Iodide-catalyzed halocyclization/cycloaddition/elimination cascade reaction

Article abstract of DOI:10.1021/jo302676g

An iodocyclization reaction of o-alkynylphenyl carboxaldehydes is reported that is truly catalytic with respect to the electrophilic iodine source. With a combination of tetrabutylammonium iodide (TBAI), Oxone as non-nucleophilic and easy to handle co-oxidant, and fluorinated protic solvents, highly substituted 1-naphthalenones could be prepared in high yields of up to 91%.

Full text of DOI:10.1021/jo302676g

Note
pubs.acs.org/joc
Iodide-Catalyzed Halocyclization/Cycloaddition/Elimination Cascade
Reaction
Ulrich Kloeckner, Peter Finkbeiner, and Boris J. Nachtsheim*
Institute of Organic Chemistry, Eberhard Karls University Tuebingen, Auf der Morgenstelle 18, D-72076 Tuebingen, Germany
S
* Supporting Information
ABSTRACT: An iodocyclization reaction of o-alkynylphenyl
carboxaldehydes is reported that is truly catalytic with respect to
the electrophilic iodine source. With a combination of tetrabuty-
lammonium iodide (TBAI), Oxone as non-nucleophilic and easy to
handle co-oxidant, and fluorinated protic solvents, highly
substituted 1-naphthalenones could be prepared in high yields of
up to 91%.
he electrophilic iodine-induced cyclization of ortho-
Scheme 2. Electrophilic Halogen-Induced Cyclization of o-
T
substituted arylalkynes is a powerful method for the
Alkynylarenecarboxaldehydes4g
construction of benzannulated carbo- and heterocycles.1 The
electrophilic iodine atom activates the alkyne through
formation of an iodonium ion that is attacked by carbon-,2
nitrogen-,3 oxygen-,4 sulfur-,5 or selenium-containing nucleo-
philes6 to give a highly functionalized carbo- or heterocycle
(Scheme 1). As electrophilic iodine sources mostly NIS,
Scheme 1. Electrophilic Halogen-Induced Cyclization of
Arylalkynes through a Halonium Ion Intermediate
iodonium ion A. In a consecutive step, in situ formed B is
trapped by an alkene. A cycloaddition yields intermediate C and
subsequently D, which readily eliminates an iodide anion to
give the desired 2-substituted 1-naphthalenone 2. Similar
substituted naphthalenones could so far only be observed by
Au(III)-catalyzed benzannulations between o-alkynylbenzalde-
hydes and alkynes.8a,b However, since in this transformation the
iodine atom is not part of the final product this transformation
could be conducted much more efficient with only catalytic
amounts of an iodine source, if the electrophilic iodine atom
can be recovered in situ by oxidation.
IPy2BF4 (Barluenga’s reagent), ICl, or I2 are utilized. These
alkyne-based halocyclization reactions are useful and metal-free
alternatives to gold-catalyzed alkyne cyclizations.7 However,
their major drawback is still the need for stoichiometric
amounts of the halogen source. Of course, if the iodine atom is
supposed to be part of the final reaction product, as it is in
many cases, the use of stoichiometric amounts of these
iodination reagents is mandatory. However, one could in
principle imagine halocyclization-based cascade reactions,
where the iodinated intermediate reacts further under loss of
iodide, for example, through a subsequent substitution or
elimination process. In this case, only catalytic amounts of an
iodide source would be necessary if a co-oxidant is present in
the reaction mixture.
The in situ oxidation of iodide salts to electrophilic iodine
species such as (hypo)iodites and their subsequent use as
environmental benign catalysts in oxidative C−C and C−X
bond-forming reactions has been investigated intensively
In 2006, Barluenga and co-workers reported the reaction of
o-alkynylarenecarboxaldehydes 1 with stoichiometric amounts
of IPy2BF4 (Scheme 2).4g In this reaction, a benzo[c]pyrillium
ion B is formed through intramolecular ring closure of the
Received: December 12, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo302676g | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Table 1. Optimization Studies
entry
cat (mol %)
additive (equiv)
AcOH (3)
solvent
T (°C)
time (h)
yield of 2a (%)
1
TBAI (10)
TBAI (10)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
KI (20)
MeCN
MeCN
MeCN
MePh
DCM
DMF
TFE
70
70
70
70
rt
72
72
72
72
72
72
2
29
traces
31
0
2
3
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
4
5
0
6
70
70
70
70
70
70
70
70
70
70
70
50
50
0
7
72
65
49
12
0
8
TFE
21
21
3
9
I2 (20)
TFE
10
11
12
13
14
15
16
17
18
I2 (120)
TFE
TBABr (20)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
TBAI (20)
TFE
72
21
12
12
12
12
15
3
TFE
64
64
23
traces
22
24
91
NaOAc (3)
TFA (1)
TFE
TFE
HBF4·OEt2 (1)
CSA (3)
TFE
TFE
AcOH (3)
HFIP
HFIP
a
General reaction conditions: 0.1 mmol of 1a, 0.2 mmol (2 equiv) of styrene, catalyst, additive, and 0.15 mmol (1.5 equiv) of Oxone in 1 mL of
b
c
solvent. 0.3 mmol (3 equiv) of Oxone. Isolated yield after flash column chromatography.
recently.9,10 In this context, our group has developed a direct
oxidative amination protocol for benzo[d]oxazoles using simple
tetrabutylammonium iodide (TBAI) and aqueous solutions of
tert-butyl hydroperoxide (TBHP) or hydrogen peroxide as co-
oxidants.11 In this paper, we report the first application of
(hypo)iodite catalysis in Barluenga’s iodocyclization/cyclo-
addition/elimination cascade reaction.12,13
Brønsted acids such as TFA, CSA, or HBF4, yields dropped
significantly to 22−23% (entries 14−16). Finally we tested
HFIP (1,1,1,3,3,3-hexafluoro-2-propanol) as an alternative
fluorinated protic solvent. When AcOH was added to the
reaction mixture the yield was significantly lower compared to
TFE (24%, entry 17). However, due to the remarkable low pKa
of HFIP (9.3) we thought an acidic additive might be
unnecessary, and therefore, we repeated the experiment, this
time without an additional Brønsted acid. To our great delight,
we observed that the reaction was very clean and 2a could be
isolated in excellent yields of 91% (entry 18). We propose that
the significant influence of the solvent and/or acetic acid might
be the result of stable in situ formed hypoiodite species such as
AcOI or (CF3)2HCOI.
With these optimized reaction conditions in hand, we next
elucidated the substrate scope of the iodocyclization/cyclo-
addition/elimination cascade reaction. First, we reacted various
o-alkynylphenyl carboxaldehydes 1 with styrene (Table 2).
Electron-rich o-alkynylaryl aldehydes such as 1b could be
transformed into the corresponding 1-naphthalenone 2b in
82% yield. Remarkably, no significant iodination of the arene
was observed.15 Furthermore, various alkyl-substituted alkynyl
derivatives 1c−f were tested. All gave the corresponding 1-
napthalenones 2c−f in good yields between 60% and 81% after
short reaction times. The t-Bu-substituted alkyne 1g gave 2g in
85% yield. An alkynyl ester was tolerated as well giving 2h in
30% yield. With example 2i we could surprisingly show that
even o-alkynyl substituted acetophenones gave the cyclized 1-
naphthalenone in 53% yield after 5 h. Here no significant
Oxone-mediated oxidation of the ketone to the corresponding
dioxirane was observed.
TBHP, which was intensively used as co-oxidant in previous
(hypo)iodite catalyzed reactions, seemed to be a nonsuitable
co-oxidant due to the nucleophilic properties of the emerging t-
BuO− anion which could undergo undesired nucleophilic
addition to the benzo[c]pyrilium intermediate B. Therefore, a
co-oxidant was needed that, after its reduction, yields a non-
nucleophilic anion. Here, Oxone (KHSO5/KHSO4/K2SO4)
was chosen as an alternative because of the non-nucleophilic
character of the resulting KSO4− anion. Furthermore, Oxone is,
just as TBHP, cheap and easy to handle.14 In a first experiment,
we were pleased to find that with Oxone in acetonitrile and
acetic acid as an additive the desired 1-naphthalenone 2a could
be isolated, although in only 29% yield (Table 1, entry 1).
Without an acid additive only traces of 2a could be observed
(entry 2). Increasing catalyst loading from 10 to 20 mol %
increased the yield of 2a slightly to 31% (entry 3). In aromatic
and chlorinated solvents as well as in other polar aprotic
solvents such as DMF, the reaction did not proceed at all (entry
4−6).
However we were pleased to find that in TFE (2,2,2-
trifluoroethanol) yields increased significantly to 72% (entry 7).
Other iodine sources were not as effective as TBAI, and with
the corresponding bromine salt (TBABr) no reaction was
observed at all (entries 8−11). Next, we tested the influence of
the additive. In TFE we found that the reaction gave 2a still in
good yields even without addition of acetic acid. Addition of
NaOAc was also effective (entries 12 and 13). With stronger
However nitrogen-containing heterocycles, such as nicoti-
naldehyde are not tolerated, most likely due to an undesired N-
oxidation.
B
dx.doi.org/10.1021/jo302676g | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Table 2. Reaction of Various o-Alkynylarenecarboxaldehydes
and -ketones 1 with Styrene
Table 3. Reaction of Various Alkenes with 2-
(Phenylethynyl)benzaldehyde 1a
a
a
a
General reaction conditions: 0.1 mmol of 1a, 0.2 mmol (2 equiv) of
styrene, TBAI, and Oxone in 1 mL of 1,1,1,3,3,3-hexafluoro-2-
propanol. The given equivalents are related to 1.
Next we elaborated the influence of various alkenes on the
reaction with 1a (Table 3). A variety of halogen-substituted
styrenes (2-Cl, 4-Cl, and 3-Br) could be reacted with 1a giving
the desired products 2j−l in 66−87% yield. 3-CF3-substituted
styrene gave 2m in 89% yield.
a
General reaction conditions: 0.1 mmol of 1a, 0.2 mmol (2 equiv) of
dienophile, TBAI, and Oxone in 1 mL of 1,1,1,3,3,3-hexafluoro-2-
3-Methylstyrene also reacted smoothly to give 2n in 82%
yield. However, with 4-methylstyrene as dienophile yields
dropped significantly to 45% (2o). In general, highly electron-
rich methoxy-substituted styrenes gave rather complex reaction
mixtures. Here, only traces of the desired product could be
observed. However, indene gave 2p in 75% yield, and ethyl
cinnamate gave the 3-carboxylated 1-naphthalenone 2q in 83%
yield. Stilbene gave naphthalenone 2r in 70% yield. Alkenes
that do not contain an aryl substituent, such as cyclohexene, do
not give the desired 1-naphthalenones. Interestingly, undesired
oxidation products such as epoxides or carboxylic acids could
not be observed in significant amounts. Furthermore, it is worth
mentioning that no undesired iodine-containing starting
materials were observed in significant amounts. This undesired
halogenation is one of the major side reactions in
halocyclizations in which stoichiometric amounts of the
electrophilic iodine source must be used.
In summary, we have developed the first truly catalytic
iodonium-mediated benzannulation protocol. The key to the
success of this efficient iodine-catalyzed transformation was the
use of fluorinated protic solvents, in particular, HFIP and
Oxone as the co-oxidant. With only 20 mol % of TBAI, a
variety of highly functionalized 1-naphthalenones could be
isolated in excellent yields of up to 91%. On the basis of this
novel catalytic procedure, many other truly catalytic iodonium-
initiated cyclization/elimination cascades should be possible.
b
propanol. 0.3 mmol (3 equiv) of 1H-indene was added dropwise over
6 h. The given equivalents are related to 1a.
EXPERIMENTAL SECTION
■
1H NMR spectra were recorded on a 400 MHz instrument. Chemical
shifts for H NMR were reported as δ (parts per million) relative to
1
the signal of CHCl3 at 7.26(s) ppm. Chemical shifts for 13C NMR
were reported as δ (parts per million) relative to the CDCl3 triplet at
77.0 ppm. The following abbreviations were used to describe splitting
patterns: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m
= multiplet. Coupling constants J are given in Hz. Mass spectra were
recorded using the EI or FAB method. High-resolution mass spectra
were recorded using the ESI method with a FT-ICR mass analyzer.
Unless otherwise stated, all chemicals were used as received from a
commercial supplier. Solvents for flash column and thin-layer
chromatography including cyclohexane, ethyl acetate, toluene, and
diethyl ether were distilled prior to use. Thin-layer chromatography
was performed on fluorescence indicator marked precoated silica gel
60 plates and visualized by either UV light (254 nm/366 nm) or stains
of 2,4-dinitrophenylhydrazine or potassium permanganate. Flash
column chromatography was performed on silica gel (0.040−0.063
mm). For air- or moisture-sensitive reactions, standard Schlenk
techniques were applied under an argon atmosphere.
Compounds 1a−i were prepared following the procedure reported
by Larock and co-workers.16a To a solution of the appropriate 2-
bromobenzaldehyde (2.00 mmol, 1.0 equiv) and alkyne (2.40 mmol,
1.2 equiv) in Et3N (8 mL) was added (PPh3)2PdCl2 (2 mol %) under
C
dx.doi.org/10.1021/jo302676g | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
an argon atmosphere. After being stirred for 5 min at rt, CuI (1 mol
%) was added, and the resulting dark solution was heated to 50 °C
until TLC analysis indicated complete consumption of the starting
material. The reaction mixture was diluted with water and extracted
with DCM (3 × ). The combined organic layers were dried over
anhydrous Na2SO4, filtered, and concentrated. The residue was
purified by flash column chromatography on silica gel to afford 1a−i.
The resulting compounds 1a−c,e−g,i were in accordance with the
known literature data.16
2H), 1.86−1.75 (m, 1H), 1.57−1.51 (m, 5H), 1.25−1.14 (m, 2H),
1.07−0.99 (m, 1H), 0.67−0.57 (m, 2H). 13C NMR (CDCl3, 100
MHz): δ = 209.1, 140.3, 138.5, 135.9, 132.5, 129.6, 129.1 (2×), 128.6,
128.2, 127.8, 127.5, 127.3, 126.2, 124.8, 52.7, 33.0, 32.8, 26.1, 26.0.
HRMS (ESI): calcd for C24H24ONa m/z 351.171936, found
351.172170.
Cyclopentyl(2-phenylnaphthalen-1-yl)methanone (2e). Yield:
24.3 mg (81%); light yellow oil; EtOAc/cyclohexane (1:70). 1H
NMR (CDCl3, 400 MHz): δ = 7.94 (d, 3JHH = 8.3 Hz, 1H), 7.92−7.88
(m, 1H), 7.85−7.81 (m, 1H), 7.57−7.50 (m, 3H), 7.49−7.37 (m, 5H),
2.72−2.64 (m, 1H), 1.75−1.70 (m, 2H), 1.66−1.59 (m, 2H), 1.43−
1.27 (m, 4H). 13C NMR (CDCl3, 100 MHz): δ = 212.5, 140.5, 138.8,
136.2, 132.5, 129.6 (2×), 129.3, 128.7, 128.1, 127.8, 127.5, 127.3,
126.2, 125.2, 53.6, 29.5, 26.0. HRMS (ESI): calcd for C22H20ONa m/z
323.140636, found 323.140649.
2-(3-Cyclohexylprop-1-ynyl)benzaldehyde (1d). Yield: 191
mg (42%); brown liquid; toluene/cyclohexane (1:20). 1H NMR
(CDCl3, 400 MHz): δ = 10.55 (d, 4JHH = 0.8 Hz, 1H), 7.88 (dt, 3JHH
=
4
7.7 Hz, JHH = 0.9 Hz, 1H), 7.52−7.49 (m, 2H), 7.41−7.35 (m, 1H),
2.38 (d, 3JHH = 6.6 Hz, 2H), 1.89−1.85 (m, 2H), 1.78−1.73 (m, 2H),
1.71−1.55 (m, 2H), 1.34−1.03 (m, 5H). 13C NMR (CDCl3, 100
MHz): δ = 192.2, 136.0, 133.7, 133.3, 128.0, 127.8, 126.9, 97.1, 77.2,
37.4, 32.8, 27.4, 26.2, 26.1. HRMS (ESI): calcd for C16H19O m/z
227.143042, found 227.142894.
1-(2-Phenylnaphthalen-1-yl)pentan-1-one (2f). Yield: 17.3 mg
(60%); light yellow oil; EtOAc/cyclohexane (1:70). 1H NMR (CDCl3,
3
400 MHz): δ = 7.94 (d, JHH = 8.4 Hz, 1H), 7.92−7.89 (m, 1H),
Ethyl 5-(2-Formylphenyl)pent-4-ynoate (1h). Yield: 207 mg
7.83−7.80 (m, 1H), 7.57−7.51 (m, 3H), 7.47−7.38 (m, 5H), 2.28 (t,
3JHH = 7.4 Hz, 2H), 1.47−1.40 (m, 2H), 1.13−1.04 (m, 2H), 0.70 (t,
3JHH = 7.4 Hz, 3H). 13C NMR (CDCl3, 100 MHz): δ = 210.0, 140.4,
138.5, 135.9, 132.5, 129.4, 129.2, 128.7, 128.2, 127.9, 127.4, 127.3,
126.3, 124.9, 119.6, 44.9, 25.7, 22.0, 13.6. MS (FAB): m/z = 289.1 [M
+ H]+.4b
(45%); yellow oil; EtOAc/cyclohexane (1:10); 1H NMR (CDCl3, 400
4
MHz): δ = 10.49 (d, JHH = 0.8 Hz, 1H), 7.89−7.87 (m, 1H), 7.53−
3
7.47 (m, 2H), 7.41−7.37 (m, 1H), 4.19 (q, JHH = 7.1 Hz, 2H), 2.80
(t, 3JHH = 7.2 Hz, 2H), 2.65 (t, 3JHH = 7.0 Hz, 2H), 1.27 (t, 3JHH = 7.1
Hz, 3H). 13C NMR (CDCl3, 100 MHz): δ = 191.9, 171.6, 136.1,
133.6, 133.3, 128.2, 127.2, 127.0, 95.7, 76.9, 60.8, 33.3, 15.6, 14.2.
HRMS (ESI): calcd for C14H14O3Na m/z 253.083515, found
253.083394.
(4-tert-Butylphenyl)(2-phenylnaphthalen-1-yl)methanone (2g).
Yield: 31.0 mg (85%); light yellow solidified oil; EtOAc/cyclohexane
(1:30). 1H NMR (CDCl3, 400 MHz): δ = 8.00 (d, 3JHH = 8.4 Hz, 1H),
General Procedure for the Preparation of the 1-Naphtha-
lenone Derivatives (Tables 2 and 3). A solution of the
corresponding 2-alkynylbenzaldehyde 1 (0.10 mmol, 1 equiv), the
appropriate alkene (0.20 mmol, 2 equiv), and TBAI (7.40 mg, 0.02
mmol, 20 mol %) in HFIP (1 mL) was heated to 50 °C, before Oxone
(92.3 mg, 0.15 mmol, 1.5 equiv) was added. The resulting
inhomogeneous mixture was stirred at 50 °C until the starting
material was completely converted. The reaction mixture was allowed
to cool to rt and then treated with saturated aqueous solutions of
Na2S2O3 and NaHCO3. The aqueous phase was extracted with EtOAc
(3×), and the combined organic layers were dried over anhydrous
Na2SO4, filtered, and concentrated. The residue was purified by flash
column chromatography on silica gel to afford 2a−r.
3
3
7.93 (d, JHH = 8.1 Hz, 1H), 7.71 (d, JHH = 8.5 Hz, 1H), 7.58−7.55
(m, 3H), 7.53−7.49 (m, 1H), 7.46−7.42 (m, 1H), 7.39−7.36 (m, 2H),
7.26−7.15 (m, 5H), 1.24 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ =
199.2, 156.9, 140.3, 137.2, 136.0, 135.4, 132.4, 130.6, 129.6, 129.5,
129.2, 128.1 (2×), 127.7, 127.3, 127.1, 126.2, 125.7, 125.2, 35.0, 30.9.
HRMS (ESI): calcd for C27H24ONa m/z 387.171936, found
387.172144.
Ethyl 4-Oxo-4-(2-phenylnaphthalen-1-yl)butanoate (2h). Yield:
10.1 mg (30%); light yellow solidified oil; EtOAc/cyclohexane (1:15).
1H NMR (CDCl3, 400 MHz): δ = 7.95 (d, 3JHH = 8.4 Hz, 1H), 7.92−
7.89 (m, 1H), 7.86−7.84 (m, 1H), 7.58−7.51 (m, 3H), 7.48−7.38 (m,
5H), 4.11 (q, 3JHH = 7.1 Hz, 2H), 2.61 (t, 3JHH = 6.6 Hz, 2H), 2.43 (t,
3
3JHH = 6.6 Hz, 2H), 1.24 (t, JHH = 7.1 Hz, 3H). 13C NMR (CDCl3,
Phenyl(2-phenylnaphthalen-1-yl)methanone (2a). Yield: 28.1 mg
(91%); white solidified oil; toluene/cyclohexane (1:1). 1H NMR
100 MHz): δ = 207.7, 172.5, 140.2, 137.6, 135.9, 132.5, 129.5, 129.3,
129.2, 128.8, 128.1, 128.0, 127.5, 127.3, 126.4, 124.9, 60.6, 39.8, 28.3,
14.1. HRMS (ESI): calcd for C22H20O3Na m/z 355.130466, found
355.130460.
3
3
(CDCl3, 400 MHz): δ = 8.02 (d, JHH = 8.4 Hz, 1H), 7.95 (d, JHH
=
8.0 Hz, 1H), 7.73 (d, 3JHH = 8.6 Hz, 1H), 7.63−7.60 (m, 2H), 7.58 (d,
3JHH = 8.5 Hz, 1H), 7.55−7.50 (m, 1H), 7.48−7.44 (m, 1H), 7.41−
(1-Methyl-3-phenylnaphthalen-4-yl)(phenyl)methanone (2i).
Yield: 17.2 mg (53%); colorless solidified oil; EtOAc/cyclohexane
(1:25). 1H NMR (CDCl3, 400 MHz): δ = 8.10 (d, 3JHH = 8.4 Hz, 1H),
7.75 (d, 3JHH = 8.4 Hz, 1H), 7.63−7.60 (m, 2H), 7.58−7.54 (m, 1H),
7.48−7.43 (m, 1H), 7.43 (d, 4JHH = 0.7 Hz, 1H), 7.40−7.32 (m, 3H),
7.37 (m, 1H), 7.36−7.33 (m, 2H), 7.25−7.20 (m, 4H), 7.19−7.15 (m,
1H). 13C NMR (CDCl3, 100 MHz): δ = 199.6, 140.2, 137.9, 137.4,
135.7, 133.2, 132.4, 130.7, 129.6, 129.5 (2×), 128.3, 128.2, 128.1,
127.6, 127.4, 127.2, 126.3, 125.5. MS (EI): m/z = 308.2 [M]+.4b
(2,3-Dimethoxy-6-phenylnaphthalen-5-yl)(phenyl)methanone
(2b). Yield: 30.2 mg (82%); light yellow solidified oil; EtOAc/
4
7.25−7.13 (m, 5H), 2.81 (d, JHH = 0.8 Hz, 3H). 13C NMR (CDCl3,
1
3
100 MHz): δ = 199.9, 140.3, 138.2, 137.1, 136.0, 134.1, 133.1, 131.6,
130.8, 129.6, 129.4, 128.3, 128.2, 128.1, 127.3, 126.8, 126.2, 126.1,
124.3, 19.7. MS (FAB): m/z = 323.2 [M + H]+.8a
cyclohexane (1:5). H NMR (CDCl3, 400 MHz): δ = 7.86 (d, JHH
=
3
8.3 Hz, 1H), 7.60−7.57 (m, 2H), 7.42 (d, JHH = 8.4 Hz, 1H), 7.39−
7.35 (m, 1H), 7.32−7.29 (m, 2H), 7.23−7.11 (m, 6H), 7.04 (s, 1H),
4.03 (s, 3H), 3.81 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ = 200.2,
150.4, 149.7, 140.6, 138.1, 136.3, 134.1, 133.0, 129.4, 128.5, 128.1
(2×), 127.9, 127.1, 126.3, 125.8, 106.4, 104.1, 55.9, 55.8. MS (FAB)
m/z = 369.2 [M + H]+.8a
2-(2-Chlorophenyl)naphthalen-1-yl)(phenyl)methanone (2j).
Yield: 22.7 mg (66%); yellow solidified oil; toluene/cyclohexane
(1:1). 1H NMR (CDCl3, 400 MHz): δ = 7.98 (d, 3JHH = 8.4 Hz, 1H),
3
3
7.95 (d, JHH4 = 8.2 Hz, 1H), 7.73 (d, JHH = 8.5 Hz, 1H), 7.63 (dd,
3JHH = 8.3, JHH = 1.3 Hz, 2H), 7.56−7.50 (m, 2H), 7.48−7.43 (m,
Cyclopropyl(2-phenylnaphthalen-1-yl)methanone (2c). Yield:
1
1H), 7.42−7.37 (m, 1H), 7.26−7.17 (m, 4H), 7.13−7.06 (m, 2H). 13
C
16.9 mg (62%); colorless oil; EtOAc/cyclohexane (1:25). H NMR
3
(CDCl3, 400 MHz): δ = 7.95 (d, JHH = 8.5 Hz, 1H), 7.92−7.87 (m,
NMR (CDCl3, 100 MHz): δ = 198.9, 138.0, 137.8, 136.7, 134.7, 133.3,
132.9, 132.7, 132.5, 130.7, 129.5, 129.4, 129.1, 128.6, 128.2, (2×),
128.0, 127.2, 126.6, 126.2, 125.6. MS (FAB): m/z = 343.1 [M +
H]+.17a
2H), 7.57−7.51 (m, 3H), 7.51−7.37 (m, 5H), 1.90−1.84 (m, 1H),
1.14−1.11 (m, 2H), 0.74−0.69 (m, 2H). 13C NMR (CDCl3, 100
MHz): δ = 209.1, 140.6, 138.8, 136.7, 132.6, 129.7, 129.4, 129.2, 128.4,
128.1, 127.7, 127.6, 127.3, 126.2, 125.3, 24.7, 13.1. HRMS (ESI): calcd
for C20H16ONa m/z 295.109336, found 295.109561.
2-(4-Chlorophenyl)naphthalen-1-yl)(phenyl)methanone (2k).
Yield: 27.0 mg (79%); yellow solidified oil; toluene/cyclohexane
(2:3); 1H NMR (CDCl3, 400 MHz): δ = 8.00 (d, 3JHH = 8.4 Hz, 1H),
2-Cyclohexyl-1-(2-phenylnaphthalen-1-yl)ethanone (2d). Yield:
25.9 mg (79%); light yellow solidified oil; EtOAc/cyclohexane (1:70).
1H NMR (CDCl3, 400 MHz): δ = 7.94−7.88 (m, 2H), 7.84−7.80 (m,
1H), 7.57−7.50 (m, 3H), 7.47−7.37 (m, 5H), 2.19 (d, 3JHH = 6.4 Hz,
3
3
7.93 (d, JHH = 8.1 Hz, 1H), 7.69 (d, JHH = 8.5 Hz, 1H), 7.62−7.59
(m, 2H), 7.54−7.40 (m, 4H), 7.29−7.17 (m, 6H). 13C NMR (CDCl3,
100 MHz): δ = 199.4, 138.6, 137.7, 136.0, 135.8, 133.6, 133.5, 132.5,
D
dx.doi.org/10.1021/jo302676g | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
130.7, 130.6, 129.6, 129.5, 128.4 (2×), 128.2, 127.4, 127.2, 126.5,
125.6. MS (FAB): m/z = 343.1 [M + H]+.17a
129.8, 129.4, 128.2, 128.1, 127.7, 127.1, 126.8, 126.7, 126.6, 125.4.
HRMS (ESI): calcd for C29H20ONa m/z 407.140636, found
407.140410.
2-(3-Bromophenyl)naphthalen-1-yl)(phenyl)methanone (2l).
Yield: 33.5 mg (87%); yellow oil; toluene/cyclohexane (2:3). 1H
3
NMR (CDCl3, 400 MHz): δ = 8.03 (d, JHH = 8.4 Hz, 1H), 7.95 (d,
ASSOCIATED CONTENT
■
3
3JHH = 8.1 Hz, 1H), 7.72 (d, JHH = 8.5 Hz, 1H), 7.63−7.61 (m, 2H),
S
* Supporting Information
7.56−7.52 (m, 2H), 7.50−7.41 (m, 3H), 7.32−7.25 (m, 4H), 7.08 (m,
1H). 13C NMR (CDCl3, 100 MHz): δ = 199.2, 142.2, 137.9, 136.0,
135.7, 133.4, 132.6, 132.3, 130.6, 130.4, 129.7, 129.6, 129.5, 128.4,
128.2 (2×), 127.4, 127.1, 126.6, 125.6, 122.3. HRMS (ESI): calcd for
C23H15BrONa m/z 409.019849, found 409.019608.
1H and 13C NMR spectra of o-alkynyl carboxaldehydes 1d and
1h and of all 1-naphthalenones (2a−r). This material is
available free of charge via the Internet at http://pubs.acs.org.
2-(3-(Trifluoromethyl)phenyl)naphthalen-1-yl)(phenyl)-
AUTHOR INFORMATION
Corresponding Author
*E-mail: boris.nachtsheim@uni-tuebingen.de.
Notes
■
methanone (2m). Yield: 33.6 mg (89%); light yellow oil; toluene/
1
3
cyclohexane (2:3). H NMR (CDCl3, 400 MHz): δ = 8.05 (d, JHH
=
8.4 Hz, 1H), 7.97 (d, 3JHH = 8.0 Hz, 1H), 7.76 (d, 3JHH = 8.5 Hz, 1H),
7.61−7.58 (m, 3H), 7.56−7.47 (m, 4H), 7.44−7.40 (m, 2H), 7.34 (t,
3JHH = 7.8 Hz, 1H), 7.25 (t, JHH = 7.8 Hz, 2H). 13C NMR (CDCl3,
3
The authors declare no competing financial interest.
100 MHz): δ = 199.3, 141.0, 137.9, 136.3, 135.8, 133.5, 132.7 (2×),
2
130.6, 130.5 (q, JCF = 32.3 Hz), 129.8, 129.5, 128.7, 128.4, 128.2,
ACKNOWLEDGMENTS
127.5, 127.0, 126.7, 126.2 (q, 3JCF = 3.8 Hz), 125.6, 124.1 (q, 3JCF = 3.8
Hz), 123.8 (q, 1JCF = 272.4 Hz). HRMS (ESI): calcd for C24H15F3ONa
m/z 399.096721, found 399.096576.
■
We thank the DFG (NA 955/1-1) and the Fonds der
Chemischen Industrie (Sachkostenzuschuss) for financial
support.
Phenyl(2-m-tolylnaphthalen-1-yl)methanone (2n). Yield: 26.4 mg
1
(82%); yellow oil; Et2O/cyclohexane (1:20). H NMR (CDCl3, 400
3
3
MHz): δ = 8.01 (d, JHH = 8.4 Hz, 1H), 7.94 (d, JHH = 8.0 Hz, 1H),
7.74 (d, 3JHH = 8.6 Hz, 1H), 7.63 (dd, 3JHH = 8.3, 4JHH = 1.2 Hz, 2H),
7.58 (d, 3JHH = 8.5 Hz, 1H), 7.54−7.50 (m, 1H), 7.48−7.44 (m, 1H),
7.42−7.38 (m, 1H), 7.27−7.23 (m, 2H), 7.17−7.14 (m, 2H), 7.10 (t,
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3
3JHH = 7.4 Hz, 1H), 6.98 (d, JHH = 7.4 Hz, 1H), 2.25 (s, 3H). 13C
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3
MHz): δ = 8.00 (d, JHH = 8.4 Hz, 1H), 7.93 (d, JHH = 8.0 Hz, 1H),
7.71−7.69 (m, 1H), 7.65−7.62 (m, 2H), 7.56 (d, 3JHH = 8.5 Hz, 1H),
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199.8, 137.9, 137.4, 137.3, 137.1, 135.5, 133.2, 132.3, 130.7, 129.6,
129.4, 129.3, 129.0, 128.3, 128.1, 127.8, 127.1, 126.2, 125.5, 21.1. MS
(FAB): m/z = 323.2 [M + H]+.17b
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3
3
MHz): δ = 8.07 (s, 1H), 7.96 (d, JHH = 7.4 Hz, 2H), 7.92 (d, JHH
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8.2 Hz, 1H), 7.62−7.54 (m, 3H), 7.50−7.35 (m, 5H), 7.30−7.26 (m,
1H), 7.16 (t, 3JHH = 7.5 Hz, 1H), 4.15 (s, 2H). 13C NMR (CDCl3, 100
MHz): δ = 200.0, 144.3, 141.0, 139.3, 137.3, 136.8, 134.1, 132.5, 130.4,
130.2, 130.0, 129.0, 128.1, 127.8, 127.1, 126.2, 125.8, 125.4, 125.2,
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343.109336, found 343.109670.
́
́
̀
́
́
́
Ethyl (4-Benzoyl-3-phenyl)2-naphthalenecarboxylate (2q). Yield:
1
31.6 mg (83%); yellow solidified oil; Et2O/cyclohexane (1:10). H
́
NMR (CDCl3, 400 MHz): δ = 8.51 (s, 1H), 8.04−8.02 (m, 1H), 7.67
3
4
́
ez, J. M. Chem.Eur. J. 2006, 12,
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129.1, 129.0, 128.2, 127.2, 127.1, 125.4, 61.1, 13.5. MS (FAB): m/z =
381.1 [M + H]+.17c
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3
4
7.70 (dd, JHH = 8.4, JHH = 0.7 Hz, 1H), 7.59−7.53 (m, 3H), 7.48−
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E
dx.doi.org/10.1021/jo302676g | J. Org. Chem. XXXX, XXX, XXX−XXX

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dx.doi.org/10.1021/jo302676g | J. Org. Chem. XXXX, XXX, XXX−XXX