Palladium-Catalyzed Ligand-Controlled Regioselective Nucleophilic Aromatic Substitution of 1-(Chloromethyl)naphthalenes with Arylacetonitriles

Article abstract of DOI:10.1021/acs.joc.8b02343

The palladium-catalyzed reaction of 1-(chloromethyl)naphthalenes 1 with (hetero)arylacetonitriles 2 gives either para- or ortho-acylated naphthalenes (3 or 4) in good to high yields. The regioselectivity can be controlled by the ligand of a palladium catalyst. A sterically bulky ligand, ^tBuPPh₂, affords para-acylated products 3, whereas a sterically less bulky ligand, Me₂PPh, provides ortho-acylated products 4. Further, direct substitution product 5 at the benzylic position is not obtained essentially, although such a reaction at the benzylic position is favorable in ordinary nucleophilic substitutions. In this paper, it was revealed that the benzylpalladium intermediate could react through a different mode (η³-benzylpalladium intermediate or η¹-benzylpalladium intermediate) in nucleophilic aromatic substitution. In addition to the interesting mechanistic aspect, the present reaction provides a facile synthetic method for a wide range of diaryl ketones, some of which are not easily available through the previously known procedures.

Full text of DOI:10.1021/acs.joc.8b02343

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Article
Palladium-Catalyzed Ligand-Controlled Regio-selective Nucleophilic
Aromatic Substitution of 1-(Chloromethyl)naphthalenes with Arylacetonitriles
Sheng Zhang, Yoshinori Yamamoto, and Ming Bao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02343 • Publication Date (Web): 26 Oct 2018
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Palladium-Catalyzed Ligand-Controlled Regio-
selective Nucleophilic Aromatic Substitution of 1-
(Chloromethyl)naphthalenes with Arylacetonitriles
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†
†,§
Sheng Zhang, Yoshinori Yamamoto, and Ming Bao
*,†,‡
†State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023,
China
‡
School of Petroleum and Chemical Engineering, Dalian University of Technology, Panjin
124221, China
§
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578,
Japan and Research Organization of Science and Technology, Ritsumeikan University, Kusatsu,
Shiga 525-8577, Japan
ABSTRACT: The palladium-catalyzed reaction of 1-(chloromethyl)naphthalenes 1 with
(hetero)arylacetonitriles 2 gives either para- or ortho-acylated naphthalenes (3 or 4) in good to
high yields. The regioselectivity can be controlled by the ligand of palladium catalyst. A
t
sterically bulky ligand, BuPPh2, affords para-acylated products 3, whereas a sterically less bulky
ligand, Me2PPh, provides ortho-acylated products 4. Further, direct substitution product 5 at
benzylic position is not obtained essentially, although such a reaction at benzylic position is
favorable in ordinary nucleophilic substitutions. In this paper, it was revealed that the
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benzylpalladium intermediate could react through different mode (η -benzylpalladium
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intermediate or η -benzylpalladium intermediate) in nucleophilic aromatic substitution. In
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addition to interesting mechanistic aspect, the present reaction provides a facile synthetic method
for a wide range of diaryl ketones, some of which are not easily available through the previously
known procedures.
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KEYWORDS: Ligand-control, Regio-selective, Nucleophilic substitution, Palladium catalysis,
Diaryl ketones
INTRODUCTION
Aromatic rings are important structural frameworks frequently found in various bioactive
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molecules, organic materials, and pharmaceuticals. Therefore, numerous methods for the
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functionalization of aromatic rings have been reported over the past decades. Among these
methods, electrophilic substitution reaction of arenes, namely the Friedel-Crafts reaction, is well
known and frequently used as a standard and important approach. The transition-metal-catalyzed
direct functionalization of aromatic C–H bonds has recently emerged as a powerful tool for the
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synthesis of aromatic ring-containing complex organic molecules. In comparison with Rh, Ru,
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Ir, Co, and Cu catalysts, Pd catalysts are specifically widely used for the functionalization
mainly due to the following reasons: many Pd(II) catalysts are compatible with oxidants and the
directed C–H bond functionalization reactions usually can be performed in the presence of
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ambient air and moisture. In comparison with the above-mentioned two methods, the
nucleophilic substitution reaction is rarely reported; this method required a leaving group linked
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on aromatic ring or a metal atom coordinated to aromatic π-system. Palladium-catalyzed
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aromatic substitution via η -benzylpalladium intermediate is recently reported by Tunge,
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Kuwano, and our group as a novel complement to the method of nucleophilic substitution
reaction. Tunge and co-worker succeeded in the control of product generation (dearomatized
alicyclic ketones or α-monoarylated ketones) by using different palladium catalyst and ligand.
Kuwano and co-workers successfully proved that intramolecular aromatic nucleophilic
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substitution of η -benzylpalladium intermediates could exclusively occur at para-position.
Herein, we report ligand-controlled regio-selective nucleophilic aromatic substitution of 1-
(chloromethyl)naphthalenes with arylacetonitriles (Scheme 1). The ordinary nucleophilic
substitution reaction of 1-(chloromethyl)naphthalenes with a nucleophile normally occurs on the
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benzylic position to afford benzylated products. However, palladium-catalyzed reaction of 1-
(chloromethyl)naphthalenes with arylacetonitriles does not give substitution products at benzylic
position, instead it affords regio-divergently either para- or ortho-substituted products; a
sterically bulky ligand provides para- whereas a less bulky ligand gives ortho-substituted
products. The para- or ortho-substituted products could easily converted to diaryl ketones
through aerobic oxidation (Scheme 1).
Scheme 1. Palladium-catalyzed regio-selective nucleophilic substitution reaction of 1-
(chloromethyl)naphthalenes with arylacetonitriles: a novel method for the synthesis of diaryl
ketones.
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RESULTS AND DISCUSSION
Screening
of
Reaction
Conditions
for
Regioselective
Acylation
of
1-
Chloromethylnaphthalenes. In our initial studies, we selected the reaction of 1-
(chloromethyl)naphthalene (1a) with phenylacetonitrile (2a) as a model to optimize the reaction
conditions. The optimization included the selection of the most suitable catalyst or precatalyst,
solvent, and ligand. Table 1 shows the results. The para-acylated product (3aa) was obtained as
a sole product when tetrahydrofuran (THF), hexane, and 1,4-dioxane were used as solvents in the
presence of Pd(PPh3)4 (entries 1–3, 60%, 27%, and 70%, respectively). However, the nucleophilic
substitution reaction of 2a occurred on the benzylic position of 1a to produce 2-(naphthalen-1-
yl)-1-phenylethanone (5) in 60% yield when a strong polar solvent dimethyl sulfoxide (DMSO)
was tested (entry 4). To control the reaction regioselectivity, other phosphine ligands were then
employed in the presence of a palladium precatalyst in 1,4-dioxane. The combinations of
Pd2(dba)3 and PPh3, Pd(OAc)2 and PPh3, Pd(OAc)2 and P(p-tol)3, and Pd(OAc)2 and P(o-tol)3
afforded 3aa as a sole product (entries 5–8, 32%, 76%, 65%, and 24%, respectively). No reaction
was observed when a bidentate ligand, 1,1'-bis(diphenylphosphino)ferrocene (DPPF), was
t
examined (entry 9). The highest yield of 3aa was obtained by combining Pd(OAc)2 and Ph2PBu,
a more sterically hindered phosphine ligand (entry 10, 85%). The regioselectivity was switched
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by utilizing smaller phosphine ligands PMe3 and Me2PPh. An ortho-acylated product 4aa was
obtained in a relatively high yield (64%) and high selectivity (3aa:4aa = 9/91) with the increased
loading of Me2PPh (entry 13 vs. entries 11 and 12).
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a
Table 1. Optimization of palladium-catalyzed ligand-controlled regio-divergent acylation
Entry
Catalyst
Ligand
Solvent
Yield Ratio of 3aa
b c
(%)
to 4aa
1
2
3
4
5
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd2(dba)3
none
none
none
none
PPh3
PPh3
THF
100/0
60
d
hexane
dioxane
DMSO
dioxane
dioxane
100/0
100/0
--
27
70
e
60
f
32
100/0
6
7
Pd(OAc)2
Pd(OAc)2
76
65
100/0
100/0
P(p-tol)3 dioxane
P(o-tol)3 dioxane
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Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
24
100/0
--
g
9
DPPF
dioxane
dioxane
dioxane
dioxane
dioxane
NR
85
t
Ph2PBu
10
11
12
100/0
10/90
12/88
9/91
h
PMe3
30
Me2PPh
Me2PPh
56
64
i
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Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), NaH (1.2 mmol), catalyst (5 mol%), and ligand (10
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mol%) in solvent (5 mL) at 30 ºC under N2 atmosphere for 12 h; then, the reaction mixture was stirred under
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c
1
d
air for 12 h. Isolated yields. Ratio of 3aa to 4aa was determined by H NMR. The starting material 1a was
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recovered in 43% yield. Nucleophilic substitution reaction occurred on the benzylic position to produce 2-
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f
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(naphthalen-1-yl)-1-phenylethanone (5). The starting material 1a was recovered in 40% yield. No reaction; 1a
h
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was recovered in 70% yield. By-product 5 was also separated in 42% yield. 20 mol%of Me2PPh was used.
Para-acylation of 1-(chloromethyl)naphthalenes. The scope and limitation of this type of
para-substitution reaction was explored under the optimal reaction conditions. Scheme 2
summarizes the results. When arylacetonitriles 2b–2d bearing a methyl group on ortho-, meta- or
para-position were tested in the reaction of 1a, 84%, 86%, and 82% yields of diaryl ketones
3ab–3ad were obtained, respectively. The reactions of arylacetonitriles bearing an alkyl (tert-
butyl) or aryl (phenyl) group on the para-position of the benzene ring also proceeded smoothly
to produce para-acylated products 3ae and 3af in satisfactory yields. High yields were obtained
in the reactions of methoxyl-substituted arylacetonitriles 2g–2i. In addition, the desired product
3aj was obtained in satisfactory yield (61%) when the para-(trifluoromethoxy)phenylacetonitrile
(2j) was examined. The reaction of 2-(naphthalen-2-yl)acetonitrile (2k) with 1a proceeded also
smoothly to produce the corresponding product 3ak in 74% yield. Halogen-substituted
arylacetonitriles 2l–2p were demonstrated to be suitable substrates in this reaction. The desired
products 3al–3ap were obtained in 71%–80% yields. Notably, the bromo atom linked to the
aromatic ring were tolerated under the reaction conditions, suggesting that further manipulation
based on C–Br bond may produce useful compounds. A relatively low yield (35%) was observed
when 2-(thiophen-2-yl)acetonitrile (2q), was examined. Here, 1-methylnaphthalene, a
dechlorinated product, was obtained as a major product (50% yield). The reactions of 1b–1i with
t
2a were examined under the abovementioned optimal conditions using BuPPh2 ligand, but the
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reaction did not proceed and the starting substrates were recovered. However, the para-
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substitution reaction successfully occurred by simply changing the phosphine ligand from
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sterically quite bulky Ph2PBu to PPh3. The para-acylated products 3ba and 3ca were obtained in
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satisfactory yields in the reaction of 1-(chloromethyl)naphthalene 1b or 1c bearing an ortho-
methyl or methoxy group. Good to high yields were observed in the reactions of 1d–1g bearing
an aryl substituent on the benzylic position. However, the alkyl-substituted 1-
(chloromethyl)naphthalenes 1h and 1i provided the desired products in moderate yields because
the β-hydride elimination occurred competitively.
Scheme 2. Palladium-catalyzed ligand-controlled para-acylation of 1-
a,b
(chloromethyl)naphthalenes.
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Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), NaH (60% in oil, 1.2 mmol), Pd(OAc)2 (5 mol%), and
t
Ph2PBu (10 mol%) in 1,4-dioxane (5 mL) at 30 ºC under N2 atmosphere for 12 h; then, the reaction mixture
b
c
was stirred at 30 ºC under air for an additional 12 h. Isolated yield. 1-Methylnaphthalene was isolated in 50%
d
yield. PPh3 was used as ligand.
Ortho-acylation of 1-(chloromethyl)naphthalenes. Next, we examined the nucleophilic
aromatic substitution reaction of 1-(chloromethyl)naphthalenes by using smaller Me2PPh as a
ligand. Scheme 3 shows the results. The reactions of 1a with various arylacetonitriles having
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methyl, tert-butyl, phenyl, methoxyl, and a halogen atom on the benzene ring proceeded
smoothly to give the ortho-acylated products 4aa–4al in moderate to satisfactory yields (40%–
70%). Arylacetonitriles bearing electron-donating groups gave higher regioselectivity than which
bearing electron-withdrawing groups. Interestingly, steric effect seemed positive for controlling
regioselectivity, no para-acylated product was produced when 2-(o-tolyl)acetonitrile was used as
nucleophile. Relatively high yields were observed when the para-position of 1-
(chloromethyl)naphthalene was blocked by a substituent such as methyl, phenyl, methoxyl, or
bromine atom (4ja–4ma, 60%–76% yields). The halogen atoms (F, Cl, and Br) linked on the
benzene rings of substrates were tolerated under the reaction conditions. The ortho-acylated
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products 4 cannot be regioselectively synthesized through the Friedel–Crafts acylation reaction.
In comparison with the para-acylation reaction, the ortho-acylation provided the desired
products in relatively lower yields even when the starting materials were completely consumed.
Scheme 3. Palladium-catalyzed ligand-controlled ortho-acylation of 1-
a,b
(chloromethyl)naphthalenes.
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Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), NaH (60% in oil, 1.2 mmol), Pd(OAc)2 (5 mol%), and
Me2PPh (20 mol%) in 1,4-dioxane (5 mL) at 30 ºC under N2 atmosphere for 12 h; then, the reaction mixture
b
was stirred at 30 ºC under air for an additional 12 h. Isolated yield; the ratio of 4 to 3 is shown within
parenthesis.
Scheme 4. Scale-up reaction.
Scale-up reaction. To demonstrate the practicality of this method, scale-up reactions were
performed under the standard conditions. The results are shown in Scheme 4. The para-acylated
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product 3aa and the ortho-acylated product 4aa were obtained in 78% and 59% yileds,
respectively. These results indicated that the scale-up reactions also proceeded smoothly without
loss of efficiency.
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Scheme 5. Mechanistic study.
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Scheme 6. η -Benzylpalladium intermediate (the structure of counter anion in complex 6 was
omitted for clear).
Mechanistic study. We performed control experiments (Scheme 5) to gain insights into the
mechanism of this type of nucleophilic substitution reaction. The reaction of 1a with 2b under
t
the standard conditions (BuPPh2, NaH, 1,4-dioxane), without aftertreatment using aerobic
oxygen, gave para-substituted product 2ab in 86% yield. Then, 2ab was converted to 3ab in
90% yield upon treatment with air as oxidant under basic conditions (Eq. 1). The deuterium-
labeling experiment revealed that D atom linked on the para-position of 1a-d migrated
completely to the benzylic position of product 3aa-d (Eq. 2).
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In order to confirm possibility of the formation of a η -benzylpalladium intermediate during this
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type of substitution reaction, we synthesized it according to reported literature. The addition of
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Then, dechlorination was carried out with AgOTf in CH2Cl2. Indeed, η -benzylpalladium
intermediate 6 was obtained and its structure was confirmed by X-ray analysis (Scheme 6).
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Based on our experimental outcomes and previous computational studies, we propose plausible
catalytic cycles to account for the present regio-selective aromatic substitution reaction. Scheme
7 illustrates the mechanism for para-substitution reaction. The oxidative addition of Pd(0)
t
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species [Pd(PBuPh2)2] to 1a produces cationic palladium complex A in a polar solvent. The
t
complex subsequently undergoes a ligand-exchange reaction due to the steric effect of PBuPh2 to
3
generate η -benzylpalladium intermediate B with phenylethenimine anion ligand derived from
phenylacetonitrile in the presence of NaH. C–C bond formation, as shown in B, produces C.
Ligand-exchange reaction occurs again for the production of intermediate D, a dearomatization
product, and Pd(0) species. The intermediate K subsequently undergoes deprotonation reaction
in the presence of NaH, followed by re-aromatization to generate intermediate E, which is finally
oxidated to the para-acylated product 3aa via peroxide intermediate F in the presence of oxygen
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as the oxidant.
Scheme 7. Proposed mechanism for para-acylation reaction.
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Scheme 8 illustrates a possible mechanism for ortho-substitution reaction. Similarly, cationic
palladium complex A′ is generated in a polar solvent through the oxidative addition of Pd(0)
species [Pd(PPhMe2)2] to 1a. Phenylethenimine anion coordinated to the palladium atom in A′
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generates η -benzylpalladium intermediate B′, which then undergoes C–C bond formation at the
ortho-position for the production of intermediate C′. The dearomatization product D′ is then
released from C′ and finally converted to a ortho-acylated product 4aa through deprotonation,
re-aromatization, and oxidation.
Scheme 8. Proposed mechanism for ortho-acylation reaction.
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CONCLUSIONS
We have developed a novel ligand-controlled regio-selective nucleophilic aromatic substitution
reaction of 1-(chloromethyl)naphthalenes. The para-acylated products are obtained in the
presence of a bulky ligand, whereas the ortho-acylated products are obtained in the presence of a
less bulky ligand. In this paper, it was revealed that the benzylpalladium intermediate could react
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through different mode (η -benzylpalladium intermediate or η -benzylpalladium intermediate) in
nucleophilic aromatic substitution. In addition to interesting mechanistic aspect, the present
reaction provides a facile synthetic method for a wide range of diaryl ketones, some of which are
not easily available through the previously known procedures.
EXPERIMENTAL SECTION
General Information
All reactions were carried out under a nitrogen atmosphere unless otherwise noted. Solvents
were purified by standard techniques without special instructions. 1H and 13C{1H} NMR spectra
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were recorded on Varian Inova-400 spectrometer (400 MHz for H, 100 MHz for 13C{1H}),
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Bruker Avance II-400 spectrometer (400 MHz for 1H, 100 MHz for 13C{1H}), and Varian Inova-
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500 spectrometer (500 MHz for H, 125 MHz for 13C{1H}); CDCl3 and TMS were used as a
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solvent and an internal standard, respectively. The chemical shifts are reported in ppm downfield
(δ) from TMS, the coupling constants J are given in Hz. The peak patterns are indicated as
follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. IR spectra were recorded on a
NEXUS FT-IR spectrometer. High resolution mass spectra were recorded on either a Q-TOF
mass spectrometry or a GC-TOF mass spectrometry. TLC was carried out on SiO2 (silica gel 60
F254, Merck), and the spots were located with UV light, iodoplatinate reagent or 1% aqueous
KMnO4. Flash chromatography was carried out on SiO2 (silica gel 60, 200-300 mesh).
Diffraction intensity data were collected on a Bruker Smart APEX CCD area detector
diffractometer (graphite monochrometer, MoKα radiation, λ = 0.71073 Å) at 296(2) K. All the
(hetero)arylacetonitriles are commercially available.
General procedure
To a suspension of NaH (48.0 mg, 60% dispersion in mineral oil, 1.2 mmol) in 1, 4-dioxane (5
mL), 2-phenylacetonitrile (2a, 70.3 mg, 0.6 mmol) was added at 30 ºC. After the colour of the
resulting mixture was changed to purple, 1-(chloromethyl)naphthalene (1a, 53.0 mg, 0.3 mmol)
was added, followed by Pd(OAc)2 (3.4 mg, 0.015 mmol), PtBuPh2 (7.3 mg, 0.03 mmol). The
reaction mixture was stirred for 12 h under a N2 atmosphere, followed by stirred the solution
under the air for another 12 h. Then quenched by water (10 mL) and extracted with ethyl acetate
(10 mL × 3). The combined organic layers were dried over Na2SO4 and concentrated under
reduced pressure. The residue obtained was purified via silica gel chromatography (eluent:
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hexane/ethyl acetate = 50:1) to afford (4-methylnaphthalen-1-yl)(phenyl)methanone (3aa) in
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85% yield (62.8 mg) as a white solid.
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(4-Methylnaphthalen-1-yl)(phenyl)methanone (3aa) : White solid (62.80 mg, 85% yield), mp
°
°
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69–70 C (lit. 67–69 C). H NMR (400 MHz, CDCl3) δ 2.74 (s, 3H), 7.33 (d, J = 7.2 Hz, 1H),
7.41–7.57 (m, 6H), 7.85 (d, J = 7.6 Hz, 2H), 8.06 (d, J = 8.0 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 20.1, 124.5, 125.2, 126.4, 127.0, 128.2, 128.5, 130.5, 131.2,
133.0, 133.1, 134.8, 138.4, 138.8, 198.2.
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(4-Methylnaphthalen-1-yl)(o-tolyl)methanone (3ab): Yellowish oil (65.60 mg, 84% yield). H
NMR (400 MHz, CDCl3) δ 2.43 (s, 3H), 2.73 (s, 3H), 7.18 (dd, J = 7.2, 7.6 Hz, 1H), 7.27 (dd, J
= 7.6, 8.8 Hz, 2H), 7.34–7.40 (m, 2H), 7.44 (d, J = 7.2 Hz, 1H), 7.56–7.61 (m, 2H), 8.06–8.08
(m, 1H), 8.66–8.68 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 20.3, 20.7, 124.6, 125.4, 125.5,
126.5, 126.6, 127.7, 130.3, 130.9, 131.0, 131.3, 131.4, 133.1, 134.8, 138.1, 140.0, 140.1, 200.4;
IR (neat) 3064, 2962, 2925, 1656, 1590, 1514, 1456, 1292, 1248, 1045, 975, 877, 761, 738 cm-1;
HRMS (EI, m/z) calcd for C19H16O: 260.1201 [M]+; found: 260.1203.
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(4-Methylnaphthalen-1-yl)(m-tolyl)methanone (3ac): Yellowish oil (67.16 mg, 86% yield). H
NMR (400 MHz, CDCl3) δ 2.36 (s, 3H), 2.74 (s, 3H), 7.28–7.33 (m, 2H), 7.37 (d, J = 7.6 Hz,
1H), 7.46 (d, J = 7.2 Hz, 1H), 7.49–7.57 (m, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.71 (s, 1H), 8.06 (d,
J = 8.4 Hz, 1H), 8.18 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 20.0, 21.4, 124.5,
125.2, 126.4, 126.5, 127.0, 127.9, 128.1, 128.3, 130.8, 131.2, 132.9, 134.0, 135.0, 138.30,
138.34, 138.8, 198.4; IR (neat) 3060, 2922, 1655, 1589, 1513, 1287, 1260, 1180, 976, 761, 741
cm-1; HRMS (EI, m/z) calcd for C19H16O: 260.1201 [M]+; found: 260.1211.
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(4-Methylnaphthalen-1-yl)(p-tolyl)methanone (3ad): Yellowish oil (64.04 mg, 82% yield). H
NMR (400 MHz, CDCl3) δ 2.40 (s, 3H), 2.74 (s, 3H), 7.22 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 7.2
Hz, 1H), 7.44–7.50 (m, 2H), 7.54 (dd, J = 6.8, 7.6 Hz, 1H), 7.75 (d, J = 8.0 Hz, 2H), 8.06 (d, J =
13
8.4 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 20.0, 21.9, 124.5,
125.3, 126.4, 126.5, 126.9, 127.7, 129.2, 130.7, 131.2, 132.9, 135.2, 136.1, 138.1, 144.1, 197.9;
IR (neat) 2955, 2924, 2854, 1656, 1604, 1513, 1456, 1284, 1254, 1178, 973, 833, 762 cm-1;
HRMS (EI, m/z) calcd for C19H16O: 260.1201 [M]+; found: 260.1194.
(4-(tert-Butyl)phenyl)(4-methylnaphthalen-1-yl)methanone (3ae): Yellowish oil (72.58 mg, 80%
yield). 1H NMR (400 MHz, CDCl3) δ 1.34 (s, 9H), 2.75 (s, 3H), 7.33 (d, J = 7.2 Hz, 1H), 7.44–
7.51 (m, 4H), 7.53–7.57 (m, 1H), 7.80 (d, J = 8.4 Hz, 2H), 8.07 (d, J = 8.0 Hz, 1H), 8.16 (d, J =
13
8.4 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 20.1, 31.3, 35.3, 124.5, 125.2, 125.5, 126.4,
126.5, 126.9, 127.8, 130.6, 131.2, 133.0, 135.2, 136.0, 138.1, 157.0, 197.9; IR (neat) 3069, 2963,
2904, 2868, 1657, 1604, 1513, 1284, 1257, 1187, 1108, 974, 878, 851, 834, 785, 771, 758, 711
cm-1; HRMS (EI, m/z) calcd for C22H22O: 302.1671 [M]+; found: 302.1672.
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[1,1'-Biphenyl]-4-yl(4-methylnaphthalen-1-yl)methanone (3af): Yellowish solid (67.70 mg, 70%
yield), mp 106–107 °C. 1H NMR (400 MHz, CDCl3) δ 2.78 (s, 3H), 7.36–7.60 (m, 8H), 7.63 (d, J
= 7.2 Hz, 1H), 7.67 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H), 8.09 (d, J = 8.0 Hz, 1H), 8.18
(d, J = 8.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 20.1, 124.6, 125.3, 126.48, 126.51,
127.1, 127.2, 127.4, 128.0, 128.4, 129.1, 131.16, 131.24, 133.0, 135.0, 137.4, 138.4, 140.0,
145.9, 197.8; IR (KBr) 3059, 2924, 1653, 1601, 1514, 1422, 1284, 1256, 1111, 1007, 974, 878,
760, 746, 697 cm-1; HRMS (EI, m/z) calcd for C24H18O: 322.1358 [M]+; found: 322.1365.
(4-Methoxyphenyl)(4-methylnaphthalen-1-yl)methanone (3ag): Yellowish solid (69.64 mg, 84%
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yield), mp 77–78 C. H NMR (400 MHz, CDCl3) δ 2.73 (s, 3H), 3.83 (s, 3H), 6.89 (d, J = 8.4
Hz, 2H), 7.32 (d, J = 7.2 Hz, 1H), 7.42–7.48 (m, 2H), 7.53 (dd, J = 7.2, 8.0 Hz, 1H), 7.83 (d, J =
8.8 Hz, 2H), 8.06 (dd, J = 7.6, 8.0 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 20.0, 55.6,
113.7, 124.5, 125.3, 126.3, 126.5, 126.8, 127.1, 131.1, 131.4, 132.9, 135.5, 137.7, 163.8, 196.9;
IR (KBr) 3071, 2932, 2839, 1651, 1598, 1509, 1254, 1170, 1029, 973, 878, 845, 768 cm-1;
HRMS (EI, m/z) calcd for C19H16O2: 276.1150 [M]+; found: 276.1151.
(3,4-Dimethoxyphenyl)(4-methylnaphthalen-1-yl)methanone (3ah): Yellowish solid (79.04 mg,
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86% yield), mp 104–105 C. H NMR (400 MHz, CDCl3) δ 2.76 (s, 3H), 3.92 (s, 3H), 3.94 (s,
3H), 6.79 (d, J = 8.4 Hz, 1H), 7.29 (dd, J = 2.0, 8.4 Hz, 1H), 7.35 (d, J = 7.2 Hz, 1H), 7.45–7.51
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(m, 2H), 7.54–7.57 (m, 1H), 7.64 (d, J = 2.0 Hz, 1H), 8.07 (d, J = 8.8 Hz, 2H); C{1H} NMR
(100 MHz, CDCl3) δ 20.0, 56.16, 56.21, 109.9, 111.6, 124.5, 125.2, 126.35, 126.41, 126.5,
126.8, 127.1, 131.2, 131.5, 132.9, 135.3, 137.7, 149.2, 153.6, 197.0; IR (KBr) 3077, 2935, 2838,
1651, 1592, 1511, 1463, 1416, 1264, 1126, 1023, 979, 914, 879, 809, 765 cm-1; HRMS (EI, m/z)
calcd for C20H18O3: 306.1256 [M]+; found: 306.1263.
(3-Fluoro-4-methoxyphenyl)(4-methylnaphthalen-1-yl)methanone (3ai): Yellowish solid (71.52
mg, 81% yield), mp 92–93 °C. 1H NMR (400 MHz, CDCl3) δ 2.75 (s, 3H), 3.92 (s, 3H), 6.93 (dd,
J = 8.0, 8.4 Hz, 1H), 7.34 (d, J = 7.2 Hz, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.47–7.58 (m, 3H), 7.67
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(dd, J = 2.0, 11.6 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H); C{1H} NMR (100 MHz, CDCl3) δ 20.0,
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56.4, 112.3 (d, JC-F = 1.6 Hz), 117.8 (d, JC-F = 18.9 Hz), 124.6, 125.3, 126.3, 126.5, 127.0,
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127.4, 128.2 (d, JC-F = 3.3 Hz), 131.1, 131.7 (d, JC-F = 5.0 Hz), 133.0, 134.7, 138.2, 152.0 (d,
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1JC-F = 246.5 Hz), 152.1 (d, JC-F = 10.9 Hz), 196.0; IR (KBr) 3072, 2936, 2843, 1652, 1609,
1513, 1434, 1282, 1174, 1114, 1021, 763 cm-1; HRMS (EI, m/z) calcd for C19H15O2F: 294.1056
[M]+; found: 294.1051.
(4-Methylnaphthalen-1-yl)(4-(trifluoromethoxy)phenyl)methanone (3aj): Yellow oil (60.44 mg,
61% yield). 1H NMR (400 MHz, CDCl3) δ 2.76 (s, 3H), 7.27 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 7.2
Hz, 1H), 7.46 (d, J = 7.2 Hz, 1H), 7.51–7.60 (m, 2H), 7.90 (d, J = 8.8 Hz, 2H), 8.08 (d, J = 8.4
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Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 20.1, 120.5 (q, JC-F
=
257.2 Hz), 124.6, 125.2, 126.3, 126.5, 126.6, 127.3, 128.3, 131.1, 132.5, 133.0, 134.2, 137.1,
139.0, 152.7, 196.5; IR (neat) 3074, 2926, 2861, 1660, 1601, 1591, 1514, 1503, 1254, 1167,
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1017, 975, 877, 837, 767 cm-1; HRMS (EI, m/z) calcd for C19H13O2F3: 330.0868 [M]+; found:
330.0869.
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(4-Methylnaphthalen-1-yl)(naphthalen-2-yl)methanone (3ak): Yellow oil (65.79 mg, 74% yield).
1H NMR (400 MHz, CDCl3) δ 2.77 (s, 3H), 7.36 (d, J = 7.2 Hz, 1H), 7.46–7.59 (m, 5H), 7.79 (d,
J = 8.4 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 8.05–8.10 (m, 2H), 8.20 (d, J
= 8.4 Hz, 1H), 8.24 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 20.1, 124.6, 125.3, 125.7,
126.50, 126.53, 126.9, 127.1, 127.9, 128.1, 128.5, 128.7, 129.8, 131.3, 132.5, 132.9, 133.0,
135.1, 135.8, 136.1, 138.4, 198.2; IR (neat) 3057, 1655, 1626, 1591, 1513, 1464, 1289, 1185,
1118, 978, 821, 762 cm-1; HRMS (EI, m/z) calcd for C22H16O: 296.1201 [M]+; found: 296.1208.
(2-Chlorophenyl)(4-methylnaphthalen-1-yl)methanone (3al): Yellow oil (59.80 mg, 71% yield).
1H NMR (400 MHz, CDCl3) δ 2.73 (s, 3H), 7.24 (d, J = 7.6 Hz, 1H), 7.33–7.36 (m, 1H), 7.41–
7.43 (m, 2H), 7.47 (d, J = 7.2 Hz, 2H), 7.58–7.68 (m, 2H), 8.07 (d, J = 8.4 Hz, 1H), 8.98 (d, J =
8.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 20.4, 124.6, 125.4, 126.7, 126.76, 126.82,
128.2, 130.2, 130.4, 131.2, 131.5, 132.1, 132.4, 132.8, 133.2, 140.4, 141.4, 197.1; IR (neat)
3065, 2923, 2855, 1660, 1590, 1515, 1433, 1289, 1245, 1075, 977, 877, 763, 745 cm-1; HRMS
(EI, m/z) calcd for C18H13OCl: 280.0655 [M]+; found: 280.0663.
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(3-Chlorophenyl)(4-methylnaphthalen-1-yl)methanone (3am): White solid (63.17 mg, 75%
yield), mp 93–94 °C. 1H NMR (400 MHz, CDCl3) δ 2.76 (s, 3H), 7.34–7.39 (m, 2H), 7.47 (d, J =
7.2 Hz, 1H), 7.51–7.58 (m, 3H), 7.69 (d, J = 7.6 Hz, 1H), 7.85 (dd, J = 1.6, 2.0 Hz, 1H), 8.08 (d,
J = 8.0 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 20.1, 124.6,
125.2, 126.3, 126.6, 127.3, 128.6, 128.7, 129.8, 130.3, 131.2, 133.0, 133.1, 133.9, 134.8, 139.2,
140.5, 196.7; IR (KBr) 3066, 2923, 2859, 1660, 1589, 1568, 1514, 1423, 1285, 1250, 1201, 977,
838, 762, 743 cm-1; HRMS (EI, m/z) calcd for C18H13OCl: 280.0655 [M]+; found: 280.0656.
(4-Chlorophenyl)(4-methylnaphthalen-1-yl)methanone (3an): Yellowish oil (62.33 mg, 74%
yield). 1H NMR (400 MHz, CDCl3) δ 2.76 (s, 3H), 7.35 (d, J = 7.2 Hz, 1H), 7.41 (d, J = 8.4 Hz,
2H), 7.46 (d, J = 7.2 Hz, 1H), 7.50–7.59 (m, 2H), 7.79 (d, J = 8.4 Hz, 2H), 8.08 (d, J = 8.4 Hz,
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1H), 8.14 (d, J = 8.4 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 20.1, 124.6, 125.3, 126.3,
126.4, 126.6, 127.2, 128.2, 128.9, 131.1, 131.9, 133.0, 134.3, 137.2, 138.8, 139.7, 196.9; IR
(neat) 3069, 2923, 1657, 1587, 1514, 1422, 1284, 1254, 1089, 1013, 974, 875, 843, 764 cm-1;
HRMS (EI, m/z) calcd for C18H13OCl: 280.0655 [M]+; found: 280.0659.
(4-Fluorophenyl)(4-methylnaphthalen-1-yl)methanone (3ao): Yellow oil (63.43 mg, 80% yield).
1H NMR (400 MHz, CDCl3) δ 2.76 (s, 3H), 7.10 (dd, J = 8.8, 8.8 Hz, 2H), 7.34 (dd, J = 0.8, 7.2
Hz, 1H), 7.45 (d, J = 7.2 Hz, 1H), 7.48–7.59 (m, 2H), 7.86–7.89 (m, 2H), 8.07 (d, J = 8.0 Hz,
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1H), 8.11 (d, J = 8.4 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 20.1, 115.7 (d, JC-F = 21.8
Hz), 124.6, 125.3, 126.4, 126.6, 127.1, 127.9, 131.1, 133.0, 133.1 (d, 3JC-F =9.3 Hz), 134.6, 135.1
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(d, JC-F = 2.9 Hz), 138.6, 165.9 (d, JC-F = 253.5 Hz), 196.6; IR (neat) 3072, 2924, 1659, 1596,
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1504, 1284, 1254, 1231, 1155, 973, 851, 766, 584 cm-1; HRMS (EI, m/z) calcd for C18H13OF:
264.0950 [M]+; found: 264.0953.
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(4-Bromophenyl)(4-methylnaphthalen-1-yl)methanone (3ap): Yellow solid (71.22 mg, 73%
yield), mp 75–76 °C. 1H NMR (400 MHz, CDCl3) δ 2.76 (s, 3H), 7.34 (d, J = 7.2 Hz, 1H), 7.45
(d, J = 7.2 Hz, 1H), 7.50–7.59 (m, 4H), 7.71 (d, J = 8.0 Hz, 2H), 8.08 (d, J = 8.0 Hz, 1H), 8.15
(d, J = 8.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 20.1, 124.6, 125.2, 126.3, 126.6, 127.2,
128.3, 128.4, 131.1, 131.8, 132.0, 133.0, 134.2, 137.5, 138.4, 138.9, 197.0; IR (KBr) 3067, 2923,
2860, 1656, 1583, 1514, 1396, 1283, 1254, 1070, 1010, 974, 875, 841, 763 cm-1; HRMS (EI,
m/z) calcd for C18H13OBr: 324.0150 [M]+; found: 324.0148.
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(4-Methylnaphthalen-1-yl)(thiophen-2-yl)methanone (3aq): Yellow oil (26.49 mg, 35% yield).
1H NMR (400 MHz, CDCl3) δ 2.75 (s, 3H), 7.08 (dd, J = 3.6, 5.2 Hz, 1H), 7.35 (d, J = 7.2 Hz,
1H), 7.47 (dd, J = 1.2, 3.6 Hz, 1H), 7.50–7.59 (m, 2H), 7.63 (d, J = 7.2 Hz, 1H), 7.71 (dd, J =
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1.2, 5.2 Hz, 1H), 8.06 (d, J = 7.6 Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H); C{1H} NMR (100 MHz,
CDCl3) δ 20.1, 124.5, 125.2, 126.2, 126.5, 127.0, 127.4, 128.2, 130.8, 134.7, 135.0, 135.6, 138.5,
145.7, 189.9; IR (neat) 3076, 2923, 1635, 1589, 1514, 1411, 1352, 1291, 1258, 1232, 1057, 967,
809, 763, 726 cm-1; HRMS (EI, m/z) calcd for C16H12OS: 252.0609 [M]+; found: 252.0604.
(3,4-Dimethylnaphthalen-1-yl)(phenyl)methanone (3ba): Yellowish solid (58.57 mg, 75% yield),
mp 90–91 °C. 1H NMR (400 MHz, CDCl3) δ 2.48 (s, 3H), 2.66 (s, 3H), 7.40–7.46 (m, 4H), 7.50–
7.59 (m, 2H), 7.85 (d, J = 7.6 Hz, 2H), 8.07 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.8 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 15.2, 20.9, 124.2, 125.9, 126.3, 126.4, 128.5, 129.9, 130.5,
131.1, 132.0, 133.17, 133.21, 134.2, 135.4, 138.8, 198.4; IR (KBr) 3061, 2923, 1656, 1560,
1578, 1511, 1447, 1280, 1253, 1207, 1024, 866, 753, 715 cm-1; HRMS (EI, m/z) calcd for
C19H16O: 260.1201 [M]+; found: 260.1198.
(3-Methoxy-4-methylnaphthalen-1-yl)(phenyl)methanone (3ca): Yellowish solid (56.37 mg, 68%
°
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yield), mp 66–67 C. H NMR (400 MHz, CDCl3) δ 2.62 (s, 3H), 3.89 (s, 3H), 7.32 (d, J = 7.6
Hz, 1H), 7.35 (s, 1H), 7.45 (dd, J = 7.2, 8.0 Hz, 2H), 7.51 (dd, J = 7.6, 7.6 Hz, 1H), 7.58 (dd, J =
7.2, 7.6 Hz, 1H), 7.86 (d, J = 7.6 Hz, 2H), 7.96 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 11.2, 56.9, 115.3, 123.4, 124.0, 124.6, 126.3, 126.7, 128.6,
130.6, 133.4, 134.1, 135.8, 138.4, 153.1, 198.0; IR (KBr) 3067, 2936, 2842, 1660, 1593, 1512,
1462, 1448, 1339, 1237, 1174, 1113, 1055, 1028, 862, 756, 716 cm-1; HRMS (EI, m/z) calcd for
C19H16O2: 276.1150 [M]+; found: 276.1148.
(4-Benzylnaphthalen-1-yl)(phenyl)methanone (3da): Yellowish solid (77.37 mg, 80% yield), mp
92–93 °C. 1H NMR (400 MHz, CDCl3) δ 4.49 (s, 2H), 7.21 (d, J = 7.2 Hz, 3H), 7.28 (dd, J = 7.6,
8.0 Hz, 3H), 7.41–7.51 (m, 5H), 7.57 (dd, J = 7.2, 7.6 Hz, 1H), 7.88 (d, J = 7.6 Hz, 2H), 8.07–
8.09 (m, 1H), 8.14–8.16 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 39.5, 124.7, 125.9, 126.5,
126.6, 126.7, 127.0, 127.8, 128.6, 128.7, 128.9, 130.6, 131.6, 132.5, 133.3, 135.5, 138.5, 140.0,
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140.5, 198.2; IR (KBr) 3060, 3026, 2920, 1658, 1595, 1580, 1513, 1494, 1448, 1282, 1254, 876,
849, 765, 710 cm-1; HRMS (EI, m/z) calcd for C24H18O: 322.1358 [M]+; found: 322.1349.
(4-(4-Methylbenzyl)naphthalen-1-yl)(phenyl)methanone (3ea): Yellow oil (84.78 mg, 84%
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yield). H NMR (400 MHz, CDCl3) δ 2.31 (s, 3H), 4.46 (s, 2H), 7.10 (br, 4H), 7.30 (d, J = 7.2
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Hz, 1H), 7.42–7.51 (m, 5H), 7.57 (dd, J = 7.2, 7.6 Hz, 1H), 7.87 (d, J = 7.6 Hz, 2H), 8.08–8.10
(m, 1H), 8.13–8.16 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 21.2, 39.0, 124.7, 125.8, 126.5,
126.7, 127.0, 127.9, 128.5, 128.8, 129.4, 130.6, 131.6, 132.5, 133.3, 135.4, 136.0, 136.9, 138.5,
140.8, 198.2; IR (neat) 3048, 3022, 2920, 1658, 1595, 1579, 1513, 1448, 1283, 1253, 876, 853,
766, 714 cm-1; HRMS (EI, m/z) calcd for C25H20O: 336.1514 [M]+; found: 336.1511.
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(4-(4-Fluorobenzyl)naphthalen-1-yl)(phenyl)methanone (3fa): White solid (81.69 mg, 80%
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yield), mp 103–104 C. H NMR (400 MHz, CDCl3) δ 4.45 (s, 2H), 6.96 (dd, J = 8.4, 8.8 Hz,
2H), 7.13–7.17 (m, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.41–7.51 (m, 5H), 7.57 (dd, J = 7.2, 7.6 Hz,
1H), 7.87 (d, J = 7.2 Hz, 2H), 8.02–8.05 (m, 1H), 8.13–8.15 (m, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 38.6, 115.5 (d, 2JC-F = 21.2 Hz), 124.6, 125.9, 126.6, 126.8, 127.1, 127.7, 128.6, 130.3
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(d, JC-F = 7.8 Hz), 130.6, 131.6, 132.4, 133.4, 135.6 (d, JC-F = 3.2 Hz), 135.7, 138.5, 140.2,
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161.6 (d, JC-F = 243.0 Hz), 198.1; IR (KBr) 3065, 2919, 1657, 1597, 1580, 1509, 1448, 1283,
1254, 1221, 1158, 912, 877, 826, 788, 714 cm-1; HRMS (EI, m/z) calcd for C24H17OF: 340.1263
[M]+; found: 340.1259.
(4-(2-Chlorobenzyl)naphthalen-1-yl)(phenyl)methanone (3ga): Yellow oil (87.78 mg, 82%
yield). 1H NMR (400 MHz, CDCl3) δ 4.58 (s, 2H), 6.92 (dd, J = 1.6, 7.6 Hz, 1H), 7.08–7.12 (m,
1H), 7.16–7.20 (m, 2H), 7.42–7.46 (m, 3H), 7.48–7.52 (m, 3H), 7.55–7.59 (m, 1H), 7.86–7.89
(m, 2H), 7.99–8.01 (m, 1H), 8.15–8.18 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 36.7,
124.5, 125.7, 126.6, 126.9, 127.1, 127.2, 127.8, 128.0, 128.6, 129.6, 130.6, 130.9, 131.5, 132.5,
133.3, 134.3, 135.7, 137.6, 138.5, 139.1, 198.1; IR (neat) 3062, 2913, 1659, 1595, 1579, 1514,
1446, 1283, 1253, 1177, 1051, 909, 878, 799 cm-1; HRMS (EI, m/z) calcd for C24H17OCl:
356.0968 [M]+; found: 356.0962.
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Phenyl(4-propylnaphthalen-1-yl)methanone (3ha): Yellow oil (42.80 mg, 52% yield). H NMR
(400 MHz, CDCl3) δ 1.06 (t, J = 7.4 Hz, 3H), 1.79–1.85 (m, 2H), 3.11 (t, J = 7.6 Hz, 2H), 7.34
(d, J = 7.2 Hz, 1H), 7.44 (dd, J = 7.6, 8.0 Hz, 2H), 7.49 (d, J = 7.6 Hz, 2H), 7.53–7.60 (m, 2H),
7.86 (d, J = 7.2 Hz, 2H), 8.13 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 14.5, 24.0, 35.7, 124.4, 124.6, 126.4, 126.6, 126.9, 128.1, 128.5, 130.6, 131.6,
132.3, 133.2, 134.8, 138.7, 142.8, 198.3; IR (neat) 3060, 2959, 2930, 2870, 1658, 1560, 1579,
1514, 1448, 1275, 1252, 1176, 878, 799, 763, 714 cm-1; HRMS (EI, m/z) calcd for C20H18O:
274.1358 [M]+; found: 274.1359.
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(4-Butylnaphthalen-1-yl)(phenyl)methanone (3ia): Yellow oil (47.58 mg, 55% yield). H NMR
(400 MHz, CDCl3) δ 0.99 (t, J = 7.4 Hz, 3H), 1.44–1.53 (m, 2H), 1.73–1.81 (m, 2H), 3.13 (t, J =
7.8 Hz, 2H), 7.34 (d, J = 7.2 Hz, 1H), 7.42–7.50 (m, 4H), 7.53–7.59 (m, 2H), 7.86 (d, J = 6.8 Hz,
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2H), 8.13 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 14.2,
23.1, 33.0, 33.4, 124.4, 124.5, 126.4, 126.7, 126.9, 128.1, 128.5, 130.6, 131.6, 132.3, 133.2,
134.8, 138.8, 143.1, 198.3; IR (neat) 3060, 2956, 2930, 2870, 1658, 1560, 1580, 1514, 1448,
1282, 1254, 841, 764 cm-1; HRMS (EI, m/z) calcd for C21H20O: 288.1514 [M]+; found: 288.1512.
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(1-Methylnaphthalen-2-yl)(phenyl)methanone (4aa): Yellowish oil (42.85 mg, 58% yield). H
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NMR (400 MHz, CDCl3) δ 2.61 (s, 3H), 7.37 (d, J = 8.4 Hz, 1H), 7.45 (dd, J = 7.2, 8.0 Hz, 2H),
7.55–7.63 (m, 3H), 7.77 (d, J = 8.4 Hz, 1H), 7.84 (dd, J = 1.2, 8.0 Hz, 2H), 7.89 (dd, J = 2.4, 7.6
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Hz, 1H), 8.12 (d, J = 7.6 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 16.5, 124.79, 124.84,
126.3, 126.87, 126.93, 128.7, 128.8, 130.4, 132.8, 132.9, 133.5, 134.0, 136.6, 137.9, 199.6; IR
(neat) 3056, 2924, 1665, 1595, 1448, 1277, 1248, 1167, 933, 813, 750, 719 cm-1; HRMS (EI,
m/z) calcd for C18H14O: 246.1045 [M]+; found: 246.1042.
(1-Methylnaphthalen-2-yl)(o-tolyl)methanone (4ab): White solid (47.64 mg, 61% yield), mp 64–
°
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65 C. H NMR (400 MHz, CDCl3) δ 2.57 (s, 3H), 2.67 (s, 3H), 7.16 (dd, J = 7.2, 7.6 Hz, 1H),
7.30–7.42 (m, 4H), 7.54–7.61 (m, 2H), 7.71 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 7.2 Hz, 1H), 8.14
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(d, J = 7.6 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 16.1, 21.2, 125.0, 125.4, 125.6, 126.1,
126.7, 127.0, 128.6, 131.5, 131.7, 131.8, 132.8, 134.0, 134.1, 137.5, 138.5, 139.1, 201.6; IR
(KBr) 3055, 2925, 1662, 1597, 1569, 1453, 1242, 930, 820, 773, 751, 737 cm-1; HRMS (EI, m/z)
calcd for C19H16O: 260.1201 [M]+; found: 260.1206.
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(1-Methylnaphthalen-2-yl)(m-tolyl)methanone (4ac): Yellow oil (43.74 mg, 56% yield). H
NMR (400 MHz, CDCl3) δ 2.38 (s, 3H), 2.61 (s, 3H), 7.31–7.41 (m, 3H), 7.58–7.62 (m, 3H),
7.68 (s, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 7.2 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 16.5, 21.5, 124.8, 124.9, 126.2, 126.8, 126.9, 127.8, 128.6, 128.8,
130.7, 132.76, 132.83, 134.0, 134.4, 136.8, 138.0, 138.6, 199.9; IR (neat) 3054, 2922, 1664,
1600, 1584, 1280, 1257, 1161, 954, 825, 754 cm-1; HRMS (EI, m/z) calcd for C19H16O: 260.1201
[M]+; found: 260.1197.
(1-Methylnaphthalen-2-yl)(p-tolyl)methanone (4ad): Yellowish solid (47.64 mg, 61% yield), mp
95–96 °C. 1H NMR (400 MHz, CDCl3) δ 2.42 (s, 3H), 2.60 (s, 3H), 7.24 (d, J = 8.4 Hz, 2H), 7.36
(d, J = 8.4 Hz, 1H), 7.55–7.62 (m, 2H), 7.73 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.4 Hz, 1H), 7.89
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(d, J = 7.6 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 16.5, 21.9,
124.7, 124.8, 126.2, 126.8, 128.8, 129.5, 130.5, 132.5, 132.8, 133.9, 135.4, 136.9, 144.5, 199.3;
IR (KBr) 3053, 2922, 1661, 1603, 1446, 1277, 1250, 1166, 933, 815, 757 cm-1; HRMS (EI, m/z)
calcd for C19H16O: 260.1201 [M]+; found: 260.1207.
(4-(tert-Butyl)phenyl)(1-methylnaphthalen-2-yl)methanone (4ae): Yellowish oil (63.51 mg, 70%
yield). 1H NMR (400 MHz, CDCl3) δ 1.34 (s, 9H), 2.61 (s, 3H), 7.36 (d, J = 8.4 Hz, 1H), 7.45 (d,
J = 8.8 Hz, 2H), 7.53–7.61 (m, 2H), 7.74–7.79 (m, 3H), 7.88 (d, J = 7.6 Hz, 1H), 8.11 (d, J = 8.0
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 16.3, 31.1, 35.2, 124.6, 124.7, 125.6, 126.0, 126.7,
128.7, 130.3, 132.5, 132.7, 133.8, 135.1, 136.8, 157.3, 199.1; IR (neat) 3054, 2963, 2905, 2868,
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1663, 1604, 1463, 1278, 1253, 1169, 1108, 936, 812, 771, 748 cm-1; HRMS (EI, m/z) calcd for
C22H22O: 302.1671 [M]+; found: 302.1676.
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[1,1'-Biphenyl]-4-yl(1-methylnaphthalen-2-yl)methanone (4af): Yellow solid (48.36 mg, 50%
yield), mp 100–101 °C. 1H NMR (400 MHz, CDCl3) δ 2.64 (s, 3H), 7.37–7.40 (m, 2H), 7.46 (dd,
J = 7.2, 7.6 Hz, 2H), 7.55–7.61 (m, 4H), 7.66 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 1H), 7.90
(d, J = 8.0 Hz, 3H), 8.12 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 16.5, 124.75,
124.84, 126.3, 126.88, 126.91, 127.4, 127.5, 128.5, 128.8, 129.1, 131.0, 132.78, 132.83, 134.0,
136.57, 136.64, 140.0, 146.2, 199.2; IR (KBr) 3055, 3032, 1662, 1601, 1448, 1279, 1252, 1168,
935, 814, 753, 697 cm-1; HRMS (EI, m/z) calcd for C24H18O: 322.1358 [M]+; found: 322.1357.
(4-Methoxyphenyl)(1-methylnaphthalen-2-yl)methanone (4ag): Yellow oil (48.08 mg, 58%
yield). 1H NMR (400 MHz, CDCl3) δ 2.59 (s, 3H), 3.85 (s, 3H), 6.91 (d, J = 8.8 Hz, 2H), 7.35 (d,
J = 8.4 Hz, 1H), 7.53–7.59 (m, 2H), 7.76 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 9.2 Hz, 2H), 7.88 (d, J
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= 7.6 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 16.4, 55.7, 114.0,
124.6, 124.7, 126.2, 126.7, 126.8, 128.8, 130.9, 132.2, 132.7, 132.8, 133.9, 137.0, 164.0, 198.3;
IR (neat) 3053, 2933, 2839, 1656, 1598, 1508, 1420, 1253, 1163, 1028, 934, 816, 767 cm-1;
HRMS (EI, m/z) calcd for C19H16O2: 276.1150 [M]+; found: 276.1148.
(3,4-Dimethoxyphenyl)(1-methylnaphthalen-2-yl)methanone (4ah): White solid (51.47 mg, 56%
yield), mp 93–94 °C. 1H NMR (400 MHz, CDCl3) δ 2.61 (s, 3H), 3.94 (s, 3H), 3.95 (s, 3H), 6.81
(d, J = 8.4 Hz, 1H), 7.23 (dd, J = 2.0, 8.4 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.55–7.63 (m, 3H),
7.77 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 7.6 Hz, 1H), 8.11 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 16.3, 56.07, 56.13, 109.9, 111.0, 124.5, 124.6, 126.0, 126.4, 126.6, 126.7, 128.7,
130.8, 132.2, 132.7, 133.7, 136.8, 149.2, 153.7, 198.2; IR (KBr) 2935, 2838, 1654, 1594, 1583,
1510, 1417, 1273, 1262, 1133, 1022, 765 cm-1; HRMS (EI, m/z) calcd for C20H18O3: 306.1256
[M]+; found: 306.1250.
(3-Fluoro-4-methoxyphenyl)(1-methylnaphthalen-2-yl)methanone (4ai): White solid (48.56 mg,
55% yield), mp 100–101 °C. 1H NMR (400 MHz, CDCl3) δ 2.59 (s, 3H), 3.94 (s, 3H), 6.94 (dd, J
= 8.0, 8.4 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 7.53–7.60 (m, 3H), 7.64 (dd, J = 2.4, 12.0 Hz, 1H),
7.77 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 7.6 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100
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MHz, CDCl3) δ 16.4, 56.5, 112.4, 117.4 (d, JC-F = 18.7 Hz), 124.5, 124.8, 126.3, 126.9, 128.2
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(d, JC-F = 3.3 Hz), 128.8, 131.1, 132.5, 132.8, 133.9, 136.3, 152.2 (d, JC-F = 247.0 Hz), 152.4
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(d, JC-F = 10.8 Hz), 197.4; IR (KBr) 3059, 2936, 2846, 1660, 1608, 1514, 1433, 1281, 1117,
1022, 798, 761 cm-1; HRMS (EI, m/z) calcd for C19H15O2F: 294.1056 [M]+; found: 294.1050.
(4-Bromophenyl)(1-methylnaphthalen-2-yl)methanone (4aj): White solid (39.03 mg, 40% yield),
mp 130–131 °C. 1H NMR (400 MHz, CDCl3) δ 2.60 (s, 3H), 7.34 (d, J = 8.4 Hz, 1H), 7.56–7.63
(m, 4H), 7.69 (d, J = 8.8 Hz, 2H), 7.77 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 7.2 Hz, 1H), 8.11 (d, J =
7.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 16.5, 124.6, 124.9, 126.4, 127.0, 127.1, 128.8,
128.9, 131.8, 132.1, 132.8, 133.0, 134.1, 135.9, 136.7, 198.5; IR (KBr) 3053, 1660, 1582, 1276,
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1247, 1165, 1068, 1008, 934, 810, 757 cm-1; HRMS (EI, m/z) calcd for C18H13OBr: 324.0150
[M]+; found: 324.0142.
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°
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yield), mp 128–129 C. H NMR (400 MHz, CDCl3) δ 2.60 (s, 3H), 7.35 (d, J = 8.4 Hz, 1H),
7.43 (d, J = 8.4 Hz, 2H), 7.56–7.64 (m, 2H), 7.77 (d, J = 8.4 Hz, 3H), 7.90 (d, J =7.6 Hz, 1H),
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8.12 (d, J = 7.6 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 16.5, 124.6, 124.9, 126.4, 127.0,
127.1, 128.9, 129.1, 131.7, 132.8, 133.0, 134.1, 136.0, 136.3, 140.1, 198.3; IR (KBr) 3056, 1659,
1583, 1277, 1248, 1089, 935, 811, 759 cm-1; HRMS (EI, m/z) calcd for C18H13OCl: 280.0655
[M]+; found: 280.0659.
(3-Chlorophenyl)(1-methylnaphthalen-2-yl)methanone (4al): Yellowish oil (38.74 mg, 46%
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yield). H NMR (400 MHz, CDCl3) δ 2.61 (s, 3H), 7.34–7.41 (m, 2H), 7.54–7.61 (m, 3H), 7.68
(d, J = 7.6 Hz, 1H), 7.78 (d, J = 8.8 Hz, 1H), 7.82 (s, 1H), 7.90 (d, J = 7.2 Hz, 1H), 8.12 (d, J =
8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 16.5, 124.6, 124.9, 126.4, 127.0, 127.2, 128.5,
128.8, 130.08, 130.12, 132.8, 133.3, 133.4, 134.1, 135.1, 135.7, 139.6, 198.2; IR (neat) 3063,
1667, 1569, 1422, 1277, 1244, 1171, 1072, 945, 819, 757, 736 cm-1; HRMS (EI, m/z) calcd for
C18H13OCl: 280.0655 [M]+; found: 280.0649.
(1,4-Dimethylnaphthalen-2-yl)(phenyl)methanone (4ja): Yellowish solid (53.11 mg, 68% yield),
mp 86–87 °C. 1H NMR (400 MHz, CDCl3) δ 2.56 (s, 3H), 2.68 (s, 3H), 7.21 (s, 1H), 7.45 (dd, J
= 7.6, 7.6 Hz, 2H), 7.56–7.62 (m, 3H), 7.84 (d, J = 8.0 Hz, 2H), 8.05–8.07 (m, 1H), 8.11–8.14
(m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 16.5, 19.6, 124.9, 125.2, 125.3, 126.4, 126.7,
128.7, 130.3, 130.7, 132.5, 132.9, 133.3, 133.5, 136.3, 137.9, 199.9; IR (KBr) 3067, 2925, 2866,
1666, 1597, 1449, 1387, 1308, 1245, 1167, 929, 757, 718 cm-1; HRMS (EI, m/z) calcd for
C19H16O: 260.1201 [M]+; found: 260.1197.
(1-Methyl-4-phenylnaphthalen-2-yl)(phenyl)methanone (4ka): Yellow oil (58.03 mg, 60% yield).
1H NMR (400 MHz, CDCl3) δ 2.66 (s, 3H), 7.33 (s, 1H), 7.39–7.64 (m, 10H), 7.88 (d, J = 7.6
Hz, 2H), 7.97 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
16.6, 125.1, 125.5, 126.7, 126.98, 126.99, 127.6, 128.5, 128.8, 130.3, 130.4, 132.2, 132.3, 133.2,
133.6, 136.3, 137.9, 138.6, 140.3, 199.5; IR (neat) 3059, 2924, 2856, 1666, 1596, 1449, 1387,
1244, 1073, 944, 768, 702 cm-1; HRMS (EI, m/z) calcd for C24H18O: 322.1358 [M]+; found:
322.1348.
(4-Methoxy-1-methylnaphthalen-2-yl)(phenyl)methanone (4la): Yellowish solid (63.00 mg, 76%
yield), mp 82–83 °C. 1H NMR (400 MHz, CDCl3) δ 2.47 (s, 3H), 3.94 (s, 3H), 6.70 (s, 1H), 7.45
(dd, J = 7.6, 7.6 Hz, 2H), 7.54–7.63 (m, 3H), 7.86 (d, J = 7.2 Hz, 2H), 8.03 (d, J = 7.6 Hz, 1H),
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8.34 (d, J = 8.0 Hz, 1H); C{1H} NMR (100 MHz, CDCl3) δ 16.0, 55.7, 102.7, 122.7, 124.2,
124.6, 126.2, 126.4, 127.3, 128.8, 130.3, 133.6, 133.7, 136.3, 137.8, 153.8, 199.7; IR (KBr)
3068, 2934, 2844, 1667, 1595, 1510, 1450, 1371, 1347, 1275, 1239, 1112, 937, 810, 763, 720
cm-1; HRMS (EI, m/z) calcd for C19H16O2: 276.1150 [M]+; found: 276.1151.
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(4-Bromo-1-methylnaphthalen-2-yl)(phenyl)methanone (4ma): Yellow solid (59.51 mg, 61%
yield), mp 96–97 °C. 1H NMR (400 MHz, CDCl3) δ 2.56 (s, 3H), 7.47 (dd, J = 7.6, 8.0 Hz, 2H),
7.59–7.71 (m, 4H), 7.83 (d, J = 6.8 Hz, 2H), 8.12 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 8.0 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 16.6, 121.0, 125.3, 127.7, 128.1, 128.3, 128.4, 128.9, 130.4,
132.4, 132.8, 133.9, 134.1, 137.1, 137.4, 197.9; IR (KBr) 3068, 2924, 1668, 1596, 1449, 1325,
1270, 1244, 1176, 943, 903, 801, 757, 725 cm-1; HRMS (EI, m/z) calcd for C18H13OBr: 324.0150
[M]+; found: 324.0154.
2-(Naphthalen-1-yl)-1-phenylethan-1-one (5)21: White solid (44.34 mg, 60% yield), mp 105–106
°C (lit. 105–107 °C). 1H NMR (400 MHz, CDCl3) δ 4.74 (s, 2H), 7.36 (d, J = 7.2 Hz, 1H), 7.44–
7.51 (m, 5H), 7.56–7.60 (m, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.86–7.88 (m, 2H), 8.08 (d, J = 7.2
Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 43.1, 123.9, 125.5, 125.8, 126.3, 127.9, 128.0,
128.5, 128.7, 128.8, 131.4, 132.3, 133.3, 133.9, 136.7, 197.6.
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2-(4-Methylnaphthalen-1-yl)-2-(o-tolyl)acetonitrile (2ab): Colorless oil (70.01 mg, 86% yield).
1H NMR (400 MHz, CDCl3) δ 2.34 (s, 3H), 2.69 (s, 3H), 5.88 (s, 1H), 7.13–7.17 (m, 1H), 7.21–
7.25 (m, 3H), 7.29 (d, J = 7.2 Hz, 1H), 7.34 (d, J = 7.2 Hz, 1H), 7.48–7.56 (m, 2H), 7.78 (d, J =
8.0 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 19.5, 19.7, 36.8,
119.6, 123.3, 125.4, 126.2, 126.4, 126.6, 126.9, 127.0, 128.5, 128.58, 128.64, 130.7, 131.2,
133.4, 133.7, 135.9, 136.0; IR (neat) 3071, 3021, 2973, 2864, 2241, 1600, 1516, 1488, 1460,
1389, 1164, 1032, 910, 838, 748 cm-1; HRMS (EI, m/z) calcd for C20H17N: 271.1361 [M]+;
found: 271.1356.
Deuterated (4-methylnaphthalen-1-yl)(phenyl)methanone (3aa-d): Yellowish oil (51.94 mg, 70%
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yield, 97% D). H NMR (400 MHz, CDCl3) δ 2.74 (s, 2H), 7.34 (d, J = 7.2 Hz, 1H), 7.42–7.58
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(m, 6H), 7.85 (d, J = 8.0 Hz, 2H), 8.07 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H); C{1H}
NMR (100 MHz, CDCl3) δ 19.8 (t, J = 19.4 Hz), 124.6, 125.3, 126.47, 126.49, 127.1, 128.2,
128.5, 130.6, 131.2, 133.0, 133.2, 134.8, 138.5, 138.8, 198.2; IR (neat) 3060, 2922, 1656, 1590,
1579, 1513, 1448, 1274, 1250, 1202, 1074, 897, 828, 757, 716, 700 cm-1; HRMS (EI, m/z) calcd
for C18H13DO: 247.1107 [M]+; found: 247.1116.
Supporting Information.
Detailed descriptions of preparation of deuterium-labeled substrate and X-ray data for 3aa, 4ak
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1
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and 6 as well as copies of H and C{ H} NMR spectra are presented in the Supporting
Information. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
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Corresponding Author
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*mingbao@dlut.edu.cn
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Author Contributions
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of China (No. 21372035, 21573032,
and 21602026) and the China Postdoctoral Science Foundation (No. 2016M590226) for their
financial support.
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