Mechanism and scope of the MnIII-initiated oxidation of β-ketocarbonyl compounds: Furan synthesis

Article abstract of DOI:10.1002/ejoc.201201194

Unless the Mn^III-produced carbon-radical from β-ketocarbonyl compounds undergoes smooth intramolecular addition to alkenes, it traps molecular oxygen in the reaction medium to produce a peroxy radical, which reacts with the neighbouring carbonyl group to form 1,2-dioxetane. Thermal decomposition of 1,2-dioxetane completes the oxidation to produce α-oxo ester. This oxidation seems to be general at 50°C under aerobic conditions, and can be catalytic for Mn^III in AcOH with ultrasonic irradiation. Thus, the development of a new synthetic method for diversely substituted furans has been accomplished based on a couple of the Mn^III-initiated domino oxidation of β-ketocarbonyl compounds with a suitable α-allylic substitution. Copyright

Full text of DOI:10.1002/ejoc.201201194

FULL PAPER
DOI: 10.1002/ejoc.201201194
Mechanism and Scope of the MnIII-Initiated Oxidation of β-Ketocarbonyl
Compounds: Furan Synthesis
Chao Wang,[a,b] Zhilong Li,[a,b] Yeming Ju,[a,b] and Sangho Koo*[a,b]
Dedication to Professor Masato Koreeda on the occasion of his 70th birthday
Keywords: Reaction mechanisms / Cyclization / Oxygen heterocycles / Radicals / Manganese / Oxidation
Unless the MnIII-produced carbon-radical from β-keto-
carbonyl compounds undergoes smooth intramolecular ad-
dition to alkenes, it traps molecular oxygen in the reaction
medium to produce a peroxy radical, which reacts with the
neighbouring carbonyl group to form 1,2-dioxetane. Thermal
decomposition of 1,2-dioxetane completes the oxidation to
produce α-oxo ester. This oxidation seems to be general at
50 °C under aerobic conditions, and can be catalytic for MnIII
in AcOH with ultrasonic irradiation. Thus, the development
of a new synthetic method for diversely substituted furans
has been accomplished based on a couple of the MnIII-initi-
ated domino oxidation of β-ketocarbonyl compounds with a
suitable α-allylic substitution.
Introduction
The MnIII-initiated radical cyclisation of β-keto esters
containing a suitably substituted alkenyl chain has proven
to be a useful method for the construction of five- or six-
membered ring structures.[1] The cascade cyclisation is espe-
cially suitable for the synthesis of cyclic isoprenoids.[2] We
recently reported the unusual MnIII-initiated oxidation of
β-keto ester 1 containing a geranyl group at the α-position.
The δ-hydroxy β,γ-unsaturated α-oxo ester 4 was conceived
to be formed after two consecutive oxidations through 3
and to undergo the intramolecular hetero Diels–Alder reac-
tion to produce the bicyclic dihydropyran 2 in 74% yield
(Scheme 1).[3] We also demonstrated that this type of reac-
tion is general for β-keto esters with a similar substitution
pattern.
Scheme 1. MnIII-initiated oxidation/hetero-Diels–Alder reaction of
α-geranyl-β-keto ester 1.
Several questions consequently arose: Is this oxidation
truly general for β-keto esters and would other substitution
patterns lead to other useful structures? What is the con-
trolling factor for the reaction pathway either to the car-
bon-radical cyclisation or to the oxidation? What is the
mechanism of this unusual oxidation? Why are three equiv-
alents of Mn(OAc)3 required for the oxidation? Can it be
catalytic? To address these questions, we prepared a diverse
set of β-keto esters and extensively studied the MnIII-initi-
ated oxidation reaction under various conditions. The re-
sults are disclosed in this work.
[a] School of Pharmacy, East China University of Science and
Technology,
Results and Discussion
Meilong Road 130, Shanghai, 20037, China
[b] Department of Nano Science and Engineering; Department of
Chemistry, Myong Ji University,
The β-keto ester 5, containing an alkenyl chain with dif-
ferent methyl substitution patterns, was first prepared to
check the generality of the above oxidation, more specifi-
cally in the hope of producing a furan derivative. No car-
bon-radical cyclisation was observed under conditions in-
volving Mn(OAc)3·2H2O and Cu(OAc)2·H2O in EtOH at
room temperature for 6 h, and the δ-hydroxy β,γ-unsatu-
San 38-2, Nam-Dong, Yongin, Kyunggi-Do, 449–728, South
Korea
Fax: +82-31-335-7248
E-mail: sangkoo@mju.ac.kr
Homepage: http://www.kooslab.org
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201194.
6976
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 6976–6985

Oxidation of β-Ketocarbonyl Compounds
rated α-oxo ester 6 and the furan 7 were obtained in 19 and OAc as R3 for the sake of synthetic convenience, which can
58% yields, respectively (Scheme 2). It is clear that the be replaced by other functional groups for further manipu-
MnIII-initiated oxidation of β-keto ester 5 produced the α- lations.
oxo ester 6, containing the secondary δ-hydroxy group,
Table 1. MnIII-initiated furan synthesis of β-keto esters 8 according
which then underwent heterocyclisation to produce furan 7.
Inspired by this finding, we decided to examine the general-
ity of this furan synthesis by the MnIII-initiated oxidation
and heterocyclisation strategy.
to Scheme 3.
Entry
8
R1
R2
R3
Yield
14 [%]
1
2
3
4
5
6
7
8
9
10
a
b
c
d
e
f
OEt
OEt
OEt
Me
NEt2
OEt
OEt
OEt
OEt
OEt
Me
Me
Ph
Ph
OAc
OMe
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
57
60
74
47
41
65
52
64
63
55
Ph
p-Cl-C6H4
p-MeO-C6H4
2-naphthyl
cyclopropyl
cyclohexyl
g
h
i
j
Scheme 2. MnIII-initiated oxidation/heterocyclisation of β-keto es-
ter 5.
The β-keto ester 8c containing a phenyl group as R2 was
selected as a model case to elucidate the full mechanistic
details of the MnIII-initiated oxidation, in which the com-
petitive carbon-radical cyclisation to the phenyl ring would
possibly produce indane 15c (Scheme 4). The products and
their yields of the MnIII-initiated reaction of 8c are summa-
rized, together with the reaction conditions, in Table 2, and
detailed mechanisms are proposed in Scheme 4. Our initial
concern was to develop the possibility of controlling the
reaction pathway by directing the reaction towards either
oxidation to the furan 14c or carbon-radical cyclisation to
indane 15c.
The general structure 8 was proposed for the furan syn-
thesis, which can be prepared by coupling between β-keto-
carbonyl compounds 9 and allylic bromides 10 (Scheme 3).
Allylic bromides 10, containing various R2 substituents,
were efficiently synthesized from readily available methyl
ketones 11 following the sequence of bromination (N-bro-
mosuccinimide (NBS), cat. TMS·OTf),[4] vinylmagnesium
bromide addition, and acetylation/allylic migration (cat.
pTsOH, AcOH/Ac2O for R3 = OAc).[5] A mixture of E- and
Z-isomers was obtained in the alkenyl chain, which did not
affect the oxidation or cyclisation.
Application of the initial conditions {3 equiv. Mn(OAc)3·
2H2O, 1 equiv. Cu(OAc)2·H2O in 94% EtOH at 15 °C for
24 h in the air} produced furan 14c in 39% yield (Table 2,
entry 1). We found an interesting temperature effect on the
reaction pathway; furan formation was optimised at 50 °C,
whereas radical cyclisation was the major pathway at 80 °C
in the presence of CuII salt, which partly indicated the im-
portance of O2 solubility in the reaction medium depending
on the temperature (Table 2, entries 2 and 3). The formation
of indane 15c in up to 53% yield was optimised in anhy-
drous EtOH (Table 2, entry 4) under an argon atmosphere
after careful degassing (Table 2, entry 5). The CuII salt is
necessary for oxidative aromatisation of the cyclohexadienyl
radical. Indane 15c was not observed in the absence of CuII
salt, instead, cyclopentenone 18 (39%) was obtained to-
gether with furan 14c (15%) at 80 °C under aerobic condi-
tions (Table 2, entry 6). The water content (less than 6%)
in EtOH does not make any difference to furan formation
(Table 2, entries 2 and 7), but the CuII salt reduces the yield
Scheme 3. Preparation and MnIII-initiated furan synthesis of β-keto
esters 8.
The best conditions {3 equiv. Mn(OAc)3·2H2O in 94% by 10% at 50 °C (Table 2, entries 2 and 8). The optimised
EtOH (6% water content) at 50 °C for 5 h in the air (see yield of 14c (74%) was obtained when Mn(OAc)3·2H2O
below)} were applied to produce the diversely substituted (3 equiv.) was used in 94% EtOH at 50 °C for 5 h in the air
furans 14 in moderate to good yields (Table 1). Our furan (Table 2, entry 8).
synthesis allows a carbonyl group (ketone, ester, and amide)
It is clear that one-electron oxidation of the manga-
to be located at the 2-position, which is complementary to nese(III) enolate of β-keto ester 8c produces the α-carbon-
the Feist–Benary method, which provides a carbonyl group radical A in the first step (Scheme 4).[7] The α-peroxy radi-
at the 3-position.[6] Various alkyl, cycloalkyl, and aryl R2 cal B is then postulated to be formed from A by trapping
groups can be attached at the 4-position. We mostly utilised O2, which is dissolved in the solvent.[8] This scenario was
Eur. J. Org. Chem. 2012, 6976–6985
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6977

C. Wang, Z. Li, Y. Ju, S. Koo
FULL PAPER
Scheme 4. Products and the mechanism of the MnIII-initiated reaction of β-keto ester 8c.
Table 2. The products and yields of the MnIII-initiated reaction of dition but in the absence of O2 (Table 2, entry 9). The first
β-keto ester 8c (see Scheme 4).[a]
oxidation may be completed through the formation and
Entry MnII
CuII
Solvent
T/t
[°C/h]
Product yield [%]
fragmentation of 1,2-dioxetane C to produce α-oxo ester
16. Thermal decomposition of 1,2-dioxetanes to carbonyl
compounds is known in the literature.[9] The second oxi-
dation of 16 to 17 may proceed in a similar way. One-elec-
tron oxidation of the MnIII enolate of α-oxo ester 16, O2
trapping of the resulting δ-carbon-radical, and reduction of
the peroxy radical to peroxide and then to the hydroxy
group produces δ-hydroxy β,γ-unsaturated α-oxo ester 17.
Under these conditions, EtOH and MnII can act as a reduc-
ing agent in the above reduction.[10] Finally, δ-hydroxy β,γ-
unsaturated α-oxo ester 17 cyclised and aromatised to give
furan 14c.
(equiv.) (equiv.)
8c
14c 15c
1
2
3
4
5
3
3
3
3
3
1
1
1
1
1
EtOH[b]
EtOH[b]
EtOH[b]
EtOH[c]
EtOH[c]
Ar[d]
15/24
50/5
80/5
80/5
80/5
–
–
–
–
–
39
64
6
–
–
–
–
16
34
53
6[e]
7
8
3
3
3
3
0
1
0
0
EtOH[b]
EtOH[c]
EtOH[b]
EtOH[b]
Ar[d]
80/5
50/5
50/5
50/5
–
–
–
15
62
74
2
–
–
–
–
9
50
10[f]
3
0
EtOH[b]
15/24
–
31
–
[g]
O2
The 1,2-dioxetane formation/fragmentation and the final
cyclisation seemed to be favourable at 50 °C (the optimum
temperature for furan formation). On the other hand, the
formation of cyclopentenone 18 (39%) was the major pro-
cess at 80 °C in the air (Table 2, entry 6), which presumably
proceeds through MnIII-mediated deacetylation and intra-
molecular aldol reaction from 17. Considering the impor-
tance of O2 in the oxidation, the reaction was carried out
under a positive pressure of O2 at 15 °C (Table 2, entry 10).
Tricarbonyl compound 19 (16%) was obtained, presumably
via 1,2-diperoxide intermediate D, together with furan 14c
(31%). The stable tertiary benzylic radical generated from
the peroxy radical intermediate B would trap extra O2 in the
reaction medium to produce 1,2-diperoxide intermediate D,
which would undergo fragmentation to provide tricarbonyl
compound 19. The solvent effect on the oxidation reaction
was then checked. Acetonitrile was not a good solvent for
the oxidation; under these conditions most 8c (57%) was
recovered, and only 13% of the furan product 14c was pro-
duced (Table 2, entry 11). A little inferior but almost com-
parable yield of 14c (53%) was obtained in AcOH under
the above optimised conditions (Table 2, entry 12).
11
12
13
14
15
16
17
18
19[i]
3
3
2
1
1
0
0
0
0
0
0
0
0
0
MeCN
AcOH
50/5
50/5
50/5
50/11
15/1
50/1
15/1
15/1
15/1
57
–
–
–
–
–
–
8
6
13
53
57
35
53
47
39
40
35
–
–
–
EtOH[b]
EtOH[b]
AcOH[h]
AcOH[h]
AcOH[h]
AcOH[h]
AcOH[h]
–
29
26
18
9
1
0.3
0.1
0.1
–
[g]
O2
20
0.3
0
AcOH[j]
15/1
4
57
–
[a] The reaction was carried out in the air unless otherwise noted.
[b] 94% EtOH (6% H2O). [c] 99.9% EtOH (anhydrous). [d] The
reaction mixture was degassed by the freeze-thaw method before
argon was added. [e] 18 was also obtained in 39% yield. [f] 19 was
also obtained in 16% yield. [g] A balloon filled with O2 was at-
tached to the reaction flask. [h] Ultrasonic irradiation with 20%
intensity of maximum 130 W, 20 KHz power was continuously ap-
plied. [i] 19 was also obtained in 12% yield. [j] Ultrasonic irradia-
tion with the intensity given in footnote [h] for 60 sec and then 10
sec pause were repeatedly applied.
supported by the fact that 8c (50%) was recovered with only
2% yield of the furan product 14c under the optimised con-
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Oxidation of β-Ketocarbonyl Compounds
The oxidation can be catalytic for MnIII because MnII the intermediate peroxy and oxy radicals, which required
may be oxidised back during the formation of
C
MnIII for the oxidation of the resulting α-hydroxyethyl radi-
(Scheme 4). Thermal decomposition of C would regenerate cal to acetaldehyde, and thus 17% of the β-keto ester 20
Mn(OAc)3. Furthermore, in the second oxidation MnII can was recovered (Table 3, entry 1).
be converted into MnIII during the reduction of the peroxy
Table 3. The products and yields of the MnIII-promoted oxidation
radical. The yield of the furan product 14c was, however,
of β-keto ester 20.[a]
decreased as the amount of MnIII was reduced (Table 2, en-
Entry MnIII Solvent
[equiv.]
T/t
[°C/h]
Product [%]
Ratio
22/21
tries 13 and 14). Because, under these conditions, EtOH is
a good reducing agent, it may compete with MnII in reduc-
ing the oxy radical of 1,2-dioxetane to the corresponding
hemiacetal and/or the peroxy radical to the corresponding
peroxide, which requires another equivalent of MnIII for the
oxidation of the resulting α-hydroxyethyl radical to acetal-
dehyde.[9] This explains the requirement for three equiva-
lents of MnIII in the optimised conditions in EtOH.
With the above considerations in mind, we replaced the
solvent with AcOH, which is a much weaker hydrogen do-
nor, to develop a catalytic version of the oxidative furan
synthesis of β-keto ester 8c. We were able to reduce the
amount of MnIII from three to one equivalent in AcOH (at
15 °C for 1 h, ultrasonic irradiation) without decreasing the
yield of furan 14c (Table 2, entry 15).[11] The formation of
indane 15c (29%) was also observed in this case, which
could be explained by the activation (or possibly degassing)
effect of ultrasonic irradiation. Raising the reaction tem-
perature to 50 °C under ultrasonication did not provide any
positive effect (Table 2, entry 16). The amount of MnIII
20
21
22
1
2
3
4
5
6
7
1.0
1.0
0.3
0.3
0.1
0.1
1.0
EtOH[b]
EtOH[b]
EtOH[b]
EtOH[b]
EtOH[b]
EtOH[b]
AcOH
15/6
50/6
15/6
50/6
15/24
50/6
15/6
17
–
44
26
70
37
30
21
16
14
12
11
10
–
27
46
13
30
11
28
34
1.3
2.9
0.9
2.5
1.0
2.8
22
only
22
only
22
only
22
only
22
only
8
0.3
0.1
0.1
0.1
AcOH
AcOH
AcOH
AcOH[c]
15/6
15/6
50/6
15/1
35
56
30
–
–
–
–
–
8
6
9
10
11
21
63
[a] The reaction was carried out in the air. [b] 94% EtOH (6%
H2O). [c] Ultrasonic irradiation with 20% intensity of maximum
130 W, 20 KHz power was applied.
The assumption that α-hydroxy β-keto ester 21 might be
could be reduced to even 0.3 or 0.1 equiv. to produce a precursor of α-oxo ester 22 was ruled out because 21 did
ca. 40% yield of furan 14c in AcOH under ultrasonication not produce 22 upon treatment with 2 equiv. MnIII even at
(Table 2, entries 17 and 18). The catalytic reaction under a 50 °C for 6 h. Ester 21 and α-oxo ester 22 must be produced
positive O2 pressure may reduce the amount of carbon-radi- from the peroxy radical intermediate E by either direct re-
cal cyclisation product 15c, however, tricarbonyl compound duction or through the formation of 1,2-dioxetane. We ob-
19 (12%) was obtained instead (Table 2, entry 19). An im- served that conducting the reaction at a temperature of
proved yield of furan 14c (57%) under catalytic conditions 50 °C again favoured formation of the α-oxo ester 22. The
was obtained by the programmed application of ultrasonic yield of 22 was increased to 46% and 20 was not observed
irradiation (on for 60 sec and off for 10 sec) for 1 h to allevi- at 50 °C when one equivalent of MnIII was used in EtOH
ate the activation of the carbon-radical cyclisation (Table 2, (Table 3, entry 2). We confirmed that this temperature effect
entry 20).
was also apparent under the catalytic conditions of MnIII
The MnIII-promoted oxidation of simple β-keto ester 20, in EtOH; under these conditions ca. 1:1 yield ratio of 22/21
containing a α-hexyl group, was reinvestigated to gain a was obtained at 15 °C, whereas the ratio changed to ca.
better understanding of the temperature and the solvent ef- 2.8:1 in favour of 22 at 50 °C (Table 3, entries 3–6). Thus,
fects (Scheme 5 and Table 3). α-Hydroxy β-keto ester 21 1,2-dioxetane formation and decomposition from the per-
and α-oxo ester 22 were obtained in 21 and 27% yields, oxy radical E is favoured at 50 °C to produce α-oxo ester
respectively, when one equivalent of MnIII was used in 94% 22.
EtOH at 15 °C for 6 h. The reaction was not complete, pre-
No α-hydroxy β-keto ester 21 was observed under any
sumably because of the role of EtOH in the reduction of conditions when AcOH was used as solvent (Table 3, entries
7–11); in these cases, MnII might be the main reducing
agent for the intermediate peroxy radical E. The peroxy
radical E presumably led to 1,2-dioxetane formation and
fragmentation in AcOH instead of direct reduction medi-
ated by MnII. However, the reaction was still not catalytic
for MnIII, and an appreciable amount of β-keto ester 20
was recovered even at 50 °C (Table 3, entries 7–10). Acti-
vation by ultrasonic irradiation was necessary to induce the
formation and fragmentation of 1,2-dioxetane to produce
α-oxo ester 22. Finally, 63% yield of α-oxo ester 22 was
obtained when 0.1 equiv. MnIII was used for the oxidation
in AcOH under ultrasonication (Table 3, entry 11).
Scheme 5. MnIII-promoted oxidation of β-keto ester 20 with α-
hexyl substitution.
Eur. J. Org. Chem. 2012, 6976–6985
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6979

C. Wang, Z. Li, Y. Ju, S. Koo
FULL PAPER
A series of α-benzoyl esters 23a–d containing the aro-
matic para-substituent X (Cl, H, Me, and OMe) of a dif-
ferent electronic nature was prepared to support the 1,2-
dioxetane mechanism for the oxidation to α-oxo ester 22
(Scheme 6 and Table 4). The oxidation was carried out
using 3 equiv. MnIII in 94% EtOH at 50 °C for 6 h. We
anticipated that the electron-deficient benzoyl group would
facilitate intramolecular 1,2-dioxetane formation for the in-
termediate peroxy radical to produce 22 rather than re-
duction to 24. This idea was confirmed by the observed
increasing ratio of the yields of 22 over 24 as the electron-
withdrawing efficiency of X increased. The corresponding
benzoic acid derivatives 25a–d were also obtained in slightly
lower yield, presumably due to adsorption by silica gel dur-
ing the purification process.
Experimental Section
General Experimental: 1H and 13C NMR spectra were recorded
with a Varian 400-MR spectrometer at 400 and 100 MHz NMR
frequencies, respectively, in CDCl3 with tetramethylsilane (TMS) as
an internal reference. Solvents for extraction and chromatography
were reagent grade and used as received. Column chromatography
was performed by the method of Still with silica gel 60, 70–
230 mesh ASTM supplied by Merck, using a gradient mixture of
EtOAc/hexanes. Reactions were performed in a flask open to the
air unless noted otherwise. The reaction mixture under argon atmo-
sphere was prepared by the freeze-thaw method to remove O2 com-
pletely, and the reagents were added in a glove box filled with ar-
gon. Reactions under positive pressure of O2 were performed by
using a balloon filled with O2. Ultrasonic irradiation was applied
for a designated time period with 20% intensity of maximum
130 W, 20 KHz power.
Ethyl 2-Acetyl-4,8,12-trimethyltrideca-4,8,12-trienoate (5): To a
stirred solution of 2,6,10-trimethylundeca-2,6,10-trien-1-ol (0.50 g,
2.41 mmol) in Et2O (25 mL), was added PBr3 (0.27 g, 0.96 mmol)
at 0 °C. The mixture was stirred for 30 min, diluted with Et2O,
washed with H2O, dried with anhydrous Na2SO4, filtered, and con-
centrated under reduced pressure to give 11-bromo-2,6,10-trimeth-
ylundeca-1,5,9-triene as a light-yellow oil.
To a stirred solution of ethyl acetoacetate (0.32 g, 2.41 mmol) in
THF (20 mL) was added 60% NaH (0.20 g, 4.82 mmol) at 0 °C.
The mixture was stirred for 1 h, and the above crude bromination
product was added to the mixture. The reaction mixture was stirred
at room temperature for 12 h, diluted with EtOAc, washed with
1 m HCl solution, dried with anhydrous Na2SO4, filtered, and con-
centrated under reduced pressure. The crude product was purified
by SiO2 flash chromatography to give 5 (0.33 g, 0.11 mmol, 43%)
Scheme 6. MnIII-promoted oxidation of α-benzoyl ester 23.
Table 4. Products and yields of the MnIII-promoted oxidation of α-
benzoyl ester 23.
Entry 23 (X)
Yield 24 Yield 22 Yield 25 Ratio 22/24
1
as a clear oil. H NMR: δ = 1.26 (t, J = 7.2 Hz, 3 H), 1.59 (s, 3
[%]
[%]
[%]
H), 1.61 (s, 3 H), 1.73 (s, 3 H), 1.93–1.97 (m, 2 H), 2.01–2.08 (m,
4 H), 2.08–2.16 (m, 2 H), 2.21 (s, 3 H), 2.46–2.58 (m, 2 H), 3.61 (t,
J = 8.0 Hz, 1 H), 4.17 (q, J = 7.2 Hz, 2 H), 4.68 (s, 1 H), 4.71 (s,
1 H), 5.11 (dt, Jd = 1.2, Jt = 6.8 Hz, 1 H), 5.16 (dt, Jd = 1.2, Jt =
7.2 Hz, 1 H) ppm. 13C NMR: δ = 14.1, 15.8, 15.9, 22.5, 26.2, 26.6,
28.8, 37.8, 38.0, 39.4, 58.5, 61.3, 109.8, 124.2, 127.2, 130.9, 134.8,
1
2
a (Cl)
11
12
31
14
32
21
27
6
24
14
12
5
2.90
1.75
0.87
0.43
b (H)
3
c (Me)
d (OMe)
4[a]
[a] The reaction of 23d was slow compared to the other cases and
required 16 h.
145.9, 169.6, 203.0 ppm. IR (KBr): ν = 3074, 2967, 2925, 2856,
˜
1741, 1717, 1650, 1446, 1368, 1358, 1331, 1298, 1262, 1214, 1174,
1150, 1098, 1046, 1025, 886 cm–1. HRMS (CI+): calcd. for
C20H33O3 321.2430; found 321.2431.
Conclusions
Ethyl 5-Hydroxy-4,8,12-trimethyl-2-oxotrideca-3,8,12-trienoate (6)
and Ethyl 5-(3,7-Dimethylocta-3,7-dienyl)-4-methylfuran-2-carb-
oxylate (7): To a stirred solution of β-keto ester 5 (0.86 g,
2.68 mmol) in 94% EtOH (10 mL), were added Mn(OAc)3·2H2O
(2.24 g, 8.03 mmol) and Cu(OAc)2·H2O (0.47 g, 2.68 mmol). The
reaction mixture was stirred at 20 °C for 6 h, then the resulting
mixture was diluted with CH2Cl2, washed with 1 m HCl solution,
dried with anhydrous Na2SO4, filtered, and concentrated under re-
duced pressure. The crude product was purified by SiO2 flash col-
umn chromatography to give 6 (0.16 g, 0.50 mmol, 19%) and 7
(0.45 g, 1.55 mmol, 58%) as light-yellow oils.
Compound 6: 1H NMR: δ = 1.38 (t, J = 7.2 Hz, 3 H), 1.64 (s, 3 H),
1.72 (s, 3 H), 1.72–1.83 (m, 2 H), 2.00–2.08 (m, 2 H), 2.08–2.17 (m,
4 H), 2.18 (s, 3 H), 4.17 (dd, J = 7.8, 4.0 Hz, 1 H), 4.33 (q, J =
7.2 Hz, 2 H), 4.68 (s, 1 H), 4.71 (s, 1 H), 5.20 (t, J = 6.4 Hz, 1 H),
7.02 (s, 1 H) ppm. 13C NMR: δ = 14.0, 15.8, 16.9, 22.4, 26.0, 33.1,
35.6, 37.5, 62.3, 76.2, 109.9, 116.7, 125.4, 134.3, 145.6, 162.2, 162.7,
We developed a new method for furan synthesis by
MnIII-initiated oxidations and heterocyclisation of β-keto
esters containing α-allylic substitution. We established the
controlling factors for the reaction pathway leading to
either oxidation or to carbon-radical cyclisation. Rigorous
exclusion of O2 as well as a suitable disposition of alkenyl
groups relative to the radical centre are prerequisites for
smooth carbon-radical cyclisation, together with the assist-
ance of the CuII salt. Otherwise, oxidation of the α-carbon
radicals is the general pathway. Molecular oxygen is trapped
to give the α-peroxy radical, which could either be directly
reduced to a hydroxy group or undergo 1,2-dioxetane for-
mation and fragmentation (favoured at 50 °C) to produce
α-oxo esters. This oxidation can be catalytic in AcOH under
ultrasonication. Further work on extending this oxidation
and cyclisation to the synthesis of polycyclic compounds is
underway.
182.8 ppm. IR (KBr): ν = 3477, 3074, 2978, 2934, 1728, 1537, 1447,
˜
1371, 1315, 1261, 1192, 1095, 1022 cm–1. HRMS (CI+): calcd. for
C18H29O4 309.2066; found 309.2071.
6980
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 6976–6985

Oxidation of β-Ketocarbonyl Compounds
1
Compound 7: H NMR: δ = 1.35 (t, J = 7.2 Hz,3 H), 1.63 (s, 3 H), H), 7.30–7.37 (m, 2 H), 7.49–7.54 (m, 1 H), 7.58–7.63 (m, 1
1.71 (s, 3 H), 1.97 (s, 3 H), 1.99 (t, J = 8.4 Hz, 2 H), 2.10 (q, J =
7.2 Hz, 2 H), 2.30 (t, J = 7.6 Hz, 2 H), 2.72 (t, J = 8.0 Hz, 2 H),
4.33 (q, J = 7.2 Hz, 2 H), 4.65 (s, 1 H), 4.69 (s, 1 H), 5.12 (t, J =
6.8 Hz, 3 H), 6.95 (s, 1 H) ppm. 13C NMR: δ = 9.7, 14.4, 15.9,
22.4, 25.4, 26.1, 37.6, 37.9, 60.5, 109.8, 116.8, 121.1, 125.1, 133.7,
H) ppm. 13C NMR: δ = 14.0, 20.9, 26.1, 36.0, 61.9, 62.0, 70.2,
114.1, 120.9, 127.1, 129.0, 129.2, 140.8, 141.3, 142.7, 170.3, 170.9,
202.5 ppm. IR (KBr): ν = 2982, 2936, 1736, 1715, 1599, 1447, 1364,
˜
1221, 1153, 1022, 955 cm–1. HRMS (EI+): calcd. for C18H20O5
316.1310; found 316.1313.
145.7, 156.5, 159.0 ppm. IR (KBr): ν = 2966, 2928, 1726, 1655,
˜
Ethyl 1-Hydroxy-4-oxo-3-phenylcyclopent-2-enecarboxylate (18): To
a stirred solution of 8c (0.24 g, 0.75 mmol) in 94% EtOH (15 mL)
was added Mn(OAc)3·2H2O (0.63 g, 2.26 mmol). The reaction mix-
ture was heated at 80 °C for 5 h, and cooled to room temperature.
The resulting mixture was diluted with CH2Cl2, washed with 1 m
HCl, dried with anhydrous Na2SO4, filtered, and concentrated un-
der reduced pressure. The crude product was purified by SiO2 flash
chromatography to give furan 14c (0.033 g, 0.11 mmol, 15%) and
cyclopentenone 18 (0.072 g, 0.29 mmol, 39%) as light-yellow oils.
1535, 1448, 1369, 1313, 1192 cm–1. HRMS (CI+): calcd. for
C18H27O3 291.1960; found 291.1967.
(E)-Ethyl 6-Acetoxy-2-acetyl-4-phenyl-4-hexenoate (8c): To a stirred
solution of ethyl acetoacetate (0.51 g, 3.91 mmol) in THF (20 mL)
at 0 °C, was added 60% NaH (0.18 g, 4.56 mmol). The mixture was
stirred at 0 °C for 1 h, and a solution of 4-bromo-3-phenyl-2-bu-
tenyl acetate (10a; 0.88 g, 3.26 mmol) in THF (5 mL) was added.
The reaction mixture was slowly warmed to room temperature and
stirred for 12 h. The resulting mixture was diluted with EtOAc,
washed with 1 m HCl solution, dried with anhydrous Na2SO4, fil-
tered, and concentrated under reduced pressure. The crude product
was purified by SiO2 flash column chromatography to give 8c
(0.90 g, 2.82 mmol, 86%, 5:1 mixture of E/Z isomers) as a light-
yellow oil. Data for (E)-8c: 1H NMR: δ = 1.22 (t, J = 7.2 Hz, 3
H), 2.07 (s, 3 H), 2.11 (s, 3 H), 2.96–3.17 (m, 2 H), 3.42 (t, J =
7.2 Hz, 3 H), 4.06–4.18 (m, 2 H), 4.80 (dd, J = 6.8, 2.4 Hz, 2 H),
5.79 (t, J = 6.8 Hz, 1 H), 7.27–7.36 (m, 5 H) ppm. 13C NMR: δ =
14.0, 20.8, 28.3, 29.4, 57.7, 61.3, 61.5, 125.2, 126.7, 128.0, 128.6,
1
Data for 18: H NMR: δ = 1.28 (t, J = 7.2 Hz, 3 H), 2.81 (d, J =
18.0 Hz, 1 H), 3.10 (d, J = 18.0 Hz, 1 H), 3.89 (s, 1 H), 4.22–4.37
(m, 2 H), 7.41 (s, 1 H), 7.37–7.45 (m, 3 H), 7.70–7.76 (m, 2 H) ppm.
13C NMR: δ = 14.0, 48.7, 63.3, 76.4, 127.7, 128.5, 129.5, 129.9,
144.6, 153.4, 173.9, 203.1 ppm. IR (KBr): ν = 3453, 2982, 1717,
˜
1493, 1447, 1343, 1261, 1180, 1030, 961, 860, 764, 694 cm–1. HRMS
(CI+): calcd. for C14H15O4 247.0970; found 247.0966.
Ethyl 2-Acetyl-2-hydroxy-4-oxo-4-phenylbutanoate (19): To a stirred
solution of 8c (0.24 g, 0.75 mmol) in 94% EtOH (15 mL) was
added Mn(OAc)3·2H2O (0.63 g, 2.26 mmol). The reaction mixture
was stirred at 15 °C for 24 h under an O2 atmosphere. The resulting
mixture was diluted with CH2Cl2, washed with 1 m HCl, dried with
anhydrous Na2SO4, filtered, and concentrated under reduced pres-
sure. The crude product was purified by SiO2 flash chromatography
to give the furan 14c (0.070 g, 0.23 mmol, 31%) and 19 (0.032 g,
140.6, 141.2, 169.0, 170.7, 201.9 ppm. IR (KBr): ν = 2982, 1736,
˜
1647, 1443, 1366, 1227, 1150, 1022, 957, 856, 764, 698 cm–1. HRMS
(EI+): calcd. for C18H22O5 318.1467; found 318.1474.
COSY and NOESY spectra of 8c are included in the Supporting
Information.
1
0.12 mmol, 16%) as light-yellow oils. Data for 19: H NMR: δ =
Ethyl 5-(Acetoxymethyl)-4-phenylfuran-2-carboxylate (14c): To a
stirred solution of 8c (0.11 g, 0.35 mmol) in 94% EtOH (10 mL),
was added Mn(OAc)3·2H2O (0.29 g, 1.04 mmol). The reaction mix-
ture was heated at 50 °C for 5 h, then cooled to room temperature.
The resulting mixture was diluted with CH2Cl2, washed with 1 m
HCl solution, dried with anhydrous Na2SO4, filtered, and concen-
trated under reduced pressure. The crude product was purified by
SiO2 flash column chromatography to give 14c (0.076 g, 0.26 mmol,
74%) as a light-yellow oil. 1H NMR: δ = 1.40 (t, J = 7.2 Hz, 3 H),
2.12 (s, 3 H), 4.40 (q, J = 7.2 Hz, 2 H), 5.17 (s, 2 H), 7.27 (s, 1 H),
7.34–7.46 (m, 5 H) ppm. 13C NMR: δ = 14.4, 20.8, 57.3, 61.3,
1.28 (t, J = 7.2 Hz, 3 H), 2.36 (s, 3 H), 3.70 (d, J = 18.0 Hz, 1 H),
3.93 (d, J = 18.0 Hz, 1 H), 4.22–4.34 (m, 2 H), 4.61 (s, 1 H), 7.43–
7.51 (m, 2 H), 7.57–7.63 (m, 1 H), 7.90–7.98 (m, 2 H) ppm. 13C
NMR: δ = 13.9 (OCH2CH3), 24.6 (O=CCH3), 43.7, 62.9, 82.3,
128.2, 128.7, 133.8, 136.1, 170.2, 197.4, 204.3 ppm. IR (KBr): ν =
˜
3462, 2982, 2930, 1720, 1686, 1597, 1449, 1354, 1219, 1136, 1072,
1013, 856, 756, 689 cm–1. HRMS (CI+): calcd. for C14H17O5
265.1076; found 265.1078.
Ethyl 6-Acetoxy-2-acetyl-4-methylhex-4-enoate (8a): Following the
standard procedure for 8c, the reaction of ethyl acetoacetate
118.8, 128.0, 128.1, 128.5, 129.0, 131.4, 144.6, 148.3, 158.6, (8.66 g, 65.24 mmol) with 60% NaH (3.05 g, 76.12 mmol) and 4-
170.5 ppm. IR (KBr): ν = 2978, 2924, 2851, 1721, 1616, 1539, 1497,
bromo-3-methyl-2-butenyl acetate (11.26 g, 54.37 mmol) in THF
(40 mL) at 0 °C for 1 h and then at room temperature for 12 h,
produced 8a (11.15 g, 43.83 mmol, 80%, E/Z = 3:1) as a light-yel-
low oil after purification by SiO2 flash chromatography. Data for
˜
1451, 1370, 1315, 1223, 1153, 1107, 1022, 964, 910, 760, 729,
698 cm–1. HRMS (EI+): calcd. for C16H16O5 288.0997; found
288.0992.
1
(E)-8a: H NMR: δ = 1.27 (t, J = 6.8 Hz, 3 H), 1.71 (s, 3 H), 2.04
Ethyl
3-(2-Acetoxyethylidene)-1-acetyl-2,3-dihydro-1H-indene-1-
(s, 3 H), 2.23 (s, 3 H), 2.59 (dd, J = 7.6, 2.4 Hz, 2 H), 3.64 (t, J =
7.6 Hz, 1 H), 4.19 (q, J = 6.8 Hz, 2 H), 4.54 (d, J = 6.8 Hz, 2 H),
5.36 (dt, Jd = 1.2, Jt = 6.8 Hz, 1 H) ppm. 13C NMR: δ = 13.8,
16.1, 20.6, 28.6, 37.2, 57.7, 60.6, 61.2, 120.9, 137.6, 169.0, 170.6,
carboxylate (15c): A solution of 8c (0.24 g, 0.75 mmol) in 99.9%
EtOH (15 mL) was degassed by the freeze-thaw method, and then
charged with Ar. Mn(OAc)3·2H2O (0.63 g, 2.26 mmol) and
Cu(OAc)2·H2O (0.15 g, 0.75 mmol) were added under an Ar atmo-
sphere and the reaction mixture was heated at 80 °C for 5 h under
Ar. After cooling to room temperature, the resulting mixture was
diluted with CH2Cl2, washed with 1 m HCl, dried with anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. The
crude product was purified by SiO2 flash chromatography to give
201.7 ppm. IR (KBr): ν = 3028, 1740, 1601, 1493, 1450, 1076, 1030,
˜
964 cm–1. HRMS (CI+): calcd. for C13H19O5 255.1232; found
255.1231.
Ethyl 2-Acetyl-6-methoxy-4-methyl-4-hexenoate (8b): Following the
standard procedure for 8c, the reaction of ethyl acetoacetate
(0.53 g, 3.97 mmol) with 60% NaH (0.17 g, 4.31 mmol) and 1-
bromo-4-methoxy-2-methyl-2-butene (0.59 g, 3.31 mmol) in THF
(20 mL) at 0 °C for 1 h and then at room temperature for 12 h,
produced 8b (0.41 g, 1.77 mmol, 54%, E/Z = 4:1) as a light-yellow
1
15c (0.13 g, 0.40 mmol, 53%) as a light-yellow oil. H NMR: δ =
1.30 (t, J = 7.2 Hz, 3 H), 2.09 (s, 3 H), 2.13 (s, 3 H), 3.29 (d of A
of ABq, JAB = 17.6, Jd = 2.4 Hz, 1 H), 3.54 (d of B of ABq, JAB
= 17.6, Jd = 2.4 Hz, 1 H), 4.26 (dq, Jd = 1.6, Jq = 7.2 Hz, 2 H),
4.78 (d of A of ABq, JAB = 12.8, Jd = 7.2 Hz, 1 H), 4.81 (d of B
of ABq, JAB = 12.8, Jd = 7.6 Hz, 1 H), 6.12 (tt, J = 7.2, 2.4 Hz, 1
1
oil. Data for (E)-8b: H NMR: δ = 1.27 (t, J = 7.2 Hz, 3 H), 1.68
(s, 3 H), 2.23 (s, 3 H), 2.59 (dd, J = 7.6, 3.2 Hz, 2 H), 3.29 (s, 3 H),
Eur. J. Org. Chem. 2012, 6976–6985
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6981

C. Wang, Z. Li, Y. Ju, S. Koo
FULL PAPER
3.65 (t, J = 7.6 Hz, 1 H), 3.90 (d, J = 6.8 Hz, 2 H), 4.19 (q, J =
7.2 Hz, 2 H), 5.36 (tq, Jt = 6.8, Jq = 1.2 Hz, 1 H) ppm. 13C NMR:
δ = 14.0, 16.3, 28.8, 37.5, 57.7, 58.1, 61.4, 68.6, 123.5, 136.0, 169.3,
0.74 g, 2.47 mmol) in THF (20 mL) at 0 °C for 1 h and then at
room temperature for 12 h under an Ar atmosphere, produced 8g
(0.69 g, 1.98 mmol, 81%, 8:1 mixture of E/Z isomers) as a light-
202.4 ppm. IR (KBr): ν = 3012, 1740, 1443, 1366, 1231, 1150, 1099,
yellow oil after purification by SiO2 flash chromatography. Data
˜
1
1022, 961 cm–1. HRMS (CI+): calcd. for C12H19O4 227.1283; found for (E)-8g: H NMR: δ = 1.22 (t, J = 7.2 Hz, 3 H), 2.07 (s, 3 H),
227.1284.
2.11 (s, 3 H), 3.04–3.15 (m, 2 H), 3.43 (t, J = 7.2 Hz, 1 H), 3.81 (s,
3 H), 4.05–4.16 (m, 2 H), 4.78 (dd, J = 7.6, 2.8 Hz, 2 H), 5.74 (t,
J = 7.2 Hz, 1 H), 7.86 (d, J = 8.8 Hz, 2 H), 7.23 (d, J = 8.8 Hz, 2
H) ppm. 13C NMR: δ = 13.9, 14.1, 20.8, 28.1, 29.4, 55.1, 57.6, 61.3,
113.8, 123.6, 127.7, 132.6, 140.6, 159.4, 169.0, 170.7, 202.0 ppm.
(E)-5-Acetyl-6-oxo-3-phenylhept-2-en-1-yl Acetate (8d): To a stirred
solution of acetylacetone (0.33 g, 3.25 mmol) in acetone (35 mL)
was added anhydrous K2CO3 (0.45 g, 3.25 mmol). The mixture was
stirred at 20 °C for 1 h, and 4-bromo-3-phenyl-2-butenyl acetate
(10a; 0.88 g, 3.25 mmol) was added. The mixture was stirred at
20 °C for 12 h, diluted with EtOAc, washed with 1 m HCl, dried
with anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. The crude product was purified by SiO2 flash chromatog-
raphy to give 8d (0.38 g, 1.25 mmol, 40%, a 10:1 mixture of E/Z
IR (KBr): ν = 1734, 1717, 1607, 1510, 1443, 1364, 1229, 1179, 1026,
˜
955, 833 cm–1. HRMS (EI+): calcd. for C19H24O6 348.1573; found
348.1573.
Ethyl 6-Acetoxy-2-acetyl-4-(naphthalene-2-yl)-4-hexenoate (8h):
Following the standard procedure for 8c, the reaction of ethyl ace-
toacetate (0.49 g, 3.76 mmol) with 60% NaH (0.18 g, 4.39 mmol)
and 4-bromo-3-(naphthalen-2-yl)-2-buten-1-yl acetate (10d; 1.00 g,
3.13 mmol) in THF (10 mL) at 0 °C for 1 h and then at room tem-
perature under an Ar atmosphere, produced 8h (1.14 g, 3.09 mmol,
98%, 9:1 mixture of E/Z isomers) as a light-yellow oil after purifi-
1
isomers) as a light-yellow oil. Data for (E)-8d: H NMR: δ = 2.07
(s, 9 H), 3.10 (d, J = 7.2 Hz, 2 H), 3.65 (t, J = 7.2 Hz, 1 H), 4.80
(d, J = 6.8 Hz, 2 H), 5.80 (t, J = 6.8 Hz, 1 H), 7.25–7.37 (m, 5
H) ppm. 13C NMR: δ = 20.6, 28.2, 29.6, 29.6, 60.9, 65.3, 124.8,
126.3, 127.8, 128.4, 140.1, 140.9, 170.5, 203.0, 203.0 ppm. IR
(KBr): ν = 2978, 1728, 1315, 1234, 1188, 1153, 1096 cm–1. HRMS
1
˜
cation by SiO2 flash chromatography. Data for (E)-8h: H NMR:
(FAB+): calcd. for C17H21O4 289.1440; found 289.1435.
δ = 1.20 (t, J = 6.8 Hz, 3 H), 2.10 (s, 3 H), 2.11 (s, 3 H), 3.20 (d of
A of ABq, JAB = 14.4, Jd = 8.0 Hz, 1 H), 3.24 (d of B of ABq, JAB
= 14.4, Jd = 6.8 Hz, 1 H), 3.47 (dd, J = 8.0, 6.8 Hz, 1 H), 4.04–
4.14 (m, 2 H), 4.85 (d of A of ABq, JAB = 13.2, Jd = 6.8 Hz, 1 H),
4.88 (d of B of ABq, JAB = 13.2, Jd = 6.8 Hz, 1 H), 5.94 (t, J =
6.8 Hz, 1 H), 7.40 (dd, J = 8.4, 1.6 Hz, 1 H), 7.46–7.53 (m, 2 H),
7.74 (d, J = 1.6 Hz, 1 H), 7.80–7.86 (m, 3 H) ppm. 13C NMR: δ =
14.0, 21.0, 28.2, 29.7, 57.6, 61.5, 61.6, 124.7, 125.5, 125.7, 126.2,
126.4, 127.6, 128.1, 128.3, 132.9, 133.3, 137.8, 141.0, 169.1, 170.9,
5-(Diethylcarbamoyl)-6-oxo-3-phenylhept-2-en-1-yl Acetate (8e):
Following the standard procedure for 8c, the reaction of N,N-dieth-
ylacetoacetamide (0.39 g, 2.48 mmol) with 60% NaH (0.12 g,
2.90 mmol) and 4-bromo-3-phenyl-2-butenyl acetate (10a; 0.56 g,
2.07 mmol) in THF (20 mL) at 0 °C for 1 h and then at room tem-
perature for 12 h under an Ar atmosphere, produced 8e (0.58 g,
1.69 mmol, 68%, 3:1 mixture of E/Z isomers) as a light-yellow oil
after purification by SiO2 flash chromatography. Data for (E)-8e:
1H NMR: δ = 0.86 (t, J = 7.2 Hz, 3 H), 1.03 (t, J = 7.2 Hz, 3 H),
2.07 (s, 3 H), 2.15 (s, 3 H), 2.86–3.20 (m, 4 H), 3.23–3.38 (m, 2 H),
3.46–3.53 (m, 1 H), 4.81 (d of A of ABq, JAB = 13.2, Jd = 6.4 Hz,
1 H), 4.92 (d of B of ABq, JAB = 13.2, Jd = 7.6 Hz, 1 H), 5.83 (t,
J = 7.2 Hz, 1 H), 7.26–7.40 (m, 5 H) ppm. 13C NMR: δ = 12.7,
14.0, 20.9, 27.2, 29.2, 40.7, 42.0, 55.4, 61.5, 123.4, 125.1, 126.4,
202.1 ppm. IR (KBr): ν = 1734, 1715, 1366, 1229, 1022, 818, 627,
˜
467 cm–1. HRMS (EI+): calcd. for C22H24O5 368.1622; found
368.1623.
Ethyl 6-Acetoxy-2-acetyl-4-cyclopropyl-4-hexenoate (8i): Following
the standard procedure for 8c, the reaction of ethyl acetoacetate
(0.32 g, 2.46 mmol) with 60% NaH (0.12 g, 2.86 mmol) and 4-
bromo-3-cyclopropyl-2-buten-1-yl acetate (10e; 0.48 g, 2.05 mmol)
in THF (10 mL) at 0 °C for 1 h and then at room temperature for
12 h under an Ar atmosphere, produced 8i (0.49 g, 1.74 mmol,
85%, 2:1 mixture of stereoisomers) as a light-yellow oil after purifi-
127.8, 128.5, 140.9, 167.7, 170.7, 203.9 ppm. IR (KBr): ν = 2974,
˜
1736, 1634, 1433, 1362, 1229, 1134, 1022, 959 cm–1. HRMS (EI+):
calcd. for C20H27NO4 345.1940; found 345.1945.
(E)-Ethyl 6-Acetoxy-2-acetyl-4-(4-chlorophenyl)-4-hexenoate (8f):
Following the standard procedure for 8c, the reaction of ethyl ace-
toacetate (0.24 g, 1.87 mmol) with 60% NaH (0.09 g, 2.19 mmol)
and 4-bromo-3-(4-chlorophenyl)-2-buten-1-yl acetate (10b; 0.47 g,
1.56 mmol) in THF (10 mL) at 0 °C for 1 h and then at room tem-
perature for 12 h under an Ar atmosphere, produced 8f (0.43 g,
1.22 mmol, 78%, 5.9:1 mixture of E/Z isomers) as a light-yellow
oil after purification by SiO2 flash chromatography. Data for (E)-
1
cation by SiO2 flash chromatography. H NMR: δ = 0.43 (dd, J =
5.6, 1.6 Hz, 2 H), 0.67 (ddd, J = 8.8, 8.4, 1.6 Hz, 2 H), 1.18–1.25
(m, 1 H), 1.28 (t, J = 7.2 Hz, 3 H), 2.04 (s, 3 H), 2.26 (s, 3 H), 2.70
(d of A of ABq, JAB = 14.0, Jd = 6.4 Hz, 1 H), 2.78 (d of B of
ABq, JAB = 14.0, Jd = 8.0 Hz, 1 H),3.70 (t, J = 7.2 Hz, 1 H),* 3.83
(dd, J = 8.4, 6.8 Hz, 1 H), 4.12–4.25 (m, 2 H), 4.58 (d of A of ABq,
JAB = 12.8, Jd = 7.2 Hz, 1 H), 4.63 (d of B of ABq, JAB = 12.8, Jd
= 7.2 Hz, 1 H), 4.71 (d of A of ABq, JAB = 13.6, Jd = 7.2 Hz, 1
H),* 4.73 (d of B of ABq, JAB = 13.6, Jd = 6.8 Hz, 1 H),* 5.27 (t,
J = 7.2 Hz, 1 H), 5.39 (t, J = 6.4 Hz, 1 H) ppm. 13C NMR: δ =
4.86,* 5.19,* 5.67, 6.41, 11.2,* 13.9, 14.0,* 16.0, 20.8,* 20.9, 29.0,*
29.1, 30.1, 32.1,* 58.1, 60.7, 60.8,* 61.3,* 61.4, 118.6, 122.5,*
1
8f: H NMR: δ = 1.22 (t, J = 7.2 Hz, 3 H), 2.07 (s, 3 H), 2.12 (s,
3 H), 3.07 (d of A of ABq, JAB = 14.8, Jd = 8.0 Hz, 1 H), 3.09 (d
of B of ABq, JAB = 14.8, Jd = 6.8 Hz, 1 H), 3.38 (dd, J = 8.0,
6.8 Hz, 1 H), 4.06–4.18 (m, 2 H), 4.78 (d of A of ABq, JAB = 13.2,
Jd = 6.8 Hz, 1 H), 4.80 (d of B of ABq, JAB = 13.2, Jd = 6.8 Hz,
1 H), 5.78 (t, J = 6.8 Hz, 1 H), 7.20–7.34 (m, 4 H) ppm. 13C NMR:
δ = 13.8, 20.8, 28.0, 29.3, 57.5, 61.1, 61.5, 125.7, 127.8, 128.6, 133.7,
141.1,* 142.3, 169.1, 170.7, 202.1, 202.2* ppm. IR (KBr): ν = 2924,
˜
1736, 1717, 1447, 1362, 1231, 1146, 1022, 995 cm–1. HRMS (CI+):
calcd. for C15H23O5 283.1545; found 283.1551; * denotes peaks
from the minor Z isomer.
138.8, 139.9, 168.8, 170.6, 201.5 ppm. IR (KBr): ν = 2982, 1736,
˜
1715, 1643, 1491, 1443, 1364, 1227, 1150, 1092, 1013, 959, 824,
766 cm–1. HRMS (EI+): calcd. for C18H21ClO5 352.1078; found
352.1083.
Ethyl 6-Acetoxy-2-acetyl-4-cyclohexyl-4-hexenoate (8j): Following
the standard procedure for 8c, the reaction of ethyl acetoacetate
(E)-Ethyl 6-Acetoxy-2-acetyl-4-(4-methoxyphenyl)-4-hexenoate (8g): (0.32 g, 2.46 mmol) with 60% NaH (0.12 g, 2.86 mmol) and 4-
Following the standard procedure for 8c, the reaction of ethyl ace- bromo-3-cyclopropyl-2-buten-1-yl acetate (10f; 0.48 g, 2.05 mmol)
toacetate (0.74 g, 2.47 mmol) with 60% NaH (0.14 g, 3.45 mmol) in THF (10 mL) at 0 °C for 1 h and then at room temperature for
and 4-bromo-3-(4-methoxyphenyl)-2-buten-1-yl acetate (10c; 12 h under an Ar atmosphere, produced 8j (0.49 g, 1.74 mmol,
6982
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 6976–6985

Oxidation of β-Ketocarbonyl Compounds
85%, 2.5:1 mixture of stereoisomers) as a light-yellow oil after puri-
fication by SiO2 flash chromatography. Data for 8j: H NMR: δ =
Ethyl
5-(Acetoxymethyl)-4-(4-chlorophenyl)furan-2-carboxylate
1
(14f): Following the standard procedure for 14c, the reaction of 8f
(0.27 g, 0.78 mmol) and Mn(OAc)3·2H2O (0.64 g, 2.33 mmol) in
94% EtOH (10 mL) at 50 °C for 5 h, produced 14f (0.16 g,
0.50 mmol, 65%) as a light-yellow oil after purification by SiO2
flash chromatography. 1H NMR: δ = 1.40 (t, J = 7.2 Hz, 3 H), 2.12
(s, 3 H), 4.40 (q, J = 7.2 Hz, 2 H), 5.15 (s, 2 H), 7.29 (s, 1 H), 7.31–
7.43 (m, 4 H) ppm. 13C NMR: δ = 14.3, 20.7, 57.0, 61.3, 118.4,
127.2, 129.1, 129.1, 129.7, 134.1, 144.6, 148.3, 158.4, 170.3 ppm.
1.04–1.24 (m, 5 H), 1.27 (t, J = 7.2 Hz, 3 H), 1.64–1.82 (m, 6 H),
2.05 (s, 3 H), 2.24 (s, 3 H), 2.62 (d of A of ABq, JAB = 14.0, Jd =
6.8 Hz, 1 H), 2.64 (d of B of ABq, JAB = 14.0, Jd = 6.8 Hz, 1 H),
2.67 (d of A of ABq, JAB = 14.0, Jd = 8.8 Hz, 1 H),* 2.67 (d of B
of ABq, JAB = 14.0, Jd = 8.8 Hz, 1 H),* 3.46 (t, J = 6.4 Hz, 1 H),*
3.57 (dd, J = 8.0, 6.8 Hz, 1 H), 4.11–4.25 (m, 2 H), 4.59 (d of A of
ABq, JAB = 12.8, Jd = 7.6 Hz, 1 H), 4.63 (d of B of ABq, JAB
=
12.8, Jd = 7.2 Hz, 1 H), 5.34 (t, J = 7.6 Hz, 1 H),* 5.39 (t, J =
7.2 Hz, 1 H) ppm. 13C NMR: δ = 14.0, 21.1, 26.2, 26.7, 26.8, 28.6,
29.3, 32.6, 32.9, 43.3, 58.4, 61.2, 61.6, 119.9, 146.5, 169.3, 171.0,
IR (KBr): ν = 2972, 2930, 1746, 1711, 1595, 1551, 1493, 1441, 1366,
˜
1312, 1223, 1150, 1090, 1020, 955, 912, 826, 762, 727 cm–1. HRMS
(EI+): calcd. for C16H15ClO5 322.0608; found 322.0605.
202.3 ppm. IR (KBr): ν = 2926, 2853, 1736, 1717, 1449, 1371, 1229,
˜
Ethyl 5-(Acetoxymethyl)-4-(4-methoxyphenyl)furan-2-carboxylate
(14g): Following the standard procedure for 14c, the reaction of
8g (0.30 g, 0.85 mmol) and Mn(OAc)3·2H2O (0.68 g, 2.55 mmol) in
94% EtOH (10 mL) at 50 °C for 5 h, produced 14g (0.14 g,
1148, 1022 cm–1. HRMS (EI+): calcd. for C16H24O3 [C18H28O5
–
C2H4O2] 264.1725; found 264.1728; * denotes peaks from the
minor Z isomer.
Ethyl 5-(Acetoxymethyl)-4-methylfuran-2-carboxylate (14a): Fol- 0.44 mmol, 52%) as a light-yellow oil after purification by SiO2
lowing the standard procedure for 14c, the reaction of β-keto ester
8a (0.20 g, 0.78 mmol) and Mn(OAc)3·2H2O (0.68 g, 2.34 mmol) in
94% EtOH (20 mL) at 50 °C for 5 h, produced 14a (0.10 g,
0.44 mmol, 57%) as a light-yellow oil after purification by SiO2
flash chromatography. 1H NMR: δ = 1.40 (t, J = 7.2 Hz, 3 H), 2.13
(s, 3 H), 3.85 (s, 3 H), 4.40 (q, J = 7.2 Hz, 2 H), 5.16 (s, 2 H), 6.97
(d, J = 8.4 Hz, 2 H), 7.30 (s, 1 H), 7.33 (d, J = 8.4 Hz, 2 H) ppm.
13C NMR: δ = 14.3, 20.8, 55.3, 57.2, 61.2, 114.3, 118.7, 123.5,
1
flash column chromatography. H NMR: δ = 1.37 (t, J = 7.2 Hz,
128.1, 129.0, 144.3, 147.6, 158.6, 159.4, 170.5 ppm. IR (KBr): ν =
˜
3 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 4.36 (q, J = 7.2 Hz, 2 H), 5.06 (s,
1717, 1605, 1510, 1369, 1221, 1022, 833, 604 cm–1. HRMS (EI+):
2 H), 7.00 (s, 1 H) ppm. 13C NMR: δ = 9.7, 14.3, 20.7, 56.0, 61.0, calcd. for C17H18O6 318.1103; found 318.1107.
120.5, 122.2, 144.0, 149.0, 158.7, 170.5 ppm. IR (KBr): ν = 2986,
˜
Ethyl
5-(Acetoxymethyl)-4-(naphthalen-2-yl)furan-2-carboxylate
1736, 1543, 1443, 1373, 1319, 1196, 1103, 1026, 949 cm–1. HRMS
(EI+): calcd. for C11H14O5 226.0841; found 226.0846.
(14h): Following the standard procedure for 14c, the reaction of
8h (0.20 g, 0.53 mmol) and Mn(OAc)3·2H2O (0.44 g, 1.59 mmol) in
94% EtOH (10 mL) at 50 °C for 5 h, produced 14h (0.11 g,
0.34 mmol, 64%) as a light-yellow oil after purification by SiO2
flash chromatography. 1H NMR: δ = 1.42 (t, J = 7.2 Hz, 3 H), 2.15
(s, 3 H), 4.42 (q, J = 7.2 Hz, 2 H), 5.25 (s, 1 H), 7.44 (s, 1 H), 7.50–
7.56 (m, 2 H), 7.83–7.94 (m, 4 H) ppm. 13C NMR: δ = 14.3, 20.8,
57.3, 61.3, 118.8, 125.7, 126.5, 126.6, 127.0, 127.7, 128.0, 128.4,
128.6, 128.7, 132.7, 133.3, 144.6, 148.4, 158.5, 170.4 ppm. IR
Ethyl 5-(Methoxymethyl)-4-methylfuran-2-carboxylate (14b): Fol-
lowing the standard procedure for 14c, the reaction of β-keto ester
8b (0.10 g, 0.44 mmol) and Mn(OAc)3·2H2O (0.37 g, 1.31 mmol) in
94% EtOH (10 mL) at 50 °C for 5 h, gave 14b (0.05 g, 0.25 mmol,
60%) as a light-yellow oil after purification by SiO2 flash column
1
chromatography. H NMR: δ = 1.36 (t, J = 7.2 Hz, 3 H), 2.09 (s,
3 H), 3.36 (s, 3 H), 4.34 (q, J = 7.2 Hz, 2 H), 4.42 (s, 2 H), 7.00 (s,
1 H) ppm. 13C NMR: δ = 9.6, 14.3, 58.1, 60.8, 64.4, 120.7, 121.0, (KBr): ν = 1724, 1541, 1445, 1369, 1314, 1219, 1152, 1022, 939,
˜
143.4, 151.6, 158.8 ppm. IR (KBr): ν = 2970, 1728, 1535, 1450,
820, 750 cm–1. HRMS (EI+): calcd. for C20H18O5 338.1154; found
338.1154.
˜
1369, 1319, 1196, 1096, 1022, 952 cm–1. HRMS (CI+): calcd. for
C10H15O4 199.0970; found 199.0973.
Ethyl 5-(Acetoxymethyl)-4-cyclopropylfuran-2-carboxylate (14i):
Following the standard procedure for 14c, the reaction of 8i (0.23 g,
0.80 mmol) and Mn(OAc)3·2H2O (0.64 g, 2.40 mmol) in 94%
(5-Acetyl-3-phenylfuran-2-yl)methyl Acetate (14d): Following the
standard procedure for 14c, the reaction of β-keto ester 8d (0.10 g,
0.35 mmol) and Mn(OAc)3·2H2O (0.29 g, 1.04 mmol) in 94% EtOH (10 mL) at 50 °C for 5 h, produced 14i (0.13 g, 0.50 mmol,
EtOH (10 mL) at 50 °C for 5 h, gave 14d (0.04 g, 0.16 mmol, 47%)
as a light-yellow oil after purification by SiO2 flash column
chromatography. 1H NMR: δ = 2.13 (s, 3 H), 2.53 (s, 3 H), 5.19 (s,
2 H), 7.32 (s, 1 H), 7.36–7.47 (m, 5 H) ppm. 13C NMR: δ = 20.7,
29.6, 57.2, 117.9, 127.9, 128.1, 128.8, 129.0, 131.8, 148.4, 152.1,
63%) as a light-yellow oil after purification by SiO2 flash
1
chromatography. H NMR: δ = 0.58 (dt, Jd = 6.4, Jt = 4.8 Hz, 2
H), 0.95 (dt, Jd = 8.4, Jt = 6.4 Hz, 2 H), 1.36 (t, J = 7.2 Hz, 3 H),
1.79 (tt, J = 8.4, 4.8 Hz, 1 H), 2.10 (s, 3 H), 4.35 (q, J = 7.2 Hz, 2
H), 5.16 (s, 2 H), 6.75 (s, 1 H) ppm. 13C NMR: δ = 5.52, 7.60, 7.60,
14.3, 20.8, 56.2, 61.0, 116.1, 129.6, 144.1, 149.1, 158.5, 170.6 ppm.
170.4, 187.0 ppm. IR (KBr): ν = 2978, 1744, 1678, 1532, 1493,
˜
1451, 1370, 1323, 1223, 1146, 1026, 914, 768, 729 cm–1. HRMS
(EI+): calcd. for C15H14O4 258.0892; found 258.0892.
IR (KBr): ν = 1717, 1541, 1373, 1215, 1022, 669 cm–1. HRMS
˜
(EI+): calcd. for C13H16O5 252.0998; found 252.1001.
[5-(Diethylcarbamoyl)-3-phenylfuran-2-yl]methyl Acetate (14e): Fol-
lowing the standard procedure for 14c, the reaction of 8e (0.34 g,
0.97 mmol) and Mn(OAc)3·2H2O (0.80 g, 2.91 mmol) in 94%
EtOH (15 mL) at 50 °C for 5 h, produced 14e (0.13 g, 0.40 mmol,
Ethyl 5-(Acetoxymethyl)-4-cyclohexylfuran-2-carboxylate (14j): Fol-
lowing the standard procedure for 14c, the reaction of 8j (0.17 g,
0.52 mmol) and Mn(OAc)3·2H2O (0.44 g, 1.57 mmol) in 94%
EtOH (10 mL) at 50 °C for 5 h, produced 14j (0.08 g, 0.29 mmol,
41%) as
a
light-yellow oil after purification by SiO2 flash
55%) as a light-yellow oil after purification by SiO2 flash
chromatography. 1H NMR: δ = 1.17–1.37 (br. m, 6 H), 2.13 (s, 3
H), 3.59 (br. d, J = 25.2 Hz, 4 H), 5.18 (s, 2 H), 7.18 (s, 1 H), 7.34–
chromatography. 1H NMR: δ = 1.18–1.52 (m, 4 H), 1.37 (t, J =
7.2 Hz, 3 H), 1.70–1.86 (m, 6 H), 2.09 (s, 3 H), 2.54 (tt, J = 11.6,
7.46 (m, 5 H) ppm. 13C NMR: δ = 20.8, 57.1, 57.1, 64.3, 116.9, 3.2 Hz, 1 H), 4.36 (q, J = 7.2 Hz, 2 H), 5.07 (s, 2 H), 7.08 (s, 1
127.1, 127.9, 128.9, 129.4, 131.7, 145.6, 148.3, 159.1, 170.5 ppm.
IR (KBr): ν = 1744, 1626, 1449, 1371, 1223, 1026, 939, 854, 768,
H) ppm. 13C NMR: δ = 14.3, 20.8, 25.3, 25.8, 26.3, 28.7, 34.0, 34.1,
56.2, 61.0, 117.6, 133.0, 144.1, 147.6, 158.7, 170.6 ppm. IR (KBr):
˜
˜
700 cm–1. HRMS (EI+): calcd. for C18H21O4N 315.1470; found ν = 2928, 1715, 1539, 1315, 1188, 1022, 764 cm–1. HRMS (EI+):
315.1471.
calcd. for C16H22O5 294.1467; found 294.1467.
Eur. J. Org. Chem. 2012, 6976–6985
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6983

C. Wang, Z. Li, Y. Ju, S. Koo
FULL PAPER
General Procedure for the MnIII-Initiated Oxidation of Ethyl 2-Acet-
yloctanoate (20). Ethyl 2-Acetyl-2-hydroxyoctanoate (21) and Ethyl
2-Oxooctanoate (22)
The reaction of ethyl 3-oxo-3-phenylpropanoate (1.40 g,
7.28 mmol) with 60% NaH (0.32 g, 8.00 mol) and iodohexane
(2.10 g, 9.91 mmol) in THF (10 mL) at 0 °C to room temperature,
overnight, produced ethyl 2-benzoyloctanoate (0.95 g, 3.12 mmol,
43%) as a light-yellow oil after purification by SiO2 flash column
Method 1 (Thermal Reaction): To a stirred solution of ethyl 2-acet-
yloctanoate (20; 0.15 g, 0.70 mmol) in 94% EtOH (10 mL) was
added Mn(OAc)3·H2O (0.19 g, 0.70 mmol). The reaction mixture
was heated at 50 °C for 6 h, cooled to room temperature, and
quenched with 1 m HCl (5 mL). The mixture was extracted with
CH2Cl2, washed with brine and H2O, dried with anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. The
crude product was purified by SiO2 flash column chromatography
to give ethyl 2-acetyl-2-hydroxyoctanoate (21; 0.025 g, 0.11 mmol,
16%) and ethyl 2-oxooctanoate (22; 0.060 g, 0.32 mmol, 46%) as
light-yellow oils.
1
chromatography. H NMR: δ = 0.87 (t, J = 6.8 Hz, 3 H), 1.17 (t,
J = 7.2 Hz, 3 H), 1.20–1.40 (m, 8 H), 1.93–2.07 (m, 2 H), 4.14 (dq,
Jd = 0.8, Jq = 6.8 Hz, 2 H), 4.28 (t, J = 7.2 Hz, 1 H), 7.45–7.51
(m, 2 H), 7.56–7.62 (m, 1 H), 7.97–8.02 (m, 2 H) ppm. 13C NMR:
δ = 13.9, 14.0, 22.5, 27.5, 28.9, 29.0, 31.5, 54.3, 61.2, 128.5, 128.7,
133.4, 136.3, 170.0, 195.2 ppm.
Ethyl 2-(4-Methylbenzoyl)octanoate (23c): Following the standard
procedure for 23a, the reaction of 4-methylacetophenone (2.00 g,
14.92 mmol) with 60% NaH (1.70 g, 41.78 mol) and diethyl car-
bonate (3.50 g, 29.84 mol) in refluxing toluene (40 mL) for 30 min
produced ethyl 3-oxo-3-(4-tolyl)propanoate (2.50 g, 12.34 mmol,
83%) as a light-yellow oil after purification by SiO2 flash column
chromatography.
Method 2 (Ultrasonic Irradiation): To a stirred solution of ethyl 2-
acetyloctanoate (20; 0.16 g, 0.75 mmol) in glacial AcOH (10 mL)
was added Mn(OAc)3·H2O (0.02 g, 0.075 mmol). The reaction mix-
ture was stirred at 15 °C under ultrasonic irradiation (20% intensity
of 130 W, 20 kHz) for 1 h, and quenched with 1 m HCl (5 mL). The
mixture was extracted with CH2Cl2, washed with brine and H2O,
dried with anhydrous Na2SO4, filtered, and concentrated under re-
duced pressure. The crude product was purified by SiO2 flash col-
umn chromatography to give ethyl 2-oxooctanoate (22; 0.088 g,
0.47 mmol, 63%) as a light-yellow oil.
The reaction of ethyl 3-oxo-3-(4-tolyl)propanoate (2.40 g,
11.65 mmol) with 60% NaH (0.50 g, 12.76 mol) and iodohexane
(3.40 g, 16.24 mmol) in THF (10 mL) at 0 °C to room temperature,
overnight, produced 23c (1.80 g, 5.77 mmol, 50%) as a light-yellow
oil after purification by SiO2 flash column chromatography. 1H
NMR: δ = 0.86 (t, J = 7.2 Hz, 3 H), 1.18 (t, J = 7.2 Hz, 3 H), 1.22–
1.38 (m, 8 H), 1.93–2.06 (m, 2 H), 2.42 (s, 3 H), 4.14 (dq, Jd = 1.2,
Jq = 7.2 Hz, 2 H), 4.26 (t, J = 7.2 Hz, 1 H), 7.28 (d, J = 8.0 Hz, 2
H), 7.89 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR: δ = 14.0, 14.0, 21.6,
22.5, 27.5, 29.0, 29.0, 31.5, 54.2, 61.2, 128.7, 129.3, 133.8, 144.3,
170.2, 194.9 ppm.
Ethyl 2-(4-Chlorobenzoyl)octanoate (23a)
Step 1: To a stirred suspension of 60% NaH (1.50 g, 36.0 mmol) in
toluene (40 mL) was added diethyl carbonate (3.10 g, 26.0 mmol).
While the mixture was heated at reflux, a solution of 4-chloroaceto-
phenone (2.00 g, 13.0 mmol) in toluene (10 mL) was added over
15 min. The resulting mixture was then heated at reflux for 15–
20 min until the evolution of H2 ceased. The mixture was cooled
to room temperature and quenched by glacial acetic acid (4 mL).
Ice-water was added to the above mixture until the solid was com-
pletely dissolved. The reaction mixture was extracted with EtOAc,
washed with brine and H2O, dried with anhydrous Na2SO4, fil-
tered, and concentrated under reduced pressure. The crude product
was purified by SiO2 flash column chromatography to give ethyl 3-
(4-chlorophenyl)-3-oxopropanoate (2.23 g, 9.88 mmol, 76%) as a
light-yellow oil.
Ethyl 2-(4-Methoxybenzoyl)octanoate (23d): Following the standard
procedure for 23a, the reaction of 4-methoxyacetophenone (2.00 g,
13.33 mmol) with 60% NaH (1.50 g, 37.24 mol) and diethyl car-
bonate (3.20 g, 27.07 mol) in refluxing toluene (40 mL) for 30 min
produced ethyl 3-(4-methoxyphenyl)-3-oxopropanoate (2.48 g,
11.16 mmol, 84%) as a light-yellow oil after purification by SiO2
flash column chromatography.
The reaction of ethyl 3-(4-methoxyphenyl)-3-oxopropanoate
(2.50 g, 11.26 mmol) with 60% NaH (0.50 g, 12.39 mol) and
iodohexane (3.30 g, 15.76 mmol) in THF (10 mL) at 0 °C to room
temperature, overnight, produced 23d (1.98 g, 5.93 mmol, 53%) as
Step 2: To a stirred suspension of 60% NaH (0.40 g, 10. 67 mmol)
in THF (10 mL) at 0 °C was added ethyl 3-(4-chlorophenyl)-3-ox-
opropanoate (2.20 g, 9.73 mmol). The mixture was stirred at 0 °C
for 1 h, and a solution of iodohexane (2.90 g, 13.67 mmol) in THF
(2 mL) was added. The mixture was warmed to room temperature
and stirred overnight. The reaction mixture was quenched with 1 m
HCl, extracted with EtOAc, washed with brine and H2O, dried
with anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. The crude product was purified by SiO2 flash column
chromatography to give ethyl 2-(4-chlorobenzoyl)octanoate (23a;
a
light-yellow oil after purification by SiO2 flash column
1
chromatography. H NMR: δ = 0.86 (t, J = 7.2 Hz, 3 H), 1.18 (t,
J = 7.2 Hz, 3 H), 1.22–1.37 (m, 8 H), 1.91–2.04 (m, 2 H), 3.88 (s,
3 H), 4.14 (dq, Jd = 1.6, Jq = 7.2 Hz, 2 H), 4.24 (t, J = 7.2 Hz, 1
H), 6.95 (d, J = 8.8 Hz, 2 H), 7.99 (d, J = 8.8 Hz, 2 H) ppm. 13C
NMR: δ = 13.9, 13.9, 22.4, 27.4, 28.9, 29.0, 31.4, 53.9, 55.3, 61.0,
113.7, 129.1, 130.8, 163.6, 170.1, 193.5 ppm.
Ethyl 2-(4-Chlorobenzoyl)-2-hydroxyoctanoate (24a), Ethyl 2-
Oxooctanoate (22) and 4-Chlorobenzoic Acid (25a): Following the
standard procedure for 14c, the reaction of ethyl 2-(4-chlorobenz-
oyl)octanoate (23a; 0.21 g, 0.68 mmol) and Mn(OAc)3·H2O (0.57 g,
2.04 mmol) in 94% EtOH (10 mL) at 50 °C for 6 h, produced 24a
(0.024 g, 0.07 mmol, 11%), 22 (0.040 g, 0.22 mmol, 32%), and 25a
(0.035 g, 0.16 mmol, 24) after purification by SiO2 flash column
1
1.03 g, 3.04 mmol, 31%) as a light-yellow oil. H NMR: δ = 0.87
(t, J = 7.2 Hz, 3 H), 1.18 (t, J = 7.2 Hz, 3 H), 1.22–1.40 (m, 8 H),
1.93–2.06 (m, 2 H), 4.14 (dq, Jd = 0.8, Jq = 7.2 Hz, 2 H), 4.22 (t,
J = 7.2 Hz, 1 H), 7.45 (d, J = 8.8 Hz, 2 H), 7.93 (d, J = 8.8 Hz, 2
H) ppm. 13C NMR: δ = 14.0, 14.0, 22.5, 27.5, 28.8, 29.0, 31.5, 54.4,
61.4, 129.0, 129.9, 134.6, 139.9, 169.8, 194.0 ppm.
1
chromatography. Data for 24a: H NMR: δ = 0.85 (t, J = 6.8 Hz,
3 H), 1.19 (t, J = 7.2 Hz, 3 H), 1.17–1.34 (m, 8 H), 2.06–2.22 (m,
2 H), 4.18–4.30 (m, 2 H), 4.31 (s, 1 H), 4.22 (t, J = 7.2 Hz, 1 H),
7.42 (d, J = 8.8 Hz, 2 H), 7.95 (d, J = 8.8 Hz, 2 H) ppm. 13C NMR:
δ = 14.0, 14.1, 21.0, 22.5, 29.2, 31.4, 35.9, 60.4, 82.5, 128.9, 130.8,
Ethyl 2-Benzoyloctanoate (23b): Following the standard procedure
for 23a, the reaction of acetophenone (1.00 g, 8.30 mmol), with
60% NaH (0.90 g, 23.3 mol) and diethyl carbonate (2.00 g,
16.6 mol) in refluxing toluene (20 mL) for 30 min produced ethyl
3-oxo-3-phenylpropanoate (1.24 g, 6.43 mmol, 78%) as a light-yel-
low oil after purification by SiO2 flash column chromatography.
140.0, 171.1, 172.0, 194.8 ppm. IR (KBr): ν = 3478, 2928, 2858,
˜
1730, 1693, 1587, 1468, 1400, 1223, 1150, 1092, 1013, 845 cm–1.
HRMS (CI+): calcd. for C17H24ClO4 327.1363; found 327.1364.
6984
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 6976–6985

Oxidation of β-Ketocarbonyl Compounds
Ethyl 2-Benzoyl-2-hydroxyoctanoate (24b), Ethyl 2-Oxooctanoate
(22) and Benzoic Acid (25b): Following the standard procedure for
14c, the reaction of ethyl 2-benzoyloctanoate (23b; 0.27 g,
0.98 mmol) and Mn(OAc)3·H2O (0.82 g, 2.94 mmol) in 94% EtOH
(10 mL) at 50 °C for 6 h, produced 24b (0.033 g, 0.11 mmol, 12%),
22 (0.040 g, 0.22 mmol, 21%) and 25b (0.015 g, 0.13 mmol, 13%)
after purification by SiO2 flash column chromatography. Data for
1732, 1672, 1599, 1462, 1368, 1224, 1173, 1026, 845 cm–1. HRMS
(CI+): calcd. for C18H27O5 323.1858; found 323.1860.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures for the intermediate compounds, an-
alytical data, and 1H and 13C NMR spectra for all new compounds.
1
Acknowledgments
24b: H NMR: δ = 0.83 (t, J = 6.4 Hz, 3 H), 1.17 (t, J = 7.2 Hz, 3
H), 1.15–1.37 (m, 8 H), 2.10–2.26 (m, 2 H), 4.17–4.28 (m, 2 H),
4.44 (s, 1 H), 4.22 (t, J = 7.2 Hz, 1 H), 7.42–7.50 (m, 2 H), 7.55–
7.62 (m, 1 H), 7.94–8.02 (m, 2 H) ppm. 13C NMR: δ = 13.8, 14.0,
22.4, 22.4, 29.2, 31.4, 35.9, 62.4, 82.3, 128.6, 129.2, 130.2, 133.6,
This research was supported by the Ministry of Education, Science
and Technology (MEST), National Research Foundation of Korea
(Basic Science Research Program, grant numbers 2009-0072552,
2012-000702 and Priority Research Centres Program, grant number
2012-0006693).
171.9, 196.1 ppm. IR (KBr): ν = 3451, 2957, 1726, 1682, 1584,
˜
1454, 1325, 1290, 1186, 1026, 934, 804 cm–1. HRMS (CI+): calcd.
for C17H25O4 293.1753; found 293.1752.
[1] a) B. B. Snider, Chem. Rev. 1996, 96, 339–363; b) A. S. Demir,
M. Emrullahoglu, Curr. Org. Synth. 2007, 4, 321–350; c) B. B.
Snider, Tetrahedron 2009, 65, 10738–10744.
Ethyl 2-Hydroxy-2-(4-methylbenzoyl)octanoate (24c), Ethyl 2-
Oxooctanoate (22) and 4-Methylbenzoic Acid (25c): Following the
standard procedure for 14c, the reaction of ethyl 2-(4-methyl-
benzoyl)octanoate (23c; 0.36 g, 1.24 mmol) and Mn(OAc)3·H2O
(1.04 g, 3.72 mmol) in 94% EtOH (10 mL) at 50 °C for 6 h, pro-
duced 24c (0.117 g, 0.38 mmol, 31%), 22 (0.062 g, 0.33 mmol, 27%)
and 25c (0.020 g, 0.15 mmol, 12%) after purification by SiO2 flash
[2] a) D. Yang, X.-Y. Ye, M. Xu, K.-W. Pang, K.-K. Cheung, J.
Am. Chem. Soc. 2000, 122, 1658–1663; b) B. B. Snider, J. Y.
Kiselgof, B. M. Foxman, J. Org. Chem. 1998, 63, 7945–7952;
c) D. Yang, X.-Y. Ye, M. Xu, J. Org. Chem. 2000, 65, 2208–
2217; d) D. Yang, M. Xu, Org. Lett. 2001, 3, 1785–1788; e) D.
Yang, M. Xu, M.-Y. Bian, Org. Lett. 2001, 3, 111–114; f) B. B.
Snider, S. M. O’Hare, Synth. Commun. 2001, 31, 3753–3758.
[3] Z. Li, H. Jung, M. Park, M. S. Lah, S. Koo, Adv. Synth. Catal.
2011, 353, 1913–1917.
[4] S. K. Guha, B. Wu, B. S. Kim, W. Baik, S. Koo, Tetrahedron
Lett. 2006, 47, 291–293.
[5] a) J. H. Babler, D. O. Olsen, Tetrahedron Lett. 1974, 15, 351–
354; b) J. H. Babler, M. J. Coghlan, M. Feng, P. Fries, J. Org.
Chem. 1979, 44, 1716–1717.
1
column chromatography. Data for 24c: H NMR: δ = 0.82 (t, J =
6.8 Hz, 3 H), 1.16 (t, J = 7.2 Hz, 3 H), 1.15–1.36 (m, 8 H), 2.10–
2.25 (m, 2 H), 2.41 (s, 3 H), 4.21 (dq, Jd = 2.8, Jq = 7.2 Hz, 2 H),
4.55 (s, 1 H), 7.25 (d, J = 8.4 Hz, 2 H), 7.89 (d, J = 8.4 Hz, 2
H) ppm. 13C NMR: δ = 13.8, 14.0, 21.7, 22.4, 22.4, 29.2, 31.4, 36.0,
62.3, 82.1, 129.3, 129.4, 130.8, 144.7, 171.9, 195.7 ppm. IR (KBr):
ν = 3478, 2928, 2858, 1738, 1678, 1607, 1462, 1368, 1225, 1184,
˜
1059, 922, 837 cm–1. HRMS (CI+): calcd. for C18H27O4 307.1909;
found 307.1915.
[6] K. M. Shea, in: Name Reactions in Heterocyclic Chemistry
(Eds.: J. J. Li, E. J. Corey), John Wiley & Sons, Hoboken, New
Jersey, U.S., 2005, pp. 160–167.
Ethyl 2-Hydroxy-2-(4-methoxybenzoyl)octanoate (24d), Ethyl 2-
Oxooctanoate (22) and 4-Methoxybenzoic Acid (25d): Following the
standard procedure 14c, the reaction of ethyl 2-(4-methoxybenz-
oyl)octanoate (0.25 g, 0.81 mmol) and Mn(OAc)3·H2O (0.65 g,
2.43 mmol) in 94% EtOH (10 mL) at 50 °C for 16 h, produced 24d
(0.038 g, 0.11 mmol, 14%), 22 (0.010 g, 0.05 mmol, 6%) and 25d
(0.006 g, 0.04 mmol, 5%) after purification by SiO2 flash column
[7] B. B. Snider, J. J. Patricia, S. A. Kates, J. Org. Chem. 1988, 53,
2137–2143.
[8] M. T. Rahman, H. Nishino, Org. Lett. 2003, 5, 2887–2890.
[9] a) K. R. Kopecky, C. Mumford, Can. J. Chem. 1969, 47, 709–
711; b) T. Wilson, A. P. Schaap, J. Am. Chem. Soc. 1971, 93,
4126–4136; c) K. R. Kopecky, P. A. Lockwood, R. R. Gomez,
J.-Y. Ding, Can. J. Chem. 1981, 59, 851–858.
[10] B. B. Snider, J. E. Merritt, M. A. Dombroski, B. O. Buckman,
J. Org. Chem. 1991, 56, 5544–5553.
1
chromatography. Data for 24d: H NMR: δ = 0.83 (t, J = 6.8 Hz,
3 H), 1.17 (t, J = 7.2 Hz, 3 H), 1.13–1.37 (m, 8 H), 2.10–2.25 (m,
2 H), 3.88 (s, 3 H), 4.16–4.27 (m, 2 H), 4.61 (s, 1 H), 6.93 (d, J =
8.8 Hz, 2 H), 8.01 (d, J = 8.8 Hz, 2 H) ppm. 13C NMR: δ = 13.9,
13.9, 22.4, 22.5, 29.3, 31.5, 36.2, 55.5, 62.3, 82.0, 113.8, 126.0,
[11] T. Linker, U. Linker, Angew. Chem. 2000, 112, 934; Angew.
Chem. Int. Ed. 2000, 39, 902–904.
Received: September 6, 2012
131.8, 163.9, 172.0, 194.4 ppm. IR (KBr): ν = 3426, 2926, 2857,
Published Online: October 29, 2012
˜
Eur. J. Org. Chem. 2012, 6976–6985
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6985