Highly selective electrophile-induced cascade reactions between o-alkynylbenzaldehydes and styrene oxides leading to the formation of 1-naphthyl ketones

Article abstract of DOI:10.1002/ejoc.200900809

An efficient method for the synthesis of naphthalene derivatives through reaction of o-alkynylbenzaldehydes and styrene oxides in the presence of molecular iodine was developed. The reaction involves Meinwald rearrangement of styrene oxides to form the co

Full text of DOI:10.1002/ejoc.200900809

FULL PAPER
DOI: 10.1002/ejoc.200900809
Highly Selective Electrophile-Induced Cascade Reactions between
o-Alkynylbenzaldehydes and Styrene Oxides Leading to the Formation of
1-Naphthyl Ketones
Nitin T. Patil,*[a] Ashok Konala,[a] Vipender Singh,[a] and Vaddu V. N. Reddy[a]
Keywords: Alkynes / Enols / Cycloaddition / Domino reactions / Ketones
An efficient method for the synthesis of naphthalene deriva-
tives through reaction of o-alkynylbenzaldehydes and sty-
rene oxides in the presence of molecular iodine was devel-
oped. The reaction involves Meinwald rearrangement of sty-
rene oxides to form the corresponding aryl acetaldehydes.
The enol forms of aryl acetaldehydes might undergo [4+2]
benzannulation reactions with iodinated benzopyrilium ions,
formed in situ from o-alkynylbenzaldehydes and iodine, to
afford 1-naphthyl ketones. The reaction was found to be
highly selective, and of two possible products, only one was
formed. Mechanistic aspects are discussed.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
for the synthesis of indoles and benzofurans.[11] Pioneering
work from the laboratory of Larock revealed that simple
molecular iodine can equally be used to synthesize naph-
thalenes from alkynals and alkenes/alkynes.[12] It should be
noted that all these processes are complimentary to the
metal-catalyzed process.[13]
As a part of our continued interest in alkyne acti-
vation,[14] we considered the process shown in Figure 1 as a
potentially useful metal-free approach for the synthesis of
naphthalenes. We envisioned that in the presence of iodine,
styrene oxides would undergo Meinwald rearrangement[15]
to form enols 6, which after [4+2] cycloaddition[16] with in
situ generated 5, followed by loss of water would produce
7.[17] Intermediate 7, thus formed, may either undergo ex-
trusion of iodine or a retro Diels–Alder reaction to produce
1-naphthyl ketones 3 or iodonaphthalenes 4, respec-
tively.[11a] Notably, the substituted naphthalenes[18] are
found in several biologically important compounds[19] and
exhibit promising electronic and optical properties.[20]
Introduction
The electrophilic cyclization of alkynes has proven to be
an efficient method for constructing a variety of carbocycles
and heterocycles.[1] These reactions are generally considered
to proceed through intramolecular attack of protected or
naked carbon,[2] nitrogen,[3] oxygen,[4] sulfur,[5] selenium,[6]
or Ar-H[7] moieties to electrophile-coordinated alkynes. Re-
cently, the electrophile-induced cascade[8] cyclization has
become a highly fascinating area of study, because those
reactions offer the opportunity to access highly function-
alized final products from simple starting materials. The
majority of the reported cascade reactions, trigged by the
coordination of alkynes to electrophiles, involve the use of
a single starting material containing an alkyne functionality
tethered to one more functional group.[9] Upon treatment
with electrophiles, coordination to the alkyne initiates a re-
action sequence leading to various products. Much more
appealing strategies would involve the use of alkynes and
nucleophiles/functional groups present in two different sub-
strates.
Recently, Barluenga reported the [4+2] benzannulation
between the iodinated isobenzopyrilium ion, generated in
situ from alkynal and IPy2BF4/HBF4, with alkenes and al-
kynes for the synthesis of naphthalenes.[10] The subsequent
paper from the same research group applied this strategy
[a] Organic Chemistry Division – II, Indian Institute of Chemical
Technology,
Hyderabad 500 607, India
Fax: +91-40-27193382
E-mail: nitin@iict.res.in
patilnitint@yahoo.com
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900809.
Figure 1. Concept of electrophile-induced [4+2] benzannulation.
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5178–5184

Formation of 1-Naphthyl Ketones by Electrophile-Induced Cascade Reactions
gave desired product 3b in 90% yield (Table 2, Entry 1). The
Results and Discussion
reaction of halo-substituted epoxides 2c–e with 1a also pro-
ceeded smoothly to produce 3c, 3d, and 3e in 70, 65, and
90% yield, respectively (Table 2, Entries 2–4). Styrene ox-
ides 2f, 2g, and 2h bearing electron-donating substituents
in the aromatic ring gave products 3f, 3g, and 3h in good
yields (Table 2, Entries 5–7). However, styrene oxides, bear-
ing strong electron-donating (cf. 2i) and strong electron-
withdrawing (cf. 2j) substituents on the aromatic ring
proved to be inert (Table 2, Entries 8 and 9). We assumed
that in the case of 2i the presence of the electron-donating –
NMe2 substituent may hamper the enolization of the re-
sulting aldehyde, and substrate 2j containing the electron-
withdrawing –NO2 group might be reluctant to undergo
Meinwald rearrangement. Treatment of 2-(1-octynyl)benz-
aldehyde (1b) and 2-(1-hexynyl)benzaldehyde (1c) with vari-
ous styrene oxides gave good to acceptable yields of 1-naph-
thyl ketones 3k–n (Table 2, Entries 10–13). Substrate 1d also
reacted well with epoxides 2a and 2h to give the corre-
sponding naphthyl ketones 3o and 3p, respectively, in good
yields (Table 2, Entries 14 and 15). The reaction is very sen-
sitive to the electronic nature of the R group in the o-alk-
ynylbenzaldehydes. Substrates 1e and 1f bearing –OH and
–OMe groups, respectively, in the meta position reacted well
with 2a/2c to give desired products 3q–s in high yields
(Table 2, Entries 16–18). However, in case of 1g bearing
an –OMe group in the para position, pure product 3t could
not isolated (Table 2, Entry 19).
We first allowed o-alkynylbenzaldehyde 1a to react with
styrene oxide (2a; 1.2 equiv.) and iodine (1.2 equiv.) in
dichloroethane (DCE; Table 1, Entry 1). To our pleasure, 1-
naphthyl ketone 3a was obtained in a 30% yield. When
THF was used, the yield increased to 80% (Table 1, En-
try 2). When 1a was treated with 2a in the presence of io-
dine (1.5 equiv.), 3a was obtained in 94% yield (Table 1,
Entry 3). The use of 4 Å molecular sieves (MS) as an addi-
tive suppressed the formation of product (Table 1, Entry 4).
This observation indicated that the presence of water is nec-
essary. A small amount of HI may be generated by the reac-
tion between I2 and H2O, which might be responsible for
the enolization of phenyl acetaldehyde. The addition of car-
bonate bases such as NaHCO3, K2CO3, and Na2CO3 ham-
pers the reaction (Table 1, Entry 5–7). The strong electro-
philic reagents ICl and NIS were also examined and proved
unsatisfactory (Table 1, Entries 8 and 9). The reaction is
very sensitive to solvent, and of the various solvents scre-
ened (CH3CN, toluene, MeOH) THF proved to be the best.
It is surprising to note that in all cases only 3a was obtained
and no formation of 4 (Ar = Ph) was detected as judged
1
by H NMR spectroscopic analysis of the crude reaction
mixtures. This observation is in marked contrast to pre-
viously reported IPy2BF4/HBF4-mediated benzannulation
reactions, wherein compounds 4 were obtained exclusively
from an intermediate similar to 7.[11a]
The presence of an electron-withdrawing group had no
impact on the yield of the reaction and product 3u was
obtained from 1h in 59% yield (Table 2, Entry 20). It should
be noted that this reaction is limited only to styrene oxides.
The epoxide derived from 1-octene did not undergo the
present reaction.
Table 1. Selected screening of the reaction conditions.[a]
A plausible mechanism is depicted in Figure 2. As shown
in cycle A, the attack of the aldehydic oxygen to the I+-
coordinated alkyne (cf. 8) leads to benzopyrilium cation 5.
Benzopyrilium cation 5 would undergo [4+2] cycloaddition
with 6, generated in situ from 2a (vide infra), to produce
intermediate 9. Intermediate 9 may undergo spontaneous
dehydration to produce 7. The extrusion of I2 from 7 would
give 3a. It is interesting to note that iodonaphthalenes 4
were not obtained by retro [4+2] cycloaddition in interme-
diate 7.[21] The formation of 6 from styrene oxide (1a) is
explained in cycle B. The coordination of iodine to the oxy-
gen atom of 1a would lead to the formation of intermediate
10 and then subsequently 11. The rearrangement as shown
in 11, might produce 6 with the regeneration of iodine.
Thus, the whole process can be considered as formally cata-
lytic, although an excess amount of iodine was used.
To gain some insight into the mechanism, we treated 1a
with commercially available 1-phenyl acetaldehyde (6b) un-
der standard conditions [Equation (1)]. Indeed, product 3a
Entry
Electrophile
(equiv.)
Additives (equiv.) Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
9
I2 (1.2)
I2 (1.2)
I2 (1.5)
I2 (1.5)
I2 (1.5)
I2 (1.5)
I2 (1.5)
NIS (1.5)
ICl (1.5)
–
DCE
THF
THF
THF
THF
THF
THF
THF
THF
30
80
94
10
–
–
4 Å MS
NaHCO3 (1)
K2CO3 (1)
Na2CO3 (1)
–
[c]
–
[c]
–
30[c]
[d]
–
[d,e]
–
–
[a] Reaction conditions: 1a (0.24 mmol), 2a (1.2 equiv.), electro-
philes and additives (wherever specified), r.t., 2 h. [b] Isolated
yields. [c] Alkynal 1a was recovered in 70, 62, and 30% yield for
Entries 5, 6, and 7, respectively. [d] Starting material 1a was con-
sumed; however, the desired product could not be isolated. [e] The
reaction was run at –78 °C then brought to r.t. and stirred for 2 h.
As the optimal reaction conditions had become clear, we was isolated in 90% yield.
then investigated the generality of the reaction by using
We have also explored a metal-catalyzed version of this
various o-alkynylbenzaldehydes with styrene oxides. The re- process. The reaction of 1a with 2a in the presence of Cu-
sults are summarized in Table 2. Treatment of 1a with 2- (OTf)2 (10 mol-%) at 80 °C in either THF or DCE afforded
(4-methylphenyl)oxirane (2b) under the standard conditions a mixture of 3a and 13 in variable ratios [Equation (2)].[17]
Eur. J. Org. Chem. 2009, 5178–5184
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N. T. Patil, A. Konala, V. Singh, V. V. N. Reddy
FULL PAPER
Table 2. Reaction of o-alkynylbenzaldehydes with styrene oxides.[a]
Figure 2. The plausible mechanism.
acetaldehydes, which are rather unstable. (3) The process is
completely chemoselective and only 1-naphthyl ketones
were obtained; iodonaphthalenes were not obtained.[11a]
(4) Electrophile-mediated reactions have been reported to
give 1-naphthyl ketones of type 14;[11–13] however, the pres-
ent method produces only regioisomers of type 3 (Figure 3).
[a] Reaction conditions: 1 (0.24 mmol), 2 (0.29 mmol), iodine
(1.5 equiv.), THF (0.1 ), r.t. [b] Isolated yields. [c] Starting mate-
rial 1a was consumed; however, the desired product could not be
isolated. [d] The desired product could not be isolated in pure form.
Although a variety of iodine-mediated benzannulation
reactions between o-alkynylbenzaldehydes and electron-rich
alkenes and alkynes have been developed previously, our
method has useful and unique features: (1) The process
avoids the use of the extremely moisture-sensitive AuBr3
catalyst and employs simple molecular iodine and, there-
fore, may prove complimentary to known processes.[17]
Figure 3. 1-Naphthyl ketones of types 3 and 14.
Conclusions
An efficient metal-free process for the synthesis of 1-
(2) The process makes use of styrene oxides in place of aryl naphthyl ketones was developed by the cascade reaction be-
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5178–5184

Formation of 1-Naphthyl Ketones by Electrophile-Induced Cascade Reactions
EtOAc, 95:5). 1H NMR (300 MHz, CDCl3): δ = 8.12 (d, J =
tween o-alkynylbenzaldehydes and styrene oxides in the
presence of molecular iodine. Interestingly, the reaction is
completely selective and only 1-naphthyl ketones were ob-
tained. The tolerance of halo substituents is particularly
noteworthy, because the resulting naphthalenes can be fur-
ther functionalized using well-known organopalladium
chemistry.
1.5 Hz, 1 H), 7.99 (d, J = 7.3 Hz, 1 H), 7.91 (m, 2 H), 7.88 (d, J =
1.4 Hz, 1 H), 7.77 (d, J = 2.1 Hz, 1 H), 7.58–7.52 (m, 3 H), 7.51–
7.48 (m, 1 H), 7.44 (t, J = 8.1 Hz, 3 H), 7.24–7.21 (m, 2 H), 2.40
(s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 197.9, 138.2, 137.7,
137.2, 137.1, 136.9, 134.2, 133.3, 130.5, 129.9, 129.7, 128.6, 128.5,
128.4, 127.9, 127.2, 127.1, 126.8, 125.5, 21.1 ppm. IR (film): ν =
˜
3051, 2923, 1661, 1595, 1509, 1448, 1314, 1254, 1113, 1059, 936,
897, 814, 750 cm–1. HRMS: calcd. for C24H19O 323.1435 [M +
H]+; found 323.1450.
Experimental Section
[3-(4-Chlorophenyl)-1-naphthyl](phenyl)methanone
(3c):
Yield:
General Methods: All reactions were carried out in oven- or flame-
dried vials with magnetic stirring under a nitrogen atmosphere.
Dried solvents and liquid reagents were transferred by oven-dried
syringes or hypodermic syringe cooled to ambient temperature in
a desiccators. All experiments were monitored by analytical thin-
layer chromatography (TLC). TLC was performed on precoated
plates, Merck 60 F254. After elution, the plates were visualized un-
der UV illumination at 254 nm for UV-active materials. Further
visualization was achieved by staining with KMnO4 and charring
on a hot plate. Solvents were removed in vacuo under ca. 30 Torr
and heated with a water bath at 35 °C. Silica gel finer than
200 mesh was used for flash column chromatography. Columns
were packed as slurries of silica gel in hexane and equilibrated with
the appropriate solvent/solvent mixture prior to use. The com-
pounds were loaded neat or as a concentrated solution by using the
appropriate solvent system. The elution was assisted by applying
pressure with an air pump. Yields refer to chromatographically and
spectroscopically homogeneous materials unless otherwise stated.
Melting points are uncorrected. Infrared spectra were recorded
with a Thermo Nicolet Nexus 670 spectrometer. IR spectra were
recorded as neat liquids or KBr pellets. NMR spectra were re-
corded with 300 and 400 MHz spectrometers in appropriate sol-
vents by using TMS as internal standard or the solvent signals as
secondary standards. 13C NMR spectra were recorded with a
75 MHz spectrometer. High-resolution mass spectra were obtained
by using ESI-QTOF mass spectrometry.
58 mg, 70%; pale-yellow oil; Rf = 0.40 (1a, Rf = 0.45) (hexane/
EtOAc, 95:5). 1H NMR (300 MHz, CDCl3): δ = 8.11 (d, J =
1.5 Hz, 1 H), 8.09 (d, J = 8.1 Hz, 1 H), 7.95–7.87 (m, 2 H), 7.86
(d, J = 1.5 Hz, 1 H), 7.80 (d, J = 8.49 Hz, 1 H), 7.73 (d, J = 1.8 Hz,
1 H), 7.54–7.45 (m, 4 H), 7.42 (t, J = 8.3 Hz, 4 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 197.7, 138.5, 138.1, 137.4, 135.9, 134.1,
133.9, 133.4, 130.4, 129.5, 129.2, 128.7, 128.5, 127.4, 127.1, 126.6,
125.6 ppm. IR (film): ν = 3059, 2926, 1661, 1597, 1495, 1448, 1315,
˜
1254, 1220, 1176, 934, 897, 825, 751, 662 cm–1. HRMS: calcd. for
C23H15ClONa [M + Na]+ 365.0711; found 365.0719.
[3-(4-Bromophenyl)-1-naphthyl](phenyl)methanone
(3d):
Yield:
62 mg, 65%; pale-yellow oil; Rf = 0.42 (1a, Rf = 0.45) (hexane/
EtOAc, 95:5). 1H NMR (300 MHz, CDCl3): δ = 8.09 (d, J =
1.5 Hz, 1 H), 8.01 (d, J = 8.3 Hz, 1 H), 7.97–7.91 (m, 2 H), 7.85
(d, J = 1.5 Hz, 1 H), 7.71 (d, J = 1.5 Hz, 1 H), 7.58–7.52 (m, 5 H),
7.49–7.40 (m, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 197.6,
138.9, 137.9, 137.3, 135.9, 133.9, 133.4, 132.1, 130.4, 130.2, 128.8,
128.6, 128.5, 127.4, 127.0, 126.4, 125.5, 122.1 ppm. IR (film): ν =
˜
3058, 1660, 1596, 1492, 1448, 1314, 1254, 1214, 1176, 934, 896,
856, 750, 709 cm–1. HRMS: calcd. for C23H15BrONa [M + Na]+
409.0206; found 409.0210.
[3-(4-Fluorophenyl)-1-naphthyl](phenyl)methanone
(3e):
Yield:
72 mg, 90%; thick oil; Rf = 0.42 (1a, Rf = 0.45) (hexane/EtOAc,
95:05). 1H NMR (300 MHz, CDCl3): δ = 8.08 (d, J = 1.5, Hz, 1
H), 7.99 (d, J = 8.3 Hz, 1 H), 7.92–7.89 (m, 2 H), 7.85 (d, J =
1.5 Hz, 1 H), 7.72 (d, J = 1.5 Hz, 1 H), 7.63–7.59 (m, 2 H), 7.58–
7.41 (m, 5 H), 7.11 (t, J = 8.3 Hz, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 197.7, 164.3, 138.1, 136.1, 134.1, 133.4, 130.4, 130.1,
128.9, 128.8, 128.6, 128.5, 128.4, 127.2, 126.9, 126.7, 125.5, 115.9,
Preparation of 3a as a Representative Example: To a THF (2.0 mL,
0.1 ) solution of 1a (50 mg, 0.24 mmol) and 2a (35 mg,
0.29 mmol) in 2.5-mL screw-cap vial was added molecular iodine
(92 mg, 1.5 equiv.) under a nitrogen atmosphere. The mixture was
stirred at room temperature for 2 h. Then, the reaction mixture
was diluted with ethyl acetate (10 mL), and a saturated solution of
sodium thiosulfate (10 mL) was added. The reaction mixture was
extracted with ethyl acetate (3ϫ10 mL). The combined organic
layer was dried with anhydrous sodium sulfate, and the solvent was
removed under reduced pressure. The residue thus obtained was
purified by flash silica gel column chromatography (hexane) to ob-
tain 3a (70 mg, 94%) as a pure compound.
Phenyl(3-phenyl-1-naphthyl)methanone (3a):[17a] Yield: 70 mg, 94%;
yellow oil; Rf = 0.40 (1a, Rf = 0.45) (hexane/EtOAc, 95:5). 1H
NMR (400 MHz, CDCl3): δ = 8.14 (s, 1 H), 8.02 (d, J = 8.8 Hz, 1
H), 7.93–7.90 (m, 2 H), 7.88 (d, J = 1.4 Hz, 1 H), 7.79 (d, J =
1.4 Hz, 1 H), 7.64 (d, J = 8.0 Hz, 2 H), 7.56 (t, J = 7.32 Hz, 1 H),
7.51–7.47 (m, 1 H), 7.46–7.42 (m, 5 H), 7.32 (t, J = 7.35 Hz, 1
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 196.8, 140.1, 138.3,
137.2, 134.1, 133.1, 130.4, 130.2, 129.7, 128.9, 128.6, 128.5, 128.4,
115.7 ppm. IR (film): ν = 3059, 1660, 1510, 1447, 1313, 1228, 1159,
˜
1099, 924, 896, 832, 713, 690 cm–1. HRMS: calcd. for C23H16FO
[M + H]+ 327.1185; found 327.1189.
[3-(4-Methoxyphenyl)-1-naphthyl](phenyl)methanone (3f): Yield:
61 mg, 74%; thick liquid; Rf = 0.30 (1a, Rf = 0.45) (hexane/EtOAc,
95:05). 1H NMR (300 MHz, CDCl3): δ = 8.03 (d, J = 1.1 Hz, 1 H),
7.99 (d, J = 8.3 Hz, 1 H), 7.91–7.87 (m, 3 H), 7.75 (d, J = 1.7 Hz,
1 H), 7.60–7.52 (m, 3 H), 7.50–7.39 (m, 4 H), 6.93 (d, J = 8.6 Hz,
2 H), 3.8 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 197.9,
159.6, 136.8, 134.2, 133.3, 133.2, 132.5, 131.1, 130.4, 130.0, 128.5,
128.4, 128.3, 127.9, 127.4, 126.9, 126.8, 126.0, 125.5, 114.4,
55.3 ppm. IR (film): ν = 3055, 1660, 1604, 1512, 1449, 1389, 1251,
˜
1178, 1111, 936, 817, 733 cm–1. HRMS: calcd. for C24H19O2 [M +
H]+ 339.1385; found 339.1392.
[3-(3-Methoxyphenyl)-1-naphthyl](phenyl)methanone (3g): Yield:
64 mg, 78%; yellow oil; Rf = 0.43 (1a, Rf = 0.45) (hexane/EtOAc,
127.6, 127.3, 127.0, 126.9, 126.8, 125.7 ppm. IR (film): ν = 3057,
1
˜
95:05). H NMR (300 MHz, CDCl3): δ = 8.13 (s, 1 H), 7.99 (d, J
1660, 1591, 1497, 1449, 1313, 1253, 1209, 1169, 933, 813, 892, 762,
698 cm–1. HRMS: calcd. for C23H17O [M + H]+ 309.1280; found
309.1269.
= 7.9 Hz, 1 H), 7.93–7.89 (m, 2 H), 7.87 (d, J = 1.5 Hz, 1 H), 7.77
(d, J = 1.7 Hz, 1 H), 7.58–7.50 (m, 2 H), 7.46–7.38 (m, 3 H), 7.31
(t, J = 7.7 Hz, 1 H), 7.23–7.14 (m, 2 H), 6.85 (d, J = 8.1 Hz, 1 H),
3.80 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 196.3, 160.1,
133.3, 133.0, 131.3, 130.5, 130.4, 129.9, 129.2, 128.8, 128.5, 128.3,
[3-(4-Methylphenyl)-1-naphthyl](phenyl)methanone (3b): Yield:
71 mg, 90%; pale-yellow oil; Rf = 0.42 (1a, Rf = 0.45) (hexane/
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N. T. Patil, A. Konala, V. Singh, V. V. N. Reddy
127.1, 126.8, 126.4, 119.8, 113.2, 113.0, 111.3, 55.0 ppm. IR (film): 134.2, 132.1, 129.4, 128.8, 128.6, 127.8, 126.9, 125.9, 125.5, 112.2,
FULL PAPER
ν = 3057, 1660, 1591, 1490, 1451, 1311, 1211, 1172, 1045, 948, 886,
42.2, 29.6, 26.5, 13.9 ppm. IR (film): ν = 3058, 2951, 2927, 2869,
˜
˜
781, 689 cm–1. HRMS: calcd. for C24H19O2 [M + H]+ 339.1385;
found 339.1382.
1680, 1590, 1496, 1435, 1339, 1241, 1110, 952, 890, 860, 765,
692 cm–1. HRMS: calcd. for C21H20BrO [M + H]+ 368.0698; found
368.0689.
[3-(3-Phenoxyphenyl)-1-naphthyl](phenyl)methanone (3h): Yield:
60 mg, 61%; yellow oil; Rf = 0.30 (1a, Rf = 0.45) (hexane/EtOAc,
95:05). 1H NMR (300 MHz, CDCl3): δ = 8.14 (d, J = 1.4 Hz, 1 H),
8.02 (d, J = 8.1 Hz, 1 H), 7.90 (m, 2 H), 7.89 (d, J = 1.4 Hz, 1 H),
3-Phenyl-1-(3-phenyl-1-naphthyl)propan-1-one (3o): Yield: 54 mg,
1
75%; liquid; Rf = 0.42 (1d, Rf = 0.48) (hexane/EtOAc, 95:05). H
NMR (400 MHz, CDCl3): δ = 8.50 (d, J = 8.0 Hz, 1 H), 8.09 (s, 1
7.78 (d, J = 2.2 Hz, 1 H), 7.61–7.50 (m, 3 H), 7.47–7.44 (m, 2 H), H), 7.94 (s, 1 H), 7.85 (d, J = 8.0 Hz, 1 H), 7.59 (d, J = 8.0 Hz, 2
7.41–7.39 (m, 2 H), 7.37–7.31 (m, 3 H), 7.11–7.03 (m, 3 H), 6.99– H), 7.56–7.47 (m, 2 H), 7.43 (t, J = 7.2 Hz, 2 H), 7.36 (t, J =
6.96 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 186.2, 157.8, 8.0 Hz, 1 H), 7.20–7.24 (m, 4 H), 7.17–7.12 (m, 1 H), 3.39 (t, J =
141.9, 138.1, 137.1, 136.4, 133.3, 130.4, 130.2, 129.8, 128.8, 128.7,
128.5, 127.5, 127.3, 126.9, 126.8, 125.5, 123.4, 122.2, 118.9, 117.9,
7.2 Hz, 2 H), 3.13 (t, J = 7.2 Hz, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 203.6, 157.8, 136.8, 136.5, 134.2, 130.3, 129.9, 128.6,
128.4, 128.1, 126.9, 126.8, 126.3, 125.5, 123.5, 122.2, 118.9, 118.1,
117.8 ppm. IR (film): ν = 3060, 1661, 1584, 1448, 1409, 1313, 1250,
˜
1220, 1168, 959, 908, 846, 753, 694 cm–1. HRMS: calcd. for
C29H21O2 [M + H]+ 401.1542; found 401.1554.
117.8, 44.1, 29.7 ppm. IR (film): ν = 3057, 3028, 2927, 1681, 1599,
˜
1497, 1452, 1404, 1310, 1237, 1143, 949, 888, 857, 763, 698 cm–1.
HRMS: calcd. for C25H21O [M + H]+ 337.1593; found 337.1598.
1-(3-Phenyl-1-naphthyl)heptan-1-one (3k):[13d] Yield: 54 mg, 72%;
yellow oil; Rf = 0.48 (1b, Rf = 0.52) (hexane/EtOAc, 95:05). 1H
NMR (400 MHz, CDCl3): δ = 8.49 (d, J = 8.7 Hz, 1 H), 8.09 (s, 1
H), 8.01 (d, J = 1.4 Hz, 1 H), 7.87 (dd, J = 7.3, 2.2 Hz, 1 H), 7.66
(dd, J = 7.3, 1.4 Hz, 2 H), 7.59–7.49 (m, 2 H), 7.46 (t, J = 7.3 Hz,
2 H), 7.37 (t, J = 7.3 Hz, 1 H), 3.07 (t, J = 7.2 Hz, 2 H), 1.80
(pent., J = 7.3 Hz, 2 H), 1.44–1.38 (m, 2 H), 1.37–1.30 (m, 4 H),
0.89 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
203.7, 140.43, 137.3, 134.4, 129.7, 129.5, 129.0, 128.6, 127.7, 127.6,
1-[3-(3-Phenoxyphenyl)-1-naphthyl]-3-phenylpropan-1-one
(3p):
Yield: 72 mg, 78%; orange solid; m.p. 96–98 °C; Rf = 0.40 (1d, Rf
1
= 0.48) (hexane/EtOAc, 95:05). H NMR (400 MHz, [D6]DMSO):
δ = 8.44–8.40 (m, 1 H), 8.27 (s, 1 H), 8.17 (s, 1 H), 8.02–7.98 (m,
1 H), 7.78 (d, J = 8.4 Hz, 2 H), 7.59–7.54 (m, 3 H), 7.50 (t, J =
7.3 Hz, 3 H), 7.41 (t, J = 7.3 Hz, 2 H), 7.32–7.26 (m, 5 H), 7.18 (t,
J = 6.3 Hz, 1 H), 3.51 (t, J = 7.2 Hz, 2 H), 3.12 (t, J = 7.2 Hz, 2
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 203.3, 141.3, 139.7,
127.4, 126.8, 126.7, 125.9, 42.3, 31.8, 29.7, 24.7, 22.6, 14.2 ppm. IR 137.0, 136.9, 134.4, 130.1, 129.7, 129.2, 129.1, 129.0, 128.7, 128.5,
(film): ν = 3056, 2954, 2926, 2855, 1681, 1598, 1498, 1456, 1311,
128.0, 127.7, 127.4, 127.0, 126.9, 126.2, 125.7, 118.8, 43.6,
˜
1237, 1166, 1088, 948, 889, 762, 667 cm–1. HRMS: calcd. for
C23H25O [M + H]+ 317.1906; found 317.1912.
30.5 ppm. IR (KBr): ν = 3058, 3038, 2827, 1682, 1589, 1496, 1462,
˜
1404, 1310, 1238, 1143, 958, 886, 857, 763, 696 cm–1. HRMS: calcd.
for C31H25O2 429.1855 [M + H]+; found 429.1864.
1-[3-(3-Methoxyphenyl)-1-naphthyl]heptan-1-one (3l): Yield: 46 mg,
56%; yellow oil; Rf = 0.40 (1b, Rf = 0.52) (hexane/EtOAc, 95:05). (3-Hydroxyphenyl)(3-phenyl-1-naphthyl)methanone (3q): Yield:
1H NMR (300 MHz, CDCl3): δ = 8.49 (dd, J = 7.5, 1.5 Hz, 1 H),
8.06 (s, 1 H), 7.97 (d, J = 1.8 Hz, 1 H), 7.86 (dd, J = 7.3, 2.0 Hz,
1 H), 7.57–7.46 (m, 2 H), 7.35 (t, J = 7.9 Hz, 1 H), 7.24–7.14 (m,
2 H), 6.88 (dd, J = 7.5, 1.8 Hz, 1 H), 3.87 (s, 3 H), 3.05 (t, J =
70 mg, 80%; yellow oil; Rf = 0.40 (1e, Rf = 0.40) (hexane/EtOAc,
80:20). H NMR (400 MHz, CDCl3): δ = 8.13 (s, 1 H), 8.01 (d, J
= 8.1 Hz, 1 H), 7.92 (d, J = 8.1 Hz, 1 H), 7.80 (d, J = 1.4 Hz, 1
H), 7.64 (d, J = 8.1 Hz, 2 H), 7.48–7.39 (m, 3 H), 7.32–7.21 (m, 5
1
7.4 Hz, 2 H), 1.79 (pent., J = 7.4 Hz, 2 H), 1.44–1.25 (m, 6 H), H), 7.06 (dt, J = 8.0, 1.4 Hz, 1 H), 6.83 (br. s, 1 H, D2O exchange-
0.89 (t, J = 6.8 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
205.1, 160.1, 141.6, 137.2, 137.0, 134.2, 130.0, 129.7, 129.2, 128.6,
127.7, 126.6, 125.7, 125.6, 119.7, 113.2, 112.8, 55.3, 42.4, 31.6, 28.9,
able) ppm. 13C NMR (75 MHz, CDCl3): δ = 198.4, 156.3, 139.3,
137.1, 136.8, 134.1, 129.9, 129.8, 129.0, 128.9, 128.8, 127.8, 127.4,
126.9, 125.3, 123.2, 121.9, 121.1, 116.5 ppm. IR (film): ν = 3377,
˜
24.6, 22.4, 14.0 ppm. IR (film): ν = 3052, 2961, 2927, 2865, 1680, 3058, 1651, 1590, 1497, 1449, 1311, 1276, 1233, 1134, 1075, 959,
˜
1597, 1485, 1436, 1355, 1220, 1174, 1098, 960, 892, 760, 668 cm–1. 888, 759, 695 cm–1. HRMS: calcd. for C23H17O2 [M + H]+
HRMS: calcd. for C24H27O2 [M + H]+ 347.2012; found 347.2019.
325.1229; found 325.1234.
1-(3-Phenyl-1-naphthyl)pentan-1-one (3m): Yield: 61 mg, 78%; yel-
low oil; Rf = 0.49 (1c, Rf = 0.54) (hexane/EtOAc, 95:5). H NMR
(300 MHz, CDCl3): δ = 8.49 (d, J = 7.5 Hz, 1 H), 8.09 (s, 1 H),
8.01 (d, J = 1.8 Hz, 1 H), 7.87 (dd, J = 7.3, 2.2 Hz, 1 H), 7.67 (d,
J = 7.1 Hz, 2 H), 7.57–7.44 (m, 4 H), 7.37 (t, J = 7.3 Hz, 1 H),
3.08 (t, J = 7.3 Hz, 2 H), 1.79 (pent., J = 7.5 Hz, 2 H), 1.45 (sext.,
[3-(4-Chlorophenyl)-1-naphthyl](3-hydroxyphenyl)methanone (3r):
1
Yield: 68 mg, 70%; white solid; m.p. 158–160 °C; Rf = 0.40 (1e, Rf
1
= 0.40) (hexane/EtOAc, 80:20). H NMR (300 MHz, [D6]DMSO):
δ = 9.51 (br. s, 1 H, D2O exchangeable), 8.22 (s, 1 H), 8.01 (d, J =
8.1 Hz, 1 H), 7.93 (d, J = 8.1 Hz, 1 H), 7.75 (d, J = 1.7 Hz, 1 H),
7.70 (d, J = 8.4 Hz, 2 H), 7.61–7.42 (m, 4 H), 7.35–7.18 (m, 3 H),
J = 7.5 Hz, 2 H), 0.98 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR 7.09–7.01 (m, 1 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
(75 MHz, CDCl3): δ = 205.0, 140.1, 137.3, 137.2, 134.3, 130.3, 196.7, 157.1, 138.4, 137.7, 136.9, 135.0, 133.2, 133.0, 129.3, 128.8,
129.6, 128.9, 128.6, 127.7, 127.6, 127.3, 126.7, 126.6, 125.5, 42.1,
128.4, 127.9, 127.8, 127.5, 126.5, 126.2, 125.4, 124.8, 120.9, 120.4,
26.7, 22.4, 13.9 ppm. IR (film): ν = 3056, 2957, 2929, 2867, 1681, 115.9 ppm. IR (KBr): ν = 3357, 3056, 1641, 1590, 1496, 1459, 1321,
˜
˜
1598, 1498, 1455, 1340, 1244, 1126, 948, 888, 856, 763, 698 cm–1. 1279, 1243, 1234, 1075, 959, 898, 756, 696 cm–1. HRMS: calcd. for
HRMS: calcd. for C21H20ONa [M + Na]+ 311.1420; found
311.1411.
C23H16ClO2 [M + H]+ 359.0840; found 359.0846.
(3-Methoxyphenyl)(3-phenyl-1-naphthyl)methanone (3s): Yield:
66 mg, 92%; yellow oil; Rf = 0.32 (1f, Rf = 0.37) (hexane/EtOAc,
95:5). H NMR (300 MHz, CDCl3): δ = 8.13 (s, 1 H), 8.01 (d, J =
1-[3-(4-Bromophenyl)-1-naphthyl]pentan-1-one (3n): Yield: 50 mg,
50%; yellow oil; Rf = 0.50 (1c, Rf = 0.54) (hexane/EtOAc, 95:05).
1H NMR (400 MHz, CDCl3): δ = 8.45 (s, 1 H), 8.12 (d, J = 8.3 Hz,
1
8.3 Hz, 1 H), 7.91 (d, J = 8.3 Hz, 1 H), 7.78 (d, J = 2.2 Hz, 1 H),
1 H), 7.61 (d, J = 1.5 Hz, 1 H), 7.76–7.68 (m, 1 H), 7.46–7.42 (m, 7.65 (dd, J = 8.3, 1.5 Hz, 2 H), 7.54–7.36 (m, 5 H), 7.35–7.23 (m,
2 H), 7.36–7.32 (m, 4 H), 3.07 (t, J = 6.8 Hz, 2 H), 1.79 (pent., J
= 7.5 Hz, 2 H), 1.45 (sext., J = 7.5 Hz, 2 H), 0.97 (t, J = 7.5 Hz, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 204.9, 137.6, 136.5,
3 H), 7.09 (dt, J = 7.5, 1.5 Hz, 1 H), 3.84 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 197.6, 159.7, 139.9, 139.4, 137.0, 134.0,
129.4, 128.9, 128.7, 128.6, 127.6, 127.3, 127.1, 127.0, 126.8, 125.5,
5182
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5178–5184

Formation of 1-Naphthyl Ketones by Electrophile-Induced Cascade Reactions
1775–1789; c) D. Yue, T. Yao, R. C. Larock, J. Org. Chem.
123.6, 120.0, 113.9, 55.4 ppm. IR (film): ν = 3056, 1658, 1591, 1490,
˜
1451, 1310, 1201, 1172, 1045, 958, 886, 786, 680 cm–1. HRMS:
calcd. for C24H19O2 [M + H]+ 339.1385; found 339.1387.
2006, 71, 62–69; d) T. Yao, R. C. Larock, J. Org. Chem. 2005,
70, 1432–1437; e) M. Amjad, D. W. Knight, Tetrahedron Lett.
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z´alez, J. Am. Chem. Soc. 2003, 125, 9028–9029.
(4-Nitrophenyl)(3-phenyl-1-naphthyl)methanone (3u): Yield: 42 mg,
59%; yellow oil; Rf = 0.30 (1h, Rf = 0.41) (hexane/EtOAc, 90:10).
1H NMR (400 MHz, CDCl3): δ = 8.31 (dd, J = 8.8, 3.6 Hz, 2 H),
8.20 (s, 1 H), 8.08 (d, J = 8.1 Hz, 1 H), 8.03 (dd, J = 8.8, 2.2 Hz,
2 H), 7.96 (d, J = 8.1 Hz, 1 H), 7.78 (s, 1 H), 7.62 (d, J = 8.1,
2.0 Hz, 2 H), 7.58–7.48 (m, 2 H), 7.44 (t, J = 7.3 Hz, 2 H), 7.35 (t,
J = 7.3 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 195.8,
150.3, 143.2, 139.6, 137.2, 135.4, 134.2, 131.1, 129.9, 129.8, 129.1,
[4]
[5]
128.8, 128.2, 127.9, 127.7, 127.2, 125.2, 123.7 ppm. IR (film): ν =
˜
3060, 1660, 1591, 1496, 1441, 1350, 1301, 1211, 1172, 1045, 948,
886, 781, 689 cm–1. HRMS: calcd. for C23H16NO3 [M + H]+
354.1131; found 354.1125.
[6]
[7]
Synthesis of 3a by I2-Mediated Reaction between 1a and 6b: To a
THF (2.0 mL, 0.1 ) solution of 1a (50 mg, 0.2427 mmol) and 6b
(58 mg, 0.4854 mmol) in a 2.5-mL screw-cap vial was added molec-
ular iodine (92 mg, 1.5 equiv.). The mixture was stirred at room
temperature for 3 h. Then, the reaction mixture was diluted with
ethyl acetate (10 mL), and a saturated solution of sodium thiosul-
fate (10 mL) was added. The reaction mixture was extracted with
ethyl acetate (3ϫ10 mL). The combined organic layer was dried
with anhydrous sodium sulfate, and the solvent was removed under
reduced pressure. The residue thus obtained was purified by flash
silica gel column chromatography (hexane) to obtain 3a (67 mg,
90%) as a pure compound.
[8]
[9]
Synthesis of 3a and 13 by Cu(OTf)2-Mediated Reaction between 1a
and 6b: To a DCE/THF (2.0 mL, 0.1 ) solution of 1a (50 mg,
0.2427 mmol) and 2a (35 mg, 0.2912 mmol) in a 2.5-mL screw-cap
vial was added Cu(OTf)2 (9 mg, 10 mol-%) under a nitrogen atmo-
sphere. The mixture was stirred at 80 °C for the time specified in
Equation (2). Then, the reaction mixture was cooled and passed
through a short pad of silica gel (ethyl acetate). The combined fil-
trate was evaporated under reduced pressure. The residue thus ob-
tained was purified by flash silica gel column chromatography (hex-
ane) to obtain a mixture of compounds 3a and 13[22] in variable
yields and ratios as shown in Equation (2).
Supporting Information (see footnote on the first page of this arti-
cle): Synthesis of starting materials, experimental procedures, char-
1
acterization data, H and 13C NMR spectra.
[10]
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J. Barluenga, H. Vázquez-Villa, A. Ballesteros, J. M. González,
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Acknowledgments
We gratefully acknowledge financial support by the Council of Sci-
entific and Industrial Research, India. N.T.P. is grateful to Dr. J. S.
Yadav, Director, IICT, and Dr. T. K. Chakraborty, Director,
C.D.R.I., for their support and encouragement.
[12]
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Eur. J. Org. Chem. 2009, 5178–5184
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5183

N. T. Patil, A. Konala, V. Singh, V. V. N. Reddy
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–
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Received: July 18, 2009
Published Online: September 15, 2009
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