Copper-catalyzed oxidative cyclization of 1,5-enynes with concomitant C-C bond cleavage: An unexpected access to 3-formyl-1-indenone derivatives

Article abstract of DOI:10.1021/jo500948b

A Cu(0)/Selectfluor system-mediated oxidative cyclization of 1,5-enynes with concomitant C-C bond cleavage to access 3-formyl-1-indenone derivatives is described. Preliminary mechanistic investigations disclosed that the C-C bond cleavage involved a novel water-participated oxygen-insertion β-carbon elimination through double oxycuprations.

Full text of DOI:10.1021/jo500948b

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pubs.acs.org/joc
Copper-Catalyzed Oxidative Cyclization of 1,5-Enynes with
Concomitant C−C Bond Cleavage: An Unexpected Access to
3‑Formyl-1-indenone Derivatives
Jian Zhang, Degui Wu, Xiaoling Chen, Yunkui Liu,* and Zhenyuan Xu
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Key Laboratory of Green Pesticides and Cleaner
Production Technology of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, People’s Republic of China
S
* Supporting Information
ABSTRACT: A Cu(0)/Selectfluor system-mediated oxidative
cyclization of 1,5-enynes with concomitant C−C bond
cleavage to access 3-formyl-1-indenone derivatives is de-
scribed. Preliminary mechanistic investigations disclosed that
the C−C bond cleavage involved a novel water-participated
oxygen-insertion β-carbon elimination through double oxy-
cuprations.
generation of FCu(II)BF4 and/or FCu(II)OH species which can
easily undergo oxycupration of alkynes.16 Considering that
enynes17 are useful precursors for the construction of cyclic
compounds upon nucleometalations,18 we envisioned that the
oxycupration of alkynes in 1,5-enyne 1 followed by an insertion of
the resulting organocopper species into the CC bond would
result in the formation of a certain cyclic compound, whereby an
indenone derivative 219 was unexpectedly obtained involving an
unusual water-participated oxygen-insertion β-carbon elimination
(Scheme 1b). The indenone derivative can serve as a useful
synthetic intermediate for natural products, ligand scaffolds, and
functional materials.20
We commenced the study by treatment of 1,5-enyne 1a with
5 mol % of Cu(0) powder, 2 equiv of Selectfluor, and NaHCO3
in CH3CN/H2O (50/1, v/v) at 80 °C for 4 h, where 2a was
obtained in 43% yield and benzoyl fluoride 3a was concurrently
produced in 29% yield (entry 1, Table 1). Gradually reducing
the amount of water in CH3CN gave better yields of 2a (60−
72%, entries 2−4, Table 1), while using dried CH3CN gave a
low yield of 2a (entry 5, Table 1), indicating that the reaction is
sensitive to the amount of water in the solvent. Through
carefully optimization, the combined CH3CN/H2O = 150:1 (v/v)
solvent system proved to be the best choice of medium for the
reaction (entry 3 vs 1, 2, 4−7, Table 1). In addition, the reaction is
also sensitive to the base additives. Among several bases examined
so far, NaHCO3 proved to be the most suitable base (entry 3 vs
8−11, Table 1). Furthermore, the catalytic activity of a series of
copper and gold salts was also evaluated for the reaction. It
was found that CuI, CuSO4·5H2O, and Cu(NO3)2·3H2O
displayed slightly lower catalytic activity than that of Cu(0)
(50−63%, entries 12−14 vs 3, Table 1), while other salts showed
much lower catalytic activity than that of Cu(0) (entries 15−21
vs 3, Table 1). Selectfluor (2 equiv) was indispensable for the
INTRODUCTION
■
The catalytic and selective cleavage of C−C bonds for chemical
transformations remains one of the most challenging tasks in
organic synthesis.1 Over the past few decades, transition-metal-
involved C−C bond cleavage has proved to be the most
promising tool for this purpose.1,2 In this context, two
elemental reactions, namely oxidative addition1a,3 and β-carbon
elimination,1a,c,d,4 were explored to achieve C−C bond
cleavage. Different from the direct insertion of a transition
metal into the C−C bond by the oxidative addition process, the
β-carbon elimination process relies on the formation of a carbon−
metal (i.e., M−C−C−C)5 or heteroatom−metal species (i.e.,
M−X−C−C, X = O and N).6−11 In particular, the metal alkoxide-
based β-carbon eliminations have been increasingly applied in a
variety of novel chemical transformations in recent years.1d,6−10 A
range of substrates containing oxyl functionalities, e.g., tertiary
alcohols,2g,i,6 secondary alcohols,7 gem-diols,8 ketones,9 and
epoxides,10 are easy to generate metal alkoxides and induce
β-carbon eliminations (Scheme 1a). On the other hand, we
envision that the in situ position of oxyl groups in an unmodified
carbon−carbon backbone via tandem reactions may provide an
alternative way to achieve the alkoxide-based β-carbon elimination.
However, such examples have been rarely reported in the
literature.12 Herein, we present an unexpected observation of a
water-participated oxygen insertion β-carbon elimination in a
copper-catalyzed oxidative cyclization of 1,5-enynes in the presence
of Selectfluor (Scheme 1b).12,13
RESULTS AND DISCUSSION
■
As part of our continued interest in the application of tandem
reactions14 in efficient organic synthesis,15 we focused on the
development of tandem reactions involving the multifold formation
and/or cleavage of chemical bonds in a single synthetic step.15f,g
Recently, we have disclosed that the redox reaction between the
Cu(0) powder and Selectfluor in the presence of water enables the
Received: January 10, 2014
Published: May 7, 2014
© 2014 American Chemical Society
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Scheme 1. Strategies for Metal Alkoxide-Based β-Carbon Elimination
a
Table 1. Optimization of Reaction Conditions
yield (%)
entry
catalyst
solvent (v/v)
base
2a
3a
1
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
CuI
MeCN/H2O = 50:1
MeCN/H2 = 100:1
MeCN/H2O = 150:1
MeCN/H2O = 200:1
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
Na2CO3
NaOH
43
60
72
65
<10
16
25
26
18
31
0
29
41
46
41
2
3
4
b
5
MeCN
6
DCM/H2O = 150:1
dioxane/H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN:H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN:H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O= 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
MeCN/H2O = 150:1
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
KOH
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
63
60
50
<3
<3
30
0
40
38
CuSO4·5H2O
Cu(NO3)2·3H2O
CuBr
CuCl
CuCl2·3H2O
AuCl
AuCl3
0
Ph3PAuCl
Ph3PAuNTf2
Cu
<3
<3
c
d,e d,e
0, 10, 50
f-h f-h f-h
Cu
0 , 0 , 0
0
i
Cu
56
34
a
All reactions were carried out with 1a (0.2 mmol), Cu(0) (5 mol % based on 1a), Selectfluor (2 equiv), and base (2 equiv) in solvent (2 mL) at
b
c
d,e
80 °C for 4 h unless otherwise noted. Dried by refluxing with CaH2. In the absence of Selectfluor. In the presence of 0.5 and 1 equiv of
Selectfluor, respectively. Selectfluor was replaced by 1-fluoro-2,6-dichloropyridinium triflate, 2,6-dichloro-1-fluoropyridinium trifluoromethanesul-
fonate, and N-fluorobenzenesulfonimide, respectively. The reaction temperature is 25 °C, and the reaction time is 12 h.
f-h
i
reaction; otherwise, the yield of 2a would be reduced (entry 22,
Table 1). When Selectfluor was replaced by other F+ reagents, e.g.,
1-fluoro-2,6-dichloropyridinium triflate, 2,6-dichloro-1-fluoropyridi-
nium trifluoromethanesulfonate, or N-fluorobenzenesulfonimide,
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the reaction failed to give the desired product 2a, while 1a was
recovered quantitatively (entry 23, Table 1). Control experiments
showed that no desired product was detected in the absence of a
copper powder (entry 24, Table 1). Note that the reaction also took
place at room temperature, although a prolonged reaction time was
required (entry 25, Table 1).
With optimized reaction conditions in hand, we set out to
investigate the effect of the ortho-substituted alkyne groups in
chalcone 1 on the formation of 2 (Table 2). For substrates
chalcones 1a′, 1a″, and 1a‴ (Figure 1). Although chalcones
bearing leaving groups such as 4-methylbenzoyl, 4-chlorobenzoyl,
and acetyl could also undergo C−C bond cleavage under the
optimized reaction conditions, these leaving groups were inferior to
benzoyl group as the leaving group (4-methylbenzoyl, 48%;
4-chlorobenzoyl, 40%; acetyl, 35%; benzoyl, 72%; Figure 1 vs
entry 3, Table 1) due to the low conversion of the starting
materials 1a′−1a‴ to the desired products.
Preliminary experiments were done to gain a mechanistic
insight into the oxidative cyclization/C−C bond cleavage
processes (Scheme 2). When 1a reacted under the standard
reaction conditions except using a CH3CN/H2O18 = 150:1 (v/v)
solvent system, the double-18O-incorporated product [18O]2-2a
(m/z = 238), mono-18O-incorporated product [18O]-2a (m/z =
236), and 2a (m/z = 234), with a molar ratio of 17:48:35, were
all detected (see Figure S3, Supporting Information),21
suggesting that both of the carbonyl oxygen atoms in 2a
originated from water (eq 1). As for the product 3a, surprisingly,
both [16O]-3a (m/z = 124, see Figure S2, Supporting
Information) and the 18O-incorporated product [18O]-3a
(m/z = 126) with a molar ratio of 95:5 were detected in the
reaction mixtures (eq 1, see Figure S4, Supporting Information).
When the preparative o-alkynyl expoxide 4 was subjected to the
standard conditions, 2a could also be obtained in 60% yield,
indicating that 4 was likely an intermediate for the reaction
(eq 2). Over the course of the reaction, we could not detect the
existence of 4, probably due to the fast conversion of 4 to 2a.
Fortunately, when a chalcone 5 not containing an alkyne moiety
was subjected to the standard reaction conditions, an epoxide
product 6 was indeed isolated in 88% yield and the 18O-labeling
experiment unambiguously established that the oxygen atom of
the epoxide 6 originated from water (eq 3, see Figure S6,
Supporting Information). The reaction gave a decreased yield of
2a (65%) in the presence of 0.2 equiv of TEMPO and failed to
give 2a by using 3 equiv of TEMPO (eq 4), demonstrating that
the reaction may involve a radical process.22
Table 2. Effect of Ortho-Substituted Alkyne Groups in
Chalcone 1 on Formation of 2
a
entry
substrate 1
1a: R = Ph
product 2
yield of 2 (%)
1
2a
2b
2c
2d
2e
2f
72
b
b
b
2
1b: R = 2-MeC6H4
1c: R = 4-MeC6H4
1d: R = 4-(n-C5H11)C6H4
1e: R = 4-EtOC6H4
1f: R = 2-FC6H4
60
64
54
3
4
5
complex mixture
6
82
80
79
71
73
72
72
71
0
7
1g: R = 3-FC6H4
1h: R = 4-FC6H4
1i: R = 2-ClC6H4
1j: R = 3-ClC6H4
1k: R = 4-ClC6H4
1l: R = 3-BrC6H4
1m: R = 4-BrC6H4
1n: R = n-hexyl
2g
2h
2i
8
9
10
11
12
13
14
15
2j
2k
2l
2m
2n
2o
1o: R = cyclopropyl
0
a
All reactions were carried out with 1 (0.2 mmol), Cu(0) (5 mol %
based on 1), Selectfluor (2 equiv), and NaHCO3 (2 equiv) in solvent
b
(2 mL) at 80 °C for 4 h unless otherwise noted. The starting material
Consequently, a proposed mechanism was depicted in
Scheme 3. First, the redox reaction between copper powder
and Selectfluor may produce a cationic copper species FCu(II)BF4 7
and release a base 8.16,23 Then activation of the CC moiety of
1a by 7 followed by the nucleophilic addition of H2O18 to the
CC bond and the abstraction of a proton by the base 8 resulted
in the formation of intermediates 9 and 11.16,18a On the other
hand, in our previous work,16 we have disclosed that 7 may be
transferred into a copper species 10 in the presence of H2O18
under the basic conditions. Thus, an oxycupration of the CC
bond in 1a by 10 via an inner-sphere model could alternatively
generate the intermediate 11.16 Compound 11 could be
transferred into 12 under the basic conditions. Subsequently, 12
underwent reductive elimination to give an epoxide intermediate
[O18]-4.24 An oxycupration of the triple bond in [O18]-4 by 7
and/or 10 followed by a ring-opening of the epoxide moiety in 13
gave an intermediate 14.16 Compound 14 underwent the
alkoxide-based β-carbon elimination to deliver an intermediate
15 and benzoyl fluoride 3a. This alkoxide-based β-carbon
elimination may also proceed via a radical process in the presence
of Selectfluor.25 Finally, the aromatization of 15 under oxidative
conditions gave [O18]2-2a.13a On the other hand, 14 may also be
isomerized into 18 via an oxygen-exchanging process. Compound
18 underwent the β-carbon elimination in the presence of
Selectfluor and could thus give products [O18]-2a and [O18]-3a.
In addition, a reaction pathway to 2a involving the formation of an
intermediate 19 could not be completely excluded.
could not be completely consumed.
bearing aromatic alkyne moieties, the reaction generally
proceeded well to furnish 3-formyl-1-indenones 2 in moderate
to good yields (54−82%, entries 1−4, 6−13, Table 2) except
that (4-ethoxyphenyl)ethynyl-substituted chalcone 1e gave a
complex mixture (entry 5, Table 2). It was found that alkyne
moieties bearing electron-deficient aryl rings generally gave
better yields of 2 than those substituted with electron-rich ones
(entries 6−13 vs 2−4, Table 2). Note that aromatic alkyne
moieties bearing substitutents at different positions on the
phenyl ring afforded the desired products in similar percent
yields (entries 6−8; 9−11; 12 and 13, Table 2). An n-hexynyl-
and a cyclopropylethynyl-substituted chalcone 1n and 1o failed
to give the desired products (entries 14 and 15, Table 2).
Next, a variety of chalcones 2 with different substitutents on
both aromatic rings A and B were examined under the standard
reaction conditions (Table 3). Substrates bearing both electron-
donating (1p−s,w) and electron-withdrawing substituents (1t−
v, x−2a) on the aromatic ring A could be successfully transformed
into the desired products in moderate yields (2p−za, 60−75%).
Note that halo groups on the aromatic ring A and B were well
tolerated under the reaction conditions (2r−v, 2x−z), which
could provide opportunities for further functionalizations.
To examine the effect of different acyl groups in the chalcone
scaffold on the cleavage of the C−C bond, we synthesized
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a
Table 3. Formation of 2 from Various Substituted o-Alkynyl Chalcone 1
a
All reactions were carried out with 1 (0.2 mmol), Cu(0) (5 mol % based on 1), Selectfluor (2 equiv), and NaHCO3 (2 equiv) in solvent (2 mL) at
80 °C for 4 h unless otherwise noted.
recorded on a spectrometer at 25 °C in CDCl3 at 376 MHz, with
CF3COOH as external standard. Chemical shifts (δ) are expressed in
ppm and coupling constants J are given in Hz. The IR spectra were
recorded on an FT-IR spectrometer. GC−MS experiments were
performed with EI source; high-resolution mass spectra (HRMS) were
obtained on a TOF MS instrument with EI source.
Starting Materials. The starting material 1,5-enynes 1 were
synthesized according to the literature procedures.26
Figure 1. Effect of acyl groups on the cleavage of the C−C bond to
Typical Experimental Procedure for the Synthesis of 3-
Formyl-1-indenones 2 from 1. Compound 1 (0.2 mmol), Cu(0)
powder (0.64 mg, 5 mol %), Selectfluor (141.7 mg, 0.4 mmol, 2
equiv), NaHCO3 (33.6 mg, 0.4 mmol, 2 equiv), and CH3CN/H2O =
150:1 (v/v, 2 mL) were added to a 10 mL flask. Then the reaction
mixture was stirred at 80 °C for 4 h. Upon completion, the resulting
mixture was diluted with CH2Cl2 (10 mL) and filtered through Celite.
After evaporation of the solvent under vacuum, the residue was
purified by column chromatography on silica gel (100−200 mesh)
using petroleum ether/EtOAc (10/1, v/v) as the eluent to give pure 2.
1-Oxo-2-phenyl-1H-indene-3-carbaldehyde (2a):19a
produce 2a under the standard reaction conditions.
CONCLUSION
■
In summary, we have described an unusual copper-catalyzed
oxidative cyclization of 1,5-enynes with concomitant C−C
bond cleavage. The present procedure enabled simultaneous
formation of one C−C, one C−F, and two CO bonds as well
as cleavage of one C−C bond merely in a single synthetic step
by a single copper catalyst. To the best of our knowledge, this
is the first example of water-participated oxygen-insertion
β-carbon elimination and the oxidative cleavage of a single
C−C bond into a CO and a C−F bond.12,13 In addition, the
application of this copper-catalyzed oxygen-insertion β-carbon
elimination in other organic synthesis is currently underway in
our laboratory.
orange solid (33.7 mg, 72%); Rf = 0.48 (petroleum ether/EtOAc, 6:1);
mp 155.6−156.9 °C; IR (neat, cm−1): ν = 1722 (CO); H NMR
1
EXPERIMENTAL SECTION
■
(CDCl3, 500 MHz) 10.33 (s, 1H), 8.01 (d, J = 7.0 Hz, 1H), 7.65
(d, J = 7.0 Hz, 1H), 7.57−7.49 (m, 6H), 7.36−7.33 (m, 1H); 13C{1H}
NMR (CDCl3, 125 MHz) δ 196.9, 191.0, 145.0, 143.7, 142.3, 134.7,
130.7, 130.5, 129.5, 129.3, 128.7, 128.1, 124.23, 124.17; GC−MS (EI,
70 eV) m/z = 234 (100) [M+].
General Information. Unless otherwise stated, all reagents were
purchased from commercial suppliers and used without purifications.
Melting points are uncorrected. The H and 13C NMR spectra were
1
recorded on a spectrometer at 25 °C in CDCl3 at 500 MHz, 125 MHz,
respectively, with TMS as internal standard. 19F NMR spectra were
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Scheme 2. Preliminary Mechanistic Studies
1-Oxo-2-o-tolyl-1H-indene-3-carbaldehyde (2b):
500 MHz) δ 10.33 (s, 1H), 8.0 (d, J = 7.0 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H),
7.50−7.32 (m, 6H), 2.69 (t, J = 7.5 Hz, 2H), 1.68 (m, 2H), 1.38−1.35 (m,
4H), 0.93 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 197.2,
191.2, 146.2, 145.2, 143.1, 142.6, 134.7, 130.7, 129.6, 129.1, 128.9, 125.6,
124.2, 124.1, 36.0, 31.5, 30.9, 22.5, 14.0; GC−MS (EI, 70 eV) m/z = 304
(100) [M+]; HRMS (EI) for C21H20O2 calcd 304.1463, found 304.1456.
2-(2-Fluorophenyl)-1-oxo-1H-indene-3-carbaldehyde (2f):
orange solid (29.8 mg, 60%); Rf = 0.47 (petroleum ether/EtOAc, 6:1);
mp 175−180 °C; IR (neat, cm−1) ν = 1722 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.08 (s, 1H), 8.00 (d, J = 7.5 Hz, 1H), 7.64 (d,
J = 7.5 Hz, 1H), 7.51−7.23 (m, 6H), 2.31 (s, 3H); 13C{1H} NMR
(CDCl3, 125 MHz) δ 196.5, 190.8, 148.2, 145.1, 142.1, 137.5, 134.5,
130.9, 130.8, 130.0, 129.8, 129.3, 127.9, 125.8, 124.3, 124.2, 20.7;
GC−MS (EI, 70 eV) m/z = 248 (100) [M+]; HRMS (EI) for
C17H12O2 calcd 248.0837, found 248.0843.
orange solid (41.4 mg, 82%); Rf = 0.47 (petroleum ether/EtOAc, 6:1);
mp 150−154 °C; IR (neat, cm−1) ν =1716 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.24 (d, J = 4.0 Hz, 1H), 8.0 (d, J = 7.5 Hz,
1H), 7.65 (d, J = 7.5 Hz, 1H), 7.52−7.22 (m, 6H); 13C{1H} NMR
(125 MHz, CDCl3) δ 195.6, 190.2 (d, J = 5.0 Hz), 160.6 (d, J = 247.5
Hz), 145.0, 142.0, 139.0, 134.5, 132.3, 131.9 (d, J = 8.8 Hz), 129.9,
129.5, 124.42, 124.38, (d. J = 3.8 Hz), 124.2, 116.4 (d. J = 15.0 Hz),
116.2 (d. J = 21.3 Hz); 19F NMR (CDCl3, 376 MHz) δ −112.7; GC−
MS (EI, 70 eV) m/z = 252 (100) [M+]; HRMS (EI) for C16H9FO2
calcd 252.0587, found 252.0594.
1-Oxo-2-p-tolyl-1H-indene-3-carbaldehyde (2c):
orange solid (31.8 mg, 64%); Rf = 0.49 (petroleum ether/EtOAc, 6:1);
mp 123−127 °C; IR (neat, cm−1): ν = 1714 (CO); 1H NMR (CDCl3,
500 MHz) δ 10.32 (s, 1H); 8.00 (d, J = 7.5 Hz, 2H), 7.64 (d, J = 7.0 Hz,
1H), 7.49−7.33 (m, 6H), 2.46 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 197.2, 191.1, 145.2, 143.1, 141.2, 134.7, 130.7, 129.7, 129.5,
129.1, 128.8, 125.4, 124.2, 124.1, 21.6; GC−MS (EI, 70 eV) m/z = 248
(100) [M+]; HRMS (EI) for C17H12O2 calcd 248.0837, found 248.0841.
1-Oxo-2-(4-pentylphenyl)-1H-indene-3-carbaldehyde (2d):
2-(3-Fluorophenyl)-1-oxo-1H-indene-3-carbaldehyde (2g):
orange solid (40.4 mg, 80%); Rf = 0.48 (petroleum ether/EtOAc, 6:1);
mp 107−113 °C; IR (neat, cm−1) ν = 1717 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.34 (s, 1H), 8.0 (d, J = 7.5 Hz, 1H), 7.65 (d,
J = 7.0 Hz, 1H), 7.52−7.24 (m, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ 196.3, 190.5, 162.7 (d, J = 246.3 Hz), 144.4, 143.4, 142.0,
134.8, 130.4 (d, J = 8.8 Hz), 130.1 (d, J = 7.5 Hz), 129.7, 129.5, 126.5
orange solid (32.9 mg, 54%); Rf = 0.50 (petroleum ether/EtOAc, 6:1);
1
mp 58−63 °C; IR (neat, cm−1) ν =1720 (CO); H NMR (CDCl3,
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Scheme 3. Proposed Mechanism
(d, J = 3.8 Hz), 124.44, 124.41, 117.6, 117.4; 19F NMR (CDCl3, 376
MHz) δ −112.0; GC−MS (EI, 70 eV) m/z = 252 (100) [M+]; HRMS
(EI) for C16H9FO2 calcd 252.0587, found 252.0591.
(CDCl3, 500 MHz) δ 10.31 (s, 1H), 7.99 (d, J = 7.5 Hz, 1H), 7.64 (d, J =
7.0 Hz, 1H), 7.58−7.21 (m, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ
196.8, 190.6, 164.3 (d, J = 251.3 Hz), 143.8, 143.5, 142.2, 134.8, 132.7 (d,
J = 8.8 Hz), 129.4, 124.34, 124.30, 124.28, 124.24, 116.1 (d, J = 22.5 Hz);
19F NMR (CDCl3, 376 MHz) δ −109.0; GC−MS (EI, 70 eV) m/z = 252
(100) [M+]; HRMS (EI) for C16H9FO2 calcd 252.0587, found 252.0593.
2-(2-Chlorophenyl)-1-oxo-1H-indene-3-carbaldehyde (2i):
2-(4-Fluorophenyl)-1-oxo-1H-indene-3-carbaldehyde (2h):
orange solid (39.8 mg, 79%); Rf = 0.47 (petroleum ether/EtOAc, 6:1);
mp 150−154 °C; IR (neat, cm−1) ν = 1715 (CO); 1H NMR
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orange solid (38.2 mg, 71%), Rf = 0.50 (petroleum ether/EtOAc, 6:1);
mp 142−150 °C; IR (neat, cm−1) ν = 1714 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.33 (s, 1H), 8.0 (d, J = 7.5 Hz, 1H), 7.66
(d, J = 7.0 Hz, 1H), 7.56−7.35 (m, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ 196.2, 190.4, 144.5, 143.3, 142.0, 134.9, 134.8, 130.5, 130.4,
130.0, 129.9, 129.6, 129.5, 128.8, 124.5, 124.4; GC−MS (EI, 70 eV)
m/z = 268 (100) [M+]; HRMS (EI) for C16H9ClO2 calcd 268.0291,
found 268.0287.
7.56−7.29 (m, 7H), 2.40 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 197.2, 191.1, 144.5, 144.0, 139.7, 139.5, 134.8, 130.6, 130.3, 129.9,
128.7, 128.3, 125.2, 124.0, 21.3; GC−MS (EI, 70 eV) m/z = 248 (100)
[M+]; HRMS (EI) for C17H12O2 calcd 248.0837, found 248.0834.
6-Methyl-1-oxo-2-p-tolyl-1H-indene-3-carbaldehyde (2q):
2-(3-Chlorophenyl)-1-oxo-1H-indene-3-carbaldehyde (2j):
red solid (39.3 mg, 75%); Rf = 0.53 (petroleum ether/EtOAc, 6:1);
mp 100−108 °C; IR (neat, cm−1) ν = 1718 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.30 (s, 1H); 7.85 (d, J = 7.5 Hz, 1H), 7.46−
7.27 (m, 6H), 2.45 (s, 3H), 2.39 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 197.5, 191.1, 144.6, 143.3, 140.9, 139.7, 139.4, 134.7, 130.6, 129.9,
129.5, 125.5, 125.1, 123.8, 21.5, 21.3; GC−MS (EI, 70 eV) m/z = 262
(100) [M+]; HRMS (EI) for C18H14O2 calcd 262.0994, found 262.0986.
2-(4-Fluorophenyl)-6-methyl-1-oxo-1H-indene-3-carbaldehyde (2r):
orange solid (39.2 mg, 73%), Rf = 0.51 (petroleum ether/EtOAc, 6:1);
mp 98−105 °C; IR (neat, cm−1) ν = 1723 (CO); 1H NMR (CDCl3,
500 MHz) δ 10.14 (s, 1H), 8.01 (d, J = 7.0 Hz, 1H), 7.65 (d, J = 7.0
Hz, 1H), 7.56−7.34 (m, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ
195.5, 190.2, 145.6, 143.9, 141.7, 134.6, 134.2, 132.1, 131.1, 130.3,
129.8, 129.7, 127.7, 126.8, 124.6, 124.4; GC−MS (EI, 70 eV) m/z =
268 (100) [M+]; HRMS (EI) for C16H9ClO2 calcd 268.0291, found
268.0295.
2-(4-Chlorophenyl)-1-oxo-1H-indene-3-carbaldehyde (2k):
red solid (36.2 mg, 68%); Rf = 0.45 (petroleum ether/EtOAc, 6:1);
mp 158−163 °C; IR (neat, cm−1) ν = 1719 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.29 (s, 1H), 7.85 (d, J = 7.5 Hz, 1H), 7.56−
7.54 (m, 2H), 7.46 (s, 1H), 7.29−7.20 (m, 3H), 2.40 (s, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 197.1, 190.6, 164.1 (d, J = 251.3 Hz),
143.8, 143.2, 139.8, 139.4, 134.9, 132.6 (d, J = 8.8 Hz), 129.7, 125.2,
124.4 (d, J = 2.5 Hz), 124.0, 116.0 (d, J = 22.5 Hz), 21.3; 19F NMR
(CDCl3, 376 MHz) δ −109.4; GC−MS (EI, 70 eV) m/z = 266 (100)
[M+]; HRMS (EI) for C17H11FO2 calcd 266.0743, found 266.0750.
2-(4-Chlorophenyl)-6-methyl-1-oxo-1H-indene-3-carbaldehyde (2s):
red solid (38.7 mg, 72%); Rf = 0.53 (petroleum ether/EtOAc, 6:1);
mp 145−150 °C; IR (neat, cm−1) ν = 1717 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.31 (s, 1H), 8.0 (d, J = 7.5 Hz, 1H), 7.65
(d, J = 7.0 Hz, 1H), 7.51−7.34 (m, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ 196.5, 190.4, 143.9, 143.6, 142.1, 137.1, 134.8, 131.9,
129.53, 129.45, 129.2, 126.6, 124.4, 124.3; GC−MS (EI, 70 eV) m/z =
268 (100) [M+]; HRMS (EI) for C16H9ClO2 calcd 268.0291, found
268.0294.
2-(3-Bromophenyl)-1-oxo-1H-indene-3-carbaldehyde (2l):
red solid (41.3 mg, 73%); Rf = 0.44 (petroleum ether/EtOAc, 6:1);
mp 155−159 °C; IR (neat, cm−1) ν = 1719 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.29 (s, 1H); 7.85 (d, J = 7.5 Hz, 1H), 7.49 (s,
4H), 7.45 (s, 1H), 7.29 (d, J = 8.0 Hz, 1H), 2.40 (s, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 196.8, 190.5, 144.2, 143.0, 139.9, 139.3,
136.8, 134.9, 131.8, 129.1, 126.7, 125.3, 124.1, 21.4; GC−MS
(EI, 70 eV) m/z = 282 (100) [M+]; HRMS (EI) for C17H11ClO2
calcd 282.0448, found 282.0452.
red solid (45.1 mg, 72%); Rf = 0.53 (petroleum ether/EtOAc, 6:1);
mp 125−129 °C; IR (neat, cm−1) ν = 1720 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.31 (s, 1H), 7.99 (d, J = 7.5 Hz, 1H), 7.67−
7.33 (m, 7H); 13C{1H} NMR (125 MHz, CDCl3) δ 196.4, 190.4,
143.9, 143.6, 142.1, 134.8, 134.5, 132.1, 132.0, 129.5, 129.4, 127.4,
127.0, 125.4, 124.34, 124.31; GC−MS (EI, 70 eV) m/z = 312 (100)
[M+]; HRMS (EI) for C16H9BrO2 calcd 311.9786, found 311.9792.
2-(4-Bromophenyl)-1-oxo-1H-indene-3-carbaldehyde (2m):
6-Fluoro-1-oxo-2-phenyl-1H-indene-3-carbaldehyde (2t):
orange solid (33.8 mg, 67%); Rf = 0.52 (petroleum ether/EtOAc, 6:1);
mp 130−133 °C; IR (neat, cm−1) ν = 1723 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.31 (s, 1H), 7.99 (dd, J1 = 8.0 Hz, J2 = 4.5 Hz,
1H), 7.56−7.53 (m, 5H), 7.35−7.34 (m, 1H), 7.18−7.14 (m, 1H);
13C{1H} NMR (125 MHz, CDCl3) δ 195.7, 190.8, 163.7 (d, J = 250
Hz), 145.1 (d, J = 3.8 Hz), 143.4, 137.9 (d, J = 3.8 Hz), 131.8 (d, J =
7.5 Hz), 130.7, 130.6, 128.8, 127.9, 125.5 (d, J = 8.8 Hz), 120.2 (d, J =
21.3 Hz), 112.4 (d, J = 25.0 Hz); 19F NMR (CDCl3, 376 MHz) δ
−110.9; GC−MS (EI, 70 eV) m/z = 252 (100) [M+]; HRMS (EI) for
C16H9FO2 calcd 252.0587, found 252.0584.
red solid (44.5 mg, 71%); Rf = 0.54 (petroleum ether/EtOAc, 6:1);
mp 128−132 °C; IR (neat, cm−1) ν = 1717 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.31 (s, 1H), 8.0 (d, J = 7.5 Hz, 1H), 7.68−
7.34 (m, 7H); 13C{1H} NMR (125 MHz, CDCl3) δ 197.2, 190.8,
144.1, 143.6, 142.3, 135.1, 132.1, 132.0, 129.7, 129.6, 127.2, 125.6,
124.64, 124.55; GC−MS (EI, 70 eV) m/z = 312 (100) [M+]; HRMS
(EI) for C16H9BrO2 calcd 311.9786, found 311.9790.
6-Methyl-1-oxo-2-phenyl-1H-indene-3-carbaldehyde (2p):
6-Fluoro-2-(4-fluorophenyl)-1-oxo-1H-indene-3-carbaldehyde (2u):
red solid (35.8 mg, 72%); Rf = 0.46 (petroleum ether/EtOAc, 6:1);
mp 125−130 °C; IR (neat, cm−1) ν = 1715 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.30 (s, 1H), 7.85 (d, J = 7.5 Hz, 1H),
yellow solid (39.4 mg, 73%); Rf = 0.50 (petroleum ether/EtOAc, 6:1);
mp 175−180 °C; IR (neat, cm−1) ν = 1718 (CO); 1HNMR
(CDCl3,500 MHz) δ 10.30 (s, 1H), 7.99 (dd, J1 = 8.0 Hz, J2 = 4.5 Hz, 1H),
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7.57−7.15 (m, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 195.5,
190.3, 164.3 (d, J = 251.3 Hz), 163.7 (d, J = 250 Hz), 143.7 (d, J = 3.8
Hz), 143.2, 137.7 (d, J = 3.8 Hz), 132.6 (d, J = 8.8 Hz), 125.6 (d, J =
7.5 Hz), 124.0 (d, J = 2.5 Hz), 120.3 (d, J = 22.5 Hz), 116.2 (d, J =
21.5 Hz), 112.5, 112.4; 19F NMR (CDCl3, 376 MHz) δ −108.8,
−110.7; GC−MS (EI, 70 eV) m/z = 270 [M+]; HRMS (EI) for
C16H8F2O2 calcd 270.0492, found 270.0498.
1H NMR (CDCl3, 500 MHz) δ 10.30 (s, 1H), 8.21 (s, 1H), 7.56−7.51
(m, 7H); 13C{1H} NMR (125 MHz, CDCl3) δ 195.6, 190.5, 145.8,
144.0, 142.5, 132.2, 130.9, 130.8, 129.8, 128.9, 128.2, 127.8, 127.7,
125.2; GC−MS (EI, 70 eV) m/z = 312 (100) [M+]; HRMS (EI) for
C16H9BrO2 calcd 311.9786, found 311.9792.
5-(Trifluoromethyl)-2-phenyl-1-oxo-1H-indene-3-carbaldehyde
(2za:).
6-Chloro-1-oxo-2-phenyl-1H-indene-3-carbaldehyde (2v):
Reddish orange solid (41.1 mg, 68%), Rf = 0.44 (petroleum ether/
EtOAc, 10:1); mp 175−177 °C; IR (neat, cm−1) ν = 1726 (CO);
1H NMR (CDCl3, 500 MHz) δ 10.36 (s, 1H), 8.30 (s, 1H), 7.75 (d,
J = 7.5 Hz, 1H), 7.66 (d, J = 7.5 Hz, 1H), 7.59−7.56 (m, 5H);
13C{1H} NMR (125 MHz, CDCl3) δ 195.8, 190.5, 145.5, 143.0, 142.7,
136.1 (J = 32.5 Hz), 132.1, 131.0, 130.8, 128.9, 127.6, 126.8 (J = 3.8
Hz), 124.1, 123.4 (J = 271.3 Hz), 121.0 (J = 3.8 Hz); 19F NMR
(CDCl3, 376 MHz) δ −64.1; GC−MS (EI, 70 eV) m/z = 302 (100)
[M+]; HRMS (EI) for C17H9F3O2 calcd 302.0555, found 302.0561.
Mechanistic Studies. Reaction of 1a in CH3CN−H2O18 (150:1, v/v)
vs in CH3CN−H2O (150:1, v/v). Procedure A. 1a (61.7 mg, 0.2 mmol),
Cu(0) powder (0.64 mg, 5 mol %), Selectfluor (141.7 mg, 0.4 mmol,
2 equiv), NaHCO3 (33.6 mg, 0.4 mmol, 2 equiv), and CH3CN:H2O =
150:1 (v/v, 2 mL) were added to a 10 mL flask. Then the reaction
mixture was stirred at 80 °C for 4 h. Upon completion, the resulting
mixture was sampled for GC−MS analysis (see Figures S1 and S2,
Supporting Information).
Procedure B. 1a (61.7 mg, 0.2 mmol), Cu(0) powder (0.64 mg,
5 mol %), Selectfluor (141.7 mg, 0.4 mmol, 2 equiv), NaHCO3
(33.6 mg, 0.4 mmol, 2 equiv), and CH3CN:H2O18 = 150:1 (v/v, 2 mL)
were added to a 10 mL flask. Then the reaction mixture was stirred at
80 °C for 4 h. Upon completion, the resulting mixture was sampled for
GC−MS analysis (see Figures S3 and S4, Supporting Information).
Reaction of 4 under the Standard Reaction Conditions.
orange oil (32.2 mg, 60%); Rf = 0.45 (petroleum ether/EtOAc, 10:1); IR
(neat, cm−1) ν = 1721 (CO); 1H NMR (CDCl3, 500 MHz) δ 10.32 (s,
1H), 7.96 (d, J = 7.5 Hz, 1H), 7.61−7.46 (m, 7H); 13C{1H} NMR (125
MHz, CDCl3) δ 195.7, 190.7, 144.8, 143.3, 140.4, 135.6, 134.0, 131.7,
130.8, 130.7, 128.9, 128.6, 125.2, 124.7; GC−MS (EI, 70 eV) m/z = 268
(100) [M+]; HRMS (EI) for C16H9ClO2 calcd 268.0291, found 268.0287.
5-Methoxy-1-oxo-2-phenyl-1H-indene-3-carbaldehyde (2w):
red solid (34.9 mg, 66%); Rf = 0.45 (petroleum ether/EtOAc, 6:1);
mp 158−163 °C; IR (neat, cm−1) ν = 1719 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.28 (s, 1H), 7.62−7.52 (m, 7H), 6.75 (dd, J1 =
8.0 Hz, J2 = 2.5 Hz, 2H), 3.94 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 197.1, 190.9, 168.8, 152.0, 151.9, 140.1, 134.8, 130.6, 130.3,
129.0, 128.7, 127.8, 113.5, 112.5, 59.1; GC−MS (EI, 70 eV) m/z = 264
(100) [M+]; HRMS (EI) for C17H12O3 calcd 264.0786, found 264.0792.
5-Fluoro-2-(4-fluorophenyl)-1-oxo-1H-indene-3-carbaldehyde (2x):
orange solid (35.7 mg, 66%); Rf = 0.51 (petroleum ether/EtOAc, 6:1);
mp 144−146 °C; IR (neat, cm−1) ν = 1718 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.29 (s, 1H), 7.75 (dd, J1 = 8.5 Hz, J2 = 2.0 Hz, 1H),
7.66−7.56 (m, 3H), 7.26−7.22 (m, 2H), 7.01−6.98 (m, 1H); 13C{1H}
NMR (125 MHz, CDCl3) δ 194.8, 190.0, 166.8 (d, J = 255 Hz), 164.5 (d, J
= 251.3 Hz), 145.4 (d, J = 10 Hz), 144.9, 141.6, 132.8 (d, J = 7.5 Hz), 126.3
(d, J = 10 Hz), 125.3 (d, J = 2.5 Hz), 124.0 (d, J = 3.8 Hz), 116.3 (d, J =
21.3 Hz), 115.4 (d, J = 22.5 Hz), 113.1 (d, J = 26.3 Hz); 19F NMR (CDCl3,
376 MHz) δ −101.1, −108.3; GC−MS (EI, 70 eV) m/z = 270 (100) [M+];
HRMS (EI) for C16H8F2O2 calcd 270.0492, found 270.0487.
Compound 4 was prepared according to a modified procedure of a
reported literature.27 Procedure: (E)-1-phenyl-3-(2-(phenylethynyl)-
phenyl)prop-2-en-1-one 1a (92.5 mg, 0.3 mmol) and THF (2 mL)
were added to a screw vial equipped with a magnetic stirring bar. Urea
hydrogenperoxide (31 mg, 0.33 mmol) and DBU (11.3 μL, 1.68 mmol)
were added at 0 °C, and the mixture was gradually warmed to room
temperature. After being stirred for 24 h, the reaction mixture was
diluted with AcOEt and washed with saturated aqueous Na2S2O3. Then
the organic layer was evaporated to give an oily residue, which was
purified by silica gel column chromatography (petroleum ether/EtOAc,
6:1, v/v) to afford 4 as a white solid (77.9 mg, 80% yield).
5-Chloro-2-(4-fluorophenyl)-1-oxo-1H-indene-3-carbaldehyde (2y):
orange solid (39.6 mg, 69%); Rf = 0.49 (petroleum ether/EtOAc, 6:1);
mp 150−155 °C; IR (neat, cm−1) ν = 1716 (CO); 1H NMR
(CDCl3, 500 MHz) δ 10.29 (s, 1H), 8.03 (d, J = 1.5 Hz, 1H), 7.59−
7.22 (m, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 195.2, 190.0,
164.5 (d, J = 252.5 Hz), 144.6, 143.9, 142.3, 141.2, 132.8 (d, J = 8.8
Hz), 129.2, 127.5, 125.1, 125.0, 124.0 (d, J = 2.5 Hz), 116.3 (d, J =
22.5 Hz); 19F NMR (CDCl3, 376 MHz) δ −108.3; GC−MS (EI,
70 eV) m/z = 286 (100) [M+]; HRMS (EI) for C16H8ClFO2 calcd
286.0197, found 286.0189.
Analytical data for 4: white solid; Rf = 0.55 (petroleum ether/
EtOAc, 6:1); mp 95−100 °C; IR (neat, cm−1) ν = 3010, 1651, 1490,
1
1305, 990, 800, 755, 570; H NMR (500 MHz, CDCl3) δ 8.09−8.08
(m, 2H), 7.59−7.12 (m, 12H), 4.60 (d, J = 2.0 Hz, 1H), 4.27 (d, J =
2.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 193.2, 139.9, 137.5,
135.3, 133.9, 131.9, 131.4, 128.8, 128.5, 128.42, 128.39, 128.2, 124.2,
122.4, 95.2, 85.9, 58.4 (2C); GC−MS (EI, 70 eV) m/z = 324(100)
[M+]; HRMS (EI) for C23H16O2 calcd 324.1150, found 324.1156.
Reaction of 4 under the Standard Reaction Conditions.
Compound 4 (64.9 mg, 0.2 mmol), Cu(0) powder (0.64 mg, 5 mol
%), Selectfluor (141.7 mg, 0.4 mmol, 2 equiv), NaHCO3 (33.6 mg,
0.4 mmol, 2 equiv), and CH3CN/H2O = 150:1 (v/v, 2 mL) were
added to a 10 mL flask. Then the reaction mixture was stirred at 80 °C
for 4 h. Upon completion, the resulting mixture was diluted with
CH2Cl2 (10 mL) and filtered through Celite. After evaporation of
the solvent under vacuum, the residue was purified by column
5-Bromo-2-phenyl-1-oxo-1H-indene-3-carbaldehyde (2z):
reddish yellow solid (39.5 mg, 63%); Rf = 0.49 (petroleum ether/
EtOAc, 10:1); mp 163−165 °C; IR (neat, cm−1) ν = 1721 (CO);
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chromatography on silica gel (100−200 mesh) using petroleum ether/
EtOAc (10/1, v/v) as eluent to give pure 2a (28.1 mg, 60% yield).
Reaction of 5 under the Standard Reaction Conditions and
18O-Labeling Experiment.
Org. Biomol. Chem. 2009, 7, 2835. (g) Cramer, N.; Seiser, T. Synlett
2011, 449. (h) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610. (i) Tobisu,
M.; Chatani, N. Chem. Soc. Rev. 2008, 37, 300. (j) Crabtree, R. H.
Nature 2000, 408, 415. (k) Murakami, M.; Ito, Y. In Activation of
Unreactive Bonds and Organic Synthesis; Murai, S., Ed., Springer: Berlin,
1999; p 97. (l) Crabtree, R. H. Chem. Rev. 1985, 85, 245.
(2) For some very recent examples, see: (a) Zhang, C.; Feng, P.; Jiao,
N. J. Am. Chem. Soc. 2013, 135, 15257 and references cited therein.
(b) Zhou, W.; Yang, Y.; Liu, Y.; Deng, G.-J. Green Chem. 2013, 15, 76.
(c) Bowring, M. A.; Bergman, R. G.; Tilley, T. D. J. Am. Chem. Soc.
2013, 135, 13121. (d) Souillart, L.; Cramer, N. Chem. Sci. 2014, 5, 837.
(e) Ogata, K.; Shimada, D.; Furuya, S.; Fukuzawa, S.-I. Org. Lett. 2013,
15, 1182. (f) Zhu, Y.; Yan, H.; Lu, L.; Liu, D.; Rong, G.; Mao, J. J. Org.
Chem. 2013, 78, 9898. (g) Bour, J. R.; Green, J. C.; Winton, V. J.;
Johnson, J. B. J. Org. Chem. 2013, 78, 1665. (h) Xu, F.; Tao, T.; Zhang,
K.; Wang, X.-X.; Huang, W.; You, X.-Z. Dalton Trans. 2013, 42, 3631.
(i) Ziadi, A.; Correa, A.; Martin, R. Chem. Commun. 2013, 49, 4286.
(3) For examples on C−C bond activations via strategy of oxidative
addition involving transition metals, see: (a) Najera, C.; Sansano, J. M.
Angew. Chem. 2009, 121, 2488; Angew. Chem., Int. Ed. 2009, 48, 2452
and references cited therein. (b) Hirata, Y.; Yada, A.; Morita, E.;
Nakao, Y.; Hiyama, T.; Ohashi, M.; Ogoshi, S. J. Am. Chem. Soc. 2010,
132, 10070. (c) Murakami, M.; Amii, H.; Ito, Y. Nature 1994, 370, 540.
(d) Murakami, M.; Tsuruta, T.; Ito, Y. Angew. Chem. 2000, 112, 2600;
Angew. Chem., Int. Ed. 2000, 39, 2484. (e) Liou, S.-Y.; van der Boom,
M. E.; Milstein, D. Chem. Commun. 1998, 687. (f) Kondo, T.;
Nakamura, A.; Okada, T.; Suzuki, N.; Wada, K.; Mitsudo, T.-A. J. Am.
Chem. Soc. 2000, 122, 6319. (g) Kondo, T.; Kaneko, Y.; Taguchi, Y.;
Nakamura, A.; Okada, T.; Shiotsuki, M.; Ura, Y.; Wada, K.; Mitsudo,
T.-A. J. Am. Chem. Soc. 2002, 124, 6824.
Procedure: chalcone 5 (41.7 mg, 0.2 mmol), Cu(0) powder (0.64 mg,
5 mol %), Selectfluor (141.7 mg, 0.4 mmol, 2 equiv), NaHCO3
(33.6 mg, 0.4 mmol, 2 equiv), and CH3CN/H2O = 150:1 (v/v, 2 mL)
were added to a 10 mL flask. Then the reaction mixture was stirred at
80 °C for 4 h. Upon completion, the resulting mixture was diluted with
CH2Cl2 (10 mL) and filtered through Celite. After evaporation of the
solvent under vacuum, the residue was purified by column
chromatography on silica gel (100−200 mesh) using petroleum
ether/EtOAc (8/1, v/v) as eluent to give pure 6 in 88% yield. Using
CH3CN/H2O18 = 150:1 (v/v) as a medium under otherwise identical
conditions as the above procedure, the 18O-incorporated product
[O18]-6 was obtained. The GC−MS spectra of 6 and [O18]-6 are
shown in Figure S5, Supporting Information.
Analytical data of 6: white solid (39.4 mg, 88%); Rf = 0.55
(petroleum ether/EtOAc, 8:1); mp 88−89 °C; IR (neat, cm−1) ν =
1
1690 (CO); H NMR (500 MHz, CDCl3) δ 8.03 (dd, J1 = 7.5 Hz,
J2 = 0.5 Hz, 2H), 7.64 (t, J = 7.5 Hz, 1H), 7.51 (t, J = 8.0 Hz, 2H),
7.43−7.39 (m, 5H), 4.32 (d, J = 2.0 Hz, 1H), 4.10 (d, J = 2.0 Hz, 1H);
GC−MS (EI, 70 eV) m/z = 224(10) [M+].
Effect of Radical Scavenger TEMPO on the Model Reaction.
Procedure 1a (61.7 mg, 0.2 mmol), Cu(0) powder (0.64 mg, 5 mol
%), Selectfluor (141.7 mg, 0.4 mmol, 2 equiv), NaHCO3 (33.6 mg,
0.4 mmol, 2 equiv), TEMPO (6.25 mg, 0.2 equiv; or 93.8 mg,
3 equiv), and CH3CN/H2O = 150:1 (v/v, 2 mL) were added to a
10 mL flask. Then the reaction mixture was stirred at 80 °C for 4 h.
Upon completion, the resulting mixture was diluted with CH2Cl2
(10 mL) and filtered through Celite. After evaporation of the solvent
under vacuum, the residue was purified by column chromatography on
silica gel (100−200 mesh) using petroleum ether/EtOAc (10/1, v/v)
as eluent to give pure 2a. In the presence of 0.2 and 3 equiv of
TEMPO, 2a was obtained in 65% and 0% yield, respectively.
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(c) Chen, K.; Li, H.; Li, Y.; Zhang, X.-S.; Lei, Z.-Q.; Shi, Z.-J. Chem.
Sci. 2012, 3, 1645. (d) Chen, K.; Li, H.; Lei, Z.-Q.; Li, Y.; Ye, W.-H.;
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ASSOCIATED CONTENT
■
S
* Supporting Information
Charts for mechanistic studies as well as copies of H and 13C
1
NMR spectra of the products. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ykuiliu@zjut.edu.cn.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the Natural Science Foundation of China
(Nos. 21172197 and 21372201), Zhejiang Province (Grant No.
Y407168), and the Opening Foundation of Zhejiang Key
Course of Chemical Engineering and Technology, Zhejiang
University of Technology, for financial support.
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