Nickel catalyzed α-arylation of ketones with aryltrimethylammonium triflates

Article abstract of DOI:10.1039/c6ob01299j

Nickel-catalyzed α-arylation of ketones involving aromatic C-N cleavage has been accomplished. Intermolecular coupling of aromatic ketones with a variety of aryltrimethylammonium triflates was achieved in the presence of Ni(COD)₂, IPr·HCl, and LiOBu^t, giving α-arylated ketones in reasonable to excellent yields.

Full text of DOI:10.1039/c6ob01299j

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Nickel catalyzed α-arylation of ketones with
aryltrimethylammonium triflates†
Cite this: DOI: 10.1039/c6ob01299j
Jing Lia and Zhong-Xia Wang*a,b
Received 16th June 2016,
Accepted 18th July 2016
Nickel-catalyzed α-arylation of ketones involving aromatic C–N cleavage has been accomplished. Inter-
molecular coupling of aromatic ketones with a variety of aryltrimethylammonium triflates was achieved in
the presence of Ni(COD)2, IPr·HCl, and LiOBut, giving α-arylated ketones in reasonable to excellent yields.
DOI: 10.1039/c6ob01299j
www.rsc.org/obc
Although palladium-based catalysts were widely applied,
the use of nickel is more ideal due to its low cost and more
Introduction
Transition metal-catalyzed α-arylation of carbonyl compounds earth-abundance.11 In 2002, Buchwald and co-workers initially
is of high importance, as the resulting α-aryl carbonyl com- employed Ni(COD)2/BINAP to catalyze the α-arylation of
pounds are common structural motifs in pharmaceutical and γ-butyrolactones,12 showing that nickel is an excellent palla-
other biologically active molecules.1 After the pioneering dium surrogate. Later, Chan,13 Hartwig,4b,14 and Martin5b
studies of intermolecular palladium-catalyzed α-arylation of accomplished the asymmetric arylation of ketones using
ketones by the groups of Miura, Buchwald, and Hartwig,2
a
nickel/diphosphine systems. Besides, nickel/NHC (N-hetero-
variety of effective catalytic systems have been developed and cyclic carbenes) also proved to be an efficient combination15
the scope of carbonyl substrates has been extended to esters, especially when dealing with aryl chlorides. Here we report an
amides, and aldehydes, making this reaction an efficient strat- α-arylation of ketones with aryltrimethylammonium triflates
egy to connect between C(sp2) and C(sp3) centers.1d,3 Among using a nickel/NHC catalyst.
these reactions, electrophiles were predominantly aryl halides
and sulfonates of phenols.3,4 Only recently, the Itami group
has reported a challenging α-arylation of ketones with aryl
Results and discussion
pivalates under the catalysis of nickel, albeit a high tempera-
ture is required.5a Martin et al. carried out enantioselective
We started our investigations using the reaction of 4-methoxy-
N,N,N-trimethylbenzenaminium triflate (1a) with propio-
α-arylation of 2-methyl-1-indanone with aryl pivalates catalyzed
by nickel/BINAP.5b
phenone (2a) as a model reaction, and the results are listed in
Table 1. Inspired by previous work,14 we first tested room
In the last few years, we and other groups revealed that
temperature reaction in THF using a combination of Ni(COD)2
and IPr·HCl as the catalyst precursor and LiHMDS as the base
(entry 1). After 10 hours, the 1H NMR spectrum showed that
only about 5% product was formed. Then we tried to elevate
the temperature (entries 2–4). To our delight, it obviously pro-
moted the reaction, giving a 40% yield when the reaction was
run at 80 °C. This positive result encouraged us to optimize
other conditions to further improve the reaction. It was known
that bases strongly affected enolization of ketones which was
crucial to α-arylation. So we screened a series of bases besides
LiHMDS (entries 5–11). The results showed that LiOBut was
superior to other bases including bis(trimethylsilyl)amide
bases, sodium or potassium tert-butoxide, LiOMe and Cs2CO3.
Lithium as a countercation performed better than sodium and
potassium, and surprisingly, KOBut and KHMDS did not work
at all (entries 6 and 9).
aryltrimethylammonium salts can be used as electrophiles in
transition-metal-catalyzed C–C bond-forming reactions includ-
ing reactions with Grignard reagents,6 organozinc reagents,7
aryl boronic acids8 and oxazoles/thioazoles9 and C–B bond-
forming reactions with B2pin2.10 It is of great interest to apply
aryltrimethylammonium salts as electrophilic partners in
α-arylation reaction as it can directly transform aromatic
amines to α-aryl carbonyl compounds.
aCAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, People’s
Republic of China. E-mail: zxwang@ustc.edu.cn; Tel: +86 551 63603043
bCollaborative Innovation Center of Chemical Science and Engineering (Tianjin),
Tianjin 300072, People’s Republic of China
†Electronic supplementary information (ESI) available: Copies of 1H, 13C and
19F NMR spectra and high-resolution mass spectra of the coupling products. See
DOI: 10.1039/c6ob01299j
Other N-heterocyclic carbenes were also used in the cata-
lytic reactions and IPr showed the best efficiency. Switching
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Table 1 The optimization of reaction conditionsa
summarized in Table 2. Propiophenone, 1-(4-methoxyphenyl)
propan-1-one and 1-(4-fluorophenyl)propan-1-one respectively
represent nucleophilic precursors with electron-neutral, elec-
tron-rich, and electron-poor phenyl groups. Each of them
reacted smoothly with aryltrimethylammonium triflates,
resulting in the corresponding cross-coupling products in
41–69% yields. For the activated aryltrimethylammonium tri-
flate, 4-benzoyl-N,N,N-trimethylbenzenaminium triflate, the
reactivity of the three propiophenones showed no difference
(3b–3d). For the deactivated aryltrimethylammonium triflate,
4-methoxy-N,N,N-trimethylbenzenaminium, 1-(4-fluorophenyl)
propan-1-one showed a little lower reactivity (3a and 3e vs. 3f).
It seems that the acidity difference of α-H of propiophenones
resulting from the electron effect of the aromatic rings plays
a minor role in the α-arylation reactions, especially when
activated aromatic ammonium salts were used as the
electrophiles.
(Pro)ligand
(20 mol%)
Yieldb
(%)
Entry
Base (equiv.)
Solvent
1c
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
SIPr·HCl
IMes·HCl
ICy·HCl
PPh3
LiHMDS (1.6)
LiHMDS (1.6)
LiHMDS (1.6)
LiHMDS (1.6)
NaHMDS (1.6)
KHMDS (1.6)
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
5
14
30
40
12
Trace
52
2d
3e
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22g
23h
24
25g,h
LiOBut (1.6)
NaOBut (1.6)
33
KOBut (1.6)
Trace
Trace
Trace
16
Trace
—
Trace
Trace
Trace
46
42
43
40
74
LiOMe (1.6 eq.)
Cs2CO3 (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (1.6 eq.)
LiOBut (2.6 eq.)
LiOBut (3.4 eq.)
On the other hand, both activated and deactivated aryl-
trimethylammonium triflates can react smoothly with
propiophenones. Deactivated p-MeOC6H4NMe3+OTf− and
p-MeC6H4NMe3+OTf− displayed good reactivity, whereas
BINAPf
Dcypef
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
IPr·HCl
THF
t-AmylOH
Toluene
DME
Dioxane
THF
THF
THF
p-Me2NC6H4NMe3 OTf− exhibited relatively low reactivity. For
+
Table 2 Nickel-catalyzed α-arylation of 1-arylpropan-1-ones with
aryltrimethylammonium triflatesa,b
58
62
THF
84% (73%i)
a Unless otherwise noted, the reaction conditions were as follows:
0.2
mmol
4-methoxy-N,N,N-trimethylbenzenaminium
triflate,
0.24 mmol propiophenone, 10 mol% Ni(COD)2, 2 cm3 solvent, 80 °C,
10 h. b NMR yield. c Reaction was carried out at room temperature.
d Reaction was run at 40 °C. e Reaction was run at 60 °C. f 10 mol%
ligand loading. g 1.5 equiv. of propiophenone was used. h Reaction
time was 24 h. i Isolated yield.
IPr to a few other N-heterocyclic carbene ligands led to much
lower yields or even no desired product at all (entries 12–14).
Mono- or bidentate phosphine ligands were also tested using
LiOBut as the base and THF as the solvent at 80 °C. Only a
trace amount of the desired product was observed in each case
(entries 15–17). A study on the solvent effect showed that each
of tert-amyl alcohol, toluene, dimethoxyethane, and dioxane
was less effective than THF (entries 18–21). Excess propio-
phenone was proven to be necessary. As the amount of propio-
phenone was increased to 1.5 equivalents,
a dramatic
improvement was observed (entry 22). A further increase of a
portion of propiophenone was not helpful. In addition,
increasing the loading of LiOBut and extending the reaction
time were proven to be helpful to improve the reaction results
(entries 23 and 24). The use of excess LiOBut may increase the
equilibrium concentration of lithium enolate in the reaction
solution. Gathering all positive conditions together we got our
optimized combination (entry 25).
a Unless otherwise noted, the reaction conditions were as follows:
0.2 mmol aryltrimethylammonium triflate, 0.30 mmol 1-arylpropan-1-
one, 10 mol% Ni(COD)2, 20 mol% IPr·HCl, 3.4 equiv. of LiOBut, 2 cm3
THF, 80 °C, 24 h. b Isolated yields. c 15 mol% Ni(COD)2 and 30 mol%
IPr·HCl were employed.
With the optimized reaction conditions in hand, we
tested the reaction of propiophenone and its derivatives with
various aryltrimethylammonium triflates, and the results are
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example, reaction of p-Me2NC6H4NMe3 OTf− with propio-
phenone required a higher catalyst loading and gave only 42%
product yield (3g). 2-Naphthyltrimethylammonium triflate
showed good reactivity (3j). However, 1-naphthyltrimethyl-
ammonium triflate failed to give a reasonable result when
reacted with propiophenone under the same conditions.
This is ascribed to its steric hindrance, which may prevent
its approach to the metal center of the catalyst bearing the
sterically hindered ligand IPr. The electron-deficient aryltri-
+
Table 3 Nickel-catalyzed arylation of ketones with aryltrimethyl-
ammonium triflatesa,b
+
methylammonium salt, p-Ph(CO)C6H4NMe3 OTf−, did not
+
exhibit higher reactivity than p-MeOC6H4NMe3 OTf− and
p-MeC6H4NMe3 OTf−. As mentioned above, its reactions with
+
propiophenones gave the corresponding coupling products in
56–57% yields (3b–3d). The reaction of p-PhC6H4NMe3 OTf−
+
gave a lower product yield (3k). In the reactions studied, the
N–Me cleavage of aryltrimethylammonium salts is the main
side reaction. Aryldimethylamine as a side product can be
observed in each reaction. This may be a key reason for
relatively low product yields in some reactions. In addition,
C(O)OEt, C(O)NEt2 and CN functional groups in aryltrimethyl-
ammonium salts cannot be tolerated. Heteroaryl ketones such
as 1-(pyridin-2-yl)ethanone and 1-(furan-2-yl)ethanone and
dialkyl ketones did not suit for this transformation.
Previous studies showed that the catalytic α-arylation of
acetophenones often suffers polyarylations or aldol conden-
sations.15 Several successful examples of monoarylation of
acetone or acetophenone derivatives have been reported when
palladium catalysts are employed.1d,3,4d–f Nickel-catalyzed
monoarylation of acetophenones is still challenging.5a,15
Delightfully, our catalyst system was demonstrated to be
applicable to α-monoarylation of acetophenone derivatives
(Table 3). 1-(Naphthalen-2-yl)-ethanone, acetophenone and
their derivatives with a functional group at the C4 position
a Reaction conditions: 0.2 mmol aryltrimethylammonium triflate,
0.30 mmol aryl alkyl ketones, 10 mol% Ni(COD)2, 20 mol% IPr·HCl,
3.4 equiv. of LiOBut, 2 cm3 THF, 80 °C, 24 h. b Isolated yields.
such as 4-methoxy-, 4-dimethylamino-, and 4-fluoro- were substrates. For example, reaction of o-tolyltrimethyl-
coupled with 2-naphthalenyl-, p-methylphenyl-, p-methoxy- or ammonium triflate with acetophenone gave a cross-coupling
tert-butoxycarbonylphenyltrimethylammonium triflates to product (3u) in 46% yield, which is much lower than
furnish the expected products 3l–3t in 48% to 95% yields. It that of the reaction of p-tolyltrimethylammonium triflate
seems that changing the nucleophilic precursors from 1-aryl- (3l, 95% yield). The product yield of the reaction of
propan-1-ones to acetophenone derivatives improved the per- 1-naphthalenyltrimethylammonium triflate with acetophenone
formance, higher product yields being achieved in most cases. was also markedly lower than that of the reaction of
We suspected that the reduced hindrance of ketones may 2-naphthalenyltrimethylammonium triflate with acetophenone
facilitate the transmetalation process. As mentioned above, the (44% vs. 85%). In addition, we also tested the reaction of an
reaction cannot tolerate the C(O)OEt functional group. This acyclic ketone bulkier at the α-position of the carbonyl group,
may result from OBut/OEt exchange side reaction in the 1-phenylbutan-1-one, and
a
cyclic ketone, 3,4-dihydro-
presence of an excess of LiOBut. We did observe that the naphthalen-1(2H)-one. They were catalytically α-arylated using
C(O)OBut functional group can be tolerated. The reaction of electron-rich and electron-poor aryltrimethylammonium tri-
p-ButOOCC6H4NMe3 OTf− with acetophenone resulted in the flates in moderate product yields (3w–3y).
+
corresponding coupling product 3t in 53% yield. Nolan et al.
The detailed mechanism is not clear at this stage. Based on
reported that [Ni(IPr*)(cin)Cl] can drive α-arylation of electron- the previous reports for α-arylation reactions using aryl halides
rich acetophenones with aryl chlorides, but did not tolerate or phenol derivatives as the arylating reagents,1d,15a,b we specu-
electron-neutral and electron-poor acetophenones.15b Our cata- late that our reaction may follow a similar process because
lyst system suited for electron-rich, electron-neutral and elec- similar conditions were employed. Thus, an active catalyst,
+
tron-poor acetophenones. However, reaction of 1-(naphthalen- L2Ni, reacts with ArNMe3 OTf− to generate an oxidative
2-yl)ethanone resulted in
a much lower product yield addition species L2Ni(Ar)OTf and release NMe3. Next, C–H
in comparison with that of acetophenone (3l vs. 3r). The reac- nickelation of a ketone in the presence of LiOBut forms a
tions were also sensitive to the steric hindrance of electrophilic diorganonickel intermediate, which undergoes reductive
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elimination to form the C–C coupling product along with silica gel or preparative thin layer chromatography (100 : 1
regeneration of the active nickel species L2Ni.
mixture of petroleum ether and AcOEt) to give 2-(4-methoxy-
phenyl)-1-phenylpropan-1-one as a white solid (35.0 mg,
73%).
2-(4-Methoxyphenyl)-1-phenylpropan-1-one (3a).17 White
Conclusions
1
solid. H NMR (400 MHz, CDCl3): δ 7.96–7.92 (m, 2H), 7.44 (t,
We have developed an effective catalyst system to perform
α-arylation of ketones with aryltrimethylammonium triflates as
the arylating reagents. Activated, unactivated and deactivated
aryltrimethylammonium triflates suited for the coupling. The
ketones used in this transformation include propiophenone,
butyrophenone and acetophenone derivatives as well as a
cyclohexanone derivative. In the reactions monoarylation of
acetophenone derivatives was successfully carried out. We
believe that this methodology would provide a valuable comp-
lement to the α-arylation of ketones and enrich the utilization
of aromatic amines in synthetic chemistry.
J = 7.3 Hz, 1H), 7.35 (t, J = 7.5 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H),
6.81 (d, J = 8.8 Hz, 2H), 4.63 (q, J = 6.9 Hz, 1H), 3.71 (s, 3H),
1.50 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 200.6,
158.5, 136.5, 133.5, 132.8, 128.8, 128.8, 128.5, 114.4, 55.2,
47.0, 19.6.
2-(4-Benzoylphenyl)-1-phenylpropan-1-one (3b).15a White
solid. 1H NMR (400 MHz, CDCl3): δ 7.99–7.95 (m, 2H),
7.78–7.73 (m, 4H), 7.57 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.4 Hz,
1H), 7.48–7.38 (m, 6H), 4.79 (q, J = 6.9 Hz, 1H), 1.58 (d, J =
6.9 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 199.8, 196.4, 146.3,
137.6, 136.3, 133.3, 132.5, 131.0, 130.1, 128.9, 128.8, 128.4,
127.9, 47.9, 19.5.
2-(4-Benzoylphenyl)-1-(4-methoxyphenyl)propan-1-one (3c).15a
Light yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J =
8.9 Hz, 2H), 7.78–7.73 (m, 4H), 7.57 (t, J = 8.0 Hz, 1H), 7.45 (t,
J = 7.6 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.9 Hz, 2H),
4.74 (q, J = 6.8 Hz, 1H), 3.82 (s, 3H), 1.56 (d, J = 6.9 Hz, 3H).
13C NMR (101 MHz, CDCl3): δ 198.3, 196.4, 163.6, 146.7, 137.6,
136.2, 132.5, 131.2, 130.9, 130.1, 129.3, 128.4, 127.8, 113.9,
55.6, 47.5, 19.5.
Experimental
General information
All reactions were performed under a nitrogen atmosphere
using standard Schlenk and vacuum line techniques. THF,
toluene, DME and 1,4-dioxane were distilled under nitrogen
over sodium and degassed prior to use. ButOH and tert-
AmylOH were distilled under nitrogen over CaH2 and degassed
prior to use. Ni(COD)2 was purchased from Alfa Aesar. Methyl
triflate was purchased from Acros Organics and used as
received. Aryldimethylamines were obtained from commercial
vendors and purified by distillation under reduced pressure or
recrystallization prior to use. CDCl3 was purchased from Cam-
bridge Isotope Laboratories and used as received. ICy·HCl was
purchased from Sigma-Aldrich. Other NHC ligands were pre-
pared according to reported procedures.16 Aryltrimethyl-
ammonium triflates were prepared according to reported
procedures.6b,9 All other chemicals were obtained from com-
mercial vendors and used as received. NMR spectra were
recorded on a Bruker Avance III 400 spectrometer at ambient
2-(4-Benzoylphenyl)-1-(4-fluorophenyl)propan-1-one (3d).15a
Light yellow oil. 1H NMR (400 MHz, CDCl3): δ 8.01–7.96 (m,
2H), 7.79–7.72 (m, 4H), 7.60–7.56 (m, 1H), 7.46 (t, J = 7.6 Hz,
2H), 7.39 (d, J = 8.3 Hz, 2H), 7.08 (t, J = 8.6 Hz, 2H), 4.73 (q, J =
6.9 Hz, 1H), 1.57 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz,
CDCl3): δ 198.2, 196.3, 165.8 (d, J = 256.3 Hz), 146.1, 137.6,
136.5, 132.7 (d, J = 3.1 Hz), 132.6, 131.6 (d, J = 9.3 Hz), 131.1,
130.1, 128.4, 127.8, 115.9 (d, J = 21.9 Hz), 48.0, 19.5. 19F NMR
(376 MHz, CDCl3): δ −104.84.
1,2-Bis(4-methoxyphenyl)propan-1-one (3e).18 Colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.8 Hz, 2H), 7.20 (d,
J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 6.82 (d, J = 8.8 Hz, 2H),
4.60 (q, J = 6.8 Hz, 1H), 3.81 (s, 3H), 3.75 (s, 3H), 1.49 (d, J =
6.9 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 199.2, 163.2, 158.5,
134.1, 131.2, 129.5, 128.8, 114.4, 113.7, 55.5, 55.3, 46.7, 19.7.
1-(4-Fluorophenyl)-2-(4-methoxyphenyl)propan-1-one (3f).4e
Light yellow oil. 1H NMR (400 MHz, CDCl3): δ 8.02–7.92 (m,
2H), 7.18 (d, J = 8.7 Hz, 2H), 7.04 (t, J = 8.7 Hz, 2H), 6.83 (d, J =
8.8 Hz, 2H), 4.58 (q, J = 6.8 Hz, 1H), 3.75 (s, 3H), 1.50 (d, J =
6.8 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 199.0, 165.5 (d, J =
255.4 Hz), 158.7, 133.5, 132.9 (d, J = 2.9 Hz), 131.5 (d, J =
9.3 Hz), 128.8, 115.7 (d, J = 21.8 Hz), 114.6, 55.3, 47.2, 19.6.
19F NMR (376 MHz, CDCl3): δ −105.69.
1
temperature. The chemical shifts of the H NMR spectra were
referenced to TMS and the chemical shifts of the 13C NMR
spectra were referenced to internal solvent resonances.
The chemical shifts of the 19F NMR spectra were referenced
to external CF3COOH. High-resolution mass spectra (HR-MS)
were acquired on
spectrometer.
a Thermo Orbital XL ETD mass
The typical procedure for the nickel-catalyzed α-arylation of
aromatic ketones with aryltrimethylammonium triflates
A
Schlenk tube was charged with Ni(COD)2 (5.5 mg,
2-(4-(Dimethylamino)phenyl)-1-phenylpropan-1-one (3g).19
1
0.02 mmol), IPr·HCl (17 mg, 0.04 mmol), LiOBut (55 mg, Light yellow solid. H NMR (400 MHz, CDCl3): δ 7.97–7.94 (m,
0.68 mmol), 4-methoxy-N,N,N-trimethylbenzenaminium tri- 2H), 7.45 (t, J = 7.3 Hz, 1H), 7.36 (t, J = 7.5 Hz, 2H), 7.14 (d, J =
flate (63 mg, 0.2 mmol), propiophenone (40.2 mg, 0.3 mmol), 8.8 Hz, 2H), 6.65 (d, J = 8.8 Hz, 2H), 4.59 (q, J = 6.8 Hz, 1H),
and THF (2 cm3). The mixture was stirred at 80 °C for 2.88 (s, 6H), 1.49 (d, J = 6.8 Hz, 3H). 13C NMR (101 MHz,
24 hours. Volatiles were removed by rotary evaporation. CDCl3): δ 200.8, 149.6, 136.8, 132.6, 129.2, 128.9, 128.5, 128.5,
The residue was purified by column chromatography on 113.1, 47.0, 40.7, 19.6.
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1-Phenyl-2-(p-tolyl)propan-1-one (3h).17 White solid. 1H NMR
1-(4-(Dimethylamino)phenyl)-2-(p-tolyl)ethan-1-one
(3q).
1
(400 MHz, CDCl3): δ 7.98–7.95 (m, 2H), 7.47 (t, J = 7.4 Hz, 1H), Yellow solid. H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 9.1 Hz,
7.38 (t, J = 7.5 Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.64 (d, J =
8.0 Hz, 2H), 4.66 (q, J = 6.8 Hz, 1H), 2.29 (s, 3H), 1.53 (d, J = 9.1 Hz, 2H), 4.15 (s, 2H), 3.04 (s, 6H), 2.31 (s, 3H). 13C NMR
6.8 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 200.6, 138.6, 136.6, (101 MHz, CDCl3): δ 196.1, 153.4, 136.1, 132.8, 131.0, 129.4,
132.8, 129.8, 128.9, 128.6, 127.7, 47.6, 21.1, 19.6.
129.3, 124.6, 110.8, 44.7, 40.1, 21.2. HR-MS: m/z 254.15360
1-(4-Methoxyphenyl)-2-(p-tolyl)propan-1-one (3i).20 Light [M + H]+, calcd for C17H20NO 254.15448.
yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 9.0 Hz,
1-(Naphthalen-2-yl)-2-(p-tolyl)ethan-1-one (3r). White solid.
2H), 7.18 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 6.85 (d, J = 1H NMR (400 MHz, CDCl3): δ 8.55 (s, 1H), 8.06 (dd, J = 1.7,
9.0 Hz, 2H), 4.61 (q, J = 6.8 Hz, 1H), 3.81 (s, 3H), 2.29 (s, 3H), 8.7 Hz, 1H), 7.96 (d, J = 8.0 Hz, 2H), 7.88 (t, J = 7.6 Hz, 2H),
1.50 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 199.1, 7.63–7.53 (m, 2H), 7.21 (d, J = 7.9 Hz, 2H), 7.15 (d, J = 7.9 Hz,
163.2, 139.0, 136.5, 131.2, 129.7, 129.6, 127.7, 113.7, 55.5, 47.2, 2H), 4.38 (s, 3H), 2.32 (s, 3H). 13C NMR (101 MHz, CDCl3):
21.1, 19.7.
δ 198.0, 136.6, 135.7, 134.1, 132.6, 131.7, 130.5, 129.8, 129.6,
White 129.5, 128.6, 128.6, 127.9, 126.9, 124.5, 45.3, 21.2. HR-MS: m/z
2-(Naphthalen-2-yl)-1-phenylpropan-1-one
(3j).17
solid. 1H NMR (400 MHz, CDCl3): δ 8.02–7.98 (m, 2H), 261.12709 [M + H]+, calcd for C19H17O 261.12793.
7.81–7.77 (m, 3H), 7.73 (s, 1H), 7.48–7.41 (m, 4H), 7.37 (t, J =
1-(4-Fluorophenyl)-2-(p-tolyl)ethan-1-one (3s).21 Light yellow
7.5 Hz, 2H), 4.86 (q, J = 6.8 Hz, 1H), 1.63 (d, J = 6.8 Hz, 3H). solid. 1H NMR (400 MHz, CDCl3): δ 8.06–8.00 (m, 2H),
13C NMR (101 MHz, CDCl3): δ 200.4, 139.1, 136.5, 133.8, 133.0, 7.16–7.09 (m, 6H), 4.22 (s, 2H), 2.33 (s, 3H). 13C NMR
132.5, 128.9, 128.6, 127.8, 127.8, 126.5, 126.3, 126.1, 125.9, (101 MHz, CDCl3): δ 196.4, 165.8 (d, J = 255.8 Hz), 136.8, 133.1
48.2, 19.7.
(d, J = 3.0 Hz), 131.4 (d, J = 9.4 Hz), 131.3, 129.6, 129.3, 115.8
2-([1,1′-Biphenyl]-4-yl)-1-phenylpropan-1-one (3k).15a White (d, J = 21.9 Hz), 45.3, 21.2. 19F NMR (376 MHz, CDCl3):
solid. 1H NMR (400 MHz, CDCl3): δ 8.02–7.98 (m, 2H), δ −105.12.
7.56–7.51 (m, 4H), 7.49 (d, J = 7.2 Hz, 1H), 7.44–7.39 (m, 4H),
tert-Butyl 4-(2-oxo-2-phenylethyl)benzoate (3t). White solid.
7.37 (d, J = 8.4 Hz, 2H), 7.32 (t, J = 7.4 Hz, 1H), 4.75 (q, J = 1H NMR (400 MHz, CDCl3): δ 8.01–7.98 (m, 2H), 7.95 (d, J =
6.8 Hz, 1H), 1.58 (d, J = 6.9 Hz, 3H). 13C NMR (101 MHz, 8.3 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.31
CDCl3): δ 200.4, 140.8, 140.6, 139.9, 136.6, 133.0, 128.9, 128.9, (d, J = 8.3 Hz, 2H), 4.33 (s, 2H), 1.58 (s, 9H). 13C NMR
128.7, 128.3, 127.8, 127.4, 127.1, 47.6, 19.6.
(101 MHz, CDCl3): δ 197.1, 165.7, 139.3, 136.5, 133.5, 130.8,
1-Phenyl-2-(p-tolyl)ethan-1-one (3l).21 Light yellow oil. 129.9, 129.5, 128.8, 128.7, 81.1, 45.6, 28.3. HR-MS: m/z
1H NMR (400 MHz, CDCl3): δ 8.03 (d, J = 8.2 Hz, 2H), 7.56 (t, 297.14899 [M + H]+, calcd for C19H21O3 297.14906.
J = 7.3 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.20–7.13 (m, 4H), 4.26
(s, 2H), 2.34 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 197.9, (400 MHz, CDCl3): δ 8.02 (d, J = 6.9 Hz, 2H), 7.46–7.58 (m, 3H),
1-Phenyl-2-(o-tolyl)ethanone (3u).25 Light yellow oil. 1H NMR
136.7, 136.6, 133.2, 131.5, 129.5, 129.4, 128.7, 45.2, 21.2.
7.13–7.24 (m, 4H), 4.31 (s, 2H), 2.26 (s, 3H). 13C NMR
2-(4-Methoxyphenyl)-1-phenylethan-1-one (3m).22 White (101 MHz, CDCl3): δ 197.6, 137.0, 137.0, 133.6, 133.3, 130.5,
solid. 1H NMR (400 MHz, CDCl3): δ 8.01 (d, J = 7.3 Hz, 2H), 130.4, 128.8, 128.5, 127.4, 126.2, 43.6, 19.9.
7.56 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.19 (d, J =
8.6 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 4.23 (s, 2H), 3.79 (s, 3H). oil, H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 6.8 Hz, 2H), 7.86
13C NMR (101 MHz, CDCl3): δ 198.1, 158.7, 136.7, 133.2, 130.6, (s, 2H), 7.78 (d, J = 7.6 Hz, 1H), 7.35–7.57 (m, 7H), 4.72 (s, 2H).
2-(Naphthalen-1-yl)-1-phenylethanone (3v).25 Light yellow
1
128.8, 128.7, 126.6, 114.3, 55.4, 44.8.
13C NMR (101 MHz, CDCl3): δ 197.7, 136.8, 134.0, 133.4, 132.4,
2-(Naphthalen-2-yl)-1-phenylethan-1-one (3n).23 White solid. 131.5, 128.9, 128.8, 128.6, 128.1, 128.0, 126.4, 125.9, 125.6,
1H NMR (400 MHz, CDCl3): δ 8.09–8.03 (2H, m), 7.85–7.77 (m, 124.0, 43.2.
3H), 7.73 (s, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.50–7.38 (m, 5H),
1-Phenyl-2-(p-tolyl)butan-1-one (3w). Colorless oil, 1H NMR
4.46 (s, 2H). 13C NMR (101 MHz, CDCl3): δ 197.6, 136.5, 133.5, (400 MHz, CDCl3): δ 8.00–7.95 (m, 2H), 7.48 (t, J = 7.3 Hz, 1H),
133.2, 132.3, 132.0, 128.6, 128.6, 128.3, 128.0, 127.6, 127.6, 7.39 (t, J = 7.5 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.11 (d, J =
127.5, 126.1, 125.7, 45.7.
7.9 Hz, 2H), 4.42 (t, J = 7.3 Hz, 1H), 2.29 (s, 3H), 2.25–2.12 (m,
1-(4-Methoxyphenyl)-2-(p-tolyl)ethan-1-one (3o).21 Light 1H), 1.90–1.80 (m, 1H), 0.91 (t, J = 7.4 Hz, 3H). 13C NMR
yellow oil. 1H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 8.8 Hz, (101 MHz, CDCl3): δ 200.3, 137.2, 136.7, 136.7, 132.8, 129.7,
2H), 7.17 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 6.93 (d, 128.8, 128.6, 128.2, 55.2, 27.2, 21.1, 12.4. HR-MS: m/z
J = 8.8 Hz, 2H), 4.20 (s, 2H), 3.85 (s, 3H), 2.32 (s, 3H). 13C NMR 239.14293 [M + H]+, calcd for C17H19O 239.14358.
(101 MHz, CDCl3): δ 196.6, 163.5, 136.4, 131.9, 131.0, 129.7,
2-(4-Benzoylphenyl)-1-phenylbutan-1-one (3x). Colorless oil,
1H NMR (400 MHz, CDCl3): δ 8.01–7.96 (m, 2H), 7.79–7.72 (m,
129.5, 129.3, 113.8, 55.5, 45.0, 21.2.
1-(4-Methoxyphenyl)-2-(naphthalen-2-yl)ethan-1-one (3p).24 4H), 7.57 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 7.38–7.38
1
White solid. H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 8.8 Hz, (m, 6H), 4.57 (t, J = 7.3 Hz, 1H), 2.31–2.19 (m, 1H), 1.96–1.84
2H), 7.83–7.76 (m, 3H), 7.73 (s, 1H), 7.48–7.39 (m, 3H), 6.93 (d, (m, 1H), 0.94 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3):
J = 8.8 Hz, 2H), 4.40 (s, 2H), 3.85 (s, 3H). 13C NMR (101 MHz, δ 199.6, 196.4, 144.5, 137.6, 136.9, 136.4, 133.2, 132.5, 130.8,
CDCl3): δ 196.4, 163.7, 133.7, 132.7, 132.5, 131.1, 129.7, 128.4, 130.1, 128.8, 128.4, 128.4, 55.4, 27.3, 12.4. HR-MS: m/z
128.1, 127.8, 127.8, 127.7, 126.2, 125.8, 114.0, 55.6, 45.6.
329.15348 [M + H]+, calcd for C23H21O2 329.15415.
This journal is © The Royal Society of Chemistry 2016
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Paper
Organic & Biomolecular Chemistry
2-(p-Tolyl)-3,4-dihydronaphthalen-1(2H)-one (3y).26 White
8 S. B. Blakey and D. W. C. MacMillan, J. Am. Chem. Soc.,
2003, 125, 6046–6047.
9 F. Zhu, J.-L. Tao and Z.-X. Wang, Org. Lett., 2015, 17, 4926–
4929.
solid, 1H NMR (400 MHz, CDCl3): δ 8.11 (d, J = 7.8 Hz, 1H),
7.51 (dt, J = 1.2, 7.5 Hz, 1H), 7.35 (t, J = 7.4 Hz, 1H), 7.29 (d, J =
7.6 Hz, 1H), 7.17 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H),
3.81–3.75 (m, 1H), 3.16–3.02 (m, 2H), 2.47–2.39 (m, 2H), 2.35 10 (a) H. Zhang, S. Hagihara and K. Itami, Chem. – Eur. J.,
(s, 3H). 13C NMR (101 MHz, CDCl3): δ 198.5, 144.2, 136.8,
136.6, 133.5, 133.0, 129.4, 128.9, 128.4, 127.9, 126.8, 54.1, 31.3,
28.9, 21.2.
2015, 21, 16796–16800; (b) J. Hu, H. Sun, W. Cai, X. Pu,
Y. Zhang and Z. Shi, J. Org. Chem., 2016, 81, 14–24.
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Acknowledgements
Financial support from the National Natural Science Foun-
dation of China (grant no. 21372212) and the National Basic
Research Program of China (grant no. 2015CB856600) is
greatly acknowledged.
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