Nickel-Catalyzed Arylation/Alkenylation of tert-Cyclobutanols with Aryl/Alkenyl Triflates via a C - C Bond Cleavage

Article abstract of DOI:10.1021/acs.joc.0c02209

Herein, we first present a nickel-catalyzed arylation and alkenylation of tert-cyclobutanols with aryl/alkenyl triflates via a C-C bond cleavage. An array of γ-substituted ketones was obtained in moderate-to-good yields, thus featuring earth-abundant nick

Full text of DOI:10.1021/acs.joc.0c02209

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Nickel-Catalyzed Arylation/Alkenylation of tert-Cyclobutanols with
Aryl/Alkenyl Triflates via a C−C Bond Cleavage
Zhen Wang, Yuanyuan Hu, Hongwei Jin, Yunkui Liu, and Bingwei Zhou*
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ABSTRACT: Herein, we first present a nickel-catalyzed arylation and
alkenylation of tert-cyclobutanols with aryl/alkenyl triflates via a C−C
bond cleavage. An array of γ-substituted ketones was obtained in
moderate-to-good yields, thus featuring earth-abundant nickel catalysis,
broad substrate scope, and simple reaction conditions. Preliminary
mechanistic experiments indicated that β-carbon elimination pathways
might be involved in the catalytic cycle.
Scheme 1. Transformations of tert-Cyclobutanols to γ-
Substituted Ketones
INTRODUCTION
■
Carbon−carbon (C−C) bond is ubiquitous and usually inert
in most organic molecules. The direct transformation of the
C−C bond into new C−C or C−X (X = heteroatom) enables
an unusual disconnection of the carbon chain and then
reassembles with other coupling partners. However, it is still
challenging to achieve a selective C−C bond activation since
the C−C bond is usually co-existence with the C−H bond and
the transition-metal catalyst tends to interact with the C−H
bond.1 Up to now, considerable endeavors have been devoted
to the development of competent catalytic systems and viable
substrates.2 tert-Cyclobutanol is among the most useful
precursors3 for the synthesis of γ-substituted ketone via a
C−C bond cleavage.4 Also, it is routinely considered as an
ideal model substrate proceeding single-electron oxidation
reaction followed by a radical-mediated β-fragmentation
process in the presence of a stoichiometric amount of strong
oxidant. The formed alkyl radical could be further function-
alized known as halogenation,5 azidation,6 alkynylation,7
cyanation,7b thiolation,8 hydrazination,9 and selenation
(Scheme 1a).10 In addition, this radical pathway can also be
accessed through a visible-light-induced photocatalytic strat-
egy, enabling the formation of γ-H,11 Br,12 allyl/formyl,13
aryl,14 or alkynyl15 substituted ketones under mild reaction
conditions (Scheme 1a). An alternative transformation of tert-
cyclobutanol to γ-substituted ketone relies on organometallic
catalysis through a β-carbon elimination process (Scheme 1b).
In 1999, Uemura group presented a pioneering work on the
palladium-catalyzed dehydrogenation reaction of tert-cyclo-
butanols to give α, β-unsaturated ketones.16a After that, the
extended research work based on palladium catalysis has been
successively reported by the same group,16b−e Orellana,17
Martin,18 and Jia and Ma19 groups. In 2012, Murakami group20
disclosed a rhodium-catalyzed C−C cleavage/intramolecular
C−Br coupling reaction of 1-(2-haloaryl)cyclobutanols afford-
ing 3,3-disubstituted α-tetralones. An asymmetric reaction
could be realized by using 3,3-disubstituted 1-(2-haloaryl)-
cyclobutanols as substrates. In spite of these intriguing
achievements, precious metals such as palladium or rhodium
are used as catalysts to realize a β-carbon elimination process
and the development of base metal-catalyzed C−C bond
activation/functionalization is highly desirable.
Received: September 14, 2020
https://dx.doi.org/10.1021/acs.joc.0c02209
© XXXX American Chemical Society
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A

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a
Table 1. Reaction Parameter Screening
entry
catalyst (mol %)
NiBr2 (10)
NiBr2 (10)
NiBr2 (10)
NiBr2 (10)
ligand
PPh3
PCy3
IMes·HCl
XantPhos
base
temp (°C)
solvent
yield (%)
1
2
3
4
5
6
7
8
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
LiOtBu
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
120
60
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
5
37
0
0
0
70
78
64
65
62
18
63
0
0
0
0
0
0
0
0
NiBr2 (10)
1,10-Phen
b
Ni(PPh3)2Br2 (10)
Ni(PPh3)2Cl2 (10)
Ni(PCy3)Cl2 (10)
Ni(dppe)Cl2 (10)
Ni(dppp)Cl2 (10)
Ni(PPh3)2(CO)2 (10)
b
b
b
b
b
b
b
b
b
b
b
b
b
b
b
b
b
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Ni(PPh3)2Cl2 (5)
c
Ni(PPh3)2Cl2 (10)
Ni(PPh3)2Cl2 (10)
Ni(PPh3)2Cl2 (10)
Ni(PPh3)2Cl2 (10)
Ni(PPh3)2Cl2 (10)
Ni(PPh3)2Cl2 (10)
Ni(PPh3)2Cl2 (10)
Ni(PPh3)2Cl2 (10)
Ni(PPh3)2Cl2 (10)
Ni(PPh3)2Cl2 (10)
KOtBu
NaOEt
Na2CO3
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
MeCN
dioxane
xylene
toluene
toluene
43
61
60
a
Reaction conditions unless otherwise noted: 1k (0.2 mmol), 2c (0.3 mmol), catalyst (0.02 mmol), ligand (0.04 mmol), base (0.4 mmol), solvent
b
c
(1 mL), at 90 °C for 12 h. No ligand. No catalyst.
Nickel salts are rich abundant in earth crust and display
fantastic reactivity in catalytic coupling reactions due to the
diverse mechanistic pathways.21 To the best of our knowledge,
nickel-catalyzed ring-opening reactions of strained cyclic
ketones3g and cyclopropanols22 have been described previously
while the corresponding reaction of less-strained cyclobutanols
is still underdeveloped. Herein, we first report a nickel-
catalyzed arylation/alkenylation of tert-cyclobutanols with
aryl/alkenyl triflates (Scheme 1c). The reaction avoids the
use of the stoichiometric oxidant and utilizes readily available
nickel salt as a catalyst instead of precious metals such as
palladium and rhodium.
in the model reaction. Surprisingly, only NaOtBu (2 equiv) in
combination with toluene was proved to be efficient (entries
14−21, Table 1). Finally, either elevating or lowering the
reaction temperature gave inferior yields compared with the
optimal reaction condition at 90 °C (entries 22 and 23 vs 7,
Table 1).
We then evaluated the scope of aryl/alkenyl triflates under
the optimized reaction conditions (Scheme 2). Aryl triflates
with a range of electron-varied substitutes at the para-position
of phenyl ring proceeded smoothly (3a−3g, Scheme 2). In
general, aryl triflates with electron-donating groups exhibited
higher reactivity than those with electron-withdrawing ones
while the stronger electron-donating groups such as methoxy
(−OMe) and dimethylamino (−NMe2) groups could not
further promote the yields (3e and 3f, Scheme 2). This result
indicated that an appropriate electron effect on the phenyl ring
is preferable. More steric o-tolyl trifluoromethanesulfonate and
naphthalen-1-yl trifluoromethanesulfonate also worked effi-
ciently compared with less steric ones (3h vs 3b, 3i vs 3e,
Scheme 2). The terminal alkenyl group was found to be
compatible with the nickel catalysis giving the product 3l in
62% yield. Additionally, alkenyl triflates were also viable
substrates furnishing the reaction in good yields (3n and 3o,
Scheme 2).
RESULTS AND DISCUSSION
■
Initially, the model reaction of 1-(naphthalen-2-yl)cyclobutan-
1-ol 1k with 4-ethylphenyl trifluoromethanesulfonate 2c was
carried out using NiBr2 as a catalyst, PPh3 as a ligand, NaOtBu
as a base, and toluene as a solvent at 90 °C for 12 h. To our
delight, the desired product was isolated and characterized
albeit in a low yield (entry 1, Table 1). The yield was improved
to 37% when PCy3 was used as a ligand while other ligands
such as IMes·HCl, XantPhos, 1,10-phenanthroline failed to
produce the product (entries 2−5, Table 1, see the Supporting
Information for details). Several phosphine-ligated nickel salts
were then screened (entries 6−11, Table 1), and Ni(PPh3)2Cl2
gave the product in a 78% yield (entry 7, Table 1). Halving the
catalyst loading or removal of the nickel salt resulted in a
decreased yield and no reaction, respectively (entries 12 and
13, Table 1). Next, we examined a series of bases and solvents
Next, we continued to investigate the generality of tert-
cyclobutanols by reacting with p-tolyl trifluoromethanesulfo-
nate 2b (Scheme 3). An array of tert-cyclobutanols bearing
different para-substituted phenyl rings were readily converted
into the corresponding ketones in moderate-to-good yields
B
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a
Scheme 2. Substrate Scope of Aryl/Alkenyl Triflates
Scheme 3. Substrate Scope of tert-Cyclobutanols
a
Conditions: 1k (0.4 mmol), 2 (0.6 mmol), Ni(PPh3)2Cl2 (0.04
mmol), NaOtBu (0.8 mmol), toluene (2 mL), at 90 °C for 12 h.
a
(3p−3v, Scheme 3). Again, the methoxy and dimethylamino
groups at cyclobutanols were still unable to increase the yields
(3s and 3t, Scheme 3). Gratefully, the tert-cyclobutanols with
electron withdrawing groups such as −F and −CF3 at the
phenyl ring were workable in this case, which shaped a sharp
contrast to substrate scope of aryl triflates (3u and 3v, Scheme
3). 1-Naphthyl and thienyl cyclobutanols were suitable
substrates to deliver the products in satisfying yields (3y and
3A, Scheme 3). Furthermore, 3-mono/di-substituted aryl
cyclobutanols proceeded smoothly while 2-phenyl-substituted
one failed to give the desired products presumably due to the
facile isomerization to ketone (3B and 3C, 1p, Scheme 3). At
last, less steric alkyl cyclobutanols were chosen as substrates
and subjected to the standard reaction conditions. Expectedly,
unsymmetric dialkyl ketones were accessed in 74 and 49%
yields, respectively (3D and 3E, Scheme 3).
Conditions: 1 (0.4 mmol), 2b (0.6 mmol), Ni(PPh3)2Cl2 (0.04
mmol), NaOtBu (0.8 mmol), toluene (2 mL), at 90 °C for 12 h. NR =
No Reaction.
Scheme 4. Gram-Scale Reaction
Scheme 5. Mechanistic Experiments
To examine the synthetic utility of this reaction, a gram-scale
reaction of 1-(naphthalen-2-yl)cyclobutan-1-ol 1k with p-tolyl
trifluoromethanesulfonate 2b was performed under the
optimized reaction conditions and the product 3b could be
isolated in 87% yield (Scheme 4). This gram-scale reaction
might provide a practically useful method for the synthesis of
γ-substituted ketones.
Further experiments were conducted to clarify the possible
reaction mechanism. 2,2,6,6-Tetramethylpiperidine-1-oxyl
(TEMPO) was used as a radical trapper and added to the
model reaction (Scheme 5a). Unexpectedly, the reaction was
inhibited and neither product 3b nor TEMPO-trapped ketone
4a could be detected although 1k was totally consumed. In
contrast, a messy mixture was isolated and their structures
the Supporting Information for details). In addition, both BHT
and 1,1′-diphenylethylene were examined. To our surprise, the
reaction was not suppressed and the products were obtained in
73 and 75%, respectively. Furthermore, the reaction tert-
1
could not be characterized by H NMR and MS analysis (see
C
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and all combinations thereof can be explained by their integral parts.
Coupling constant (J) was reported in hertz unit (Hz). The high-
resolution mass spectra (HRMS) were recorded on an Agilent 6210
LC/TOF spectrometer.
cycolpentanol 1s with aryl triflate 2b was examined and no
product was detected and the starting material 1s was
recovered (Scheme 5b). It suggested that the C−C bond
cleavage might not undergo a radical β-fragmentation
process.23,24
General Procedure for Synthesizing Cyclobutanols.27 Cyclo-
butanone (5 mmol) was dissolved in 10 mL of dried THF in a 50 mL
Schlenk tube under N2. The mixture was cooled to 0 °C, and
Grignard reagent (1.1 equiv) was added dropwise with stirring under
an ice bath. Then, it was allowed to warm to room temperature and
stirred overnight. After completion, the mixture was quenched with
NH4Cl (aq). The aqueous layer was extracted with ethyl acetate (3 ×
20 mL). The combined organic layers were dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. After the
removal of the solvent in vacuo, the crude mixture was purified by
flash column chromatography on silica gel to give the desired
cyclobutanols. All the tert-cyclobutanols were synthesized according
to this general procedure. 1s was synthesized from cyclopentanone
according to this procedure. Substrates 1n and 10 are new
compounds.
We proposed the plausible reaction mechanism based on the
above experiments and previous literature (Scheme 6).25,26
Scheme 6. Plausible Reaction Mechanism
1-(Naphthalen-2-yl)-3-phenylcyclobutan-1-ol (1n). Purified by
flash column chromatography (petroleum ether/EtOAc = 20:1 to
5:1) as white solid and obtained as a diastereomer mixture. 1H NMR
(500 MHz, CDCl3) δ 8.08 (s, 1H), 7.98−7.85 (m, 4H), 7.79 (dd, J1 =
8.5, J2 = 1.5 Hz, 1H), 7.62−7.50 (m, 3H), 7.42−7.33 (m, 5H), 7.33−
7.23 (m, 2H), 3.23−3.14 (m, 3H), 2.93−2.76 (m, 1H), 2.72−2.63
(m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 144.99, 144.6, 143.8,
128.7, 128.4, 128.4, 128.3, 128.1, 128.08, 127.59, 127.6, 126.7, 126.5,
126.3, 126.2, 126.1, 126.1, 126.0, 126.0, 124.4, 123.5, 123.5, 123.0,
75.2, 72.6, 44.4, 43.1, 33.6, 30.1. HRMS (EI) m/z: [M]+ Calcd for
C20H18O 274.1358; found 274.1367.
3-Methyl-1-(naphthalen-2-yl)-3-phenylcyclobutan-1-ol (1o). Pu-
rified by flash column chromatography (petroleum ether/EtOAc =
20:1 to 5:1) as white solid and obtained as a diastereomer mixture. 1H
NMR (500 MHz, CDCl3) δ 8.03 (s, 1H), 7.97−7.88 (m, 1H), 7.84−
7.77 (m, 1H), 7.74−7.69 (m, 1H), 7.59−7.52 (m, 1H), 7.51−7.45
(m, 1H), 7.45−7.36 (m, 1H), 7.36−7.32 (m, 1H), 7.29−7.24 (m,
1H), 7.24−7.17 (m, 1H), 7.16−7.07 (m, 1H), 3.20−3.07 (m, 1H),
3.01 (d, J = 13.1 Hz, 1H), 2.78−2.66 (m, 1H), 1.81 (s, 1H), 1.33 (s,
1H). 13C{1H} NMR (125 MHz, CDCl3) δ 153.6, 151.6, 151.5, 144.5,
143.5, 133.1, 132.9, 132.7, 132.4, 129.7, 128.7, 128.4, 128.3, 128.2,
128.2, 128.1, 127.8, 127.7, 127.6, 127.5, 127.1, 126.4, 126.3, 126.3,
126.1, 126.1, 126.1, 126.0, 125.9, 125.5, 125.3, 125.3, 125.2, 125.1,
124.4, 124.0, 123.6, 123.6, 123.4, 122.8, 117.9, 109.4, 73.1, 72.5, 49.5,
48.6, 48.3, 36.1, 34.3, 32.8, 31.4, 29.4. HRMS (EI) m/z: [M]+ Calcd
for C21H20O 288.1514; found 288.1537.
The active nickel species Ni-I was generated in situ from the
reduction of Ni(PPh3)Cl2.25 An oxidative addition of aryl
triflate with Ni-I took place to form intermediate Ni-II, which
then underwent a radical process with tert-cyclobutanol in the
presence of a base. The generated nickel alcoholate Ni-III
further proceeded a β-C elimination, producing an alkylnickel
intermediate Ni-IV.26 Finally, the reductive elimination of Ni-
IV fulfilled the whole catalytic cycle to regenerate the Ni-I and
provide the product 3.
CONCLUSIONS
■
In conclusion, we have developed a nickel-catalyzed arylation/
alkenylation of tert-cyclobutanols with aryl/alkenyl triflates via
β-carbon elimination process. A number of γ-substituted
ketones were successfully obtained in moderate-to-good yields.
The present protocol features earth abundant nickel salt, broad
functional group tolerance, and easy operation. The further
exploration for the nickel-catalyzed C−C bond activation of
less-strained tert-cycloalcohols is underway in our laboratory.
General Procedure for Synthesizing Aryl Triflates.28 A 100
mL Schlenk tube was charged successively with phenol derivative (10
mmol), dry DCM (30 mL), and pyridine (2 equiv) under N2. The
solution was cooled to 0 °C in an ice bath and then treated with the
dropwise addition of triflic anhydride (1.2 equiv). The resulting
mixture was allowed to warm up to room temperature (rt) and stirred
for additional 5 h. At the end of the reaction, the mixture was filtered.
The filtrate was concentrated in vacuo and the residue was subjected
to flash chromatography (200−300 mesh silica gel, PE or PE/EtOAc
as an eluent) to afford the desired aryl triflate. Aryl triflates were
prepared from this procedure. General procedure for synthesizing
alkenyl triflates29 under N2, trifluoromethanesulfonic anhydride (20
mmol) in dichloromethane (15 mL) was added to a solution of
ketone (10 mmol) and anhydrous sodium carbonate (16.0 mmol) in
dichloromethane (15 mL) over a period of 10 min. The reaction was
stirred for an addition 24 h at room temperature. After completion,
the reaction mixture was washed with sodium hydrogen carbonate (2
× 50 mL), water (2 × 50 mL), dried with Na2SO4, and then filtered.
Then, the filtrate was concentrated and purified by silica gel column
chromatography to get the alkenyl triflates.
EXPERIMENTAL SECTION
■
Unless otherwise noted, all reactions were carried out in flame-dried
reaction vessels with Teflon screw caps under nitrogen. Solvents were
purified and dried according to standard methods prior to use. All
commercially available reagents were obtained from chemical
suppliers and used after proper purification if necessary. Flash column
chromatography was performed on silica gel (200−300 mesh) with
the indicated solvent mixtures. TLC analysis was performed on
precoated, glass-backed silica gel plates, and visualized with UV light.
An oil bath was used as a heat source.
1
The H and 13C NMR spectra were recorded on a Bruker 500 AV
spectrometer. Chemical shifts (δ) were reported as parts per million
(ppm) downfield from tetramethylsilane, and the following
abbreviations were used to identify the multiplicities: s = singlet, d
= doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of
doublets, dt = doublet of triplets, dq = doublet of quartets, br = broad,
Typical Procedure for Preparation of γ-Substituted Ke-
tones. To a 25 mL flame-dried Schlenk tube containing a stirring bar
were added Ni(PPh3)2Cl2 (0.04 mmol, 26.1 mg), NaOt-Bu (0.8
mmol, 76.8 mg), 1-(naphthalen-2-yl)cyclobutan-1-ol 1k (0.4 mmol,
79.2 mg), toluene (2.0 mL), and 4-ethylphenyl trifluoromethanesul-
D
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fonate 2c (0.6 mmol, 152.4 mg), sequentially under nitrogen. The
tube was sealed and stirred at 90 °C for 12 h. After completion, the
reaction mixture was diluted with ethyl acetate (5.0 mL) and filtered
through a short pad silica gel washing with ethyl acetate (20 mL). The
filtrate was concentrated and purified by silica gel column
chromatography (petroleum ether/EtOAc = 100:1 to 50:1) to
provide the product 3c in 80% yield.
135.4, 134.2, 133.7, 132.4, 129.6, 129.5, 129.4, 128.3, 128.3, 127.7,
126.6, 123.8, 113.8, 55.2, 37.6, 34.2, 26.1.
4-(4-(Dimethylamino)phenyl)-1-(naphthalen-2-yl)butan-1-one
(3f). Purified by flash column chromatography (petroleum ether/
EtOAc = 60:1 to 20:1) as pale-yellow solid (66 mg, 52% yield). mp:
104−106 °C. 1H NMR (500 MHz, CDCl3) δ 8.38 (s, 1H), 8.00 (dd,
J1 = 8.6 Hz, J2 = 1.7 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.85 (dd, J1 =
8.3 Hz, J2 = 4.9 Hz, 2H), 7.60−7.49 (m, 2H), 7.10 (d, J = 8.7 Hz,
2H), 6.74−6.68 (m, 2H), 3.08 (t, J = 7.3 Hz, 2H), 2.91 (s, 6H), 2.67
(t, J = 7.4 Hz, 2H), 2.13−2.06 (m, 2H). 13C{1H} NMR (125 MHz,
CDCl3) δ 200.4, 149.2, 135.5, 134.4, 132.5, 129.8, 129.6, 129.5, 129.1,
128.3, 128.3, 127.7, 126.6, 123.9, 113.0, 40.9, 37.8, 34.2, 26.2. HRMS
(ESI) m/z: [M + H]+ Calcd for C22H24NO 318.1852; found
318.1852.
Experimental Procedure for Gram-Scale Reaction. To a 100
mL flame-dried Schlenk tube containing a stirring bar were added
Ni(PPh3)2Cl2 (0.5 mmol, 327 mg), NaOt-Bu (10 mmol, 961 mg), 1-
(naphthalen-2-yl)cyclobutan-1-ol 1k (5 mmol, 991.3 mg), toluene
(25.0 mL), and p-tolyl trifluoromethanesulfonate 2b (7.5 mmol, 1800
mg), sequentially under nitrogen. The tube was sealed and stirred at
90 °C for 12 h. After completion, the reaction mixture was diluted
with ethyl acetate (30 mL) and filtered through a short pad silica gel
washing with ethyl acetate (50 mL). The filtrate was concentrated and
purified by silica gel column chromatography (petroleum ether:
EtOAc = 60:1) to provide the product 3b in 87% yield (1.25 g) as
white solid.
4-(4-Acetylphenyl)-1-(naphthalen-2-yl)butan-1-one (3g). Puri-
fied by flash column chromatography (petroleum ether/EtOAc =
10:1 to 5:1) as white solid (31 mg, 24% yield). mp: 119−121 °C. 1H
NMR (500 MHz, CDCl3) δ 8.40 (s, 1H), 8.00 (dd, J1 = 8.6 Hz, J2 =
1.7 Hz, 1H), 7.95−7.84 (m, 5H), 7.62−7.51 (m, 2H), 7.31 (d, J = 8.3
Hz, 2H), 3.11 (t, J = 7.2 Hz, 2H), 2.81 (t, 2H), 2.57 (s, 3H), 2.20−
2.11 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 199.6, 197.8,
147.5, 135.5, 135.2, 134.2, 132.4, 129.5, 129.5, 128.7, 128.6, 128.4,
127.7, 126.7, 123.7, 37.5, 35.1, 26.5, 25.4. HRMS (ESI) m/z: [M +
Na]+ Calcd for C22H20NaO2 339.1361; found 339.1356.
1-(Naphthalen-2-yl)-4-phenylbutan-1-one (3a).30a Purified by
flash column chromatography (petroleum ether/EtOAc = 100:1 to
1
50:1) as white solid (80 mg, 73% yield). mp: 72−74 °C. H NMR
(500 MHz, CDCl3) δ 8.38 (s, 1H), 8.00 (dd, J1 = 8.6 Hz, J2 = 1.7 Hz,
1H), 7.94−7.89 (m, 1H), 7.85 (dd, J1 = 8.1 Hz, J2 = 6.5 Hz, 2H),
7.61−7.49 (m, 2H), 7.33−7.27 (m, 2H), 7.26−7.17 (m, 3H), 3.09 (t,
J = 7.3 Hz, 2H), 2.75 (t, J = 7.5 Hz, 2H), 2.20−2.07 (m, 2H).
13C{1H} NMR (125 MHz, CDCl3) δ 200.0, 141.7, 135.5, 134.2,
132.5, 129.6, 129.5, 128.5, 128.4, 128.3, 128.3, 127.7, 126.7, 125.9,
123.8, 37.7, 35.2, 25.8.
1-(Naphthalen-2-yl)-4-(o-tolyl)butan-1-one (3 h).30b Purified by
flash column chromatography (petroleum ether/EtOAc = 100:1 to
1
50:1) as white solid (106 mg, 92% yield). mp: 55−57 °C. H NMR
(500 MHz, CDCl3) δ 8.40 (s, 1H), 8.00 (dd, J1 = 8.6 Hz, J2 = 1.7 Hz,
1H), 7.91 (d, J = 8.0 Hz, 1H), 7.84 (t, J = 8.2 Hz, 2H), 7.60−7.46 (m,
2H), 7.19−7.07 (m, 4H), 3.13 (t, J = 7.2 Hz, 2H), 2.76−2.67 (m,
2H), 2.32 (s, 3H), 2.13−2.03 (m, 2H). 13C{1H} NMR (125 MHz,
CDCl3) δ 199.9, 139.9, 136.0, 135.5, 134.2, 132.5, 130.2, 129.5, 129.5,
128.9, 128.3, 128.3, 127.7, 126.7, 126.0, 125.9, 123.8, 37.9, 32.6, 24.6,
19.3.
1-(Naphthalen-2-yl)-4-(p-tolyl)butan-1-one (3b).30a Purified by
flash column chromatography (petroleum ether/EtOAc = 100:1 to
1
50:1) as white solid (95 mg, 82% yield). mp: 81−83 °C. H NMR
(500 MHz, CDCl3) δ 8.38 (s, 1H), 7.99 (dd, J1 = 8.6 Hz, J2 = 1.7 Hz,
1H), 7.91 (d, J = 8.0 Hz, 1H), 7.85 (dd, J1 = 8.2 Hz, J2 = 5.7 Hz, 2H),
7.60−7.48 (m, 2H), 7.15−7.06 (m, 4H), 3.08 (t, J = 7.3 Hz, 2H),
2.71 (t, J = 7.5 Hz, 2H), 2.32 (s, 3H), 2.16−2.07 (m, 2H). 13C{1H}
NMR (125 MHz, CDCl3) δ 200.1, 138.5, 135.5, 135.3, 134.3, 132.5,
129.6, 129.5, 129.1, 128.4, 128.3, 128.3, 127.7, 126.6, 123.8, 37.7,
34.7, 25.9, 21.0.
4-(2-Methoxyphenyl)-1-(naphthalen-2-yl)butan-1-one (3i). Puri-
fied by flash column chromatography (petroleum ether/EtOAc =
1
100:1 to 50:1) as colorless oil (77 mg, 63% yield). H NMR (500
MHz, CDCl3) δ 8.40 (s, 1H), 8.00 (dd, J1 = 8.6 Hz, J2 = 1.6 Hz, 1H),
7.92 (d, J = 8.0 Hz, 1H), 7.86 (dd, J1 = 8.3 Hz, J2 = 5.5 Hz, 2H),
7.60−7.50 (m, 2H), 7.23−7.11 (m, 2H), 6.93−6.86 (m, 1H), 6.83 (d,
J = 8.1 Hz, 1H), 3.74 (s, 3H), 3.10 (t, J = 7.4 Hz, 2H), 2.77 (t, J = 7.4
Hz, 2H), 2.15−2.07 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ
200.3, 157.5, 135.5, 134.4, 132.5, 130.1, 130.0, 129.6, 129.5, 128.3,
128.2, 127.7, 127.2, 126.6, 124.0, 120.4, 110.2, 55.1, 38.0, 29.5, 24.5.
HRMS (ESI) m/z: [M + H]+ Calcd for C21H21O2 305.1542; found:
305.1536.
4-(4-Ethylphenyl)-1-(naphthalen-2-yl)butan-1-one (3c). Purified
by flash column chromatography (petroleum ether/EtOAc = 100:1 to
1
50:1) as white solid (94 mg, 80% yield). mp: 54−56 °C. H NMR
(500 MHz, CDCl3) δ 8.34 (s, 1H), 7.99−7.94 (m, 1H), 7.88−7.84
(m, 1H), 7.82−7.77 (m, 2H), 7.54−7.46 (m, 2H), 7.15−7.07 (m,
4H), 3.04 (t, J = 7.3 Hz, 2H), 2.69 (t, J = 7.5 Hz, 2H), 2.60 (q, J = 7.6
Hz, 2H), 2.13−2.07 (m, 2H), 1.21 (t, J = 7.6 Hz, 3H). 13C{1H} NMR
(125 MHz, CDCl3) δ 199.8, 141.6, 138.7, 135.3, 134.1, 132.3, 129.4,
129.3, 128.3, 128.2, 128.1, 127.7, 127.6, 126.5, 123.7, 37.6, 34.6, 28.3,
25.8, 15.5. HRMS (ESI) m/z: [M + H]+ Calcd for C22H23O
303.1749; found 303.1743.
4-(Naphthalen-1-yl)-1-(naphthalen-2-yl)butan-1-one (3j). Puri-
fied by flash column chromatography (petroleum ether/EtOAc =
1
100:1 to 50:1) as colorless oil (79 mg, 61% yield). H NMR (500
MHz, CDCl3) δ 8.34 (s, 1H), 8.12 (d, J = 8.3 Hz, 1H), 7.97 (dd, J1 =
8.6 Hz, J2 = 1.6 Hz, 1H), 7.85−7.77 (m, 4H), 7.69 (d, J = 8.0 Hz,
1H), 7.54−7.42 (m, 4H), 7.38−7.30 (m, 2H), 3.19−3.14 (m, 2H),
3.11 (t, J = 7.1 Hz, 2H), 2.27−2.20 (m, 2H). 13C{1H} NMR (125
MHz, CDCl3) δ 199.8, 137.8, 135.4, 134.2, 133.8, 132.4, 131.8, 129.5,
129.4, 128.7, 128.3, 128.3, 127.6, 126.7, 126.6, 126.1, 125.8, 125.4,
125.4, 123.9, 123.7, 37.9, 32.3, 25.1. HRMS (ESI) m/z: [M + Na]+
Calcd for C24H20NaO, 347.1412; found 347.1406.
4-(Naphthalen-1-yl)-1-(naphthalen-2-yl)butan-1-one (3k). Puri-
fied by flash column chromatography (petroleum ether/EtOAc =
100:1 to 50:1) as white solid (88 mg, 68% yield).mp: 136−138 °C.
1H NMR (500 MHz, CDCl3) δ 8.37 (s, 1H), 7.99 (dd, J1 = 8.6 Hz, J2
= 1.7 Hz, 1H), 7.89−7.82 (m, 3H), 7.82−7.74 (m, 3H), 7.65 (s, 1H),
7.60−7.55 (m, 1H), 7.54−7.49 (m, 1H), 7.47−7.39 (m, 2H), 7.37
(dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 3.12 (t, J = 7.3 Hz, 2H), 2.92 (t, J =
7.5 Hz, 2H), 2.30−2.17 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3)
δ 200.1, 139.2, 135.5, 134.3, 133.6, 132.5, 132.1, 129.6, 129.5, 128.4,
128.3, 128.0, 127.7, 127.6, 127.4, 127.3, 126.7, 126.6, 125.9, 125.2,
123.9, 37.6, 35.3, 25.7. HRMS (ESI) m/z: [M + Na]+ Calcd for
C24H20NaO 347.1412; found 347.1413.
4-([1,1′-Biphenyl]-4-yl)-1-(naphthalen-2-yl)butan-1-one (3d).
Purified by flash column chromatography (petroleum ether/EtOAc
= 100:1 to 50:1) as white solid (66 mg, 47% yield). mp: 138−140 °C.
1H NMR (500 MHz, CDCl3) δ 8.41 (s, 1H), 8.01 (dd, J1 = 8.6 Hz, J2
= 1.7 Hz, 1H), 7.94−7.89 (m, 1H), 7.86 (t, J = 8.2 Hz, 2H), 7.61−
7.55 (m, 3H), 7.55−7.49 (m, 3H), 7.45−7.39 (m, 2H), 7.35−7.28
(m, 3H), 3.13 (t, J = 7.3 Hz, 2H), 2.80 (t, J = 7.5 Hz, 2H), 2.22−2.14
(m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 200.0, 141.0, 140.8,
138.9, 135.5, 134.3, 132.5, 129.6, 129.5, 129.0, 128.7, 128.4, 128.3,
127.7, 127.1, 127.0, 127.0, 126.7, 123.9, 37.7, 34.8, 25.8. HRMS (ESI)
m/z: [M + Na]+ Calcd for C26H22NaO 373.1568; found 373.1563.
4-(4-Methoxyphenyl)-1-(naphthalen-2-yl)butan-1-one (3e)29a
.
Purified by flash column chromatography (petroleum ether/EtOAc
= 60:1 to 30:1) as white solid (51 mg, 42% yield). mp: 95−97 °C. 1H
NMR (500 MHz, CDCl3) δ 8.38 (s, 1H), 7.99 (dd, J1 = 8.6, J2 = 1.7
Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.85 (dd, J1 = 8.1 Hz, J2 = 6.1 Hz,
2H), 7.61−7.46 (m, 2H), 7.17−7.06 (m, 2H), 6.87−6.80 (m, 2H),
3.77 (s, 3H), 3.07 (t, J = 7.3 Hz, 2H), 2.69 (t, J = 7.5 Hz, 2H), 2.15−
2.05 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 200.0, 157.8,
E
https://dx.doi.org/10.1021/acs.joc.0c02209
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
4-(4-Allyl-2-methoxyphenyl)-1-(naphthalen-2-yl)butan-1-one
(3l). Purified by flash column chromatography (petroleum ether/
EtOAc = 60:1 to 30:1) as yellow solid (85 mg, 62% yield). mp: 59−
61 °C. 1H NMR (500 MHz, CDCl3) δ 8.39 (s, 1H), 8.00 (dd, J1 = 8.6
Hz, J2 = 1.6 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.85 (m, 2H), 7.54 (m,
2H), 7.08 (d, J = 7.5 Hz, 1H), 6.72 (d, J = 7.5 Hz, 1H), 6.66 (s, 1H),
6.05−5.91 (m, 1H), 5.15−5.03 (m, 2H), 3.73 (s, 3H), 3.36 (d, J = 6.7
Hz, 2H), 3.09 (t, J = 7.4 Hz, 2H), 2.73 (t, J = 7.4 Hz, 2H), 2.18−2.05
(m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 200.3, 157.5, 139.3,
137.5, 135.4, 134.4, 132.5, 129.9, 129.5, 129.5, 128.3, 128.2, 127.7,
127.7, 126.6, 123.9, 120.4, 115.7, 110.6, 55.1, 40.2, 38.0, 29.2, 24.6.
HRMS (ESI) m/z: [M + Na]+ C24H24NaO2 Calcd for 367.1674;
found 367.1669.
4-(Benzo[d][1,3]dioxol-5-yl)-1-(naphthalen-2-yl)butan-1-one
(3m). Purified by flash column chromatography (petroleum ether/
EtOAc = 100:1 to 50:1) as white solid (52 mg, 41% yield). mp: 86−
88 °C. 1H NMR (500 MHz, CDCl3) δ 8.41 (s, 1H), 8.02 (dd, J1 = 8.6
Hz, J2 = 1.7 Hz, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.90−7.84 (m, 2H),
7.62−7.52 (m, 2H), 6.78−6.73 (m, 2H), 6.70−6.66 (m, 1H), 5.92 (s,
2H), 3.09 (t, J = 7.3 Hz, 2H), 2.69 (t, J = 7.5 Hz, 2H), 2.14−2.07 (m,
2H). 13C{1H} NMR (125 MHz, CDCl3) δ 200.0, 147.6, 145.7, 135.5,
135.5, 134.2, 132.5, 129.5, 129.5, 128.3, 128.3, 127.7, 126.6, 123.8,
121.2, 108.9, 108.1, 100.7, 37.5, 34.9, 26.0. HRMS (ESI) m/z: [M +
Na]+ Calcd for C21H18NaO 341.1154; found 341.1150.
CDCl3) δ 7.88−7.84 (m, 2H), 7.46−7.42 (m, 2H), 7.09 (s, 4H), 2.94
(t, J = 7.3 Hz, 2H), 2.70−2.65 (m, 2H), 2.31 (s, 3H), 2.10−2.01 (m,
2H), 1.33 (s, 9H). 13C{1H} NMR (125 MHz, CDCl3) δ 199.8, 156.5,
138.6, 135.2, 134.4, 129.0, 128.3, 127.9, 125.4, 37.6, 35.0, 34.7, 31.0,
25.9, 20.9. HRMS (ESI) m/z: [M + Na]+ Calcd for C21H26NaO
317.1881; found 317.1876.
1-(4-Methoxyphenyl)-4-(p-tolyl)butan-1-one (3s).30c Purified by
flash column chromatography (petroleum ether/EtOAc = 100:1 to
1
50:1) as white solid (44 mg, 42% yield). mp: 76−78 °C. H NMR
(500 MHz, CDCl3) δ 7.91−7.87 (m, 2H), 7.09 (s, 4H), 6.92−6.88
(m, 2H), 3.83 (s, 3H), 2.90 (t, J = 7.3 Hz, 2H), 2.66 (t, J = 7.6 Hz,
2H), 2.31 (s, 3H), 2.07−2.00 (m, 2H). 13C{1H} NMR (125 MHz,
CDCl3) δ 198.7, 163.3, 138.6, 135.2, 130.2, 130.1, 129.0, 128.3, 113.6,
55.3, 37.3, 34.8, 26.0, 20.9.
1-(4-(Dimethylamino)phenyl)-4-(p-tolyl)butan-1-one (3t). Puri-
fied by flash column chromatography (petroleum ether/EtOAc =
100:1 to 50:1) as white solid (65 mg, 58% yield). mp: 94−96 °C. 1H
NMR (500 MHz, CDCl3) δ 7.86−7.82 (m, 2H), 7.14−7.05 (m, 4H),
6.67−6.60 (m, 2H), 3.04 (s, 6H), 2.87 (m, 2H), 2.66 (t, 2H), 2.31 (s,
3H), 2.07−2.00 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 198.4,
153.3, 138.9, 135.2, 130.2, 129.0, 128.4, 125.1, 110.6, 40.0, 37.0, 35.0,
26.5, 21.0. HRMS (ESI) m/z: [M + Na]+ Calcd for C19H23NNaO
304.1677; found 304.1672.
1-(4-Fluorophenyl)-4-(p-tolyl)butan-1-one (3u). Purified by flash
column chromatography (petroleum ether/EtOAc = 100:1 to 50:1)
1-(Naphthalen-2-yl)-4-(1,2,3,6-tetrahydro-[1,1′-biphenyl]-4-yl)-
butan-1-one (3n). Purified by flash column chromatography
(petroleum ether/EtOAc = 100:1 to 50:1) as white solid (119 mg,
1
as white solid (51 mg, 50% yield). mp: 49−51 °C. H NMR (500
MHz, CDCl3) δ 7.96−7.89 (m, 2H), 7.15−7.04 (m, 6H), 2.92 (t, J =
1
84% yield). mp: 89−91 °C. H NMR (500 MHz, CDCl3) δ 8.47 (s,
7.3 Hz, 2H), 2.67 (t, J = 7.5 Hz, 2H), 2.31 (s, 3H), 2.08−2.02 (m,
1
2H). 13C{1H} NMR (125 MHz, CDCl3) δ 198.5, 165.6 (d, JC−F
=
=
1H), 8.04 (dd, J1 = 8.6 Hz, J2 = 1.7 Hz, 1H), 7.96 (d, J = 7.8 Hz, 1H),
7.88 (dd, J1 = 11.3 Hz, J2 = 8.4 Hz, 2H), 7.61−7.50 (m, 2H), 7.31−
7.25 (m, 2H), 7.24−7.14 (m, 4H), 5.55−5.51 (m, 1H), 3.09 (t, J =
7.3 Hz, 2H), 2.79−2.66 (m, 1H), 2.30−2.06 (m, 6H), 2.01−1.90 (m,
2H), 1.82−1.71 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 200.3,
147.1, 136.9, 135.5, 134.4, 132.5, 129.6, 129.5, 128.4, 128.3, 128.28,
127.74, 126.8, 126.7, 125.9, 123.9, 121.4, 40.1, 38.0, 37.1, 33.5, 30.0,
28.7, 22.4. HRMS (ESI) m/z: [M + Na]+ Calcd for C26H26NaO
377.1881; found 377.1876.
4
3
254.3 Hz), 138.4, 135.4, 133.4 (d, JC−F = 3.0 Hz), 130.6 (d, JC−F
2
9.2 Hz), 129.1, 128.3, 115.6 (d, JC−F = 21.8 Hz), 37.5, 34.7, 25.7,
20.9. HRMS (ESI) m/z: [M + Na]+ Calcd for C17H17FNaO
279.1161; found 279.1156.
4-(p-Tolyl)-1-(4-(trifluoromethyl)phenyl)butan-1-one (3v). Puri-
fied by flash column chromatography (petroleum ether/EtOAc =
100:1 to 50:1) as white solid (90 mg, 74% yield). mp: 89−91 °C. 1H
NMR (500 MHz, CDCl3) δ 8.00 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 8.2
Hz, 2H), 7.15−7.03 (m, 4H), 2.98 (t, J = 7.3 Hz, 2H), 2.69 (t, J = 7.5
Hz, 2H), 2.32 (s, 3H), 2.10−2.04 (m, 2H). 13C{1H} NMR (125
4-(3,4-Dihydronaphthalen-1-yl)-1-(naphthalen-2-yl)butan-1-
one (3o). Purified by flash column chromatography (petroleum
ether/EtOAc = 100:1 to 50:1) as yellow oil (92 mg, 71% yield). mp:
89−91 °C. 1H NMR (500 MHz, CDCl3) δ 8.41 (s, 1H), 8.01 (dd, J1
= 8.6 Hz, J2 = 1.7 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.86 (dd, J1 = 8.2
Hz, J2 = 5.7 Hz, 2H), 7.60−7.49 (m, 2H), 7.31 (d, J = 7.6 Hz, 1H),
7.22−7.17 (m, 1H), 7.16−7.11 (m, 2H), 5.90 (t, J = 4.5 Hz, 1H),
3.13 (t, J = 7.2 Hz, 2H), 2.74 (t, J = 8.0 Hz, 2H), 2.62−2.55 (m, 2H),
2.27−2.20 (m, 2H), 2.10−1.99 (m, 2H). 13C{1H} NMR (125 MHz,
CDCl3) δ 200.2, 136.7, 135.8, 135.5, 134.6, 134.3, 132.5, 129.6, 129.5,
128.3, 128.3, 127.7, 127.6, 126. 7, 126.6, 126.4, 125.6, 123.9, 122.7,
38.0, 32.2, 28.4, 23.1, 23.1. HRMS (ESI) m/z: [M + H]+ Calcd for
C24H23O 327.1743; found; 327.1743.
2
MHz, CDCl3) δ 199.1, 139.7, 138.3, 135.5, 134.2 (q, JC−F = 32.6
Hz), 129.1, 128.4, 128.3, 125.6 (q, 3JC−F = 3.7 Hz), 123.6 (q, 1JC−F
=
271.1 Hz), 37.9, 34.6, 25.5, 21.0. HRMS (ESI) m/z: [M + Na]+ Calcd
for C18H17F3NaO 329.1129; found 329.1124.
1-(o-Tolyl)-4-(p-tolyl)butan-1-one (3w). Purified by flash column
chromatography (petroleum ether/EtOAc = 100:1 to 50:1) as yellow
1
oil (74 mg, 74% yield). H NMR (500 MHz, CDCl3) δ 7.57−7.51
(m, 1H), 7.37−7.29 (m, 1H), 7.21 (dd, J1 = 9.5 Hz, J2 = 4.2 Hz, 2H),
7.12−7.01 (m, 4H), 2.87 (t, J = 9.5 Hz, J2 = 5.1 Hz, 2H), 2.65 (t, J =
7.6 Hz, 2H), 2.47 (s, 3H), 2.31 (s, 3H), 2.05−1.98 (m, 2H). 13C{1H}
NMR (125 MHz, CDCl3) δ 204.4, 138.5, 138.2, 137.7, 135.3, 131.8,
131.0, 129.0, 128.3, 128.2, 125.5, 40.7, 34.7, 25.9, 21.1, 20.9. HRMS
(ESI) [M + Na]+ Calcd for C18H20NaO 275.1412; found 275.1406.
1-(m-Tolyl)-4-(p-tolyl)butan-1-one (3x). Purified by flash column
chromatography (petroleum ether/EtOAc = 100:1 to 50:1) as
1-Phenyl-4-(p-tolyl)butan-1-one (3p).30c Purified by flash column
chromatography (petroleum ether/EtOAc = 100:1 to 50:1) as
1
colorless oil (74 mg, 78% yield). H NMR (500 MHz, CDCl3) δ
7.94−7.88 (m, 2H), 7.55−7.49 (m, 1H), 7.46−7.39 (m, 2H), 7.09 (s,
4H), 2.96 (t, J = 7.3 Hz, 2H), 2.71−2.61 (m, 2H), 2.31 (s, 3H),
2.10−2.01 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 200.1,
138.5, 137.0, 135.3, 132.8, 129.0, 128.5, 128.3, 128.0, 37.6, 34.7, 25.7,
20.9.
1
colorless oil (78 mg, 78% yield). H NMR (500 MHz, CDCl3) δ
7.71 (dd, J1 = 6.1 Hz J2 = 5.0 Hz, 2H), 7.37−7.29 (m, 2H), 7.09 (s,
4H), 2.94 (t, J = 7.3 Hz, 2H), 2.67 (t, J = 7.5 Hz, 2H), 2.39 (s, 3H),
2.31 (s, 3H), 2.08−2.01 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3)
δ 200.4, 138.6, 138.3, 137.0, 135.3, 133.6, 129.0, 128.5.128.4, 125.2,
37.7, 34.7, 25.9, 21.3, 21.0. HRMS (ESI) m/z: [M + Na]+ Calcd for
C18H20NaO 275.1412; found 275.1407.
1,4-Di-p-tolylbutan-1-one (3q). Purified by flash column chroma-
tography (petroleum ether/EtOAc = 100:1 to 50:1) as white solid (88
1
mg, 87% yield). mp: 73−75 °C. H NMR (500 MHz, CDCl3) δ
7.84−7.79 (m, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.09 (s, 4H), 2.93 (t, J =
7.3 Hz, 2H), 2.72−2.61 (m, 2H), 2.39 (s, 3H), 2.31 (s, 3H), 2.08−
2.01 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 199.8, 143.6,
138.6, 135.3, 134.6, 129.2, 129.0, 128.4, 128.1, 37.6, 34.8, 25.9, 21.6,
21.0. HRMS (ESI) m/z: [M + Na]+ Calcd for C18H20NaO 275.1412;
found 275.1406.
1-(4-(tert-Butyl)phenyl)-4-(p-tolyl)butan-1-one (3r). Purified by
flash column chromatography (petroleum ether/EtOAc = 100:1 to
50:1) as colorless oil (86 mg, 74% yield). 1H NMR (500 MHz,
1-(Naphthalen-1-yl)-4-(p-tolyl)butan-1-one (3y). Purified by flash
column chromatography (petroleum ether/EtOAc = 100:1 to 50:1)
as yellow oil (70 mg, 61% yield). 1H NMR (500 MHz, CDCl3) δ 8.54
(d, J = 8.6 Hz, 1H), 7.93 (d, J = 8.2 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H),
7.75 (d, J = 7.2 Hz, 1H), 7.55 (m, 1H), 7.49 (t, J = 7.5 Hz, 1H),
7.45−7.39 (m, 1H), 7.08 (s, 4H), 3.02 (t, J = 7.3 Hz, 2H), 2.69 (t, J =
7.6 Hz, 2H), 2.30 (s, 3H), 2.13−2.06 (m, 2H). 13C{1H} NMR (125
MHz, CDCl3) δ 204.5, 138.4, 136.2, 135.3, 133.9, 132.3, 130.1, 129.0,
128.3, 127.7, 127.1, 126.3, 125.7, 124.3, 41.3, 34.7, 26.2, 20.9. HRMS
F
https://dx.doi.org/10.1021/acs.joc.0c02209
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(ESI) m/z: [M + Na]+ Calcd for C21H20NaO 311.1412; found
311.1406.
List of starting materials, table of optimization, and
1
copies of H and 13C NMR spectra of all compounds
1-(Benzo[d][1,3]dioxol-5-yl)-4-(p-tolyl)butan-1-one (3z). Purified
by flash column chromatography (petroleum ether/EtOAc = 100:1 to
(PDF)
1
50:1) as white solid (80 mg, 71% yield). mp: 59−61 °C. H NMR
(500 MHz, CDCl3) δ 7.52−7.47 (m, 1H), 7.40 (d, J = 1.7 Hz, 1H),
7.08 (s, 4H), 6.80 (d, J = 8.1 Hz, 1H), 6.00 (s, 2H), 2.87 (t, J = 7.3
Hz, 2H), 2.65 (t, J = 7.5 Hz, 2H), 2.31 (s, 3H), 2.07−1.99 (m, 2H).
13C{1H} NMR (125 MHz, CDCl3) δ 198.2, 151.5, 148.1, 138.5,
135.3, 131.9, 129.0, 128.3, 124.1, 107.8, 107.7, 101.7, 37.4, 34.7, 26.0,
20.9. HRMS (ESI) m/z: [M + Na]+ Calcd for C18H18NaO3 305.1154;
found 305.1148.
AUTHOR INFORMATION
■
Corresponding Author
Bingwei Zhou − College of Chemical Engineering, Zhejiang
University of Technology, Hangzhou 310014, China;
orcid.org/0000-0002-8014-5482; Email: zhoubw@
zjut.edu.cn
1-(Thiophen-2-yl)-4-(p-tolyl)butan-1-one (3A). Purified by flash
column chromatography (petroleum ether/EtOAc = 100:1 to 50:1)
as yellow oil (52 mg, 54% yield). 1H NMR (500 MHz, CDCl3) δ 7.63
(dd, J1 = 3.8, J2 = 1.1 Hz, 1H), 7.59 (dd, J1 = 5.0 Hz, J2 = 1.1 Hz, 1H),
7.12−7.05 (m, 5H), 2.89 (t, J = 7.3 Hz, 2H), 2.69−2.65 (m, 2H),
2.31 (s, 3H), 2.09−2.02 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3)
δ 193.1, 144.4, 138.4, 135.4, 133.3, 131.7, 129.0, 128.3, 128.0, 38.5,
34.7, 26.1, 21.0. HRMS (ESI) m/z: [M + Na]+ Calcd for
C15H16NaOS 267.0820; found 267.0814.
1-(Naphthalen-2-yl)-3-phenyl-4-(p-tolyl)butan-1-one (3B). Puri-
fied by flash column chromatography (petroleum ether/EtOAc =
100:1 to 50:1) as white solid (50 mg, 35% yield). mp: 118−120 °C.
1H NMR (500 MHz, CDCl3) δ 8.29 (s, 1H), 7.92−7.86 (m, 2H),
7.82 (dd, J1 = 8.2 Hz, J2 = 5.0 Hz, 2H), 7.58−7.50 (m, 2H), 7.26−
7.21 (m, 4H), 7.17−7.13 (m, 1H), 7.05−6.98 (m, 4H), 3.76−3.65
(m, 1H), 3.44−3.37 (m, 2H), 2.98 (d, J = 7.4 Hz, 2H), 2.28 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3) δ 198.9, 144.3, 136.7, 135.5,
Authors
Zhen Wang − College of Chemical Engineering, Zhejiang
University of Technology, Hangzhou 310014, China
Yuanyuan Hu − College of Chemical Engineering, Zhejiang
University of Technology, Hangzhou 310014, China
Hongwei Jin − College of Chemical Engineering, Zhejiang
University of Technology, Hangzhou 310014, China
Yunkui Liu − College of Chemical Engineering, Zhejiang
University of Technology, Hangzhou 310014, China;
orcid.org/0000-0001-8614-458X
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02209
Author Contributions
All authors have given approval to the final version of the
manuscript.
135.5, 134.5, 132.4, 129.6, 129.5, 129.2, 128.9, 128.4, 128.3, 128.3,
127.7, 127.7, 126.7, 126.4, 123.9, 44.2, 43.4, 42.6, 21.0. HRMS(ESI)
m/z: [M + Na]+ Calcd for C27H24NaO 387.1725; found 387.1720.
3-Methyl-1-(naphthalen-2-yl)-3-phenyl-4-(p-tolyl)butan-1-one
(3C). Purified by flash column chromatography (petroleum ether/
Notes
The authors declare no competing financial interest.
1
EtOAc = 100:1 to 50:1) as light yellow oil (110 mg, 73% yield). H
ACKNOWLEDGMENTS
■
NMR (500 MHz, CDCl3) δ 8.32 (s, 1H), 7.90 (dd, J1 = 15.3 Hz, J2 =
8.4 Hz, 2H), 7.82 (t, J = 7.0 Hz, 2H), 7.60−7.47 (m, 2H), 7.33−7.24
(m, 4H), 7.19−7.10 (m, 1H), 6.95 (d, J = 7.6 Hz, 2H), 6.76 (d, J =
7.3 Hz, 2H), 3.66 (d, J = 16.5 Hz, 1H), 3.37 (d, J = 16.5 Hz, 1H),
3.17 (q, J = 13.1 Hz, 2H), 2.26 (s, 3H), 1.51 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3) δ 198.7, 147.1, 135.6, 135.5, 135.3, 134.9, 132.4,
130.6, 129.5, 129.4, 128.3, 128.2, 128.2, 128.0, 127.7, 126.6, 126.2,
125.8, 123.8, 48.5, 47.9, 41.5, 25.1, 21.0. HRMS (ESI) m/z: [M +
Na]+ Calcd for C28H26NaO 401.1881; found 401.1876.
We are grateful to the Natural Science Foundation of Zhejiang
Province (LQ20B020012), the Natural Science Foundation of
China (nos. 21772176 and 21372201) for financial support.
REFERENCES
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1
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267.1719.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02209.
G
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