HNTf2-catalyzed regioselective preparation of polysubstituted naphthalene derivatives through alkyne-aldehyde coupling

Article abstract of DOI:10.1021/acs.joc.5b00353

We report herein the preparation of polysubstituted naphthalene derivatives by the original Br?nsted-acid-catalyzed benzannulation reaction of phenylacetaldehydes with alkynes. This reaction, which was usually performed with Lewis acids under thermal activation, is efficiently promoted by 15 mol % of triflimide (HNTf₂) at room temperature under metal-free and mild reaction conditions and leads with a perfect regioselectivity to a wide variety of diversely functionalized naphthalenes in 41-78% yield. A catalytic cycle is proposed together with some further applications of this catalytic system in the related benzannulation transformations of epoxide and acetal derivatives.

Full text of DOI:10.1021/acs.joc.5b00353

Article
pubs.acs.org/joc
HNTf ‑Catalyzed Regioselective Preparation of Polysubstituted
2
Naphthalene Derivatives Through Alkyne−Aldehyde Coupling
́
Sudipta Ponra, Maxime R. Vitale,* Veronique Michelet,* and Virginie Ratovelomanana-Vidal*
PSL Research University, Chimie ParisTech - CNRS, Institut de Recherche de Chimie Paris, 75005, Paris, France
*
S Supporting Information
ABSTRACT: We report herein the preparation of polysub-
stituted naphthalene derivatives by the original Brønsted-acid-
catalyzed benzannulation reaction of phenylacetaldehydes with
alkynes. This reaction, which was usually performed with Lewis
acids under thermal activation, is efficiently promoted by 15
mol % of triflimide (HNTf ) at room temperature under
2
metal-free and mild reaction conditions and leads with a
perfect regioselectivity to a wide variety of diversely function-
alized naphthalenes in 41−78% yield. A catalytic cycle is proposed together with some further applications of this catalytic system
in the related benzannulation transformations of epoxide and acetal derivatives.
INTRODUCTION
acetaldehydes with alkynes (Scheme 2, eq 3). Whereas this
■
efficient benzannulation reaction was successfully realized by
Substituted naphthalene derivatives are an important class of
compounds that possesses widespread applications. They are
found in numerous optical and electronic materials and
constitute the core of many biologically relevant molecules
including the vast family of arylnaphthalene lignans (Scheme
10
using TiCl or FeCl in stoichiometric quantities, Li and
4
3
1
Balamurugan independently reported the use of more
6,7
expensive GaCl or AuCl /AgSbF catalytic systems. In the
3
3
6
restricted case of terminal phenylacetylenes, boron trifluoride8
2
etherate complex was also described as an appropriate catalyst.
1).
Notably, all these last methods are based on the use of Lewis-
acid mediators, and to the best of our knowledge, the use of
simple Brønsted-acid catalyst has not yet been reported. In this
Scheme 1. Representative Examples of Arylnaphthalene
Lignans
context, we report herein that triflimide (HNTf ) is an efficient
2
organocatalyst for the benzannulation of phenylacetaldehyde
11
derivatives with alkynes. This metal-free reaction proceeds at
room temperature and leads, under mild reaction conditions, to
a wide variety of highly substituted naphthalene compounds
with perfect regioselectivity (Scheme 2, eq 4).
RESULTS AND DISCUSSION
■
In the course of our studies concerning the α-alkenylation of
1
2
aldehydes with alkynes under synergistic catalysis, we
discovered that 20 mol % of indium(III) chloride in 1,2-
dichloroethane (DCE) at 100 °C partially promoted the
benzannulation reaction of 2-phenylpropionaldehyde 1 with 2
equiv of 1-phenyl-1-propyne 2 (Table 1, entry 1). In these
conditions after 5 h, naphthalene 3 was formed with
encouraging 74% GC yield and with total regioselectivity,
which prompted us to further study this transformation (Table
1). Under milder reaction conditions, at room temperature for
Accordingly, many efforts have been devoted to their
regioselective synthesis in past decades, the contribution of
3
catalysis to this field being particularly remarkable. Among the
different strategies examined so far, the catalyzed construction
of the second aromatic ring of the naphthalene core through
the incorporation of a two-carbon alkyne unit and following a
4
−9
formal [4 + 2] process is undeniably straightforward.
Such
2
4 h, we still observed some reactivity with indium(III)
kind of catalytic transformation typically includes Larock’s
palladium(0)-catalyzed cyclizations of vinyl/aryl iodides or
triflates (Scheme 2, eq 1) and the benzannulation reactions of
chloride (Table 1, entry 2). However, better reaction rates and
GC yields were obtained when indium(III) bromide, indium-
(
III) trifluoromethanesulfonate, and indium(III) triflimidate
2
-alkynylbenzaldehydes under π-Lewis-acid metal catalysis
originally described by Asao and Yamamoto (Scheme 2, eq
4
,5
2). Alternatively, the regioselective synthesis of naphthalene
Received: February 13, 2015
derivatives may also arise from the condensation of phenyl-
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00353
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Scheme 2. Catalytic Formal [4 + 2] Benzannulation Approaches to Naphthalenes with Alkynes
Table 1. Optimization of the Aldehyde−Alkyne Benzannulation Reaction
a
a
entry
catalyst
InCl3
y
x
solvent
t (h)
conv. (%)
yield (%)
b
1
20
20
20
20
20
20
20
20
20
20
20
15
10
5
2
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
5
90
74
2
3
4
5
6
7
8
9
InCl3
2
24
24
24
8
56
33
InBr3
2
80
60
In(OTf)3
In(NTf2)3
HNTf2
TfOH
2
>95
>95
>95
73
68
2
85
2
8
84
2
8
59
MsOH
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
2
8
26
3
2.5
1.5
1
8
>95
>95
87
85
c
c
10
11
12
13
14
15
16
17
18
8
86, [70]
77
8
1.5
1.5
1.5
1.5
1.5
1.5
1.5
13
24
24
13
10
10
10
>95
84
85, [70]
73
83
64
15
15
15
15
CH Cl2
95
78
2
toluene
60
38
Et O
2
40
3
hexane
94
71
a
b
c
Determined by GC analysis using tridecane as internal standard. Performed at 100 °C. Yield.
were employed (Table 1, entries 3−5). In this last case, we
solvents such as dichloromethane, toluene, diethyl ether, or
hexane did not give better results (Table 1, entries 15−18).
With these optimized reaction conditions in hand, we then
studied the scope of this Brønsted-acid-catalyzed benzannula-
tion reaction. The influence of the carbonyl reactant was first
examined by submitting 1-phenyl-1-propyne 2 to various
phenylacetaldehydes 4a−i (Scheme 3).
This benzannulation reaction well tolerated the use of
phenylacetaldehydes bearing electron-donating groups at the 4
position of their aromatic moiety. Accordingly, naphthalene 5a
and 5b were obtained in 70% and 62%, respectively. Moreover,
the 4-nitro- and 4-bromo-substituted phenylacetaldehydes 4c
and 4d reacted well, which indicated that electron-withdrawing
groups on the aromatic ring were also compatible with this
catalytic benzannulation process. Steric hindrance at the 2
position of the phenyl ring did not significantly hamper this
method. Indeed, the reaction of 4-bromo- and 2-bromo-phenyl
propionaldehydes 4d and 4e yielded the corresponding
naphthalenes 5d and 5e with similar yields. The α substitution
were pleased to observe almost complete conversion after only
8
h and 85% GC yield of naphthalene 3 (Table 1, entry 5).
Unexpectedly and gratifyingly, a control experiment using 20
mol % of triflimide (HNTf ) led to comparable results, thus
2
indicating for the first time that this transformation could also
be efficiently catalyzed by simple Brønsted acids (Table 1, entry
6
). Comparatively, the use of trifluoromethanesulfonic (TfOH)
and methanesulfonic (MsOH) acids led to limited reactivity
Table 1, entries 7 and 8). Further optimization studies
(
including the variation of the quantity of alkyne and the
catalytic charge of HNTf allowed us to determine that 1.5
2
equiv of alkyne in the presence of 15 mol % catalyst was
optimum to promote the desired transformation (Table 1,
entries 9−14). Under these metal-free conditions, after 13 h at
room temperature, naphthalene 3 was obtained in 70% isolated
yield (Table 1, entry 12), which compares favorably to the
result obtained by Li et al. in the presence of 13 mol % of GaCl3
6
in refluxing dichloromethane during 24 h (70% yield). Other
B
DOI: 10.1021/acs.joc.5b00353
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Scheme 3. Aldehyde Scope for the HNTf -Catalyzed
Benzannulation Reaction
Scheme 4. Alkyne Scope for the HNTf -Catalyzed
Benzannulation Reaction
2
2
of the aldehyde group could also be successfully modified since
2-ethyl-, 2-cyclohexyl-, and 2-phenyl-substituted phenylacetal-
dehydes 4f−h allowed the formation of naphthalenes 5f−h in
good yields ranging from 69% to 78%. Furthermore, the α
substitution on the aldehyde partner was not essential as the
reaction of phenylacetaldehyde 4i afforded the expected
naphthalene 5i with a slight diminution of yield. It is worth
noting that in all cases only one regioisomer was obtained.
We next studied the influence of the alkyne partner in the
catalytic benzannulation reaction of 2-phenylpropionaldehyde 1
(
Scheme 4). We were satisfied to observe that 2-phenyl-2-
propyne could be successfully replaced by alkynes possessing a
longer alkyl chain. Indeed, under the optimized reaction
conditions, 1-phenyl-but-1-yne 6a, 1-phenyl-pent-1-yne 6b, and
1
-phenyl-hex-1-yne 6c yielded the corresponding naphthalene
naphthalene 7j in 41% yield. Under the corresponding reaction
conditions, the 4-fluoro- and 4-bromo-phenylacetylenes
afforded naphthalenes 7k and 7l with similar results. Gratify-
ingly, this protocol could also be extended to the use of
halogen-substituted phenylacetylenes 6m and 6n, which were
compounds 7a−c in good 66−70% yield. In the related aryl−
alkyl alkyne family, substitution of the aromatic ring was
examined. The reaction of 4-chloro-, 4-bromo-, and 4-methyl-
substituted alkynes 6d−f afforded the desired products 7d−f
with comparable good results (62−69% yield). Diaryl-
substituted alkynes were also prone to react under these mild
catalytic conditions. In these cases, longer reaction times were
needed and a reversed aldehyde/alkyne ratio was found to be
successful to easily separate the desired product from the
starting alkyne. The benzannulation of symmetrical alkynes 6g
and 6h led to naphthalenes 7g and 7h in 46% and 49% yield,
respectively. The effectiveness of this catalytic reaction was
further demonstrated by reacting 4-phenyl-but-3-yn-2-one 6i,
which afforded the corresponding 2-acetyl-substituted naph-
thalene 7i in moderate 46% isolated yield. To the best of our
knowledge, this represents the first example based on the use of
an alkyne deactivated by an electron-withdrawing group in
8
scarcely employed in related benzannulation reactions. The
corresponding 2-chloro- and 2-bromo-substituted aromatic
compounds 7m and 7n were obtained in useful 43% and
42% yields, respectively. Noteworthy, these 2-halo-naphthalene
derivatives might serve as valuable building blocks in well-
13
established palladium cross-coupling reactions. Under the
reaction conditions reported herein, terminal and internal
aliphatic alkynes such as hex-1-yne and oct-3-yne reacted
sluggishly with 2-phenylpropionaldehyde, which emphasized
the key stabilizing role of the aromatic moiety of the
phenylacetylenes that were employed.
To further demonstrate the efficiency of this HNTf2-
catalyzed aldehyde−alkyne benzannulation process, we per-
formed a gram-scale control experiment under open air
reaction conditions. Pleasingly, starting from 2-phenylpropio-
naldehyde 1 and 1-phenyl-1-propyne 2, the reaction worked
perfectly well and led to naphthalene 3 in almost identical yield
(Scheme 5). Accordingly, this Brønsted-acid-catalyzed benzan-
related aldehyde−alkyne benzannulation processes. Similarly to
the GaCl -catalyzed transformation developed by Li et al., we
observed inferior reactivity for phenylacetylene 6j. Modifying
the reaction conditions by increasing the amount of alkyne to 3
equivalents allowed the formation of 4-methyl-1-phenyl-
6
3
C
DOI: 10.1021/acs.joc.5b00353
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The Journal of Organic Chemistry
Article
Scheme 5. Gram-Scale HNTf -Catalyzed Benzannulation
presence of 15 mol % HNTf in DCE at room temperature
2
2
under Open Air Reaction Conditions
(Scheme 7).
Scheme 7. Benzannulation Approaches to Naphthalenes with
Epoxides and Dimethylacetals
nulation reaction was demonstrated to be a particularly robust
solution for the larger scale production of naphthalene
derivatives in mild and easy to setup reaction conditions.
On the basis of the above experimental results and
6
−8
literature,
we propose the following catalytic cycle for this
Brønsted-acid-catalyzed benzannulation reaction (Scheme 6).
Scheme 6. Reaction Mechanism Proposal
Pleasingly, in both cases the desired naphthalene 5h was
obtained in 60−61% yield. Therefore, our Brønsted-acid
catalytic approach to naphthalenes with phenylacetaldehydes
may also find some interesting applications in the related
benzannulation reactions of styrene oxides and 2-aryl-acetals.
CONCLUSION
In the course of this study, we demonstrated that triflimide
■
(
HNTf ) is an efficient Brønsted-acid catalyst for benzannula-
2
tion reaction of phenylacetaldehyde derivatives with aryl−
alkynes at room temperature. Noteworthy, in all cases only one
naphthalene isomer is obtained, which implies a total
regioselectivity for this formal [4 + 2] process. This novel
protocol clearly distinguishes itself from already reported
catalytic systems, which are mostly based on the use of metal
Lewis acids and often require thermal activation. A study of the
scope of this reaction has been realized which has allowed us to
access to a wide variety of polysubstituted naphthalene
compounds in fair to good yields and to suggest a catalytic
cycle for this transformation. The mild reaction conditions
tolerate the use of diversely functionalized aldehydes as well as
internal and terminal aromatic alkynes. Further studies aiming
The initial protonation of the aldehyde oxygen atom with
11
HNTf , favored by the high acidity of this Brønsted acid,
2
would lead to an oxocarbenium ion A whose high electro-
philicity would trigger the regioselective nucleophilic attack of
the alkyne partner. The resulting vinylic carbocation B,
stabilized by the aromatic ring which is present in its α
at broadening the scope of this HNTf -catalyzed benzannula-
2
1
4
tion methodology to the use of styrene oxides and 2-aryl-acetals
are currently underway and will be reported in due course.
position, would then undergo an intramolecular electrophilic
aromatic substitution with the proximal phenyl ring leading to a
dihydro-β-naphtol C. In a last step, the Brønsted-acid-mediated
elimination of a water molecule would account for the
formation of the naphthalene product together with the
EXPERIMENTAL SECTION
All reactions were performed under argon atmosphere. 1,2-Dichloro-
■
ethane was distilled from CaH . All products were purified by flash
2
regeneration of the catalyst. The superiority of HNTf2
1
13
chromatography using silica gel (230−400 mesh). H NMR and
NMR spectra were recorded in CDCl with chemical shifts reported
C
compared to other Brønsted acids might then be rationalized
−
3
by the fact that its counteranion NTf2 displays a negligible
1
relative to the residual CHCl peak for H NMR (7.26 ppm) or the
3
nucleophilicity which may hamper competitive deactivation
pathways such as the quenching of the transitory vinylic
13
central peak of CDCl for C NMR (77.16 ppm). HRMS data for
3
new compounds were obtained using an atmospheric pressure
photoionization source (APPI) coupled to a LTQ-Orbitrap high-
resolution detector. Unless otherwise noted, all reagents were ordered
and used without further purification. Aldehydes 4a−i were
7
a
carbocation.
Finally, with this mechanistic proposition in mind, we
envisioned that this Brønsted-acid-catalyzed benzannulation
reaction could rationally be extended to the use of epoxides or
1
7
synthesized by using a literature procedure, and their NMR
1
7,18
1
5
analytical data matched those previously reported.
Alkynes 6d−f
acetals. Indeed, under protic reaction conditions the
and 6h were prepared according to literature procedures, and their
NMR analytical data matched those previously reported.
Meinwald rearrangement of epoxides and α elimination of
19,20
16
acetals are believed to form transitory oxocarbenium ions. To
assess this hypothesis, we performed some preliminary
experiments in which trans-stilbene oxide 8 and dimethyl-acetal
Halogenated alkynes 6m and 6n were synthesized according to the
2
1
literature.
General Procedure for the Benzannulation Reaction. In a
9
were submitted to 1.5 equiv of 1-phenyl-1-propyne in the
screw cap vial under argon atmosphere were sequentially added the
D
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The Journal of Organic Chemistry
Article
aldehyde, epoxide, or acetal (1.0 mmol, 1 equiv), the alkyne (1.5
(d, J = 8.8 Hz, 1H), 7.55−7.43 (m, 5H), 7.28 (s, 1H), 7.24−7.21 (m,
2H), 2.69 (d, J = 0.7 Hz, 3H), 2.18 (s, 3H). 13C{ H} NMR (75 MHz,
1
mmol, 1.5 equiv), 1,2-dichloroethane (1 mL), and HNTf (42 mg,
2
0
.15 mmol, 0.15 equiv). The resulting mixture was stirred at room
temperature until TLC analysis showed completion of the reaction
vide infra). The reaction mixture was then diluted with dichloro-
CDCl ): δ 139.2, 136.0, 134.5, 134.2, 133.5, 130.3, 130.0, 129.7, 128.8,
3
128.7, 128.0, 127.3, 125.9, 120.2, 20.9, 19.4. HRMS (APPI) m/z:
+
•
(
[M] calcd for C H Br 310.0352, found 310.0356.
18 15
methane (5 mL) and water (15 mL) and transferred to a separating
funnel. The aqueous phase was extracted with dichloromethane (3 ×
5-Bromo-2,4-dimethyl-1-phenylnaphthalene (5e). Starting
from 2-(2-bromophenyl)-propanal 4e (106 mg, 0.50 mmol) and 1-
phenyl-1-propyne 2 (87 mg, 0.75 mmol) and following the general
procedure, after 16 h of reaction the crude material was purified by
flash column chromatography on silica gel using cyclohexane as eluent.
1
4
5 mL), and the combined organic extracts were washed by water (2 ×
0 mL) and brine (40 mL) before being dried over MgSO . After
4
filtration and evaporation of the solvents under reduced pressure, the
crude material was purified by flash column chromatography on silica
gel to afford the desired naphthalene. In specific cases, this first
purification step was followed by a bulb to bulb distillation under
reduced pressure in order to remove residual alkyne.
The desired naphthalene 5e was obtained as a low melting point white
1
solid (92 mg, 59% yield). H NMR (300 MHz, CDCl ): δ 7.78 (dd, J
3
= 7.4, 1.3 Hz, 1H), 7.57−7.39 (m, 4H), 7.34 (s, 1H), 7.27−7.20 (m,
2H), 7.06 (dd, J = 8.5, 7.4 Hz, 1H), 3.18 (d, J = 0.7 Hz, 3H), 2.19 (s,
3H). 13C{ H} NMR (75 MHz, CDCl ): δ 140.3, 137.7, 136.3, 134.4,
1
2
,4-Dimethyl-1-phenylnaphthalene (3). Starting from 2-
3
phenylpropionaldehyde 1 (134 mg, 1.0 mmol) and 1-phenyl-1-
propyne 2 (174 mg, 1.5 mmol) and following the general procedure,
after 13 h of reaction the crude material was purified by flash column
chromatography on silica gel using cyclohexane as eluent. The desired
133.9, 133.7, 132.4, 130.3, 129.9, 128.7, 127.5, 127.2, 125.4, 120.2,
+•
26.5, 20.6. HRMS (APPI) m/z: [M] calcd for C H Br 310.0352,
18
15
found 310.0357.
4-Ethyl-2-methyl-1-phenylnaphthalene (5f). Starting from 2-
phenylbutanal 4f (148 mg, 1.0 mmol) and 1-phenyl-1-propyne 2 (174
mg, 1.5 mmol) and following the general procedure, after 13 h of
reaction the crude material was purified by flash column chromatog-
raphy on silica gel using petroleum ether as eluent. The desired
1
naphthalene 3 was obtained as a white solid (162 mg, 70% yield). H
NMR (300 MHz, CDCl ): δ 8.01 (d, J = 8.2 Hz, 1H), 7.54−7.39 (m,
3
5
3
1
1
H), 7.37−7.30 (m, 1H), 7.30−7.24 (m, 3H), 2.73 (d, J = 0.7 Hz,
1
3
1
H), 2.21 (s, 3H). C{ H} NMR (75 MHz, CDCl ): δ 139.7, 136.2,
3
32.8 (2C), 132.1, 130.7, 129.9, 129.0, 127.9, 126.5, 126.4, 125.1,
naphthalene 5f was obtained as a white solid (192 mg, 78% yield); mp
1
24.2, 123.5, 20.3, 18.9. These analytical data are in accordance with
75−77 °C. H NMR (300 MHz, CDCl ): δ 8.19 (d, J = 8.4 Hz, 1H),
3
6
the literature.
7.66−7.50 (m, 5H), 7.49−7.36 (m, 4H), 3.26 (q, J = 7.5 Hz, 2H), 2.35
(s, 3H), 1.57 (t, J = 7.5 Hz, 3H). 13C{ H} NMR (75 MHz, CDCl ): δ
1
2,4,7-Trimethyl-1-phenylnaphthalene (5a). Starting from 2-(p-
3
tolyl)-propanal 4a (148 mg, 1.0 mmol) and 1-phenyl-1-propyne 2
140.2, 139.4, 136.6, 133.5, 132.9, 130.5, 130.3, 128.5, 127.9, 127.1,
127.0, 125.5, 124.7, 123.7, 26.0, 21.0, 15.3. HRMS (APPI) m/z: [M]+
calcd for C H 246.1403, found 246.1407.
•
(
174 mg, 1.5 mmol) and following the general procedure, after 16 h of
reaction the crude material was purified by flash column chromatog-
19
18
raphy on silica gel using petroleum ether as eluent. The desired
naphthalene 5a was obtained as a colorless oil (173 mg, 70% yield). H
4-Cyclohexyl-2-methyl-1-phenylnaphthalene (5g). Starting
from 2-cyclohexyl-2-phenylacetaldehyde 4g (202 mg, 1.0 mmol) and
1-phenyl-1-propyne 2 (174 mg, 1.5 mmol) and following the general
procedure, after 14 h of reaction the crude material was purified by
flash column chromatography on silica gel using petroleum ether as
1
NMR (300 MHz, CDCl ): δ 8.02 (d, J = 8.5 Hz, 1H), 7.68−7.50 (m,
3
3
H), 7.44−7.30 (m, 5H), 2.82 (s, 3H), 2.49 (s, 3H), 2.31 (s, 3H).
1
3
1
C{ H} NMR (75 MHz, CDCl ): δ 140.3, 136.1, 135.2, 133.3 (2C),
3
1
1
2
32.9, 130.5, 129.4, 128.7, 128.5, 126.9 (2C), 125.9, 124.0, 21.9, 20.9,
eluent. The desired naphthalene 5g was obtained as a white solid (209
+
•
1
9.5. HRMS (APPI) m/z: [M] calcd for C H 246.1403, found
mg, 69% yield); mp 151−153 °C. H NMR (300 MHz, CDCl
3
): δ
19
18
46.1409.
-Methoxy-2,4-dimethyl-1-phenylnaphthalene (5b). Starting
8.27 (d, J = 8.5 Hz, 1H), 7.66−7.49 (m, 5H), 7.48−7.35 (m, 4H),
7
3.60−3.39 (m, 1H), 2.36 (s, 3H), 2.23 (t, J = 10.1 Hz, 2H), 2.15−1.91
13
1
from 2-(4-methoxyphenyl)propanal 4b (164 mg, 1.0 mmol) and 1-
phenyl-1-propyne 2 (174 mg, 1.5 mmol) and following the general
procedure, after 20 h of reaction the crude material was purified by
flash column chromatography on silica gel using cyclohexane as eluent.
(m, 3H), 1.86−1.62 (m, 4H), 1.60−1.39 (m, 1H). C{ H} NMR (75
MHz, CDCl
127.2, 127.0, 125.3 (2C), 124.6, 123.1, 39.3, 34.4, 27.5, 26.8, 21.2.
): δ 142.9, 140.3, 136.4, 133.5, 132.8, 130.5, 129.9, 128.5,
3
+
•
HRMS (APPI) m/z: [M] calcd for C23H24 300.1872, found
The desired naphthalene 5b was obtained as a pale yellow oil (161 mg,
300.1876.
1
6
7
2% yield). H NMR (300 MHz, CDCl ): δ 8.02 (d, J = 9.1 Hz, 1H),
.57 (m, 3H), 7.43−7.35 (m, 2H), 7.27−7.20 (m, 2H), 6.88 (d, J = 2.6
2-Methyl-1,4-diphenylnaphthalene (5h). Starting from 2,2-
diphenylacetaldehyde 4h (196 mg, 1.0 mmol) and 1-phenyl-1-propyne
2 (174 mg, 1.5 mmol) and following the general procedure, after 16 h
of reaction the crude material was purified by flash column
chromatography on silica gel using cyclohexane as eluent. The desired
3
13
1
Hz, 1H), 3.77 (s, 3H), 2.79 (s, 3H), 2.30 (s, 3H). C{ H} NMR (75
MHz, CDCl ): δ 157.4, 140.3, 135.7, 134.5, 133.5, 133.4, 130.4, 128.6,
3
1
27.5, 127.0, 126.6, 125.7, 116.6, 105.9, 55.1, 20.9, 19.5. HRMS
+•
1
(APPI) m/z: [M] calcd for C H O 262.1352, found 262.1354.
naphthalene 5h was obtained as a white solid (202 mg, 69% yield). H
19
18
2,4-Dimethyl-7-nitro-1-phenylnaphthalene (5c). Starting from
NMR (300 MHz, CDCl
7.53 (s, 1H), 7.46 (m, 4H), 2.41 (s, 3H). C{ H} NMR (75 MHz,
CDCl ): δ 141.0, 140.0, 139.6, 137.9, 133.4, 132.8, 130.4, 130.3 (2C),
129.8, 128.6, 128.4, 127.3, 127.2, 126.7, 126.0, 125.8, 125.0, 21.0.
3
): δ 8.11−8.01 (m, 1H), 7.72−7.54 (m, 9H),
13 1
2
-(4-nitrophenyl)-propanal 4c (70 mg, 0.39 mmol) and 1-phenyl-1-
propyne 2 (70 mg, 0.59 mmol) and following the general procedure,
after 13 h of reaction the crude material was purified by flash column
chromatography on silica gel using cyclohexane:ethyl acetate (98:2) as
3
22
These analytical data are in accordance with the literature.
eluent. The desired naphthalene 5c was obtained as a pale yellow solid
2-Methyl-1-phenylnaphthalene (5i). Starting from phenyl-
acetaldehyde 4i (120 mg, 1.0 mmol) and 1-phenyl-1-propyne 2
(174 mg, 1.5 mmol) and following the general procedure, after 16 h of
reaction the crude material was purified by flash column chromatog-
raphy on silica gel using cyclohexane as eluent. The desired
1
(
8
50 mg, 46% yield); mp 120−122 °C. H NMR (300 MHz, CDCl ): δ
3
.37 (d, J = 2.3 Hz, 1H), 8.19 (dd, J = 9.2, 2.3 Hz, 1H), 8.09 (d, J = 9.2
Hz, 1H), 7.59−7.43 (m, 4H), 7.29−7.20 (m, 2H), 2.76 (d, J = 0.7 Hz,
1
3
1
3
1
1
H), 2.24 (s, 3H). C{ H} NMR (75 MHz, CDCl ): δ 145.5, 138.9,
3
38.3, 135.5, 133.8, 133.4, 132.4, 130.3, 128.9, 128.3, 127.9, 125.8,
naphthalene 5i was obtained as a low melting point white solid
23.6, 118.1, 20.9, 19.5. HRMS (APPI) m/z: [M]+ calcd for
•
1
(106 mg, 49% yield). H NMR (300 MHz, CDCl
): δ 7.94 (d, J = 8.1
3
C H NO 277.1097, found 277.1101.
Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.64−7.34 (m, 9H), 2.35 (s, 3H).
18
15
2
13 1
7
-Bromo-2,4-dimethyl-1-phenylnaphthalene (5d). Starting
C{ H} NMR (75 MHz, CDCl ): δ 139.9, 138.3, 133.2, 133.1, 132.1,
3
from 2-(4-bromophenyl)-propanal 4d (213 mg, 1.0 mmol) and 1-
phenyl-1-propyne 2 (174 mg, 1.5 mmol) and following the general
procedure, after 20 h of reaction the crude material was purified by
flash column chromatography on silica gel using cyclohexane as eluent.
130.3, 128.7, 128.5, 127.9, 127.4, 127.1, 126.3, 125.9, 124.9, 21.0.
These analytical data are in accordance with the literature.
2-Ethyl-4-methyl-1-phenylnaphthalene (7a). Starting from 2-
phenylpropionaldehyde 1 (134 mg, 1.0 mmol) and 1-phenyl-but-1-yne
6a (195 mg, 1.5 mmol) and following the general procedure, after 15 h
of reaction the crude material was purified by flash column
6
The desired naphthalene 5d was obtained as a pale yellow solid (203
1
mg, 66% yield); mp 87−89 °C. H NMR (300 MHz, CDCl ): δ 7.85
3
E
DOI: 10.1021/acs.joc.5b00353
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
chromatography on silica gel using cyclohexane as eluent. The desired
general procedure, after 15 h of reaction the crude material was
purified by flash column chromatography on silica gel using petroleum
ether as eluent followed by bulb to bulb distillation of residual alkyne
at 100 °C/0.3 Torr during 1 h. The desired naphthalene 7f was
naphthalene 7a was obtained as a pale yellow solid (170 mg, 69%
1
yield); mp 63−65 °C, H NMR (300 MHz, CDCl ): δ 8.00 (d, J = 8.3
3
Hz, 1H), 7.53−7.38 (m, 4H), 7.37−7.23 (m, 5H), 2.74 (d, J = 0.8 Hz,
H), 2.50 (q, J = 7.6 Hz, 2H), 1.11 (t, J = 7.6 Hz, 3H). C{ H} NMR
13
1
1
3
obtained as a low melting point white solid (153 mg, 62% yield). H
(
1
(
75 MHz, CDCl ): δ 139.9, 139.1, 136.1, 133.8, 133.4, 131.2, 130.7,
NMR (300 MHz, CDCl ): δ 8.12 (d, J = 8.2 Hz, 1H), 7.66−7.52 (m,
3
3
28.3, 128.1, 127.2, 127.0, 125.6, 124.8, 124.0, 27.1, 19.7, 16.2. HRMS
2H), 7.50−7.36 (m, 4H), 7.33−7.25 (m, 2H), 2.84 (s, 3H), 2.59 (s,
+•
13
1
APPI) m/z: [M] calcd for C H 246.1403, found 246.1407.
3H), 2.35 (s, 3H). C{ H} NMR (75 MHz, CDCl ): δ 137.1, 136.7,
19
18
3
4
-Methyl-1-phenyl-2-(n-propyl)-naphthalene (7b). Starting
136.5, 133.4, 133.3, 132.9, 131.2, 130.4, 129.6, 129.2, 127.0, 125.5,
124.7, 124.0, 21.4, 20.9, 19.5. HRMS (APPI) m/z: [M]+ calcd for
C H 246.1403, found 246.1408.
•
from 2-phenylpropionaldehyde 1 (134 mg, 1.0 mmol) and 1-phenyl-
pent-1-yne 6b (216 mg, 1.5 mmol) and following the general
procedure, after 15 h of reaction the crude material was purified by
flash column chromatography on silica gel using cyclohexane as eluent
followed by bulb to bulb distillation at 100 °C/0.3 Torr during 1 h in
order to remove traces of starting alkyne. The desired naphthalene 7b
19
18
4-Methyl-1,2-diphenylnaphthalene (7g). Starting from 2-
phenylpropionaldehyde 1 (201 mg, 1.5 mmol) and diphenylacetylene
6g (178 mg, 1.0 mmol) and following the general procedure, after 48 h
of reaction the crude material was purified by flash column
chromatography on silica gel using petroleum ether as eluent. The
was obtained as a low melting point white solid (172 mg, 66%
1
yield). H NMR (300 MHz, CDCl ): δ 8.00 (d, J = 8.3 Hz, 1H), 7.52−
desired naphthalene 7g was obtained as a white solid (134 mg, 46%
3
1
7
(
(
.37 (m, 4H), 7.37−7.23 (m, 5H), 2.73 (d, J = 0.8 Hz, 3H), 2.51−2.41
yield); mp 141−143 °C. H NMR (300 MHz, CDCl ): δ 8.28−8.18
3
13
1
m, 2H), 1.62−1.47 (m, 2H), 0.82 (t, J = 7.3 Hz, 3H). C{ H} NMR
(m, 1H), 7.89 (d, J = 8.5 Hz, 1H), 7.68 (ddd, J = 8.4, 6.8, 1.4 Hz, 1H),
7.64−7.60 (m, 1H), 7.56 (ddd, J = 8.3, 6.7, 1.3 Hz, 1H), 7.49−7.23
75 MHz, CDCl ): δ 139.9, 137.5, 136.5, 133.5, 133.4, 131.2, 130.8,
3
(m, 10H), 2.94 (d, J = 1.0 Hz, 3H). 13C{ H} NMR (75 MHz, CDCl ):
1
1
28.6, 128.3, 127.2, 127.0, 125.5, 124.8, 124.0, 35.9, 24.9, 19.7, 14.3.
3
6
These analytical data are in accordance with the literature.
-(n-Butyl)-4-methyl-1-phenylnaphthalene (7c). Starting from
-phenylpropionaldehyde 1 (134 mg, 1.0 mmol) and 1-phenyl-hex-1-
yne 6c (237 mg, 1.5 mmol) and following the general procedure, after
5 h of reaction the crude material was purified by flash column
δ 142.2, 139.3, 138.1, 136.1, 133.9, 132.9, 132.0, 131.8, 130.2, 129.2,
2
127.9, 127.7, 127.6, 126.7, 126.3, 126.0, 125.7, 124.2, 19.7. HRMS
+•
2
(APPI) m/z: [M] calcd for C H 294.14031352, found 294.1407.
23 18
10a
These analytical data are in accordance with the literature.
1
4-Methyl-1,2-di(m-tolyl)-naphthalene (7h). Starting from 2-
phenylpropionaldehyde 1 (201 mg, 1.5 mmol) and 1,2-di(m-tolyl)-
ethyne 6h (206 mg, 1.0 mmol) and following the general procedure,
after 48 h of reaction the crude material was purified by flash column
chromatography on silica gel using petroleum ether as eluent. The
chromatography on silica gel using cyclohexane as eluent followed
bulb to bulb distillation of residual alkyne at 100 °C/0.3 Torr during 1
h. The desired naphthalene 7c was obtained as a low melting point
1
pale yellow solid (192 mg, 70% yield). H NMR (300 MHz, CDCl ):
3
δ 7.99 (d, J = 8.3 Hz, 1H), 7.52−7.38 (m, 4H), 7.37−7.23 (m, 5H),
desired naphthalene 7h was obtained as a white solid (158 mg, 49%
1
2
1
.73 (d, J = 0.8 Hz, 3H), 2.53−2.43 (m, 2H), 1.54−1.43 (m, 2H),
yield); mp 106−108 °C. H NMR (300 MHz, CDCl ): δ 8.16−8.08
3
13
1
.29−1.14 (m, 2H), 0.79 (t, J = 7.3 Hz, 3H). C{ H} NMR (75 MHz,
(m, 1H), 7.82−7.74 (m, 1H), 7.58 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.51
(d, J = 1.1 Hz, 1H), 7.47 (ddd, J = 8.3, 6.7, 1.4 Hz, 1H), 7.24 (t, J = 7.5
Hz, 1H), 7.17−6.96 (m, 7H), 2.84 (d, J = 1.0 Hz, 3H), 2.36 (s, 3H),
CDCl ): δ 139.9, 137.8, 136.4, 133.5, 133.4, 131.2, 130.8, 128.6, 128.3,
3
1
27.2, 127.0, 125.6, 124.8, 124.0, 34.0, 33.6, 22.8, 19.7, 14.0. HRMS
+•
13
1
(
APPI) m/z: [M] calcd for C H 274.1716, found 274.1724.
2.31 (s, 3H). C{ H} NMR (75 MHz, CDCl ): δ 142.2, 139.3, 138.1,
21
22
3
2
-(n-Butyl)-1-(4-chlorophenyl)-4-methylnaphthalene (7d).
Starting from 2-phenylpropionaldehyde 1 (134 mg, 1.0 mmol) and
-chloro-4-(hex-1-ynyl)benzene 6d (289 mg, 1.5 mmol) and following
137.2, 137.1, 136.3, 133.6, 133.0, 132.5, 132.0, 131.0 (2C), 129.3,
128.8, 127.7, 127.5, 127.4, 127.3, 126.9, 125.9, 125.6, 124.1, 21.6, 21.5,
+
•
1
19.7. HRMS (APPI) m/z: [M] calcd for C H 322.1716, found
25 22
the general procedure, after 15 h of reaction the crude material was
purified by flash column chromatography on silica gel using petroleum
ether as eluent followed by bulb to bulb distillation of residual alkyne
at 100 °C/0.3 Torr during 1 h. The desired naphthalene 7d was
322.1721.
2-Acetyl-4-methyl-1-phenylnaphthalene (7i). Starting from 2-
phenylpropionaldehyde 1 (134 mg, 1.0 mmol) and 4-phenylbut-3-yn-
2-one 6i (216 mg, 1.5 mmol) and following the general procedure,
after 13 h of reaction the crude material was purified by flash column
chromatography on silica gel using cyclohexane:ethyl acetate (98:2) as
eluent followed by bulb to bulb distillation of residual alkyne at 100
°C/0.3 Torr during 1 h. The desired naphthalene 7i was obtained as a
1
obtained as a white solid (212 mg, 69% yield); mp 79−81 °C. H
NMR (300 MHz, CDCl ): δ 8.01 (dt, J = 8.4, 1.0 Hz, 1H), 7.50−7.41
3
(
m, 3H), 7.36−7.28 (m, 3H), 7.24−7.16 (m, 2H), 2.74 (d, J = 0.9 Hz,
3
0
1
1
H), 2.52−2.41 (m, 2H), 1.56−1.42 (m, 2H), 1.33−1.14 (m, 2H),
.82 (t, J = 7.3 Hz, 3H). 13C{ H} NMR (75 MHz, CDCl ): δ 138.3,
1
1
3
low melting point pale yellow solid (120 mg, 46% yield). H NMR
(300 MHz, CDCl ): δ 8.06 (d, J = 8.4 Hz, 1H), 7.72 (ddd, J = 8.6, 1.4,
37.9, 135.0, 134.0, 133.2, 133.0, 132.2, 131.2, 128.5 (2C), 126.9,
3
25.7, 124.9, 124.1, 34.0, 33.6, 22.8, 19.7, 14.1. HRMS (APPI) m/z:
0.7 Hz, 1H), 7.60 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.53−7.42 (m, 5H),
+
•
13
1
[
M] calcd for C H Cl 308.1326, found 308.1330.
7.40−7.34 (m, 2H), 2.76 (d, J = 1.0 Hz, 3H), 1.92 (s, 3H). C{ H}
21
21
1
-(4-Bromophenyl)-2-(n-butyl)-4-methylnaphthalene (7e).
Starting from 2-phenylpropionaldehyde 1 (134 mg, 1.0 mmol) and
-bromo-4-(hex-1-ynyl)benzene 6e (356 mg, 1.5 mmol) and following
NMR (75 MHz, CDCl ): δ 205.2, 138.6, 137.8, 136.9, 134.5, 133.8,
3
132.1, 130.9, 128.6, 128.1, 128.0, 127.2, 126.4, 124.9, 124.2, 30.8, 19.6.
HRMS (APPI) m/z: [M + H] calcd for C H O 261.1274, found
+
1
19
16
the general procedure, after 15 h of reaction the crude material was
purified by flash column chromatography on silica gel using petroleum
ether as eluent followed by bulb to bulb distillation of residual alkyne
at 100 °C/0.3 Torr during 1 h. The desired naphthalene 7e was
261.1274.
1-Methyl-4-phenylnaphthalene (7j). Starting from 2-phenyl-
propionaldehyde 1 (134 mg, 1.0 mmol) and phenylacetylene 6j (306
mg, 3.0 mmol) and following the general procedure, after 21 h of
reaction the crude material was purified by flash column chromatog-
raphy on silica gel using petroleum ether as eluent. The desired
1
obtained as a white solid (238 mg, 68% yield); mp 83−85 °C. H
NMR (300 MHz, CDCl ): δ 8.00 (dt, J = 8.4 Hz, 1.1 Hz, 1H), 7.66−
3
7
7
1
.57 (m, 2H), 7.54−7.39 (m, 1H), 7.36−7.32 (m, 2H), 7.29 (s, 1H),
naphthalene 7j was obtained as a low melting point white solid (89
1
.19−7.11 (m, 2H), 2.74 (d, J = 0.6 Hz, 3H), 2.52−2.43 (m, 2H),
mg, 41% yield). H NMR (300 MHz, CDCl ): δ 8.18−8.11 (m, 1H),
3
1
3
1
.57−1.41 (m, 2H), 1.31−1.17 (m, 2H), 0.82 (t, J = 7.3 Hz, 3H).
8.05−7.98 (m, 1H), 7.66−7.38 (m, 9H), 2.82 (s, 3H). C{ H} NMR
1
3
1
C{ H} NMR (75 MHz, CDCl ): δ 138.8, 137.8, 134.9, 134.0, 133.1,
(75 MHz, CDCl ): δ 141.2, 138.8, 133.9, 132.9, 131.8, 130.3, 128.3,
3
3
1
2
2
32.5, 131.5, 131.2, 128.5, 126.8, 125.7, 124.9, 124.1, 121.2, 34.0, 33.6,
127.2, 126.8 (2C), 126.3, 125.8 (2C), 124.5, 19.7. These analytical
data are in accordance with the literature.
1-(4-Fluorophenyl)-4-methylnaphthalene (7k). Starting from
2-phenylpropionaldehyde 1 (67 mg, 0.50 mmol) and 4-fluoropheny-
lacetylene 6k (180 mg, 1.5 mmol) and following the general
procedure, after 21 h of reaction the crude material was purified by
+
•
+
6
2.8, 19.7, 14.1. MS (EI) m/z 352 (80) [M] , 273 (5) [M − Br] ,
+
•
30 (100) [M − C H − Br] .
3
7
2
,4-Dimethyl-1-(p-tolyl)-naphthalene (7f). Starting from 2-
phenylpropionaldehyde 1 (134 mg, 1.0 mmol) and 1-methyl-4-
prop-1-ynyl)benzene 6f (195 mg, 1.5 mmol) and following the
(
F
DOI: 10.1021/acs.joc.5b00353
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
flash column chromatography on silica gel using petroleum ether as
National de la Recherche Scientifique (CNRS). S.P. is grateful
to the “Fondation Pierre Gilles de Gennes pour la Recherche”
for a postdoctoral grant. The authors thank C. Charvy
eluent. The desired naphthalene 7k was obtained as a white solid (50
1
mg, 42% yield); mp 87−89 °C. H NMR (300 MHz, CDCl ): δ 8.12
3
(
ddd, J = 8.5, 1.5, 0.6 Hz, 1H), 7.92 (ddd, J = 8.4, 1.5, 0.6 Hz, 1H),
(
University Pierre et Marie Curie, Paris) for HMRS measure-
7
7
.60 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.54−7.44 (m, 3H), 7.42 (dd, J =
ments.
.1, 1.0 Hz, 1H), 7.34 (d, J = 7.1 Hz, 1H), 7.27−7.16 (m, 2H), 2.80 (d,
1
3
1
1
J = 0.9 Hz, 3H). C{ H} NMR (75 MHz, CDCl ): δ 162.3 (d, J
=
C−F
3
3
2
1
1
45.7 Hz), 137.7, 137.1, 137.0, 134.1, 132.9, 131.8 (d, J
= 7.8 Hz),
= 21.1 Hz),
REFERENCES
C−F
2
■
26.8, 126.5, 126.3, 125.9, 125.8, 124.6, 115.2 (d, J
C−F
9.7. 1 F NMR (282 MHz, CDCl ): δ −116.48 to −116.79 (m).
9
(1) For selected references, see: (a) Guan, X. L.; Zhang, L. Y.; Zhang,
Z. L.; Shen, Z.; Chen, X. F.; Fan, X. H.; Zhou, Q. F. Tetrahedron 2009,
3
+
•
HRMS (APPI) m/z: [M] calcd for C H F 236.0996, found
17
13
6
1
5, 3728−3732. (b) Lee, J. J.; Noll, B. C.; Smith, B. D. Org. Lett. 2008,
2
36.0998.
-(4-Bromophenyl)-4-methylnaphthalene (7l). Starting from
-phenylpropionaldehyde 1 (67 mg, 0.50 mmol) and 4-bromopheny-
0, 1735−1738. (c) Watson, M. D.; Fechtenkotter, A.; Mullen, K.
̈
̈
1
Chem. Rev. 2001, 101, 1267−1300.
(
2
2) For selected references, see: (a) Bringmann, G.; Lombe, B. K.;
lacetylene 6l (271 mg, 1.5 mmol) and following the general procedure,
after 15 h of reaction the crude material was purified by flash column
chromatography on silica gel using petroleum ether as eluent. The
Steinert, C.; Ioset, K. N.; Brun, R.; Turini, F.; Heubl, G.; Mudogo, V.
Org. Lett. 2013, 15, 2590−2593. (b) Pinto-Bazurco Mendieta, M. A.
E.; Hu, Q.; Engel, M.; Hartmann, R. W. J. Med. Chem. 2013, 56,
6101−6107. (c) Wetzel, M.; Marchais-Oberwinkler, S.; Perspicace, E.;
desired naphthalene 7l was obtained as a white solid (61 mg, 41%
1
yield); mp 129−131 °C. H NMR (300 MHz, CDCl ): δ 8.13−8.06
3
(
m, 1H), 7.93−7.84 (m, 1H), 7.68−7.60 (m, 2H), 7.57 (ddd, J = 8.3,
Mo
̈
ller, G.; Adamski, J.; Hartmann, R. W. J. Med. Chem. 2011, 54,
̈
6
.7, 1.4 Hz, 1H), 7.47 (ddd, J = 8.3, 6.7, 1.4 Hz, 1H), 7.42−7.34 (m,
7547−7557. (d) Karakurt, A.; Ozalp, M.; Is i̧ k, Ş.; Stables, J. P.;
3
H), 7.31 (d, J = 7.2 Hz, 1H), 2.77 (d, J = 1.0 Hz, 3H). 13C{ H} NMR
1
Dalkara, S. Bioorg. Med. Chem. 2010, 18, 2902−2911. (e) Fang, J.;
Akwabi-Ameyaw, A.; Britton, J. E.; Katamreddy, S. R.; Navas, F.;
Miller, A. B.; Williams, S. P.; Gray, D. W.; Orband-Miller, L. A.;
Shearin, J.; Heyer, D. Bioorg. Med. Chem. Lett. 2008, 18, 5075−5077.
(f) Krohn, K.; Kouam, S. F.; Cludius-Brandt, S.; Draeger, S.; Schulz, B.
Eur. J. Org. Chem. 2008, 70, 3615−3618. (g) Dai, J.; Liu, Y.; Zhou, Y.
D.; Nagle, D. G. J. Nat. Prod. 2007, 70, 1824−1826. (h) Dorbec, M.;
Florent, J.-C.; Monneret, C.; Rager, M.-N.; Bertounesque, E. Synlett
(
75 MHz, CDCl ): δ 140.0, 137.4, 134.4, 132.9, 132.0, 131.5 (2C),
3
1
26.7, 126.4, 126.3, 126.0, 125.9, 124.6, 121.4, 19.7. HRMS (APPI) m/
+•
z: [M] calcd for C H Br 296.0195, found 296.0199.
17
13
2
-Chloro-4-methyl-1-phenylnaphthalene (7m). Starting from
2
-phenylpropionaldehyde 1 (134 mg, 1.0 mmol) and 2-chloroethy-
nylbenzene 6m (205 mg, 1.5 mmol) and following the general
procedure, after 20 h of reaction the crude material was purified by
flash column chromatography on silica gel using petroleum ether as
eluent. The desired naphthalene 7m was obtained as a pale yellow
2
4
2
006, 50, 591−594. (i) Silva, O.; Gomes, E. T. J. Nat. Prod. 2003, 66,
47−449. (j) Apers, S.; Vlietnick, A.; Pieters, L. Phytochem. Rev. 2003,
1
solid (113 mg, 43% yield); mp 103−105 °C. H NMR (300 MHz,
̈
̈ ̈
, 201−217. (k) Demirezer, O.; Kuruuzum, A.; Bergere, I.; Schiewe, H.
CDCl ): δ 8.11−7.99 (m, 1H), 7.67−7.32 (m, 9H), 2.77 (d, J = 1.1
3
J.; Zeeck, A. Phytochemistry 2001, 56, 399−402. (l) Ukita, T.;
Nakamura, Y.; Kubo, A.; Yamamoto, Y.; Takahashi, M.; Kotera, J.;
Ikeo, T. J. Med. Chem. 1999, 42, 1293−1305. (m) Ward, R. S. Nat.
Prod. Rep. 1995, 12, 183−205. (n) Kuo, Y.-H.; Yu, M.-T. Heterocycles
13
1
Hz, 3H). C{ H} NMR (75 MHz, CDCl ): δ 137.9, 135.8 (2C),
3
1
1
33.9, 131.4, 130.6 (2C), 130.4, 128.4, 127.8, 127.1, 126.6, 125.8,
24.3, 19.4. HRMS (APPI) m/z: [M]+• calcd for C H Cl 252.0700,
17
13
found 252.0706.
1
993, 36, 529−535. (o) Gozler, B.; Arar, G.; Gozler, T.; Hesse, M.
2
-Bromo-4-methyl-1-phenylnaphthalene (7n). Starting from
Phytochemistry 1992, 31, 2473−2475. (p) Trujillo, J. M.; Elena Jorge,
2
-phenylpropionaldehyde 1 (134 mg, 1 mmol) and 2-bromoethy-
R.; Navarro, E.; Boada, J. Phytochemistry 1990, 29, 2991−2993.
nylbenzene 6n (271 mg, 1.5 mmol) and following the general
procedure, after 20 h of reaction the crude material was purified by
flash column chromatography on silica gel using petroleum ether as
(
3) For reviews, see: (a) de Koning, C. B.; Rousseau, A. L.; van
Otterlo, W. A. L. Tetrahedron 2003, 59, 7−36. (b) Toyota, S.; Iwanaga,
T. Naphthalenes, Anthracenes, 9H-Fluorenes, and Other Acenes. In
Science of Synthesis: Houben-Weyl Methods of Molecular Transformations;
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1
(
124 mg, 42% yield); mp 103−105 °C. H NMR (300 MHz, CDCl ):
3
δ 8.11−8.00 (m, 1H), 7.67−7.33 (m, 9H), 2.77 (d, J = 1.1 Hz, 3H).
C{ H} NMR (75 MHz, CDCl ): δ 139.9, 138.2, 135.8, 134.0, 131.7,
1
3
1
3
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ASSOCIATED CONTENT
■
*
S
Supporting Information
1
13
H NMR and C NMR spectra for all naphthalene derivatives.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(
2
(
9
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AUTHOR INFORMATION
Corresponding Authors
E-mail: maxime.vitale@chimie-paristech.fr.
E-mail: veronique.michelet@chimie-paristech.fr.
E-mail: virginie.vidal@chimie-paristech.fr.
■
*
*
*
(
̈
̈
̈
I. M.; Dyker, G. Chem. Commun. 2006, 696, 2260−2261. (g) Fang, X.-
L.; Tang, R.-Y.; Zhang, X.-G.; Zhong, P.; Deng, C.-L.; Li, J.-H. J.
Organomet. Chem. 2011, 696, 352−356. (h) Umeda, R.; Kaiba, K.;
Morishita, S.; Nishiyama, Y. ChemCatChem 2011, 3, 1743−1746.
Notes
The authors declare no competing financial interest.
(6) Viswanathan, G. S.; Wang, M.; Li, C.-J. Angew. Chem., Int. Ed.
ACKNOWLEDGMENTS
This work was supported by the Minister
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