Various α-oxygen functionalizations of β-dicarbonyl compounds mediated by the hypervalent iodine(III) reagent p-iodotoluene difluoride with different oxygen-containing nucleophiles

Article abstract of DOI:10.1002/adsc.200900737

p-Iodotoluene difluoride (p-Tol-IF₂) has been found to be a general reagent for the effective introduction of various oxygen-containing functionalities including tosyloxy, mesyloxy, acetoxy, phosphoryloxy, methoxy, ethoxy and isopropoxy at the α-position of β-dicarbonyl compounds. These transformations can be readily realized by the use of the combined reagent of p-iodotoluene difluoride and various oxygen-containing nucleophilic compounds such as p-toluenesulfonic acid, methanesulfonic acid, acetic acid, diphenyl phosphate, methanol, ethanol and propan-2-ol under mild conditions, respectively. And, the in situ generated hypervalent iodine(III) species via ligand exchange between p-iodotoluene difluoride and the respective oxygen-containing nucleophiles are believed to be the real oxidizing agents in such transformations.

Full text of DOI:10.1002/adsc.200900737

FULL PAPERS
DOI: 10.1002/adsc.200900737
Various a-Oxygen Functionalizations of b-Dicarbonyl Compounds
Mediated by the Hypervalent Iodine(III) Reagent p-Iodotoluene
G
Difluoride with Different Oxygen-Containing Nucleophiles
Jun Yu,a Jun Tian,a and Chi Zhanga,*
a
The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, Peopleꢀs Republic of
China
Fax : (+86)-22-2349-9247; phone: (+86)-022-2350-9243; e-mail: zhangchi@nankai.edu.cn
Received: October 24, 2009; Published online: February 9, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900737.
Abstract: p-Iodotoluene difluoride (p-Tol-IF2) has and propan-2-ol under mild conditions, respectively.
been found to be a general reagent for the effective And, the in situ generated hypervalent iodineACHTUNGTRENNUNG(III)
introduction of various oxygen-containing functional- species via ligand exchange between p-iodotoluene
ities including tosyloxy, mesyloxy, acetoxy, phosphor- difluoride and the respective oxygen-containing nu-
yloxy, methoxy, ethoxy and isopropoxy at the a-posi- cleophiles are believed to be the real oxidizing
tion of b-dicarbonyl compounds. These transforma- agents in such transformations.
tions can be readily realized by the use of the com-
bined reagent of p-iodotoluene difluoride and vari-
ous oxygen-containing nucleophilic compounds such Keywords: b-dicarbonyl compounds; hypervalent
as p-toluenesulfonic acid, methanesulfonic acid, compounds; p-iodotoluene difluoride; nucleophiles;
acetic acid, diphenyl phosphate, methanol, ethanol oxidation
Introduction
bonyl compounds in methanol or ethanol, respective-
ly.[11] To sum up, it is obvious that different oxidizing
The introduction of various oxygen functionalities reagents usually have to be employed for different a-
such as tosyloxy, mesyloxy, acetoxy, phosphoryloxy, oxygen functionalizations on b-dicarbonyl com-
methoxy, ethoxy and isopropoxy at the a-position of pounds. Ideally, it would be more convenient to use
b-dicarbonyl compounds is an important transforma- the same oxidizing reagent with different nucleophiles
tion in organic synthesis since the resulting products to realize all the above a-oxygen functionalizations
are the key intermediates for the synthesis of a varie- on b-dicarbonyl compounds. However, as far as we
ty of heterocyclic[1] and natural products.[2] Methods know, methods for introducing various oxygen func-
for the direct a-tosyloxylation of b-dicarbonyl com- tionalities at the a-position of b-dicarbonyl com-
pounds involve the use of various reagents such as N- pounds by using the same oxidant have not been re-
methyl-O-tosylhydroxylamine,[3]
iodobenzene (HTIB)[4,5] and 1-(p-toluenesulfonyloxy)- such a general and thus convenient method.
1,2-benziodoxol-3(1H)-one.[6]
[Hydroxy- (Difluoro)iodoarenes are powerful and selective
hydroxy(tosylACTHNGUTERNNUoG xy)- ported. Therefore, it was highly desirable to develop
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
(mesyloxy)iodo]benzene (HMIB)[7] is used for the fluorinating reagents. Using p-iodotoluene difluoride
preparation of a-mesyloxylated b-dicarbonyl com- (p-Tol-IF2), various b-dicarbonyl compounds,[12] a-
pounds. Lead tetraacetate[8] and phenyliodine diace- (phenylthio)acetamides,[13] a-(phenylthio) esters,[14] a-
tate (PIDA)[9] are usually employed for a-acetoxyla- seleno carboxylic acid derivatives[15] and silyl enol
tion of b-dicarbonyl compounds. (Hydroxy- ethers[16] can be selectively fluorinated at the a-posi-
ACHTUNGTRENNUNG
{[bis(phenyloxy)phosphoryl]oxy}iodo)benzene[10] can tion. Alkenes can also be fluorinated with p-iodoto-
be used for the synthesis of a-phosphoryloxylated b- luene difluoride to give the rearranged geminal di-
dicarbonyl compounds. In addition, boron trifluoride- fluorides[17] or vic-difluoro products.[18] Also, the phe-
etherate activated iodosobenzene has been utilized nylselenofluorination[19] and iodofluorination[20] of al-
for the a-methoxylation and ethoxylation of b-dicar- kenes can be achieved with the combined reagents p-
Adv. Synth. Catal. 2010, 352, 531 – 546
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
531

Jun Yu et al.
FULL PAPERS
Scheme 1. a-Tosyloxylation of 1a with the combined reagent of p-Tol-IF2 and TsOH·H2O in dichloromethane.
Tol-IF2/PhSeSePh and p-Tol-IF2/I2, respectively. In ad- loxylated product ethyl a-tosyloxybenzoylacetate (2a)
dition, (difluoro)iodoarenes are usually involved for was obtained in 94% yield together with the forma-
the synthesis of various hypervalent iodonium salts.[21] tion of 4-[hydroxy
ACTHNUTRGNEU(GN tosyloxy)iodo]toluene in 15% yield
Besides the applications as the fluorinating reagents, (based on the amount of p-iodotoluene difluoride).
(difluoro)iodoarenes can be used as oxidizing re- Importantly, when a decreased amount of p-toluene-
agents as well and there have been some good exam- sulfonic acid monohydrate (1.5 equivalents) was used,
ples. Koser et al. reported the conversion of silyl enol the reaction gave a similar result and a 22% yield of
ethers to tris-ketol phosphates by a mixed reagent of 4-[hydroxy
p-iodotoluene difluoride and phosphoric acid.[22] (Scheme 1).
Zhdankin et al. developed a convenient procedure for To demonstrate the generality of this method, the
A
was
obtained
the preparation of 1,4-diketones by the treatment of scope of the reaction was investigated and the results
silyl enol ethers with iodonium species generated in are summarized in Table 1. It was found that the reac-
situ from (difluoroiodo)benzene and boron trifluor- tion conditions shown in Scheme 1 were suitable for a
ide.[23] In addition, Myers et al. have applied range of b-keto esters, b-diketones and a b-ketoamide
(difluoroACHTUNGTRENNUNGiodo)benzene for the oxidation of N-tert-bu- all of which went to completion within 10 min. For re-
tyldimethylsilylhydrazones to generate diazoalkanes actions of b-keto esters, both aromatic and aliphatic
in situ which react with carboxylic acids to form the ones gave the corresponding a-tosyloxylated products
esters.[24] However, to the best of our knowledge, in high to excellent yields (Table 1, entries 1–9). As
there is no report on the introduction of oxygen func- for b-diketones 1j, 1k and 1l, the reactions also pro-
tionalities to the a-position of b-dicarbonyl com- vided the desired products 2j, 2k and 2l in high to ex-
pounds mediated by (difluoro)iodoarenes. As part of cellent yields (entries 10–12). Similarly, a b-ketoamide
our continuing investigations on oxidation reactions N,N-dimethyl-3-oxobutanamide (1m)
was also
induced by hypervalent iodine reagents,[25] we herein smoothly a-tosyloxylated to yield the expected prod-
report a general, convenient and efficient method for uct 1-(dimethylamino)-1,3-dioxobutan-2-yl 4-methyl-
the introduction of various oxygen functionalities in- benzenesulfonate (2m) in 94% yield (entry 13).
cluding tosyloxy, mesyloxy, acetoxy, phosphoryloxy,
Not surprisingly, a-mesyloxylation also worked on
methoxy, ethoxy and isopropoxy groups to the a-posi- the substrate 1a by using the combined reagent of p-
tion of b-dicarbonyl compounds by using p-iodoto- iodotoluene difluoride and methanesulfonic acid
luene difluoride with different nucleophiles at room (Scheme 2).
temperature.
Results and Discussion
The Combination of p-Iodotoluene Difluoride with
Organic Acids
Scheme 2. a-Mesyloxylation of ethyl benzoylacetate (1a)
with the combined reagent of p-Tol-IF2 and MsOH in di-
chloromethane.
a-Tosyloxylation of b-Dicarbonyl Compounds with
the Combined Reagent of p-Iodotoluene Difluoride
and p-Toluenesulfonic Acid Monohydrate in
Dichloromethane
a-Acetoxylation of b-Dicarbonyl Compounds with
the Combined Reagent of p-Iodotoluene Difluoride
Initially, ethyl benzoylacetate (1a) (1 mmol) was and Acetic Acid in Dichloromethane
chosen as the model substrate to react with 1.5 equiv-
alents of p-iodotoluene difluoride and 3.0 equivalents With the same oxidizing agent p-iodotoluene difluor-
of p-toluenesulfonic acid monohydrate in 5 mL of di- ide, the a-acetoxylation of b-dicarbonyl compounds
chloromethane at room temperature. After 10 min, it can be realized as well. In a preliminary experiment,
was interesting to find that the corresponding a-tosy- ethyl benzoylacetate (1a) was treated with 1.5 equiva-
532
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 531 – 546

Various a-Oxygen Functionalizations of b-Dicarbonyl Compounds
Table 1. a-Tosyloxylation of b-dicarbonyl compounds with the combined reagent of p-Tol-IF2 and TsOH·H2O in dichloro-
ACHTUNGTRENNUNG
methane.[a,b]
Entry
1
Substrate
Product
Time [min]
10
Yield [%][c]
90[d]
1a
1b
2a
2b
2
5
94
3
4
5
1c
1d
1e
2c
2d
2e
5
93
93
91
5
10
6
7
8
9
1f
1g
1h
1i
2f
2g
2h
2i
10
5
86
85
98
91
5
5
10
1j
2j
5
5
91
85
11
12
1k
2k
1l
2l
5
5
82
94
13
1m
2m
[a]
Reactions were conducted with 1 mmol of b-dicarbonyl compounds under the conditions shown in Scheme 1.
4-[HydroxyACHTUNGTRENNUNG(tosyloxy)iodo]toluene was obtained in the yield range of 6-22% except for substrate 1m.
Isolated yield.
[b]
[c]
[d]
1% of ethyl 2-fluoro-3-oxo-3-phenylpropionate was detected.
Adv. Synth. Catal. 2010, 352, 531 – 546
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
533

Jun Yu et al.
FULL PAPERS
lents of p-iodotoluene difluoride in 5 mL of acetic ketones 3j and 3k in high yields within short reaction
acid at room temperature. It was encouraging to ob- times (entries 10 and 11). This method can be success-
serve the formation of ethyl 2-acetoxy-3-oxo-3-phe- fully extended to
nylpropanoate (3a) in 80% yield although the reac- (entry 12).
tion proceeded slowly (16 h) (Scheme 3).
a b-ketoamide 1m as well
In order to improve the efficiency of the reaction
and simplify its work-up, the reaction conditions were a-Phosphoryloxylation of b-Dicarbonyl Compounds
optimized via introduing dichloromethane as the sol- with the Combined Reagent of p-Iodotoluene
vent and subsequently changing the volume ratio of Difluoride and Diphenyl Phosphate in
acetic acid and dichloromethane (Table 2). Firstly, Dichloromethane
substrate 1a was subjected to 1.5 equivalents of p-io-
dotoluene difluoride and acetic acid (0.172 mL, p-Iodotoluene difluoride could also be utilized for the
3.0 equivalents) in 5 mL of dichloromethane. It was a-phosphoryloxylation of b-dicarbonyl compounds
found that the reaction was completed in a shorter (Table 4). When 1a was subjected to 1.5 equivalents
time (4 h) but afforded a lower yield of 3a (60%) of p-iodotoluene difluoride and 3.0 equivalents of di-
(Table 2, entry 2). When 1 mL of acetic acid was em- phenyl phosphate in 5 mL of dichloromethane at
ployed (17.5 equivalents), the reaction was completed room temperature, the reaction provided the corre-
in 1.5 h and the yield of 3a was improved to 72% sponding a-phosphoryloxylated product 4a in 86%
(entry 3). Increasing the amount of acetic acid up to yield within 15 min (Table 4, entry 1). Under the same
3 mL (52.5 equivalents) resulted in a complete reac- conditions, a b-diketone 1j and a b-ketoamide 1m
tion within 50 min and an excellent yield of 3a could also be smoothly converted to their correspond-
(entry 5).
ing a-phosphoryloxylated products 4j and 4m in good
With the optimized conditions in hand, we investi- yields, respectively (entries 2 and 3).
gated the substrate generality of this method and the
results are shown in Table 3. The ethyl benzoylacetate
derivatives bearing either electron-donating groups or The Combination of p-Iodotoluene Difluoride with
electron-withdrawing groups on the phenyl rings 1b, Alcohols
1c and 1d afforded excellent results (Table 3, en-
tries 2–4). Other b-keto esters were also efficiently a-Methoxylation of b-Dicarbonyl Compounds with
transformed to their corresponding a-acetoxylated p-Iodotoluene Difluoride in Methanol
products in high yields (entries 5–9). Two b-diketones
1j and 1k also reacted smoothly under the optimized We also examined whether p-iodotoluene difluoride
conditions to provide the desired a-acetoxylated b-di- would be effective for the a-methoxylation of b-dicar-
bonyl compounds. To our delight, the reaction of 1a
with 1.5 equivalents of p-iodotoluene difluoride in
5 mL of methanol was completed in 4 h at room tem-
perature to afford ethyl 2-methoxy-3-oxo-3-phenyl-
propanoate (5a) in 83% yield (Scheme 4).
A variety of b-dicarbonyl compounds including b-
keto esters, b-diketones and a b-ketoamide were
tested using this new a-methoxylation protocol
(Table 5). The para-substituted ethyl benzoylacetates
1b, 1c, 1d were smoothly converted to their corre-
sponding a-methoxylated products 5b, 5c and 5d in
high yields within 4 h (Table 5, entries 2–4). Other ar-
omatic ring systems such as naphthalene and furan
were well tolerared as indicated by the successful
transformation of substrates 1e and 1f (entries 5 and
6). Methyl 1-oxo-2-indanecarboxylate (1n) can also be
readily oxidized to the corresponding a-methoxylated
product 5n in an excellent yield (entry 7). In the case
of ethyl 3-oxo-3-(pyridin-2-yl)propanoate (1o), the
mono-methoxylated product 5o was obtained in 50%
yield together with formation of the dimethoxylated
product in 29% yield (entry 8). As for aliphatic b-
keto esters 1g, 1h and 1p, their corresponding a-me-
thoxylated products 5g, 5h and 5p were obtained in
Scheme 3. a-Acetoxylation of 1a with p-Tol-IF2 in AcOH.
Table 2. Optimization of the reaction conditions of a-acetox-
ylation on 1a.
Entry
AcOH/CH2Cl2 [mL/mL]
Time [h]
Yield [%][a]
1
2
3
4
5
5/0
0.172/5
1/5
2/5
3/5
16
4
1.5
1
80
60
72
84
94
50 min
[a]
Isolated yield.
534
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 531 – 546

Various a-Oxygen Functionalizations of b-Dicarbonyl Compounds
Table 3. a-Acetoxylation of b-dicarbonyl compounds with the combined reagent of p-Tol-IF2 and AcOH in dichloro-
ACHTUNGTRENNUNG
methane.[a]
Entry
1
Substrate
Product
Time [min]
50
Yield [%][b]
94
1a
1b
3a
3b
2
20
93
3
4
5
1c
1d
1e
3c
3d
3e
35
75
35
88
90
80
6
7
8
9
1f
1g
1h
1i
3f
3g
3h
3i
30
60
80
60
80
78
85
70
10
11
1j
3j
15
81
1k
3k
20
30
70
75
12
1m
3m
[a]
Reactions were conducted with 1 mmol of b-dicarbonyl compounds, 1.5 mmol of p-Tol-IF2 in 3 mL of AcOH and 5 mL of
dichloromethane at room temperature.
Isolated yield.
[b]
high yields (entries 9-11). Two b-diketones 1j and 1k N,N-dimethyl-3-oxobutanamide (1m), was examined
were also smoothly a-methoxylated to give 5j and 5k as well and the reaction afforded the expected a-me-
in high yields, respectively (entries 12 and 13). Nota- thoxylated product 5m in an excellent yield within 1 h
bly, three equivalents of methanol were enough for (entry 14).
the completion of these two reactions. A b-ketoamide,
Adv. Synth. Catal. 2010, 352, 531 – 546
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
535

Jun Yu et al.
FULL PAPERS
Table 4. a-Phosphoryloxylation of b-dicarbonyl compounds with the combined reagent of p-iodotoluene difluoride and di-
phenyl phosphate in dichloromethane.[a]
Entry
1
Substrate
Product
Time [min]
15
Yield [%][b]
86[c]
1a
1j
4a
4j
2
20
20
66
75
3
1m
4m
[a]
Reactions were conducted with 1 mmol of b-dicarbonyl compounds, 1.5 mmol of p-iodotoluene difluoride and 3.0 mmol
of diphenyl phosphate in 5 mL of dichloromethane at room temperature.
Isolated yield.
[b]
[c]
1% of ethyl 2-fluoro-3-oxo-3-phenylpropionate was detected.
Ethoxylation and Isopropoxylation of 1a with
p-Iodotoluene Difluoride in Ethanol or 2-Propanol
The ethoxylation was also tried still using 1a as the
substrate and it was found that the use of ethanol as
the solvent could successfully lead to the formation of
the corresponding a-ethoxylated product (5q) in high
Scheme 4. a-Methoxylation of 1a with p-Tol-IF2 in metha-
yield (Scheme 5). However, as for isopropoxylation,
nol.
Table 5. a-Methoxylation of b-dicarbonyl compounds with p-Tol-IF2 in methanol.[a]
Entry
Substrate
Product
Time [h]
4
Yeld [%][b]
83[c]
1
1a
1b
1c
1d
5a
5b
5c
5d
2
3
4
4
4
4
87
83
89
5
6
1e
1f
5e
5f
11
1
80
88
536
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 531 – 546

Various a-Oxygen Functionalizations of b-Dicarbonyl Compounds
Table 5. (Continued)
Entry
Substrate
Product
Time [h]
4
Yeld [%][b]
91
7
1n
1o
5n
5o
8
4
50[d]
9
1g
1h
1p
5g
5h
5p
4
70[e]
70
10
11
24
4
81
12
13
1j
5j
0.5
75[f]
1k
5k
5
1
72[f]
90
14
1m
5m
[a]
Unless otherwise indicated, the reactions were conducted with 1 mmol of b-dicarbonyl compounds under the conditions
shown in Scheme 4.
Isolated yield.
[b]
[c]
[d]
[e]
[f]
2% of ethyl 2-fluoro-3-oxo-3-phenylpropionate was detected.
The a-dimethoxylated product was obtained in 29% yield.
GC yield.
The reaction was carried out with 1 mmol of b-diketone, 1.5 mmol of p-iodotoluene difluoride and 3.0 mmol of methanol
in 5 mL of dichloromethane at room temperature.
the desired a-isopropoxylated product (5r) was ob- of starting material being 63% even after 16 h. This is
tained in a moderate yield (53%) with the conversion largely the consequence of the bulkiness of 2-propa-
nol compared with that of methanol and ethanol.
Mechanism Considerations
The Mechanism of p-Iodotoluene Difluoride-
Mediated a-Tosyloxylation, Acetoxylation and
Phosphoryloxylation of b-Dicarbonyl Compounds
The mechanism of our new a-tosyloxylation reactions
is outlined in Scheme 6. The isolation of 4-[hydroxy-
AHCTUNGTREG(NNNU tosyloxy)iodo]toluene in the synthesis of a-tosyloxy-
lated b-dicarbonyl compounds indicated that two
steps were involved in our tosyloxylation reaction.
Scheme 5. The ethoxylation and isopropoxylation of 1a with
p-iodotoluene difluoride in ethanol or 2-propanol.
Adv. Synth. Catal. 2010, 352, 531 – 546
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
537

Jun Yu et al.
FULL PAPERS
Several experiments were carried out to probe the
reactive intermediate of our a-phosphoryloxylation
reaction. p-Iodotoluene difluoride was mixed with
2.0 equivalents of diphenyl phosphate in CDCl3 and
monitored by 1H NMR and 31P NMR spectroscopy.
1
The H NMR spectrum of the mixture revealed that
p-iodotoluene difluoride was consumed after 15 min
and a new compound was formed which was believed
to be p-CH3C6H4IACHTNUTRGENN(UG OPOCAHTUNGTREN(NNGU OPh)2)2 (A2) on the basis of
its H NMR spectrum (Figure 1). The 31P NMR spec-
trum suggested the change of diphenyl phosphate and
the formation of a new compound since the signal of
diphenyl phosphate (À10.58 ppm) disappeared and a
new signal appeared at À11.89 ppm (Figure 2). The
mass spectrum for the reaction mixture of p-iodoto-
luene difluoride (1 mmol) and diphenyl phosphate
(2.0 mmol) in 5 mL of dichloromethane showed that a
peak appeared at m/z=717 (Figure 3), corresponding
to [M+H]+ (molecular weight of A2: 716). All these
results indicated the presence of A2, which acted as
the real oxidizing reagent in our phosphoryloxylation
reaction (Scheme 8).
1
Scheme 6. Plausible mechanism of p-iodotoluene difluoride
mediated a-tosyloxylation of b-dicarbonyl compounds.
Firstly, p-iodotoluene difluoride reacted with p-tolu-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
which promoted the formation of the enol form of
the b-dicarbonyl compounds. Then, electrophilic addi-
tion of A to the enol form of the b-dicarbonyl com-
pounds gave the intermediate B which was followed
by the nucleophilic attack of TsOH upon the a-
Scheme 7. Ligand exchange reaction between 2-difluoroio-
do-1,3,5-trimethylbenzene and AcOH.
carbon-bearing iodineACTHNUTRGNE(UNG III) structural unit in B to
yield the corresponding a-tosyloxylated products with
the concomitant reductive elimination of p-iodoto-
luene[4]. In our initial procedure, ethyl benzoylacetate
(1a) was converted to ethyl a-tosyloxybenzoylacetate
(2a) in 94% yield within 10 min by using 1.5 equiva-
lents of p-iodotoluene difluoride and 3.0 equivalents
of TsOH·H2O. However, according to the first step of
the mechanism shown in Scheme 6 in which the nu-
clephilic attack of water was considered, a 1:1 mixture
of TsOH·H2O and p-iodotoluene difluoride should be
enough to produce the intermediate A. Therefore,
1.5 equivalents of TsOH·H2O were employed and the
reaction proceeded well as expected (Scheme 1 and
Table 1).
Shreeve et al. have reported that 2-difluoroiodo-
1,3,5-trimethylbenzene could be quickly converted
into its diacetate in quantitative yield when treated
with acetic acid (Scheme 7).[26,27] Thus, in our new a-
acetoxylation reactions, a similar ligand exchange re-
action between p-iodotoluene difluoride and acetic
acid should be involved to generate the active inter-
mediate A1 shown in Scheme 8. Then, the intermedi-
ate A1 oxidized the enol form of the b-dicarbonyl
compounds to provide the corresponding a-acetoxy-
lated products via the intermediate B1 (Scheme 8).[9]
Scheme 8. Plausible mechanism of p-iodotoluene difluoride
mediated a-acetoxylation, phosphoryloxylation and alkoxy-
lation of b-dicarbonyl compounds.
538
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 531 – 546

Various a-Oxygen Functionalizations of b-Dicarbonyl Compounds
Figure 1. 1H NMR spectrum (400 MHz) of p-iodotoluene difluoride (top) and that of the reaction mixture of p-iodotoluene
difluoride (0.05 mmol) and diphenyl phosphate (0.1 mmol) in 1 mL of CDCl3 after 3 min (middle) and 15 min (bottom), re-
spectively.
The Mechanism of p-Iodotoluene Difluoride-
Mediated a-Alkoxylation of b-Dicarbonyl
Compounds
of various oxygen functionalities including tosyloxy,
mesyloxy, acetoxy, phosphoryloxy, methoxy, ethoxy
and isopropoxy to the a-position of b-dicarbonyl com-
pounds. It is significant that all these transformations
Moriarty et al. have reported that boron trifluoride- were accomplished by using the same reagent p-iodo-
etherate activated iodosobenzene could be utilized toluene difluoride, which is readily available. In addi-
for the a-alkoxylation of b-dicarbonyl compounds in tion, these reactions are tolerant of a range of func-
alcohols.[11] Here, the in situ generated alkoxyiodine- tional groups and thus effective for a broad scope of
ACHTUNGTRENNUNG(III) reagents PhI(OR)2 (R=Me, Et) were believed substrate. The in situ generated active hypervalent
to be the key intermediates of these transforma- iodine species are believed to be the real oxidizing
tions.[11,28] Thus, the mechanism of our a-alkoxylation agent in these reactions. Considering the generality,
reaction was also believed to involve an initial ligand convenience and efficiency of the present method, it
exchange reaction between p-iodotoluene difluoride should be an attractive method to synthesize various
and alcohols to generate the alkoxyiodineACHTUNTRGNEUNG(III) inter- a-oxygen functionalized b-dicarbonyl compounds.
mediates p-CH3C6H4I(OR)2 (A3). Then, the inter-
mediate A3 oxidized the enol form of the b-dicarbon-
yl compounds to yield the corresponding a-alkoxylat-
ed products via the intermediate B3 (Scheme 8).
Experimental Section
Materials and Methods
Conclusions
p-Iodotoluene difluoride was prepared according to the re-
ported method.[14b] Alcohols, acetic acid, p-toluenesulfonic
acid monohydrate, methanesulfonic acid and diphenyl phos-
The reported hypervalent iodine reagent, p-iodoto-
luene difluoride, was found to effect the introduction phate were purchased from commercial suppliers. The
Adv. Synth. Catal. 2010, 352, 531 – 546
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
539

Jun Yu et al.
FULL PAPERS
Figure 2. 31P NMR spectrum (121 MHz) of diphenyl phosphate (top) and that of the mixture of p-iodotoluene difluoride
(0.05 mmol) and diphenyl phosphate (0.1 mmol) in 1 mL of CDCl3 after 15 min (bottom).
1H NMR spectra were recorded at 400 MHz and 13C NMR
spectra were measured at 100 MHz using a Bruker AV400
instrument with CDCl3 or DMSO-d6 as the solvent. The
19F NMR spectrum was recorded at 376 MHz and 31P NMR
spectra were measured at 121 MHz still using a Bruker
AV400 instrument with CDCl3 as the solvent. IR spectra
were recorded on a FT-IR Bruker EQUINOX55 spectrome-
ter in KBr pellets. High resolution mass spectral analyses
(HR-MS) were performed on a high resolution ESI-FTICR
or MALDI-FTICR mass spectrometer (Varian 7.0 T). MS-
APCI data were colleted using a ThermoFisher Scientific
mass spectrometer system (Surveyor MSQ Plus). GC analy-
ses were carried out on a Shimadzu 2014 series GC system
equipped with an Rtx-5 column (30 m, ID 0.25 mm) and an
FID. Petroleum ether (PE), where used, had the boiling
point range 60–908C.
NaHCO3 (5 mL) and saturated aqueous Na2S2O3 (5 mL).
The separated aqueous phase was extracted with dichloro-
methane (20 mL). The combined organic layer was washed
with brine, dried over anhydrous Na2SO4 and concentrated
in vacuo to afford the crude product which was purified by
flash column chromatograpy (PE-EtOAc, 17:3) to give 2a as
a colorless oil; yield: 326 mg (90%).[4a] 1H NMR (400 MHz,
CDCl3): d=1.17 (t, J=7.2 Hz, 3H), 2.43 (s, 3H), 4.14–4.22
(m, 2H), 5.99 (s, 1H), 7.29 (t, J=8.0 Hz, 2H), 7.46 (t, J=
8.0 Hz, 2H), 7.61(t, J=8.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 2H),
7.92 (d, J=8.0 Hz, 2H); 13C NMR (100 MHz): d=13.79,
21.67, 62.83, 78.06, 128.29, 128.73, 129.39, 129.83, 132.40,
133.30, 134.37, 145.65, 164.15, 188.20.
4-[Hydroxy
G
White
solid,
1
mp:137–1388C. H NMR (400 MHz, DMSO-d6): d=2.26 (s,
3H), 2.38 (s, 3H), 7.09 (d, J=7.6 Hz, 2H), 7.37 (d, J=
7.6 Hz, 2H), 7.45 (d, J=7.6 Hz, 2H), 8.06 (d, J=7.6 Hz,
2H), 9.63 (bs, 1H); 13C NMR (100 MHz, DMSO-d6): d=
22.10, 22.33, 121.65, 126.82, 129.49, 132.94, 136.06, 139.35,
144.25, 146.30.
Typical Procedure for a-Tosyloxylation of b-
Dicarbonyl Compounds
To a solution of ethyl benzoylacetate (1a) (192 mg, 1 mmol)
in 5 mL of dichloromethane in a 10-mL round-bottom flask
were added p-toluenesulfonic acid monohydrate (285 mg,
1.5 mmol) and p-iodotoluene difluoride (384 mg, 1.5 mmol).
The reaction mixture was stirred at room temperature and
monitored by TLC. After 10 min, the white solid was col-
lected by filtration and washed with 20 mL of dichlorome-
Ethyl 2-fluoro-3-oxo-3-phenylpropionate:[12c] Colorless oil.
1H NMR (400 MHz, CDCl3): d=1.26 (t, J=7.2 Hz, 3H),
4.27–4.33 (m, 2H), 5.87 (d, J=48.8 Hz, 1H), 7.50 (t, J=
7.2 Hz, 2H), 7.64 (t, J=7.2 Hz, 1H), 8.04 (d, J=8.4 Hz,
2H); 13C NMR (100 MHz): d=13.92, 62.69, 90.08 (d, J=
196.5 Hz), 128.81, 129.49, 133.36, 134.51, 164.90 (d, J=
23.8 Hz), 189.53 (d, J=20.2 Hz); 19F NMR (376 MHz): d=
À190.32.
thane to afford 4-[hydroxy
ACHTUNGTRNE(NUNG tosyloxy)iodo]toluene; yield:
135 mg. The filtrate was washed with saturated aqueous
540
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 531 – 546

Various a-Oxygen Functionalizations of b-Dicarbonyl Compounds
Figure 3. The mass spectrum (APCI) of the reaction mixture of p-iodotoluene difluoride (1 mmol) and diphenyl phosphate
(2.0 mmol) in 5 mL of dichloromethane.
Ethyl 3-(4-methoxyphenyl)-3-oxo-2-(tosyloxy)propanoate
(2b): White solid, mp: 88–908C. IR (KBr): n=3434, 3012,
2988, 2962, 2841, 1766, 1753, 1676, 1599, 1515, 1463, 1366,
1340, 1329, 1310, 1272, 1244, 1203, 1192, 1123, 1038, 897,
830, 813, 847, 798, 738, 723, 687, 654, 643, 586, 556,
Ethyl 3-oxo-3-p-tolyl-2-(tosyloxy)propanoate (2d): Color-
less oil. IR (KBr): n=3036, 2983, 2926, 1766, 1693, 1606,
1573, 1447, 1409, 1372, 1294, 1235, 1177, 1191, 1122, 1096,
1060, 1041, 963, 898, 813, 791, 750, 713, 678, 553, 473 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=1.10 (t, J=7.2 Hz, 3H),
2.34 (s, 3H), 2.36 (s, 3H), 4.08–4.14 (m, 2H), 5.89 (s, 1H),
7.18 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 7.72 (d, J=
8.0 Hz, 2H), 7.76 (d, J=8.0 Hz, 2H); 13C NMR (100 MHz):
d=13.80, 21.67, 21.79, 62.75, 78.03, 128.29, 129.46, 129.55,
129.80, 130.84, 132.50, 145.59, 145.62, 164.30, 187.66; HR-
MS (ESI): m/z=399.0869, calcd. for C19H20O6SNa [M+
Na]+: 399.0873.
525 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=1.17 (t, J=
7.2 Hz, 3H), 2.42 (s, 3H), 3.87 (s, 3H), 4.12–4.21 (m, 2H),
5.94 (s, 1H), 6.92 (d, J=8.4 Hz, 2H), 7.30 (d, J=8.4 Hz,
2H), 7.79 (d, J=8.4 Hz, 2H), 7.93(d, J=8.4 Hz, 2H);
13C NMR (100 MHz): d=13.82, 21.67, 55.57, 62.71, 78.07,
114.02, 126.23, 128.29, 129.80, 131.97, 132.51, 145.57, 164.43,
164.53, 186.37; HR-MS (ESI): m/z=415.0817, calcd. for
C19H20O7SNa [M+Na]+: 415.0822.
Ethyl 3-(naphthalen-2-yl)-3-oxo-2-(tosyloxy)propanoate
(2e): Colorless oil. IR (KBr): n=3061, 2983, 2939, 1766,
1690, 1626, 1597, 1469, 1372, 1293, 1226, 1192, 1178, 1125,
1095, 1047, 1021, 978, 935, 912, 864, 813, 767, 751, 706, 692,
Ethyl
3-(4-chlorophenyl)-3-oxo-2-(tosyloxy)propanoate
(2c): White solid, mp 73–758C. IR (KBr): n=3501, 3431,
3378, 3094, 2991, 2945, 2925, 2908, 1760, 1698, 1590, 1572,
1490, 1474, 1403, 1366, 1360, 1343, 1312, 1294, 1232, 1205,
1176, 1115, 1095, 1041, 1010, 927, 895, 827, 816, 711, 683,
1
661, 552, 476 cmÀ1; H NMR (400 MHz, CDCl3): d=1.18 (t,
J=7.2 Hz, 3H), 2.39 (s, 3H), 4.16–4.25 (m, 2H), 6.13 (s,
1H), 7.24 (s, 1H), 7.26 (s, 1H), 7.57 (t, J=8.0 Hz, 1H), 7.64
(t, J=8.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 2H), 7.87 (d, J=
8.0 Hz, 2H), 7.93 (t, J=8.0 Hz, 2H), 8.49 (s, 1H); 13C NMR
(100 MHz): d=13.89, 21.70, 62.92, 78.15, 124.16, 127.11,
127.81, 128.33, 128.72, 129.43, 129.87, 130.02, 130.68, 132.06,
132.23, 132.49, 136.03, 145.70, 164.35, 188.14; HR-MS (ESI):
m/z=413.1054, calcd. for C22H20O6SNa [M+H]+: 413.1053.
1
569, 540 cmÀ1; H NMR (400 MHz, CDCl3): d=1.17 (t, J=
7.2 Hz, 3H), 2.43 (s, 3H), 4.13–4.22 (m, 2H), 5.91 (s, 1H),
7.30 (d, J=8.4 Hz, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.70 (d, J=
8.4 Hz, 2H), 7.87 (d, J=8.4 Hz, 2H); 13C NMR (100 MHz):
d=13.77, 21.66, 62.95, 78.12, 128.25, 129.09, 129.86, 130.78,
131.54, 132.19, 141.02, 145.80, 163.92, 187.20; HR-MS (ESI):
m/z: 397.0505, calcd. for C18H17O6SCl [M+H]+: 397.0507.
Adv. Synth. Catal. 2010, 352, 531 – 546
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
541

Jun Yu et al.
FULL PAPERS
Ethyl 3-(furan-2-yl)-3-oxo-2-(tosyloxy)propanoate (2f):
Light red oil. IR (KBr): n=3328, 3131, 2980, 2935, 1770,
1747, 1681, 1634, 1597, 1572, 1494, 1463, 1399, 1371, 1295,
1262, 1178, 1122, 1095, 1067, 1031, 993, 930, 881, 815, 790,
13C NMR (100 MHz): d=21.55, 22.60, 26.56, 29.66, 84.57,
127.71, 127.76, 127.97, 128.16, 128.44, 128.65, 128.69, 129.41,
129.44, 129.96, 130.94, 131.42, 133.28, 134.40, 145.28, 179.72,
191.51.
2,4-Dioxopentan-3-yl 4-methylbenzenesulfonate (2l):[5]
White solid, mp 828C. 1H NMR (400 MHz, CDCl3, enol
form): d=1.95 (s, 6H), 2.48 (s, 3H), 7.39 (d, J=7.6 Hz, 2H),
7.82 (d, J=7.6 Hz, 2H), 14.76 (s, 1H); 13C NMR (100 MHz):
d=21.31, 21.73, 128.50, 130.16, 132.29, 146.04, 187.33.
1-(Dimethylamino)-1,3-dioxobutan-2-yl 4-methylbenzene-
sulfonate (2m): White solid, mp: 80–828C. IR (KBr): n=
3454, 3085, 3051, 3029, 2945, 1952, 1838, 1735, 1651, 1595,
1496, 1455, 1417, 1401, 1384, 1365, 1301, 1255, 1190, 1172,
1122, 1093, 1042, 1015, 969, 880, 817, 797, 733, 708, 697, 684,
742, 688, 664, 592, 555, 536 cmÀ1
;
1H NMR (400 MHz,
CDCl3): d=1.18 (t, J=7.2 Hz, 3H), 2.44 (s, 3H), 4.13–4.22
(m, 2H), 5.83 (s, 1H), 6.59 (dd, J=1.6 Hz, 3.6 Hz, 1H), 7.33
(d, J=8.4 Hz, 2H), 7.44 (t, J=3.6 Hz, 1H), 7.65 (s, 1H),
7.82 (d, J=8.4 Hz, 2H); 13C NMR (100 MHz): d=13.81,
21.70, 62.88, 112.97, 121.54, 128.30, 129.85, 132.40, 145.69,
148.29, 149.32, 163.69, 176.13; HR-MS (ESI): m/z=
375.0504, calcd. for C16H16O7SNa [M+Na]+: 375.0509.
Ethyl 4-methyl-3-oxo-2-(tosyloxy)pentanoate (2g): Color-
less oil. IR (KBr): n=3447, 2979, 2938, 2877, 1760, 1732,
1652, 1598, 1494, 1467, 1448, 1374, 1293, 1267, 1211, 1192,
1179, 1093, 1077, 1022, 1001, 953, 875, 816, 755, 705, 670,
534 cmÀ1; 1H NMR (400 MHz, CDCl3): d=1.08 (d, J=
6.8 Hz, 6H), 1.20 (t, J=7.2 Hz, 3H), 2.45 (s, 3H), 3.01–3.11
(m, 1H), 4.13 (q, J=7.2 Hz, 2H), 5.35 (s, 1H), 7.36 (d, J=
7.2 Hz, 2H), 7.83 (d, J=7.2 Hz, 2H); 13C NMR (100 MHz):
d=13.82, 17.60, 17.87, 21.69, 37.32, 62.63, 79.03, 128.25,
129.92, 132.33, 145.75, 163.83, 202.91; HRMS (ESI): m/z=
351.0868, calcd. for C15H20O6SNa [M+Na]+: 351.0873.
665, 633, 600, 569, 482 cmÀ1 1H NMR (400 MHz, CDCl3):
;
d=2.24 (s, 3H), 2.45 (s, 3H), 2.85 (s, 3H), 3.00 (s, 3H), 5.53
(s, 1H), 7.36 (d, J=8.0 Hz, 2H) 7.83 (d, J=8.0 Hz, 2H);
13C NMR (100 MHz): d=21.71, 26.54, 36.15, 37.28, 79.83,
128.18, 129.93, 132.42, 145.79, 162.87, 199.88; HR-MS (ESI):
m/z=322.0723, calcd. for C13H17NO5SNa [M+Na]+:
322.0719.
Ethyl
2-(methylsulfonyloxy)-3-oxo-3-phenylpropanoate
(2n):[7] Light yellow oil. 1H NMR (400 MHz, CDCl3): d=
1.24 (t, J=7.2 Hz, 3H), 3.27 (s, 3H), 4.29 (q, J=7.2 Hz,
2H), 6.22 (s, 1H), 7.52 (t, J=7.6 Hz, 2H), 7.66 (t, J=7.6 Hz,
1H), 8.03 (d, J=7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d=13.82, 39.65, 63.04, 77.44, 128.93, 129.37, 133.42, 134.65,
164.55, 187.99.
Ethyl 4,4-dimethyl-3-oxo-2-(tosyloxy)pentanoate (2h):
White solid, mp 42–438C. IR (KBr): n=3430, 2977, 2938,
2910, 2875, 1926, 1756, 1725, 1596, 1476, 1400, 1367, 1335,
1294, 1252, 1216, 1188, 1176, 1095, 1069, 1039, 10247, 994,
935, 907, 873, 832, 814, 752, 707, 697, 659, 630, 591, 5587,
547 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=1.18 (t, J=
7.6 Hz, 3H), 1.19 (s, 9H), 2.43 (s, 3H), 4.08–4.15 (m, 2H),
5.70 (s, 1H), 7.33 (d, J=8.0 Hz, 2H), 7.82 (d, J=8.0 Hz,
2H); 13C NMR (100 MHz): d=13.74, 21.62, 26.09, 44.94,
62.46, 75.22, 128.21, 129.75, 132.68, 145.56, 164.33, 203.05;
HR-MS (ESI): m/z=365.1024, calcd. for C16H22O6SNa [M+
Na]+: 365.1029.
Typical Procedure for a-Acetoxylation of b-
Dicarbonyl Compounds
To a solution of ethyl benzoylacetate (1a) (192 mg, 1 mmol)
in 5 mL of dichloromethane in a 10-mL round-bottom flask
was added acetic acid (3 mL) and p-iodotoluene difluoride
(384 mg, 1.5 mmol). The reaction mixture was stirred at
room temperature and monitored by TLC. After 50 min, the
resulting mixture was diluted with dichloromethane
(50 mL). Then, the mixture was washed with saturated aque-
ous NaHCO3 (30 mL) and saturated aqueous Na2S2O3
(5 mL). The separated aqueous phase was extracted with di-
chloromethane (50 mL). The combined organic layer was
washed with brine, dried over anhydrous Na2SO4 and con-
centrated under vacuum to afford the crude product which
was purified by flash column chromatograpy (PE-EtOAc,
9:1) to give 3a as a colorless oil; yield: 235 mg (94%).[9d]
1H NMR (400 MHz, CDCl3): d=1.22 (t, J=7.2 Hz, 3H),
2.23 (s, 3H), 4.25 (q, J=7.2 Hz, 2H), 6.33 (s, 1H), 7.50 (t,
J=7.2 Hz, 2H), 7.63 (t, J=7.2 Hz, 1H), 8.01 (d, J=7.2 Hz,
2H); 13C NMR (100 MHz): d=13.88, 20.51, 62.51, 74.47,
128.47, 128.77, 129.20, 134.19, 134.21, 165.15, 169.55, 189.66.
Ethyl 3-oxo-2-(tosyloxy)butanoate (2i):[3] Colorless oil.
1H NMR (400 MHz, CDCl3, keto-enol): d=1.07 (t, J=
7.2 Hz, 0.62H), 1.19 (t, J=7.2 Hz, 3H), 1.98 (s, 0.6H), 2.27
(s, 3H), 2.44 (s, 3H), 4.00 (q, J=7.2 Hz, 0.39H), 4.13 (q, J=
7.2 Hz, 2H), 5.17 (s, 1H), 7.35 (d, J=7.6 Hz, 2H), 7.81 (d,
J=7.6 Hz, 2H), 11.54 (s, 0.18H); 13C NMR (100 MHz): d=
13.61, 13.68, 14.04, 17.32, 21.51, 21.56, 26.46, 29.53, 61.22,
62.66, 80.45, 118.09, 128.09, 128.34, 129.56, 129.91, 132.04,
133.09, 145.27, 145.80, 163.30, 170.84, 196.93.
1,3-Dioxo-1,3-diphenylpropan-2-yl 4-methylbenzenesulfo-
nate (2j):[5] White solid, mp 898C. 1H NMR (400 MHz,
CDCl3, keto-enol): d=2.21 (s, 3H), 2.31 (s, 1H), 6.59 (s,
0.34H), 6.79 (d, J=8.0 Hz, 2H), 7.12 (d, J=8.0 Hz, 0.71H),
7.17 (d, J=8.0 Hz, 2H), 7.27–7.40 (m, 7H), 7.49 (t, J=
7.2 Hz, 0.85H), 7.61 (d, J=8.0 Hz, 0.71H), 7.70 (d, J=
7.2 Hz, 4H), 7.87 (d, J=7.2 Hz, 1.5H), 15.55 (s, 1H);
13C NMR (100 MHz): d=21.50, 83.82, 126.93, 128.02, 128.20,
128.40, 128.65, 129.16, 129.28, 129.64, 129.76, 130.61, 130.79,
131.94, 132.36, 133.58, 134.05, 134.31, 145.05, 145.57, 183.39,
189.88.
1,3-Dioxo-1-phenylbutan-2-yl 4-methylbenzenesulfonate
(2k):[29] White solid, mp 89–908C. 1H NMR (400 MHz,
CDCl3, keto-enol): d=2.28 (s, 0.51H), 2.32 (s, 3H), 2.39 (s,
3H), 2.42 (s, 0.51H), 5.96 (s, 0.15H), 6.95 (d, J=8.0 Hz,
2H), 7.20 (t, J=7.6 Hz, 2H), 7.34 (d, J=8.0 Hz, 3H) 7.42
(d, J=7.6 Hz, 2H), 7.59 (t, J=7.6 Hz, 0.23H), 7.74 (d, J=
8.0 Hz, 0.29H), 7.83 (d, J=7.6 Hz, 0.30H), 15.18 (s, 1H);
Ethyl
2-acetoxy-3-(4-methoxyphenyl)-3-oxopropanoate
(3b): Colorless oil. IR (KBr): n=2983, 2940, 2910, 2844,
1751, 1686, 1601, 1575, 1513, 1464, 1445, 1423, 1374, 1311,
1264, 1229, 1208, 1174, 1094, 1026, 953, 923, 842, 813,
657 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=1.23 (t, J=
7.2 Hz, 3H), 2.23 (s, 3H), 3.89 (s, 3H), 4.25 (q, J=7.2 Hz,
2H), 6.29 (s, 1H), 6.97 (d, J=8.8 Hz, 2H), 8.01 (d, J=
8.8 Hz, 2H); 13C NMR (100 MHz): d=13.90, 20.52, 55.55,
62.38, 74.37, 114.00, 127.05, 131.70, 164.40, 165.39, 169.58,
187.86; HR-MS (ESI): m/z=303.0846, calcd. for
C14H16O6Na [M+Na]+: 303.0839.
542
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 531 – 546

Various a-Oxygen Functionalizations of b-Dicarbonyl Compounds
Ethyl 2-acetoxy-3-(4-chlorophenyl)-3-oxopropanoate (3c):
Colorless oil. IR (KBr): n=3095, 2984, 2940, 1754, 1698,
1590, 1572, 1402, 1374, 1225, 1205, 1093, 1024, 1013, 943,
1,3-Dioxo-1,3-diphenylpropan-2-yl acetate (3j):[9b] White
solid, mp 94–958C. H NMR (400 MHz, CDCl3): d=2.24 (s,
1
3H), 7.00 (s, 1H), 7.47 (t, J=7.6 Hz, 4H), 7.60 (t, J=7.6 Hz,
2H), 8.04 (d, J=7.6 Hz, 4H); 13C NMR (100 MHz): d=
20.64, 79.99, 128.76, 129.41, 134.20, 134.28, 169.33, 191.04.
1,3-Dioxo-1-phenylbutan-2-yl acetate (3k):[31] Colorless
oil. 1H NMR (400 MHz, CDCl3): d=2.24 (s, 3H), 2.30 (s,
3H), 6.26 (s, 1H), 7.49 (t, J=7.2 Hz, 2H), 7.62 (t, J=7.2 Hz,
1H), 8.00 (d, J=7.2 Hz, 2H); 13C NMR (100 MHz): d=
20.54, 26.85, 82.22, 128.34, 128.75, 129.47, 134.30, 169.30,
190.84, 199.45.
1-(Dimethylamino)-1,3-dioxobutan-2-yl acetate (3m): Col-
orless oil. IR (KBr): n=3481, 2940, 1739, 1653, 1501, 1405,
1373, 1231, 1148, 1073, 1009, 987, 920, 860, 824, 717, 671,
605, 558, 533, 486 cmÀ1;1H NMR (400 MHz, CDCl3): d=2.22
(s, 3H), 2.29 (s, 3H), 2.98 (s, 3H), 3.12 (s, 3H), 5.72 (s, 1H);
13C NMR (100 MHz): d=20.52, 26.73, 36.16, 37.33, 77.21,
164.26, 169.51, 200.66; HR-MS (ESI): m/z=210.0745, calcd.
for C8H13NO4Na [M+Na]+: 210.0737.
921, 838, 788, 771 cmÀ1 1H NMR (400 MHz, CDCl3): d=
;
1.16 (t, J=7.2 Hz, 3H), 2.16 (s, 3H), 4.18 (q, J=7.2 Hz,
2H), 6.19 (s, 1H), 7.41 (d, J=8.4 Hz, 2H), 7.88 (d, J=
8.4 Hz, 2H); 13C NMR (100 MHz): d=13.89, 20.47, 62.64,
74.55 129.15, 130.59, 132.47, 140.84, 164.88, 169.44, 188.55;
HR-MS (ESI): m/z=285.0524, calcd. for C13H14O5 [M+H]+:
285.0524.
Ethyl 2-acetoxy-3-oxo-3-p-tolylpropanoate (3d): Colorless
oil. IR (KBr): n=3447, 2984, 2940, 1751, 1694, 1607, 1446,
1410, 1374, 1229, 1210, 1185, 1094, 1025, 942, 922, 887, 850,
825, 728, 657, 606, 565 cmÀ1 1H NMR (400 MHz, CDCl3):
;
d=1.15 (t, J=7.2 Hz, 3H), 2.15 (s, 3H), 2.36 (s, 3H), 4.17
(q, J=7.2 Hz, 2H), 6.24 (s, 1H), 7.22 (d, J=8.0 Hz, 2H),
7.83 (d, J=8.0 Hz, 2H); 13C NMR (100 MHz): d=13.89,
20.52, 21.77, 62.42, 74.41, 129.34, 129.47, 131.65, 145.37,
165.28, 169.55, 189.14; HR-MS (ESI): m/z=287.0898, calcd.
for C14H16O5Na [M+Na]+: 287.0890.
Ethyl
2-acetoxy-3-(naphthalen-2-yl)-3-oxopropanoate
Typical Procedure for a-Phosphoryloxylation of b-
Dicarbonyl Compounds
(3e): Colorless oil. IR (KBr): n=3060, 2984, 2939, 1751,
1692, 1627, 1597, 1468, 1373, 1220, 1126, 1094, 1023, 961,
933, 866, 821, 753 cmÀ1 1H NMR (400 MHz, CDCl3): d=
;
To a solution of ethyl benzoylacetate (1a) (192, 1 mmol) in
5 mL of dichloromethane in a 10-mL round-bottom flask
were added diphenyl phosphate (750 mg, 3.0 mmol) and p-
iodotoluene difluoride (384 mg, 1.5 mmol). The reaction
mixture was stirred at room temperature and monitored by
TLC. After 15 min, the resulting mixture was diluted with
dichloromethane (50 mL). Then, the mixture was washed
with saturated aqueous NaHCO3 (5 mL) and saturated
aqueous Na2S2O3 (5 mL). The separated aqueous phase was
extracted with dichloromethane (20 mL). The combined or-
ganic layer was washed with brine, dried over anhydrous
Na2SO4 and concentrated under vacuum to afford the crude
product which was purified by flash column chromatograpy
(PE-EtOAc, 4:1) to give 4a as a light red oil; yield: 378 mg
(86%). IR (KBr): n=3373, 3071, 3046, 2986, 2938, 1699,
1596, 1499, 1473, 1451, 1375, 1317, 1217, 1167, 1112, 1071,
1.11 (t, J=7.2 Hz, 3H), 2.15 (s, 3H), 4.16 (q, J=7.2 Hz,
2H), 6.41 (s, 1H), 7.48 (t, J=7.2 Hz, 1H), 7.54 (t, J=7.2 Hz,
1H), 7.78 (d, J=8.0 Hz, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.90
(d, J=8.0 Hz, 1H), 7.94 (d, J=8.8 Hz, 1H), 8.48 (s, 1H);
13C NMR (100 MHz): d=13.82, 20.45, 62.43, 74.42, 124.07,
126.99, 127.73, 128.64, 129.14, 129.79, 131.43, 131.50, 132.21,
135.90, 165.16, 169.54, 189.47; HR-MS (ESI): m/z=
323.0886, calcd. for C17H16O5Na [M+Na]+: 323.0890.
Ethyl 2-acetoxy-3-(furan-2-yl)-3-oxopropanoate (3f): Col-
orless oil. IR (KBr): n=3467, 3137, 2986, 2942, 2910, 1755,
1684, 1568, 1465, 1395, 1374, 1215, 1164, 1084, 1023, 954,
906, 884, 863, 774, 593, 509 cmÀ1
;
1H NMR (400 MHz,
CDCl3): d=1.24 (t, J=7.2 Hz, 3H), 2.25 (s, 3H), 4.26 (q, J=
7.2 Hz, 2H), 6.17 (s, 1H), 6.62 (dd, J=1.6 Hz, 3.6 Hz, 1H),
7.42 (d, J=3.6 Hz, 1H), 7.69 (s, 1H); 13C NMR (100 MHz):
d=13.90, 20.45, 62.54, 74.06, 112.83, 120.50, 147.93, 150.20,
164.75, 169.43, 177.72; HR-MS (ESI): m/z=263.0532, calcd.
for C11H12O6Na [M+Na]+: 263.0526.
1
1025, 1000, 982, 830, 755, 690, 509 cmÀ1; H NMR (400 MHz,
CDCl3): d=1.16 (t, J=7.2 Hz, 3H), 4.22 (q, J=7.2 Hz, 2H),
6.11 (d, J=9.2 Hz, 1H), 7.11–7.14 (m, 3H), 7.19–7.26 (m,
3H), 7.29–7.37 (m, 4H), 7.42 (t, J=7.6 Hz, 2H), 7.58 (t, J=
7.6 Hz, 1H), 7.95 (d, J=7.6 Hz, 2H); 13C NMR (100 MHz):
d=13.79, 62.75, 77.85 (d, J=5.5 Hz), 120.09 (d, J=4.8 Hz),
120.20 (d, J=4.8 Hz), 125.61, 128.69, 129.38, 129.71 (d, J=
3.7 Hz), 133.48, 134.23, 149.94 (d, J=7.5 Hz), 150.28 (d, J=
7.5 Hz), 164.86 (d, J=5.7 Hz), 188.82 (d, J=6.9 Hz);
31P NMR (121 MHz, CDCl3): d=À12.80; HR-MS (ESI):
m/z=441.1097, calcd. for C23H22NO7P [M+H]+: 441.1098.
1,3-Dioxo-1,3-diphenylpropan-2-yl diphenyl phosphate
(4j):[10] White solid, mp 102–1048C. 1H NMR (400 MHz,
CDCl3): d=6.86 (d, J=8.8 Hz, 1H), 7.15–7.19 (m, 6H),
7.25–7.28 (m, 4H), 7.38 (t, J=7.2 Hz, 4H), 7.53 (t, J=
7.2 Hz, 2H), 8.00 (d, J=7.2 Hz, 4H); 13C NMR (100 MHz):
d=84.01 (d, J=6.7 Hz), 115.28, 120.15 (d, J=4.8 Hz),
125.65, 128.70, 129.65, 129.75, 133.61, 134.29, 150.08 (d, J=
7.4 Hz), 190.26 (d, J=5.3 Hz); 31P NMR (121 MHz, CDCl3):
d=À13.10.
Ethyl 2-acetoxy-4-methyl-3-oxopentanoate (3g):[30] Color-
1
less oil. H NMR (400 MHz, CDCl3): d=1.12 (d, J=6.8 Hz,
3H), 1.17 (d, J=6.8 Hz, 3H), 1.30 (t, J=7.2 Hz, 3H), 2.22
(s, 3H), 3.00–3.07 (m, 1H), 4.28 (q, J=7.2 Hz, 2H), 5.65 (s,
1H); 13C NMR (100 MHz): d=13.98, 17.67, 18.37, 20.44,
38.11, 62.42, 76.12, 164.82, 169.47, 203.74.
Ethyl 2-acetoxy-4,4-dimethyl-3-oxopentanoate (3h): Col-
orless oil. IR (KBr): n=3649, 3430, 2977, 2940, 2911, 2876,
1757, 1722, 1480, 1372, 1341, 1205, 1088, 1048, 1021, 944,
854, 727, 656, 600, 568 cmÀ1 1H NMR (400 MHz, CDCl3):
;
d=1.21 (s, 9H), 1.26 (t, J=7.2 Hz, 3H), 2.17 (s, 3H), 4.22
(q, J=7.2 Hz, 2H), 5.89 (s, 1H); 13C NMR (100 MHz): d=
13.88, 20.34, 26.10, 44.60, 62.20, 72.09, 165.32, 169.40, 204.99;
HR-MS (ESI): m/z=253.1054, calcd. for C11H18O5Na [M+
Na]+: 253.1046.
Ethyl 2-acetoxy-3-oxobutanoate (3i):[1e] Colorless oil.
1H NMR (400 MHz, CDCl3): d=1.28 (t, J=7.2 Hz, 3H),
2.20 (s, 3H), 2.31 (s, 3H), 4.25 (q, J=7.2 Hz, 2H), 5.46 (s,
1H); 13C NMR (100 MHz): d=13.90, 20.30, 27.10, 62.41,
76.68, 164.39, 169.38, 197.46.
1-(Dimethylamino)-1,3-dioxobutan-2-yl diphenyl phos-
phate (4m): Light red oil. IR (KBr): n=3354, 2947, 1728,
1645, 1606, 1595, 1500, 1473, 1408, 1361, 1229, 1167, 1089,
Adv. Synth. Catal. 2010, 352, 531 – 546
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
543

Jun Yu et al.
FULL PAPERS
1024, 960, 888, 830, 813, 757, 693, 658, 618, 529, 510 cmÀ1
;
129.32, 129.47, 131.58, 145.01, 167.56, 192.06; HR-MS (ESI):
1H NMR (400 MHz, CDCl3): d=2.15 (s, 3H), 2.85 (s, 3H),
2.93 (s, 3H), 5.57 (d, J=8.4 Hz, 1H), 7.13–7.21 (m, 6H),
7.27–7.31 (m, 4H); 13C NMR (100 MHz): d=26.20, 36.25,
37.30, 79.89 (d, J=5.9 Hz), 120.10 (d, J=4.9 Hz), 120.29 (d,
J=4.7 Hz), 125.76, 129.81, 129.90, 150.21 (d, J=6.9 Hz),
163.61 (d, J=4.8 Hz), 200.74 (d, J=7.0 Hz); 31P NMR
(121 MHz, CDCl3): d=À12.80; HR-MS (MALDI): m/z=
400.0924, calcd. for C18H20NO6PNa [M+Na]+: 400.0921.
m/z=259.0947, calcd. for C13H16O4Na [M+Na]+: 259.0941.
Ethyl
2-methoxy-3-(naphthalen-2-yl)-3-oxopropanoate
(5e): Colorless oil. IR (KBr): n=3629, 3546, 3464, 2984,
2941, 2909, 2878, 1751, 1465, 1447, 1374, 1300, 1241, 1098,
1
1241, 1098, 1048, 938, 918, 847, 786, 635, 608 cmÀ1; H NMR
(400 MHz, CDCl3): d=1.19 (t, J=7.2 Hz, 3H), 3.58 (s, 3H),
4.21–4.29 (m, 2H), 5.05 (s, 1H), 7.55–7.65 (m, 2H), 7.89 (t,
J=9.2 Hz, 2H), 8.00 (d, J=8.0 Hz, 1H), 8.08 (d, J=8.0 Hz,
1H), 8.69 (s, 1H); 13C NMR (100 MHz): d=13.98, 58.65,
61.99, 85.36, 124.37, 126.85, 127.75, 128.51, 129.01, 130.00,
131.37, 131.81, 132.37, 135.94, 167.56, 192.47; HR-MS (ESI):
m/z=295.0945, calcd. for C16H16O4Na [M+Na]+: 295.0941.
Ethyl 3-(furan-2-yl)-2-methoxy-3-oxopropanoate (5f):
Colorless oil. IR (KBr): n=3628, 3550, 3464, 2985, 2942,
2909, 2086, 1889, 1739, 1568, 1479, 1466, 1447, 1374, 1241,
Typical Procedure for a-Methoxylation of b-
Dicarbonyl Compounds
To a solution of ethyl benzoylacetate (1a) (192 mg, 1 mmol)
in 5 mL of methanol in a 10-mL round-bottom flask was
added p-iodotoluene difluoride (384 mg, 1.5 mmol). The re-
action mixture was stirred at room temperature and moni-
tored by TLC. After 4 h, the resulting mixture was diluted
with dichloromethane (50 mL). Then, the mixture was
washed with saturated aqueous NaHCO3 (5 mL) and satu-
rated aqueous Na2S2O3 (5 mL). The separated aqueous
phase was extracted with dichloromethane (20 mL). The
combined organic layer was washed with brine, dried over
anhydrous Na2SO4 and concentrated under vacuum to
afford the crude product which was purified by flash column
chromatograpy (PE-EtOAc, 9:1) to give 5a as a colorless
oil; yield: 184 mg (83%). IR (KBr): n=3629, 3546, 3464,
2985, 2941, 2909, 2878, 2085, 1890, 1741, 1466, 1448, 1374,
1
1098, 1047, 938, 918, 847, 786, 810, 635, 608 cmÀ1; H NMR
(400 MHz, CDCl3): d=1.24 (t, J=7.2 Hz, 3H), 3.55 (s, 3H),
4.25 (q, J=7.2 Hz, 2H), 4.82 (s, 1H), 6.59–6.60 (m, 1H),
7.50 (d, J=3.6 Hz, 1H), 7.70 (s, 1H); 13C NMR (100 MHz):
d=13.77, 58.53, 61.75, 84.03, 112.39, 120.71, 147.59, 149.86,
166.68, 180.61; HR-MS (ESI): m/z=235.0577, calcd. for
C10H12O5Na [M+Na]+: 235.0577.
Methyl 2-methoxy-1-oxo-2,3-dihydro-1H-indene-2-carbox-
ylate (5n): Colorless oil. IR (KBr): n=3629, 3566, 3464,
2985, 2942, 2909, 2878, 1740, 1466, 1447, 1373, 1301, 1240,
1098, 1240, 1098, 1047, 938, 917, 847, 787, 635, 608 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=3.32 (d, J=17.2 Hz, 1H),
3.53 (s, 3H), 3.67 (d, J=17.2 Hz, 1H), 3.77 (s, 3H), 7.43 (t,
J=7.6 Hz, 1H), 7.49, (d, J=7.6 Hz, 1H), 7.67 (t, J=7.6 Hz,
1H), 7.81 (d, J=7.6 Hz, 1H); 13C NMR (100 MHz): d=
37.67, 52.48, 53.97, 85.35, 124.79, 126.28, 127.91, 133.89,
135.83, 151.40, 169.70, 198.19; HR-MS (ESI): m/z=
243.0632, calcd. for C12H12O4Na [M+Na]+: 243.0628.
1301, 1240, 1098, 1047, 938, 918, 847, 786, 635, 608 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=1.20 (t, J=7.2 Hz, 3H),
3.54 (s, 3H), 4.25 (q, J=7.2 Hz, 2H), 4.94 (s, 1H), 7.48 (t,
J=7.2 Hz, 2H), 7.61 (t, J=7.2 Hz, 1H), 8.07 (d, J=7.2 Hz,
2H); 13C NMR (100 MHz): d=13.90, 58.59, 61.91, 85.02,
128.58, 129.31, 130.09, 133.92, 167.44, 192.46; HR-MS (ESI):
m/z=245.0786, calcd. for C12H14O4 Na [M+Na]+: 245.0784.
Ethyl 2-methoxy-3-(4-methoxyphenyl)-3-oxopropanoate
(5b): Colorless oil. IR (KBr): n=3630, 3552, 3464, 2984,
2941, 2908, 2878, 1741, 1601, 1448, 1374, 1301, 1241, 1173,
Ethyl 2-methoxy-3-oxo-3-(pyridin-2-yl)propanoate (5o):
Colorless oil. IR (KBr): n=3629, 3546, 3464, 2985, 2941,
2909, 2256, 2087, 1739, 1479, 1466, 1447, 1300, 1243, 1098,
1
1047, 938, 918, 847, 787, 736, 704, 644, 608 cmÀ1; H NMR
1
1098, 1048, 938, 847, 787, 634, 608 cmÀ1; H NMR (400 MHz,
(400 MHz, CDCl3): d=1.17 (t, J=7.2 Hz, 3H), 3.61 (s, 3H),
4.21 (q, J=7.2 Hz, 2H), 5.57 (s, 1H), 7.49–7.52 (m, 1H),
7.86–7.90 (m, 1H), 8.08 (d, J=7.2 Hz, 1H), 8.68 (d, J=
4.4 Hz, 1H); 13C NMR (100 MHz): d=13.84, 59.21, 61.50,
81.91, 122.63, 127.61, 137.05, 148.88, 151.56, 167.32, 193.11;
HR-MS (ESI): m/z=224.0921, calcd. for C11H14NO4 [M+
H]+: 224.0917.
CDCl3): d=1.21 (t, J=7.2 Hz, 3H), 3.52 (s, 3H), 3.88 (s,
3H), 4.24 (q, J=7.2 Hz, 2H), 4.88 (s, 1H), 6.94 (d, J=
9.2 Hz, 2H), 8.08 (d, J=9.2 Hz, 2H); 13C NMR (100 MHz):
d=13.98, 55.48, 58.46, 61.85, 85.27, 113.85, 127.04, 131.86,
164.18, 167.70, 190.90; HR-MS (ESI): m/z=253.1075, calcd.
for C13H17O5 [M+H]+: 253.1070.
Ethyl 2-dimethoxy-3-oxo-3-(pyridin-2-yl)propanoate: Col-
orless oil. IR (KBr): n=3056, 2964, 2941, 2838, 1765, 1720,
1583, 1466, 1439, 1391, 1369, 1305, 1286, 1260, 1242, 1203,
1141, 1097, 1064, 1032, 997, 888, 906, 857, 838, 757, 742, 779,
Ethyl
3-(4-chlorophenyl)-2-methoxy-3-oxopropanoate
(5c): Colorless oil. IR (KBr): n=3629, 3546, 3464, 2985,
2942, 2909, 1739, 1479, 1465, 1448, 1374, 1241, 1097, 1047,
938, 918, 848, 787, 635, 608 cmÀ1
;
1H NMR (400 MHz,
1
687, 633, 619 cmÀ1; H NMR (400 MHz, CDCl3): d=1.29 (t,
CDCl3): d=1.21 (t, J=7.2 Hz, 3H), 3.53 (s, 3H), 4.25 (q, J=
7.2 Hz, 2H), 4.86 (s, 1H), 7.45 (d, J=8.8 Hz, 2H), 8.03 (d,
J=8.8 Hz, 2H); 13C NMR (100 MHz): d=13.96, 58.68,
62.06, 85.38, 128.97, 130.85, 132.27, 140.53, 167.26, 191.39;
HR-MS (ESI): m/z=257.0577, calcd. for C12H14O4 [M+H]+:
257.0575.
J=7.2 Hz, 3H), 3.32 (s, 6H), 4.23 (q, J=7.2 Hz, 2H), 7.43–
7.47 (m, 1H), 7.82–7.86 (dt, J=1.6 Hz, 8.0 Hz, 1H), 8.08 (d,
J=8.0 Hz, 1H), 8.61–8.62 (m, 1H); 13C NMR (100 MHz):
d=13.76, 50.86, 61.69, 98.10, 123.28, 127.46, 136.99, 148.49,
150.51, 165.44, 190.52; HR-MS (ESI): m/z=254.1021, calcd.
for C12H16NO5 [M+H]+: 254.1023.
Ethyl 2-methoxy-3-oxo-3-p-tolylpropanoate (5d): Color-
less oil. IR (KBr): n=3465, 2985, 2941, 2909, 1742, 1466,
Ethyl 2-methoxy-4-methyl-3-oxopentanoate (5g): Color-
less oil. IR (KBr): n=2962, 2928, 2875, 2835, 1749, 1724,
1464, 1457, 1373, 1338, 1260, 1197, 1133, 1025, 995, 858, 803,
1448, 1374, 1242, 1098, 1047, 938, 847, 787, 635, 608 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=1.21 (t, J=7.2 Hz, 3H),
2.41 (s, 3H), 3.52 (s, 2H), 4.24 (q, J=7.2 Hz, 2H), 4.91 (s,
1H), 7.27 (d, J=8.4 Hz, 2H), 7.97 (d, J=8.4 Hz, 2H);
13C NMR (100 MHz): d=13.96, 21.72, 58.53, 61.87, 85.11,
693 cmÀ1 1H NMR (400 MHz, CDCl3): d=1.08–1.11 (m,
;
6H), 1.29 (t, J=7.2 Hz, 3H), 3.05–3.11 (m, 1H), 3.47 (s,
3H), 4.23–4.29 (m, 2H), 4.39 (s, 1H); 13C NMR (100 MHz):
544
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 531 – 546

Various a-Oxygen Functionalizations of b-Dicarbonyl Compounds
d=14.09, 17.90, 18.14, 36.98, 58.65, 61.87, 85.58, 167.24,
207.44; HR-MS (ESI): m/z=211.0944, calcd. for C9H16O4Na
[M+Na]+: 211.0941.
168.32, 193.29; HR-MS (ESI): m/z=273.1102, calcd. for
C14H18O4Na [M+Na]+: 273.1097.
Ethyl 2-methoxy-4,4-dimethyl-3-oxopentanoate (5h): Col-
orless oil. IR (KBr): n=3420, 2971, 2934, 2875, 1759, 1716,
1179, 1465, 1395, 1369, 1247, 1197, 1124, 1096, 1065, 1034,
Supporting Information
NMR, IR and mass spectra are provided in the Supporting
Information.
941, 856, 822, 719, 579 cmÀ1 1H NMR (400 MHz, CDCl3):
;
d=1.21 (s, 9H), 1.28 (t, J=7.2 Hz, 3H), 3.47 (s, 3H), 4.24
(q, J=7.2 Hz, 2H), 4.64 (s, 1H); 13C NMR (100 MHz): d=
13.78, 25.90, 44.19, 58.53, 61.27, 81.74, 167.50, 206.78; HR-
MS (ESI): m/z=225.1105, calcd. for C10H18O4Na [M+Na]+:
225.1097.
Acknowledgements
Ethyl 1-methoxy-2-oxocyclopentanecarboxylate (5p): Col-
orless oil. IR (KBr): n=3635, 3552, 3465, 2986, 2942, 2909,
2878, 1743, 1465, 1448, 1374, 1301, 1240, 1098, 1047, 938,
This work was financially supported by The National Natural
Science Foundation of China (No. 20572046 and No.
20872064), Program for New Century Excellent Talents in
University (NCET-07-0461), and the Tianjin Natural Science
Foundation (09JCYBJC05900).
847, 787, 635, 608 cmÀ1 1H NMR (400 MHz, CDCl3): d=
;
1.29 (t, J=7.2 Hz, 3H), 1.99–2.13 (m, 2H), 2.17–2.34 (m,
1H), 2.34–2.44 (m, 3H), 3.46 (s, 3H), 4.23–4.28 (m, 2H);
13C NMR (100 MHz): d=14.11, 18.43, 34.63, 36.54, 54.24,
61.55, 84.57, 169.80, 210.46; HR-MS (ESI): m/z=209.0787,
calcd. for C9H14O4Na [M+Na]+: 209.0784.
References
2-Methoxy-1,3-diphenylpropane-1,3-dione (5j):[32] Color-
1
less oil. H NMR (400 MHz, CDCl3, keto-enol): d=3.24 (s,
[1] a) R. M. Moriarty, B. K. Vaid, M. P. Duncan, S. G.
Levy, O. Prakash, S. Goyal, Synthesis 1992, 845–846;
b) R. S. Varma, D. Kumar, P. J. Liesen, J. Chem. Soc.
Perkin Trans. 1 1998, 4093–4096; c) L. Valgimigli, G.
Brigati, G. F. Pedulli, G. A. Dilabio, M. Mastragostino,
C. Arbizzani, D. A. Pratt, Chem. Eur. J. 2003, 9, 4997–
5010; d) M. Altuna-Urquijo, S. P. Stanforth, B. Tarbit,
Tetrahedron Lett. 2005, 46, 6111–6113; e) M. Altuna-
Urquijo, A. Gehre, S. P. Stanforth, B. Tarbit, Tetrahe-
dron 2009, 65, 975–984; f) A. Gehre, S. P. Stanforth, B.
Tarbit, Tetrahedron 2009, 65, 1115–1118.
[2] a) A. Takeda, E. Amano, S. Tsuboi, Bull. Chem. Soc.
Jpn. 1977, 50, 2191–2192; b) S. J. Hecker, K. M.
Werner, J. Org. Chem. 1993, 58, 1762–1765; c) D.
Chen, T. J. Sprules, J.-F. Lavallꢂe, Bioorg. Med. Chem.
Lett. 1995, 5, 759–762; d) J. L. Wood, B. M. Stoltz, H.-
J. Dietrich, D. A. Pflum, D. T. Petsch, J. Am. Chem.
Soc. 1997, 119, 9641–9651.
3H), 3.55 (s, 1.6H), 5.65 (s, 0.54H), 7.42–7.56 (m, 10H),
8.09–8.14 (m, 5H), 15.80 (s, 1H); 13C NMR (100 MHz): d=
58.55, 61.44, 91.24, 128.29, 128.60, 129.11, 129.62, 130.08,
131.69, 133.98, 134.45, 134.84, 137.35, 181.90, 194.19.
2-Methoxy-1-phenyl-1,3-butanedione (5k):[33] Colorless
1
oil. H NMR (400 MHz, CDCl3, keto-enol): d=2.25 (s, 1H),
2.32 (s, 3H), 3.42 (s, 3H), 3.47 (s, 1H), 4.97 (s, 0.3H), 7.43–
7.48 (m, 4H), 8.03–8.06 (m, 3H), 14.98 (s, 1H); 13C NMR
(100 MHz): d=22.36, 26.12, 58.38, 61.29, 92.41, 128.35,
128.67, 128.75, 129.47, 130.07, 131.37, 133.68, 134.10, 136.94,
173.25, 194.76.
2-Methoxy-N,N-dimethyl-3-oxobutanamide (5m): Color-
less oil. IR (KBr): n=3445, 2940, 2834, 2602, 2081, 1732,
1652, 1506, 1456, 1417, 1358, 1281, 1250, 1198, 1114, 1062,
1015, 978, 848, 383, 618, 562 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d=2.24 (s, 3H), 2.96 (s, 3H), 3.03 (s, 3H), 3.42 (s,
3H), 4.52 (s, 1H); 13C NMR (100 MHz): d=26.14, 36.10,
36.83, 58.03, 87.71, 166.09, 203.85; HR-MS (ESI): m/z=
182.0794, calcd. for C7H13NO3Na [M+Na]+: 182.0788.
Ethyl 2-ethoxy-3-oxo-3-phenylpropanoate (5q):[11] Color-
[3] O. R. S. John, N. M. Killeen, D. A. Knowles, S. C. Yau,
M. C. Bagley, N. C. O. Tomkinson, Org. Lett. 2007, 9,
4009–4012.
[4] a) G. F. Koser, A. G. Relenyi, A. N. Kalos, L. Rebrovic,
R. H. Wettach, J. Org. Chem. 1982, 47, 2487–2489;
b) A. Tuncay, J. A. Dustman, G. Fisher, C. I. Tuncay,
Tetrahedron Lett. 1992, 33, 7647–7650; c) J. C. Lee,
Y. S. Oh, S. H. Cho, Bull. Korean Chem. Soc. 1996, 17,
989–991; d) J. C. Lee, J. H. Choi, Synlett 2001, 234–
235; e) S. Abe, K. Sakuratani, H. Togo, Synlett 2001,
22–24; f) T. Nabana, H. Togo, J. Org. Chem. 2002, 67,
4362–4365; g) A. Moroda, H. Togo, Tetrahedron 2006,
62, 12408–12414; h) Y. Yamamoto, Y. Kawano, P. H.
Toy, H. Togo, Tetrahedron 2007, 63, 4680–4687.
[5] M. S. Yusubov, T. Wirth, Org. Lett. 2005, 7, 519–521.
[6] N. N. Karade, G. B. Tiwari, S. V. Shinde, S. V. Gampa-
war, J. M. Kondre, Tetrahedron Lett. 2008, 49, 3441–
3443.
1
less oil. H NMR (400 MHz, CDCl3): d=1.19 (t, J=7.2 Hz,
3H), 1.27 (t, J=7.2 Hz, 3H), 3.60–3.68 (m, 1H), 3.70–3.78
(m, 1H), 4.23 (q, J=7.2 Hz, 2H), 5.01 (s, 1H), 7.44–7.50 (m,
2H), 7.57–7.61 (m, 1H), 8.07–8.10 (m, 2H); 13C NMR
(100 MHz): d=13.96, 15.06, 61.85, 66.89, 83.72, 128.56,
129.42, 130.18, 133.85, 167.84, 192.87.
Ethyl 2-isopropoxy-3-oxo-3-phenylpropanoate (5r): Color-
less oil. IR (KBr): n=3446, 3067, 2977, 2932, 1756, 1688,
1598, 1580, 1465, 1450, 1465, 1385, 1282, 1229, 1202, 1181,
1115, 1024, 942, 891, 841, 770, 692, 593 cmÀ1 1H NMR
;
(400 MHz, CDCl3, keto-enol): d=1.05 (d, J=6.4 Hz,
0.98H), 1.16–1.20 (m, 6H), 1.28 (d, J=6.4 Hz, 3H), 1.40 (t,
J=7.2 Hz, 0.46H), 3.78–3.84 (m, 1H), 4.22 (q, J=7.2 Hz,
2H), 4.35 (q, J=7.2 Hz, 0.29H), 5.05 (s, 1H), 7.39–7.40 (m,
0.51H), 7.46 (t, J=7.2 Hz, 2H), 7.58 (t, J=7.2 Hz, 1H),
7.96–7.97 (m, 0.32H), 8.09 (d, J=7.2 Hz, 2H), 11.76 (s,
0.14H); 13C NMR (100 MHz): d=13.90, 21.89, 61.72, 73.22,
81.94, 127.76, 128.44, 128.86, 129.49, 130.03, 133.66, 134.17,
[7] J. S. Lodaya, G. F. Koser, J. Org. Chem. 1988, 53, 210–
212.
[8] N. Sugiyama, M. Yamamoto, T. Takano, C. Kashima,
Bull. Chem. Soc. Jpn. 1967, 40, 2909–2913.
Adv. Synth. Catal. 2010, 352, 531 – 546
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
545

Jun Yu et al.
FULL PAPERS
[9] a) F. Mizukami, M. Ando, T. Tanaka, J. Imamura, Bull.
1992, 57, 2433–2437; b) T. M. Kasumov, N. S. Pirgu-
liyev, V. K. Brel, Y. K. Grishin, N. S. Zefirov, P. J. Stang,
Tetrahedron 1997, 53, 13139–13148; c) S. Hara, M.
Yoshida, T. Fukuhara, N. Yoneda, Chem. Commun.
1998, 965–966; d) S. Hara, K. Yamamoto, M. Yoshida,
T. Fukuhara, N. Yoneda, Tetrahedron Lett. 1999, 40,
7815–7818; e) M. Yoshida, S. Hara, T. Fukuhara, N.
Yoneda, Tetrahedron Lett. 2000, 41, 3887–3890; f) M.
Yoshida, D. Ota, T. Fukuhara, N. Yoneda, S. Hara, J.
Chem. Soc. Perkin Trans. 1 2002, 384–389; g) M. Yoshi-
da, K. Kawakami, S. Hara, Synthesis 2004, 2821–2824;
h) M. Yoshida, K. Osafune, S. Hara, Synthesis 2007,
1542–1546; i) M. Ochiai, M. Hirobe, A. Yoshimura, Y.
Nishi, K. Miyamoto, M. Shiro, Org. Lett. 2007, 9, 3335–
3338; j) H.-J. Frohn, A. Wenda, U. Flçrke, Z. Anorg.
Allg. Chem. 2008, 634, 764–770; k) H.-J. Frohn, V. V.
Bardin, Z. Anorg. Allg. Chem. 2008, 634, 82–86.
[22] G. F. Koser, K. Chen, Y. Huang, C. A. Summers, J.
Chem. Soc. Perkin Trans. 1 1994, 1375–1376.
[23] N. S. Zefirov, N. S. Samsoniya, T. G. Kutateladze, V. V.
Zhdankin, Zh. Org. Khim. 1991, 27, 220.
ˇ
Chem. Soc. Jpn. 1978, 51, 335–336; b) B. Podolesov, J.
Org. Chem. 1984, 49, 2644–2646; c) M. Ochiai, Y.
Takeuchi, T. Katayama, T. Sueda, K. Miyamoto, J. Am.
Chem. Soc. 2005, 127, 12244–12245; d) J. Sheng, X. Li,
M. Tang, B. Gao, G. Huang, Synthesis 2007, 1165–1168.
[10] G. F. Koser, J. S. Lodaya, D. G. Ray, III, P. B. Kokil, J.
Am. Chem. Soc. 1988, 110, 2987–2988.
[11] R. M. Moriarty, R. K. Vaid, V. T. Ravikumar, B. K.
Vaid, T. E. Hopkins, Tetrahedron 1988, 44, 1603–1607.
[12] a) S. Hara, M. Sekiguchi, A. Ohmori, T. Fukuhara, N.
Yoneda, Chem. Commun. 1996, 1899–1900; b) S. Hara,
T. Hatakeyama, S.-Q. Chen, K. Ishi-i, M. Yoshida, M.
Sawaguchi, T. Fukuhara, N. Yoneda, J. Fluorine Chem.
1998, 87, 189–192; c) M. Yoshida, K. Fujikawa, S. Sato,
S. Hara, ARKIVOC 2003, 6, 36–42.
[13] a) J. J. Edmunds, W. B. Mothewell, J. Chem. Soc. Chem.
Commun. 1989, 1348–1349; b) S. Caddick, L. Gazzard,
W. B. Motherwell, J. A. Wilkinson, Tetrahedron 1996,
52, 149–156; c) M. F. Greaney, W. B. Motherwell, Tet-
rahedron Lett. 2000, 41, 4467–4470; d) M. F. Greaney,
W. B. Motherwell, D. A. Tocher, Tetrahedron Lett.
2001, 42, 8523–8526; e) W. B. Motherwell, M. F. Grea-
ney, J. J. Edmunds, J. W. Steed, J. Chem. Soc. Perkin
Trans. 1 2002, 2816–2826.
[14] a) M. F. Greaney, W. B. Motherwell, Tetrahedron Lett.
2000, 41, 4463–4466; b) W. B. Motherwell, M. F. Grea-
ney, D. A. Tocher, J. Chem. Soc. Perkin Trans. 1 2002,
2809–2815.
[15] M. A. Arrica, T. Wirth, Eur. J. Org. Chem. 2005, 395–
403.
[16] S. Sato, M. Yoshida, S. Hara, Synthesis 2005, 2602–
2605.
[17] a) W. Carpenter, J. Org. Chem. 1966, 31, 2688–2689;
b) T. B. Patrick, J. J. Scheibel, W. E. Hall, Y. H. Lee, J.
Org. Chem. 1980, 45, 4492–4494; c) S. Hara, J. Nakahi-
gashi, K. Ishi-i, T. Fukuhara, N. Yoneda, Tetrahedron
Lett. 1998, 39, 2589–2592.
[18] S. Hara, J. Nakahigashi, K. Ishi-i, M. Sawaguchi, H.
Sakai, T. Fukuhara, N. Yoneda, Synlett 1998, 495–496.
[19] B. Panunzi, A. Picardi, M. Tingoli, Synlett 2004, 2339–
2342.
[24] M. E. Furrow, A. G. Myers, J. Am. Chem. Soc. 2004,
126, 12222–12223.
[25] a) X.-F. Zhao, C. Zhang, Synthesis 2007, 551–557;
b) X.-Q. Li, X.-F. Zhao, C. Zhang, Synthesis 2008,
2589–2593; c) X.-Q. Li, C. Zhang. Synthesis 2009,
1163–1169; d) J. Yu, C. Zhang, Synthesis 2009, 2324–
2328; e) X.-Q. Li, W.-K. Wang, C. Zhang. Adv. Synth.
Catal. 2009, 351, 2342–2350.
[26] C. Ye, B. Twamley, J. M. Shreeve, Org. Lett. 2005, 7,
3961–3964.
[27] a) D. Naumann, J. Baumanns, J. Fluorine Chem. 1976,
8, 177–182; b) V. Padelidakis, W. Tyrra, D. Naumann,
J. Fluorine Chem. 1999, 99, 9–15.
[28] B. C. Schardt, C. L. Hill, Inorg. Chem. 1983, 22, 1563–
1565.
[29] U. S. Mahajan, K. G. Akamanchi, Synlett 2008, 987–
990.
[30] T. Komiyama, Y. Takaguchi, S. Tsuboi, Synthesis 2006,
1767–1770.
[31] Z. Ahmed, C. Fischer, A. Spannenberg, P. Langer, Tet-
rahedron Tetrahedron. 2006, 62, 4800–4806.
[20] P. Conte, B. Panunzi, M. Tingoli, Tetrahedron Lett.
[32] M. Regitz, A. Schꢃfer, Liebigs Ann. Chem. 1981, 1172–
1185.
[33] Y. Sawaki, H. Inoue, Y. Ogata, Bull. Chem. Soc. Jpn.
1983, 56, 1133–1138.
2006, 47, 273–276.
[21] a) N. S. Zefirov, A. S. Koz’min, T. Kasumov, K. A. Pote-
khin, V. D. Sorokin, V. K. Brel, E. V. Abramkin, Y. T.
Struchkov, V. V. Zhdankin, P. J. Stang, J. Org. Chem.
546
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 531 – 546