Catalytic oxidations of enolizable ketones using 2-alkylidene-4- oxothiazolidine vinyl bromide

Article abstract of DOI:10.1016/j.tet.2011.08.022

Direct oxidation of enolizable ketones to α-hydroxy derivatives, vicinal dicarbonyls or tricarbonyl compounds has been achieved by a catalytic amount of 2-alkylidene-4-oxothiazolidine vinyl bromide in DMSO as a solvent. The yields range from moderate to good.

Full text of DOI:10.1016/j.tet.2011.08.022

Tetrahedron 67 (2011) 8000e8008
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Catalytic oxidations of enolizable ketones using 2-alkylidene-4-oxothiazolidine
vinyl bromide
a
,
b
,
a
,
b
b
Marija Baranac-Stojanovi ꢀc *, Rade Markovi ꢀc , Milovan Stojanovi ꢀc
a
Faculty of Chemistry, University of Belgrade, Studentski trg 16, P.O. Box 158, 11000 Belgrade, Serbia
Center for Chemistry ICTM, P.O. Box 473, 11000 Belgrade, Serbia
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 May 2011
Received in revised form 19 July 2011
Accepted 8 August 2011
Available online 16 August 2011
Direct oxidation of enolizable ketones to
pounds has been achieved by a catalytic amount of 2-alkylidene-4-oxothiazolidine vinyl bromide in
DMSO as a solvent. The yields range from moderate to good.
a
-hydroxy derivatives, vicinal dicarbonyls or tricarbonyl com-
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
2-Alkylidene-4-oxothiazolidine vinyl
bromide
Enolizable ketones
Catalytic oxidation
Dimethyl sulfoxide
1
9
1
. Introduction
a-hydroxyketones include the reaction of enolates or silyl enol
2
0
ethers with sources of electrophilic oxygen, or direct hydroxyl-
ations by iodine or hypervalent iodine reagents. Catalytic
droxylations are multistep syntheses involving the preformation of
pure enol ethers, though the direct proline-catalyzed a-oxy-
a-acetoxylation, alanine-
or metal-catalyzed hydroxylations with molecular oxygen have
also been reported. The formation of tertiary alcohols from
dicarbonyl compounds is usually accomplished by metal-catalyzed
21
22
The oxidation of enolizable ketones is an important trans-
formation leading to synthetic intermediates, such as -diketones,
glyoxals and -hydroxyketones, which are of considerable signifi-
cance in organic and medicinal chemistry. A popular method for the
preparation of
-diketones and glyoxals from methylene2 and
a-hy-
a
2
3
a
1
23
24
23
amination, iodobenzene-catalyzed
a
methyl ketones,1 respectively, is the oxidation with selenium di-
oxide. An alternative is DMSO-based oxidations. Conversion of
bromoacetophenones to arylglyoxals through the agency of DMSO
e,3
25
b-
a
-
2
6
27
a
-hydroxylation with O
use of a slight excess of 2-iodoxybenzoic acid (IBX) for the
droxylation of -dicarbonyl compounds has also been reported.
Hydroxyketones are also accessible by ketohydroxylation of al-
2
or dimethyl dioxirane (DMDO). The
4
5
was reported by Kornblum et al. and later improved by Floyd et al.
who showed that acetophenones can be directly oxidized to aryl-
glyoxals with an excess of 48% aq HBr in DMSO. The latter procedure
was also applied for the oxidation of
corresponding
a
-hy-
2
8
b
2
3,29
30
a
-methylene ketones to the
-diketones. An attempted catalytic oxidation of
kenes,
or by partial reduction of a-diketones.
6
a
In the course of our studies on reactivity of pushepull 2-
alkylidene-4-oxothiazolidines 1 we have found that vinyl bro-
mides 2, easily prepared by bromination of 1, can undergo an easy
acetophenoneby 48%aq HBr in DMSO, however, resulted in low yield
of the product (10%). Other oxidation methods for the formation of
7
31
31,32
a-diketones involve oxidation of various substrates: (i) olefins with
cleavage of the CeBr bond in the presence of a nucleophile.
8
9
selenium dioxide or potassium permanganate, (ii) acetylenes with
Depending on the type of nucleophile used, this cleavage can end
up in reductive dehalogenation (path A, Scheme 1), bromine sub-
stitution (path B) or bromine migration to the C(5) position of the
ring (path C). This last path is the basis for the C(5) functionalization
10
11
12
potassium permanganate, PdCl
MeSO -hydroxyketones or the corresponding
H/HBr/DMSO,13 (iii)
tautomeric 1,2-dihydroxyethenes with iodine, atmospheric oxy-
gen, sodium hypobromite, bismuth nitrateecopper(II) acetate,
or a catalytic amount of trichlorooxovanadium. The routes to
2 2
/DMSO, NBS/DMSO, or HCO H/
3
a
14
15
16
17
31,32b
of N-unsubstituted 2-alkylidene-4-oxothiazolidines.
18
In DMSO, the CeBr dissociation is spontaneous and the bro-
monium ion, released into the solution, is trapped by the C(5) of
another vinyl bromide 2 yielding dibromide 3 (Scheme 2). Sub-
*
Corresponding author. Tel.: þ381 11 3336740; fax: þ381 11 2636061; e-mail
3
3
address: mbaranac@chem.bg.ac.rs (M. Baranac-Stojanovi ꢀc ).
sequent hydrolysis gives the alcohols 4 and liberates HBr.
0
040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.022

M. Baranac-Stojanovi ꢀc et al. / Tetrahedron 67 (2011) 8000e8008
8001
l
Scheme 1.
Oxidation of HBr by DMSO (Scheme 3)34 results in the formation of
molecular bromine, which reacts with 1 (Scheme 2), thus regen-
erating the starting vinyl bromide 2. Now, 2 can enter the reaction
cycle again giving the products 4 in moderate to good yields
The second mechanism was suggested by Floyd et al., based on
their experimental observations (Scheme 5). It involves the hy-
5
drolysis of a-bromoacetophenone to a-hydroxyketone 6. Molecular
bromine, formed by the oxidation of liberated HBr by DMSO, then
reacts with 6 to give the intermediate 7, which is rapidly hydrolyzed
to glyoxal 8.
(
55e72%).33
Scheme 5.
According to both mechanisms HBr is liberated. Since its oxi-
dation (Scheme 3) can regenerate the source of electrophilic
l
-
2
bromine (Br or vinyl bromide 2), we reasoned that a catalytic
amount of 2 would be enough for the reaction. In addition, di-
methyl sulfide is also formed in the oxidation step (Scheme 3). As
5
its accumulation can lead to formation of by-products and de-
13
pletion of bromine, it should be removed from the reaction
mixture. In this paper, we report on the catalytic oxidation of
various enolizable ketones and b-dicarbonyl compounds by vinyl
Scheme 2.
Scheme 3.
bromide 2 in DMSO.
2. Results and discussion
Our investigation began with the oxidation of acetophenone 9a
(Table 1). Thus, a mixture of the substrate 9a/vinyl bromide 2a/
We saw a possible synthetic application of this reaction in the
3
6
presence of a second component, which could be brominated and
DMSO in a molar ratio 1:0.1:13 was heated in an open flask, at the
4
ꢀ
further oxidized by DMSO, as described by Kornblum et al. and
temperature of an oil bath of 80 C (entry 1). The oxidation did
Floyd et al.5 In fact, two mechanisms were proposed for this oxi-
occur, though in low yield. Since the catalyst 2a can react with
37
dation. According to the first, the DMSOeadduct 5, formed from
bromine according to the Scheme 2, two other 5-substituted
bromides 2b and 2c (Table 1), not undergoing C(5) bromination,
were also tried as catalysts (entries 2 and 3). Although the
DMSO and
sulfide (Scheme 4).
a-bromoketone, is decomposed to glyoxal and dimethyl
35
Scheme 4.

8002
M. Baranac-Stojanovi ꢀc et al. / Tetrahedron 67 (2011) 8000e8008
conversion of 9a to phenylglyoxal hydrate 10a occurred in similar
yields, the reaction time was almost triple than that with 2a. For
this reason all other reactions were performed with the bromide
of 12a and 14a by column chromatography. The pure 14a could be
obtained starting from the -hydroxyketone 13a (entry 12). In
fact, this oxidation required higher reaction temperature: in-
a
ꢀ
ꢀ
2
a. The dilution of the reaction mixture by increasing the amount of
creasing the temperature from 110 C to 145 C resulted in in-
crease in the yield of 14a from 12% to 38%. By contrast, the more
activated methylene group in 12b was oxidized under milder
conditions and in higher yield (entries 13 and 14). Thus, heating of
the solvent, DMSO, increased the yield from 36% to 57% (compare
entries 1 and 4e6). The best molar ratio was 1:0.1:26 and further
dilution did not have an effect on the reaction time and yield of the
product (entries 5 and 6). We were intrigued to see if even lower
quantity of the catalyst could affect the transformation with similar
outcome. With one molar percent of catalyst the reaction was ex-
tremely slow and after 5 days there was still appreciable amount of
unreacted substrate 9a (not shown in the Table). Five molar percent
of the catalyst under the same conditions gave lower yield of the
product (entry 7), while in a more concentrated solution the yield
was even lower (entry 8).
ꢀ
deoxybenzoin 12b at the temperature of 85e90 C for 12 h
resulted in the formation of a-hydroxy compound 13b (entry 13),
which was further oxidized to 14b in good yield by simple pro-
longation of the reaction time (entry 14). Raising the temperature
increases the yield of 14b and reduces the reaction time (entry 14).
Vinyl bromide-catalyzed reaction also enabled the introduction of
a
-hydroxy group in the substrates 12c and 12d, the structure of
which is such that an easy dehydrogenation would be expected.
Table 1
a
Oxidation of acetophenone 9a under different conditions
O
O
OH
OH
O
R
H
N
2
Br
DMSO
2a: R= H; EWG = CONHPh
S
EWG 2b: R = Me; EWG CONHPh
9a
10a
2
2c: R
=
Me; EWG = COPh
Entry
Catalyst
Molar ratio
Time (h)
Yieldb of 10a (%)
Substrate/catalyst/DMSO
1
2
3
4
5
6
7
8
2a
2b
2c
2a
2a
2a
2a
2a
1:0.1:13
1:0.1:13
1:0.1:13
1:0.1:19
1:0.1:26
1:0.1:52
1:0.05:26
1:0.05:13
12
34
34
48
47
48
48
48
36
30
38
36
57
57
35
22
a
ꢀ
All reactions were heated at the temperature of an oil bath of 80 C in an open flask in order to remove dimethyl sulfide.
Isolated yield after column chromatography.
b
Thus we chose the conditions as presented in Table 1, entry 5,
The secondary and tertiary alcohols 13c and 13d were obtained
under standard reaction conditions, albeit in reduced yields (en-
tries 15 and 17), as both reactions were accompanied by con-
comitant dehydrogenation. In the case of 12c, under the
conditions specified (entry 15), the alkene 15 was isolated in 13%
yield, resulting in total conversion of 58%. With 12d as the sub-
strate, the dehydrogenation ended in the formation of 2,5-
dihydroxyacetophenone 16 in 12% yield, making an overall con-
version of 42% (entry 17). It is assumed that the formation of 16
and attempted to oxidize a series of methyl ketones 9beg, as shown
in Table 2 (entries 3e8). All substrates 9bef underwent oxidation to
the corresponding arylglyoxal hydrates 10bef under the selected
reaction conditions, in moderate yields. In the case of 2-
acetylthiophene 9g only hemiacetal dimer 10g was isolated. By
comparison, the use of 0.1 equiv of HBr (as 48% aq HBr) for the
oxidation of 9a and 9b under analogous reaction conditions affor-
ded products 10a and 10b in 37% and 33% yields, respectively. In-
creasing the reaction temperature resulted in shortening of the
reaction time with the same product yield in the case of 9e as
a substrate (entry 6). Unfortunately, higher reaction temperature
was not suitable for the conversion of other substrates to aryl-
glyoxals due to increased rate of decomposition/by-products
formation.38
comes from an allylic bromination of primarily formed
saturated compound, followed by hydrolysis and subsequent
aromatization, via -keto bromination and dehydrobromination.
a,b-un-
a
Raising the reaction temperature increased the yield of dehydro-
genated products 15 and 16 from 13% to 33% and 12% to 19%, re-
spectively (entries 16 and 18), though in the latter case the
improvement was only slight. In both reactions the secondary and
tertiary alcohols 13c and 13d were also isolated and the total
conversion of the substrates 12c and 12d, under the conditions
specified in entries 16 and 18, was 59% and 42%, respectively. An
attempted oxidation of cyclohexanone 12e gave only the bromi-
nated product 17 (entry 19), obviously by a primary oxidation to
The vinyl bromide-catalyzed oxidation is not confined to
methyl ketones. Under analogous conditions (substrate/2a/DMSO
1
:0.1:26)
a
-methylene ketones were oxidized to the correspond-
-diketones. A judicious choice of the
ing -hydroxyketones and
a
a
reaction conditions allows one to obtain one or another product.
Thus, heating of propiophenone 12a with 0.1 equiv of 2a in DMSO
ꢀ
at the temperature of 115 C for 2 h yielded the
a
-hydroxyketone
enolized
a-diketone, which was then quickly brominated. Oxida-
13a as the main product (entry 9). Prolongation of the reaction
tion of -dicarbonyl compounds 18a and 18b proceeded smoothly
b
time or higher temperature resulted in further oxidation to the
diketone 14a (entries 10 and 11). It should be noted that the purity
of 14a obtained by direct oxidation of propiophenone 12a was
a
-
at somewhat elevated temperature to give the vicinal tricarbonyl
compounds 19a and 19b (entries 20 and 21), which were isolated
as a mixture of keto and hydrated form. Since most established
synthetic routes to this preparatively useful class of compounds
9
0e95%, since the conversion of the starting material was never
3
9
complete and the similarity in structures did not allow separation
involve oxidation of preformed
a-substituted derivatives, this

M. Baranac-Stojanovi ꢀc et al. / Tetrahedron 67 (2011) 8000e8008
8003
Table 2
Oxidation of enolizable ketones and dicarbonyl compounds with a catalytic amount of vinyl bromide 2a in DMSOa
Entry
Substrate
Product
Reaction conditions
Temperature ( C)/Time (h)
Yieldb (%)
ꢀ
O
O
O
O
OH
OH
1
9a
9a
9b
9c
10a
11
80/47
80/11
80/36
80/48
57
8
OH
2
3
4
O
O
O
OH
OH
10b
10c
52
65
O
2
N
O
2N
O
OH
OH
Ph
F
Ph
F
O
O
OH
5
6
9d
9e
10d
10e
80/48
65
OH
OH
O
O
O
OH
80/24; 110/4
65; 66
Br
Br
O
OH
7
8
9f
10f
80/48
61
43
OH
O
O
O
S
10g
S
O
S
95e100/27
9g
OH OH
O
O
O
O
O
9
12a
12a
12a
13a
12b
13a
14a
14a
14a
13b
115/2
60
OH
O
O
O
10
11
12
13
115/25
135/24
145/2
39c
46c
38
O
O
O
OH
O
O
85e90/12
65
(
continued on next page)
OH

8004
M. Baranac-Stojanovi ꢀc et al. / Tetrahedron 67 (2011) 8000e8008
Table 2 (continued )
Entry
Substrate
Product
Reaction conditions
Temperature ( C)/Time (h)
Yieldb (%)
71; 85
ꢀ
O
O
14
12b
14b
85e90/36; 135/7
O
O
O
OEt
OEt
OEt
OEt
45 (58)d
33 (59)e
1
5
6
12c
12c
13c
15
80/28
O
O
OH
O
O
O
O
1
140/1.5
O
O
O
O
O
O
OH
1
1
7
8
12d
12d
13d
16
110e115/7.5
130e135/3
30 (42)f
OH
O
19 (42)g
OH
O
O
OH
Br
19
12e
17
80/14h
7i/68j
O
O
O
O
2
0
1
18a
18b
19a
19b
130e135/2
55
59
O
O
O
O
O
2
120/4
OEt
OEt
O
a
b
c
d
e
f
The reactions were performed using substrate/catalyst/DMSO 1:0.1:26 molar ratio.
Isolated yield after column chromatography.
The purity ranges from 90% to 95%.
Total conversion of the substrate 12c into
Total conversion of the substrate 12c into alkene 15 and
a
-hydroxy derivative 13c and alkene 15, which was obtained in 13% yield under the specified conditions.
-hydroxy derivative 13c, which was obtained in 26% yield under the specified conditions.
a
Total conversion of the substrate 12d into tertiary alcohol 13d and 16, which was obtained in 12% yield under the specified conditions.
Total conversion of the substrate 12d into 16 and tertiary alcohol 13d, which was obtained in 23% yield under the specified conditions.
The reaction concentration was doubled.
Yield based on cyclohexanone.
Yield based on the available bromine, i.e., vinyl bromide.
g
h
i
j
direct oxidation of readily available
should be of particular interest.
b
-dicarbonyl compounds
obtained solvent without any further purification.40 Water is also
produced during the oxidation of the liberated HBr by DMSO
(Schemes 3 and 6). Molecular bromine, formed in the same step,
From a mechanistic point of view, the first step in the oxidation
reactions is -bromination to 20 by electrophilic bromine released
from the vinyl bromide 2a (Scheme 6). Two mechanisms have been
suggested for the oxidation of -bromoketones by DMSO, as
depicted in Schemes 4 and 5. The isolation of -hydroxy de-
rivatives 13 goes in favour of the second mechanism proposed by
Floyd et al.5 In addition, the
-hydroxyacetophenone 11 was iso-
lated as the intermediate in the oxidation of acetophenone (Table
, entry 2). The water necessary for this hydrolytic step was
present in small amount in DMSO, as we used the commercially
a
may react with the
a
-hydroxy compounds 11 and 13 to give the
-bromo intermediates 21 or with the
unobservable -hydroxy-
a
a
a
parent 4-oxothiazolidine 1a, thus regenerating the catalyst 2a. The
last step is the rapid hydrolysis of 21 to products 10, 14 and 19. All
a
a-keto aldehydes (arylglyoxals) were isolated as hydrates, tri-
a
carbonyl compounds as a mixture of hydrate and keto form, and a-
diketones in the keto form. Finally, the catalyst 2a is turned into
the 5-hydroxy derivative 4 (Scheme 2), which needs to be removed
2
2 3
by aq Na CO only before the purification of arylglyoxals 10 by

M. Baranac-Stojanovi ꢀc et al. / Tetrahedron 67 (2011) 8000e8008
8005
column chromatography (see Experimental section). The fact that
the analogous HBr-catalyzed oxidations of 9a and 9b proceeded in
lower yields (37% and 33%, respectively, see Results and discussion
section) may be rationalized by drop in the equilibrium concen-
tration of bromine (Scheme 3) due to the increased amount of
water, added as 48% aq HBr.
gradient petrolether/ethyl acetate) of the extract gave the pure
products. The products were characterized on the basis of spectral
data and where possible by comparison with the literature data.
4.2.1. Phenylglyoxal hydrate (10a). Compound 10a was obtained
from 9a (74.5 mg, 0.62 mmol) and 2a (19.4 mg, 0.062 mmol) in
Scheme 6.
3
. Conclusion
DMSO (1.2 mL) according to general procedure. Column chroma-
tography (eluent: gradient petrolether/ethyl acetate 100:0 to
ꢀ
We have presented a novel, catalytic method for the direct ox-
80:20) gave pure 10a (53.9 mg, 57%) as a white solid, mp 72e74 C
3
c
ꢀ
idation of enolizable ketones that allows the introduction of a sec-
ondary or tertiary hydroxy group, or creation of vicinal dicarbonyl
and tricarbonyl structural unit. The catalyst is non-toxic and readily
obtainable. The method is operationally simple and reaction con-
ditions are neutral. This procedure has circumvented the use of
stoichiometric amounts of oxidants, or toxic transition-metal cat-
alysts. It has also avoided highly acidic reaction medium as in the
HBreDMSO oxidations, or selenium-containing contaminants,
which often accompany products of selenium dioxide oxidations.
(lit. 73e91 C, depending on the degree of hydration); R
f
¼0.25
13
(petrolether/ethyl acetate 4:1); IR (KBr):
1448, 1111, 714, 684 cm ; H NMR (200 MHz, DMSO-d
n
max 3407, 1697, 1596,
ꢁ1
1
13
ꢀ
6
, 25 C):
d
5.71 (br s,1H, CH), 6.77 (d, J¼6.4 Hz, 2H, 2ꢂ OH), 7.46e7.68 (m, 3H,
13 13
m- and p-Ph), 8.08 (d, J¼6.8 Hz, 2H, o-Ph); C NMR (50.3 MHz,
ꢀ
DMSO-d
calcd for C
6
, 25 C):
d
89.4, 128.7, 129.6, 133.6, 134.0, 196.5; HRMS
ꢁ
8
H
7
O
3
(MꢁH) : 151.0401; found: 151.0411.
4.2.2. 2-Hydroxyacetophenone (11). Compound 11 was obtained
from 9a (70.6 mg, 0.59 mmol) and 2a (18.4 mg, 0.059 mmol) in
DMSO (1.1 mL) according to general procedure. Column chroma-
tography (eluent: gradient petrolether/ethyl acetate 100:0 to
4
4
. Experimental
ꢀ
.1. General
80:20) gave pure 11 (6.5 mg, 8%) as a pale yellow solid, mp 81e82 C
2
2b
ꢀ
(
lit.
80e82 C); R
f
¼0.35 (petrolether/ethyl acetate 4:1); IR
2
2b
ꢁ1
1
Melting points were determined on a Stuart SMP10 apparatus
(KBr):
NMR
n
max 3446, 1691, 1597, 1449, 1097, 1019, 757, 689 cm ; H
2
2b
ꢀ
and are uncorrected. The IR spectra were recorded on a Per-
kineElmer FT-IR 1725X spectrophotometer and are reported as
wave numbers (cm ). The NMR spectra were recorded on a Varian
(200 MHz, CDCl
3
, 25 C):
d
3.51 (t, J¼4.2 Hz, 1H, OH), 4.89
(d, J¼4.2 Hz, 2H, CH
Ph), 7.91e7.97 (m, 2H, o-Ph); C NMR (50.3 MHz, CDCl
8 7 2
65.4, 127.7, 129.0, 133.6, 134.3, 198.4; HRMS calcd for C H O
2
), 7.47e7.55 (m, 2H, m-Ph), 7.60e7.69 (m,1H, p-
ꢁ
1
13
ꢀ
3
, 25 C):
1
13
Gemini 2000 spectrometer ( H at 200 MHz, C at 50.3 MHz) in
DMSO-d or CDCl . Chemical shifts are reported in parts per million
ppm) on the scale from TMS as an internal standard. HRMS was
d
ꢁ
6
3
(MꢁH) : 135.0452; found: 135.0455.
(
d
carried out on 6210 TOF LC/MS coupled with HPLC 1200 Series
Agilent Technologies. Thin-layer chromatography (TLC) was carried
out on Kieselgel G nach Stahl and spots were visualized by iodine or
4.2.3. p-Nitrophenylglyoxal hydrate (10b). Compound 10b was
obtained from 9b (101.7 mg, 0.62 mmol) and 2a (19.3 mg,
0.062 mmol) in DMSO (1.2 mL) according to general procedure.
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 90:10 to 70:30) gave pure 10b (63.0 mg, 52%) as a pale yellow
by 50% H
2 4 2
SO . Column chromatography was carried out on SiO
ꢁ
(
silica gel 60 A, 12e26, ICN Biomedicals). Solvents used for column
ꢀ
3a
ꢀ
chromatography were distilled before use. All liquid substrates
were distilled before use. DMSO was used without purification.
Vinyl bromide 2a was synthesized according to the published
procedure.31 It should be kept in a freezer.
solid, mp 90e91 C (lit. 97e100 C); R
f
¼0.22 (petrolether/ethyl
acetate 7:3); IR (KBr):
n
max 3328, 1694, 1605, 1534, 1350, 1012,
ꢁ1
1
41
ꢀ
855 cm
;
H NMR (200 MHz, DMSO-d
6
, 25 C):
d
5.67 (t,
J¼6.2 Hz, 1H, CH), 7.07 (d, J¼6.2 Hz, 2H, 2ꢂ OH), 8.26e8.37 (m, 4H,
13
41
ꢀ
Ph); C NMR (50.3 MHz, DMSO-d , 25 C): d 90.3, 123.8, 131.1,
6
4
.2. General procedure for the oxidation
138.8, 150.1, 195.6; no molecular ion was detected by HRMS.
A
mixture of
0.06 mmol) in DMSO (1.1 mL) was heated in an open flask (the
temperature of an oil bath and the reaction time are specified inTable
). After the completion of the reaction (checked by TLC), the reaction
a
substrate (0.6 mmol), vinyl bromide 2a
4.2.4. (p-Phenyl)phenylglyoxal hydrate (10c). Compound 10c was
obtained from 9c (120.0 mg, 0.61 mmol) and 2a (19.2 mg,
0.061 mmol) in DMSO (1.1 mL) according to general procedure.
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 100:0 to 80:20) gave pure 10c (91.2 mg, 65%) as a pale yellow
(
2
mixture was diluted with water (11 mL), saturated with NaCl and
extracted with ethyl acetate (5ꢂ4 mL). Only in the case of the syn-
thesis of arylglyoxals the organic layer was additionally washed with
ꢀ
42
ꢀ
solid, mp 109e110 C (lit. 113e117 C); R
f
¼0.24 (petrolether/ethyl
acetate 7:3); IR (KBr):
nmax 3436, 3376, 1694, 1603, 1449, 1126, 865,
ꢁ
1
1
ꢀ
Na
2
CO
3
(0.12 mmol in 2 mL of water), with saturated aq NaCl and
SO . Column chromatography (eluent:
752, 692 cm ; H NMR (200 MHz, DMSO-d
6
, 25 C):
d
5.75 (br s,
dried with anhydrous Na
2
4
1H, CH), 6.83 (br d, J¼6.4 Hz, 2H, 2ꢂ OH), 7.42e7.55 (m, 3H, m- and

8006
M. Baranac-Stojanovi ꢀc et al. / Tetrahedron 67 (2011) 8000e8008
p-Ph), 7.23e7.84 (m, 4H, o- and m-Ph), 8.19 (d, J¼8.4 Hz, 2H, o-Ph);
o-Ph); 13C NMR44 (50.3 MHz, CDCl
, 25 C): d 22.2, 69.2,128.6,128.8,
ꢀ
3
133.3, 134.0, 202.4; no molecular ion was detected by HRMS.
13
ꢀ
C NMR (50.3 MHz, DMSO-d
6
, 25 C):
d
89.6, 126.9, 127.3, 128.7,
1
29.4, 130.4, 132.7, 139.3, 144.9, 196.1; HRMS calcd for dehydrated
þ
form C14
H
11
O
2
(MþH) : 211.0754; found: 211.0749.
4.2.10. 1-Phenylpropane-1,2-dione (14a). Compound 14a was
obtained from 13a (90.5 mg, 0.60 mmol) and 2a (18.9 mg,
0.060 mmol) in DMSO (1.1 mL) according to general procedure.
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 100:0 to 90:10) gave pure 14a (34.1 mg, 38%) as a yellow oil;
4
.2.5. p-Fluorophenylglyoxal hydrate (10d). Compound 10d was
obtained from 9d (83.7 mg, 0.61 mmol) and 2a (19.0 mg,
.061 mmol) in DMSO (1.1 mL) according to general procedure.
0
Column chromatography (eluent: gradient petrolether/ethyl ace-
R
f
¼0.79 (petrolether/ethyl acetate 9:1); IR (KBr):
n
max 1711, 1671,
ꢁ
1
1
45
ꢀ
tate 100:0 to 80:20) gave pure 10d (66.5 mg, 65%) as a pale yellow
1596, 1159, 701 cm ; H NMR (200 MHz, CDCl
3H, CH
3
, 25 C):
d
2.53 (s,
ꢀ
3b
ꢀ
solid, mp 80e81 C (lit. 80e82 C); R
f
¼0.26 (petrolether/ethyl
3
), 7.50 (t, J¼7.4 Hz, 2H, m-Ph), 7.65 (t, J¼7.4 Hz, 1H, p-Ph),
13 45
ꢀ
3
, 25 C):
acetate 7:3); IR (KBr):
nmax 3348, 1699, 1597, 1505, 1231, 1061,
8.02 (d, J¼7.4 Hz, 2H, o-Ph); C NMR (50.3 MHz, CDCl
ꢁ1
1
ꢀ
8
04 cm
;
H NMR (200 MHz, DMSO-d
6
, 25 C):
d
5.65 (br s, 1H,
26.3, 128.9, 130.3, 131.8, 134.6, 191.4, 200.6; no molecular ion was
detected by HRMS.
CH), 6.84 (br s, 2H, 2ꢂ OH), 7.28e7.39 (m, 2H, m-Ph), 8.11e8.20 (m,
2
H, o-Ph); 13C NMR (50.3 MHz, DMSO-d
, 25 C): d 89.9, 115.6, 116.0,
ꢀ
6
1
C
32.7, 132.9, 162.8, 167.8, 195.2; HRMS calcd for dehydrated form
4.2.11. 2-Hydroxy-1,2-diphenylethanone (benzoin, 13b). Compound
13b was obtained from 12b (110.0 mg, 0.56 mmol) and 2a
þ
H
8 6
FO
2
(MþH) : 153.0346; found: 153.0342.
(17.6 mg, 0.056 mmol) in DMSO (1.1 mL) according to general
4
.2.6. p-Bromophenylglyoxal hydrate (10e). Compound 10e was
obtained from 9e (110.0 mg, 0.55 mmol) and 2a (17.3 mg,
.055 mmol) in DMSO (1.0 mL) according to general procedure.
procedure. Column chromatography (eluent: gradient petro-
lether/ethyl acetate 100:0 to 90:10) gave pure 13b (77.4 mg, 65%)
ꢀ
22b
ꢀ
0
as a pale yellow solid, mp 132e133 C (lit.
(petrolether/ethyl acetate 9:1); IR (KBr):
126e128 C); R
f
¼0.18
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 100:0 to 80:20) gave pure 10e (83.0 mg, 65%) as a pale yellow
solid, mp 108e109 C (lit. 125 C); R
acetate 7:3); IR (KBr):
NMR (200 MHz, DMSO-d
2
n
max 3413, 3378, 1679,
ꢁ
1
1
22b
1595, 1449, 1068, 755, 701 cm
;
H NMR
3
(200 MHz, CDCl ,
ꢀ
43
ꢀ
ꢀ
f
¼0.32 (petrolether/ethyl
25 C):
d
4.57 (d, J¼5.9 Hz, 1H, OH), 5.96 (d, J¼5.9 Hz, 1H, CH),
ꢁ
1
1
13
n
max 3376, 1693, 1582, 1008, 806 cm
;
H
7.25e7.56 (m, 8H, arom.), 7.89e7.94 (m, 2H, o-Ph); C NMR
1
e
ꢀ
ꢀ
6
, 25 C):
d
5.63 (br s, 1H, CH), 6.87 (br s,
(50.3 MHz, CDCl
3
, 25 C):
d
76.1, 127.7, 128.6, 128.7, 129.1, 133.4,
13
þ
H, 2ꢂ OH), 7.71e7.77 (m, 2H, m-Ph), 7.99e8.03 (m, 2H, o-Ph);
C
133.9, 139.0, 198.9; HRMS calcd for
235.0730; found: 235.0727.
C
14
H
12
O
2
Na (MþNa) :
1
e
ꢀ
NMR (50.3 MHz, DMSO-d
95.7; HRMS calcd for C
6
, 25 C):
BrClO
d
89.9, 127.6, 131.7, 131.8, 132.9,
ꢁ
1
2
8
H
7
3
(MþCl) : 264.9273; found:
64.9289.
4.2.12. 1,2-Diphenylethane-1,2-dione (benzil, 14b). Compound 14b
was obtained from 12b (106.2 mg, 0.54 mmol) and 2a (16.9 mg,
0.054 mmol) in DMSO (1.0 mL) according to general procedure.
Column chromatography (eluent: gradient petrolether/ethyl ac-
etate 100:0 to 90:10) gave pure 14b (96.9 mg, 85%) as a pale
4
.2.7. Naphthalen-2-yl-oxoacetaldehyde hydrate (10f). Compound
10f was obtained from 9f (90.1 mg, 0.53 mmol) and 2a (16.6 mg,
0
.053 mmol) in DMSO (1.0 mL) according to general procedure.
ꢀ
12
ꢀ
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 100:0 to 80:20) gave pure 10f (65.1 mg, 61%) as a white solid,
mp 84e86 C (lit. 108e111 C); R
yellow solid, mp 93e94 C (lit. 94e95 C); R
f
¼0.60 (petrolether/
13
ethyl acetate 9:1); IR (KBr):
n
max 1675, 1662, 1594, 1449, 1211,
ꢀ
1e
ꢀ
ꢁ1
1
13
ꢀ
f
¼0.35 (petrolether/ethyl acetate
720 cm ; H NMR (200 MHz, CDCl
3
, 25 C):
d
7.47e7.55 (m, 2H,
ꢁ1
1
13
7:3); IR (KBr):
n
max 3406, 1685, 1624, 1095, 798, 746 cm
;
H
m-Ph), 7.62e7.71 (m, 1H, p-Ph), 7.95e8.00 (m, 2H, o-Ph);
C
1
e
ꢀ
13
ꢀ
NMR (200 MHz, DMSO-d
6
, 25 C):
d
5.83 (t, J¼7.4 Hz, 1H, CH), 6.84
NMR (50.3 MHz, CDCl
194.6; HRMS calcd for C14
211.0748.
3
, 25 C):
d
129.0, 129.9, 132.9, 134.9,
(MþH) : 211.0754; found:
þ
(
4
d, J¼7.4 Hz, 2H, 2ꢂ OH), 7.58e7.72 (m, 2H, arom.), 7.98e8.12 (m,
H
11
O
2
1
3
1e
H, arom.), 8.78 (s, 1H, arom.); C NMR (50.3 MHz, DMSO-d
5
6
,
ꢀ
2
C): d 89.5, 124.9, 127.2, 127.9, 128.3, 129.0, 129.9, 131.2, 131.7,
132.2, 135.3, 196.5; no molecular ion was detected by HRMS.
4.2.13. Ethyl 3-hydroxy-4-oxo-4-phenylbutanoate (13c). Compound
3c was obtained from 12c (120.2 mg, 0.58 mmol) and 2a (18.3 mg,
1
4
.2.8. Thiophen-2-yl-oxoacetaldehyde hemiacetal dimer (10g).
Compound 10g was obtained from 9g (74.3 mg, 0.59 mmol) and 2a
18.5 mg, 0.059 mmol) in DMSO (1.1 mL) according to general
0.058 mmol) in DMSO (1.1 mL) according to general procedure.
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 100:0 to 70:30) gave pure 13c (58.7 mg, 45%) as a pale yellow
(
procedure. Column chromatography (eluent: gradient petrolether/
ethyl acetate 90:10 to 60:40) gave pure 10g (37.7 mg, 43%) as a pale
oil; R
f
¼0.29 (petrolether/ethyl acetate 4:1); IR (KBr):
nmax 3439,
ꢁ
1
1
46
1730, 1684, 1596, 1164, 1097, 692 cm ; H NMR (200 MHz, CDCl
3
,
ꢀ
yellow oil; R
f
¼0.15 (petrolether/ethyl acetate 7:3); IR (KBr):
n
max
25 C):
d
1.25 (t, J¼7.2 Hz, 3H, CH
3
), 2.57e2.94 (m, 2H, CH
O), 5.43 (dd, JAX¼7.9 Hz, JBX¼3.9 Hz, 1H, CH
A
H
B
), 4.16
),
ꢁ
1 1
3
2
412, 1666, 1408, 1056, 729 cm
;
H NMR (200 MHz, DMSO-d
6
,
(q, J¼7.2 Hz, 2H, CH
2
X
ꢀ
13
5 C):
d
5.88 (d, J¼7.4 Hz, 1H, CH), 7.24e7.28 (m, 1H, arom.), 7.54
7.46e7.66 (m, 3H, m- and p-Ph), 7.92e7.97 (m, 2H, o-Ph); C NMR
13
ꢀ
(
(
d, J¼7.4 Hz, 1H, OH), 8.03e8.09 (m, 2H, arom.);
C NMR
(50.3 MHz, CDCl
134.0, 170.44, 199.9; HRMS calcd for C12
found: 223.0955.
3
, 25 C):
d
13.9, 40.2, 61.0, 70.1, 128.6, 128.9, 133.3,
ꢀ
þ
50.3 MHz, DMSO-d
6
, 25 C):
d
91.4, 129.1, 135.8, 136.1, 139.9, 187.5;
Na (MþNa) : 320.9862; found:
H
15
O
4
(MþH) : 223.0965;
þ
HRMS calcd for
C
12
H
10
O
5
S
2
3
20.9856.
4.2.14. Ethyl 4-oxo-4-phenylbut-2-enoate (15). Compound 15 was
4
.2.9. 2-Hydroxy-1-phenyl-1-propanone (13a). Compound 13a was
obtained from 12c (118.9 mg, 0.58 mmol) and 2a (18.1 mg,
0.058 mmol) in DMSO (1.1 mL) according to general procedure.
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 100:0 to 70:30) gave pure 15 (39.1 mg, 33%) as a light yellow
obtained from 12a (69.7 mg, 0.52 mmol) and 2a (16.3 mg,
.052 mmol) in DMSO (1.0 mL) according to general procedure.
0
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 100:0 to 90:10) gave pure 13a (46.8 mg, 60%) as a pale yellow
oil; R
f
¼0.77 (petrolether/ethyl acetate 4:1); IR (KBr):
n
max 1720,
H NMR (200 MHz, CDCl
), 4.31 (q, J¼7.2 Hz, 2H, CH O), 6.89
ꢁ
1
1
47
oil; R
f
¼0.24 (petrolether/ethyl acetate 9:1); IR (KBr):
n
max 3457,
H NMR (200 MHz, CDCl
), 3.84 (br s, 1H. OH), 5.17 (q,
J¼7.2 Hz, 1H, CH), 7.46e7.67 (m, 3H, m- and p-Ph), 7.91e7.97 (m, 2H,
1670, 1295, 1165, 729, 688 cm
;
3
,
ꢁ
1
1
44
ꢀ
1679, 1596, 1127, 968, 697 cm
;
3
,
25 C):
d
1.35 (t, J¼7.2 Hz, 3H, CH
3
2
ꢀ
2
5
C):
d
1.46 (d, J¼7.2 Hz, 3H, CH
3
(d, J¼15.0 Hz, 1H, ]CH), 7.47e7.67 (m, 3H, m- and p-Ph), 7.91 (d,
13 47
J¼15.0 Hz, 1H, CH]), 7.98e8.02 (m, 2H, o-Ph);
C NMR

M. Baranac-Stojanovi ꢀc et al. / Tetrahedron 67 (2011) 8000e8008
8007
ꢀ
(
1
50.3 MHz, CDCl
3
, 25 C):
d
14.1, 61.3,128.9,132.6,133.9,136.4,137.0,
ethyl acetate 4:1); IR (KBr):
1102, 687 cm ; H NMR (200 MHz, CDCl
n
max 3419, 1745, 1693, 1598, 1236, 1129,
ꢁ1
1
28
ꢀ
65.6, 189.6; no molecular ion was detected by HRMS.
3
, 25 C): Ethyl 2,3-dioxo-
3
-phenylpropanoate:
d
1.38 (t, J¼7.4 Hz, 3H, CH
O), 7.43e7.75 (m, 3H, m- and p-Ph), 7.98e8.02 (m, 2H, p-Ph),
1.07 (t, J¼7.4 Hz, 3H,
3
), 4.42 (q, J¼7.4 Hz,
4.2.15. 2-Acetyl-2-hydroxycyclohexanone (13d). Compound 13d
2H, CH
2
was obtained from 12d (76.7 mg, 0.55 mmol) and 2a (17.1 mg,
.055 mmol) in DMSO (1.0 mL) according to general procedure.
ethyl 2,3-dioxo-3-phenylpropanoate hydrate:
CH
(m, 3H, m- and p-Ph), 8.04e8.12 (m, 2H, p-Ph); C NMR
d
0
3
), 4.21 (q, J¼7.4 Hz, 2H, CH O), 5.48 (br s, 2H, 2ꢂ OH), 7.43e7.75
2
13 28
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 100:0 to 70:30) gave pure 13d (25.5 mg, 30%) as a pale yellow
ꢀ
(50.3 MHz, CDCl
3
, 25 C): ethyl 2,3-dioxo-3-phenylpropanoate hy-
oil; R
f
¼0.46 (petrolether/ethyl acetate 4:1); IR (KBr):
n
max 3450,
, 25 C):
drate:
calcd for ketone C11
HRMS calcd for hydrate C11
247.0578.
d
13.5, 63.1, 91.7, 128.7, 130.1, 134.6, 135.5, 169.8, 191.6. HRMS
ꢁ
1
1
28
ꢀ
þ
1707, 1355, 1122 cm
;
H NMR (200 MHz, CDCl
3
H
11
O
4
(MþH) : 207.0652; found: 207.0651;
þ
d
1.56e1.96 (m, 4H, CH
2
CH
2
), 2.00e2.17 (m, 1H, CHH), 2.24 (s, 3H,
), 4.63 (s, 1H,
H
12
O
5
Na (MþNa) : 247.0577; found:
CH
3
), 2.34e2.50 (m, 1H, CHH), 2.56e2.81 (m, 2H, CH
2
1
3
28
ꢀ
OH); C NMR (50.3 MHz, CDCl
9.3, 85.3, 207.5, 209.0; HRMS calcd for C
found: 157.0877.
3
, 25 C):
d
21.6, 25.5, 27.2, 38.4,
þ
3
8
H
13
O
3
(MþH) : 157.0859;
Acknowledgements
This work was supported by the Ministry of Science of the Re-
public of Serbia, Grant No. 142007 (to R.M.).
4
.2.16. 2,5-Dihydroxyacetophenone (16). Compound 16 was
obtained from 12d (68.7 mg, 0.49 mmol) and 2a (15.4 mg,
.049 mmol) in DMSO (0.9 mL) according to general procedure.
0
References and notes
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 100:0 to 70:30) gave pure 16 (14.1 mg, 19%) as a yellow solid,
1. For a-dicarbonyl compounds, see: (a) Quiroga, J.; Acosta, P. A.; Cruz, S.; Abonia,
ꢀ
48
ꢀ
R.; Insuasty, B.; Nogueras, M.; Cobo, J. Tetrahedron Lett. 2010, 51, 5443; (b)
Lecinska, P.; Corres, N.; Moreno, D.; Garcia-Valverde, M.; Marcaccini, S.; Torroba,
T. Tetrahedron 2010, 66, 6783; (c) Shibata, I.; Kojima, R.; Tsunoi, S.; Nozaki, T.;
Watanabe, T.; Ninomiya, A.; Yasuda, M.; Baba, A. Org. Biomol. Chem. 2010, 8,
2009; (d) Sanudo, M.; Garcia-Valverde, M.; Marcaccini, S.; Delgado, J. J.; Rojo, J.;
Torroba, T. J. Org. Chem. 2009, 74, 2189; (e) Reid, C. M.; Ebikeme, C.; Barrett, M.
P.; Patzewitz, E.-M.; M u€ ller, S.; Robins, D. J.; Sutherland, A. Bioorg. Med. Chem.
Lett. 2008, 18, 2455; (f) Khalili, B.; Jajarmi, P.; Eftekhari-Sis, B.; Hashemi, M. M. J.
Org. Chem. 2008, 73, 2090; (g) Arrault, A.; Dubuisson, M.; Gharbi, S.; Marchand,
C.; Verbeuren, T.; Rupin, A.; Cordi, A.; Bouskela, E.; Rees, J.-F.; Marchand-Bry-
mp 184e186 C (lit. 197e199 C); R
f
¼0.20 (petrolether/ethyl ac-
4
8
etate 4:1); IR (KBr):
nmax 3385, 3269, 1643, 1619, 1581, 1499, 1305,
ꢁ
1
1
48
ꢀ
6
, 25 C): d 2.57
1
214, 788, 713 cm ; H NMR (200 MHz, DMSO-d
s, 3H, CH
), 6.79 (d, J¼9.0 Hz, 1H, H(3)-Ph), 6.96e7.02 (dd, J¼9.0,
.4 Hz, 1H, H(4)-Ph), 7.17 (d, J¼3.4 Hz, 1H, H(6)-Ph), 9.72 (s, 1H, OH),
(
3
3
1
1.3 (s, 1H, OH); 13C NMR (50.3 MHz, DMSO-d
, 25 C):
ꢀ
d
28.0, 115.7,
6
1
18.6, 120.5, 124.8, 149.7, 154.1, 204.4; HRMS calcd for C
H
8 7
O
3
ꢁ
(
MꢁH) : 151.0401; found: 151.0419.
naert, J. Bioorg. Med. Chem. Lett. 2003, 13, 653 For a-hydroxyketones, see: (h)
Mengel, A.; Reiser, O. Chem. Rev. 1999, 99, 1191; (i) Ghosh, A. K.; McKee, S. P.;
Sanders, W. M. Tetrahedron Lett. 1991, 32, 711; (j) Roush, W.; Michaelides, M.;
Tai, D.; Chong, W. J. Am. Chem. Soc. 1987, 109, 7575; (k) Lin, J.; Nikaido, M.; Clark,
G. J. Org. Chem. 1987, 52, 3745; (l) Kido, F.; Kitahara, H.; Yoshikoshi, A. J. Org.
Chem. 1986, 51, 1478; (m) Shono, T.; Matsamura, S.; Matsamura, Y.; Inoue, K.;
Iwasaki, F. J. Chem. Soc., Perkin Trans. 1 1986, 73.
. (a) Chang, L. L.; Sidler, K. L.; Cascieri, M. A.; de Laszlo, S.; Koch, G.; Li, B.;
MacCoss, M.; Mantlo, N.; O’Keefe, S.; Pang, M.; Rolando, A.; Hagmann, W. K.
Bioorg. Med. Chem. Lett. 2001, 11, 2549; (b) Buehler, C. A.; Addleburg, J. W.;
Glenn, D. M. J. Org. Chem. 1955, 20, 1350.
. (a) Steinbach, L.; Becker, E. I. J. Am. Chem. Soc. 1954, 76, 5808; (b) Minor, J. T.;
Vanderwerf, C. A. J. Org. Chem. 1952, 17, 1425; (c) Riley, H. A.; Grey, A. R. Org.
Synth. 1947, II, 509.
4. Kornblum, N.; Powers, J. W.; Anderson, G. J.; Jones, W. J.; Larson, H. O.; Levand,
O.; Weaver, W. M. J. Am. Chem. Soc. 1957, 79, 6562.
4
.2.17. 3-Bromo-2-hydroxycyclohex-2-enone (17). Compound 17
was obtained from 12e (56.5 mg, 0.58 mmol) and 2a (18.0 mg,
.058 mmol) in DMSO (0.6 mL) according to general procedure.
0
Column chromatography (eluent: gradient petrolether/ethyl ace-
tate 90:10 to 70:30) gave pure 17 (7.5 mg, 7% based on 12e, 68%
based on 2a) as a white solid, mp 100e102 C (lit. 103e104 C);
R
2
ꢀ
49
ꢀ
f
¼0.62 (petrolether/ethyl acetate 7:3); IR (KBr):
n
max 3255, 1666,
ꢁ1
1
ꢀ
3
1641, 1321, 1162 cm
;
H NMR (200 MHz, CDCl
3
, 25 C):
d
2.08
(
quintet, J¼6.4 Hz, 2H, CH
2
), 2.57 (t, J¼6.4 Hz, 2H, CH
2
C]), 2.89 (t,
13
J¼6.4 Hz, 2H, CH
2
C]O), 6.41 (s,1H, OH); C NMR (50.3 MHz, CDCl
3
,
ꢀ
2
5
C):
BrO
d
22.9, 34.4, 35.5, 119.4, 146.0, 209.6; HRMS calcd for
þ
5. Floyd, M. B.; Du, M. T.; Fabio, P. F.; Jacob, L. A.; Johnson, B. D. J. Org. Chem. 1985,
C
6
H
7
2
Na (MþNa) : 212.9522; found: 212.9523.
50, 5022.
6
. (a) McKenna, J. M.; Halley, F.; Souness, J. E.; McLay, I. M.; Pickett, S. D.; Collis, A.
J.; Page, K. M.; Ahmed, I. J. Med. Chem. 2002, 45, 2173; (b) Collis, A. J.; Foster, M.
L.; Halley, F.; Maslen, C.; McLay, I. M.; Page, K. M.; Redford, E. J.; Souness, J. E.;
Wilsher, N. E. Bioorg. Med. Chem. Lett. 2001, 11, 693.
4
1
0
.2.18. 1,3-Diphenylpropane-1,2,3-trione/hydrate (19a). Compound
9a was obtained from 18a (115.8 mg, 0.52 mmol) and 2a (16.2 mg,
.052 mmol) in DMSO (1.0 mL) according to general procedure.
7
. Schipper, E.; Cinnamon, M.; Rascher, L.; Chiang, Y. H.; Oroshnik, W. Tetrahedron
Column chromatography (eluent: gradient petrolether/ethyl ace-
Lett. 1968, 6201.
8
9
. Buehler, C. A.; Harris, J. O.; Arendale, W. F. J. Am. Chem. Soc. 1950, 72, 4953.
. Barta, T. E.; Stealey, M. A.; Collins, P. W.; Weier, R. M. Bioorg. Med. Chem. Lett.
tate 100:0 to 80:20) gave pure 19a (70.6 mg, 55%, ketone/hydrate
ꢀ ꢀ
50
1
:1.6 molar ratio) as a yellow solid, mp 62e63 C (lit. 66 C);
1998, 8, 3443.
R
f
¼0.26 (petrolether/ethyl acetate 4:1); IR (KBr):
n
max 3395, 1680,
10. Walsh, C. J.; Mandal, B. K. J. Org. Chem. 1999, 64, 6102.
11. Yusubov, M. S.; Zholobova, G. A.; Vasilevsky, S. F.; Tretyakov, E. V.; Knight, D. W.
Tetrahedron 2002, 58, 1607.
ꢁ
1
1
28
ꢀ
1
1
7
596,1449,1117, 725, 686 cm ; H NMR (200 MHz, CDCl
,3-Diphenylpropane-1,2,3-trione:
.67e7.76 (m, 1H, p-Ph), 8.06e8.10 (m, 2H, o-Ph), Diphenylpropane-
3
, 25 C):
d 7.51e7.59 (m, 2H, m-Ph),
12. Wolfe, S.; Pilgrim, W. R.; Garrard, T. F.; Chamberlain, P. Can. J. Chem. 1971, 49,
1099.
13. Wan, Z.; Jones, C. D.; Mitchell, D.; Pu, J. Y.; Zhang, T. Y. J. Org. Chem. 2006, 71,
1,2,3-trione hydrate:
d
5.93 (s, 2H, 2ꢂ OH), 7.31e7.39 (m, 2H, m-Ph),
13 28
826.
7.47e7.56 (m, 1H, p-Ph), 7.92e7.96 (m, 2H, o-Ph); C NMR
1
4. (a) Heirtzler, F.; Neuburger, M.; Kulike, K. J. Chem. Soc., Perkin Trans. 1 2002, 809;
ꢀ
(
50.3 MHz, CDCl
3
, 25 C): Diphenylpropane-1,2,3-trione:
d
129.1,
(b) Bark, T.; Weyherm u€ ller, T.; Heirtzler, F. Chem. Commun. 1998, 1475.
1
5. (a) Katritzky, A. R.; Lang, H.; Wang, Z.; Zhang, Z.; Song, H. J. Org. Chem. 1995, 60,
619; (b) Buehler, C. A.; Harris, J. O. J. Am. Chem. Soc. 1950, 72, 5015.
6. Chang, H. S.; Woo, J. C.; Lee, K. M.; Ko, Y. K.; Moon, S.-S.; Kim, D.-W. Synth.
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9. (a) Mishra, J. K. Synlett 2005, 543; (b) Crimmins, M. T.; Pace, J. M.; Nantermet, P.
130.2, 132.1, 135.4, 188.2, 192.5, Diphenylpropane-1,2,3-trione hy-
7
drate:
C
d
94.0, 128.8, 130.2, 132.0, 134.7, 194.0; HRMS calcd for
(MꢁH) : 255.0663; found: 255.0677.
1
ꢁ
H
15 11
O
4
1
1
4
.2.19. Ethyl 2,3-dioxo-3-phenylpropanoate/hydrate (19b). Compo
und 19b was obtained from 18b (96.8 mg, 0.50 mmol) and 2a
15.8 mg, 0.050 mmol) in DMSO (1.0 mL) according to general
1
1
(
G.; Kim-Meade, A. S.; Thomas, J. B.; Watterson, S. H.; Wagman, A. S. J. Am. Chem.
Soc. 2000, 122, 8453; (c) Ichinari, D.; Ueki, T.; Yoshihara, K.; Kinoshita, T. Chem.
Commun. 1997, 1743; (d) Davis, F. A.; Clark, C.; Kumar, A.; Chen, B. C. J. Org. Chem.
procedure. Column chromatography (eluent: gradient petrolether/
ethyl acetate 100:0 to 80:20) gave pure 19b (65.8 mg, 59%, ketone/
1994, 59, 1184; (e) Guertin, K. R.; Chan, T.-H. Tetrahedron Lett. 1991, 32, 715; (f)
hydrate 1:5.7 molar ratio) as a yellow oil; R
f
¼0.23 (petrolether/
Reissig, H. U. Org. Synth. Highlights 1991, 40; (g) Masui, M.; Ando, A.; Shiori, T.

8008
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When working with larger quantities dimethyl sulfide should be distilled off.
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38. One of by-products formed at elevated temperatures was alkene ArCOC(SMe)]
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2
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2
2
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2
2
2
3
3
1. (a) Baranac-Stojanovi ꢀc , M.; Tatar, J.; Stojanovi ꢀc , M.; Markovi ꢀc , R. Tetrahedron
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2
3
2