Straightforward and highly efficient synthesis of α-acetoxy ketones through gold-catalyzed intermolecular oxidation of terminal alkynes

Article abstract of DOI:10.1055/s-0033-1338513

A variety of terminal alkynes were efficiently converted into the corresponding α-acetoxy ketones through gold-catalyzed intermolecular oxidation in the presence of 8-methylquinoline 1-oxide as the oxidant. The reaction probably proceeds through an α-oxo gold carbene intermolecular O-H insertion.

Full text of DOI:10.1055/s-0033-1338513

PAPER
▌2605
paper
Straightforward and Highly Efficient Synthesis of α-Acetoxy Ketones through
Gold-Catalyzed Intermolecular Oxidation of Terminal Alkynes
α-Acetoxy Ketones by Catalytic Oxidation of Terminal Alkynes
Chao Wu,a Zhiwu Liang,a Dong Yan,b Weimin He,*a Jiannan Xiang*a
a
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University,
Changsha 410082, P. R. of China
Fax +86(731)88821742; E-mail: wmhe@hnu.edu.cn; E-mail: jnxiang@hnu.edu.cn
b
Hunan Chemical Industry Vocation Technology Institute, Zhuzhou 412004, P. R. of China
Received: 11.05.2013; Accepted after revision: 03.07.2013
methyl ketones from simple terminal alkynes by using 8-
Abstract: A variety of terminal alkynes were efficiently converted
methylquinoline 1-oxide as the oxidant.13 In the course of
into the corresponding α-acetoxy ketones through gold-catalyzed
this study, α-oxo gold carbenes were shown to be highly
intermolecular oxidation in the presence of 8-methylquinoline 1-ox-
electrophilic and capable of effective abstraction of halo-
gens from halogenated solvents. We therefore surmised
that the α-oxo gold carbenes might be used to replace α-
diazo ketones in the synthesis of α-acetoxy ketones from
alkynes, thereby establishing a short, safe, and potentially
highly efficient route to this class of α-carbonyl com-
pounds.
ide as the oxidant. The reaction probably proceeds through an α-oxo
gold carbene intermolecular O–H insertion.
Key words: alkynes, homogeneous catalysis, gold, oxidations, car-
bene complexes, ketones, esters
α-Acetoxy ketones are not only important building blocks
in the synthesis of natural and pharmacologically active
compounds,1 but they also serve as plausible precursors
for the preparation of α-hydroxy ketones2 or optically ac-
tive 1,2-diols.3 Most of the current approaches to α-ace-
toxy ketones involve the acetolysis of α-diazo ketones4 or
α-bromo ketones5 or the oxidation of ketones or ketone
derivatives (enol silyl ethers or acetates) by toxic heavy-
metal oxidants.6 However, these procedures suffer from
several drawbacks, such as low yields, harsh operating
conditions, or environmental problems. In addition, most
of the general methods are limited to ketone or ketone de-
rivatives, which are always prepared from alkynes. There
are very few methods for synthesizing α-acetoxy ketones
in a single step from readily available alkynes. To the best
of our knowledge, only Hou et al.7 have described an ele-
gant oxidation reaction that gives α-acetoxy ketones from
the corresponding terminal alkynes with diacetyl(phenyl)-
λ3-iodane as the oxidant.7 There is therefore still a need to
develop an alternative method that involves a mild and
convenient pathway.
First, we performed a set of experiments with ethynylben-
zene as a model substrate. Acetic acid was chosen as the
model carboxylic acid partner and also served as the sol-
vent.9d,13 In the presence of 1.3 equivalents of 8-methyl-
quinoline 1-oxide, 1.1 equivalents of methanesulfonic
acid, and 5 mol% of (triphenylphosphine)[bis(triflic)ami-
no]gold(I) (Ph3PAuNTf2), the expected product, 2-oxodo-
decyl acetate (2a) was obtained in good yield by a gold-
catalyzed intermolecular oxidation process (Table 1, entry
1). Under these reaction conditions, the replacement of 8-
methylquinoline 1-oxide with several other quinoline or
pyridine N-oxides gave disappointing results (entries 2–
8). Additionally, several different ligands and counterions
were screened, but even in the most favorable cases, only
moderate yields were obtained (entries 9–16). One of the
side products from these reactions was the mesylate 3,9c
probably formed through reaction of the α-oxo gold car-
bene with methanesulfonic acid. Note that the control ex-
periments showed that the presence of the gold catalyst is
necessary in this protocol (entries 17–18).
In recent decades, homogeneous gold catalysis has
emerged as a rapidly growing field of synthetic organic
chemistry as a result of the unique Lewis acid carbophilic
properties of gold.8 Recently, the use of α-oxo gold car-
benes derived from alkynes and oxygen nucleophiles,
such as pyridine or quinolone N-oxides,9 sulfoxides,9g,10
or nitrones,9g,11 has become well established.12 This strat-
egy circumvents the use of hazardous and potentially ex-
plosive α-diazo ketone precursors in a range of new
synthetic transformations. We have previously reported a
gold-catalyzed synthesis of α-chloromethyl and α-bromo-
Having identified the optimized conditions, we investigat-
ed the scope of the reaction with various alkynes (Table
2). A series of substituted ethynylbenzenes, some contain-
ing electron-donating groups (R = Me, OMe) and some
containing electron-withdrawing groups (R = F, Br, CF3),
were converted into the corresponding products in excel-
lent yields (Table 2, 2b–h). In the case of 1-bromo-2-ethy-
nylbenzene (2i), the ortho substituent decreased the
reaction yield substantially, probably as a result of steric
hindrance, although the reaction is still useful.14 When the
aryl alkyne contained a naphthyl group (2j), the corre-
sponding α-acetoxy ketone was obtained in good yield.
Many synthetically important substituents including phe-
nyl (2k), alkyl (2l), chloro (2m), ester (2n), sulfonoxyl
(2o, 2p), silyl ether (2q), and ether groups (2r and 2s) are
well tolerated, with yields of the desired isolated products
SYNTHESIS 2013, 45, 2605–2611
Advanced online publication: 30.07.2013
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0
3
9
-
7
8
8
1
1
4
3
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DOI: 10.1055/s-0033-1338513; Art ID: SS-2013-H0349-OP
© Georg Thieme Verlag Stuttgart · New York

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Table 1 Screening for Optimal Conditions
O
O
[Au] (5mol%)
[O] (1.3 equiv)
OAc
OMs
+
MsOH (1.1 equiv)
AcOH
1a
2a
3a
4d R = H
4a R = H
4b R = Me
4c R = Et
R
4e R = 2-Br
4f R = 2,4-Cl2
4g R = 2,6-Cl2
4h R = 3,5-Cl2
N
O
N
O
R
Entrya
Catalyst
Oxidant
Timeb (h)
Yieldc (%)
1
2
Ph3PAuNTf2
Ph3PAuNTf2
Ph3PAuNTf2
Ph3PAuNTf2
Ph3PAuNTf2
Ph3PAuNTf2
Ph3PAuNTf2
Ph3PAuNTf2
4b
4a
4c
4d
4e
4f
8
8
85d
62
81
19
39
43
37
32
30
44
51
51
78
35
39
28
–
3
8
4
8
5
8
6
8
7
4g
4h
4b
4b
4b
4b
4b
4b
4b
4b
4b
4b
8
8
8
e
9
IPrAuNTf2
8
e
10
11
12
13
14
15
16
17
18
BrettPhosAuNTf2
8
e
XPhosAuNTf2
8
Et3PAuNTf2
8
Cy3PAuNTf2
8
Ph3PAuCl/AgBF4
8
Ph3PAuCl/AgSbF6
Ph3PAuCl/AgOTf
AgNTf2
8
9
24
24
–
–
a Reaction conditions: 1a (0.05 M), r.t., in vials.
b Monitored by TLC.
c NMR yield with diethyl phthalate as the internal reference.
d Isolated yield.
e IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene; BrettPhos = dicyclohexyl(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phos-
phine; XPhos = dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine.
ranging from 61 to 90%. Interestingly, reactions with sub- We postulated a plausible mechanism based on that of the
strates bearing bulky groups, such as the tert-butyl group, previously reported halide abstractions by α-oxo gold
the cyclohex-1-en-1-yl group, or the cyclopropyl group, carbenes13 and copper(II) complex-mediated metal car-
also proceeded smoothly (2t–v). The reaction failed in the bene insertions into the O–H bonds of carboxylic acids.4
case of aliphatic internal alkynes because of the ease with Coordination of the gold(I) cation to the alkyne facilitates
which the enone is formed.9a In addition, functionalized attack by 8-methylquinoline 1-oxide, which results in the
propargylic alcohols and but-3-yn-1-ol were not suitable formation of the α-oxo gold carbene A (Scheme 1). Gold
as substrates owing to a competitive intramolecular cycli- carbene A inserts into the carboxylic O–H bonds via the
zation reaction.9c,d Various carboxylic acids gave good oxygenium intermediate B; the gold enolate intermediate
yields of the corresponding α-carboalkoxy ketone prod- C is then protodeaurated to give keto ester 2 and cationic
ucts 2w–y.
gold(I). Alternatively, the gold carbene A can insert into
methanesulfonic acid to afford the mesylate 3.
Synthesis 2013, 45, 2605–2611
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α-Acetoxy Ketones by Catalytic Oxidation of Terminal Alkynes
2607
Table 2 Reaction Scope
O
Ph3PAuNTf2 (5 mol%)
O
R2
4b (1.3 equiv), MsOH (1.1 equiv)
R1
R1
R2CO2H, r.t., 8 h
O
1
2
R2 = Me, Et, n-Bu, Ph
Entry
1a
Product, yield
Entry
Product, yield
Entry
3
Product, yield
O
O
O
OAc
OAc
OAc
2
MeO
2b, 90%b
2d, 82%
2c, 78%
O
O
O
MeO
MeO
OAc
OAc
OAc
4
5
6
Br
F
OMe
2g, 86%
2f, 89%
2e, 80%
O
O
O
OAc
OAc
F3C
OAc
OAc
OAc
7
8
9
Br
2h, 85%
2k, 71%
2j, 83%
2i, 61%
O
O
O
OAc
Cl
10
11
12
3
8
2l, 75%
O
2m, 61%
O
O
OAc
OAc
OAc
OAc
AcO
TsO
MsO
13
16
14
17
15
18
3
3
3
2n, 71%
2o, 76%
2p, 67%
O
O
O
OAc
OAc
TBSO
MeO
BnO
2
3
3
2q, 68%
2s, 63%
2r, 72%
O
O
O
OAc
OAc
OAc
19
20
21
2v, 90%
2t, 79%
2u, 72%
O
O
O
O
O
O
3
22c
23d
24e
O
O
O
2w, 77%
2x, 69%
2y, 74%
a Reaction conditions: 1 (0.05 M), in vials (applies to all reactions).
b All yields are isolated yields.
c EtCO2H was used as the solvent.
d BuCO2H was used as the solvent.
e PhCl was used as the solvent and three equivalents of the acid were used.
© Georg Thieme Verlag Stuttgart · New York
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O
OAc
R
R
O
2
1
H
Au
Au
R
N
R
O
O
O
O
Au+
OMs
H
R
3
C
H
N
O
O
Au
O
R
R
O
Au
O
Au
R
S
Me
H
O
O
O
H
B
MsOH
O
O
Au
Au
N
R
R
AcOH
A
Scheme 1 Proposed reaction mechanism
IR (neat): 2978, 1749, 1696, 1361, 1189, 997, 856 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.23 (s, 3 H), 2.42 (s, 3 H), 5.33
(s, 2 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.82 (d, J = 8.0 Hz, 2 H).
In conclusion, we have developed a straightforward pro-
tocol for the synthesis of α-acetoxy ketones from terminal
alkynes through a gold-catalyzed intermolecular oxida-
tion reaction.15 The method is an attractive alternative to
13C NMR (100 MHz, CDCl3): δ = 20.6, 21.7, 65.9, 127.8, 129.5,
classical procedures as it does not require harsh conditions 131.5, 144.8, 170.5, 191.7.
HRMS (EI): m/z [M+] calcd for C11H12O3: 192.0786; found:
192.0781.
or toxic reagents. A broad range of aromatic and aliphatic
alkynes are tolerated and a wide variety of α-acetoxy ke-
tones can be prepared in moderate to excellent yields. In
view of the ready availability of the starting materials, this
approach may find practical applications in organic syn-
thesis.
2-(4-Methoxyphenyl)-2-oxoethyl Acetate (2c)16
White solid; yield: 48.3 mg (78%); mp 60–62 °C.
IR (neat): 2980, 2867, 1754, 1704, 1602, 1349, 1171, 973 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.23 (s, 3 H), 3.87 (s, 3 H), 5.30
(s, 2 H), 6.95 (d, J = 8.8 Hz, 2 H), 7.89 (d, J = 8.8 Hz, 2 H).
NMR spectroscopy was performed on a Bruker Avance spectrome-
ter operated at 400 MHz (1H NMR), 100 MHz (13C NMR), or 376
MHz (19F NMR). Melting points were measured with a XRC-1
melting-point apparatus. Fourier-transform IR spectra were record-
ed by using a Nicolet 5DX spectrometer. Mass spectrometric anal-
ysis was performed on a MAT 95 XP instrument (Thermo
Finnigan).
13C NMR (100 MHz, CDCl3): δ = 20.6, 55.5, 65.7, 114.0, 127.1,
130.0, 164.0, 170.5, 190.6.
HRMS (EI): m/z [M+] calcd for C11H12O4: 208.0736; found:
208.0730.
2-Oxo-2-(2-tolyl)ethyl Acetate (2d)
Yellow oil; yield: 47.5 mg (82%).
IR (neat): 2979, 1750, 1696, 1360, 1022, 896 cm–1.
Keto Acetates 2a–y; General Procedure
A mixture of 8-methylquinoline 1-oxide (62.0 mg, 0.39 mmol),
MsOH (32.4 mg, 0.33 mmol), and Ph3PAuNTf2 (11.4 mg, 0.015
mmol) was added to a soln of the appropriate alkyne 1 (0.30 mmol)
in AcOH (5 mL), and the mixture was stirred at r.t. until the reaction
was complete (TLC). The mixture was then concentrated and the
residue was purified by chromatography (silica gel, hexanes–
EtOAc).
1H NMR (400 MHz, CDCl3): δ = 2.23 (s, 3 H), 2.41 (s, 3 H), 5.33
(s, 2 H), 7.37–7.43 (m, 2 H), 7.69–7.72 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 20.6, 21.3, 66.0, 124.8, 128.2,
128.7, 134.1, 134.7, 138.7, 170.5, 192.3.
HRMS (EI): m/z [M+] calcd for C11H12O3: 192.0786; found:
192.0781.
2-Oxo-2-phenylethyl Acetate (2a)7
2-Oxo-2-(3,4,5-trimethoxyphenyl)ethyl Acetate (2e)
Yellow oil; yield: 45.2 mg (85%).
White solid; yield: 63.2 mg (80%); mp 85–87 °C.
IR (neat): 2936, 1751, 1705, 1598, 1375, 1220 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.23 (s, 3 H), 5.35 (s, 2 H), 7.49
(t, J = 8.0 Hz, 2 H), 7.61 (t, J = 7.6 Hz, 1 H), 7.91 (d, J = 7.2 Hz, 2
H).
13C NMR (100 MHz, CDCl3): δ = 20.6, 66.0, 127.7, 128.8, 133.9,
134.0, 170.4, 192.1.
HRMS (EI): m/z [M+] calcd for C10H10O3: 178.0630; found:
178.0627.
IR (neat): 2980, 2867, 1748, 1698, 1602, 1349, 1171, 973 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.23 (s, 3 H), 3.90 (s, 6 H), 3.91
(s, 3 H), 5.31 (s, 2 H), 7.15 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 20.6, 56.3, 61.0, 65.8, 105.2,
129.3, 143.2, 153.2, 170.5, 191.0.
HRMS (EI): m/z [M+] calcd for C13H16O6: 268.0947; found:
268.0944.
2-(4-Fluorophenyl)-2-oxoethyl Acetate (2f)17
2-Oxo-2-(4-tolyl)ethyl Acetate (2b)7
White solid; yield: 51.6 mg (90%); mp 84–86 °C.
Brown solid; yield: 51.8 mg (89%); mp 50–51 °C.
IR (neat): 2958, 1747, 1701, 1599, 1505, 1375, 1221, 830 cm–1.
Synthesis 2013, 45, 2605–2611
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α-Acetoxy Ketones by Catalytic Oxidation of Terminal Alkynes
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1H NMR (400 MHz, CDCl3): δ = 2.18 (s, 3 H), 5.27 (s, 2 H), 7.12
(t, J = 8.4 Hz, 2 H), 7.89–7.93 (m, 2 H).
HRMS (EI): m/z [M+] calcd for C12H14O3: 206.0943; found:
206.0940.
13C NMR (100 MHz, CDCl3): δ = 20.4, 65.7, 115.9 (d, J = 22.3 Hz),
130.3 (d, J = 10.4 Hz), 164.7, 167.2, 170.3, 190.6.
19F NMR (376 MHz, CDCl3): δ = –103.5
HRMS (EI): m/z [M+] calcd for C10H9FO3: 196.0536; found:
196.0530.
2-Oxododecyl Acetate (2l)
White solid; yield: 54.0 mg (75%); mp 64–65 °C.
IR (neat): 2960, 1753, 1726, 1370, 1229, 1064 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.87 (t, J = 6.8 Hz, 3 H), 1.25 (s,
14 H), 1.61 (t, J = 7.2 Hz, 2 H), 2.17 (s, 3 H), 2.41 (t, J = 7.2 Hz, 2
H), 4.65 (s, 2 H).
2-(4-Bromophenyl)-2-oxoethyl Acetate (2g)17
Tan solid; yield: 65.6 mg (86%); mp 84–86 °C.
13C NMR (100 MHz, CDCl3): δ = 14.1, 20.5, 22.6, 23.3, 29.1, 29.3,
29.3, 29.4, 29.5, 31.9, 38.8, 67.9, 170.3, 204.1.
HRMS (EI): m/z [M+] calcd for C14H26O3: 242.1882; found:
242.1877.
IR (neat): 2989, 1746, 1695, 1586, 1431, 1227, 1001, 816 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.20 (s, 3 H), 5.27 (s, 2 H), 7.60
(d, J = 8.4 Hz, 2 H), 7.75 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 20.4, 65.7, 129.0, 129.1, 132.1,
132.7, 170.3, 191.2.
6-Chloro-2-oxohexyl Acetate (2m)
Colorless oil; yield: 34.7 mg (61%).
IR (neat): 3200, 2348, 1732, 1405, 1231, 1063, 665 cm–1.
HRMS (EI): m/z [M+] calcd for C10H9BrO3: 255.9735; found:
1H NMR (400 MHz, CDCl3): δ = 1.78–1.80 (m, 4 H), 2.17 (s, 3 H),
2.47 (t, J = 6.8 Hz, 2 H), 3.54 (t, J = 6.0 Hz, 2 H), 4.65 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 20.3, 20.4, 31.7, 37.8, 44.5, 67.9,
255.9733.
2-Oxo-2-[3-(trifluoromethyl)phenyl]ethyl Acetate (2h)
Yellow oil; yield: 61.1 mg (85%).
170.3, 203.3.
IR (neat): 3410, 2841, 1747, 1733, 1692, 1023, 845 cm–1.
HRMS (EI): m/z [M+] calcd for C8H13ClO3: 192.0553; found:
192.0550.
1H NMR (400 MHz, CDCl3): δ = 2.24 (s, 3 H), 5.34 (s, 2 H), 7.65
(t, J = 7.6 Hz, 1 H), 7.87 (d, J = 7.6 Hz, 1 H), 8.10 (d, J = 8.0 Hz,
1 H), 8.16 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 20.5, 65.9, 123.5 (q, J = 271.9
Hz), 124.6 (q, J = 3.5 Hz), 129.6, 130.2 (q, J = 3.4 Hz), 130.9, 131.6
(q, J = 32.4 Hz), 134.7, 170.3, 191.1.
19F NMR (376 MHz, CDCl3): δ = –62.9.
HRMS (EI): m/z [M+] calcd for C11H9F3O3: 246.0504; found:
2-Oxohexane-1,6-diyl Diacetate (2n)
Yellow solid; yield: 46.5 mg (71%); mp 62–63 °C.
IR (neat): 2977, 1753, 1749, 1726, 1370, 1231, 1058, 928 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.62–1.63 (m, 4 H), 2.00 (s, 3 H),
2.13 (s, 3 H), 2.43 (t, J = 6.8 Hz, 2 H), 4.01 (t, J = 6.0 Hz, 2 H), 4.61
(s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 19.5, 20.3, 20.8, 27.8, 37.9, 63.8,
246.0499.
67.8, 170.2, 171.0, 203.4.
HRMS (EI): m/z [M+] calcd for C10H16O5: 216.0998; found:
2-(2-Bromophenyl)-2-oxoethyl Acetate (2i)
White oil; yield: 46.2 mg (61%).
216.0993.
IR (neat): 2991, 2952, 1745, 1697, 1601, 1225, 997, 856 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.18 (s, 3 H), 5.16 (s, 2 H), 7.33–
7.43 (m, 2 H), 7.49–7.51 (m, 1 H), 7.63–7.65 (m, 1 H).
2-Oxo-6-(tosyloxy)hexyl Acetate (2o)
Yellow solid; yield: 73.6 mg (76%); mp 102–103 °C.
IR (neat): 2939, 1746, 1733, 1598, 1350, 1168, 1092, 806 cm–1.
13C NMR (100 MHz, CDCl3): δ = 20.4, 67.7, 119.2, 127.5, 129.4,
1H NMR (400 MHz, CDCl3): δ = 1.65–1.66 (m, 4 H), 2.15 (s, 3 H),
2.40 (t, J = 6.8 Hz, 2 H), 2.45 (s, 3 H), 4.01 (t, J = 6.0 Hz, 2 H), 4.60
(s, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.77 (d, J = 8.0 Hz, 2 H).
132.5, 133.8, 138.2, 170.3, 196.5.
HRMS (EI): m/z [M+] calcd for C10H9BrO3: 255.9735; found:
255.9729.
13C NMR (100 MHz, CDCl3): δ = 19.1, 20.4, 21.6, 28.0, 37.6, 67.9,
70.0, 127.8, 129.8, 132.8, 144.8, 170.2, 203.2.
HRMS (EI): m/z [M+] calcd for C15H20O6S: 328.0981; found:
328.0985.
2-(2-Naphthyl)-2-oxoethyl Acetate (2j)16
Yellow solid; yield: 55.4 mg (83%); mp 78–80 °C.
IR (neat): 3014, 2937, 1752, 1740, 1692, 1500, 1196, 1023, 845
cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.27 (s, 3 H), 5.49 (s, 2 H), 7.56–
7.65 (m, 2 H), 7.88–8.00 (m, 4 H), 8.43 (s, 1 H).
6-(Mesyloxy)-2-oxohexyl Acetate (2p)
White solid; yield: 50.7 mg (67%); mp 71–72 °C.
IR (neat): 2966, 2879, 1748, 1730, 1349, 1171, 936 cm–1.
13C NMR (100 MHz, CDCl3): δ = 20.6, 66.1, 123.2, 127.0, 127.9,
1H NMR (400 MHz, CDCl3): δ = 1.76–1.77 (m, 4 H), 2.17 (s, 3 H),
2.49 (t, J = 6.8 Hz, 2 H), 3.02 (s, 3 H), 4.23 (t, J = 6.0 Hz, 2 H), 4.65
(s, 2 H).
128.8, 128.9, 129.4, 129.5, 131.4, 132.3, 135.8, 170.5, 192.1.
HRMS (EI): m/z [M+] calcd for C14H12O3: 228.0786; found:
228.0781.
13C NMR (100 MHz, CDCl3): δ = 19.1, 20.5, 28.3, 37.3, 37.6, 67.9,
69.5, 170.3, 203.3.
HRMS (EI): m/z [M+] calcd for C9H16O6S: 252.0668; found:
252.0661.
2-Oxo-4-phenylbutyl Acetate (2k)18
Yellow solid; yield: 43.2 mg (71%); mp 44–46 °C.
IR (neat): 2932, 1748, 1733, 1592, 1375, 1222, 1046 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.17 (s, 3 H), 2.75 (t, J = 7.6 Hz,
2 H), 2.94 (t, J = 7.6 Hz, 2 H), 4.62 (s, 2 H), 7.19–7.22 (m, 3 H),
7.23–7.27 (m, 2 H).
5-{[tert-Butyl(dimethyl)silyl]oxy}-2-oxopentyl Acetate (2q)
Yellow oil; yield: 55.7 mg (68%).
IR (neat): 2937, 1749, 1728, 1602, 1307, 1021, 849 cm–1.
13C NMR (100 MHz, CDCl3): δ = 20.4, 29.1, 40.3, 68.0, 126.2,
128.2, 128.5, 140.4, 170.2, 203.0.
© Georg Thieme Verlag Stuttgart · New York
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IR (neat): 2932, 1744, 1702, 1598, 1420, 1375, 1218 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.21 (t, J = 7.6 Hz, 3 H), 2.52 (q,
J = 7.6 Hz, 2 H), 5.34 (s, 2 H), 7.47 (t, J = 7.6 Hz, 2 H), 7.59 (t,
J = 7.6 Hz, 1 H), 7.90 (d, J = 7.6 Hz, 2 H).
1H NMR (400 MHz, CDCl3): δ = 0.03 (s, 6 H), 0.88 (s, 9 H), 1.79–
1.85 (m, 2 H), 2.17 (s, 3 H), 2.50 (t, J = 7.2 Hz, 2 H), 3.61 (t, J = 6.0
Hz, 2 H), 4.67 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = –5.4, 18.3, 20.5, 25.9, 26.3, 35.2,
61.8, 68.0, 170.3, 203.9.
HRMS (EI): m/z [M+] calcd for C13H26O4Si: 274.1600; found:
13C NMR (100 MHz, CDCl3): δ = 9.0, 27.1, 65.8, 127.6, 128.8,
133.8, 134.0, 173.8, 192.2.
274.1596.
HRMS (EI): m/z [M+] calcd for C11H12O3: 192.0786; found:
192.0784.
6-Methoxy-2-oxohexyl Acetate (2r)
Colorless oil; yield: 40.1 mg (72%).
2-Oxo-2-phenylethyl Pentanoate (2x)
Gray solid; yield: 44.9 mg (69%); mp 75–76 °C.
IR (neat): 2926, 2851, 1751, 1728, 1430, 1220, 980 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.55–1.61 (m, 2 H), 1.63–1.70 (m,
2 H), 2.16 (s, 3 H), 2.44 (t, J = 7.2 Hz, 2 H), 3.30 (s, 3 H), 3.35 (t,
J = 6.0 Hz, 2 H), 4.64 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 20.0, 20.5, 28.8, 38.4, 58.5, 67.9,
72.2, 170.3, 203.7.
IR (neat): 2989, 1743, 1703, 1603, 1447, 1373, 1220, 1022 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.94 (t, J = 7.6 Hz, 3 H), 1.38–
1.44 (m, 2 H), 1.66–1.73 (m, 2 H), 2.50 (t, J = 7.6 Hz, 2 H), 5.35 (s,
2 H), 7.48 (t, J = 7.6 Hz, 2 H), 7.60 (t, J = 7.2 Hz, 1 H), 7.91 (d,
J = 7.2 Hz, 2 H).
HRMS (EI): m/z [M+] calcd for C9H16O4: 188.1049; found:
13C NMR (100 MHz, CDCl3): δ = 13.7, 22.2, 26.9, 33.6, 65.8,
188.1044.
127.7, 128.8, 133.8, 134.1, 173.3, 192.3.
HRMS (EI): m/z [M+] calcd for C13H16O3: 220.1099; found:
220.1094.
6-(Benzyloxy)-2-oxohexyl Acetate (2s)
White solid; yield: 48.9 mg (62%); mp 101–102 °C.
IR (neat): 2925, 2864, 1748, 1731, 1348, 1176, 976, 739 cm–1.
2-Oxo-2-phenylethyl Benzoate (2y)7
White solid; yield: 52.7 mg (74%); mp 88–89 °C.
1H NMR (400 MHz, CDCl3): δ = 1.54–1.60 (m, 2 H), 1.62–1.67 (m,
2 H), 2.17 (s, 3 H), 2.45 (t, J = 7.2 Hz, 2 H), 3.47 (t, J = 6.0 Hz, 2
H), 4.49 (s, 2 H), 4.64 (s, 2 H), 7.32–7.34 (m, 5 H).
IR (neat): 3027, 2912, 1744, 1701, 1602, 1447, 1375, 1218, 1020
cm–1.
13C NMR (100 MHz, CDCl3): δ = 20.0, 20.5, 28.9, 38.3, 67.9, 69.7,
1H NMR (400 MHz, CDCl3): δ = 5.60 (s, 2 H), 7.46–7.53 (m, 4 H),
72.8, 127.5, 127.6, 128.3, 138.3, 170.3, 203.8.
7.59–7.65 (m, 2 H), 7.98 (d, J = 7.2 Hz, 2 H), 8.16 (d, J = 7.2 Hz, 2
H).
HRMS (EI): m/z [M+] calcd for C15H20O4: 264.1362; found:
264.1359.
13C NMR (100 MHz, CDCl3): δ = 66.4, 127.8, 128.4, 128.9, 129.3,
129.9, 133.3, 133.9, 134.2, 166.0, 192.1.
HRMS (EI): m/z [M+] calcd for C15H12O3: 240.0786; found:
240.0781.
3,3-Dimethyl-2-oxobutyl Acetate (2t)7
Yellow oil; yield: 37.2 mg (79%).
IR (neat): 2956, 1753, 1726, 1371, 1232, 1063 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.18 (s, 9 H), 2.15 (s, 3 H), 4.86
(s, 2 H).
Acknowledgment
13C NMR (100 MHz, CDCl3): δ = 20.5, 26.1, 42.7, 64.4, 170.3,
207.9.
HRMS (EI): m/z [M+] calcd for C8H14O3: 158.0943; found:
158.0935.
This work was supported by NSFC (21276068), Department of
Science and Technology Foundation of Hunan Province
(2010SK2001), Hunan Natural Science Foundation (11JJ5008), and
the Training Program for Young Teachers in Hunan University.
2-Cyclohex-1-en-1-yl-2-oxoethyl Acetate (2u)19
Supporting Information for this article is available online at
Yellow oil; yield: 39.2 mg (72%).
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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IR (neat): 2935, 1749, 1685, 1437, 1366, 1208, 1071, 601 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.63–1.64 (m, 4 H), 2.18 (s, 3 H),
2.24–2.25 (m, 4 H), 5.04 (s, 2 H), 6.86 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 20.6, 21.4, 21.6, 22.7, 26.0, 65.1,
137.1, 140.7, 170.5, 192.5.
HRMS (EI): m/z [M+] calcd for C10H14O3: 182.0943; found:
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Synthesis 2013, 45, 2605–2611
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α-Acetoxy Ketones by Catalytic Oxidation of Terminal Alkynes
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2605–2611