Controllable single- or double-oxa-Michael addition of ynones with alcohols: Synthesis of 3-alkoxyprop-2-en-1-ones and 3,3-dialkoxypropan-1-ones

Article abstract of DOI:10.1016/j.tet.2018.09.054

Single- or double-oxa-Michael addition of ynones with various alcohols was achieved at room temperature. (E)-3-Alkoxyprop-2-en-1-ones and 3,3-dialkoxypropan-1-ones were efficiently synthesized by time-controlling approach. This protocol has advantages of

Full text of DOI:10.1016/j.tet.2018.09.054

Accepted Manuscript
Controllable single- or double-oxa-Michael addition of ynones with alcohols: Synthesis
of 3-alkoxyprop-2-en-1-ones and 3,3-dialkoxypropan-1-ones
Zheng Li, Jiaojiao He, Xiao Chen, Ya Cheng, Jingya Yang
PII:
S0040-4020(18)31165-7
10.1016/j.tet.2018.09.054
TET 29826
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 July 2018
Revised Date: 13 September 2018
Accepted Date: 28 September 2018
Please cite this article as: Li Z, He J, Chen X, Cheng Y, Yang J, Controllable single- or double-
oxa-Michael addition of ynones with alcohols: Synthesis of 3-alkoxyprop-2-en-1-ones and 3,3-
dialkoxypropan-1-ones, Tetrahedron (2018), doi: https://doi.org/10.1016/j.tet.2018.09.054.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Controllable Single- or Double-oxa-Michael Addition of Ynones with
Alcohols:
Synthesis
of
3-Alkoxyprop-2-en-1-ones
and
3,3-Dialkoxypropan-1-ones
Zheng Li,* Jiaojiao He, Xiao Chen, Ya Cheng, Jingya Yang
College of Chemistry and Chemical Engineering, Northwest Normal University,
Lanzhou, Gansu, 730070, P. R. China. E-mail: lizheng@nwnu.edu.cn (Z. Li)
Abstract: Single- or double-oxa-Michael addition of ynones with various alcohols
was achieved at room temperature. (E)-3-Alkoxyprop-2-en-1-ones and
3,3-dialkoxypropan-1-ones were efficiently synthesized by time-controlling approach.
This protocol has advantages of wide range of substrates, no transition metal catalyst,
mild condition, high yield and high stereoselectivity.
Keywords: ynone, alcohol, oxa-Michael addition, (E)-3-alkoxyprop-2-en-1-one,
3,3-dialkoxypropan-1-one
1. Introduction
3-Alkoxyprop-2-en-1-ones as important building blocks in organic synthesis
have attracted much attention, which can be used as versatile intermediates for the
construction of various fine chemicals.1 Numerous methods have been developed for
the formation of 3-alkoxyprop-2-en-1-ones in literatures (Scheme 1). For example, the
1

ACCEPTED MANUSCRIPT
typical methods for the preparation of 3-methoxyprop-2-en-1-one include i) the
ytterbium triflate catalyzed reaction of β-diketone with methanol;2 ii) the substitution
reaction of 2-ethylthio-1-alkenyl ketone with sodium methoxide in methanol and
benzene;3 iii) the reaction of α,β-dibromoketone with sodium methoxide in methanol.4
In addition, some other methods also reported for analogues of
3-methoxyprop-2-en-1-one.5 However, these methods often suffer from major or
minor limitations, such as drastic reaction conditions, low yields, tedious work-up
procedures and co-occurrence of several side reactions. Therefore, the development of
more efficient routes which use more suitable materials is still desirable.
3,3-Dialkoxypropan-1-ones as precursors of β-diketones may play an important
role in organic synthesis. However, the reports related to their preparations are very
scarce. Therefore the exploration for the efficient synthetic methods is quite
necessary.
Previous work
O
O
Yb(OTf)3
MeOH
MeONa
MeONa
+
r.t., 12 h, 76%
SEt O
O
MeOH/C6H6
+
r.t., 15 h, 27%
MeO
Br
O
MeOH
+
Br
O
This work
O
R1
R3O
R2
NaOH, r.t., 0.5 h
Single oxa-Michael addition
H
R1
+ R3OH
R1
O
R2
R3O
R3O
NaOH, r.t., 6 h
R2
Double oxa-Michael addition
H H
Scheme 1 Preparation of 3-alkoxyprop-2-en-1-ones and 3,3-dialkoxypropan-1-ones
2

ACCEPTED MANUSCRIPT
In this paper, we report an efficient method to controllably synthesize
(E)-3-alkoxyprop-2-en-1-ones and 3,3-dialkoxypropan-1-ones through single- or
double-oxa-Michael addition of ynones with various alcohols at room temperature
under transition metal-free and mild condition.
2. Results and Discussion
Initially, the reaction of 1,3-diphenylprop-2-yn-1-one (1a) with methanol, which
was used as both reactant and solvent, as a model reaction was attempted at room
temperature, but no any products were observed (Table 1, entry 1). Then 1 equiv of
t-BuOLi as a base was added. After the mixture was stirred at room temperature for
0.5 h, two kinds of products were isolated, which were identified as
(E)-3-methoxy-1,3-diphenylprop-2-en-1-one (2a) as a major product in 69% and
3,3-dimethoxy-1,3-diphenylpropan-1-one (3a) as a minor product in 12% (Table 1,
entry 2). The similar result was also obtained using MeONa as a base (Table 1, entry
3). The stereochemical structure of 2a was determined according to literature reports.1,
5a
No Z- isomer was observed. This implied that this reaction showed high
stereoselectivity for E- structure. In order to further improve the yield and selectivity
of 2a or 3a, the bases and reaction time were optimized. It was found that some
inorganic bases (Na2CO3, NaHCO3 and K2CO3) and organic bases (DMAP, Et3N,
DBU and DABCO) gave the desired products 2a and 3a in low yield (Table 1, entries
4−6 and 9−12). In contrast, KOH and NaOH as bases could give 2a in high yield after
the mixture was stirred for 0.5 h at room temperature (Table 1, entries 7, 8). The best
yield was obtained using NaOH as a base (Table 1, entry 8). Reaction time played an
important role in the reaction. When the reaction time was prolonged in the presence
of NaOH, the yield of 3a could be greatly improved (Table 1, entry 13). When the
reaction mixture was stirred at room temperature for 6 h, 3a as a major product could
be obtained in 82%. Meanwhile the yield for 2a as a minor product could be greatly
minimized (Table 1, entry 14). This result implied that the reaction selectivity for
products 2a and 3a could be realized by simply controlling reaction time. In addition,
3

ACCEPTED MANUSCRIPT
o
the yield of 3a at elevated temperature (65 C) could not further improve (Table 1,
entry 15).
Table 1 Optimization of reaction conditionsa
O
OMe
MeO
O
O
Base, r.t.
Time
H
+
+
MeOH
H
MeO
H
2a
1a
3a
Yield (%)b
Entry
Base
Time (h)
2a
0
3a
0
1
2
None
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2
t-BuOLi
MeONa
Na2CO3
NaHCO3
K2CO3
KOH
69
63
11
8
12
12
3
3
4
5
5
6
9
4
7
72
78
12
17
11
13
10
8
10
15
6
8
NaOH
DMAP
Et3N
9
10
11
12
13
14
15c
4
DBU
4
DABCO
NaOH
NaOH
NaOH
5
79
82
80
6
6
9
a Reaction conditions: ynone 1a (0.5 mmol), MeOH (2 mL) and base (0.5 mmol) at
room temperature for appropriate time.
b Isolated yield.
c At 65 oC.
4

ACCEPTED MANUSCRIPT
Based on the aforementioned findings, a series of reactions of ynones with
alcohols were examined for the single oxa-Michael addition at room temperature for
0.5 h using NaOH as a base. The reactions of ynones 1a-t with methanol could
proceed smoothly and produce corresponding (E)-3-methoxyprop-2-en-1ones 2a−t in
satisfactory yield (Table 2). The products were isolated only as E-isomers. It was
found that ynones bearing aromatic rings, heteroaromatic rings (furanyl and thienyl),
and cycloalkyls (cyclopropyl and cyclohexyl) could participate in single oxa-Michael
addition to give the corresponding products in good to high yield.
Table 2 Scope of single oxa-Michael addition of ynones 1a-t with methanol for the
synthesis of 2a-ta
5

ACCEPTED MANUSCRIPT
O
O
O
O
O
O
H
O
H
O
H
O
H
2d 62%
2c 72%
2a 78%
2b 75%
Br
O
O
O
O
O
F
Cl
O
H
O
H
O
H
O
H
2f 63%
2g 64%
2h 66%
2e 73%
O
O
O
O
O
CF3
Br
O
H
O
H
H
O
O
H
2j 67%
2k 76%
2l 56%
2i 70%
Bu
O
H
O
S
O
O
O
O
H
O
H
O
H
2m 46%
2n 54%
2o 76%
2p 73%
H3CO
F
Cl
O
O
O
O
O
H
H
O
O
H
O
H
2q 70%
2r 65%
2s 74%
2t 74%
a Reaction conditions: ynones 1a-t (0.5 mmol), MeOH (2 mL) and NaOH (0.5 mmol)
at room temperature for 0.5 h.
In addition, the reactions of ynone 1a with various alcohols were also examined
for the single oxa-Michael addition at room temperature for 0.5 h using NaOH as a
base (Table 3). The C2-5 alcohols could participate in the reactions with no obvious
carbon chain effect for the yield of products (2u-z). Benzyl alcohol could also give
the corresponding product in satisfactory yield (2y). Although isopropanol could
afford the corresponding product 2z in good yield, tertiary butanol could not undergo
the oxa-Michael addition probably because of the large steric hindrance. In addition, it
is worthy to mention that when phenol as analogue of alcohols was used to react with
1a in acetonitrile, Z-, E- configuration products (Z/E = 1:1) with a mixed yield of 55%
were obtained with no stereoselectivity (2*). This result may be caused by the
6

ACCEPTED MANUSCRIPT
mandatory usage of different solvent media.
Table 3 Scope of single oxa-Michael addition of ynone 1a with various alcohols for
the synthesis of 2u-za
a Reaction conditions: ynone 1a (0.5 mmol), alcohol (2 mL), and NaOH (0.5 mmol) at
room temperature for 0.5 h. b Phenol (0.5 mmol) in MeCN (2 mL) medium.
Double oxa-Michael addition of ynones with methanol to synthesize
3,3-dimethoxypropan-1-ones could be carried out at room temperature for 6 h using
NaOH as a base (Table 4). Ynones bearing aromatic rings and aromatic heterocyclic
ring (furanyl) could react with methanol to give the double oxa-Michael addition
products in high yield with no obvious differences (3a-f). However, when ethanol was
used as an alcohol to react with ynone 1a, only trace amount of the corresponding
o
double oxa-Michael addition product was observed at elevated temperature (60 C).
This result may be caused by the large steric hindrance due to the increase of carbon
chain of alcohols.
Table 4 Scope of double oxa-Michael addition of ynones with alcohols for the
7

ACCEPTED MANUSCRIPT
synthesis of 3a-fa
O
O
O
O
O
O
O
O
O
O
O
O
O
Cl
3a
3b
80%
82%
O
3d
78%
3c
76%
O
O
O
O
O
O
O
O
H3CO
Cl
Traceb
3e
75%
3f
75%
a
Reaction conditions: ynone (0.5 mmol), alcohol (2 mL) and NaOH (0.5 mmol) at
room temperature for 6 h. b At 60 oC for 8 h.
It is worthy to mention that the controlled synthesis of 2a and 3a could also be
performed on gram-scale and give the corresponding products in good yield (Scheme
2). The reaction of 1.03 g of 1a with 10 mL of methanol in the presence of 0.20 g of
NaOH was performed at room temperature for 0.5 h to give 2a in 55% yield (0.65 g)
isolated yield. If the reaction was prolonged to 6 h, 3a was obtained in 58% yield
(0.78 g). The success of this gram scale reaction further showed the potency of
optimized condition for the bulk processes.
8

ACCEPTED MANUSCRIPT
Scheme 2 Gram-scale synthesis of 2a and 3a
3. Conclusions
Single- or double-oxa-Michael addition of ynones with various alcohols at room
temperature has developed. (E)-3-Alkoxyprop-2-en-1-ones and
3,3-dialkoxypropan-1-ones were efficiently synthesized by time-controlling approach.
This protocol has advantages of wide range of substrates, no transition metal catalyst,
mild condition, high yield and high stereoselectivity, providing a practical and
versatile method for the synthesis of a wide range of 3-alkoxyenones and
3,3-dialkoxyketones.
4. Experimental
4.1. General Information
1H NMR and 13C NMR spectra were recorded on a Mercury-600 MB instrument
using DMSO-d6 as solvent and Me4Si as internal standard. Elemental analyses were
performed on a Vario El Elemental Analysis instrument. Melting points were
observed in an electrothermal melting point apparatus. Ynones were synthesized
according to literature method.6
4.2. Typical procedure for synthesis of 3-alkoxyprop-2-en-1-ones 2a-z
9

ACCEPTED MANUSCRIPT
The mixture of ynones (0.5 mmol), alcohol (2 mL) and sodium hydroxide (0.5
mmol) was stirred at room temperature for 0.5 h. The reaction progress was
monitored by TLC. After the completion of the reaction, the mixture was extracted
with ethyl acetate (3×10 mL), and the liquor was washed with saturated brine (3×10
mL). The resulting organic phase was dried over anhydrous sodium sulfate, and
concentrated under reduced pressure. The residue was isolated by column
chromatography using petroleum ether and ethyl acetate (v/v 8:1) as eluent to give
pure product. The analytical data for products are given below.
4.2.1. (E)-3-Methoxy-1,3-diphenylprop-2-en-1-one (2a)
Yellow oil (92 mg, 78%). 1H NMR (600 MHz, DMSO-d6): δ 7.90 (dd, J = 8.3, 1.4 Hz,
2H), 7.54 (t, J = 7.4 Hz, 1H), 7.48 – 7.42 (m, 2H), 7.40 – 7.28 (m, 4H), 6.38 (s, 1H),
3.92 (s, 3H). 13C NMR (150 MHz, DMSO-d6): δ 189.47, 171.00, 139.62, 135.99,
132.66, 129.92, 129.22, 128.86, 128.39, 128.12, 98.75, 57.32. Anal. Calcd. For
C16H14O2: C, 80.65; H, 5.92. Found: C, 80.58; H, 5.94.
4.2.2. (E)-3-Methoxy-3-phenyl-1-(m-tolyl)prop-2-en-1-one (2b)
Yellow oil (94 mg, 75%). 1H NMR (600 MHz, DMSO-d6): δ 7.72 (d, J = 1.6 Hz, 2H),
13
7.38 – 7.29 (m, 7H), 6.37 (s, 1H), 3.91 (s, 3H), 2.33 (s, 3H). C NMR (150 MHz,
DMSO-d6): δ 189.62, 170.80, 139.62, 138.16, 136.04, 133.25, 129.88, 129.20, 128.90,
128.75, 128.10, 125.63, 98.91, 57.29, 21.33. Anal. Calcd. For C17H16O2: C, 80.93; H,
6.39. Found: C, 80.98; H, 6.36.
4.2.3. (E)-3-Methoxy-3-phenyl-1-(p-tolyl)prop-2-en-1-one (2c)
Yellow oil (90 mg, 72%). 1H NMR (600 MHz, DMSO-d6): δ 7.82 (d, J = 8.2 Hz, 2H),
7.38 – 7.29 (m, 5H), 7.25 (d, J = 7.5 Hz, 2H), 6.37 (s, 1H), 3.90 (s, 3H), 2.33 (s, 3H).
13C NMR (150 MHz, DMSO-d6): δ 189.01, 170.55, 142.90, 137.03, 136.07, 129.84,
129.43, 129.19, 128.54, 128.10, 98.67, 57.22, 21.51. Anal. Calcd. For C17H16O2: C,
80.93; H, 6.39. Found: C, 80.85; H, 6.41.
4.2.4. (E)-3-Methoxy-1-(3-methoxyphenyl)-3-phenylprop-2-en-1-one (2d)
Yellow oil (83 mg, 62%). 1H NMR (600 MHz, DMSO-d6): δ 7.53 (d, J = 7.7 Hz, 1H),
7.40 – 7.29 (m, 7H), 7.11 (dd, J = 8.1, 2.8 Hz, 1H), 6.36 (s, 1H), 3.91 (s, 3H), 3.77 (s,
3H). 13C NMR (150 MHz, DMSO-d6): δ 189.13, 171.13, 159.74, 141.12, 136.01,
10

ACCEPTED MANUSCRIPT
130.00, 129.92, 129.20, 128.11, 120.91, 118.63, 113.08, 98.78, 57.35, 55.68. Anal.
Calcd. For C17H16O3: C, 76.10; H, 6.01; Found: C, 76.05; H, 6.03.
4.2.5. (E)-3-Methoxy-1-(4-methoxyphenyl)-3-phenylprop-2-en-1-one (2e)
Yellow oil (97 mg, 73%). 1H NMR (600 MHz, DMSO-d6): δ 7.90 (d, J = 8.8 Hz, 2H),
7.38 – 7.29 (m, 5H), 6.97 (d, J = 8.8 Hz, 2H), 6.35 (s, 1H), 3.89 (s, 3H), 3.80 (s, 3H).
13C NMR (150 MHz, DMSO-d6): δ 188.14, 169.97, 162.97, 136.15, 132.32, 130.67,
129.76, 129.17, 128.08, 114.07, 98.69, 57.15, 55.89. Anal. Calcd. For C17H16O3: C,
76.10; H, 6.01; Found: C, 76.17; H, 6.00.
4.2.6. (E)-1-(4-Fluorophenyl)-3-methoxy-3-phenylprop-2-en-1-one (2f)
1
Yellow oil (80 mg, 63%). H NMR (600 MHz, DMSO-d6): δ 8.00 – 7.95 (m, 2H),
7.39 – 7.35 (m, 1H), 7.34 – 7.29 (m, 4H), 7.28 – 7.23 (m, 2H), 6.37 (s, 1H), 3.92 (s,
13
3H). C NMR (150 MHz, DMSO-d6): δ 187.62, 170.69, 164.39 (d, J = 250.0 Hz),
135.71 (d, J = 2.6 Hz), 135.42, 130.77 (q, J = 8.4 Hz), 129.45, 128.70, 127.62, 115.25
(d, J = 21.7 Hz), 98.10, 56.87. Anal. Calcd. For C16H13FO2: C, 74.99; H, 5.11; Found:
C, 75.06; H, 5.09.
4.2.7. (E)-1-(4-Chlorophenyl)-3-methoxy-3-phenylprop-2-en-1-one (2g)
Yellow oil (87 mg, 64%). 1H NMR (600 MHz, DMSO-d6): δ 7.91 (d, J = 8.5 Hz, 2H),
7.50 (d, J = 8.5 Hz, 2H), 7.39 – 7.35 (m, 1H), 7.32 (dd, J = 7.6, 1.5 Hz, 4H), 6.36 (s,
1H), 3.92 (s, 3H). 13C NMR (150 MHz, DMSO-d6): δ 188.32, 171.58, 138.29, 137.50,
135.86, 130.33, 130.03, 129.23, 128.91, 128.15, 98.49, 57.45. Anal. Calcd. For
C16H13ClO2: C, 70.46; H, 4.80; Found: C, 70.40; H, 4.81.
4.2.8. (E)-1-(3-Bromophenyl)-3-methoxy-3-phenylprop-2-en-1-one (2h)
Yellow oil (100 mg, 66%). 1H NMR (600 MHz, DMSO-d6): δ 8.00 (t, J = 1.8 Hz, 1H),
7.89 (dt, J = 7.8, 1.3 Hz, 1H), 7.72 (ddd, J = 7.9, 2.0, 1.0 Hz, 1H), 7.42 – 7.35 (m, 2H),
13
7.35 – 7.29 (m, 4H), 6.36 (s, 1H), 3.93 (s, 3H). C NMR (150 MHz, DMSO-d6): δ
188.12, 172.05, 141.72, 135.84, 135.21, 131.08, 130.96, 130.10, 129.23, 128.17,
127.43, 122.35, 98.52, 57.60. Anal. Calcd. For C16H13BrO2: C, 60.59; H, 4.13; Found:
C, 60.64; H, 4.11.
4.2.9. (E)-1-(4-Bromophenyl)-3-methoxy-3-phenylprop-2-en-1-one (2i)
11

ACCEPTED MANUSCRIPT
1
Yellow oil (110 mg, 70%). H NMR (600 MHz, DMSO-d6): δ 7.83 (d, J = 8.5 Hz,
2H), 7.64 (d, J = 8.5 Hz, 2H), 7.41 – 7.35 (m, 1H), 7.35 – 7.29 (m, 4H), 6.35 (s, 1H),
3.92 (s, 3H). 13C NMR (150 MHz, DMSO-d6): δ 188.47, 171.61, 138.63, 135.85,
131.87, 130.48, 130.04, 129.23, 128.16, 126.59, 98.45, 57.46. Anal. Calcd. For
C16H13ClO2: C, 60.59; H, 4.13; Found: C, 60.54; H, 4.14.
4.2.10. (E)-3-Methoxy-3-phenyl-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-one (2j)
1
Yellow oil (102 mg, 67%). H NMR (600 MHz, DMSO-d6): δ 8.05 (d, J = 7.9 Hz,
13
2H), 7.79 (d, J = 8.2 Hz, 2H), 7.40 – 7.29 (m, 5H), 6.40 (s, 1H), 3.94 (s, 3H). C
NMR (150 MHz, DMSO-d6): δ 188.17, 171.82, 142.59, 135.19, 131.66, 131.45,
129.67, 128.78, 128.71, 127.68, 125.28 (q, J = 3.0 Hz), 98.21, 57.09. Anal. Calcd. For
C17H13F3O2: C, 66.67; H, 4.28; Found: C, 66.72; H, 4.26.
4.2.11. (E)-3-Methoxy-1-(naphthalen-2-yl)-3-phenylprop-2-en-1-one (2k)
Yellow oil (109 mg, 76%). 1H NMR (600 MHz, DMSO-d6): δ 8.64 (s, 1H), 8.09 (d, J
= 8.0 Hz, 1H), 7.97 – 7.90 (m, 3H), 7.64 – 7.56 (m, 2H), 7.40 – 7.33 (m, 3H), 7.31 (t,
J = 7.1 Hz, 2H), 6.56 (s, 1H), 3.98 (s, 3H). 13C NMR (150 MHz, DMSO-d6): δ 189.45,
170.93, 136.89, 136.07, 135.10, 132.67, 129.91, 129.82, 129.79, 129.24, 128.59,
128.46, 128.14, 128.02, 127.15, 124.54, 98.96, 57.41. Anal. Calcd. For C20H16O2: C,
83.31; H, 5.59; Found: C, 83.23; H, 5.62.
4.2.12. (E)-1-(Furan-2-yl)-3-methoxy-3-phenylprop-2-en-1-one (2l)
Yellow oil (64 mg, 56%). 1H NMR (600 MHz, DMSO-d6): δ 7.89 (dd, J = 1.8, 0.8 Hz,
1H), 7.44 – 7.30 (m, 6H), 6.66 (dd, J = 3.5, 1.7 Hz, 1H), 6.29 (s, 1H), 3.89 (s, 3H).
13C NMR (150 MHz, DMSO-d6): δ 176.76, 171.23, 154.03, 147.18, 135.79, 130.03,
129.23, 128.03, 117.03, 112.79, 97.44, 57.35. Anal. Calcd. For C14H12O3: C, 73.67; H,
5.30; Found: C, 73.59; H, 5.32.
4.2.13. (E)-3-Methoxy-3-phenyl-1-(thiophen-2-yl)prop-2-en-1-one (2m)
Yellow oil (56 mg, 46%). 1H NMR (600 MHz, DMSO-d6): δ 8.01 (dd, J = 3.8, 1.2 Hz,
1H), 7.87 (dd, J = 5.0, 1.1 Hz, 1H), 7.41 – 7.32 (m, 5H), 7.19 (q, J = 4.9, 3.8 Hz, 1H),
6.41 (s, 1H), 3.92 (s, 3H). 13C NMR (150 MHz, DMSO-d6): δ 181.40, 171.08, 147.45,
135.87, 134.18, 132.07, 129.97, 129.22, 128.86, 128.05, 97.86, 57.44. Anal. Calcd.
For C14H12O2S: C, 68.83; H, 4.95; Found: C, 68.78; H, 4.96.
12

ACCEPTED MANUSCRIPT
4.2.14. (E)-1-Cyclohexyl-3-methoxy-3-phenylprop-2-en-1-one (2n)
Yellow oil (65 mg, 54%). 1H NMR (600 MHz, DMSO-d6): δ 7.38 (t, J = 7.2 Hz, 1H),
7.33 (t, J = 7.5 Hz, 2H), 7.28 (dd, J = 8.3, 1.5 Hz, 2H), 5.77 (s, 1H), 3.76 (s, 3H), 2.29
13
(m, J = 11.0, 3.5 Hz, 1H), 1.77 – 1.64 (m, 4H), 1.22 – 1.11 (m, 6H). C NMR (150
MHz, DMSO-d6): δ 201.11, 169.31, 135.97, 129.81, 129.09, 128.05, 128.04, 100.70,
56.92, 50.80, 28.99, 25.97, 25.75. Anal. Calcd. For C16H20O2: C, 78.65; H, 8.25;
Found: C, 78.58; H, 8.28.
4.2.15. (E)-3-Methoxy-1-phenyl-3-(p-tolyl)prop-2-en-1-one (2o)
Yellow oil (95 mg, 76%). 1H NMR (600 MHz, DMSO-d6): δ 7.91 (dd, J = 8.2, 1.3 Hz,
2H), 7.54 (t, J = 7.3 Hz, 1H), 7.47 – 7.43 (m, 2H), 7.25 (d, J = 8.1 Hz, 2H), 7.12 (d, J
= 7.6 Hz, 2H), 6.34 (s, 1H), 3.90 (s, 3H), 2.29 (s, 3H). 13C NMR (150 MHz,
DMSO-d6): δ 189.44, 171.08, 139.76, 139.66, 133.02, 132.58, 129.25, 128.85, 128.66,
128.36, 98.44, 57.21, 21.37. Anal. Calcd. For C17H16O2: C, 80.93; H, 6.39. Found: C,
80.88; H, 6.40.
4.2.16. (E)-3-(4-butylphenyl)-3-methoxy-1-phenylprop-2-en-1-one (2p)
1
Yellow oil (107 mg, 73%). H NMR (600 MHz, DMSO-d6) δ 7.90 (dd, J = 8.2, 1.2
Hz, 2H), 7.52 (t, J = 7.3 Hz, 1H), 7.45 – 7.41 (m, 2H), 7.26 (d, J = 8.2 Hz, 2H), 7.11
(d, J = 8.2 Hz, 2H), 6.33 (s, 1H), 3.89 (s, 3H), 2.54 (t, J = 7.7 Hz, 2H), 1.51 (p, J = 7.6
Hz, 2H), 1.26 (h, J = 7.4 Hz, 2H), 0.86 (t, J = 7.4 Hz, 3H). 13C NMR (150 MHz,
DMSO-d6) δ 189.55, 171.11, 144.49, 139.74, 133.20, 132.52, 129.29, 128.79, 128.38,
127.96, 98.46, 57.20, 35.12, 33.34, 22.16, 14.18. Anal. Calcd. For C20H22O2: C, 81.60;
H, 7.53; Found: C, 81.54; H, 7.56.
4.2.17. (E)-3-methoxy-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (2q)
Yellow oil (93 mg, 70%). 1H NMR (600 MHz, DMSO-d6) δ 7.89 (d, J = 7.3 Hz, 2H),
7.53 (t, J = 7.3 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.32 (d, J = 8.7 Hz, 2H), 6.86 (d, J =
8.7 Hz, 2H), 6.30 (s, 1H), 3.89 (s, 3H), 3.74 (s, 3H). 13C NMR (150 MHz, DMSO-d6)
δ 189.41, 170.92, 160.86, 139.87, 132.53, 131.08, 128.84, 128.34, 127.83, 113.45,
97.93, 57.19, 55.62. Anal. Calcd. For C17H16O3: C, 76.10; H, 6.01; Found: C, 76.05;
H, 6.03.
4.2.18. (E)-3-(4-fluorophenyl)-3-methoxy-1-phenylprop-2-en-1-one (2r)
13

ACCEPTED MANUSCRIPT
Yellow oil (83 mg, 65%). 1H NMR (600 MHz, DMSO-d6) δ 7.91 (d, J = 6.9 Hz, 2H),
7.54 (t, J = 7.3 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.41 (dd, J = 8.8, 5.4 Hz, 2H), 7.14 (t,
J = 8.9 Hz, 2H), 6.40 (s, 1H), 3.91 (s, 3H). 13C NMR (150 MHz, DMSO-d6) δ 189.32,
170.04, 163.14 (d, J = 245.3 Hz), 139.57, 132.71, 132.31 (d, J = 3.3 Hz), 131.69 (d, J
= 8.5 Hz), 128.88, 128.40, 115.09 (d, J = 21.7 Hz), 98.73, 57.39. Anal. Calcd. For
C16H13FO2: C, 74.99; H, 5.11; Found: C, 75.06; H, 5.09.
4.2.19. (E)-3-(4-Chlorophenyl)-3-methoxy-1-phenylprop-2-en-1-one (2s)
Yellow oil (97 mg, 72%). 1H NMR (600 MHz, DMSO-d6): δ 7.92 (dd, J = 8.3, 1.3 Hz,
2H), 7.56 (t, J = 7.3 Hz, 1H), 7.49 – 7.44 (m, 2H), 7.42 – 7.32 (m, 4H), 6.44 (s, 1H),
3.92 (s, 3H). 13C NMR (150 MHz, DMSO-d6): δ 188.73, 169.32, 138.95, 134.33,
134.11, 132.29, 130.60, 128.40, 127.90, 127.74, 98.50, 56.98. Anal. Calcd. For
C16H13ClO2: C, 70.46; H, 4.80; Found: C, 70.50; H, 4.78.
4.2.20. (E)-3-cyclopropyl-3-methoxy-1-phenylprop-2-en-1-one (2t)
Yellow solid (75 mg, 74%). M.p. 92 oC. 1H NMR (600 MHz, DMSO-d6): δ 7.94 (dd,
J = 8.3, 1.4 Hz, 2H), 7.54 (t, J = 7.3 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 6.31 (s, 1H),
3.71 (s, 3H), 3.40 (tt, J = 8.3, 5.0 Hz, 1H), 0.94 – 0.90 (m, 2H), 0.85 – 0.82 (m, 2H).
13C NMR (150 MHz, DMSO-d6): δ 189.39, 176.97, 140.82, 132.20, 128.85, 127.91,
96.33, 56.34, 12.65, 8.19. Anal. Calcd. For C13H14O2: C, 77.20; H, 6.98; Found: C,
77.14; H, 7.00.
4.2.21. (E)-3-Ethoxy-1,3-diphenylprop-2-en-1-one (2u)
Yellow oil (98 mg, 78%). 1H NMR (600 MHz, DMSO-d6): δ 7.89 (dd, J = 8.3, 1.3 Hz,
2H), 7.53 (t, J = 7.3 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.38 – 7.29 (m, 5H), 6.36 (s,
1H), 4.17 (q, J = 7.0 Hz, 2H), 1.36 (t, J = 7.0 Hz, 3H). 13C NMR (150 MHz,
DMSO-d6): δ 189.46, 170.26, 139.70, 136.19, 132.58, 129.84, 129.25, 128.84, 128.36,
128.08, 99.09, 65.52, 14.59. Anal. Calcd. For C17H16O2: C, 80.93; H, 6.39; Found: C,
80.97; H, 6.38.
4.2.22. (E)-1,3-diphenyl-3-propoxyprop-2-en-1-one (2v)
1
Yellow oil (110 mg, 83%). H NMR (600 MHz, DMSO-d6): δ 7.89 (dd, J = 8.3, 1.3
Hz, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.44 (dd, J = 8.3, 7.2 Hz, 2H), 7.40 – 7.29 (m, 5H),
6.36 (s, 1H), 4.09 (t, J = 6.4 Hz, 2H), 1.80 – 1.73 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H).
14

ACCEPTED MANUSCRIPT
13C NMR (150 MHz, DMSO-d6): δ 189.45, 170.35, 139.67, 136.18, 132.60, 129.90,
129.22, 128.84, 128.36, 128.12, 99.09, 71.19, 22.12, 10.90. Anal. Calcd. For
C18H18O2: C, 81.17; H, 6.81; Found: C, 81.22; H, 6.78.
4.2.23. (E)-3-Butoxy-1,3-diphenylprop-2-en-1-one (2w)
1
Yellow oil (106 mg, 76%). H NMR (600 MHz, DMSO-d6): δ 7.89 (dd, J = 8.3, 1.4
Hz, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.47 – 7.42 (m, 2H), 7.39 – 7.28 (m, 5H), 6.37 (s,
1H), 4.12 (t, J = 6.4 Hz, 2H), 1.75 – 1.70 (m, 2H), 1.44 (m, 2H), 0.93 (t, J = 7.4 Hz,
3H). 13C NMR (150 MHz, DMSO-d6): δ 189.46, 170.37, 139.69, 136.20, 132.58,
129.87, 129.21, 128.83, 128.37, 128.11, 99.09, 69.45, 30.77, 19.25, 14.08. Anal.
Calcd. For C19H20O2: C, 81.40; H, 7.19; Found: C, 81.33; H, 7.22.
4.2.24. (E)-3-(pentyloxy)-1,3-diphenylprop-2-en-1-one (2x)
1
Yellow oil (108 mg, 74%). H NMR (600 MHz, DMSO-d6): δ 7.89 (dd, J = 8.3, 1.4
Hz, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.38 – 7.29 (m, 5H), 6.36 (s,
1H), 4.11 (t, J = 6.4 Hz, 2H), 1.77 – 1.72 (m, 2H), 1.43 – 1.37 (m, 2H), 1.36 – 1.31 (m,
2H), 0.88 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, DMSO-d6): δ 189.44, 170.36,
139.69, 136.20, 132.58, 129.87, 129.21, 128.83, 128.36, 128.12, 99.09, 69.73, 28.38,
28.17, 22.24, 14.29. Anal. Calcd. For C20H22O2: C, 81.60; H, 7.53; Found: C, 81.55;
H, 7.55.
4.2.25. (E)-3-(Benzyloxy)-1,3-diphenylprop-2-en-1-one (2y)
Yellow solid (108 mg, 70%). M.p. 94 oC. 1H NMR (600 MHz, DMSO-d6): δ 7.89 (dd,
J = 8.2, 1.3 Hz, 2H), 7.54 (t, J = 7.3 Hz, 1H), 7.50 (d, J = 6.8 Hz, 2H), 7.48 – 7.29 (m,
13
10H), 6.53 (s, 1H), 5.26 (s, 2H). C NMR (150 MHz, DMSO-d6): δ 189.51, 169.61,
139.57, 136.41, 135.95, 132.72, 129.98, 129.33, 129.00, 128.87, 128.62, 128.48,
128.42, 128.17, 100.08, 71.43. Anal. Calcd. For C22H18O2: C, 84.05; H, 5.77; Found:
C, 83.97; H, 5.79.
4.2.26. (E)-3-Isopropoxy-1,3-diphenylprop-2-en-1-one (2z)
Yellow solid (89 mg, 67%). M.p. 80 oC. 1H NMR (600 MHz, DMSO-d6): δ 7.86 (dd,
J = 8.2, 1.2 Hz, 2H), 7.52 (t, J = 7.4 Hz, 1H), 7.45 (t, 2H), 7.37 – 7.33 (m, 1H), 7.33 –
13
7.28 (m, 4H), 6.38 (s, 1H), 4.83 (m, 1H), 1.34 (d, J = 6.0 Hz, 6H). C NMR (150
MHz, DMSO-d6): δ 189.52, 169.12, 139.78, 136.55, 132.52, 129.75, 129.28, 128.84,
15

ACCEPTED MANUSCRIPT
128.31, 128.07, 99.64, 71.70, 21.82. Anal. Calcd. For C18H18O2: C, 81.17; H, 6.81;
Found: C, 81.23; H, 6.78.
4.3. Typical procedure for synthesis of 3-phenoxy-1,3-diphenylprop-2-en-1-one (2*)
The mixture of ynone 1a (0.5 mmol), phenol (0.5 mmol) and sodium hydroxide
(0.5 mmol) in 2 mL of acetonitrile was stirred at room temperature for 0.5 h. The
reaction progress was monitored by TLC. After the completion of the reaction, the
mixture was extracted with ethyl acetate (3×10 mL), and the liquor was washed with
saturated brine (3×10 mL). The resulting organic phase was dried over anhydrous
sodium sulfate, and concentrated under reduced pressure. The residue was isolated by
column chromatography using petroleum ether and ethyl acetate (v/v 8:1) as eluent to
give pure product. The analytical data for products are given below.
4.3.1. (Z)-3-Phenoxy-1,3-diphenylprop-2-en-1-one (2*-Z)
Yellow oil (19 mg, 23%). 1H NMR (600 MHz, DMSO-d6): δ 7.68 (d, J = 7.5 Hz, 2H),
7.56 – 7.44 (m, 6H), 7.39 (t, J = 7.6 Hz, 3H), 7.35 (t, J = 7.5 Hz, 2H), 7.30 (d, J = 7.8
Hz, 2H), 7.24 (t, J = 8.0 Hz, 1H), 6.12 (s, 1H).13C NMR (150 MHz, DMSO-d6): δ
190.00, 168.63, 154.45, 138.85, 134.07, 133.06, 130.72, 130.61, 129.76, 129.01,
128.37, 128.27, 125.91, 121.31, 105.53. Anal. Calcd. For C21H16O2: C, 83.98; H, 5.37;
Found: C, 84.05; H, 5.35.
4.3.2. (E)-3-Phenoxy-1,3-diphenylprop-2-en-1-one (2*-E)
Yellow oil (18 mg, 22%). 1H NMR (600 MHz, DMSO-d6): δ 7.97 (d, J = 7.5 Hz, 2H),
7.76 (dd, J = 7.6, 1.5 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.41
(q, J = 6.4 Hz, 3H), 7.35 (s, 1H), 7.20 (t, J = 7.9 Hz, 2H), 6.91 (t, J = 9.0 Hz, 3H).13C
NMR (150 MHz, DMSO-d6): δ 188.95, 159.65, 157.18, 138.53, 134.27, 133.35,
131.11, 129.98, 129.28, 129.06, 128.66, 127.72, 122.67, 116.80, 111.85. Anal. Calcd.
For C21H16O2: C, 83.98; H, 5.37; Found: C, 83.92; H, 5.39.
4.4. Typical procedure for synthesis of 3,3-dialkoxypropan-1-ones 3a-f
The mixture of ynones (0.5 mmol), alcohol (2 mL) and sodium hydroxide (0.5
mmol) was stirred at room temperature for 6 h. The reaction progress was monitored
by TLC. After the completion of the reaction, the mixture was extracted with ethyl
acetate (3×10 mL), and the liquor was washed with saturated brine (3×10 mL). The
16

ACCEPTED MANUSCRIPT
resulting organic phase was dried over anhydrous sodium sulfate, and concentrated
under reduced pressure. The residue was isolated by column chromatography using
petroleum ether and ethyl acetate (v/v 8:1) as eluent to give pure product. The
analytical data for products are given below.
4.4.1. (E)-3-Methoxy-1,3-diphenylprop-2-en-1-one (3a)
Yellow oil (110 mg, 82%).1H NMR (600 MHz, DMSO-d6): δ 7.64 (dd, J = 8.0, 1.1
Hz, 2H), 7.46 (t, J = 7.4 Hz, 1H), 7.38 – 7.34 (m, 2H), 7.33 – 7.27 (m, 2H), 7.20 (t, J
13
= 7.5 Hz, 2H), 7.14 (t, J = 7.3 Hz, 1H), 3.63 (s, 2H), 3.11 (s, 6H). C NMR (150
MHz, DMSO-d6): δ 196.18, 140.43, 137.76, 133.07, 128.65, 128.36, 128.08, 127.29,
101.94, 48.88, 45.45. Anal. Calcd. For C17H18O3: C, 75.53; H, 6.71; Found: C, 75.47;
H, 6.74.
4.4.2. 3,3-Dimethoxy-3-phenyl-1-(p-tolyl)propan-1-one (3b)
o
Yellow solid (112 mg, 80%). M.p. 52 C. 1H NMR (600 MHz, DMSO-d6): δ 7.55 (d,
J = 8.3 Hz, 2H), 7.38 – 7.34 (m, 2H), 7.21 (t, J = 7.4 Hz, 2H), 7.15 (t, J = 7.3 Hz, 1H),
7.11 (d, J = 7.9 Hz, 2H), 3.59 (s, 2H), 3.11 (s, 6H), 2.26 (s, 3H). 13C NMR (150 MHz,
DMSO-d6): δ 195.54, 143.38, 140.50, 135.33, 129.22, 128.52, 128.07, 128.04, 127.28,
101.98, 48.86, 45.29, 21.44. Anal. Calcd. For C18H20O3: C, 76.03; H, 7.09; Found: C,
75.96; H, 7.12.
4.4.3. 1-(4-Chlorophenyl)-3,3-dimethoxy-3-phenylpropan-1-one (3c)
1
Yellow oil (115 mg, 76%). H NMR (600 MHz, DMSO-d6): δ 7.63 (d, J = 8.5 Hz,
2H), 7.36 – 7.31 (m, 4H), 7.19 (t, J = 7.3 Hz, 2H), 7.14 (t, J = 7.2 Hz, 1H), 3.61 (s,
2H), 3.11 (s, 6H). 13C NMR (150 MHz, DMSO-d6): δ 195.35, 140.25, 138.04, 136.37,
130.30, 128.69, 128.13, 127.25, 101.88, 48.91, 45.63. Anal. Calcd. For C17H17ClO3: C,
67.00; H, 5.62; Found: C, 66.94; H, 5.64.
4.4.4. 1-(Furan-2-yl)-3,3-dimethoxy-3-phenylpropan-1-one (3d)
1
Yellow oil (101 mg, 78%). H NMR (600 MHz, DMSO-d6): δ 7.73 (dd, J = 1.6, 0.6
Hz, 1H), 7.36 (dd, J = 8.2, 1.1 Hz, 2H), 7.23 (t, J = 7.5 Hz, 2H), 7.18 (t, J = 1.3 Hz,
1H), 7.07 (dd, J = 3.6, 0.6 Hz, 1H), 6.46 (dd, J = 3.6, 1.5 Hz, 1H), 3.41 (s, 2H), 3.12
13
(s, 6H). C NMR (150 MHz, DMSO-d6): δ 183.66, 152.72, 148.03, 140.20, 128.17,
17

ACCEPTED MANUSCRIPT
128.14, 127.20, 119.25, 112.62, 101.92, 48.93, 45.52. Anal. Calcd. For C15H16O4: C,
69.22; H, 6.20; Found: C, 69.14; H, 6.22.
4.4.5. 3,3-Dimethoxy-3-(p-tolyl)-1-phenylpropan-1-one (3e)
1
Yellow oil (112 mg, 75%). H NMR (600 MHz, DMSO-d6): δ 7.65 (d, J = 7.8 Hz,
2H), 7.46 (t, J = 7.3 Hz, 1H), 7.31 (t, J = 7.7 Hz, 2H), 7.24 (d, J = 8.1 Hz, 2H), 7.00
(d, J = 8.0 Hz, 2H), 3.61 (s, 2H), 3.09 (s, 6H), 2.17 (s, 3H). 13C NMR (150 MHz,
DMSO-d6): δ 196.15, 137.78, 137.55, 137.15, 133.02, 128.65, 128.38, 127.22, 101.95,
48.77, 45.48, 21.01. Anal. Calcd. For C18H20O3: C, 76.03; H, 7.09; Found: C, 76.11;
H, 7.07.
4.4.6. 3-(4-Chlorophenyl)-3,3-dimethoxy-1-phenylpropan-1-one (3f)
1
Yellow oil (114 mg, 75%). H NMR (600 MHz, DMSO-d6): δ 7.69 (d, J = 8.1 Hz,
2H), 7.49 (t, J = 7.4 Hz, 1H), 7.39 – 7.31 (m, 4H), 7.26 (d, J = 8.6 Hz, 2H), 3.67 (s,
2H), 3.09 (s, 6H). 13C NMR (150 MHz, DMSO-d6): δ 196.04, 139.53, 137.60, 133.23,
132.83, 129.35, 128.74, 128.39, 128.07, 101.60, 48.89, 45.20. Anal. Calcd. For
C17H17ClO3: C, 67.00; H, 5.62; Found: C, 67.07; H, 5.60.
Acknowledgement
The authors thank the National Natural Science Foundation of China (21462038)
for the financial support of this work.
Appendix A. Supplementary data
Supplementary data related to this article can be found.
References
1. Chen W, Wang H, Zhang Y, Hu T, Jia J, Wu H. Tetrahedron Lett.
2017;58:3262–3266.
2. Curini M, Epifano F, Genovese S. Tetrahedron Lett. 2006; 47:4697–4700.
18

ACCEPTED MANUSCRIPT
3. Nishio T, Omote Y. Synthesis 1980;1013–1015.
4. El-Kattan Y, McAtee J. e-EROS Encyclopedia of Reagents for Organic Synthesis.
1–6, 2006.
5. (a) Mareev AV, Ushakov IA, Rulev AY. Tetrahedron 2015;71:1971–1974;
(b) Mansilla H, Afonso MM. Synth Commun. 2008;38:2607–2618;
(c) Clerici A, Pastori N, Porta O. Tetrahedron 2001;57: 217–225;
(d) Xie M, Zhang J, Ning P, Zhang Z, Liu X, Wang L. Tetrahedron Lett.
2014;55:1065–1067;
(e) Dehmlow EV, Kaiser M, Bollhöfer J. New J Chem. 2001; 25:588–590;
(f) Guarda EA, Marzari MRB, Frizzo CP, Guarda PM, Zanatta N, Bonacorso HG,
Martins MAP. Tetrahedron Lett. 2012; 53:170–172.
6. Palimkar SS, Kumar PH, Jogdand NR, Daniel T, Lahoti RJ, Srinivasan KV.
Tetrahedron Lett. 2006;47:5527–5530.
19