Tert -butyl peroxybenzoate-promoted α-methylation of 1,3-dicarbonyl compounds

Article abstract of DOI:10.1021/jo502204a

A tert-butyl peroxybenzoate (TBPB)-promoted direct α-methylation of 1,3-dicarbonyl compounds has been developed, providing α-methyl derivatives in moderate to good yields. In this procedure, TBPB plays a dual role, serving as both the methyl source and radical initiator. This work represents a key complement to the traditional α-methylation of 1,3-dicarbonyl compounds using methyl iodide.

Full text of DOI:10.1021/jo502204a

Note
pubs.acs.org/joc
tert-Butyl Peroxybenzoate-Promoted α‑Methylation of 1,3-
Dicarbonyl Compounds
Songjin Guo, Qian Wang, Yan Jiang, and Jin-Tao Yu*
School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Jiangsu Province Key
Laboratory of Fine Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China
S
* Supporting Information
ABSTRACT: A tert-butyl peroxybenzoate (TBPB)-promoted
direct α-methylation of 1,3-dicarbonyl compounds has been
developed, providing α-methyl derivatives in moderate to good
yields. In this procedure, TBPB plays a dual role, serving as
both the methyl source and radical initiator. This work
represents a key complement to the traditional α-methylation
of 1,3-dicarbonyl compounds using methyl iodide.
he methylation of C−H bonds is one important
various peroxides have been widely applied in the methylation
Ttransformation in organic chemistry and the pharmaceut- of arenes, carboxylic acids, amides, and activated alkenes.22−27
ical industry because the introduction of a methyl group can
improve a molecule’s biological activity and physical properties,
which is known as the magical methyl effect.1−8 Thus, it is
common that medicinal chemists examine methylated variants
of a drug lead after replacing C−H with C−Me. In many
instances, however, methylation of an advanced drug
intermediate can be achieved only through de novo synthesis.
Compared with sp2 C−H methylation,9−11 the methylation of
sp3 C−H bonds has been less investigated because of their low
polarity.12−14 Recently, a lot of progress in the α-methylation of
carbonyl compounds has been made. For example, Donohoe
reported Rh-catalyzed α-methylation of ketones using methanol
as the methylating reagent under mild conditions.15 Xiao and
co-workers also developed the Ru-catalyzed methylation of
ketone compounds with DMF as the carbon source.16
However, in the case of 1,3-dicarbonyl compounds, α-
methylation is generally limited to a two-step procedure:
deprotonation of the activated methenyl by a strong base
followed by quenching of the intermediate anion with an
electrophile such as methyl iodide (Scheme 1, eq 1).17−21 Such
a methylation reagent is poisonous and generates halogen-
containing wastes. Nevertheless, this method is valid as long as
the substrate tolerates strongly basic reaction conditions. Very
recently, the in situ-formed methyl radicals derived from
Meanwhile, the radical coupling of 1,3-dicarbonyl compounds
in C−C bond formation has been well-documented.28−41 As a
result, the development of a one-step direct methylation of such
a compound by the in situ-formed methyl radical is reasonable
(Scheme 1, eq 2). Herein we report our study on such a
method. This procedure features (1) selective monomethyla-
tion under nearly neutral reaction conditions and (2) the use of
tert-butyl peroxybenzoate (TBPB) rather than methyl iodide as
the methyl source, thus avoiding the generation of halogen-
containing waste.
We selected the combination of ethyl 3-oxo-3-phenyl-
propanoate (1a), di-tert-butyl peroxide (DTBP) (2 equiv),
and Bu4NI (5 mol %) in chlorobenzene (3 mL) at 100 °C as
the model reaction. Fortunately, the monomethylated product
3a was selectively obtained, although in a low yield of 10%
(Table 1, entry 1). Under similar reaction conditions, a 22%
yield of 3a was isolated by catalysis using FeCl2 (entry 2), but
other catalysts, such as Fe2(SO4)3, I2, Cu(OTf)2, and CuF2,
failed to promote this transformation (entries 3−6). Further
optimization showed that when Cu(BF4)2 was utilized, the yield
of 3a increased dramatically to 43% (entry 7). To obtain better
results, other potential methyl sources, such as TBHP, DCP,
and TBPB were analyzed (entries 8−10). TBPB was found to
be the best, allowing 3a to be isolated in 78% yield (entry 10).
Other copper salts, including Cu(OTf)2 and Cu(acac)2, were
less effective under exactly the same conditions (entries 11 and
12). Solvent screening showed that common solvents such as
MeCN, DMF, and THF were not effective at all (entries 13−
15). In addition, reducing the amount of solvent or elevating
the reaction temperature decreased the total yield because of
the formation of an increased amount of acetophenone as a
byproduct, as detected by GC−MS (entries 16 and 17). A
Scheme 1. α-Methylation of 1,3-Dicarbonyl Compounds
Received: September 25, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo502204a | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Table 1. Selected Results for Screening the Optimized
Reaction Conditions
Scheme 2. Scope of Dicarbonyl Compounds
a
entry
catalyst
2
solvent
yield (%)
1
2
Bu4NI
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
TBHP
DCP
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
MeCN
DMF
THF
PhCl
PhCl
PhCl
10
22
<1
<1
<1
<5
43
<1
32
78
70
32
<1
<1
<5
65
60
<1
FeCl2
3
Fe2(SO4)3
I2
4
5
Cu(OTf)2
CuF2
6
7
Cu(BF4)2
Cu(BF4)2
Cu(BF4)2
Cu(BF4)2
Cu(OTf)2
Cu(acac)2
Cu(BF4)2
Cu(BF4)2
Cu(BF4)2
Cu(BF4)2
Cu(BF4)2
−
8
9
10
11
12
13
14
15
TBPB
TBPB
TBPB
TBPB
TBPB
TBPB
TBPB
TBPB
TBPB
b
16
c
17
18
a
Reaction conditions: 1a (0.5 mmol), catalyst (5 mol %), and 2 (1.0
mmol, 2 equiv) (TBHP = tert-butyl hydroperoxide, DTBP = di-tert-
butyl peroxide, TBPB = tert-butyl peroxybenzoate, DCP = dicumyl
peroxide) in PhCl (3 mL) at 100 °C under N2 for 2 h in a sealed tube.
b
c
TBHP (70% in water), Cu(BF4)2 (45% in water). PhCl (1 mL). At
120 °C.
control experiment revealed that no product was detected in
the absence of any catalyst (entry 18). Ultimately, the optimal
reaction conditions were found to be the following: 1,3-
dicarbonyl compound 1a reacting with TBPB in chlorobenzene
(3 mL) catalyzed by Cu(BF4)2 at 100 °C for 2 h.
Under the optimized reaction conditions, the substrate scope
of 1,3-dicarbonyl compounds was studied, as shown in Scheme
2. As expected, almost all of the substrates reacted smoothly
under the standard procedure. Methyl, ethyl, and benzyl esters
were all well-tolerated. Generally, the reaction was not sensitive
to the electronic property of the substituent on the phenyl ring,
as both electron-donating and electron-withdrawing groups
could provide the corresponding products in good yields (3a−
k). Notably, the tolerance of halogens offers an opportunity for
subsequent functionalizations to synthesize various α-methy-
lated 1,3-dicarbonyl derivatives (3e−i). A substrate with an
ortho substituent resulted in a lower yield, maybe because of
steric hindrance (3h). Particularly, an α-substituted 1,3-
dicarbonyl substrate also reacted smoothly to produce the
quaternary carbon center (3l). To our delight, heteroaryl keto
esters were also suitable substrates in this methylation process,
and 3m and 3n were isolated in 57% and 68% yield,
respectively. Generally, alkyl and alkenyl keto esters gave
lower yields than their aryl keto ester analogues (3o and 3p).
Unfortunately, acyclic 1,3-diketone compounds failed to
produce the desired product. On the contrary, a cyclic 1,3-
diketone gave the α-methylated product in moderate yield
(3q). A compound with two 1,3-dicarbonyl substituents also
worked well, and the dual-methylated product was obtained in
moderate yield (3r). To further evaluate the practicability of
a
Reaction conditions: 1 (0.5 mmol), Cu(BF4)2 (0.025 mmol, 5 mol
%), and TBPB (1.0 mmol, 2 equiv) in PhCl (3 mL) at 100 °C under
b
N2 for 2 h in a sealed tube. Isolated yields are shown. 1a (5 mmol),
Cu(BF4)2 (0.25 mmol, 5 mol %), and TBPB (10.0 mmol, 2 equiv) in
PhCl (30 mL) at 100 °C under N2 for 3 h in a sealed tube. 4 equiv of
TBPB was used.
c
this procedure, the reaction was conducted on a 5 mmol scale,
and the desired product 3a was obtained in a comparable 68%
yield.
To gain some insight into the reaction mechanism, we
investigated the reaction in the presence of the radical
scavenger 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO).
After the addition of 2.0 equiv of TEMPO into the standard
reaction procedure, the methylation process was completely
shut off and no 3a was detected. In addition, the TEMPO−
CH3 adduct A was detected by GC−MS (Scheme 3; also see
the Supporting Information), which could indicate that this
methylation involves free radical intermediates.
A tentative mechanism for this novel α-methylation process
by the reaction of 1,3-dicarbonyl compounds with TBPB is
proposed in Scheme 4. First, thermally promoted homolytic
cleavage of the radical initiator TBPB produces the tert-butoxy
radical tBuO·, which converts to the methyl radical by releasing
B
dx.doi.org/10.1021/jo502204a | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(CDCl3, 300 MHz): δ 7.98−7.95 (m, 2H), 7.60−7.54 (m, 1H), 7.49−
7.44 (m, 2H), 4.37 (q, J = 7.1 Hz, 1H), 4.13 (q, J = 7.1 Hz, 2H), 1.48
(d, J = 7.1 Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (CDCl3,
75 MHz): δ 195.8, 170.8, 135.8, 133.4, 128.6, 128.5, 61.3, 48.3, 13.9,
13.7.
Scheme 3. Radical Capture Experiment
Methyl 2-Methyl-3-oxo-3-phenylpropanoate (3b).43 Flash
column chromatography on silica gel (ethyl acetate/petroleum ether
1
1:100) gave 3b (69.3 mg, 72% yield) as a colorless oil. H NMR
(CDCl3, 400 MHz): δ 7.98−7.95 (m, 2H), 7.57 (t, J = 7.4 Hz, 1H),
7.47 (t, J = 7.4 Hz, 2H), 4.41 (q, J = 7.1 Hz, 1H), 3.67 (s, 3H), 1.49 (d,
J = 7.1 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 195.8, 171.3,
135.6, 133.5, 128.7, 128.5, 52.4, 48.0, 13.8.
Scheme 4. Proposed Mechanism
Methyl 3-(4-Methoxyphenyl)-2-methyl-3-oxopropanoate
(3c).44 Flash column chromatography on silica gel (ethyl acetate/
petroleum ether 1:10) gave 3c (83.0 mg, 75% yield) as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.95 (d, J = 8.9 Hz, 2H), 6.94 (d, J =
8.9 Hz, 2H), 4.36 (q, J = 7.1 Hz, 1H), 3.86 (s, 3H), 3.67 (s, 3H), 1.47
(d, J = 7.1 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.3,
171.5, 163.8, 130.9, 128.6, 113.9, 55.5, 52.4, 47.7, 13.9.
Methyl 2-Methyl-3-oxo-3-(p-tolyl)propanoate (3d).45 Flash
column chromatography on silica gel (ethyl acetate/petroleum ether
1:30) gave 3d (75.4 mg, 73% yield) as a colorless oil. 1H NMR
(CDCl3, 400 MHz): δ 7.88 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.0 Hz,
2H), 4.40 (q, J = 7.1 Hz, 1H), 3.68 (s, 3H), 2.41 (s, 3H), 1.49 (d, J =
7.1 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 195.4, 171.4,
144.4, 133.1, 129.4, 128.7, 52.3, 47.8, 21.6, 13.8.
Methyl 3-(4-Bromophenyl)-2-methyl-3-oxopropanoate
(3e).46 Flash column chromatography on silica gel (ethyl acetate/
petroleum ether 1:100) gave 3e (96.0 mg, 71% yield) as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.82 (d, J = 8.6 Hz, 2H), 7.60 (d, J =
8.6 Hz, 2H), 4.33 (q, J = 7.1 Hz, 1H), 3.66 (s, 3H), 1.47 (d, J = 7.1 Hz,
3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.7, 170.9, 134.4, 132.0,
130.0, 128.7, 52.5, 48.0, 13.6.
Methyl 3-(4-Chlorophenyl)-2-methyl-3-oxopropanoate
(3f).47 Flash column chromatography on silica gel (ethyl acetate/
petroleum ether 1:30) gave 3f (83.0 mg, 73% yield) as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.89 (d, J = 8.6 Hz, 2H), 7.42 (d, J =
8.6 Hz, 2H), 4.34 (q, J = 7.1 Hz, 1H), 3.65 (s, 3H), 1.46 (d, J = 7.1 Hz,
3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.5, 170.9, 139.9, 134.0,
129.9, 129.0, 52.5, 47.9, 13.6.
Methyl 3-(2,4-Dichlorophenyl)-2-methyl-3-oxopropanoate
(3g). Flash column chromatography on silica gel (ethyl acetate/
petroleum ether 1:100) gave 3g (72.0 mg, 55% yield) as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 12.55 (s, 0.74H), 7.46−7.44 (m,
2.50H), 7.33−7.29 (m, 1.73H), 7.27−7.25 (m, 1.07H), 4.33 (q, J = 7.1
Hz, 0.93H), 3.84 (s, 2.34H), 3.68 (s, 3.00H), 1.58 (s, 2.34H), 1.47 (d,
J = 7.1 Hz, 3.00H). 13C{1H} NMR (CDCl3, 100 MHz): δ 197.7, 173.6,
170.4, 166.2, 137.7, 136.6, 135.8, 133.4, 132.8, 132.0, 130.7, 130.4,
130.4, 129.7, 127.4, 127.2, 99.0, 52.5, 52.0, 51.6, 13.1, 12.1. MS (EI):
260 (M+). HRMS (ESI-TOF): calcd for C11H11Cl2O3 (M + H)+
261.0080, found 261.0107. IR (KBr) ν 3090, 2953, 2853, 1747, 1709,
1657, 1626, 1583, 1555, 1439, 1348, 1273, 1238, 1159, 1103, 1061,
825, 812 cm−1.
1 equiv of acetone.26 Then the copper(II) reacts with the 1,3-
dicarbonyl compound to generate copper enolate intermediate
4. Finally, the methyl radical reacts with enolate 4 to produce
the α-methylated 1,3-dicarbonyl compound 3 and regenerate
Cu(I), which is oxidized to Cu(II) for further reactions.
Alternatively, the reaction could be considered as a simple free-
radical addition onto a double bond of a copper benzoylace-
tate.42 At the current stage, neither of these two possible
pathways could be thoroughly ruled out.
In conclusion, we have developed a direct and selective
TBPB-promoted monomethylation of 1,3-dicarbonyl com-
pounds in moderate to good yields. This procedure tolerates
a series of functional groups and avoids the use of poisonous
methyl iodide. Thus, it represents a facile and straightforward
pathway leading to α-methyl 1,3-dicarbonyl compounds.
EXPERIMENTAL SECTION
■
General Information. All chemicals were used as received without
further purification unless stated otherwise. H NMR and 13C NMR
1
spectra were recorded at ambient temperature on a 300 or 400 MHz
NMR spectrometer (75 or 100 MHz for 13C). NMR chemical shifts
(δ) are reported in parts per million (ppm) and were referenced to
CDCl3 (7.26 or 77.0 ppm) as the internal standard. Coupling
constants (J) are given in hertz. Column chromatography was
performed using EM Silica gel (300−400 mesh). IR spectra were
recorded on a spectrometer using KBr discs.
Methyl 3-(2-Chlorophenyl)-2-methyl-3-oxopropanoate
(3h).48 Flash column chromatography on silica gel (ethyl acetate/
petroleum ether 1:30) gave 3h (60.1 mg, 53% yield) as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 12.59 (s, 0.38H), 7.47−7.30 (m,
5.71H), 4.35 (q, J = 7.1 Hz, 0.94H), 3.83 (s, 1.31H), 3.67 (s, 3.00H),
1.58 (s, 1.34H), 1.47 (d, J = 7.2 Hz, 3.00H). 13C{1H} NMR (CDCl3,
100 MHz): δ 199.0, 173.8, 170.6, 167.4, 138.4, 134.2, 132.4, 132.0,
130.9, 130.5, 130.4, 129.8, 129.8, 129.3, 127.0, 126.8, 98.6, 52.4, 51.9,
51.8, 13.2, 12.1.
Experimental Procedure for the Methylation of 1,3-
Dicarbonyl Compounds. Under N2, a Schlenk tube equipped
with a stir bar was charged with 1,3-dicarbonyl compound 1 (0.5
mmol), Cu(BF4)2 (45% in water, 7 μL, 0.025 mmol, 5 mol %), TBPB
(190 μL, 1.0 mmol, 2 equiv), and PhCl (3 mL) and sealed. The
reaction mixture was stirred at 100 °C for 2 h. After completion of the
reaction (as monitored by TLC), the solvent was concentrated in
vacuum, and the residue was purified by flash column chromatography
on silica gel with petroleum ether/EtOAc as the eluent to give the
desired product.
Methyl 3-(4-Fluorophenyl)-2-methyl-3-oxopropanoate (3i).
Flash column chromatography on silica gel (ethyl acetate/petroleum
1
ether 1:30) gave 3i (77.4 mg, 74% yield) as a colorless oil. H NMR
(CDCl3, 400 MHz): δ 8.02−7.97 (m, 2H), 7.16−7.10 (m, 2H), 4.35
(q, J = 7.1 Hz, 1H), 3.67 (s, 3H), 1.47 (d, J = 7.1 Hz, 3H). 13C{1H}
NMR (CDCl3, 100 MHz): δ 194.1, 171.1, 165.9 (d, JC−F = 254.2 Hz),
Ethyl 2-Methyl-3-oxo-3-phenylpropanoate (3a).17 Flash col-
umn chromatography on silica gel (ethyl acetate/petroleum ether
132.1 (d, JC−F = 3.0 Hz), 131.2 (d, JC−F = 9.4 Hz), 115.9 (d, JC−F
=
1
1:100) gave 3a (80.6 mg, 78% yield) as a colorless oil. H NMR
21.8 Hz), 52.5, 48.0, 13.7. MS (EI): 210 (M+). HRMS (ESI-TOF):
C
dx.doi.org/10.1021/jo502204a | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
calcd for C11H12FO3 (M + H)+ 211.0765, found 211.0766. IR (KBr) ν
2993, 2955, 1747, 1688, 1682, 1599, 1506, 1456, 1435, 1329, 1302,
1286, 1231, 1159, 1101, 1084, 978, 951, 849, 606, 569 cm−1.
colorless oil. 1H NMR (CDCl3, 400 MHz): δ 8.54 (s, 1H), 8.17 (d, J =
7.8 Hz, 2H), 7.60 (t, J = 7.8 Hz, 1H), 4.43 (q, J = 7.1 Hz, 2H), 3.68 (s,
6H), 1.49 (d, J = 7.1 Hz, 6H). 13C{1H} NMR (CDCl3, 100 MHz): δ
194.9, 170.8, 136.3, 136.2, 133.1, 133.1, 129.4, 129.4, 128.6, 128.5,
52.6, 48.1, 48.0, 13.6. MS (EI): 306 (M+). HRMS (ESI-TOF): calcd
for C16H19O6 (M + H)+ 307.1176, found 307.1180. IR (KBr) ν 3069,
2993, 2953, 2880, 2845, 1747, 1693, 1597, 1456, 1435, 1207, 1086,
945, 862, 679, 588 cm−1.
Ethyl 2-Methyl-3-(4-nitrophenyl)-3-oxopropanoate (3j).49
Flash column chromatography on silica gel (ethyl acetate/petroleum
ether 1:30) gave 3j (76.9 mg, 61% yield) as a pale-yellow oil. 1H NMR
(CDCl3, 400 MHz): δ 8.29 (d, J = 8.8 Hz, 2H), 8.11 (d, J = 8.8 Hz,
2H), 4.36 (q, J = 7.0 Hz, 1H), 4.12 (q, J = 7.1 Hz, 2H), 1.49 (d, J = 7.0
Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz):
δ 194.3, 170.0, 150.3, 140.4, 129.5, 123.8, 61.7, 48.8, 13.8, 13.3.
Methyl 2-Methyl-3-(naphthalen-2-yl)-3-oxopropanoate (3k).
Flash column chromatography on silica gel (ethyl acetate/petroleum
ASSOCIATED CONTENT
■
S
* Supporting Information
Radical capture experiments and H and 13C NMR spectra of
1
1
ether 1:30) gave 3k (74.9 mg, 62% yield) as a colorless oil. H NMR
compounds 3a−r. This material is available free of charge via
the Internet at http://pubs.acs.org.
(CDCl3, 400 MHz): δ 8.50 (s, 1H), 8.04−8.02 (m, 1H), 7.98−7.96
(m, 1H), 7.91−7.86 (m, 2H), 7.63−7.53 (m, 2H), 4.58 (q, J = 7.1 Hz,
1H), 3.69 (s, 3H), 1.56 (d, J = 7.1 Hz, 3H). 13C{1H} NMR (CDCl3,
100 MHz): δ 195.7, 171.3, 135.7, 133.0, 132.4, 130.4, 129.6, 128.7,
128.6, 127.7, 126.9, 124.0, 52.5, 48.0, 13.9. MS (EI): 242 (M+). HRMS
(ESI-TOF): calcd for C15H15O3 (M + H)+ 243.1016, found 243.1018.
IR (KBr) ν 3059, 2951, 2878, 2845, 1747, 1682, 1626, 1595, 1466,
1454, 1435, 1281, 1202, 933, 866, 825, 758, 476 cm−1.
AUTHOR INFORMATION
Corresponding Author
*E-mail: yujintao@cczu.edu.cn.
■
Notes
The authors declare no competing financial interest.
Methyl 2-Methyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-
carboxylate (3l).50 Flash column chromatography on silica gel
(ethyl acetate/petroleum ether 1:30) gave 3l (48.9 mg, 45% yield) as a
ACKNOWLEDGMENTS
■
1
pale-yellow oil. H NMR (CDCl3, 300 MHz): δ 8.06−8.03 (m, 1H),
We thank the National Natural Science Foundation of China
(21272028 and 21202013), Jiangsu Key Laboratory of
Advanced Catalytic Materials and Technology (BM2012110),
and Changzhou University for financial support.
7.49−7.44 (m, 1H), 7.33−7.28 (m, 1H), 7.23−7.20 (m, 1H), 3.66 (s,
3H), 3.08−2.87 (m, 2H), 2.64−2.56 (m, 1H), 2.09−2.00 (m, 1H),
1.50 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 196.0, 173.4, 143.1,
133.5, 131.5, 128.7, 128.0, 126.7, 53.8, 52.4, 33.9, 25.9, 20.7.
Methyl 3-(Furan-2-yl)-2-methyl-3-oxopropanoate (3m).48
Flash column chromatography on silica gel (ethyl acetate/petroleum
ether 1:20) gave 3m (52.2 mg, 57% yield) as a colorless oil. 1H NMR
(CDCl3, 400 MHz): δ 7.63 (s, 1H), 7.30 (d, J = 3.6 Hz, 1H), 6.59−
6.57 (m, 1H), 4.20 (q, J = 7.2 Hz, 1H), 3.71 (s, 3H), 1.48 (d, J = 7.2
Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 184.5, 170.8, 151.6,
146.9, 118.3, 112.5, 52.4, 48.2, 13.1.
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■
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matography on silica gel (ethyl acetate/petroleum ether 1:50) gave 3o
(46.6 mg, 45% yield) as a colorless oil. 1H NMR (CDCl3, 400 MHz):
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3.66 (s, 3H), 2.25−2.22 (m, 4H), 1.61−1.59 (m, 4H), 1.33 (d, J = 7.0
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197.1172. IR (KBr) ν 3312, 2937, 2862, 1744, 1666, 1636, 1450, 1435,
1383, 1215, 1088, 1072, 986, 901, 856 cm−1
2,5,5-Trimethylcyclohexane-1,3-dione (3q). Flash column
chromatography on silica gel (ethyl acetate/petroleum ether 1:10)
gave 3q (38.1 mg, 49% yield) as a colorless oil. 1H NMR (CDCl3, 300
MHz): δ 5.35 (s, 1H), 3.68 (s, 3H), 2.25 (s, 2H), 2.19 (s, 2H), 1.05 (s,
6H). 13C{1H} NMR (CDCl3, 75 MHz): δ 199.5, 177.0, 101.1, 55.6,
50.7, 42.6, 32.5, 28.2, 28.2. MS (EI): 154 (M+). HRMS (ESI-TOF):
calcd for C9H15O2 (M + H)+ 155.1067, found 155.1068. IR (KBr) ν
2958, 2941, 2872, 1661, 1609, 1373, 1225, 1153 cm−1.
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D
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