Cyclization reaction for the synthesis of polysubstituted naphthalenes in the presence of Au(I) precatalysts

Article abstract of DOI:10.1021/jo201339z

Au(I)-catalyzed cyclization of alkenyl carbonyl compounds leading to a variety of substituted naphthalenes has been developed. This process exploits a dual function of the Au(I) catalyst: (1) the oxophilic nature of the Au(I) catalyst, counterintuitive to the π-acidic reactivities generally associated with Au catalysts, and (2) olefin isomerization supported by the outcome of isotope scrambling experiments. It cannot be completely excluded that TfOH is a true operative catalyst in this protocol. In view of the practicality, the unnecessity of isomerically pure starting material in this reaction is particularly attractive and valuable.

Full text of DOI:10.1021/jo201339z

ARTICLE
pubs.acs.org/joc
Cyclization Reaction for the Synthesis of Polysubstituted
Naphthalenes in the Presence of Au(I) Precatalysts
Arun R. Jagdale, Jong Hyub Park, and So Won Youn*
Department of Chemistry and Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Korea
S Supporting Information
b
ABSTRACT: Au(I)-catalyzed cyclization of alkenyl carbonyl com-
pounds leading to a variety of substituted naphthalenes has been
developed. This process exploits a dual function of the Au(I) catalyst:
(1) the oxophilic nature of the Au(I) catalyst, counterintuitive to the π-
acidic reactivities generally associated with Au catalysts, and (2) olefin
isomerization supported by the outcome of isotope scrambling
experiments. It cannot be completely excluded that TfOH is a true
operative catalyst in this protocol. In view of the practicality, the unnecessity of isomerically pure starting material in this reaction is
particularly attractive and valuable.
Scheme 1. Au(I)-Catalyzed Reactions of Alkenyl β-Keto
’ INTRODUCTION
Esters
Substituted naphthalenes have attracted considerable attention
owing to their prevalence in a variety of compounds possessing
important physical and biological properties.1 Consequently, a
number of synthetic strategies have been reported for the con-
struction of these privileged structural motifs.2 Recently, we
reported a Au(I)-catalyzed3 cyclization of 2-alkenylphenyl carbo-
nyl compounds to afford a variety of indenes, indenols, and
indanones (Scheme 1(1)).4 In this process, Au(I) exhibited
oxophilic Lewis acidity5 to activate the carbonyl group of alde-
hydes, ketones, and β-keto esters in the presence of CꢀC multiple
bonds. During the course of this study, we also uncovered the
influence of olefin substitution in determining the reaction path-
ways. In this context, while disubstituted styrenes (type A) led to
the indene product (type B) as previously described, trisubstituted
styrenes (type 1a) underwent CꢀC bond formation at γ (allylic)
position to furnish the corresponding naphthalenes derivatives 2a
and 3a (Scheme 1, (1) vs (2)).
’ RESULTS AND DISCUSSION
Having uncovered this unexpected and novel transformation,
we set out to explore the utility and scope of this process
(Tables 1 and 2). Indeed, our initial result was particularly
encouraging, where a reaction condition consists of 5 mol % of
Ph3PAuCl/AgOTf (1:1) in ClCH2CH2Cl (0.025 M) at 100 °C
for 1.5 h to afford naphthalene products 2a/3a with a combined
yield of 95%. The cyclization process could also take place
uneventfully at higher concentrations (0.1 M), and both catalyst
loading and reaction temperature could be reduced without
incurring penalty on the reaction yield, albeit a longer reaction
time was required (Table 1, entry 1). Substrates bearing either
electron-donating or electron-withdrawing substituents on the
aromatic moiety were well tolerated, leading to the correspond-
ing products in good to excellent yields. We also discovered
that the isomeric form of the starting alkene substrates is
Before proceeding with the discussion, a few cursory words
from the mechanistic perspective will be instructive and serve
to highlight the novelty of this unexpected transformation.
First and foremost, the formation of naphthalenes (2a and 3a)
suggested that the methyl substituent of substrate 1a (i.e., R = Me)
had participated in the carbonꢀcarbon bond forming process,
presumably through the intermediacy of 1aC (an isomeric form
of 1a).
The γ-carbon in 1aC then undergoes nucleophilic attack to
the keto carbon of the proximal β-keto ester motif, thereby
leading to the naphthalene backbone of products 2a and 3a
(Scheme 2, path b).6 This observation is indeed counterintui-
tive in the context of Au(I) catalysis, where 1aC is expected to
undergo a 6-exo-trig cyclization originating from the nucleo-
philic attack of the 1,3-dicarbonyl to the π-activated alkene, a
net process generally referred to as the Conia-ene reaction7
(Scheme 2, path a).
Received: July 4, 2011
Published: July 22, 2011
r
2011 American Chemical Society
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Scheme 2. Transition-Metal-Catalyzed Reactions between 1,3-Dicarbonyl and Olefin Functionalities
inconsequential to the reaction outcome, where both isomeri-
cally pure 2-methyl-1-propenyl- (1g, 6h) and 2-methylallyl-
substituted (1h, 6i) substrates afforded the same products in
comparable yields. Allylic substrates with no substituents at β
position (1i, 6jꢀl) failed to undergo any productive cyclizations.
Lastly, the reactions of 1g and 1h afforded significant amount of
isochromane (4a), presumably through the competitive intramole-
cular nucleophilic addition of β-keto ester oxygen to alkene group.8
Next, we examined the reaction of 6h in the presence of other
Lewis acids and protic acids (Table 3). With the exception of
AgOTf, Cu(OTf)2, Bi(OTf)3, and TfOH, most of the Lewis and
Brønsted acids examined were ineffective with the recovery of 6h.
It is noteworthy that the reaction did not take place in the absence
of cationic Au(I) catalyst (Table 3, entry 2). On the other hand,
AuCl3 did not promote the reaction at all (Table 3, entry 3).
Considering the well-known π-philic Lewis acidity of Au(I) that
activates the alkene moiety toward nucleophlic attack by 1,3-
dicarbonyls,7cꢀe and recognizing Au(III) is more oxophilic than
Au(I),9 our findings are particularly noteworthy. We suspected
that trace amounts of protic acid could conceivably be generated
in situ and thereby catalyze the reaction.10 Indeed, TfOH did result
in the production of 7h, albeit in moderate yield (45%, Table 3,
entry 12). In sharp contrast, other protic acids such as trifluoroacetic
acid (CF3CO2H) did not show the ability to produce the desired
product 7h. In addition, Sc(OTf)3 and Zn(OTf)2 were totally
ineffective and other triflate salts (e.g., AgOTf, Cu(OTf)2, and
Bi(OTf)3) gave lower conversions than the combination of
Ph3PAuCl and AgOTf. These results suggest that cationic Au(I)
plays a somehow important role in this transformation, although the
catalytic system consisting of Ph3PAuCl/AgOTf could serve as a
precatalyst for the generation of the likely operative catalyst, TfOH.
To gain further mechanistic insights into this reaction, an isotope
scrambling experiment was performed as shown in Scheme 3. In
sharp contrast to the use of only either Ph3PAuCl or AgOTf, upon
treatment of R-methylstilbene 8 with D2O in the presence of
Ph3PAuCl/AgOTf, significant deuterium exchange was observed
along with a trace amount of the thermodynamically less stable
alkene derivative 80. These findings are in support of a Au(I)-
catalyzed olefin isomerization,11 where 2-alkyl-1-propenyl-substi-
tuted substrates (e.g., 1bꢀg, 5d, 6c,d,fꢀh) also led to the corre-
sponding naphthalene products.
amount of the required alkene isomer. Activation of the carbonyl
functionality through the participation of the Lewis acidic Au(I)
catalyst (or TfOH) (C) precedes the intramolecular nucleophlic
attack by the pendant alkene moiety, thereby generating a newly
formed carbonꢀcarbon bond (D). Subsequent proton transfer
leads to tertiary alcohol E and regenerates the Au(I) (or H+)
catalyst, where the former species undergoes further aromaticity-
driven dehydration to give the naphthalenes. Considering allylic
substrates bearing no substituents at the β position (1i, 6jꢀl)
failed to give any of the desired products, the stabilization of a
charge-delocalized species (i.e., C to D) appears to be an essential
feature for the cyclization reaction to take place.
’ CONCLUSION
In summary, we have developed a Au(I)-catalyzed cyclization
reaction of alkenyl carbonyl compounds to afford a variety of
substituted naphthalenes.13ꢀ15 In this process, Au(I) served to
activate the carbonyl group of β-keto esters as well as aldehydes
and ketones, preferentially exhibiting oxophilicity in the presence
of CꢀC multiple bonds that is counterintuitive to the π-philic
nature of Au(I) catalyst.16 Furthermore, we also secured evi-
dence pointing toward a Au(I)-catalyzed olefin isomerization. An
alternative or synergistic mechanistic pathway involving TfOH as
a true operative catalyst cannot be completely excluded. In
addition, the isomeric mixture of starting material is inconsequen-
tial, where an isomerization process was believed to have taken place
during the reaction and thereby funneling all isomeric reactants to
the naphthalene products. This is particularly attractive on the
practical standpoint where the preparation of isomerically pure
starting material is not necessary. It is much anticipated that these
findings and the associated new reactivities unveiled will lead to
further advancements in the field of Au-catalyzed reaction, and our
continued efforts in this area will be reported in due course.
’ EXPERIMENTAL SECTION
General Information. Nuclear magnetic resonance spectra were
recorded on 400 MHz instrument. Spectra were recorded in CDCl3 solutions
referenced to TMS or solvent residual peak. High-resolution mass spectra
were measured using EI at 70 eV. GCꢀMS spectra were recorded with EI
ionization and an Elite-1 column (0.25 mm ꢁ 30 m, film: 0.25 μm). For
control of the conversion and characterization of the products, the following
method was used: The method starts with the injection temperature T0
(50 °C); after holding this temperature for 20 min, the column is heated to
the temperature T1 (ramp, 300 °C) and held for an additional 3 min. Flash
chromatography was performed on silica gel 230ꢀ400 mesh. All catalysts
were purchased as higher quality and used as received. Unless otherwise
On the basis of our experimental findings and by analogy with
the mechanism proposed for the related cyclization reaction of
alkenyl carbonyl compounds,12 a plausible mechanism is out-
lined in Scheme 4. Although the exact mechanism for this process
is yet to be fully elucidated, a plausible starting point may involve
a Au(I)-promoted olefin isomerization to generate a small
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Table 1. Au(I)-Catalyzed Cyclization Reaction of Alkenyl β-Keto Esters 1
a Performed in CH2Cl2 at 60 °C.
noted, all commercially obtained reagents were used as received. THF and
benzene were distilled from sodium benzophenone ketyl immediately prior
to use. CH2Cl2 was distilled from CaH2 immediately prior to use. Thin layer
chromatograms (TLC) were visualized via UV and anisaldehyde stain.
General Procedures for the Preparation of Alkenylben-
zaldehydes. Method A. To the solution of the corresponding
2-bormobenzaldehyde, R-methylstyrene (5.0 equiv), and DIPEA
(1.5 equiv) in DMA (0.1 M) in a round-bottom flask were added
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Table 2. Au(I)-Catalyzed Cyclization Reaction of Alkenylaryl Ketones 5 and Alkenylbenzaldehydes 6
a Performed at 100 °C. b Performed with 4 mol % Ph3PAuCl/AgOTf.
Pd(OAc)2 (2 mol %) and P(o-Tol)3 (2 mol %) under argon atmo-
sphere. The reaction mixture was heated at 135 °C for 2ꢀ12 h. The
reaction mixture was quenched with H2O and extracted with
CH2Cl2 (three times). The combined organic layer was washed with
brine, dried over MgSO4, and concentrated in vacuo. The residue
was purified by column chromatography on silica gel (EtOAc/n-
hexane = 1:10ꢀ1:50) to afford the desired product.
corresponding 2-bormobenzaldehyde (1.0 equiv) was added to form a
light red solution. After 2 h, the reaction mixture was quenched with
satd NH4Cl/water (1:1) and extracted with CH2Cl2 (three times).
The combined organic layer was washed with brine, dried over
MgSO4, and concentrated in vacuo. The residue was purified by
column chromatography on silica gel to afford the desired 1-alkenyl-
2-bromobenzene product. To a solution of the corresponding 1-alke-
nyl-2-bromobenzene in THF was added n-BuLi (1.6 M solution in
hexane, 1.5 equiv) dropwise slowly at ꢀ78 °C. The resulting solution
was stirred for 3 h at ꢀ78 °C, and DMF (1.5 equiv) was slowly added.
Method B. To the suspension of phosphonium salt (1.2 equiv) in
THF was slowly added n-BuLi (1.6 M solution in hexane, 1.2 equiv) at
0 °C. The resulting solution was stirred for 30 min at 0 °C, and the
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Table 3. Cyclization Reaction of 6h Catalyzed by Various
Lewis Acids and Brønsted Acids
Scheme 3. Deuterium Exchange Experiment
entry
catalyst
yielda (%)
1
2
Ph3PAuCl/AgOTf (1:1)
Ph3PAuCl
AuCl3
80
0
3
0
4
AgOTf
54
7
5
Sc(OTf)3
Cu(OTf)2
Bi(OTf)3
Zn(OTf)2
AlCl3
6
57
51
8
7
Scheme 4. Proposed Mechanism for the Au(I)-Catalyzed
Cyclization Reaction of Alkenyl Carbonyl Compounds
8
9
0
10
11
12
13
ZnCl2
0
BF3 Et2O
0
3
TfOH
45
0
CF3CO2H
1
a Yields were determined by H NMR using trichloroethylene as an
internal standard.
After 0.25ꢀ1 h, the reaction mixture was quenched with satd NH4Cl
solution and extracted with CH2Cl2 (three times). The combined
organic layer was washed with brine, dried over MgSO4, and concen-
trated in vacuo. The residue was purified by column chromatography on
silica gel (EtOAc/n-hexane = 1:20ꢀ1:50) to afford the desired product.
Method C. To a solution of the 2-formylphenylboronic acid and
corresponding allyl halide (1ꢀ1.2 equiv) in THF (0.2 M) in a round-
bottom flask were added PdCl2(PPh3)2 (2.5 mol %) and aq Na2CO3
(1 M, 2 equiv) solution. The reaction mixture was heated at reflux for
3ꢀ4 h. The reaction mixture was quenched with H2O and extracted with
CH2Cl2 (threetimes). Thecombinedorganiclayerwaswashedwithbrine,
dried overMgSO4, and concentratedinvacuo. The residue was purifiedby
column chromatography on silica gel (EtOAc/n-hexane = 1:50) to afford
the desired product.
2H, E), 7.55ꢀ7.59 (m, 2H, allyl), 7.63 (dd, J = 2.8, 8.8 Hz, 1H, E),
7.97 (dd, J = 6.0, 8.8 Hz, 1H, Z), 10.18 (d, J = 2.8 Hz, 1H, Z), 10.19
(d, J = 2.4 Hz, 1H, allyl), 10.23 (d, J = 2.8 Hz, 1H, E); 13C NMR
(CDCl3, 100 MHz) δ 17.1, 25.6, 36.7, 114.1 (d, J = 22.0 Hz), 114.2
(d, J = 22.0 Hz), 115.0, 116.4 (d, J = 21.2 Hz), 120.5 (d, J = 21.2 Hz),
120.77 (d, J = 21.3 Hz), 120.81 (d, J = 22.0 Hz), 121.6, 122.3, 125.8,
127.2, 127.80, 127.84, 128.2, 128.3, 128.4, 128.5, 132.4 (d, J = 6.8
Hz), 133.0 (d, J = 6.8 Hz), 133.3 (d, J = 6.8 Hz), 135.38, 135.44,
135.47, 135.52, 137.3, 137.4, 137.5, 137.6, 137.7, 139.9, 140.4, 141.2,
142.0, 142.9, 147.4, 161.3 (d, J = 247.4 Hz), 161.7 (d, J = 247.4 Hz),
165.6 (d, J = 255.8 Hz), 190.4, 190.5, 190.8; HRMS (EI) [M]+ m/z
calcd for C16H13FO 240.0950, found 240.0953.
4-Fluoro-2-(2-phenylprop-1-enyl)benzaldehyde (6c). Following method
B using 2-bromo-5-fluorobenzaldehyde (807.9 mg, 4 mmol) and triphenyl-
(1-phenylethyl)phosphonium bromide (2.230 g, 5.0 mmol), 6c was ob-
tained: 511.2 mg (53%, E/Z = 81:19); 1H NMR (CDCl3, 400 MHz) δ 2.11
(s, 3H, Z), 2.32 (s, 3H, E), 6.67 (dd, J = 2.6, 9.8 Hz, 1H, E), 6.89 (s, 1H, E),
6.93 (td, J = 2.8, 8.4 Hz, 1H, E), 7.03ꢀ7.07 (m, 2H of E and 1H of Z), 7.12
(td, J = 1.8, 8.4 Hz, 1H, Z), 7.15 (s, 1H, Z), 7.18ꢀ7.21 (m, 3H, E), 7.35
(d, J = 6.8 Hz, 1H, Z), 7.41 (t, J = 7.4 Hz, 2H, Z), 7.57 (d, J = 7.2 Hz, 2H, Z),
7.77 (dd, J = 6.2, 8.6 Hz, 1H, E), 7.97 (dd, J = 6.0, 8.4 Hz, 1H, Z), 10.15
(s, 1H, E), 10.20 (s, 1H, Z); 13C NMR (CDCl3, 100 MHz) δ 17.3, 25.9,
114.3 (d, J = 22.0 Hz), 114.7 (d, J = 22.0 Hz), 117.3 (d, J = 22.0 Hz), 117.7
(d, J = 22.0 Hz), 121.8, 122.5, 127.5, 128.0, 128.32, 128.35, 128.5, 130.1,
131.7 (d, J = 9.9 Hz), 139.8, 141.4, 142.0, 143.6, 144.3 (d, J = 9.8 Hz), 144.5
(d, J = 9.9 Hz), 165.4 (d, J = 254.3 Hz), 165.6 (d, J = 255.7 Hz), 190.3, 190.6
(3 carbons are missing due to overlapping); HRMS (EI) [M]+ m/z calcd for
C16H13FO 240.0950, found 240.0952.
2-(2-Phenylprop-1-enyl)benzaldehyde (6a).13e. Following method
A using 2-bormobenzaldehyde (1.851 g, 10 mmol) for 12 h, 6a was
obtained: 1.325 g (60%, E/Z/allyl = 61:18:21); 1H NMR (CDCl3,
400 MHz) δ 2.09 (d, J = 1.2 Hz, 3H, E), 2.32 (d, J = 1.6 Hz, 3H, Z), 4.25
(s, 2H, allyl), 4.72 (s, 1H, allyl), 5.47 (s, 1H, allyl), 6.94 (s, 1H, Z), 7.01
(d, J = 7.6 Hz, 1H, Z), 7.04 (dd, J = 2.2, 7.4 Hz, 2H, Z), 7.14ꢀ7.18 (m,
2H, allyl), 7.21 (s, 1H, E), 7.28ꢀ7.53 (m, 5H of E, 5H of Z, and 6H of
allyl), 7.58 (d, J = 7.2 Hz, 2H, E), 7.61 (td, J = 1.4, 7.8 Hz, 1H, E), 7.75
(dd, J = 1.2, 7.6 Hz, 1H, Z), 7.88 (dd, J = 1.2, 7.6 Hz, 1H, allyl), 7.95
(d, J = 7.6 Hz, 1H, E), 10.23 (s, 1H, Z), 10.24 (s, 1H, allyl), 10.28 (s, 1H,
E); 13C NMR (CDCl3, 100 MHz) δ 17.1, 25.7, 37.4, 114.7, 123.0, 123.6,
125.8, 126.6, 126.9, 127.0, 127.1, 127.58, 127.61, 128.0, 128.2, 128.3,
128.4, 128.8, 128.9, 130.5, 131.1, 131.3, 131.4, 133.0, 133.3, 133.4, 133.6,
133.8, 140.2, 140.7, 141.2, 141.4, 141.5, 142.0, 142.3, 147.3, 191.8, 192.0,
192.1 (3 carbons are missing due to overlapping).
5-Fluoro-2-(2-phenylprop-1-enyl)benzaldehyde (6b). Following
method A using 2-bromo-5-fluorobenzaldehyde (1.01 g, 5 mmol) for
1
2 h, 6b was obtained: 571.0 mg (48%, E/Z/allyl = 68:11:21); H
NMR (CDCl3, 400 MHz) δ 2.06 (s, 3H, E), 2.31 (d, J = 0.8 Hz, 3H,
Z), 4.19 (s, 2H, allyl), 4.71 (s, 1H, allyl), 5.48 (s, 1H, allyl), 6.85
(s, 1H, Z), 6.98ꢀ7.07 (m, 1H of Z and 2H of allyl), 7.10 (s, 1H, E),
7.15ꢀ7.18 (m, 2H, allyl), 7.22 (dd, J = 2.6, 8.2 Hz, 1H, allyl),
7.29ꢀ7.46 (m, 5H of E, 6H of Z, and 1H of allyl), 7.56 (d, J = 7.2 Hz,
5-Methyl-2-(2-phenylprop-1-enyl)benzaldehyde (6d). Following
method B using 2-bromo-4-methylbenzaldehyde (399.9 mg, 2.0 mmol)
and triphenyl(1-phenylethyl)phosphonium bromide (1.07 g, 2.4 mmol),
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1
6d was obtained: 272.9 mg (60%, E/Z = 91:9); H NMR (CDCl3,
400 MHz) δ 2.08 (s, 3H, Z), 2.30 (s, 3H, E), 2.31 (s, 3H, E), 2.43
(s, 3H, Z), 6.89 (d, J = 7.6 Hz, 1H, E), 6.90 (s, 1H, E), 7.04ꢀ7.06 (m,
2H, E), 7.12 (d, J = 7.6 Hz, 1H, E), 7.16ꢀ7.20 (m, 3H, E), 7.26ꢀ7.43
(m, 7H, Z), 7.55 (s, 1H, E), 7.57 (d, J = 9.6 Hz, 1H, Z), 7.75 (s, 1H, Z),
10.20 (s, 1H, E), 10.25 (s, 1H, Z); 13C NMR (CDCl3, 100 MHz) δ
17.2, 20.8, 20.9, 25.8, 122.9, 123.6, 125.8, 127.0, 127.6, 128.1, 128.4,
128.5, 129.1, 129.2, 130.5, 131.1, 133.2, 133.7, 134.1, 134.5, 136.5,
137.1, 138.6, 138.8, 140.1, 140.4, 141.7, 192.2, 192.5 (1 carbon is
missing due to overlapping); HRMS (EI) [M]+ m/z calcd for
C17H16O 236.1201, found 236.1204.
δ 0.74 (t, J = 7.4 Hz, 3H, E), 0.97 (t, J = 7.4 Hz, 3H, Z), 1.32 (sextet,
J= 7.2 Hz, 2H, E), 1.48 (sextet, J= 7.2 Hz, 2H, Z), 2.48(t, J=7.6Hz, 2H, E),
2.60 (t, J = 7.4 Hz, 2H, Z), 6.91 (s, 1H, Z), 6.97 (d, J = 7.6 Hz, 2H, Z),
7.03 (s, 1H, E), 7.15ꢀ7.23 (m, 3H, Z), 7.28ꢀ7.45 (m, 3H, Z),
7.33ꢀ7.36 (m, 2H, E), 7.40 (t, J = 7.4 Hz, 2H, E), 7.44 (t, J = 7.6
Hz, 1H, E), 7.51 (d, J = 7.6 Hz, 2H, E), 7.61 (t, J = 7.0 Hz, 1H, E), 7.74
(d, J = 6.4 Hz, 1H, Z), 7.94 (d, J = 7.6 Hz, 1H, E), 10.26 (s, 1H, Z),
10.32 (s, 1H, E); 13C NMR (CDCl3, 100 MHz) δ 13.7, 16.1, 17.7, 21.3,
32.1, 38.2, 124.3, 125.3, 126.6, 127.2, 127.4, 127.5, 128.0, 128.4, 128.6,
128.9, 129.0, 129.8, 130.4, 131.2, 133.7, 133.9, 134.2, 139.5, 140.6,
141.7, 141.8, 145.8, 192.39, 192.42 (2 carbons are missing due to
overlapping); HRMS (EI) [M]+ m/z calcd for C18H18O 250.1358,
found 250.1356.
5-Methoxy-2-(2-phenylprop-1-enyl)benzaldehyde (F). Following
method A using 2-bromo-5-methoxybenzaldehyde (1.060 g, 5 mmol)
for 2 h, F was obtained: 298.0 mg (24%, E/Z/allyl = 80:6:14);
1H NMR (CDCl3, 400 MHz) δ 2.07 (s, 3H, E), 2.30 (s, 3H, Z),
3.80 (s, 3H, Z), 3.86 (s, 3H, allyl), 3.89 (s, 3H, E), 4.15 (s, 2H, allyl),
4.70 (s, 1H, allyl), 5.46 (s, 1H, allyl), 6.85 (s, 1H, Z), 6.89 (dd, J = 2.4,
8.4 Hz, 1H, Z), 6.93 (d, J = 8.4 Hz, 1H, Z), 7.05 (d, J = 8.0 Hz, 1H,
allyl), 7.08 (dd, J = 2.4, 8.4 Hz, 1H, allyl), 7.13 (s, 1H, E), 7.17
(dd, J = 2.8, 8.4 Hz, 1H, E), 7.16ꢀ7.47 (m, 6H of Z and 6H of allyl),
7.26 (d, J = 2.8 Hz, 1H, E), 7.33ꢀ7.42 (m, 3H, E), 7.44 (d, J = 2.4 Hz,
1H, E), 7.56 (d, J = 7.6 Hz, 2H, E), 10.20 (s, 2H, Z), 10.21 (s, 2H, allyl),
10.24 (s, 2H, E); 13C NMR (CDCl3, 100 MHz) δ 17.0, 25.6, 36.4,
55.23, 55.24, 110.7, 111.9, 113.5, 114.5, 120.5, 120.7, 121.0, 122.2,
123.0, 125.69, 125.73, 126.9, 127.5, 127.6, 128.0, 128.19, 128.24,
128.4, 129.8, 131.7, 132.3, 132.6, 133.8, 134.1, 134.3, 134.4, 134.6,
140.0, 140.2, 140.6, 141.4, 142.3, 147.8, 158.1, 158.4, 158.6, 191.3,
191.7, 191.8 (1 carbon is missing due to overlapping); HRMS (EI)
[M]+ m/z calcd for C17H16O2 252.1150, found 252.1151.
4,5-Dimethoxy-2-(2-phenylprop-1-enyl)benzaldehyde (6e). Following
method A using 2-bromo-4,5-dimethoxybenzaldehyde (1.225 g, 5 mmol)
for 3 h, 6e was obtained: 790.0 mg (56%, E/Z/allyl = 72:17:11); 1H NMR
(CDCl3, 400 MHz) δ 2.07 (s, 3H, E), 2.31 (s, 3H, Z), 3.51 (s, 3H, Z),
3.88 (s, 3H, Z), 3.89 (s, 3H, allyl), 3.93 (s, 3H, allyl), 3.965 (s, 3H, E), 3.972
(s, 3H, E), 4.18 (s, 2H, allyl), 4.78 (s, 1H, allyl), 5.48 (s, 1H, allyl),
6.37 (s, 1H, Z), 6.75 (s, 1H, allyl), 6.77 (s, 1H, E), 6.95 (s, 1H, Z), 7.08
(s, 1H, Z), 7.10 (s, 1H of E and 1H of allyl), 7.16ꢀ7.22 (m, 2H ofZ and 1H
of allyl), 7.29ꢀ7.62 (m, 3H of Z and 4H of allyl), 7.34ꢀ7.42 (m, 3H, E),
7.46 (s, 1H, E), 7.56 (d, J = 7.6 Hz, 2H, E), 10.13 (s, 1H, E), 10.15 (s, 1H,
allyl), 10.20 (s, 1H, Z); 13C NMR (CDCl3, 100 MHz) δ 17.1, 25.7, 36.5,
55.3, 55.5, 55.70, 55.74, 55.86, 108.6, 108.9, 110.1, 110.8, 111.9, 113.0,
113.3, 114.7, 121.9, 122.8, 125.6, 125.7, 126.5, 126.9, 127.0, 127.5, 128.07,
128.14, 128.2, 136.2, 136.6, 137.0, 140.5, 140.56, 140.64, 141.85, 141.94,
147.5, 147.6, 148.1, 152.8, 153.37, 153.43, 189.6, 189.9, 190.3 (4 carbons
are missing due to overlapping); HRMS (EI) [M]+ m/z calcd for C18H18O3
282.1256, found 282.1253.
2-(2-Methylprop-1-enyl)benzaldehyde (6h)13e. Following method B
using 2-bromobenzaldehyde (370.1 mg, 2.0 mmol) and isopropyltri-
phenylphos-phonium iodide (950.5 mg, 2.2 mmol), 6h was obtained:
1
152.5 mg (69%); H NMR (CDCl3, 400 MHz) δ 1.65 (s, 3H), 1.96
(s, 3H), 6.58 (s, 1H), 7.23 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.4 Hz, 1H),
7.53 (t, J = 7.4 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 10.21 (s, 1H); 13C
NMR (CDCl3, 100 MHz) δ 19.4, 26.0, 121.2, 126.8, 128.0, 130.7, 133.5,
133.7, 139.2, 142.2, 192.7.
2-(2-Methylallyl)benzaldehyde (6i)17. Following method C using
3-bromo-2-methylprop-1-ene (334.9 mg, 2.5 mmol, 1.2 equiv), 6i was
obtained: 142.2 mg (44%); 1H NMR (CDCl3, 400 MHz) δ 1.77 (s, 3H),
3.73 (s, 2H), 4.45 (s, 1H), 4.84 (s, 1H), 7.27 (d, J = 7.6 Hz, 1H), 7.39
(t, J = 7.6 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H), 10.24
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 22.8, 40.1, 112.4, 126.9, 130.5,
131.6, 133.8, 134.3, 142.0, 145.2, 192.0.
2-Allylbenzaldehyde (6j)13e. Following method C using allyl bro-
mide (303 μL, 2.5 mmol, 1 equiv), 6j was obtained: 223.0 mg (61%);
1H NMR (CDCl3, 400 MHz) δ 3.82 (d, J = 6.0 Hz, 2H), 4.99
(dd, J = 1.8, 17.0 Hz, 1H), 5.09 (dd, J = 1.4, 10.2 Hz, 1H), 6.04
(ddt, J = 6.2, 10.4, 17.2 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.40 (t, J = 7.6
Hz, 1H), 7.53 (td, J = 1.4, 7.4 Hz, 1H), 7.85 (d, J = 7.6 Hz, 1H), 10.26
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 36.3, 116.2, 126.7, 130.9,
131.4, 133.7, 133.8, 136.8, 142.0, 192.1.
2-Cinnamylbenzaldehyde (6k)18. Following method C using cinna-
myl bromide (492.7 mg, 2.5 mmol, 1.2 equiv), 6k was obtained:
1
253.2 mg (57%); H NMR (CDCl3, 400 MHz) δ 3.99ꢀ4.00 (m, 1H),
6.39ꢀ6.41 (m, 2H), 7.20 (t, J = 7.0 Hz, 1H), 7.28 (t, J = 7.2 Hz, 2H), 7.33
(d, J = 7.2 Hz, 2H), 7.37 (d, J = 7.6 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.55
(td, J = 1.2, 7.4 Hz, 1H), 7.86 (dd, J = 1.0, 7.4 Hz, 1H), 10.30
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 35.7, 126.1, 126.9, 127.2,
128.4, 128.5, 131.0, 131.5, 132.1, 133.8, 133.9, 137.1, 142.4, 192.4.
2-(But-3-en-2-yl)-3,4-dimethoxybenzaldehyde (6l). Prepared fol-
lowing the procedure in the literature:19 1H NMR (CDCl3, 400 MHz)
δ 1.50 (d, J = 7.2 Hz, 3H), 3.81 (s, 3H), 3.94 (s, 3H), 4.55ꢀ4.61
(m, 1H), 5.03 (d, J = 17.2 Hz, 1H), 5.08 (d, J = 10.4 Hz, 1H), 6.24 (ddd,
J = 4.6, 10.0, 17.2 Hz, 1H), 6.91 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 8.8 Hz,
1H), 10.26 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 20.7, 33.7, 55.7,
60.9, 109.9, 113.6, 127.8, 128.1, 142.0, 143.1, 147.0, 157.4, 191.1; HRMS
(EI) [M]+ m/z calcd for C13H16O3 220.1099, found 220.1095.
Synthesis of R-Methylstilbene 8.20. Following method B using benzal-
dehyde (204 μL, 2.0 mmol) and triphenyl(1-phenylethyl)phosphonium
bromide (892.2 mg, 2.0 mmol), 8 was obtained 226.3 mg (58%, E/Z =
86:14): 1H NMR (CDCl3, 400 MHz) δ 2.22 (d, J = 1.2 Hz, 3H, Z), 2.30
(d, J = 0.8 Hz, 3H, E), 6.49 (s, 1H, Z), 6.85 (s, 1H, E), 6.95 (d, J = 6.4 Hz,
2H, Z), 7.08ꢀ7.13 (m, 3H, Z), 7.20 (dd, J = 1.6, 7.6 Hz, 2H, Z),
7.24ꢀ7.30 (m, 3H, E), 7.27ꢀ7.32 (m, 2H of E and 3H of Z), 7.37ꢀ7.41
(m, 6H, E), 7.54 (d, J = 7.6 Hz, 2H, E); 13C NMR (CDCl3, 100 MHz) δ
17.4 (E), 27.0 (Z), 125.9 (E), 126.0 (Z), 126.4 (E), 126.5 (Z), 126.8 (Z),
127.1 (E), 127.6 (E), 127.8 (Z), 128.1 (E), 128.2 (E), 128.4 (Z), 128.9
(Z), 129.1 (E), 137.3 (E), 137.5 (Z), 138.3 (E), 138.6 (Z), 142.0 (Z),
143.8 (E) (1 carbon is missing due to overlapping).
4,5-Methylenedioxy-2-(2-phenylprop-1-enyl)benzaldehyde (6f).
Following method B using 2-bromo-4,5-methylenedioxybenzaldehyde
(227.9 mg, 1.0 mmol) and triphenyl(1-phenylethyl)phosphonium bro-
mide (446 mg, 1.0 mmol), 6f was obtained: 152.5 mg (58%, E/Z =
82:18); 1H NMR (CDCl3, 400 MHz) δ 2.06 (d, J = 1.2 Hz, 3H, Z), 2.29
(d, J = 1.2 Hz, 3H, E), 5.95 (s, 2H, E), 6.08 (s, 2H, Z), 6.42 (s, 1H, E),
6.76 (s, 1H, Z), 6.81 (s, 1H, E), 7.07 (s, 1H, Z), 7.07 (dd, J = 7.6 Hz, 2H,
E), 7.14ꢀ7.21(m, 3H, E), 7.21 (s, 1H, E), 7.33 (t, J = 7.2 Hz, 1H, Z), 7.40
(t, J = 7.4 Hz, 2H, Z), 7.40 (s, 1H, Z), 7.54 (d, J = 7.6 Hz, 2H, Z), 10.10
(s, each 1H of E and Z); 13C NMR (CDCl3, 100 MHz) δ 17.2, 25.6,
101.6, 101.9, 106.3, 106.4, 109.7, 110.19, 110.21, 122.1, 122.9, 125.7,
127.1, 127.7, 128.1, 128.28, 128.33, 128.8, 139.0, 139.2, 140.0, 140.9,
142.0, 142.3, 146.9, 147.3, 151.9, 152.2, 189.7, 190.0; HRMS (EI) [M]+
m/z calcd for C17H14O3 266.0943, found 266.0945.
2-(2-Phenylpent-1-enyl)benzaldehyde (6g). Following method B
using 2-bromobenzaldehyde (555.1 mg, 3.0 mmol) and triphenyl
(1-phenylbutyl)phosphonium bromide (1.707 g, 3.6 mmol), 6g was
obtained: 298.5 mg (66%, E/Z = 93:7); 1H NMR (CDCl3, 400 MHz)
7209
dx.doi.org/10.1021/jo201339z |J. Org. Chem. 2011, 76, 7204–7215

The Journal of Organic Chemistry
ARTICLE
General Procedures for the Preparation of Alkenylaryl β-Keto Esters.
To a solution of the corresponding 2-alkenylbenzaldehyde and Zn
(1.5 equiv) in benzene (0.2 M) in a two-neck round-bottom flask was
added methyl bromoacetate (1.2ꢀ2.0 equiv). The resulting mixture was
heated at 90ꢀ100 °C for 1ꢀ2 h. The reaction mixture was quenched
with satd NH4Cl and extracted with CH2Cl2 (three times). The
combined organic layer was dried over MgSO4 and concentrated in
vacuo. The residue was purified by column chromatography on silica gel
to give the corresponding alkenyl β-hydroxy ester product. To a solution
of the corresponding alkenyl β-hydroxy ester in CH2Cl2 (0.1 M) in a
round-bottom flask was added PCC (2.5 equiv) at 25 °C. The reaction
mixture was stirred at 25 °C for 0.25ꢀ9.5 h. After the reaction was
completed, ∼1 g of Celite was added and the mixture stirred for 5ꢀ
10 min. The rection mixture was flitered through Celite and concen-
trated in vacuo. The residue was purified by column chromatography on
silica gel (EtOAc/n-hexane =1:20) to give the corresponding product 1.
Methyl 3-oxo-3-(2-(2-phenylprop-1-enyl)phenyl)propanoate (1a):
step 1, 84% (from 6a); step 2, 60% (6 h), E/Z/allyl = 60 (keto 45 + enol
15):20 (keto 15 + enol 5):20 (keto 15 + enol 5), keto/enol = 3:1: 1H
NMR (CDCl3, 400 MHz) δ 2.09 (s, 3H, E of keto), 2.16 (s, 3H, E of
enol), 2.25 (s, 3H, Z of enol), 2.26 (s, 3H, Z of keto), 3.69 (s, 3H, E of
keto), 3.73 (s, 3H, Z of keto), 3.76 (s, 3H, E of enol), 3.77 (s, 3H, allyl of
keto), 3.79 (s, 3H, allyl of enol), 3.82 (s, 3H, Z of enol), 3.94 (s, each 2H,
Z of keto and allyl of keto), 3.96 (s, 2H, E of keto), 4.03 (s, 2H, allyl of
enol), 4.14 (s, 2H, allyl of keto), 4.78 (s, 1H, allyl of keto), 4.85 (s, 1H,
allyl of enol), 5.33 (s, 1H, allyl of enol), 5.435 (s, 1H, allyl of keto), 5.444
(s, 1H, E of enol), 5.48 (s, 1H, Z of enol), 5.49 (s, 1H, allyl of enol), 6.63
(s, 1H, Z of enol), 6.79 (s, 1H, Z of keto), 6.84 (d, J = 8.0 Hz, 1H, Z of
enol), 6.91 (d, J = 7.2 Hz, 1H, Z of keto), 6.97 (s, 1H, E of enol), 7.12
(s, 1H, E of keto), 7.03ꢀ7.60 (m, 6H of E of keto, 8H of E of enol, 7H of
Z of keto, 8H of Z of enol, 9H of allyl of keto, 9H of allyl of enol), 7.58
(d, J = 7.6 Hz, 2H, E of keto), 7.66 (d, J = 7.6 Hz, each 1H, E of enol and Z
of keto), 7.74 (d, J = 7.6 Hz, 1H, E of keto), 12.42 (s, 1H, allyl of enol),
12.43 (s, 1H, Z of enol), 12.44 (s, 1H, E of enol); 13C NMR (CDCl3, 100
MHz) δ 17.3, 17.4, 25.9, 26.0, 39.0, 39.1, 48.0, 48.3, 48.4, 51.6, 52.47,
52.54, 91.7, 91.9, 92.4, 114.5, 115.0, 126.08, 126.12, 126.17, 126.25,
126.33, 126.5, 126.6, 126.8, 126.9, 127.1, 127.2, 127.5, 127.66, 126.70,
128.25, 128.30, 128.46, 128.53, 128.57, 128.62, 128.8, 128.9, 129.0,
129.2, 129.4, 129.8, 130.1, 130.3, 130.89, 130.94, 131.4, 131.6, 131.8,
132.0, 132.1, 132.3, 132.4, 133.7, 134.0, 134.9, 136.7, 136.9, 137.07,
137.11, 137.2, 137.9, 138.0, 138.7, 138.9, 139.0, 139.4, 140.2, 141.1,
141.2, 141.3, 143.0, 143.4, 147.1, 147.4, 168.0, 168.2, 173.28, 173.34,
173.37, 173.44, 173.6, 174.9, 195.5, 195.85, 195.93; HRMS (EI) [M]+
m/z calcd for C19H18O3 294.1256, found 294.1253.
Methyl 3-(5-fluoro-2-(2-phenylprop-1-enyl)phenyl)-3-oxopropano-
ate (1b): step 1, 67% (from 6b); step 2, 66% (8 h), E/Z = 82 (keto 53 +
enol 29):18 (keto 11 + enol 7); 1H NMR (CDCl3, 400 MHz) δ 2.06
(s, 3H, E of keto), 2.14 (s, 3H, E of enol), 2.24 (s, 3H, Z of enol),
2.25 (s, 3H, Z of keto), 3.68 (s, 3H, E of keto), 3.768 (s, 3H, Z of keto),
3.774 (s, 3H, E of enol), 3.82 (s, 3H, Z of enol), 3.90 (s, 2H, Z of keto),
3.92 (s, 2H, E of keto), 5.46 (s, 1H, E of enol), 5.54 (s, 1H, Z of enol), 6.54
(s, 1H, Z of enol), 6.69 (s, 1H, Z of keto), 6.75ꢀ6.79 (m, 1H, Z of keto),
6.87 (s, 1H of E of enol and 2H of Z of keto), 7.01 (s, 1H, E of keto),
7.04ꢀ7.49 (m, 6H of E of keto, 6H of E of enol, 5H of Z of keto, 7H of Z
of enol), 7.52 (d, J = 8.0 Hz, 2H, E of enol), 7.55 (d, J = 7.6 Hz, 2H, E of
keto), 7.97 (d, J = 8.0 Hz, 1H, Z of enol), 12.43 (s, each 1H, Z of enol and
E of enol); 13C NMR (CDCl3, 100 MHz) δ 17.09, 17.14, 25.7, 47.7,
48.0, 51.5, 52.3, 92.2, 92.7, 114.7 (d, J = 23.5 Hz), 115.1 (d, J = 22.8 Hz),
115.2 (d, J = 22.0 Hz), 115.8 (d, J = 22.8 Hz), 116.7 (d, J = 20.5Hz), 116.8
(d, J = 20.5 Hz), 118.7 (d, J = 21.2 Hz), 118.9 (d, J = 21.2 Hz), 124.7,
124.9, 125.3, 125.6, 125.8, 125.9, 126.99, 127.03, 127.4, 127.6, 128.1,
128.25, 128.32, 128.35, 128.38, 128.5, 132.4 (d, J = 7.6 Hz), 132.876
(d, J = 7.6 Hz), 132.883, 133.1, 133.2 (d, J = 7.6 Hz), 133.9
(d, J = 6.8 Hz), 134.2 (d, J = 3.8 Hz), 134.5, 135.4 (d, J = 7.6 Hz),
137.2, 138.0, 138.48, 138.54, 138.7, 138.9, 139.9, 140.6, 140.8, 142.4,
142.9, 160.6 (d, J= 246.7 Hz), 161.2 (d, J= 247.4 Hz), 161.3 (d, J=245.8Hz),
162.1, 167.4, 167.6, 171.2 (d, J = 2.2 Hz), 171.5, 173.0, 173.1, 194.2,
194.7 (d, J = 1.5 Hz); HRMS (EI) [M]+ m/z calcd for C19H17FO3
312.1162, found 312.1164.
Methyl 3-(4-fluoro-2-(2-phenylprop-1-enyl)phenyl)-3-oxopropano-
ate (1c): step 1, 66% (from 6c); step 2, 77% (5 h), E/Z = 77 (keto 57 +
1
enol 20):23 (keto 18 + enol 5); H NMR (CDCl3, 400 MHz) δ 2.11
(s, 3H, Z of keto), 2.18 (s, 3H, Z of enol), 2.24 (s, 3H, E of enol), 2.26
(s, 3H, E of keto), 3.69 (s, 3H, Z of keto), 3.76 (s, each 3H, E of keto and
Z of enol), 3.81 (s, 3H, E of enol), 3.92 (s, 2H, E of keto), 3.94
(s, 2H, Z of keto), 5.41 (s, 1H, Z of enol), 5.46 (s, 1H, E of enol), 6.50
(dd, J = 2.4, 10.4 Hz, 1H, Z of keto), 6.56 (dd, J = 2.4, 10.0 Hz, each 1H, E
of keto and E of enol), 6.76 (s, 1H, E of keto), 6.81ꢀ6.90 (m, each 1H,
E of keto, E of enol, and Z of keto), 7.05ꢀ7.22 (m, 5H of E of keto, 2H of
E of enol, 4H of Z of keto, 5H of Z of enol), 7.31 (t, J = 7.4 Hz, 1H of E of
enol and 2H of Z of enol), 7.39 (t, J = 7.4 Hz, 2H of E of enol and 1H
of Z of keto), 7.50ꢀ7.54 (m, 2H, Z of keto), 7.57 (d, J = 8.0 Hz, 2H, E of
enol), 7.63 (dd, J = 6.0, 8.8 Hz, 1H of E of keto and 2H of Z of enol), 7.79
(dd, J = 5.6, 9.2 Hz, 1H, Z of keto), 12.44 (s, 1H, E of enol), 12.46 (s, 1H,
Z of enol); 13C NMR (CDCl3, 100 MHz) δ 16.9, 17.0, 25.5, 25.6, 47.5,
47.7, 51.2, 52.06, 52.14, 91.6, 92.0, 113.2 (d, J = 22.0 Hz), 113.3
(d, J = 22.0 Hz), 113.7 (d, J = 22.0 Hz), 117.2 (d, J = 22.0 Hz), 117.6
(d, J = 22.0 Hz), 117.9 (d, J = 21.3 Hz), 118.7 (d, J = 22.0 Hz), 124.6,
125.1, 125.4, 125.67, 125.71, 125.8, 127.06, 127.12, 127.4, 127.5, 128.01,
128.04, 128.1, 128.2, 129.6, 130.0 (d, J = 8.3 Hz), 130.3 (d, J = 9.1 Hz),
131.4 (d, J = 9.1 Hz), 131.9 (d, J = 9.8 Hz), 132.5 (d, J = 3.0 Hz), 132.8,
137.8, 138.2, 139.4 (d, J = 9.2 Hz), 139.9, 140.2 (d, J = 8.8 Hz), 140.4,
141.8 (d, J = 9.1 Hz), 142.1 (d, J = 9.1 Hz), 142.3, 142.6, 162.8
(d, J = 248.2 Hz), 163.8 (d, J = 252.7 Hz), 164.1 (d, J = 253.5 Hz),
167.5, 167.7, 171.8, 172.1, 172.9, 173.0, 193.5, 193.7; HRMS (EI) [M]+
m/z calcd for C19H17FO3 312.1162, found 312.1166.
Methyl 3-(5-methyl-2-(2-phenylprop-1-enyl)phenyl)-3-oxopropano-
ate (1d): step 1, 79% (from 6d); step 2, 76% (6 h); E/Z = 91 (keto 68 +
enol 23):9 (keto 7 + enol 2); 1H NMR (CDCl3, 400 MHz) δ 2.08 (s, 3H,
Z of keto), 2.16 (s, 3H, Z of enol), 2.23 (s, 3H, E of enol), 2.24 (s, 3H, E
of keto), 2.27 (s, 3H, E of enol), 2.29 (s, 3H, E of keto), 2.40 (s, 3H, Z of
enol), 2.42 (s, 3H, Z of keto), 3.68 (s, 3H, Z of keto), 3.76 (s, each 3H, E
of keto and Z of enol), 3.81 (s, 3H, E of enol), 3.93 (s, 2H, E of keto),
3.95 (s, 2H, Z of keto), 5.43 (s, 1H, Z of enol), 5.49 (s, 1H, E of enol),
6.58 (s, 1H, E of enol), 6.72 (s, 1H, E of enol), 6.73 (s, 1H, E of keto),
6.79 (d, J = 7.6 Hz, 1H, E of keto), 6.86 (d, J = 7.2 Hz, 1H, E of enol), 6.97
(d, J = 8.0 Hz, 1H, E of keto), 7.07ꢀ7.53 (m, 5H of E of keto, 6H of E of
enol, 6H of Z of keto, 9H of Z of enol), 7.38 (s, 1H, E of keto), 7.56
(d, J = 7.6 Hz, 2H, Z of keto), 7.97 (d, J = 7.2 Hz, 1H, Z of keto), 12.43
(s, 1H, E of enol), 12.44 (s, 1H, Z of enol); 13C NMR (CDCl3, 100
MHz) δ 17.00, 17.04, 20.8, 20.9, 25.61, 25.64, 26.4, 47.7, 48.0, 51.2, 52.2,
91.5, 125.6, 125.8, 126.4, 126.7, 127.2, 127.9, 128.0, 128.1, 128.2, 128.3,
128.4, 128.5, 128.7, 129.1, 129.5, 130.3, 130.5, 130.9, 131.1, 131.9, 132.3,
132.5, 132.9, 133.2, 133.9, 135.3, 135.6, 135.86, 135.90, 136.4, 136.6,
136.8, 137.9, 138.6, 141.0, 141.2, 167.9, 173.1, 173.4, 195.4, 195.8;
HRMS (EI) [M]+ m/z calcd for C20H20O3 308.1412, found 308.1411.
Methyl 3-(5-methoxy-2-(2-phenylprop-1-enyl)phenyl)-3-oxopropano-
ate (1e): step 1, 72% (from F); step 2, 63% (0.5 h); E/Z/allyl = 87
(keto 62 + enol 25):13 (keto 9 + enol 4):trace; 1H NMR (CDCl3, 400
MHz) δ 2.07 (s, 3H, E of keto), 2.15 (d, J = 1.2 Hz, 3H, E of enol), 2.22
(d, J = 1.2 Hz, 3H, Z of enol), 2.24 (d, J = 1.6 Hz, 3H, Z of keto), 3.67
(s, 3H, E of keto), 3.76 (s, each 3H, Z of keto and Z of enol), 3.77 (s, each
3H, Z of keto and E of enol), 3.82 (s, 3H, Z of enol), 3.86 (s, 3H, E of
enol), 3.87 (s, 3H, E of keto), 3.92 (s, 2H, Z of keto), 3.93 (s, 2H, E of
keto), 5.45 (s, 1H, E of enol), 5.51 (s, 1H, Z of enol), 6.54 (s, 1H,
Z of enol), 6.61 (dd, J = 2.4, 8.8 Hz, 1H, Z of enol), 6.68 (s, 1H, Z of
keto), 6.72 (dd, J = 2.8, 8.8 Hz, 1H, Z of keto), 6.75 (d, J = 8.8 Hz, 1H,
Z of enol), 6.82 (d, J = 8.8 Hz, 1H, Z of keto), 6.89 (s, 1H, E of enol), 7.00
7210
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ARTICLE
(dd, J = 2.8, 8.8 Hz, 1H, E of enol), 7.02 (s, 1H, E of keto), 7.08 (dd, J =
3.0, 8.6 Hz, each 1H, E of keto and E of enol), 7.12ꢀ7.31 (m, 2H of E of
enol, 6H of Z of keto, 6H of Z of enol), 7.17 (d, J = 7.6 Hz, 1H, E of enol),
7.21 (d, J = 2.4 Hz, 1H, E of enol), 7.24 (d, J = 2.4 Hz, 1H, E of keto), 7.29
(d, J = 7.6 Hz, 1H, E of keto), 7.38 (t, J = 7.4 Hz, 3H, E of keto), 7.52
(d, J = 7.4 Hz, 2H, E of enol), 7.55 (d, J = 7.2 Hz, 2H, E of keto), 12.44
(s, 1H, Z of enol), 12.45 (s, 1H, E of enol); 13C NMR (CDCl3, 100
MHz) δ 16.98, 17.04, 25.6, 47.9, 48.1, 51.3, 52.1, 52.2, 55.1, 55.18, 55.24,
55.3, 91.8, 92.3, 112.4, 112.9, 113.5, 113.8, 115.9, 117.3, 117.6, 125.3,
125.7, 125.8, 125.9, 126.1, 126.7, 127.0, 127.3, 128.0, 128.20, 128.22,
128.5, 129.2, 129.3, 130.4, 130.7, 131.8, 132.2, 132.5, 133.1, 134.7, 135.9,
137.6, 138.1, 138.4, 141.0, 141.2, 142.7, 143.2, 157.6, 158.2, 167.6, 167.8,
172.5, 172.8, 173.0, 195.2, 195.7; HRMS (EI) [M]+ m/z calcd for
C20H20O4 324.1362, found 324.1365.
Methyl 3-oxo-3-(2-(2-phenylpent-1-enyl)phenyl)propanoate (1f):
step 1, 86% (from 6g); step 2, 83% (9.5 h); E/Z = >99:1, keto/enol =
71:29; 1H NMR (CDCl3, 400 MHz) δ 0.74 (t, J = 7.2 Hz, 3H, keto), 0.79
(t, J = 7.4 Hz, 3H, enol), 1.24ꢀ1.39 (m, each 2H, keto and enol), 2.49
(t, J = 7.8 Hz, 2H, keto), 2.57 (t, J = 7.6 Hz, 2H, enol), 3.68 (s, 3H, keto),
3.77 (s, 3H, enol), 3.95 (s, 2H, keto), 5.47 (s, 1H, enol), 6.79 (s, 1H,
enol), 6.94 (s, 1H, keto), 7.28ꢀ7.47 (m, 5H of keto and 8H of enol),
7.51 (d, J = 7.2 Hz, 2H, keto), 7.53 (t, J = 8.0 Hz, 1H, keto), 7.66 (d, J =
7.6 Hz, 1H, enol), 7.74 (d, J = 7.6 Hz, 1H, keto), 12.41 (s, 1H, enol); 13C
NMR (CDCl3, 100 MHz) δ 13.6, 13.8, 21.3, 21.4, 31.7, 31.8, 47.9, 51.1,
52.0, 92.0, 126.5, 126.6, 126.7, 126.8, 127.0, 127.1, 127.3, 127.5, 127.9,
128.2, 128.8, 129.1, 129.8, 130.2, 130.8, 131.8, 133.6, 136.6, 136.9, 138.4,
141.9, 142.26, 142.32, 142.8, 167.6, 172.9, 173.0, 195.2; HRMS (EI)
[M]+ m/z calcd for C21H22O3 322.1569, found 322.1564.
Methyl 3-(2-(2-methylprop-1-enyl)phenyl)-3-oxopropanoate (1g):
step 1, 84% (from 6h); step 2, 77% (8 h); keto/enol = 75:25; 1H NMR
(CDCl3, 400 MHz) δ 1.67 (s, 3H, keto), 1.75 (s, 3H, enol), 1.90 (s, 3H,
enol), 1.92 (s, 3H, keto), 3.73 (s, 3H, keto), 3.79 (s, 3H, enol), 3.91
(s, 2H, keto), 5.39 (s, 1H, enol), 6.34 (s, 1H, enol), 6.47 (s, 1H, keto),
7.23 (d, J = 7.2 Hz, 1H, keto), 7.23ꢀ7.33 (m, 2H, enol), 7.31 (t, J = 7.8
Hz, 1H, keto), 7.37 (t, J = 7.0 Hz, 1H, enol), 7.46 (t, J = 7.2 Hz, 1H,
keto), 7.59 (d, J = 8.0 Hz, 1H, enol), 7.64 (d, J = 8.0 Hz, 1H, keto), 12.39
(s, 1H, enol); 13C NMR (CDCl3, 100 MHz) δ 19.2, 25.98, 26.04, 48.2,
51.2, 52.12, 52.14, 91.8, 123.9, 124.0, 124.1, 126.2, 126.4, 128.0, 128.6,
129.6, 130.6, 131.0, 131.5, 133.3, 135.4, 137.1, 137.2, 138.1, 167.8, 173.1,
173.2, 196.4; HRMS (EI) [M]+ m/z calcd for C14H16O3 232.1099,
found 232.1101.
Methyl 3-(2-(2-methylallyl)phenyl)-3-oxopropanoate (1h): step 1,
86% (from 6i); step 2, 68% (7 h); keto/enol = 74:26; 1H NMR (CDCl3,
400 MHz) δ 1.70 (s, 3H, enol), 1.73 (s, 3H, keto), 3.51 (s, 2H, enol),
3.60 (s, 2H, keto), 3.74 (s, 3H, keto), 3.80 (s, 3H, enol), 3.93 (s, 2H,
keto), 4.44 (s, 1H, keto), 4.55 (s, 1H, enol), 4.80 (s, 1H, keto), 4.83
(s, 1H, enol), 5.30 (s, 1H, enol), 7.24ꢀ7.33 (m, each 2H, keto and enol),
7.37 (t, J = 7.0 Hz, 1H, enol), 7.42 (d, J = 8.0 Hz, 1H, enol), 7.45 (t, J =
7.0 Hz, 1H, keto), 7.62 (d, J = 7.6 Hz, 1H, keto), 12.39 (s, 1H, enol); 13C
NMR (CDCl3, 100 MHz) δ 22.4, 22.7, 41.0, 41.2, 48.2, 51.2, 52.2, 91.3,
111.7, 112.2, 126.1, 126.2, 128.57, 128.63, 129.9, 130.6, 131.7, 134.6,
137.0, 137.8, 139.9, 144.6, 145.0, 167.7, 173.0, 174.6, 195.8 (1 carbon is
missing due to overlapping); HRMS (EI) [M]+ m/z calcd for C14H16O3
232.1099, found 232.1097.
128.8, 130.1, 130.2, 131.3, 132.1, 134.2, 136.2, 137.0, 138.3, 140.6, 167.7,
172.9, 174.7, 195.6 (1 carbon is missing due to overlapping); HRMS
(EI) [M]+ m/z calcd for C13H14O3 218.0943, found 218.0943.
General Procedures for the Preparation of Alkenylaryl Ketones. To a
solution of the corresponding 2-alkenylbenzaldehyde in dry THF (0.2 M)
in a two-neck round-bottom flask was added MeMgBr, PhMgBr, or n-BuLi
(1.5 equiv) at ꢀ78 °C. After being stirred at ꢀ78 °C for 0.5ꢀ1 h, the
reaction mixture was quenched with satd NH4Cl and extracted with
CH2Cl2 (three times). The combined organic layer was dried over
MgSO4 and concentrated in vacuo. The residue was purified by column
chromatography on silica gel to give the corresponding 2-alkenylaryl
alcohol product. To a solution of the corresponding 2-alkenylaryl
alcohol in CH2Cl2 (0.1 M) in a round-bottom flask was added PCC
(2.5 equiv) at 25 °C. The reaction mixture was stirred at 25 °C for 2ꢀ3 h.
After the reaction was completed, ∼1 g of Celite was added and the
mixture stirred for 5ꢀ10 min. The rection mixture was flitered through
Celite and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (EtOAc/n-hexane = 1:20ꢀ1:50) to give
the corresponding product 5.
1-(2-(2-Phenylprop-1-enyl)phenyl)ethanone (5a): step 1, 85% (from
6a); step 2, 86%; E/Z/allyl = 58:18:24; 1H NMR (CDCl3, 400 MHz) δ
2.09 (d, J = 1.2 Hz, 3H, E), 2.25 (d, J = 1.6 Hz, 3H, Z), 2.49 (s, 3H, Z),
2.55 (s, 3H, allyl), 2.57 (s, 3H, E), 4.12 (s, 2H, allyl), 4.74 (d, J = 1.2 Hz,
1H, allyl), 5.39 (s, 1H, allyl), 6.77 (s, 1H, Z), 6.91 (dd, J = 2.4, 6.8 Hz,
1H, Z), 7.06 (dd, J = 2.0, 7.2 Hz, 2H, Z), 7.14 (s, 1H, E), 7.14ꢀ7.18 (m,
2H of Z and 3H of allyl), 7.25ꢀ7.40 (m, 5H of E, 4H of Z, and 3H of
allyl), 7.44 (d, J = 7.2 Hz, 2H, allyl), 7.51 (t, J = 6.8 Hz, 1H, E), 7.57 (d, J =
7.2 Hz, 2H, E), 7.66 (d, J = 7.6 Hz, 1H, allyl), 7.75 (dd, J = 1.2, 7.4 Hz,
1H, E); 13C NMR (CDCl3, 100 MHz) δ 17.0, 25.6, 29.3, 29.5, 29.7, 38.7,
113.9, 125.8, 126.0, 126.1, 126.3, 126.7, 127.20, 127.21, 127.4, 127.9,
128.1, 128.2, 128.45, 128.53, 128.88, 128.91, 130.7, 130.8, 131.1, 131.2,
131.6, 131.7, 136.8, 137.8, 138.1, 138.17, 138.21, 138.4, 138.8, 141.0,
141.1, 142.9, 147.7, 201.4, 201.6, 202.0 (3 carbons are missing due to
overlapping); HRMS(EI) [M]+ m/z calcd for C17H16O 236.1201, found
236.1205.
1-(2-(2-Phenylprop-1-enyl)phenyl)pentan-1-one (5b): step 1, 77%
(from 6a); step 2, 81%; E/Z/allyl = 62:18:20; 1H NMR (CDCl3,
400 MHz) δ 0.88 (t, J = 7.2 Hz, 3H, E), 0.92 (t, J = 7.2 Hz, 3H, allyl),
0.95 (t, J = 7.4 Hz, 3H, E), 1.23ꢀ1.42 (m, each 2H of E, Z, and allyl), 1.65
(sextet, J = 7.2 Hz, each 2H of E, Z, and allyl), 2.08 (d, J = 1.2 Hz, 3H, E),
2.24 (d, J = 1.2 Hz, 3H, Z), 2.82 (t, J = 7.4 Hz, 2H, allyl), 2.84 (t, J = 7.4
Hz, 3H, Z), 2.87 (t, J = 7.4 Hz, 3H, E), 4.07 (s, 2H, allyl), 4.77 (d, J = 0.8
Hz, 1H, allyl), 5.40 (s, 1H, allyl), 6.72 (s, 1H, Z), 6.89 (d, J = 7.6 Hz,
1H, Z), 7.07ꢀ7.21 (m, each 2H of E, Z, and allyl), 7.24ꢀ7.57 (m, 5H of
E, 6H of Z, and 7H of allyl), 7.55 (d, J = 7.6 Hz, 2H, E), 7.65 (dd, J = 1.2,
7.6 Hz, 1H, E); 13C NMR (CDCl3, 100 MHz) δ 13.7, 13.79, 13.82, 17.0,
22.26, 22.29, 25.6, 26.2, 26.3, 26.5, 38.5, 41.1, 41.5, 41.6, 114.1, 125.8,
125.9, 125.98, 126.00, 126.1, 126.6, 126.9, 127.2, 127.3, 127.7, 127.8,
127.9, 128.0, 128.1, 128.2, 128.4, 130.2, 130.5, 130.6, 131.3, 131.6, 137.0,
137.2, 137.4, 138.23, 138.24, 138.6, 138.9, 139.0, 141.00, 141.03, 142.9,
147.5, 204.4, 204.8, 205.0 (3 carbons are missing due to overlapping);
HRMS (EI) [M]+ m/z calcd for C20H22O 278.1671, found 278.1672.
Phenyl(2-(2-phenylprop-1-enyl)phenyl)methanone (5c): step 1, 76%
(from 6a); step 2, 79%; E/Z/allyl = 57:19:24; 1H NMR (CDCl3,
400 MHz) δ 2.05 (d, J = 1.2 Hz, 3H, E), 2.06 (d, J = 1.6 Hz, 3H, Z),
3.96 (s, 2H, allyl), 4.91 (d, J = 1.2 Hz, 1H, allyl), 5.36 (s, 1H, allyl), 6.51
(s, 1H, Z), 6.68 (s, 1H, E), 6.97 (dd, J = 3.6, 6.0 Hz, 1H, Z), 7.07ꢀ7.30
(m, each 6H of E, Z, and allyl), 7.35ꢀ7.46 (m, 4H of E, 3H of Z, and 4H of
allyl), 7.51ꢀ7.60 (m, each2HofE, Z, andallyl), 7.73ꢀ7.77 (m, each2Hof
E, Z, and allyl); 13C NMR (CDCl3, 100 MHz) δ 17.2, 25.9, 38.3, 115.0,
124.6, 125.4, 125.6, 125.97, 126.04, 126.4, 126.7, 127.0, 127.2, 127.9,
128.0, 128.09, 128.13, 128.2, 128.3, 128.55, 128.61, 129.5, 129.6, 128.8,
129.9, 130.0, 130.1, 130.55, 130.63, 132.7, 132.9, 137.18, 137.24, 137.45,
137.51, 137.8, 138.2, 138.3, 138.4, 138.5, 138.7, 139.7, 140.4, 141.0, 142.9,
Methyl 3-(2-allylphenyl)-3-oxopropanoate (1i): step 1, 62% (from
6j); step 2, 59% (6 h); keto/enol = 77:23; 1H NMR (CDCl3, 400 MHz)
δ 3.57 (d, J = 6.4 Hz, 2H, enol), 3.66 (d, J = 6.5 Hz, 2H, keto), 3.74
(s, 3H, keto), 3.80 (s, 3H, enol), 3.95 (s, 2H, keto), 3.97 (s, 2H, keto),
4.98ꢀ5.07 (m, each 2H, keto and enol), 5.31 (s, 1H, enol), 5.93ꢀ6.05
(m, each 1H, keto and enol), 7.23ꢀ7.27 (m, 2H, enol), 7.31 (t, J = 7.2
Hz, 1H, keto), 7.32 (d, J = 7.6 Hz, 1H, keto), 7.33ꢀ7.36 (m, 1H, enol),
7.39 (t, J = 7.1 Hz, 1H, enol), 7.45 (t, J = 7.2 Hz, 1H, keto), 7.64 (d, J =
7.6 Hz, 1H, keto), 12.40 (s, 1H, enol); 13C NMR (CDCl3, 100 MHz) δ
37.6, 37.8, 48.0, 51.2, 52.2, 91.4, 115.76, 115.84, 126.1, 126.2, 128.6,
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ARTICLE
146.6, 197.7, 198.0, 198.1 (5 carbons are missing due to overlapping);
HRMS (EI) [M]+ m/z calcd for C22H18O 298.1358, found 298.1360.
1-(4-Fluoro-2-(2-phenylprop-1-enyl)phenyl)ethanone (5d): step 1,
76% (from 6c); step 2, 88%; E/Z = 79:21; 1H NMR (CDCl3, 400 MHz)
δ 2.10 (d, J = 1.2 Hz, 3H, Z), 2.25 (d, J = 1.6 Hz, 3H, E), 2.49 (s, 3H, E),
2.56 (s, 3H, Z), 6.57 (dd, J = 2.6, 10.2 Hz, 1H, E), 6.75 (s, 1H, E), 6.84
(dt, J = 2.8, 8.2 Hz, 1H, E), 7.03ꢀ7.07 (m, each 2H of E and Z), 7.11
(s, 1H, Z), 7.15ꢀ7.22 (m, 3H, E), 7.31 (t, J = 7.4 Hz, 1H, Z), 7.39
(t, J = 7.6 Hz, 2H, Z), 7.57 (d, J = 7.2 Hz, 2H, Z), 7.62 (dd, J = 6.0, 8.8 Hz,
1H, E), 7.80 (dd, J = 5.4, 9.2 Hz, 1H, Z); 13C NMR (CDCl3, 100 MHz) δ
16.9, 25.6, 29.1, 29.4, 113.1 (d, J = 21.3 Hz), 113.5 (d, J = 21.3 Hz), 117.6
(d, J = 21.3 Hz), 118.3 (d, J = 21.2 Hz), 125.5, 125.8, 126.3 (d, J = 2.5
Hz), 127.0, 127.4, 128.0, 128.2, 128.3, 131.1 (d, J = 9.2 Hz), 131.7 (d, J =
9.9 Hz), 134.1 (d, J = 3.1 Hz), 134.2 (d, J = 3.1 Hz), 137.3, 139.5, 140.4,
141.16 (d, J= 9.1 Hz), 141.20 (d, J= 9.1 Hz), 142.6, 163.5 (d, J= 250.4 Hz),
163.8 (d, J = 251.9 Hz), 199.5 (1 carbon is missing due to overlapping);
HRMS (EI) [M]+ m/z calcd for C17H15FO 254.1107, found 254.1103.
1-(4,5-Dimethoxy-2-(2-phenylprop-1-enyl)phenyl)ethanone (5e):
(dd, J = 5.4, 9.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 39.3, 52.3,
111.9 (d, J = 20.5 Hz), 116.5 (d, J = 25.1 Hz), 125.2 (d, J = 5.4 Hz), 126.3
(d, J = 9.1 Hz), 127.2, 127.4, 127.7, 128.3, 128.9, 131.3, 135.2 (d, J = 9.1
Hz), 139.4, 140.3, 160.8 (d, J = 245.2 Hz), 171.7; HRMS (EI) [M]+ m/z
calcd for C19H15FO2 294.1056, found 294.1058.
Methyl 2-(7-methyl-3-phenylnaphthalen-1-yl)acetate (2d): 1H NMR
(CDCl3, 400 MHz) δ 2.57 (s, 3H), 3.71 (s, 3H), 4.12 (s, 2H), 7.37 (d, J =
8.0 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.67 (s, 1H),
7.72 (d, J = 7.2 Hz, 2H), 7.77 (s, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.96
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 22.2, 39.1, 52.2, 122.7, 125.6,
127.25, 127.29, 127.8, 128.5, 128.8, 128.9, 130.3, 131.4, 132.3, 136.2,
137.2, 140.8, 172.0; HRMS (EI) [M]+ m/z calcd for C20H18O2 290.1307,
found 290.1307.
Methyl 2-(7-methoxy-3-phenylnaphthalen-1-yl)acetate (2e): 1H
NMR (CDCl3, 400 MHz) δ 3.70 (s, 3H), 3.96 (s, 3H), 4.09 (s, 2H),
7.20 (dd, J = 2.0, 9.2 Hz, 1H) 7.30 (s, 1H), 7.37 (t, J = 7.2 Hz, 1H), 7.48
(t, J = 7.2 Hz, 2H), 7.68 (s, 1H), 7.71 (d, J = 7.2 Hz, 2H), 7.83 (d, J = 8.8
Hz, 1H), 7.94 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 39.6, 52.2, 55.3,
102.4, 118.7, 125.6, 127.1, 127.2, 128.3, 128.8, 129.5, 129.8, 130.5, 132.4,
135.9, 140.8, 158.1, 172.0; HRMS (EI) [M]+ m/z calcd for C20H18O3
306.1256, found 306.1256.
1
step 1, 92% (from 6e); step 2, 70%; E/Z/allyl = 65:18:17; H NMR
(CDCl3, 400 MHz) δ 2.08 (s, 3H, E), 2.27 (s, 3H, Z), 2.53 (s, 3H, E),
2.55 (s, 3H, Z), 2.58 (s, 3H, allyl), 3.37 (s, 3H, allyl), 3.83 (s, 3H, allyl),
3.87 (s, 3H, Z), 3.91 (s, 3H, Z), 3.95 (s, 3H, E), 3.96 (s, 3H, E), 4.14
(s, 2H, allyl), 4.80 (s, 1H, allyl), 5.39 (s, 1H, allyl), 6.31 (s, 1H, allyl), 6.76
(s, 1H, allyl), 6.78 (s, 1H, E), 6.82 (s, 1H, Z), 7.10 (s, 1H, Z), 7.12 (s, 1H,
E), 7.10ꢀ7.32 (m, 4H of Z and 5H of allyl), 7.30 (t, J = 7.2 Hz, 1H, E),
7.35 (s, 1H, E), 7.39 (t, J = 7.6 Hz, 2H, E), 7.45 (d, J = 7.2 Hz, 2H, Z),
7.57 (d, J = 7.2 Hz, 2H, E); 13C NMR (CDCl3, 100 MHz) δ 17.1, 25.7,
29.5, 29.8, 30.1, 39.0, 55.4, 55.9, 56.0, 56.1, 111.6, 112.0, 113.0, 113.2,
113.8, 114.2, 114.7, 125.8, 126.1, 126.7, 126.8, 127.4, 127.5, 127.7, 128.2,
128.3, 128.4, 128.5, 130.0, 130.3, 130.8, 132.6, 132.8, 134.1, 136.8, 138.3,
141.3, 141.6, 142.8, 146.5, 146.7, 147.4, 147.9, 150.8, 151.4, 151.5, 199.7,
199.88, 199.92 (2 carbons are missing due to overlapping); HRMS (EI)
[M]+ m/z calcd for C19H20O3 296.1412, found 296.1415.
General Procedure for Au(I)-Catalyzed Cyclization Reaction of Alkenyl
Carbonyl Compounds. The mixture of Ph3PAuCl (2 mol %, 1.9 mg, 0.00391
mmol) and AgOTf (2 mol %, 1.0 mg, 0.00391 mmol) in ClCH2CH2Cl
(977 μL, 0.2 M) was stirred vigorously for 1 h. To the resulting solution was
added alkenyl carbonyl compound 1, 5, or 6 (0.195 mmol) in ClCH2CH2Cl
(977 μL, 0.2 M). The resulting mixture was stirred at the 80 °C for the
reported time. After the reaction was complete, solvent was evaporated in
vacuo. The residue was purified by column chromatography on silica gel
(EtOAc/n-hexane = 1:20 (for 2), 1:50ꢀ1:100 (for 3, 7aꢀg), 1:10 (for 4a);
only n-hexane (for 7h)) to afford the corresponding product.
Methyl 2-(2-ethyl-3-phenylnaphthalen-1-yl)acetate (2f): 1H NMR
(CDCl3, 400 MHz) δ 1.02 (t, J = 7.4 Hz, 3H), 2.83 (t, J = 7.2 Hz, 3H),
3.72 (s, 3H), 4.24 (s, 2H), 7.38ꢀ7.48 (m, 6H), 7.53 (t, J = 7.6 Hz, 1H),
7.64 (s, 1H), 7.80 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ 15.1, 23.7, 34.5, 52.1, 123.6, 125.3, 126.4, 126.9,
127.7, 127.9, 128.5, 129.1, 129.4, 131.7, 132.3, 139.6, 141.0, 142.4, 172.3;
HRMS (EI) [M]+ m/z calcd for C21H20O2 304.1463, found 304.1470.
1-Methyl-3-phenylnaphthalene (3a): 1H NMR (CDCl3, 400 MHz)
δ 2.80 (s, 3H), 7.41 (t, J = 7.4 Hz, 1H), 7.50ꢀ7.56 (m, 4H), 7.64 (s, 1H),
7.76 (d, J = 7.2 Hz, 2H), 7.92ꢀ7.95 (m, 2H), 8.03ꢀ8.06 (m, 1H); 13C
NMR (CDCl3, 100 MHz) δ 19.5, 124.0, 124.2, 125.8, 126.0, 126.3,
127.2, 127.4, 128.77, 128.82, 131.8, 133.8, 134.8, 138.2, 141.2; GC/MS
Rt = 15.83 min; MS (EI) m/z 218 (M+), 202, 189, 165, 141, 115, 108,
101, 77, 65, 51, 39. Spectral data of 3a were consistent with data reported
in the literature.21
1
7-Fluoro-1-methyl-3-phenylnaphthalene (3b): H NMR (CDCl3,
400 MHz) δ 2.71 (s, 3H), 7.30 (td, J = 2.4, 8.6 Hz, 1H), 7.38 (t, J = 7.4
Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.61 (dd, J = 2.0, 11.0 Hz, 1H), 7.63
(s, 1H), 7.71 (d, J = 7.6 Hz, 2H), 7.87ꢀ7.91 (m, 1H), 7.90 (s, 1H); 13C
NMR (CDCl3, 100 MHz) δ 19.5, 107.7 (d, J = 21.2 Hz), 116.2 (d, J =
25.1 Hz), 124.0, 127.21, 127.29, 127.32, 128.8, 130.8, 131.1 (d, J = 9.1
Hz), 132.7 (d, J = 8.4 Hz), 134.2 (d, J = 6.1 Hz), 137.5 (d, J = 3.1 Hz),
140.9, 160.7 (d, J = 244.3 Hz); HRMS (EI) [M]+ m/z calcd for C17H13F
236.1001, found 236.1002.
Methyl 2-(3-phenylnaphthalen-1-yl)acetate (2a): 1H NMR (CDCl3,
400 MHz) δ 3.71 (s, 3H), 4.15 (s, 2H), 7.40 (t, J = 7.4 Hz, 1H), 7.50
(t, J = 7.6 Hz, 2H), 7.53ꢀ7.58 (m, 2H), 7.71 (s, 1H), 7.74 (d, J = 7.6 Hz,
2H), 7.93 (dd, J = 2.0, 6.4 Hz, 1H), 8.01 (s, 1H), 8.02 (dd, J = 2.4, 6.8 Hz,
1H); 13C NMR (CDCl3, 100 MHz) δ 39.1, 52.2, 123.7, 125.8, 126.2,
126.4, 127.37, 127.42, 127.8, 128.8, 129.0, 131.0, 131.3, 134.1, 138.1,
140.7, 171.9; HRMS (EI) [M]+ m/z calcd forC19H16O2 276.1150, found
276.1153.
1
6-Fluoro-1-methyl-3-phenylnaphthalene (3c): H NMR (CDCl3,
400 MHz) δ 2.76 (s, 3H), 7.30 (td, J = 2.6, 8.8 Hz, 1H), 7.41 (t, J = 7.4
Hz, 1H), 7.49ꢀ7.54 (m, 1H), 7.51 (t, J = 8.0 Hz, 2H), 7.57 (s, 1H), 7.73
(d, J = 6.8 Hz, 2H), 7.85 (s, 1H), 8.01 (dd, J = 5.6, 9.4 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ 19.6, 111.6 (d, J = 19.7 Hz), 115.8 (d, J = 25.0 Hz),
123.5, 123.6, 125.7 (d, J = 2.2 Hz), 126.5 (d, J = 8.4 Hz), 127.4, 127.5,
128.8, 134.8 (d, J = 9.1 Hz), 135.0, 139.4, 140.8, 160.8 (d, J = 244.4 Hz);
HRMS (EI) [M]+ m/z calcd for C17H13F 236.1001, found 236.0996.
1,7-Dimethyl-3-phenylnaphthalene (3d): 1H NMR (CDCl3,
400 MHz) δ 2.59 (s, 3H), 2.76 (s, 3H), 7.38 (d, J = 8.4 Hz, 1H), 7.39
(t, J = 7.8 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.60 (s, 1H), 7.74 (d, J = 7.6
Hz, 2H), 7.80 (s, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.90 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 19.5, 22.1, 123.1, 124.0, 126.3, 127.1, 127.3, 128.2,
128.6, 128.7, 131.95, 132.01, 134.1, 135.4, 137.2, 141.3; GC/MS tR =
16.34 min; EI m/z 232 (M+), 215, 202, 189, 165, 152, 125, 108, 101, 94,
75, 65, 51. Spectral data of 3d were consistent with data reported in the
literature.21a
Methyl 2-(7-fluoro-3-phenylnaphthalen-1-yl)acetate (2b): 1H NMR
(CDCl3, 400 MHz) δ 3.72 (s, 3H), 4.08 (s, 2H), 7.31 (td, J = 2.0, 8.4 Hz,
1H), 7.39 (t, J = 7.2 Hz, 1H), 7.49 (t, J = 7.4 Hz, 2H), 7.63 (dd, J = 1.8,
11.0 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.72 (s, 1H), 7.91(dd, J = 6.0, 8.8
Hz, 1H), 7.99 (s, J = 1H); 13C NMR (CDCl3, 100 MHz) δ 39.1, 52.3,
107.6 (d, J = 22.2 Hz), 116.6 (d, J = 25.0 Hz), 125.7, 127.3, 127.5, 128.8,
128.9, 130.6 (d, J = 6.1 Hz), 131.1, 131.4 (d, J = 9.1 Hz), 132.2 (d, J = 8.3
Hz), 137.5 (d, J = 3.1 Hz), 140.4, 161.0 (d, J = 245.2 Hz), 171.6; HRMS
(EI) [M]+ m/z calcd for C19H15FO2 294.1056, found 294.1055.
Methyl 2-(6-fluoro-3-phenylnaphthalen-1-yl)acetate (2c): 1H NMR
(CDCl3, 400 MHz) δ 3.70 (s, 3H), 4.12 (s, 2H), 7.31 (td, J = 2.4, 8.8 Hz,
1H), 7.40 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 8.0 Hz, 2H), 7.53 (dd, J = 2.4,
10.0 Hz, 1H), 7.64 (s, 1H), 7.71 (d, J = 7.2 Hz, 2H), 7.93 (s, 1H), 8.01
7-Methoxy-1-methyl-3-phenylnaphthalene (3e): 1H NMR (CDCl3,
400 MHz) δ 2.74 (s, 3H), 3.99 (s, 3H), 7.22 (d, J = 8.8 Hz, 1H), 7.26
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(s, 1H), 7.38 (t, J = 7.0 Hz, 1H), 7.49 (t, J = 7.4 Hz, 2H), 7.61 (s, 1H),
7.73 (d, J = 7.6 Hz, 2H), 7.83 (d, J = 8.8 Hz, 1H), 7.88 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 19.7, 55.3, 102.6, 118.3, 124.0, 126.8, 126.9, 127.2,
128.7, 129.2, 130.4, 132.9, 133.4, 135.9, 141.3, 157.7; HRMS (EI) [M]+
m/z calcd for C18H16O 248.1201, found 248.1198.
(d, J = 25.1 Hz), 125.7, 126.6, 127.3, 127.4, 127.7 (d, J = 5.4 Hz), 128.9,
130.5 (d, J = 9.1 Hz), 130.7, 133.2 (d, J = 9.1 Hz), 137.9 (d, J = 3.0 Hz),
140.8, 160.6 (d, J = 244.3 Hz); HRMS (EI) [M]+ m/z calcd for C16H11F
222.0845, found 222.0840.
2-Fluoro-7-phenylnaphthalene (7c): 1H NMR (CDCl3, 400 MHz)
δ 7.28 (td, J = 2.4, 8.8 Hz, 1H), 7.41 (t, J = 7.2 Hz, 1H), 7.51 (t, J = 7.8
Hz, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 7.2 Hz, 2H), 7.72ꢀ7.74
(m, 1H), 7.86 (dd, J = 5.6, 8.8 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.99
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 111.1 (d, J = 20.5 Hz), 116.2
(d, J = 25.0 Hz), 124.9 (d, J = 2.3 Hz), 125.1 (d, J = 5.3 Hz), 127.4, 127.6,
128.4, 128.9, 129.6, 130.0 (d, J = 9.1 Hz), 134.4 (d, J = 9.8 Hz), 139.6,
140.7, 160.9 (d, J = 245.1 Hz); HRMS (EI) [M]+ m/z calcd for C16H11F
222.0845, found 222.0848.
2-Ethyl-1-methyl-3-phenylnaphthalene (3f): 1H NMR (CDCl3,
400 MHz) δ 1.07 (t, J = 7.2 Hz, 3H), 2.75 (s, 3H), 2.80 (t, J = 7.6 Hz,
3H), 7.38ꢀ7.48 (m, 6H), 7.53 (t, J = 7.4 Hz, 1H), 7.58 (s, 1H), 7.80 (d,
J = 7.6 Hz, 1H), 8.09 (d, J = 8.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz)
δ 14.7, 15.1, 23.8, 123.9, 125.1, 125.7, 126.7, 127.1, 127.8, 128.3, 129.4,
131.2, 131.5, 132.4, 138.1, 141.1, 142.9; HRMS (EI) [M]+ m/z calcd
for C19H18 246.1409, found 246.1406.
1,3-Dimethylnaphthalene (3g): 1H NMR (CDCl3, 400 MHz) δ 2.49
(s, 3H), 2.68 (s, 3H), 7.19 (s, 1H), 7.45 (dd, J = 3.2, 6.4 Hz, 2H), 7.50
(s, 1H), 7.77 (dd, J = 3.2, 6.0 Hz, 1H), 7.96 (dd, J = 3.4, 5.8 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 19.2, 21.6, 123.9, 124.8, 125.2, 125.6, 127.8,
128.9, 130.8, 133.8, 134.0, 135.0; GC/MS tR = 12.12 min; EI m/z 156
(M+), 141, 128, 115, 102, 89, 77, 63, 51, 39. Spectral data of 3g were
consistent with data reported in the literature.22
2-Methyl-6-phenylnaphthalene (7d): 1H NMR (CDCl3, 400 MHz)
δ 2.55 (s, 3H), 7.36 (d, J = 7.2 Hz, 1H), 7.39 (t, J = 7.2 Hz, 1H), 7.50
(t, J = 7.8 Hz, 2H), 7.65 (s, 1H), 7.74 (d, J = 7.2 Hz, 3H), 7.82 (d, J = 10.4
Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 8.02 (s, 1H); 13C NMR (CDCl3, 100
MHz) δ 21.7, 125.5, 125.6, 126.6, 127.2, 127.3, 127.7, 128.0, 128.6,
128.8, 131.9, 132.8, 135.6, 137.6, 141.2; GC/MS tR = 15.80 min; EI m/z
218 (M+), 218, 202, 189, 179, 165, 152, 141, 115, 109,101, 94, 87, 75, 63,
51. Spectral data of 7d were consistent with data reported in the
literature.26
1-Butyl-3-phenylnaphthalene (3h): 1H NMR (CDCl3, 400 MHz) δ
1.04 (t, J = 7.4 Hz, 3H), 1.54 (sextet, J = 7.4 Hz, 2H), 1.83 (quintet, J =
7.6 Hz, 2H), 3.18 (t, J = 7.6 Hz, 2H), 7.41 (t, J = 7.2 Hz, 1H), 7.51ꢀ7.56
(m, 4H), 7.65 (s, 1H), 7.77 (d, J = 7.6 Hz, 2H), 7.94 (d, J = 7.2 Hz, 1H),
7.95 (s, 1H), 8.10 (dd, J = 2.6, 7.6 Hz, 1H); 13C NMR (CDCl3, 100
MHz) δ 14.0, 22.9, 33.0, 33.1, 123.8, 124.3, 125.6, 125.7, 125.8, 127.2,
127.4, 128.8, 129.0, 131.1, 134.2, 138.1, 139.6, 141.3; HRMS (EI) [M]+
m/z calcd for C20H20 260.1565, found 260.1565.
2,3-Dimethoxy-6-phenylnaphthalene (7e): 1H NMR (CDCl3, 400
MHz) δ 4.03 (s, 6H), 7.16 (s, 1H), 7.19 (s, 1H), 7.37 (t, J = 7.2 Hz,
1H), 7.48 (t, J = 7.6 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 7.0
Hz, 2H), 7.77 (d, J = 8.4 Hz, 1H), 7.92 (s, 1H); 13C NMR (CDCl3, 100
MHz) δ 55.8, 106.0, 106.5, 123.8, 124.3, 126.8, 127.0, 127.2, 128.3,
128.8, 129.4, 137.0, 141.3, 149.5, 149.8 (1 carbon is missing due to
overlapping); HRMS (EI) [M]+ m/z calcd for C18H16O2 264.1150,
found 264.1143.
1,3-Diphenylnaphthalene (3i): 1H NMR (CDCl3, 400 MHz) δ 7.39
(t, J = 7.4 Hz, 1H), 7.42ꢀ7.57 (m, 9H), 7.72 (d, J = 1.6 Hz, 1H), 7.76
(d, J = 7.2 Hz, 2H), 7.91 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 8.07
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 125.4, 125.9, 126.1, 126.2,
126.7, 127.36, 127.43, 128.3, 128.6, 128.9, 130.1, 130.8, 134.2, 138.0,
140.7, 140.8, 140.9 (1 carbon is missing due to overlapping); GC/MS tR =
18.17 min; EI m/z 280 (M+), 263, 252, 239, 202, 189, 176, 165, 150, 138,
125, 113, 89, 75, 65, 51. Spectral data of 3i were consistent with data
reported in the literature.23
1
2,3-Methylenedioxy-6-phenylnaphthalene (7f): H NMR (CDCl3,
400 MHz) δ 6.05 (s, 2H), 7.15 (s, 1H), 7.18 (s, 1H), 7.38 (t, J = 7.4 Hz,
1H), 7.48 (t, J = 7.8 Hz, 2H), 7.60 (dd, J = 1.4, 8.6 Hz, 1H), 7.70 (d, J =
7.2 Hz, 2H), 7.74 (d, J = 8.4 Hz, 1H), 7.88 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ 101.0, 103.6, 104.1, 124.0, 125.0, 127.1, 127.2, 127.4,
128.8, 129.6, 130.7, 137.2, 141.1, 147.7, 147.9; GC/MS tR = 17.11 min;
EI m/z 248 (M+), 218, 202, 189, 178, 163, 150, 139, 124, 111, 94, 81,
75, 63. Spectral data of 7f were consistent with data reported in the
literature.25a
6,7-Dimethoxy-1-methyl-3-phenylnaphthalene (3j): 1H NMR
(CDCl3, 400 MHz) δ 2.71 (s, 3H), 4.03 (s, 3H), 4.06 (s, 3H) 7.21
(s, 1H), 7.23 (s, 1H), 7.36 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H),
7.49 (s, 1H), 7.72 (d, J = 7.6 Hz, 2H), 7.80 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 19.7, 55.8, 102.8, 107.2, 122.8, 124.7, 126.9,
127.2, 127.4, 128.7, 129.6, 133.2, 136.7, 141.4, 149.3, 149.4 (1
carbon is missing due to overlapping); HRMS (EI) [M]+ m/z calcd
for C19H18O2 278.1307, found 278.1310.
2-Ethyl-3-phenylnaphthalene (7g): 1H NMR (CDCl3, 400 MHz) δ
1.22 (t, J = 7.6 Hz, 3H), 2.82 (q, J = 7.6 Hz, 2H), 7.43ꢀ7.54 (m, 7H),
7.74 (s, 1H), 7.81 (s, 1H), 7.86 (d, J = 9.6 Hz, 1H), 7.89 (d, J = 7.6 Hz,
1H); 13C NMR (CDCl3, 100 MHz) δ 15.2, 26.6, 125.4, 125.8,
126.4, 126.9, 127.1, 127.5, 128.0, 128.6, 129.3, 131.7, 133.0, 140.1,
140.7, 141.8; HRMS (EI) [M]+ m/z calcd for C18H16 232.1252, found
232.1255.
1
(Z)-Methyl 2-(3,3-dimethylisochroman-1-ylidene)acetate (4a): H
NMR (CDCl3, 400 MHz) δ 1.40 (s, 6H), 2.91 (s, 2H), 3.71 (s, 3H), 5.64
(s, 1H), 7.14 (d, J = 7.6 Hz, 1H), 7.26 (t, J = 7.6 Hz, 1H), 7.36 (t, J = 7.4
Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 27.0,
40.1, 50.6, 76.7, 91.8, 124.9, 127.1, 128.1, 128.8, 130.7, 134.2, 161.7,
166.4; HRMS (EI) [M]+ m/z calcd for C14H16O3 232.1099, found
232.1097. The chemical structure of compound 4a was assigned on the
basis of spectral correlation with its ethyl ester congener.24
1
2-Methylnaphthalene (7h): H NMR (CDCl3, 400 MHz) δ 2.53
(s, 3H), 7.34 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 7.0 Hz, 1H), 7.46 (t, J = 6.2
Hz, 1H), 7.63 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 7.6 Hz, 1H),
7.81 (d, J = 7.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.7, 124.9,
125.8, 126.8, 127.2, 127.6, 127.7, 128.1, 131.7, 133.6, 135.4; GC/MS tR =
11.22 min; EI m/z 142 (M+), 128, 115, 102, 89, 77, 69, 63, 57, 51, 39.
Spectral dataof7h were consistent with data reportedintheliterature.26,27
1
2-Phenylnaphthalene (7a): H NMR (CDCl3, 400 MHz) δ 7.41
(t, J = 7.2 Hz, 1H), 7.50ꢀ7.56 (m, 4H), 7.76 (d, J = 8.4 Hz, 1H), 7.77
(t, J = 9.0 Hz, 2H), 7.89ꢀ7.96 (m, 3H), 8.08 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ 125.6, 125.8, 125.9, 126.3, 127.3, 127.4, 127.6, 128.2, 128.4,
128.8, 132.6, 133.7, 138.5, 141.1; GC/MS tR = 15.22 min; EI m/z 204
(M+), 204, 176, 150, 126, 101, 89, 74, 63, 51, 39. Spectral data of 7a were
consistent with data reported in the literature.25
’ ASSOCIATED CONTENT
S
Supporting Information. Copies of NMR spectra. This
b
material is available free of charge via the Internet at http://pubs.
acs.org.
2-Fluoro-6-phenylnaphthalene (7b): 1H NMR (CDCl3, 400 MHz)
δ 7.30 (td, J = 2.4, 8.8 Hz, 1H), 7.40 (t, J = 7.4 Hz, 1H), 7.49 (d, J =
8.0 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.72 (d, J = 7.6 Hz, 2H), 7.79 (d, J =
8.8 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.89 (dd, J = 5.6, 9.2 Hz, 1H), 8.04
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 110.7 (d, J = 20.5 Hz), 116.7
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: sowony73@hanyang.ac.kr.
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ARTICLE
’ ACKNOWLEDGMENT
R. A. J. Org. Chem. 2004, 69, 1738. (d) Wang, Y.-H.; Zhu, L.-L.; Zhang,
Y.-X.; Chen, Z. Chem. Commun. 2010, 577.
This work was supported by the Mid-career Researcher Pro-
gram (No. R01-2009-008-3940) and Basic Science Research
Program (Nos. 2010-0017149 and 2010-0007737) through the
National Research Foundation of Korea (NRF) grant funded
by the Ministry of Education, Science and Technology (MEST).
A.R.J. is grateful for 2009 NRF Postdoctoral Fellowship Program
for Foreign Researchers (No. K20802001473-10B120004500).
We gratefully acknowledge Professor Juyoung Yoon (Department
of Chemistry and Nano Science, Ewha Womans University) for his
generous support.
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