Different reaction patterns in the Baylis-Hillman reaction of aryl aldehydes with phenyl vinyl ketone, phenyl acrylate and phenyl thioacrylate

Article abstract of DOI:10.3390/71000721

In the Baylis-Hillman reaction of aryl aldehydes with phenyl vinyl ketone we have observed exclusive formation of diadducts 4, and that the yields of diadduct can reach 80% with increasing amounts of phenyl vinyl ketone. On the other hand, for phenyl acrylate and phenyl thioacrylate, only the normal Baylis-Hillman adduct was obtained. The effects of substituents were also examined and a plausible reaction mechanism is proposed for the formation of compounds 4.

Full text of DOI:10.3390/71000721

Molecules 2002, 7, 721-733
molecules
ISSN 1420-3049
http://www.mdpi.org
Different Reaction Patterns in the Baylis-Hillman Reaction of
Aryl Aldehydes with Phenyl Vinyl Ketone, Phenyl Acrylate and
Phenyl Thioacrylate
Min Shi*, Chao-Qun Li and Jian-Kang Jiang
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032 China, Fax: (+86)-21-64166128
*
Author to whom correspondence should be addressed; e-mail: mshi@pub.sioc.ac.cn
Received: 27 August 2002; in revised form: 10 October 2002 / Accepted: 11 October 2002 / Published:
1 October 2002
3
Abstract: In the Baylis-Hillman reaction of aryl aldehydes with phenyl vinyl ketone we
have observed exclusive formation of diadducts 4, and that the yields of diadduct can
reach 80% with increasing amounts of phenyl vinyl ketone. On the other hand, for phenyl
acrylate and phenyl thioacrylate, only the normal Baylis-Hillman adduct was obtained.
The effects of substituents were also examined and a plausible reaction mechanism is
proposed for the formation of compounds 4.
Keywords: Baylis-Hillman reaction; Lewis base; Phenyl vinyl ketone (PVK); Phenyl
acrylate; DABCO; Conjugate addition; DMAP.
Introduction
Great progress has been made in the implementation of the Baylis-Hillman reaction [1], since
Baylis and Hillman first reported in 1972 the reaction of acetaldehyde with ethyl acrylate and
acrylonitrile in the presence of catalytic amounts of 1,4-diazabicyclo[2,2,2]octane (DABCO) [2], and
even a catalytic asymmetric version has been published [3]. During our own investigations of this
simple and useful reaction [4], we found that in the reaction of aryl aldehydes with methyl vinyl ketone
(MVK) catalyzed by DABCO, the reaction products are not as simple as those reported before. For

Molecules 2002, 7
722
example, using p-nitrobenzaldehyde (1.0 eq) and MVK (2.0 eq) as substrates in the presence of
catalytic amounts of DABCO (0.1 eq) in DMSO or DMF, we found that, besides the normal Baylis-
Hillman reaction product 1a, compound 2a was also formed at the same time as a 2:3 mixture of syn-
and anti-isomers [5] (Scheme 1) and the substituent effects of aryl aldehydes were also examined in
detail [5].
Scheme 1
OH
CH
O
C
O
C
Lewis base
solvent
p-O NPh CHO
+
C
2
p-O NPh
Me
Me
2
Me
CH2
1a
O
OH
CHa
C
CHb
p-O NPh
2
O
+
H C
2
C
C
Me
CH2
2a
This interesting result stimulated us to further examine the influence of the R group of the Baylis-
Hillman acceptor [C=C-C(O)R] on this reaction. Thus, we synthesized phenyl vinyl ketone (PVK) [6],
phenyl acrylate [7], and phenyl thioacrylate [8] as the Baylis-Hillman acceptors and carefully examined
the reaction products formed under the traditional Baylis-Hillman reaction conditions.
Results and Discussion
We found that, in the reaction of p-nitrobenzaldehyde (1.0 eq.) with PVK (1.0 eq.) in the presence
of DABCO (10 mol-%) in DMF, the corresponding Baylis-Hillman adduct 3a (i.e., the normal Baylis-
Hillman adduct) was not formed at all. The major reaction product was a mixture of syn- and anti-
isomers of the 1:2 adduct 4a, along with some PVK dimer (Scheme 2). Of course, as expected, 4a was
obtained in higher yields when 1.0 eq. p-nitrobenzaldehyde and 2.0 eq. of PVK were used in the
presence of DABCO (10 mol-%). Results are summarized in Table 1. When the reaction was carried
out in DMSO, THF or dichloromethane (CH Cl ), similar results were obtained (Table 1, Entries 1-3).
2
2
Using 4-(dimethylamino)pyridine (DMAP) as the Lewis base under the same reaction conditions, 4a
was obtained in lower yields (Table 1, entries 4-5). Increasing the amounts of PVK did not improve the
o
yields of 4a (Table 1, Entries 6-7). At lower temperatures (-30 C), 4a was obtained in 70% yield
(
Table 1, Entry 9) and with PBu as the Lewis base, only traces of 4a were obtained. The optimized
3
reaction conditions were found to be reaction of 1.0 eq. aryl aldehyde with 2.0 eq. PVK in the presence
of 10 mol-% DABCO in DMF.

Molecules 2002, 7
723
Scheme 2
OH
CH
O
C
C
Ph
p-O NPh
2
CH2
3
a
O
C
Lewis base
solvent
p-O NPh CHO +
2
O
C
OH
CHa
Ph
Ph
O
O
p-O NPh
2
CHb
O
+
Ph
Ph
H C
CH2
PVK dimer
2
C
C
Ph
CH2
4a
Table 1. Baylis-Hillman reactions of p-nitrobenzaldehyde (1.0 eq.) with
phenyl vinyl ketone (2.0 eq.) in the presence of Lewis base (0.1 eq.).
Yield [%]a)
Temp.
Time
[h]
entry
solvent
Lewis base
o
4ae)
PVK dimer
[
C]
1
2
3
DABCO
DABCO
DABCO
DMSO
DMF
20
60
60
60
75
88
81
10
14
12
20
20
20
CH Cl2
2
4
DABCO
THF
60
78
65
16
5
6
7
8
9
DMAP
DMAP
DABCO
DABCO
PBu3
DMSO
20
60
60
21
20
11
13
36
8
DMF
20
20
20
20
-30
63
80
DMFb)
DMFc)
DMF
60
60
60
60
60
trace
70
1
0
DABCO
DMF
a)
c)
Isolated yields. b) Mole ratio of p-nitrobenzaldehyde:PVK= 1:3.0.
Mole ratio of p-nitrobenzaldehyde:PVK= 1:4. d) syn:anti= 2:3.
We next investigated the reactions of other aryl aldehydes with PVK under the optimized reaction
conditions (Scheme 3). With electron deficient aryl aldehydes, such as nitrobenzaldehydes or
pyridylaldehydes, the reaction proceeded smoothly to give 4 in good yields. However, with

Molecules 2002, 7
724
p-chlorobenzaldehyde or benzaldehyde, only trace amounts of the 1:2 adduct 4 were obtained and the
PVK dimer was formed almost exclusively (Scheme 3, Table 2) [7]. In all cases, the normal Baylis-
Hillman adduct 3 was not formed.
Scheme 3
OH
CH
O
C
O
O
O
C
Lewis base
Ph
R
R CHO
+
CH
+
Ph
Ph
O
o
CH2
Ph
DMF, 20 C
H C
2
C
C
Ph
PVK dimer
CH2
b: R= m-NO Ph, c: R= o-NO Ph, d: R=2-pyridyl,
4
2
2
e: R= 3-pyridyl, f: R= Ph, g: R= p-ClPh.
Table 2. Baylis-Hillman reactions of aryl aldehydes (1.0 eq) with phenyl
vinyl ketone (2.0 eq.) in the presence of DABCO (0.1 eq).
Time
h]
Yield [%]a)
entry
Lewis base
R
[
4b) PVK dimer
15
1
2
3
m-NO Ph
DABCO
DABCO
DABCO
60
76 (2:3)
79 (3:4)
82 (3:5)
2
6
0
0
16
20
o-NO Ph
2
2-pyridyl
7
70
81 (2:3)
trace
16
4
5
6
3
-pyridyl
Ph
DABCO
DABCO
DABCO
70
33
29
p-ClPh
70
trace
a)
Isolated yields. b)syn- and anti mixture.
On the other hand, the Baylis-Hillman reactions with phenyl acrylate or phenyl thioacrylate as an
acceptor were also examined (Schemes 4 and 5; results are summarized in Table 3). With phenyl
acrylate as the acceptor, the normal Baylis-Hillman adducts 5 was exclusively obtained in most cases
(Table 3, entries 1-2 and 4-8). Only in the reaction of o-nitrobenzaldehyde with phenyl acrylate, was
diadduct 6c formed in 29% (Table 3, Entry 3). However, with phenyl thioacrylate as a Baylis-Hillman
acceptor, only in the reaction of p-chlorobenzaldehyde with phenyl thioacrylate, the corresponding
Baylis-Hillman adduct 7 was obtained in good yield (Scheme 5). The reactions of other aryl aldehydes
with phenyl thioacrylate were either very sluggish or gave many unidentified products.

Molecules 2002, 7
725
Scheme 4
OH
CH
OH
CH
O
C
O
C
O
C
Lewis base
R CHO
+
+
o
R
C
OPh
OPh
R
OPh solvent, 20 C
CH
O
C
CH2
5
H C
2
C
OPh
a: R= p-NO Ph, b: R= m-NO Ph, c: R= o-NO Ph,
2
2
2
CH2
d: R= p-BrPh, e: R= p-ClPh, f: R= Ph, g: R= PhCH=CH,
6
h: R= 3-pyridyl.
Table 3. Baylis-Hillman reactions of aldehydes (1.0 eq) with phenyl
acrylate (2.0 eq) in the presence of Lewis base (0.1 eq).
Yield [%]a)
Time
entry
R
Lewis base
solvent
[
h]
5
6
1
2
3
p-NO Ph
DABCO
DABCO
DABCO
DMSO
DMF
40
40
40
75
0
2
m-NO Ph
74
53
0
2
o-NO Ph
DMF
29
2
p-BrPh
p-ClPh
Ph
DABCO
DABCO
DABCO
DMF
50
50
50
78
71
79
57
78
0
0
0
0
0
4
5
6
7
DMF
DMF
DMF
DMF
PhCH=CH
DABCO
DABCO
40
40
3
-pyridyl
8
a)
Isolated yields.
Scheme 5
OH
CH
O
C
O
O
O
C
DABCO
+
R CHO
+
SPh
o
R
C
PhS
SPh
SPh
DMF, 20 C
CH2
8
CH2
, 75%
7
R= p-ClPh,
To the best of our knowledge, the exclusive formation of a diadduct in the traditional Baylis-
Hillman reaction in which phenyl vinyl ketone (PVK) is used as the acceptor has never been disclosed
before. To clarify the mechanism of formation of 4, we carried out reactions of p-nitrobenzaldehyde

Molecules 2002, 7
726
(1.0 equiv.) with PVK dimer (1.0 equiv.) in the presence of catalytic amounts of DABCO (0.1 equiv.).
Since we found that no reaction occurred under these conditions (Scheme 6), we believe that the
diadduct 4 was derived from a second reaction of normal Baylis-Hillman adduct 3 with PVK because
we have already proven that the diadduct 2a can be obtained from the reaction of 1a with MVK in the
presence of DABCO (10 mol-%) in DMF (Scheme 6).
Scheme 6
O
O
DABCO
no reaction
p-O NPh CHO
+
2
Ph
Ph
DMSO or DMF, r.t
CH2
OH
CH
O
OH
CH
O
O
DABCO
C
Me
Me
C
+
p-O NC H
2 6
p-O NC H
Me
4
2
6
4
CH
O
Me
CH2
DMF, r.t
H C
C
2
1
a
CH2
2a
Scheme 7
N
N
O
C
Ar CHO
N
N
+
+
N
+
-
O
N
Ph
O
Ar
Ph
Ph
-
O
OH
O
N
N
CH
Ar
C
Ph
+
CH2
1
OH
CH
-
O
OH
CH
N
O
N
N
Ar
Ph
+
C
Ph
N
+
Ar
-
CH2
CH2
O
O
1
Ph
Ph
O
C
OH
CH
Ph
+
N
N
Ar
CH
O
H C
2
C
Ph
CH2
2

Molecules 2002, 7
727
In Scheme 7, we formulate a plausible reaction mechanism. Two reactions occur for the traditional
Baylis-Hillman reaction of aryl aldehydes with PVK. One is the normal Baylis-Hillman reaction, which
involves the 1,2-addition of the PVK-derived anion to p-nitrobenzaldehyde. Another is the conjugated
addition (Michael addition) of the anion derived from a second molecule of PVK to 3 via intermediate
4’ (Scheme 7). Thus, the normal Baylis-Hillman adduct 3 formed can more easily undergo the next
conjugate addition (Michael addition) of the anion derived from a second molecule of PVK to afford
exclusively the diadduct 4.
Conclusions
We have found that a diadduct 4 was formed exclusively in the Baylis-Hillman reaction of aryl
aldehydes with phenyl vinyl ketone (PVK). It was confirmed the 4 was derived from a second reaction
of the normal Baylis-Hillman adduct with PVK via a conjugate addition reaction. On the other hand,
with phenyl acrylate or phenyl thioacrylate as acceptors, only the normal Baylis-Hillman reaction
products were produced. Efforts are currently underway to further elucidate the mechanistic details of
this reaction and to disclose its scope and limitations.
Acknowledgements
We thank the State Key Project of Basic Research (Project 973) (No. G2000048007) and the
National Natural Science Foundation of China for financial support (20025206). We also thank the
Inoue Photochirogenesis Project (ERATO, JST) for the donation of chemical reagents.
Experimental
General
1
IR spectra were recorded on a Nicolet AV-360 spectrometer. H-NMR spectra (300 MHz) were
recorded for CDCl solutions on a Bruker AM-300 spectrometer with tetramethylsilane (TMS) as
3
internal standard; J-values are in Hz. Mass spectra were recorded with a HP-5989 instrument and
HRMS were measured on a Finnigan MA+ mass spectrometer. Organic solvents were dried by
standard methods when necessary. Commercially obtained reagents were used without further
purification. All reactions were monitored by TLC using Huanghai GF254 silica gel coated plates. Flash
Column Chromatography was carried out using 200-300 mesh silica gel under pressure. The syn- and
1
anti-isomers of 4 were not separable, thus, the ratios of syn and anti isomers are determined from H-
NMR spectroscopic data and their HRMS data were obtained from anti- and syn-mixtures as well.

Molecules 2002, 7
728
Preparation of phenyl vinyl ketone.
The phenyl vinyl ketone starting material was prepared according to Scheme 8 [6].
Scheme 8
O
O
Steam distillation
+
Me N
3
Ph
Ph
Cl-
o
A solution of the ammonium salt (5 g) in water (200 mL) was distilled at 90 C. The distillate was
extracted with ether (3 x 20 mL) and the organic layer was dried over anhydrous Na SO . The solvent
2
4
was removed under reduced pressure and residue was purified by flash silica gel chromatography
(
eluent: ethyl acetate/petroleum ether = 1/10) to give phenyl vinyl ketone (PVK) (1.6 g, 30%) as a
1
colorless oil; H-NMR: δ 5.94 (1H, dd, J = 10.5, 1.8 Hz, =CH), 6.45 (1H, dd, J = 16.8, 1.8 Hz, =CH),
7.17 (1H, dd, J = 16.8, 10.5 Hz, =CH), 7.46-7.51 (2H, m, Ar), 7.56-7.59 (1H, m, Ar), 7.94-7.97 (2H, m,
Ar).
Preparation of phenyl acrylate.
The phenyl acrylate starting material was prepared according to Scheme 9 [7]. Acroylchloride (7.28
g, 80 mmol) in dichloromethane (10 mL) was added within 0.5 h. to a solution of phenol (7.5 g, 80
mmol) and triethylamine (10.1 g, 100 mmol) in dichloromethane (20 mL).
Scheme 9
OH
O
O
Et N
3
+
CH Cl2
Cl
2
O
The reaction mixture was stirred at room temperature for 24 h, then washed with water (2 x 30 mL)
and extracted with dichloromethane (2 x 10 mL). The organic layer was dried over anhydrous Na SO .
2
4
The solvent was removed under reduced pressure and residue was purified by flash silica gel
chromatography (eluent: petroleum ether) to give phenyl acrylate (9.0 g, 76%) as a colorless oil;
1
H-NMR: δ 6.00 (1H, d, J = 11.1 Hz, =CH), 6.32 (1H, dd, J = 17.1, 11.1 Hz, =CH), 6.60 (1H, d, J =
17.1 Hz, =CH), 7.11-7.14 (2H, m, Ar), 7.24-7.26 (1H, m, Ar), 7.37-7.42 (2H, m, Ar).
Typical reaction procedure for the Baylis-Hillman reaction.
Phenyl vinyl ketone (PVK) (138 mg, 1.0 mmol) was added to a solution of DABCO (6 mg, 0.05
mmol) and p-nitrobenzaldehyde (76 mg, 0.50 mmol) in DMF (0.50 mL) and the reaction mixture was
stirred at room temperature for 60 h. The reaction product was extracted with dichloromethane (10.0

Molecules 2002, 7
729
mL) and washed with water (10.0 mL x 3). The organic layer was dried over anhydrous MgSO , the
4
solvent was removed under reduced pressure and the residue was purified by flash silica gel column
chromatography (eluent: 1:4 ethyl acetate-petroleum ether) to give the product 4a (a 2:3 syn and anti
mixture, 180 mg, 88%) and PVK dimer (25 mg, 14%) as colorless oils. The syn and anti ratio of 4a
1
was determined from the H-NMR spectral data based on the J values of H and H (see Scheme 1)
a
b
because the anti-isomer usually shows a bigger J value (for anti-4a: JHaHb = 6.3 Hz, for syn-4a: JHaHb
=
2.8 Hz).
2
-[Hydroxy-(4-nitrophenyl)methyl]-4-methylene-1,5-diphenylpentane-1,5-dione (4a): syn-4a: IR
-1
1
(KBr): ν 1649 and 1668 cm (C=O); H-NMR: δ 2.86-2.93 (2H, m, CH ), 4.09 (1H, d, J = 2.6 Hz,
2
OH), 4.20-4.30 (1H, m, CH), 5.16 (1H, dd, J = 4.8, 2.6 Hz, CH), 5.55 (1H, s), 5.82 (1H, s), 7.20-7.60
+
(
10H, m, Ar), 7.87 (2H, d, J = 8.6 Hz, Ar), 8.10 (2H, d, J = 8.6 Hz, Ar); EI-MS: m/e 397 (M -18, 0.2),
+
+
+
3
78 (M -37, 0.2), 159 (M -256, 50.1), 105 (M -310, 100); HRMS: C H O requires 264.1150,
1
8
16
2
+
-1
1
found: (EI) m/z 264.1135 (M -151.0270); anti-4a: IR (KBr): ν 1649 and 1668 cm (C=O); H-NMR: δ
2
.93-3.10 (2H, m, CH ), 4.30-4.40 (1H, m, CH), 4.42 (1H, d, J = 8.2 Hz, OH), 5.06 (1H, dd, J = 8.2,
2
4
.6 Hz, CH), 5.74 (1H, s), 6.07 (1H, s), 7.20-7.60 (10H, m, Ar), 7.87 (2H, d, J = 8.6 Hz, Ar), 8.10 (2H,
+
+
+
+
d, J = 8.6 Hz, Ar); EI-MS: m/e 397 (M -18, 0.2), 378 (M -37, 0.2), 159 (M -256, 50.1), 105 (M -310,
+
1
00); HRMS: C H O requires 264.1150, found: (EI) m/z 264.1135 (M -151.0270).
1
8
16
2
4
-Methylene-1,5-diphenylpentane-1,5-dione (PVK dimer): a colorless oil; IR (KBr): ν 1650 and 1680
-1
1
cm (C=O); H-NMR: δ 2.91 (2H, t, J = 7.3 Hz, CH ), 3.23 (2H, t, J = 7.3 Hz, CH ), 5.67 (1H, s), 5.96
2
2
+
(1H, s), 7.30-7.55 (6H, m, Ar), 7.70-7.75 (2H, m, Ar), 7.90-8.0 (2H, m, Ar); EI-MS: m/e 264 (M , 1.0),
+
+
+
159 (M -105, 63.8), 105 (M -159, 100), 77 (M -187, 54.2); HRMS: C H O requires 264.1150,
18 16 2
+
found: (EI) m/z 264.1185 (M ).
2
-[Hydroxy-(3-nitrophenyl)methyl]-4-methylene-1,5-diphenylpentane-1,5-dione (4b) (syn- and anti-
-1
1
mixture= 2:3): syn-4b: a colorless oil; IR (KBr): ν 1645, 1675 cm (C=O); H-NMR: δ 2.90-3.0 (1H,
m, CH ), 3.10 (1H, dd, J = 13.7, 8.6 Hz, CH ), 4.09 (1H, d, J = 2.6 Hz, OH), 4.20-4.30 (1H, m), 5.17
2
2
(
1H, dd, J = 2.6, 2.6 Hz), 5.56 (1H, s, CH), 5.82 (1H, s, CH), 7.20-7.52 (9H, m, Ar), 7.55-7.82 (1H, m,
+
Ar), 7.83-7.95 (2H, m, Ar), 8.0-8.08 (1H, m, Ar), 8.33 (1H, s, Ar); EI-MS: m/e 397 (M -18, 0.12), 378
+
+
+
(
(
(
M -37, 1.0), 159 (M -256, 55.0), 105 (M -310, 100); HRMS: C H NO requires 415.1420, found:
25 21 5
+
-1
1
EI) m/z 415.1431 (M ); anti-4b: a colorless oil; IR (KBr): ν 1645, 1675 cm (C=O); H-NMR: δ 2.95
2H, dd, J = 14.2 7.4 Hz, CH ), 4.32 (1H, d, J = 5.2 Hz, OH), 4.38-4.45 (1H, m, CH), 5.12 (1H, dd, J =
2
5
7
1
4
.2 2.0 Hz), 5.73 (1H, s, CH), 6.07 (1H, s, CH), 7.20-7.52 (9H, m, Ar), 7.55-7.82 (1H, m, Ar), 7.83-
+
+
.95 (2H, m, Ar), 8.0-8.08 (1H, m, Ar), 8.24 (1H, s, Ar); EI-MS: m/e 397 (M -18, 0.12), 378 (M -37,
+
+
.0), 159 (M -256, 55.0), 105 (M -310, 100); HRMS: C H NO requires 415.1420, found: (EI) m/z
2
5
21
5
+
15.1431 (M ).

Molecules 2002, 7
730
2
-[Hydroxy-(2-nitrophenyl)methyl]-4-methylene-1,5-diphenylpentane-1,5-dione (4c) (syn- and anti-
-1
1
mixture = 3:4): syn-4c: a colorless oil; IR (KBr): ν 1645, 1675 cm (C=O); H-NMR: δ 2.85 (1H, dd, J
13.4 4.3 Hz, CH), 3.01 (1H, dd, J = 13.4, 6.5 Hz, CH), 4.33 (1H, s, OH), 4.40-5.02 (1H, m, CH),
.47 (1H, s, CH), 5.74 (1H, d, J = 2.4 Hz, CH), 5.79 (1H, s, CH), 7.10-7.80 (12H, m, Ar), 7.98 (1H, d,
=
5
+
+
J = 8.6 Hz, Ar), 8.02 (1H, dd, J = 8.0 7.3 Hz, Ar); EI-MS: m/e 378 (M -37, 0.6), 264 (M -151, 7.6),
+
+
159 (M -256, 63.5), 105 (M -310, 100); HRMS: C H NO requires 415.1420, found: (EI) m/z
25 21 5
+
-1
1
415.1233 (M ); anti-4c: a colorless oil; IR (KBr): ν 1645, 1675 cm (C=O); H-NMR: δ 2.99 (2H, dd,
J = 13.7 10.0 Hz, CH ), 4.40-5.02 (1H, m, CH), 4.94 (1H, d, J = 8.5 Hz, OH), 5.61 (1H, dd, J = 4.3, 3.8
2
Hz, CH), 5.88 (1H, s, CH), 6.20 (1H, s, CH), 7.10-7.80 (12H, m, Ar), 7.81 (1H, d, J = 8.6 Hz, Ar), 7.88
+
+
+
(
1H, d, J = 8.6 Hz, Ar); EI-MS: m/e 378 (M -37, 0.6), 264 (M -151, 7.6), 159 (M -256, 63.5), 105
+
+
(
M -310, 100); HRMS: C H NO requires 415.1420, found: (EI) m/z 415.1233 (M ).
2
5
21
5
2
-(Hydroxy-pyridin-2-yl-methyl)-4-methylene-1,5-diphenylpentane-1,5-dione (4d) (syn- and anti-
-1
1
mixture= 3:5): syn-4d: a colorless oil; IR (KBr): ν 1645, 1675 cm (C=O); H-NMR: δ 2.90-3.05 (2H,
m, CH), 4.30-4.41 (1H, m, CH), 4.53 (1H, d, J = 3.2 Hz, OH), 5.02 (1H, t, J = 4.2 Hz, CH), 5.48 (1H,
s, CH), 5.83 (1H, s, CH), 7.0-7.70 (11H, m, Ar), 7.80-7.92 (2H, m, Ar), 8.47 (1H, d, J = 4.7 Hz, Ar);
+
+
+
EI-MS: m/e 264 (M -107, 4.8), 159 (M -212, 67.5), 105 (M -266, 100); HRMS: C H O requires
1
8
16
2
+
264.1150, found: (EI) m/z 264.1129 (M -107.0371); anti-4d: a colorless oil; IR (KBr): ν 1645, 1675
-1
1
cm (C=O); H-NMR: δ 2.90-3.05 (2H, m, CH), 4.30-4.41 (1H, m, CH), 4.52 (1H, br., s, OH), 5.10
1H, t, J = 5.1 Hz, CH), 5.67 (1H, s, CH), 6.03 (1H, s, CH), 7.0-7.70 (11H, m, Ar), 7.80-7.92 (2H, m,
(
+
+
+
Ar), 8.38 (1H, d, J = 4.7 Hz, Ar); EI-MS: m/e 264 (M -107, 4.8), 159 (M -212, 67.5), 105 (M -266,
+
1
00); HRMS: C H O requires 264.1150, found: (EI) m/z 264.1129 (M -107.0371).
1
8
16
2
2
-(Hydroxy-pyridin-3-yl-methyl)-4-methylene-1,5-diphenylpentane-1,5-dione (4e) (syn- and anti-
-1
1
mixture = 2:3): syn-4e: a colorless oil; IR (KBr): ν 1645, 1675 cm (C=O); H-NMR: δ 2.70-3.0 (2H,
m, CH), 4.25-4.37 (1H, m, CH), 5.02 (1H, d, J = 4.3 Hz, CH), 5.12 (1H, br., s, OH), 5.53 (1H, s, CH),
5
.83 (1H, s, CH), 7.0-7.50 (10H, m, Ar), 7.78 (1H, d, J = 7.3 Hz, Ar), 7.93 (1H, d, J = 7.5 Hz, Ar), 8.25
+
+
(
(
(
(
1H, dd, J = 7.5 1.9 Hz, Ar), 8.51 (1H, s, Ar); EI-MS: m/e 264 (M -107, 1.0), 238 (M -133, 6.2), 159
+
+
+
M -212, 18.1), 105 (M -266, 36.5), 84 (M -212, 100); HRMS: C H NO requires 371.1521, found:
2
4
21
3
+
-1
1
EI) m/z 371.1512 (M ); anti-4e: a colorless oil; IR (KBr): ν 1645, 1675 cm (C=O); H-NMR: δ 3.07
2H, dd, J = 8.0 7.6 Hz, CH ), 4.25-4.37 (1H, m, CH), 5.02 (1H, d, J = 4.3 Hz, CH), 5.18 (1H, br., s,
2
OH), 5.59 (1H, s, CH), 5.92 (1H, s, CH), 7.0-7.50 (10H, m, Ar), 7.70 (1H, d, J = 7.3 Hz, Ar), 7.93 (1H,
+
d, J = 7.5 Hz, Ar), 8.35 (1H, dd, J = 7.5 1.9 Hz, Ar), 8.47 (1H, s, Ar); EI-MS: m/e 264 (M -107, 1.0),
+
+
+
+
2
38 (M -133, 6.2), 159 (M -212, 18.1), 105 (M -266, 36.5), 84 (M -212, 100); HRMS: C H NO
24 21
3
+
requires 371.1521, found: (EI) m/z 371.1512 (M ).
-
2
-[Hydroxy-(4-nitrophenyl)methyl]acrylic acid phenyl ester (5a): a colorless oil; IR (KBr): ν 1723 cm
1
1
(
C=O); H-NMR: δ 3.27 (1H, d, J = 5.6 Hz, OH), 5.75 (1H, d, J = 5.2 Hz, CH), 6.12 (1H, s, CH),
6.68 (1H, s, CH), 7.03 (2H, d, J = 7.7 Hz, Ar), 7.25 (1H, t, J = 7.5 Hz, Ar), 7.36 (2H, t, J = 7.7 Hz, Ar),

Molecules 2002, 7
731
+
+
7
3
2
.63 (2H, d, J = 8.4 Hz, Ar), 8.23 (2H, d, J = 8.4 Hz, Ar); EI-MS: m/e 205 (M -94, 1.1), 161 (M -138,
+
+
1.6), 115 (M -184, 24.4), 94 (M -205, 100); HRMS: C H NO requires 299.0744, found: (EI) m/z
1
6
13
5
+
99.0733 (M ).
-
2
-[Hydroxy-(3-nitrophenyl)methyl]acrylic acid phenyl ester (5b): a colorless oil; IR (KBr): ν 1724 cm
1
1
(
C=O); H-NMR: δ 3.23 (1H, d, J = 5.8 Hz, OH), 5.80 (1H, d, J = 5.8 Hz, CH), 6.16 (1H, s, CH),
6.69 (1H, s, CH), 7.03 (2H, dd, J = 8.0, 0.7 Hz, Ar), 7.27 (1H, t, J = 7.2 Hz, Ar), 7.40 (2H, t, J = 7.5
Hz, Ar), 7.56 (1H, t, J = 7.5 Hz, Ar), 7.81 (1H, d, J = 8.0 Hz, Ar), 8.12 (1H, d, J = 8.0 Hz, Ar), 8.33
+
+
+
+
(
1H, s, Ar); EI-MS: m/e 299 (M , 0.6), 161 (M -138, 22.7), 115 (M -184, 19.2), 94 (M -205, 100);
+
HRMS: C H O N requires 299.0794, found: (EI) m/z 299.0781 (M ).
1
6
13
5
-
1
2
-[Hydroxy-(2-nitrophenyl)methyl]acrylic acid phenyl ester (5c): a colorless oil; IR (KBr): ν 1720 cm
1
(
C=O); H-NMR: δ 3.58 (1H, s, OH), 5.93 (1H, m, CH), 6.30 (1H, s, CH), 6.62 (1H, s, CH), 7.02 (2H,
d, J = 7.7 Hz, Ar), 7.22 (1H, t, J = 7.5 Hz, Ar), 7.36 (2H, t, J = 7.7 Hz, Ar), 7.48 (1H, t, J = 7.5 Hz,
Ar), 7.70 (1H, t, J = 7.5 Hz, Ar), 7.82 (1H, d, J = 7.7 Hz, Ar), 7.98 (1H, d, J = 7.7 Hz, Ar); EI-MS: m/e
+
+
+
+
2
60 (M -39, 1.4), 206 (M -93, 21.9), 188 (M -256, 4.9), 94 (M -205, 100); HRMS: C H NO requires
10 8 4
+
2
06.0453, found: (EI) m/z 206.0477 (M -93.0341).
2
-[Hydroxy-(4-bromophenyl)methyl]acrylic acid phenyl ester (5d): a colorless oil; IR (KBr): ν 1731
-1
1
cm (C=O); H-NMR: δ 3.02 (1H, s, OH), 5.52 (1H, s, CH), 5.96 (1H, s, CH), 6.52 (1H, s, CH), 6.97
+
(2H, d, J = 7.2 Hz, Ar), 7.10-7.43 (5H, m, Ar), 7.40 (2H, J = 7.2 Hz, Ar); EI-MS: m/e 315 (M -18, 2.1),
+
+
+
239 (M -94, 30.9), 160 (M -173, 72.2), 116 (M -217, 100); HRMS: C H BrO requires 239.9786,
10 9 2
+
found: (EI) m/z 239.9768 (M -92.0262).
-[Hydroxy-(4-chlorophenyl)methyl]acrylic acid phenyl ester (5e): a colorless oil; IR (KBr): ν 1730
2
-1
1
cm (C=O); H-NMR: δ 2.97 (1H, s, OH), 5.53 (1H, s, CH), 5.98 (1H, s, CH), 6.56 (1H, s, CH), 6.94-
+
+
6.98 (2H, m, Ar), 7.10-7.23 (1H, m, Ar), 7.20-7.38 (6H, m, Ar); EI-MS: m/e 288 (M , 1.1), 271 (M -
+
+
17, 10.5), 195 (M -93, 100), 115 (M -173, 88.4); HRMS: C H ClO requires 288.0553. Found: (EI)
1
6
13
3
+
m/z 288.0572 (M ).
-
1
2
-(Hydroxy-phenylmethyl)acrylic acid phenyl ester (5f): a colorless oil; IR (KBr): ν 1732 cm (C=O);
1
H-NMR: δ 2.96 (1H, s, OH), 5.56 (1H, s, CH), 5.97 (1H, s, CH), 6.53 (1H, s, CH), 6.94-6.98 (2H, m,
+
+
Ar), 7.10-7.23 (1H, m, Ar), 7.20-7.42 (7H, m, Ar); EI-MS: m/e 254 (M , 1.4), 161 (M -93, 77.5), 133
+
+
(
M -121, 34.1), 115 (M -139, 100); HRMS: C H O requires 254.0943, found: (EI) m/z 254.1015
16 14 3
+
(M ).
3
-Hydroxy-2-methylene-5-phenylpent-4-enoic acid phenyl ester (5g): a colorless oil; IR (KBr): ν 1727
-1
1
cm (C=O); H-NMR: δ 3.04 (1H, d, J = 5.5 Hz, OH), 5.23 (1H, t, J = 5.5 Hz, CH), 6.11 (1H, s, CH),
.29 (1H, dd, J = 15.9 6.3 Hz, CH), 6.54 (1H, s, CH), 6.70 (1H, d, J = 15.9 Hz, CH), 7.02-7.12 (2H, m,
6

Molecules 2002, 7
732
+
+
+
Ar), 7.12-7.42 (8H, m, Ar); EI-MS: m/e 280 (M , 3.9), 187 (M -93, 73.1), 169 (M -111, 39.2), 141
+
+
(
M -139, 100); HRMS: C H O requires 280.1099, found: (EI) m/z 280.1093 (M ).
18 16 3
-
1
2
-(Hydroxy-pyridin-3-yl-methyl)-acrylic acid phenyl ester (5h): a colorless oil; IR (KBr): ν 1727 cm
1
(
C=O); H-NMR: δ 5.25 (1H, s, OH), 5.69 (1H, s, CH), 6.27 (1H, s, CH), 6.63 (1H, s, CH), 7.02 (2H,
d, J = 7.7 Hz, Ar), 7.22 (1H, t, J = 7.5 Hz, Ar), 7.20 (1H, dd, J = 2.9 0.82 Hz, Ar), 7.36 (2H, t, J = 7.7
Hz, Ar), 7.76 (1H, d, J = 8.0 Hz, Ar), 8.36 (1H, dd, J = 3.9 0.82 Hz, Ar), 8.48 (1H, s, Ar); EI-MS: m/e
+
+
+
+
2
56 (MH , 1.0), 162 (M -93, 100), 144 (M -112, 17.2), 94 (M -162, 68.6); HRMS: C H O N
15 12 2
+
requires 238.0868, found: (EI) m/z 238.0871 (M -17.0027).
2
-[(4-Chlorophenyl)-hydroxy-methyl]thioacrylic acid S-phenyl ester (7): a colorless oil; IR (KBr): ν
-1
1
1674 cm (C=O); H-NMR: δ 2.98 (1H, d, J = 4.7 Hz, OH), 5.56 (1H, d, J = 4.7 Hz, CH), 5.97 (1H, s,
+
+
+
CH), 6.45 (1H, s, CH), 7.20-7.45 (9H, m, Ar); EI-MS: m/e 304 (M , 9.0), 195 (M -109, 100), 167 (M -
+
137, 45.2), 115 (M -189, 79.9); HRMS: C H ClO S requires 304.0325, found: (EI) m/z 304.0332
1
6
13
2
+
(
M ).
References
1
. (a) Ciganek, E. Org. React., 1997, 51, 201; (b) Basavaiah, D.; Rao, P. D.; Hyma, R. S.
Tetrahedron, 1996, 52, 8001; (c) Drewes, S. E.; Roos, G. H. P. Tetrahedron, 1988, 44, 4653; (d)
Brzezinski, L. J.; Rafel, S.; Leahy, J. M. J. Am. Chem. Soc., 1997, 119, 4317; (e) Miyakoshi, T.;
Saito, S. Nippon Kagaku Kaishi, 1983, 1623; Chem. Abstr., 1984, 100, 156191g; (f) Marko, I. E.;
Giles, P. G.; Hindley, N. J. Tetrahedron, 1997, 53, 1015; (g) Richter, H.; Jung, G. Tetrahedron
Lett., 1998, 39, 2729; (h) Barrett, A. G. M.; Cook, A. S.; Kamimura, A. Chem. Commun., 1999,
2
533; (i) Kunidig, E. P.; Xu, L. H.; Romanens, P.; Bernardinelli, G. Tetrahedron Lett., 1993, 34,
049; (j) Aggarwal, V. K.; Mereu, A.; Tarver, G. J.; MaCague, R. J. Org. Chem., 1998, 63, 7183;
7
(k) Kawamura, M.; Kobayashi, S. Tetrahedron Lett., 1999, 40, 1539; (l) Li, G.-G.; Wei, H.-X.;
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Enright, M. Org. Lett. 2000, 2, 617.
2
. (a) Baylis, A. B.; Hillman, M. E. D. Ger. Offen., 1972, 2, 155, 113 [Chem. Abstr. 1972, 77,
3
4174q]; (b) Hillman, M. E. D.; Baylis, A. B. U. S. Patent, 1973, 3,743,669; (c) Morita, K.;
Suzuki, Z.; Hirose, H. Bull. Chem. Soc. Jpn., 1968, 41, 2815.
3
. Iwabuchi, Y.; Nakatani, M.; Yokoyama, N.; Hatakeyama, S. J. Am. Chem. Soc., 1999, 121, 10219.
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K.; Cui, S.-C.; Feng, Y.-S. J. Chem. Soc., Perkin Trans. 1, 2001, 390.
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5
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7
. Shi, M.; Li, C.-Q.; Jiang, J.-K. J. Chem. Soc., Chem. Commun., 2001, 833.
. (a) Maxwell, C. E. Org. Synth. Coll. Vol 3, 1955, 305; (b) Heilner, M. Chem. Ber., 1922, 55, 359.
. Douglas, K. T.; Williams, A. J. Chem. Soc., Perkin Trans II, 1983, 131.

Molecules 2002, 7
733
8. Baker, M. V.; Ghitgas, C.; Hayhes, R. K.; Hilliker, A. E.; Lynch, G. J.; Sherwood, G. V.; Yeo, H.-
L. Aus. J. Chem., 1984, 37, 2037.
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2002 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.
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