, 1738, 1692, 1529, 1348, 1234, 1143, 1079,
817, 754, 737, 693 cm–1. HRMS (EI-TOF): calcd. for C23H23NO6
[M]+ 409.1525; found 409.1518.
C
¯
Mr = 433.31, T = 291(2) K, triclinic, space group P1, a =
10.9377(5) Å, b = 10.9571(5) Å, c = 11.0854(6) Å, α = 67.781(5)°,
˜
β = 61.343(5)°, γ = 86.701(6)°, V = 1066.63(9) Å3, Z = 2, ρcalcd.
=
1.349 gcm–3, crystal size: 0.50ϫ0.40ϫ0.40 mm, F(000) = 452,
μ(Mo-Kα) = 0.331 mm–1, min. transmission 0.8521, max. trans-
mission: 0.8791, 2θmax. = 52.04°, 8824/4198 measured/independent
reflections [R(int) = 0.0184], 3196/266 reflections used/number of
parameters, refinement against |F|, GOF = 1.067, final R indices
were R1 = 0.0333 [I Ͼ 2σ(I)] and wR2 = 0.0877 [I Ͼ 2σ(I)]. Mo-
Kα radiation (λ = 0.71073). The data collection routine, unit-cell
refinement, and data processing were carried out with the program
CrysAlis.[11] The structure was solved by direct methods and re-
fined by full-matrix least-squares methods with the SHELXL-97
programs.[12]
2-Hydroxy-5,5-dimethyl-2-[1-(4-nitrophenyl)-3-oxo-3-phenyl-
propyl]cyclohexane-1,3-dione (6g): According to general pro-
cedure C, Michael adduct 3g (78.7 mg, 0.2 mmol) was employed.
Column chromatography gave 6g as a yellow solid (76.2 mg, 93%).
1H NMR (300 MHz, CDCl3): δ = 0.79 (s, 3 H, CH3), 1.34 (s, 3 H,
CH3), 2.44 (dd, J = 13.6, 2.8 Hz, 1 H, CH2), 2.58 (dd, J = 14.4,
2.8 Hz, 1 H, CH2), 3.02 (d, J = 13.6 Hz, 1 H, CH2), 3.39 (d, J =
14.4 Hz, 1 H, CH2), 3.43 (dd, J = 18.8, 6.9 Hz, 1 H, CH2), 3.54
(dd, J = 18.8, 5.2 Hz, 1 H, CH2), 4.12 (s, 1 H, OH), 4.48 (t, J =
6.0 Hz, 1 H, CH), 7.44 (t, J = 7.6 Hz, 2 H, ArH), 7.57 (t, J =
7.8 Hz, 1 H, ArH), 7.61 (d, J = 8.8 Hz, 2 H, ArH), 7.88 (t, J =
7.8 Hz, 2 H, ArH), 8.14 (d, J = 8.8, Hz, 2 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 205.1, 204.0, 197.0, 147.7, 145.5, 134.8,
134.0, 129.7 (2 C), 128.9 (2 C), 128.2 (2 C), 124.0 (2 C), 91.2, 51.9,
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H and 13C NMR spectra of compounds 3a–i, 4a,
5a–i, and 6a–i.
Acknowledgments
51.6, 46.8, 39.8, 31.7, 30.8, 26.4 ppm. FTIR (KBr): ν = 3490, 2952,
˜
1732, 1693, 1596, 1515, 1449, 1353, 1237, 1143, 1080, 1002, 970,
873, 859, 752, 686 cm–1. HRMS (EI-TOF): calcd. for C23H23NO6
[M]+ 409.1525; found 409.1530.
We are grateful for financial support from the Knowledge
Innovation Project of the Chinese Academy of Sciences
(KJCX2.YW.H16), the National Natural Science Foundation of
China (20772117, 91021004), the National Basic Research Program
of China (2011CB921402), and the Natural Science Foundation of
Anhui Province Education Department (KJ2010B049).
2-[3-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-oxopropyl]-2-hydroxy-
5,5-dimethylcyclohexane-1,3-dione (6h): According to general pro-
cedure C, Michael adduct 3h (82.6 mg, 0.2 mmol) was employed.
Column chromatography gave 6h as a white solid (81.5 mg, 95%).
1H NMR (300 MHz, CDCl3): δ = 0.77 (s, 3 H, CH3), 1.31 (s, 3 H,
CH3), 2.40 (dd, J = 13.5, 2.7 Hz, 1 H, CH2), 2.53 (dd, J = 14.4,
2.7 Hz, 1 H, CH2), 3.03 (d, J = 13.5 Hz, 1 H, CH2), 3.34 (dd, J =
18.3, 7.5 Hz, 1 H, CH2), 3.40 (d, J = 14.4 Hz, 1 H, CH2), 3.41 (dd,
J = 18.3, 4.2 Hz, 1 H, CH2), 3.85 (s, 3 H, OCH3), 4.07 (s, 1 H,
OH), 4.36 (t, J = 5.9 Hz, 1 H, CH), 6.89 (d, J = 8.6 Hz, 2 H, ArH),
7.24 (d, J = 8.7 Hz, 2 H, ArH), 7.33 (d, J = 8.6 Hz, 2 H, ArH),
7.85 (d, J = 8.7 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3):
δ = 205.5, 204.4, 195.9, 164.0, 136.8, 134.0, 130.6 (2 C), 130.0 (2
C), 129.5, 129.0 (2 C), 113.9 (2 C), 91.7, 55.6, 51.8, 51.7, 46.7, 39.6,
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4437

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Received: March 18, 2011
Published Online: June 15, 2011
4438
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4429–4438