Regioselective arene functionalization: Simple substitution of carboxylate by alkyl groups

Article abstract of DOI:10.1002/chem.200901774

Arenes with various alkyl side-chains were synthesized in high yields and excellent regioselectivities. Starting from toluic and naphthoic acids, the carboxylate group was conveniently substituted by alkyl halides by Birch reduction and subsequent decarbonylation. The method is characterized by inexpensive starting materials and reagents, and methylation of arenes was realized. Besides simple alkyl substituents, the scope of arene functionalization was extended by benzyl, fluoro, amino, and ester groups. We were able to control the alkylation of 1-naphthoic acid during Birch reduction by the addition of tert-butanol. This allowed the regioselective synthesis of mono and bis-substituted naphthalenes from the same starting material.

Full text of DOI:10.1002/chem.200901774

DOI: 10.1002/chem.200901774
Regioselective Arene FunctionACTHNUTRGENNUaG lization: Simple Substitution of HCATUNGTRENCNGUN arboxylate
by Alkyl Groups
Tobias Krꢀger, Katja Vorndran, and Torsten Linker*[a]
Abstract: Arenes with various alkyl
side-chains were synthesized in high
yields and excellent regioselectivities.
Starting from toluic and naphthoic
acids, the carboxylate group was con-
veniently substituted by alkyl halides
by Birch reduction and subsequent de-
carbonylation. The method is charac-
terized by inexpensive starting materi-
als and reagents, and methylation of
arenes was realized. Besides simple
alkyl substituents, the scope of arene
functionalization was extended by
benzyl, fluoro, amino, and ester groups.
We were able to control the alkylation
of 1-naphthoic acid during Birch reduc-
tion by the addition of tert-butanol.
This allowed the regioselective synthe-
sis of mono and bis-substituted naph-
thalenes from the same starting materi-
al.
Keywords: alkylation
·
aromatic
compounds · Birch reduction · car-
boxylic acids · decarbonylation
Introduction
Arene functionalizations are of current interest in organic
chemistry, and many industrial processes are based on such
transformations.[1] The formation of C C bonds represents
À
one of the most important reactions, and the traditional
Friedel–Crafts alkylation,[2] especially in combination with
new catalysts,[3] is often applied, although the moderate re-
gioselectivities and bis-alkylations are disadvantageous.
Modern methodologies such as Heck reactions or Stille and
Suzuki couplings proceed in the presence of palladium cata-
lysts under mild conditions and afford exclusively one regio-
Scheme 1. Examples of aromatic substitution reactions.
Another very attractive approach for arene functionaliza-
tion was developed by Gooßen,[7] with inexpensive aromatic
carboxylic acids as precursors. Heck reactions and biaryl
syntheses were realized in high yields under decarboxyla-
isomer.[4] However, the synthesis of the aromatic precursors
2
À
À
is often tedious, and many C C couplings are limited to sp
tion, but C C couplings with alkyl groups have not been de-
and sp centers due to competing b-hydride eliminations. To
scribed until now (Scheme 1, bottom).
overcome these problems, iron-catalyzed cross-coupling re-
During the course of our investigations on singlet oxygen
chemistry,[8] we discovered an unrepresented aromatization
of 1,4-cyclohexadienes 2 to arenes 3 under acidic reaction
conditions (Scheme 2).[9] The dienes 2 are easily available
from benzoic acids 1 by Birch reduction and alkylation in
high yields.[10] Thus, we developed a convenient two-step
ipso substitution of aromatic carboxylic acids by alkyl
À
actions have become an important and versatile tool for C
C bond formation during the last decade.[5] Thus, simple aryl
chlorides couple with Grignard reagents to afford alkyl-sub-
stituted arenes in excellent yields (Scheme 1, top). Very re-
cently, similar products were obtained by oxidative coupling
between organozinc reagents.[6] However, the introduction
of methyl groups into aromatic rings was not possible by
using such strategies.
[a] T. Krꢀger, Dr. K. Vorndran, Prof. Dr. T. Linker
Department of Chemistry, University of Potsdam
Karl-Liebknecht-Str. 24–25, 14476 Potsdam (Germany)
Fax : (+49)331-9775606
Scheme 2. Two-step ipso substitution of aromatic carboxylic acids 1 to
arenes 3.
E-mail: linker@uni-potsdam.de
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Chem. Eur. J. 2009, 15, 12082 – 12091

FULL PAPER
ACHTUNGTRENNUNGhalides. The method is characterized by simple precursors
and the exclusive formation of one regioisomer, and is appli-
cable for the introduction of methyl groups into arenes.
However, in our initial communication we investigated only
toluic acids and simple alkyl halides.[9] Herein we present
À
our results on the scope and limitation of such arene C C
bond formations, the tolerance of functional groups, and in-
teresting applications with naphthoic acid.
Results and Discussion
Scheme 3. Proposed mechanism for the reaction of cyclohexadienes 2
with chlorosulfonic acid.
Alkylation of toluic acids: Toluic acids 1a–c represent very
inexpensive commercially available starting materials. Fur-
thermore, the Birch reduction of such arenes proceeds with
high yield, and the regioselective formation of 2,5-cyclohex-
adiene-1-carboxylates 2 is accomplished.[10,11] The best con-
ditions were found with lithium as the alkali metal in liquid
ammonia, and the reactions could be performed on a large
scale. Thus, we were able to introduce various alkyl groups
ties as well. The aromatization proceeded smoothly, and cy-
clohexadienes derived from ortho- and para-toluic acid (1a
and 1c), and various arenes 3 were isolated in high yields
(Table 2). On the other hand, “meta”-substituted cyclohexa-
dienes 2b, 2e, 2h and 2k afforded lactones 4 as by-products.
This can be rationalized by a competing protonation of the
electron-rich double bond and intramolecular trapping of
the intermediary carbenium ion by the acid group
(Scheme 3).
at the 1-position of cyclohexadienes
2 (Table 1). The
method is applicable to simple primary alkyl halides (en-
tries 1–6), secondary halides (entries 7–9), and alkyl groups
with longer chains (entries 10–12). We isolated the products
in analytically pure form and synthesized many cyclohexa-
dienes 2 for the first time.
Table 2. Regioselective synthesis of arenes 3 and lactones 4.
Entry Cyclohexadiene 2 [%][a]
R
Arene 3 [%][a] Lactone 4 [%][a]
Table 1. Birch reduction and alkylation of toluic acids 1.
1
2
3
4
5
6
7
8
2a (ortho-Me)
2b (meta-Me)
2c (para-Me)
2d (ortho-Me)
2e (meta-Me)
2 f (para-Me)
2g (ortho-Me)
2h (meta-Me)
2i (para-Me)
2j (ortho-Me)
2k (meta-Me)
2l (para-Me)
Me
Me
Me
Et
Et
Et
iPr
iPr
iPr
3a (95)
3b (32)
3c (81)
3d (86)
3e (38)
3 f (87)
3g (98)
3h (35)
3i (93)
4a (0)
4b (53)
4c (0)
4d (0)
4e (52)
4 f (0)
4g (0)
4h (49)
4i (0)
Entry
Toluic acid 1
RX
Cyclohexadiene 2 [%][a]
1
2
3
4
5
6
7
8
9
1a (ortho-Me)
1b (meta-Me)
1c (para-Me)
1a (ortho-Me)
1b (meta-Me)
1c (para-Me)
1a (ortho-Me)
1b (meta-Me)
1c (para-Me)
1a (ortho-Me)
1b (meta-Me)
1c (para-Me)
MeI
MeI
MeI
EtBr
EtBr
EtBr
iPrBr
iPrBr
iPrBr
nHexBr
nHexBr
nHexBr
2a (98)
2b (99)
2c (92)[b]
2d (86)
2e (89)
2 f (87)[b]
2g (98)
2h (89)
2i (86)[b]
2j (87)
9
10
11
12
nHex 3j (90)
nHex 3k (39)
nHex 3l (88)
4j (0)
4k (53)
4l (0)
[a] Yield of isolated product after column chromatography or distillation.
10
11
12
Tolerance of functional groups: In our previous studies, we
investigated only toluic acids and simple alkylations.[9] How-
ever, functionalized arene precursors or electrophiles would
extend the scope of substitution reactions of aromatic car-
boxylic acids. For the tolerance of functional groups, the
conditions of the Birch reduction and subsequent decarbon-
ylation are problematic. For instance, the first step requires
strongly basic, and the second step requires strongly acidic
reagents. Indeed, chloro, bromo, or iodo substituents at the
aromatic ring are not tolerated during Birch reduction.[10]
On the other hand, meta-fluorobenzoic acid (1d) can be em-
ployed as a commercially available substrate, but alkylations
were hitherto unknown, and only the unsubstituted 1,4-cy-
clohexadiene was synthesized in moderate yield.[12] There-
fore, we examined the introduction of methyl, ethyl, and iso-
propyl groups onto meta-fluorobenzoic acid (1d) by Birch
2k 82)
2l (89)[b]
[a] Yield of isolated product after column chromatography or crystalliza-
tion. [b] Mixture of cis and trans isomer.
To completely substitute the carboxylate by the alkyl
À
groups in the next step, the C C bond in the 1-position had
to be cleaved under rearomatization. For this purpose, we
developed a convenient protocol in the presence of strong
Brønsted acids.[9] The mechanism of this surprising reaction
has been investigated previously and proceeds by protona-
tion of the carboxylic acid, dehydration, decarbonylation,
and deprotonation of the allylic cation (Scheme 3). The best
conditions were found with chlorosulfonic acid, which is not
only a strong mineral acid but possesses dehydrating proper-
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T. Linker et al.
À
Table 3. Transformations of ortho-toluic acid (1a) with halides R X.
reduction, which proceeded smoothly and afforded the 2,5-
cyclohexadiene-1-carboxylic acids 2m–o in good yields
(Scheme 4). Finally, the desired arenes 3m–o were isolated
Entry
RX
Cyclohexadiene 2 [%][a]
Arene 3 [%][a]
1
2
3
4
BnBr
allylBr
2s (87)
2t (98)
2u (88)
2v (84)
3s (95)
3t (0)[b]
4u (92)[d]
3v (87)
HOCH2CH2Br[c]
MeO2CCH2Cl
[a] Yield of isolated product after column chromatography or crystalliza-
tion. [b] Only polymeric material was obtained. [c] OH group protected
as trimethyl silyl ether. [d] Formation of lactone 4u.
95% yield (Table 3, entry 1). This is an important result for
synthetic applications, because Friedel–Crafts benzylations
of toluene afford only mixtures of ortho and para-iso-
mers.[3,14] On the other hand, an allyl group was not tolerat-
ed in the presence of chlorosulfonic acid, and only polymer-
ic material was isolated (entry 2). The alcohol 2u reacted to
a single product, but no decarbonylation was observed and
an interesting spirolactone 4u was isolated in 92% yield
[Eq. (1)]. This result can be explained in accordance with
Scheme 4. Two-step ipso substitution of aromatic carboxylic acids 1d and
1e with fluoro and amino groups to arenes 3m–r.
in analytically pure form after subsequent decarbonylation
in the presence of chlorosulfonic acid. Unfortunately, ortho-
and para-fluorobenzoic acids were unsuitable substrates for
Birch reductions, due to the intermediary radical anions,
which are destabilized by the fluoro substituent (in the
meta-position unfavorable mesomeric structures are not in-
volved). However, meta-fluoro alkyl arenes are of great syn-
thetic interest, because Friedel–Crafts alkylations of fluoro-
benzene afford only mixtures of ortho- and para-isomers.[13]
Thus, the reaction sequence Birch reduction/decarbonyla-
tion opens a highly regioselective and convenient access to
such compounds.
the literature by an acid-catalyzed cyclization[15] that is
À
faster than the cleavage of the C C bond so that aromatiza-
Another attractive substrate for the substitution of the ar-
omatic carboxylic acid group by alkyl halides was found
with commercially available para-(aminomethyl)benzoic
acid (1e), because the amino group is tolerated in both reac-
tion steps. The Birch reductions afforded cyclohexadienes
2p–r in slightly lower yields due to problems during work-
up of the zwitterionic amino acids and the formation of cis/
trans-isomers. However, the decarbonylation proceeded
smoothly, and the para-substituted arenes 3p–r were easily
accessible in high regioselectivity (Scheme 4).
Finally, functional groups can be introduced through the
electrophile during the Birch reduction.[10] Again, the drastic
conditions of the subsequent decarbonylation had to be
taken into account. We selected ortho-toluic acid (1a) as
substrate for the functionalizations because it provides high
yields in Birch reductions and forms no lactones 4 under
acidic conditions. Indeed, various bromides reacted smooth-
ly with ortho-toluic acid (1a) to afford the corresponding cy-
clohexadienes 2s–v in good to high yields (Table 3). For the
alcohol-substituted cyclohexadiene 2u (entry 3), the OH
group had to be silylated before Birch reduction, but the
protecting group was directly cleaved during work up.
Firstly, we investigated the decarbonylation of the benzyl-
substituted cyclohexadiene 2s and obtained the arene 3s in
tion cannot compete. Importantly, an ester group gave no
side-reaction during the decarbonylation and afforded the
arene 3v in high yield (entry 4). This alkylation with methyl
chloroacetate is very attractive, because it is an inexpensive
reagent and the product 3v represents an Arndt–Eistert ho-
mologue of the starting material 1a.[16]
Reactions of naphthoic acid: In contrast to toluic acids,
Birch reductions of naphthoic acids found less synthetic ap-
plications, because over-reduction and the formation of re-
gioisomers is problematic.[10] 1-Naphthoic acid (5) reacts
more selectively than the corresponding 2-isomer, and the
methylation of the anionic intermediate has been described
previously.[17] This is very important for our concept of re-
gioselective arene functionalization because Friedel–Crafts
alkylations of naphthalene afford only a/b-mixtures or the
2-isomer as the main product.[14,18] The ipso substitution of
À
the carboxylate group would control the C C bond forma-
tion with high selectivity. Therefore, we investigated the re-
ductive alkylation of 1-naphthoic acid (5) with various elec-
trophiles for the first time (Table 4).
All Birch reductions proceeded smoothly with lithium in
ammonia and afforded alkylation products in high yields.
For instance, the methylated 1,4-dihydronaphthalene 6a was
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Chem. Eur. J. 2009, 15, 12082 – 12091

Regioselective Arene Functionalization
FULL PAPER
Table 4. Birch reduction and alkylation of 1-naphthoic acid (5).
(Table 4, entries 5 and 6). Additionally, the reactivity and
steric hindrance of the electrophiles has to be taken into ac-
count. Thus, the secondary and long-chain halides attack in
the first step preferentially the sterically less shielded 4-posi-
tion, which results in the observed bis-alkylated products 7c
and 7d, whereas the functionalized halides are more reac-
tive and afford exclusively mono-alkylated 1,4-dihydronaph-
thalenes 6g and 6h (entries 7 and 8).
Entry
RX
Mono-alkylated
Bis-alkylated
product 6 [%][a]
product 7 [%][a,b]
1
2
3
4
5
6
7
8
9
MeI
EtBr
iPrBr
n-HexBr
BnBr
6a (96)
6b (9)
6c (0)
7a (0)
7b (88)
7c (97)
7d (83)
7e (0)
7 f (0)
7g (0)
7h (0)
7b (0)
7c (0)
7d (0)
To further elucidate the mechanism of the reaction and to
influence the product distribution, we investigated different
concentrations of the alkyl halides, changed the counterion
(e.g., Me2SO4 or EtI), and altered the alkali metal (Na, K).
However, the same products were obtained in somewhat
lower yields. This result is contradictory to a recent study on
the ethylation of 1-naphthoic acid (5), which showed a re-
markable influence of the reaction conditions and even the
formation of tris-alkylated products.[19] Finally, we applied a
convenient procedure for the selective synthesis of mono-al-
kylated products 6b–d in high to excellent yields by the ad-
dition of tert-butanol prior to the alkyl halide (Table 4, en-
tries 9–11). In this case the alcohol protonates the 4-position
of trianion 8 in the first step, but is not acidic enough for
the enolate, which is exclusively attacked by the electrophile
in the second step (Scheme 5). Thus, although the mecha-
nism of the Birch reduction of 1-naphthoic acid (5) is still
debatable, we found a selective entry to both isomers from
the same precursor for some substrates (b–d); this is impor-
tant for future applications of arene functionalizations.
The decarbonylation of the 1,4-dihydronaphthalenes 6
and 7 proceeded again smoothly with chlorosulfonic acid at
08C, and the naphthalenes 9 were isolated in high yields in
analytically pure form (Table 5). The regioselective forma-
tion of the 1-substituted products is important because Frie-
del–Crafts alkylations of naphthalene afford only a/b-mix-
tures or the 2-isomer as the main product.[14,18] Additionally,
less-reactive electrophiles offer direct access to 1,4-bis-alky-
6d (11)
6e (92)[c]
6 f (90)
6g (83)
6h (84)
6b (85)
6c (98)
6d (87)
allylBr
Me3SiOCH2CH2Br
MeO2CCH2Cl
EtBr[c]
10
11
iPrBr[c]
n-HexBr[c]
[a] Yield of isolated product after column chromatography or crystalliza-
tion. [b] Mixture of cis and trans isomer. [c] Addition of 1 equiv tert-buta-
nol prior to alkyl halide.
isolated in 96% yield in analytically pure form (Table 4
entry 1). Interestingly, we obtained mainly the bis-alkylated
product 7b during the reaction with ethyl bromide (entry 2).
The same behavior was observed with isopropyl and n-hexyl
bromide, which afforded the bis-substituted 1,4-dihydro-
naphthalenes 7c and 7d in good to excellent yields as a mix-
ture of cis and trans-isomers (entries 3 and 4). The forma-
tion of such products can be rationalized by a trianionic in-
termediate 8, which is often postulated during Birch reduc-
tions of polycyclic aromatic acids (Scheme 5).[10] Thus, the
alkylation can occur at the 1- and 4-position in the same re-
action step.
Table 5. Decarbonylation of 1,4-dihydronapthalenes 6 and 7 to naphtha-
lenes 9.
Entry Dihydronaphthaline 6,7 R1
R2 Naphthalene 9 [%][a]
1
2
3
4
5
6
7
8
9
6a
6b
6c
6d
6e
6 f
6g
6h
7b
7c
7d
Me
Et
iPr
nHex
Bn
allyl
HOCH2CH2-
MeO2CCH2-
Et
H
H
H
H
H
H
H
H
9a (90)
9b (95)
9c (98)
9d (87)
9e (91)
9 f (0)[b]
9g (98)[c]
9h (89)
Scheme 5. Proposed mechanism for the formation of mono- or bis-alky-
lated 1,4-dihydronaphthalenes (6 or 7).
Our explanation for the selective mono-alkylation with
methyl iodide is based on a fast oxidation of the 4-position
by an electron-transfer (ET) process, which is not possible
with the slower reacting bromides (especially iPrBr). This
hypothesis is in accordance to the benzylation and allylation,
because again ET is favored and the mono-alkylated prod-
ucts 6e and 6 f were isolated as single isomers in high yields
R1 9i (92)
R1 9j (94)
R1 9k (94)
10
11
iPr
n-Hex
[a] Yield of isolated product after column chromatography or crystalliza-
tion. [b] Only polymeric material was obtained. [c] Formation of a lac-
tone in analogy to 4u.
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T. Linker et al.
chromatography. Melting points were measured on a Bꢀchi SMP 20 ap-
lated naphthalenes 9i–k from 1-naphthoic acid (5) in only
two steps (entries 9–11). Furthermore, the simple addition
of tert-butanol allows the controlled and regioselective syn-
thesis of mono- and bis-alkylated products for such sub-
strates. Although the allyl-substituted 1,4-dihydronaphtha-
lene 6e afforded only polymeric material (entry 6), and the
alcohol 6g cyclized to a lactone (entry 7), benzyl and ester
groups were tolerated during the decarbonylation (entries 5
and 8). Again, the alkylation with methyl chloroactetate is
interesting because an Arndt–Eistert homologue 9h of 1-
naphthoic acid is easily accessible.
paratus (uncorrected), and IR spectra were recorded on
a Perkin–
Elmer 1600 FT-IR spectrometer. NMR spectra were recorded on
a
Bruker AC 300 by using the deuterated solvent as the internal standard.
Elemental analyses were performed on an ELEMENTAR vario EL ana-
lysor.
General procedure for the Birch reductions: Li (0.3–0.6 g, 43–86 mmol)
was added in small portions at À608C to a solution of the carboxylic acid
1 or 5 (30 mmol) in liquid ammonia (250 mL) until the blue color persist-
ed. After 30 min at this temperature, the alkyl halide (100 mmol) was
added slowly over a period of 5 min. For mono-alkylations of naphthoic
acid (5), tBuOH (2.2 g, 30 mmol) was added prior to the alkyl halide.
Ammonia was evaporated over night, and the residue was dissolved in
H2O (100 mL). Concd HCl was then added to reach pH 1–2, and the so-
lution extracted with EtOAc (3ꢂ100 mL). The combined organic phases
were washed with H2O (50 mL) and then dried over Na2SO4. After re-
moval of the solvent, the products 2, 6 or 7 were purified by recrystalliza-
tion or column chromatography.
Conclusion
We have developed a new concept for the regioselective
functionalization of arenes with inexpensive starting materi-
als. The method is based on the Birch reduction/alkylation
of aromatic carboxylic acids and subsequent decarbonyla-
tion in the presence of chlorosulfonic acid. Both steps can
be performed on large scales and provide good to high
yields. In contrast to classical Friedel–Crafts alkylations, our
procedure afforded only one regioisomer, and we were able
to introduce even methyl groups into arenes. Long alkyl
chains reacted smoothly and provided high yields as well.
For the first time, the scope of the two-step ipso substitution
was extended by fluoro, amino, benzyl, or ester groups,
which were tolerated under the reaction conditions. Further-
more, we found an inexpensive large-scale alternative to
Arndt–Eistert homologations by the alkylation with methyl
chloroacetate. Thus, benzoic acids are suitable and inexpen-
sive substrates for regioselective arene functionalizations.
Additionally, we applied the two-step ipso substitution to
1-naphthoic acid for the first time. This resulted in the regio-
selective synthesis of 1-substituted naphthalenes in high
yields, which are not accessible by using the Friedel–Crafts
method. Sterically more hindered electrophiles afforded bis-
alkylation products during the Birch reduction, and allowed
the introduction of two substituents into arenes after the de-
carbonylations. We controlled the degree of mono- and bis-
alkylation by the simple addition of tert-butanol during the
Birch reduction. Thus, two different products are accessible
selectively from the same precursor. In summary, the ipso
substitution of aromatic carboxylic acids by alkyl halides is a
valuable concept in arene chemistry, and should comple-
ment transition-metal-catalyzed functionalizations. Due to
the large-scale procedure, tolerance of functional groups,
and high yields, we expect future synthetic applications of
our method.
1,2-Dimethyl-2,5-cyclohexadiene-1-carboxylic acid (2a): White solid
(98%); Rf =0.56 (CH2Cl2/MeOH/AcOH, 98:2:0.1); m.p. 75–768C (lit.
1
768C)[11a]; H NMR (300 MHz, CDCl3): d=1.37 (s, 3H; H7), 1.67 (s, 3H;
H8), 2.70 (dt, J=3.6, 1.6 Hz, 2H; H4), 5.56–5.64 (m, 2H; H3, H6), 5.84
(ddt, J=9.6, 3.6, 1.6 Hz, 1H; H5), 10.8 ppm (brs, 1H; COOH); 13C NMR
(75 MHz, CDCl3): d=19.9 (C8), 23.9 (C7), 27.1 (C4), 47.7 (C1), 122.0,
125.5, 129.2 (C3, C5, C6), 131.4 (C2), 180.1 ppm (s, COOH); IR (KBr):
n˜ =3500–2500 (COOH), 1680 (C=O), 1435, 1390, 1260 cmÀ1
.
1,3-Dimethyl-2,5-cyclohexadiene-1-carboxylic acid (2b): White solid
(99%); Rf =0.69 (CH2Cl2/MeOH/AcOH, 98:2:0.1); m.p. 42–438C (lit. 43–
458C)[11a] 1H NMR (300 MHz, CDCl3): d=1.14 (s, 3H; H7), 1.54 (d, J=
;
1.6 Hz, 3H; H8), 2.36 (brs, 2H; H4), 5.28 (qdddd, J=1.6, 1.6, 1.6, 1.6,
1.6 Hz, 1H; H2), 5.56 (ddd, J=10.0, 1.6, 1.6 Hz, 1H; H6), 5.64 (ddt, J=
10.0, 3.1, 1.6 Hz, 1H; H5), 9.80 ppm (brs, 1H; COOH); 13C NMR
(75 MHz, CDCl3): d=23.6 (C8), 27.6 (C7), 31.1 (C4), 45.3 (C1), 123.1,
125.2, 128.3 (C2, C5, C6), 133.0 (C3), 182.3 ppm (s; COOH); IR (KBr):
n˜ =3600–2500 (COOH), 1700 (C=O), 1453, 1390, 1291 cmÀ1
.
1,4-Dimethyl-2,5-cyclohexadiene-1-carboxylic acid (2c): Yellow oil
(92%); Rf =0.46 (CH2Cl2/MeOH/AcOH, 98:2:0.1); 1H NMR (300 MHz,
CDCl3): d=0.89 (d, J=7.4 Hz, 3H; H8), 0.92 (d, J=7.4 Hz, 3H; H8’’),
1.20 (s, 3H; H7), 1.22 (s, 3H; H7’), 2.73, 2.74 (2q, J=7.4 Hz, 2H; H4,
H4’), 5.57–5.58 (m, 8H; H2, H2’, 3H, 3H’, H5, H5’, H6, H6’), 10.5 ppm
(brs, 1H; COOH); 13C NMR (75 MHz, CDCl3): d=21.9, 22.0 (C8, C8’),
27.5, 28.0 (C7, C7’), 30.8, 31.3 (C4, C4’), 44.3, 44.4 (C1, C1’), 127.3, 127.4
(C3, C3’, C5, C5’), 131.6, 131.7 (C2, C2’, C6, C6’), 181.8 ppm (COOH);
IR (film): n˜ =3600–2500 (COOH), 1703 (C=O), 1455, 1415, 1293 cmÀ1; el-
emental analysis calcd (%) for C9H12O2: C 71.03, H 7.94; found: C 71,07,
H 7.74.
1-Ethyl-2-methyl-2,5-cyclohexadiene-1-carboxylic acid (2d): White solid
(86%); Rf =0.52 (CH2Cl2/MeOH/AcOH, 98:2:0.1); m.p. 66–678C (lit. 64–
678C)[11a] 1H NMR (300 MHz, CDCl3): d=0.75 (t, J=7.5 Hz, 3H; H8),
;
1.65 (s, 3H; H9), 1.90 (q, J=7.5 Hz, 2H; H7), 2.47–2.80 (m, 2H; H4),
5.44 (dt, J=9.9, 2.0 Hz, 1H; H3), 5.69–5.76 (m, 1H; H6), 5.90–6.05 (m,
1H; H5), 10.90 ppm (brs, 1H; COOH); 13C NMR (75 MHz, CDCl3): d=
10.8 (C8), 19.8 (C9), 27.1, 27.3 (C4, C7), 52.2 (C1), 124.2, 127.2, 127.4
(C3, C5, C6), 130.5 (C2), 181.2 ppm (COOH); IR (KBr): n˜ =3500–2600
(COOH), 1680 (C=O), 1390, 1370, 1260 cmÀ1
.
1-Ethyl-3-methyl-2,5-cyclohexadiene-1-carboxylic acid (2e): White solid
(89%); Rf =0.60 (CH2Cl2/MeOH/AcOH, 98:2:0.1); m.p. 53–548C;
1H NMR (300 MHz, CDCl3): d=0.80 (t, J=7.4 Hz, 3H; H8), 1.71 (q, J=
7.4 Hz, 2H; H7), 1.79 (s, 3H; H9), 2.49–2.55 (m, 2H; H4), 5.41 (ddd, J=
1,8, 1,8, 1.8 Hz, 1H; H2), 5.70 (ddd, J=10.1, 1.8, 1.8, 1.8 Hz, 1H; H6),
5.92 (ddt, J=10.1, 3.3, 1.8 Hz, 1H; H5), 11.7 ppm (brs, 1H; COOH);
13C NMR (75 MHz, CDCl3): d=8.9 (C8), 23.6 (C9), 31.4 (C4), 32.8 (C7),
49.8 (C1), 121.4, 121.8, 126.6 (C2, C5, C6), 134.3 (C3), 182.0 ppm
(COOH); IR (KBr): n˜ =3500–2500 (COOH), 1700 (C=O), 1400, 1325,
1278 cmÀ1; elemental analysis calcd (%) for C10H14O2: C 72.26, H 8.49;
found: C 71.97, H 8.61.
Experimental Section
General methods: Solvents and commercially available chemicals were
purified by standard methods or used as purchased. TLC was performed
on aluminum sheets coated with silica gel 60F254 (Merck, Darmstadt).
Silica gel (63–200 mm, Woelm, Erlangen, Germany) was used for column
1-Ethyl-4-methyl-2,5-cyclohexadiene-1-carboxylic acid (2 f): Yellow oil
(87%); Rf =0.48 (CH2Cl2/MeOH/AcOH, 98:2:0.1); 1H NMR (300 MHz,
12086
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Chem. Eur. J. 2009, 15, 12082 – 12091

Regioselective Arene Functionalization
FULL PAPER
CDCl3): d=0.83 (t, J=7.4 Hz, 6H; H8, H8’), 1.00 (d, J=7.3 Hz, 3H;
H9), 1.01 (d, J=7.3 Hz, 3H; 9H’), 1.65 (q, J=7.4 Hz, 2H; H7), 1.66 (q,
J=7.4 Hz, 2H; H7’), 2.62–2.82 (m, 2H; H4, H4’), 5.58 (ddd, J=10.2, 2.1,
2.1 Hz, 2H; H3, H5), 5.61 (ddd, J=10.2, 2.1, 2.1 Hz; 2H; H3’, H5’), 5.83
(ddd, J=10.2, 2.8, 2.8 Hz, 4H; H2, H2’, H6, H6’), 10.7 ppm (brs, 1H;
COOH); 13C NMR (75 MHz, CDCl3): d=8.9, 9.1 (C8, C8’), 21.8, 21.9
(C9, C9’), 30.8, 31.1 (C4, C4’), 32.2, 32.7 (C7, C7’), 48.8 (C1), 125.5, 125.6
(C3, C3’, C5, C5’), 132.9, 133.0 2 (C2, C2’, C6, C6’), 181.8 ppm (COOH);
IR (film): n˜ =3400–2400 (COOH), 1704 (C=O), 1397, 1280 cmÀ1; elemen-
tal analysis calcd (%) for C10H14O2: C 72.26, H 8.49; found: C 72.32, H
8.51.
0.87 (d, J=6.9 Hz, 3H; H12), 1.06 d, J=7.5 Hz, 3H; H13), 1.11–1.30 (m,
8H; H8–11), 1.65–1.72 (m, 2H; H7), 2.62–2.79 (m, 2H; H4), 5.66 (dt, J=
10.1, 1.8 Hz, 2H; H2), 5.77 (dt, J=10.1, 3.7 Hz, 2H; H3), 11.4 ppm (brs,
1H; COOH); 13C NMR (75 MHz, CDCl3): d=14.0 (C12), 21.4 (C13),
22.5, 24.0, 24.4, 31.6 (C8–11), 29.4 (C4), 39.2 (C7), 48.0 (C1), 125.6, 132.1
(C2, C3), 181.6 ppm (s, COOH); IR (film): n˜ =3200–2600 (COOH), 1697
(C=O), 1456, 1264 cmÀ1; elemental analysis calcd (%) for C14H22O2: C
75.63, H 9.97; found: C 75.48, H 10.26.
3-Fluoro-1-methyl-2,5-cyclohexadiene-1-carboxylic acid (2m): Colorless
oil (80%); Rf =0.30 (CH2Cl2/MeOH/AcOH, 98:2:0.1); 1H NMR
(300 MHz, CDCl3): d=1.41 (s, 3H; H7), 2.84 (s, 2H; H4), 5.36 (d, JH,F
=
1-Isopropyl-2-methyl-2,5-cyclohexadiene-1-carboxylic acid (2g): White
solid (98%); Rf =0.59 (CH2Cl2/MeOH/AcOH, 98:2:0.1); m.p. 99–1018C
17.1 Hz, 1H; H2), 5.76 (d, J=5.1 Hz, 2H; H5, H6), 11.9 ppm (brs, 1H;
COOH); 13C NMR (75 MHz, CDCl3): d=26.6 (2ꢂt, JC,F =105 Hz, C4),
27.3 (C7), 46.4 (d, JC,F =33 Hz, C1), 104.7 (2ꢂd, JC,F =72 Hz, C2), 122.4
1
(lit. 101–1028C)[11a]; H NMR (300 MHz, CDCl3): d=0.65, 0.88 (2ꢂd, J=
7.0 Hz, 6H; H8), 1.68 (s, 3H; H9), 2.40 (sept, J=7.0 Hz, 1H; H7), 2.60–
2.78 (m, 2H; H4), 5.45 (t, J=2.3 Hz, 1H; H3), 5.65–5.75 (m, 1H; H6),
5.98–6.09 (m, 1H; H5), 10.7 ppm (brs, 1H; COOH); 13C NMR (75 MHz,
CDCl3): d=17.4, 18.0 (C8), 19.8 (C9), 27.2 (C4), 31.4 (C7), 55.5 (C1),
123.3, 124.9, 127.2 (C3, C5, C6), 131.4 (C2), 180.1 ppm (COOH); IR
(2ꢂd, JC,F =45 Hz, C5), 128.2, (2ꢂd, JC,F =9 Hz, C6), 156.5 (d, JC,F
=
1017 Hz, C3), 180.9 ppm (s, COOH); IR (film): n˜ =3050–2300 (COOH),
2441 (C=CH), 1718 (C=O), 1455, 1251 cmÀ1; elemental analysis calcd
(%) for C8H9FO2: C 61.53, H 5.81, F 12.17; found: C 61.30, H 6.06.
1-Ethyl-3-fluoro-2,5-cyclohexadiene-1-carboxylic acid (2n): Colorless oil
(72%); Rf =0.47 (CH2Cl2/MeOH/AcOH, 98:2:0.1); 1H NMR (300 MHz,
CDCl3): d=0.84 (t, J=7.5 Hz, 3H; H8), 1.76 (q, J=7.5 Hz, 2H; H7),
2.82–2.84 (m, 2H; H4), 5.32 (dd, JC,F =17.4, JH,H =1.5 Hz, 1H; H2), 5.68–
5.72 (m, 1H; H5) 5.81–5.84 (m, 1H; H6), 10.3–11.1 ppm (brs, 1H;
COOH); 13C NMR (75 MHz, CDCl3): d=8.4 (C8), 26.7, 27.0 (C4), 32.4
(C7), 50.9, 51.0 (C1), 102.7, 102.9 (C2), 123.6, 123.8 (C5), 126.7, 126.8
(C6), 156.9, 160.2 (C3), 180.9 ppm (COOH); IR (film): n˜ =3060–2600
(COOH), 2936 (C=CH), 1704 (C=O), 1456, 1269 cmÀ1; elemental analysis
calcd (%) for C8H9FO2: C 63.52, H 6.51, F 11.16; found: C 63.56, H 6.48.
(KBr): n˜ =3200–2500 (COOH), 3039 (C=CH), 1704 (C=O), 1458 cmÀ1
.
1-Isopropyl-3-methyl-2,5-cyclohexadiene-1-carboxylic acid (2h): White
solid (89%); Rf =0.62 (CH2Cl2/MeOH/AcOH, 98:2:0.1); m.p. 698C (lit.
678C)[11c] 1H NMR (300 MHz, CDCl3): d=0.83 (d, J=6.8 Hz, 6H; H8),
;
1.72 (s, 3H; H9), 2.11 (sept, J=6.8 Hz, 1H; H7), 2.54 (brs, 2H; H4),
5.40–5.43 (m, 1H; H2), 5.72 (ddd, J=10.1, 1.9, 1.9 Hz, 1H; H6), 5.95 (dt,
J=10.1, 3.2 Hz, 1H; H5), 12.1 ppm (brs, 1H; COOH); 13C NMR
(75 MHz, CDCl3): d=17.8 (C8), 23.7 (C9), 31.7 (C4), 36.3 (C7), 53.6
(C1), 120.4, 125.2, 127.2 (C2, C5, C6), 134.8 (C3), 182.2 ppm (COOH);
IR (KBr): n˜ =3600–2500 (COOH), 3039 (C=CH), 1700 (C=O), 1453,
3-Fluoro-1-isopropyl-2,5-cyclohexadiene-1-carboxylic acid (2o): Colorless
oil (84%); Rf =0.51 (CH2Cl2/MeOH/AcOH, 98:2:0.1); 1H NMR
(300 MHz, CDCl3): d=0.85 (d, J=6.8 Hz, 6H; H8), 2.23 (sept., J=
6.8 Hz, 1H; H7), 2.84 (s, 2H; H4), 5.33 (d, JH,F =17.0 Hz, 1H; H2), 5.73
(d, J=5.1 Hz, 2H; H5, H6), 11.9 ppm (brs, 1H; COOH); 13C NMR
(75 MHz, CDCl3): d=18.1, 18.5 (C8), 26.4 (JC,F =110 Hz, C4), 36.3 (C7),
46.5 (JC,F =35 Hz, C1), 104.4 (JC,F =70 Hz, C2), 122.1 (JC,F =45 Hz, C5),
128.3, (JC,F =10 Hz, C6), 156.0 (JC,F =1020 Hz, C3), 180.9 ppm (COOH);
IR (film): n˜ =3060–2450 (COOH), 2437 (C=CH), 1706 (C=O), 1452,
1239 cmÀ1; elemental analysis calcd (%) for C10H13FO2: C 65.20, H 7.11,
F 10.31; found: C 65.23, H 7.31.
1406, 1291 cmÀ1
.
1-Isopropyl-4-methyl-2,5-cyclohexadiene-1-carboxylic acid (2i): White
solid (86%); Rf =0.50 (CH2Cl2/MeOH/AcOH, 98:2:0.1); m.p. 38–398C;
1H NMR (300 MHz, CDCl3): d=1.07 (d, J=6.8 Hz, 6H; H8), 1.09 (d, J=
6.8 Hz, 6H; H8’), 1.27 (d, J=7.5 Hz, 3H; H9), 1.29 (d, J=7.5 Hz, 3H;
H9’), 2.31 (sept, J=6.8 Hz, 1H; H7), 2.34 (sept, J=6.8 Hz, 1H; H7’),
2.90–3.00 (m, 2H; H4, H4’), 5.87 (dt, J=10.4, 1.8 Hz, 2H; H3, H5), 5.92
(dt, J=10.4, 1.8 Hz, 2H; H3’, H5’), 6.06 (dt, J=10.4, 2.1 Hz, 4H; H2,
H2’, H6, H6’), 10.4 ppm (brs, 1H; COOH); 13C NMR (75 MHz, CDCl3):
d=17.7 (C8), 18.1 (C8’), 21.6 (C9), 21.8 (C9’), 31.1 (C4), 31.3 (C4’), 35.0
(C7), 36.1 (C7’), 52.5 (C1, C1’), 124.3, 124.4 (d, C3, C3’, C5, C5’), 133.4,
133.6 (C2, C2’, C6, C6’), 181.7 ppm (COOH); IR (KBr): n˜ =3400–2400
(COOH), 1704 (C=O), 1468, 1397, 1280 cmÀ1; elemental analysis calcd
(%) for C11H16O2: C 73.30, H 8.95; found: C 73.03, H 8.69.
1-Methyl-4-methylamino-2,5-cyclohexadiene-1-carboxylic
acid
(2p):
Sticky crystals (65%); 1H NMR (300 MHz, D2O): d=1.29, (s, 3H; H6),
1.30 (s, 3H; H6ꢃ), 3.13–3.17 (m, H5, H5’) 3.21–3.26 (m, 2H; H4, H4’),
5.74 (dd, J=9.9, 3.3 Hz, 4H; H3, H3’), 6.03 ppm (d, J=9.9 Hz, 4H; H2,
H2’), COOH (not detected due to the zwitterionic form); 13C NMR
(75 MHz, D2O): d=30.0. 30.9 (C6), 37.9, 38.0 (C5), 46.9 (C4), 51.5 (C1),
127.0, 127.7 (C3), 139.3, 140.0 (C2), 186.8, 186.9 ppm (COOH); IR
(KBr): n˜ =3020–2030 (COOH), 2867 (C=CH), 1631 (C=O), 1509 (NH2),
1-Hexyl-2-methyl-2,5-cyclohexadiene-1-carboxylic acid (2j): Pale-yellow
oil (87%); Rf =0.41 (hexane/EtOAc, 4:1); 1H NMR (300 MHz, CDCl3):
d=0.88 (d, J=6.9 Hz, 3H; H12), 1.10–1.28 (m, 8H; H8–11), 1.63 (ddd,
J=13.6, 11.4, 4.3 Hz, 1H; H7), 1.74 (d, J=1.5 Hz, 3H; H13), 1.88 (ddd,
J=13.6, 12.3, 4.8 Hz, 1H; H7’), 2.60–2.80 (m, 2H; H4), 5.48 (dt, J=10.0,
1.9 Hz, 1H; H6), 5.64–5.72 (m, 1H; H3), 5.93 (dtd, J=10.0, 3.3, 1.3 Hz,
1H; 5H); 11.2 ppm (brs, 1H; COOH); 13C NMR (75 MHz, CDCl3): d=
14.0 (C12), 19.7 (C13), 22.6, 23.9, 26.9, 29.5, 31.7 (C7–11), 34.3 (C4), 51.5
(C1), 123.6, 126.6, 127.4 (C3, C5, C6), 130.7 (C2), 181.0 ppm (COOH);
IR (film): n˜ =3200–2600 (COOH), 1698 (C=O), 1455, 1263 cmÀ1; elemen-
tal analysis calcd (%) for C14H22O2: C 75.63, H 9.97; found: C 75.40, H
10.04.
1357 cmÀ1
.
1-Ethyl-4-methylamino-2,5-cyclohexadiene-1-carboxylic acid (2q): Sticky
crystals (62%); 1H NMR (300 MHz, D2O): d=0.74 (t, J=7.5 Hz, 3H;
H6), 0.77 (t, J=7.5 Hz, 3H; H6’), 1.66 (q, J=7.5 Hz, 2H; H5, H5’), 1.68
(q, J=7.5 Hz, 2H; H5’’, H5’’’), 3.12–3.16 (m, 4H; H7, H7’), 3.18–3.21 (m,
2H; H4, H4’), 5.77 (dd, J=10.4, 2.3 Hz, 2H; H3), 5.81 (dd, J=10.4,
3.6 Hz, 2H; H3’), 5.93 (dd, J=10.4, 1.4 Hz, 2H; H2), 5.99 ppm (dd, J=
10.4, 1.4 Hz, 2H; H2’), COOH (not detected due to the zwitterionic
form); 13C NMR (75 MHz, D2O): d=8.2 (C6), 35.3, 35.7, 38.3, 38.7 (C5,
C7), 47.0, 47.5 (C4), 58.9, 59.5 (C1), 128.5, 129.6 (C3), 137.5, 138.1 (C2),
186.4, 186.5 ppm (COOH); IR (KBr): n˜ =3010–2020 (COOH), 2870 (C=
1-Hexyl-3-methyl-2,5-cyclohexadiene-1-carboxylic acid (2k): White solid
(82%); Rf =0.30 (hexane/EtOAc, 10:1); m.p. 36–378C; 1H NMR
(300 MHz, CDCl3): d=0.88 (d, J=7.0 Hz, 3H; 12H), 1.08–1.26 (m, 8H;
H8–11), 1.63–1.69 (m, 2H; H7), 1.74 (s, 3H; H13), 2.52–2.56 (m, 2H;
H4), 5.42–5.62 (m, 1H; H2), 5.74 (ddd, J=10.1, 3.8, 1.8 Hz, 1H; H6),
5.89 (dt, J=10.1, 3.2 Hz, 1H; H5), 11.7 ppm (brs, 1H; COOH);
13C NMR (75 MHz, CDCl3): d=14.0 (C12), 23.1 (C13), 22.6, 24.1, 29.5,
31.0 (C8–11), 31.7 (C4), 39.8 (C7), 49.0 (C1), 121.5, 125.6, 126.7 (C2, C5,
C6), 133.3 (C3), 181.9 ppm (s, COOH); IR (KBr): n˜ =3200–2600
(COOH), 1697 (C=O), 1440, 1263 cmÀ1; elemental analysis calcd (%) for
C14H22O2: C 75.63, H 9.97; found: C 75.31, H 9.90.
CH), 1622 (C=O), 1504 (NH2), 1362 cmÀ1
.
1-Isopropyl-4-methylamino-2,5-cyclohexadiene-1-carboxylic acid (2r):
Sticky crystals (68%); 1H NMR (300 MHz, D2O): d=0.81 (d, J=6.9 Hz,
12H; H6, H6’), 2.09 (sept, J=6.9 Hz, 2H; H5, H5’), 3.08–3.11 (m, 2H;
H4, H4’), 3.14–3.19 (m, 4H; H7, H7’), 5.75 (dd, J=10.2, 2.4 Hz, 2H; 3H,
H3’), 5.78 (dd, J=10.2 Hz, 3.4 Hz, 2H; H3’’, H3’’’), 5.98 ppm (dt, J=10.2,
1.7 Hz, 4H; H2, H2’, H2’’, H2’’’), COOH (not detected due to the zwit-
terionic form); 13C NMR (75 MHz, D2O): d=21.5, 21.8 (C6), 38.4, 38.6
(C5), 38.7, 38.9 (C7), 47.2, 47.8 (C4), 59.1, 59.7 (C1), 128.7, 129.0 (C3),
1-Hexyl-4-methyl-2,5-cyclohexadiene-1-carboxylic acid (2l): Yellow oil
(89%); Rf =0.31 (hexane/EtOAc, 4:1); 1H NMR (300 MHz, CDCl3): d=
Chem. Eur. J. 2009, 15, 12082 – 12091
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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12087

T. Linker et al.
137.1, 137.7 (C2), 186.9, 187.0 ppm (COOH); IR (KBr): n˜ =3010–2020
(COOH), 2870 (C=CH), 1622 (C=O), 1504 (NH2), 1361 cmÀ1
1-Benzyl-2-methyl-2,5-cyclohexadiene-1-carboxylic acid (2s): White solid
(87%); Rf =0.42 (hexane/EtOAc, 8:2); m.p. 1258C (lit. 125–1268C)[11b]
1,4-Diethyl-1,4-dihydro-1-naphthoic acid (7b): Yellow oil (88%); Rf =
0.32 (cyclohexane/EtOAc, 10:1); 1H NMR (300 MHz, CDCl3): d=0.82,
0.96 (2t, 6H; J=7.4 Hz, H12, H14), 1.82–1.93, 2.10–2.23 (2 m, 4H; 11H,
H13), 3.55 (d, J=2.0 Hz, 1H; H4), 5.86 (dd, J=10.3, 1.6 Hz, 1H; H2),
5.96 (dd, J=10.3, 2.1 Hz, 1H; H3), 7.30–7.48 (m, 4H; H5, H6, H7, H8),
11.43 ppm (brs, COOH); 13C NMR (75 MHz, CDCl3): d=9.7, 11.1 (C12,
C14), 31.1, 32.8 (C11, C13), 39.4 (C4), 52.1 (C1), 126.7, 127.2, 127.4,
127.6, 128.4, 131.3 (C2, C3, C5, C6, C7, C8), 135.0, 138.6 (C9, C10),
181.9 ppm (COOH); IR (film): n˜ =3800–2700 (COOH), 2970 (C=CH),
1688 (C=O), 1486, 1403, 1271 cmÀ1; elemental analysis calcd (%) for
C15H18O2: C 78.23, H 7.88; found: C 77.93, H 7.68.
.
;
1H NMR (300 MHz, CDCl3): d=1.98 (d, J=1.7 Hz, 3H; H8), 2.18
(ddddq, J=22.9, 3.6, 2.1, 1.7, 1.7 Hz, 1H; H4), 2.63 (ddddq, J=22.9, 3.6,
2.1, 1.7, 1.7 Hz, 1H; H4’), 3.21 (d, J=17.3 Hz, 1H; H7), 3.27 (d, J=
17.3 Hz, 1H; H7’), 5.67–5.75 (m, 2H; H3, H6), 5.95 (ddt, J=10.1, 3.6,
1.7 Hz, 1H; H5), 7.15–7.24 (m, 5H; H10, H11, H12), 10.2 ppm (brs, 1H;
COOH); 13C NMR (75 MHz, CDCl3): d=20.4 (C8), 27.0 (C4), 40.7 (C7),
53.3 (C1), 125.2, 126.6, 127.0, 127.5 (C3, C5, C6, C12), 127.9 (C11), 130.4
(C2), 131.0 (C10), 137.4 (C9), 180.4 ppm (COOH); IR (KBr): n˜ =3400–
1-Isopropyl-1,4-dihydro-1-naphthoic acid (6c): White solid (98%); Rf =
0.61 (hexane/EtOAc, 4:1); m.p. 938C; 1H NMR (300 MHz, CDCl3): d=
0.46, 0.94 (2d, 6H; J=6.8 Hz, Me), 2.56 (sept, J=6.8 Hz, 1H; H11),
3.21–3.45 (m, 2H; H4), 5.77 (ddd, J=10.1, 4.2, 1.2 Hz, 1H; H3), 6.13 (dt,
J=10.1, 1.3 Hz, 1H; H2), 7.30–7.50 (m, 4H; H5, H6, H7, H8), 11.21 ppm
(brs, COOH); 13C NMR (75 MHz, CDCl3): d=16.9, 18.3 (Me), 29.2
(C11), 36.7 (C4), 53.9 (C1), 1264.2, 125.5, 126.0, 126.3 126.4, 127.8 (C2,
C3, C5, C6, C7, C8), 134.1, 135.5 (C9, C10), 175.1 ppm (s, COOH); IR
(film): n˜ =3800–2750 (COOH), 2964 (C=CH), 1692 (C=O), 1489, 1453,
1263 cmÀ1; elemental analysis calcd (%) for C14H16O2: C 77.75, H 7.46;
found: C 77.46, H 7.44.
2400 (COOH), 2857 (C=CH), 1703 (C=O), 1453, 1398, 1274 cmÀ1
.
1-Allyl-2-methyl-2,5-cyclohexadiene-1-carboxylic acid (2t): White solid
(98%); Rf =0.27 (hexane/EtOAc, 4:1); m.p. 508C; 1H NMR (300 MHz,
CDCl3): d=1.73 (s, 3H; H10), 2.45–2.72 (m, 4H; H4, H7), 4.95–5.09 (m,
2H; H10), 5.58–5.72 (m, 3H; H3, H6, H9), 5.94 (ddt, J=10.0, 3.6, 1.8 Hz,
1H; H5), 11.6 ppm (brs, 1H; COOH); 13C NMR (75 MHz, CDCl3): d=
19.6 (C8), 26.9 (C4), 39.0 (C7), 51.2 (C1), 117.6 (C10), 123.8, 126.8, 126.9,
133.5 (C3, C5, C6, C9), 130.4 (C2), 180.4 ppm (COOH); IR (KBr): n˜ =
3400–2400 (COOH), 2976 (C=CH), 1686 (C=O), 1402, 1381, 1263 cmÀ1
;
elemental analysis calcd (%) for C11H14O2: C 74.13, H 7.92; found: C
73.94, H 7.74.
1,4-Disopropyl-1,4-dihydro-1-naphthoic acid (7c): White solid (97%);
Rf =0.25 (hexane/EtOAc, 10:1); m.p. 1488C; 1H NMR (300 MHz,
CDCl3): d=0.37, 0.49, 0,98, 1.05 (4d, J=6.7 Hz, each 3H; 4ꢂMe), 2.14
(dsept, J=1.3, 6.7 Hz, 1H; H12), 2.58 (sept, J=6.7 Hz, 1H; H11), 3.30
(d, J=1.3 Hz, 1H; H4), 5.88 (dd, J=9.4, 1.2 Hz, 1H; H2), 6.03 (dd, J=
9.4, 2.6 Hz, 1H; H3), 7.19–7.22 (m, 3H; H5, H6, H7), 7.57–7.62 (m, 1H;
H8); 10.42 ppm (brs, COOH); 13C NMR (75 MHz, CDCl3): d=17.4, 17.6,
18.8, 21.5 (4ꢂMe), 35.7, 38.0 (C11, C12), 44.6 (C4), 54.6 (C1), 124.3,
126.5, 127.2, 127.4, 127.9, 128.0 (C2, C3, C5, C6, C7, C8), 135.6, 139.2
(C9, C10), 181.3 ppm (s, COOH); IR (KBr): n˜ =3800–2700 (COOH),
2065 (C=CH), 1697 (C=O), 1487, 1385, 1267 cmÀ1; elemental analysis
calcd (%) for C17H22O2: C 79.03, H 8.58; found: C 79.38, H 8.64.
1-(2-Hydroxyethyl)-2-methyl-2,5-cyclohexadiene-1-carboxylic acid (2u):
White solid (88%); Rf =0.20 (hexane/EtOAc, 1:1); m.p. 112–1138C;
1H NMR (300 MHz, DMSO): d=1.63 (d, J=1.5 Hz, 3H; 8H), 1.79 (ddd,
J=13.4, 10.8, 5.4 Hz, 1H; H7), 1.98 (ddd, J=13.4, 10.8, 5.4 Hz, 1H; H7’),
2.58 (brs, 2H; H4), 3.15 (td, J=10.8, 5.4 Hz, 1H; H9), 3.25 (td, J=10.8,
5.4 Hz, 1H; H9’), 5.45 (dt, J=10.0, 1.9 Hz, 1H; H6), 5.53–5.58 (m, 1H;
H3), 5.81 (dtd, J=10.0, 3.2, 1.4 Hz, 1H; H5), 10.32 ppm (brs, 1H;
COOH); 13C NMR (75 MHz, DMSO): d=19.4 (C8), 26.4 (C4), 37.1 (C7),
49.2 (C1), 57.6 (C9), 122.1, 125.0, 127.8 (C3, C5, C6), 131.0 (C2),
180.4 ppm (COOH); IR (KBr): n˜ =3500–2400 (COOH), 1699 (C=O),
1407, 1256 cmÀ1; elemental analysis calcd (%) for C10H14O3: C 65.92, H
7.74; found: C 65.82, H 7.72.
1-Hexyl-1,4-dihydro-1-naphthoic acid (6d): White solid (87%); Rf =0.40
(hexane/EtOAc, 10:1); m.p. 598C; 1H NMR (300 MHz, CDCl3): d=0.86
(t, 3H; J=6.9 Hz, Me), 1.10–1.30 (m, 8H; 4 CH2), 1.90–2.00 (m, 1H;
11H), 2.10–2.20 (m, 1H; 11- Hꢃ), 3.42 (ddd, J=16.6, 2.2, 1.1 Hz, 1H; 4H),
3.51 (ddd, J=16.6, 2.2, 1.1 Hz, 1H; 4- Hꢃ), 5.75 (dt, J=10.2, 1.1 Hz, 1H;
2H), 6.16 (dd, J=10.2, 2.2 Hz, 1H; 3H), 7.12–7.30 (m, 3H; 5H, 6H, 7H),
7.37–7.42 (m, 1H; 8H); 10.31 ppm (brs, COOH); 13C NMR (75 MHz,
CDCl3): d=14.0 (Me), 22.5, 24.0, 29.5, 29.7, 31.7 (5ꢂCH2), 38.9 (C4),
51.0 (C1), 126.4, 126.5, 126.9, 127.0, 127.7, 128.5 (C2, C3, C5, C6, C7,
C8), 134.5, 134.2 (C9, C10), 181.3 ppm (s, COOH); IR (KBr): n˜ =3500–
2700 (COOH), 2925 (C=CH), 1689 (C=O), 1491, 1400, 1270 cmÀ1; ele-
mental analysis calcd (%) for C17H22O2: C 79.03, H 8.58; found: C 78.97,
H 8.59.
1-Methoxycarbonylmethyl-2-methyl-2,5-cyclohexadiene-1-carboxylic acid
(2v): Colorless oil (84%); Rf =0.18 (CH2Cl2/MeOH, 9:1); 1H NMR
(300 MHz, CDCl3): d=1.79 (d, J=1.6 Hz, 3H; H9), 2.67 (dm, J=
21.5 Hz, 1H; H4), 2.69 (d, J=15.0 Hz, 1H; H7), 2.74 (dm, J=21.5 Hz,
1H; H4’), 3.01 (d, J=15.0 Hz, 1H; H7’), 3.64 (s, 3H; OMe), 5.71–5.74
(m, 1H; H3), 5.84 (dt, J=10.0, 2.0 Hz, 1H; H6), 5.98 (ddt, J=10.0, 3.3,
1.2 Hz, 1H; H5), 11.5 ppm (brs, 1H; COOH); 13C NMR (75 MHz,
CDCl3): d=19.7 (C9), 26.7 (C4), 40.4 (C7), 49.4 (C1), 51.6 (OMe), 124.4,
126.0, 126.8 (C3, C5, C6), 130.0 (C2), 171.1 (COOMe), 178.8 ppm
(COOH); IR (KBr): n˜ =3040–2510 (COOH), 2819 (C=CH), 1706 (C=O),
1438, 1398, 1199 cmÀ1; elemental analysis calcd (%) for C11H14O4: C
62.85, H 6.71; found: C 63.03, H 6.71.
1,4-Dihexyl-1,4-dihydro-1-naphthoic acid (7d): Colorless oil (83%); Rf =
0.71 (hexane/EtOAc, 10:1); 1H NMR (300 MHz, CDCl3): d=0.83, 0.86
(2t, J=6.7 Hz, 6H; Me), 1.10–1.40 (m, 16H; 8ꢂCH2), 1.65–1.80 (m, 2H;
H12), 1.90–2.30 (m, 2H; H11), 3.39–3.48 (m, 1H; H4), 5.71 (dd, J=10.1,
0.8 Hz, 1H; H2), 6.14 (dd, J=10.1, 4.2 Hz, 1H; H3), 7.16–7.30 (m, 3H;
H5, H6, H7), 7.37–7.45 (m, 1H; H8); 11.10 ppm (brs, COOH); 13C NMR
(75 MHz, CDCl3): d=14.0, 14.1 (2ꢂMe), 22.5, 22.6, 23.9, 26.2, 29.4, 29.5,
31.5, 31.7 (5ꢂCH2), 38.7, 39.2 (C11, C12), 38.8 (C4), 50.8 (C1), 126.1,
127.0, 127.1, 127.2, 128.0, 131.0 (C2, C3, C5, C6, C7, C8), 134.4, 139.2
(C9, C10), 181.3 ppm (COOH); IR (film): n˜ =3300–2700 (COOH), 2925
(C=CH), 1696 (C=O), 1488, 1465, 1401, 1264 cmÀ1; elemental analysis
calcd (%) for C23H34O2: C 80.65, H 10.00.; found: C 80.58, H 10.14.
1-Methyl-1,4-dihydro-1-naphthoic acid (6a): White solid (96%); Rf =0.30
(cyclohexane/EtOAc, 10:1); m.p. 98–998C; 1H NMR (300 MHz, DMSO):
d=1.50 (s, 3H; H11), 3.38 (s, 2H; H4), 5.78 (dd, J=9.7, 1.2 Hz, 1H; H2),
5.96 (dt, J=9.7, 2.8 Hz, 1H; H3), 7.14–7.30 (m, 4H; H5, H6, H7, H8),
12.40 ppm (brs, COOH); 13C NMR (75 MHz, DMSO): d=28.1 (C11),
30.1 (C4), 47.4 (C1), 125.2, 127.1, 127.4, 129.2, 130.4, 131.1 (C2, C3, C5,
C6, C7, C8), 133.9, 138.7 (C9, C10), 176.7 ppm (s, COOH); IR (KBr): n˜ =
3800–2700 (COOH), 3029 (C=CH), 1699 (C=O), 1441, 1408, 1272 cmÀ1
;
elemental analysis calcd (%) for C12H12O2: C 76.57, H 6.43; found: C
76.30, H 6.48.
1-Ethyl-1,4-dihydro-1-naphthoic acid (6b): Yellow oil (85%); Rf =0.34
(cyclohexane/EtOAc, 10:1); 1H NMR (300 MHz, CDCl3): d=0.70 (t, J=
7.5 Hz, 3H; H12), 2.07 (dt, J=13.2, 7.5 Hz, 1H; H11), 2.25 (dt, J=13.2,
7.5 Hz, 1H; H11’), 3.47–3.51 (2H; H4), 5.75 (dd, J=12.0, 4.1 Hz, 1H;
H3), 6.22 (dd, J=12.0, 2.8 Hz, 1H; H2), 7.24–7.41 (m, 4H; H5, H6, H7,
H8), 11.40 ppm (brs, COOH); 13C NMR (75 MHz, CDCl3): d=8.4 (C12),
29.7 (C4), 31.6 (C11), 51.4 (C1), 126.4, 126.6, 126.9, 127.1, 127.5, 128.5
(C2, C3, C5, C6, C7, C8), 134.1, 134.4 (2 s, C9, C10), 181.3 ppm (s,
COOH); IR (film): n˜ =3800–2700 (COOH), 3028 (C=CH), 1692 (C=O),
1454, 1401, 1263 cmÀ1; elemental analysis calcd (%) for C13H14O2: C
77.20, H 6.98; found: C 76.97, H 7.17.
1-Benzyl-1,4-dihydro-1-naphthoic acid (6e): White solid (92%); Rf =0.25
(hexane/EtOAc, 4:1); m.p. 1738C; 1H NMR (300 MHz, DMSO): d=2.67
(d, J=21.0 Hz, 1H; H11), 3.20 (d, J=21.0 Hz, 1H; H11’), 3.34–3.38 (m,
2H; H4), 5.83 (t, J=9.8, Hz, 1H; H2), 6.05 (dt, J=9.8, 2.2 Hz, 1H; H3),
6.89–7.28 (m, 8H; H5, H6, H7, Ar), 7.54–7.56 (m, 1H; H8); 9.05 ppm
(brs, COOH); 13C NMR (75 MHz, DMSO): d=29.6 (C11), 45.8 (C4),
52.7 (C1), 126.3, 126.5, 126.7, 126.9, 127.4, 128.0, 128.2, 128.4, 129.0 (C2,
C3, C5, C6, C7, C8, Ar), 135.2, 136.2, 137.9 (3 s, C9, C10, Ar), 176.3 ppm
(COOH); IR (KBr): n˜ =3500–2700 (COOH), 3026 (C=CH), 1707 (C=O),
12088
www.chemeurj.org
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 12082 – 12091

Regioselective Arene Functionalization
FULL PAPER
1494, 1451, 1274 cmÀ1; elemental analysis calcd (%) for C18H16O2: C
81.79, H 6.10; found: C 81.51, 6.26.
2.23 (s, 3H; H9), 2.52 (q, J=7.6 Hz, 2H; H7), 6.85–6.6.97 (m, 3H; Ar),
7.08 ppm (t, J=7.9 Hz, 1H; H5); 13C NMR (75 MHz, CDCl3): d=17.3
(C8), 23.1 (C9), 30.5 (C7), 126.5, 128.0, 129.9, 130.4 (Ar), 139.5 (C3),
1-Allyl-1,4-dihydro-1-naphthoic acid (6 f): White solid (90%); Rf =0.38
145.9 ppm (C1); IR (film): n˜ =2962, 2929, 1610, 1456 cmÀ1
.
1
(hexane/EtOAc, 4:1); m.p. 2198C; H NMR (300 MHz, CDCl3): d=2.80–
3.00 (m, 2H; H11), 3.43 (ddd, J=22.0, 3.6, 1.7 Hz, 1H; H4), 3.53 (ddd,
J=22.0, 3.6, 1.7 Hz, 1H; H4’), 5.00–5.05 (m, 2H; H13), 5.70–5.85 (m,
1H; H12), 5.83 (dt, J=10.1, 1.7 Hz, 1H; H2), 6.20 (dt, J=10.1, 3.6 Hz,
1H; H3), 7.19–7.29 (m, 3H; H5, H6, H7), 7.40–7.47 (m, 1H; H8);
10.10 ppm (brs, COOH); 13C NMR (75 MHz, CDCl3): d=29.7 (C11),
43.4 (C4), 50.6 (C1), 118.3 (C13), 126.2, 126.5, 127.0, 127.1, 127.4, 128.0,
(C2, C3, C5, C6, C7, C8), 133.2 (C12), 134.1, 134.2 (C9, C10), 180.7 ppm
(COOH); IR (KBr): n˜ =3500–2700 (COOH), 3028 (C=CH), 1692 (C=O),
1488, 1442, 1268 cmÀ1; elemental analysis calcd (%) for C14H14O2: C
78.48, H 6.59; found: C 78.12, H 6.55.
1-Ethyl-4-methylbenzene (3 f): Colorless liquid (87%); n2D0 =1.4956 (lit.
1.4959)[20] 1H NMR (300 MHz, CDCl3): d=1.13 (t, J=7.0 Hz, 3H; H8),
;
2.15 (s, 3H; H9), 3.40 (q, J=7.0 Hz, 2H; H7), 6.98–7.08 ppm (m, 4H;
Ar); 13C NMR (75 MHz, CDCl3): d=16.9 (C8), 21.4 (C9), 29.1 (C7),
127.4, 131.2 (C2, C3), 138.1 (C4), 141.2 ppm (C1); IR (film): n˜ =2923,
1495, 1466, 1384 cmÀ1
.
1-Isopropyl-2-methylbenzene (3g): Colorless liquid (98%); n2D0 =1.5007
(lit. 1.5006)[20] 1H NMR (300 MHz, CDCl3): d=1.24 (d, J=7.0 Hz, 6H;
;
H8), 2.35 (s, 3H; H9), 3.15 (sept, J=7.0 Hz, 1H; H7), 7.05–7.29 ppm (m,
4H; Ar); 13C NMR (75 MHz, CDCl3): d=21.1 (C8), 24.9 (C9), 30.7 (C7),
124.8, 125.8, 126.1, 129.7 (Ar), 134.8 (C2), 147.1 ppm (C1); IR (film): n˜ =
1-(2-Hydroxyethyl)-1,4-dihydro-1-naphthoic acid (6g): White solid
(83%); Rf =0.51 (hexane/EtOAc, 4:1); m.p. 1288C; 1H NMR (300 MHz,
DMSO): d=2.05–2.35 (m, 2H; H11), 2.90–2.94 (m, 1H; H12), 3.23–3.27
(m, 1H; H12’), 3.30–3.35 (m, 2H; H4), 5.72 (dt, J=10.1, 1.3 Hz, 1H;
H2), 6.04 (dd, J=10.1, 3.6 Hz, 1H; H3), 7.15–7.22 (m, 3H; H5, H6, H7),
7.25–7.35 (m, 1H; H8); 12.55 ppm (brs, COOH); 13C NMR (75 MHz,
DMSO): d=29.1 (C11), 41.6 (C4), 48.7 (C1), 57.5 (C12), 125.0, 126.2,
126.4, 126.5, 128.0, 128.3 (C2, C3, C5, C6, C7, C8), 133.6, 135.4 (C9, C10),
175.3 ppm (COOH); IR (KBr): n=3600–3200 (COOH), 3026 (C=CH),
1698 (C=O), 1490, 1412, 1270 cmÀ1; elemental analysis calcd (%) for
C13H14O3: C 71.54, H 6.47; found: C 71.45, H 6.60.
2961, 1488, 1455, 1264 cmÀ1
.
1-Isopropyl-3-methylbenzene (3h): Colorless liquid (35%); n2D0 =1.4928
(lit. 1.4930)[20] 1H NMR (300 MHz, CDCl3): d=1.24 (d, J=7.0 Hz, 6H;
;
H8), 2.31 (s, 3H; H9), 2.88 (sept, J=7.0 Hz, 1H; H7), 7.00–7.40 ppm (m,
4H; Ar); 13C NMR (75 MHz, CDCl3): d=23.2 (C8), 25.0 (C9), 35.8 (C7),
125.1, 128.2, 128.9, 130.1 (Ar), 139.5 (C3), 150.5 ppm (C1); IR (film): n˜ =
2958, 1490, 1461, 1362, 1088 cmÀ1
.
1-Isopropyl-4-methylbenzene (3i): Colorless liquid (93%); n2D0 =1.4989
(lit. 1.4909)[20] 1H NMR (300 MHz, CDCl3): d=1.14 (d, J=7.0 Hz, 6H;
;
H8), 2.21 (s, 3H; H9), 2.77 (sept, J=7.0 Hz, 1H; H7), 7.05 ppm (s, 4H;
2H, H3); 13C NMR (75 MHz, CDCl3): d=21.4 (C8), 24.6 (C9), 34.1 (C7),
126.7 (C3), 129.0 (C2), 135.6 (C4), 146.3 ppm (C1); IR (film): n˜ =2959,
1-Methoxycarbonylmethyl-1,4-dihydro-1-naphthoic acid (6h): White solid
(84%); Rf =0.41 (hexane/EtOAc, 4:1); m.p. 848C; 1H NMR (300 MHz,
DMSO): d=2.78 (d, J=16.5 Hz, 1H; H11), 3.14 (d, J=16.5 Hz, 1H;
H11’), 3.38 (brs, 2H; H4), 3.50 (s, 3H; OMe), 6.06 (brs, 2H; H2, H3),
7.15–7.22 (m, 3H; H5, H6, H7), 7.32–7.40 (m, 1H; H8); 12.21 ppm (brs,
COOH); 13C NMR (75 MHz, DMSO): d=29.1 (C11), 43.9 (C4), 48.1
(C1), 51.1 (OMe), 125.3, 126.0, 126.3, 126.8, 127.7, 128.3 (C2, C3, C5, C6,
C7, C8), 134.0, 135.1 (C9, C10), 170.6 (COOMe), 175.3 ppm (COOH);
IR (KBr): n˜ =3600–3200 (COOH), 2952 (C=CH), 1733, 1698 (C=O),
1489, 1436, 1271 cmÀ1; elemental analysis calcd (%) for C14H14O4: C
68.28, H 5.73; found: C 68.21, H 5.64.
1515, 1463, 814 cmÀ1
.
1Hexyl-2-methylbenzene (3j): Colorless liquid (90%); n2D0 =1.4920 (lit.
1
1.4923)[21]; H NMR (300 MHz, CDCl3): d=1.03 (t, J=6.8 Hz, 3H; H12),
1.36–1.55 (m, 6H; H9–11), 1.65–1.75 (m, 2H; H8), 2.43 (s, 3H; H13),
2.71 (t, J=7.9 Hz, 2H; H7), 7.20–7.28 ppm (m, 4H; Ar); 13C NMR
(75 MHz, CDCl3): d=14.1 (C12), 19.2 (C13), 22.7, 29.4, 30.3, 31.8, 33.4
(C7–11), 125.7, 125.8, 128.8, 130.1 (Ar), 135.7 (C2), 141.0 ppm (C1); IR
(film): n˜ =2955, 2931, 1493, 1460, 1378 cmÀ1; elemental analysis calcd
(%) for C13H20: C 88.57, H 11.43; found: C 88.38, H 11.33.
General procedure for the decarbonylation reactions: The cyclohexa-
dienes 2 or dihydronaphthalenes 6 or 7 (5.0 mmol) were dissolved in dry
CH2Cl2 (20 mL) and chlorosulfonic acid (60 mg, 0.5 mmol) was added at
08C, which resulted in the evolution of CO. After 10 min at this tempera-
ture TLC showed complete conversion, and the solution was neutralized
with solid K2CO3 (275 mg, 2.0 mmol). The mixture was filtered over
Celite, and the pad was washed with CH2Cl2 (4ꢂ20 mL). The filtrate was
concentrated under reduced pressure, and the residue was purified by
column chromatography.
1-Hexyl-3-methylbenzene (3k): Colorless liquid (39%); n2D0 =1.4879 (lit.
1
1.4885)[21]; H NMR (300 MHz, CDCl3): d=0.97 (t, J=6.5 Hz, 3H; H12),
1.36–1.47 (m, 6H; H9–11), 1.65–1.75 (m, 2H; H8), 2.43 (s, 3H; H13),
2.68 (t, J=7.8 Hz, 2H; H7), 7.05–7.12 (m, 3H; H2, H4, H6), 7.26 ppm (t,
J=7.8 Hz, 1H; H5); 13C NMR (75 MHz, CDCl3): d=14.1 (C12), 21.4
(C13), 22.6, 29.1, 31.5, 31.8, 35.9 (C7–11), 125.4, 126.3, 128.1, 129.2 (Ar),
137.7 (C3), 142.9 ppm (C1); IR (film): n˜ =2955, 2924, 1488, 1456,
1377 cmÀ1; elemental analysis calcd (%) for C13H20: C 88.57, H 11.43;
found: C 88.82, H 11.71.
1,2-Dimethylbenzene (3a): Colorless liquid (95%); n2D0 =1.5053 (lit.
1-Hexyl-4-methylbenzene (3l): Colorless liquid (88%); n2D0 =1.4875 (lit.
1.5055)[20]
;
1H NMR (300 MHz, CDCl3): d=2.19 (s, 6H; Me), 7.01–
1.48854)[21] 1H NMR (300 MHz, CDCl3): d=0.99 (t, J=6.6 Hz, 3H;
;
7.08 ppm (m, 4H; Ar); 13C NMR (75 MHz, CDCl3): d=19.6 (Me), 126.1
(C3), 129.9 (C2), 136.4 ppm (C1); IR (film): n˜ =3015, 2969, 1601,
H12), 1.35–1.49 (m, 6H; H9–11), 1.65–1.75 (m, 2H; H8), 2.41 (s, 3H;
H13), 2.66 (t, J=7.6 Hz, 2H; H7), 7.12 ppm (s, 4H; H2, H3); 13C NMR
(75 MHz, CDCl3): d=14.1 (C12), 20.9 (C13), 22.6, 29.0, 31.6, 31.8, 35.6
(C7–11), 128.3, 128.9 (C2, C3), 134.9 (C4), 139.9 ppm (C1); IR (film): n˜ =
2955, 2924, 1514, 1456, 1378 cmÀ1; elemental analysis calcd (%) for
C13H20: C 88.57, H 11.43; found: C 88.32, H 11.66.
1466 cmÀ1
.
1,3-Dimethylbenzene (3b): Colorless liquid (32%); n2D0 =1.4974 (lit.
1.4972)[20] 1H NMR (300 MHz, CDCl3): d=2.23 (s, 6H; Me), 6.76–6.99
;
(m, 3H; 2H, 4H, 6H), 7.06 ppm (t, J=7.5 Hz, 1H; 5H); 13C NMR
(75 MHz, CDCl3): d=20.3 (q, Me), 125.0 (d, C4, C6), 127.1 (d, C2), 128.9
3-Fluoro-1-methylbenzene (3m): Colorless liquid (82%); n2D0 =1.4707
(d, C5), 136.7 ppm (s, C1, C3); IR (film): n˜ =3017, 2920, 1613, 1491 cmÀ1
.
(lit. 1.4691)[20] 1H NMR (300 MHz, CDCl3): d=2.35 (s, 3H; H7), 6.82–
;
1,4-Dimethylbenzene (3c): Colorless liquid (81%); n2D0 =1.4960 (lit.
1.4958)[20] 1H NMR (300 MHz, CDCl3): d=2.48 (s, 6H; Me), 7.17 ppm
(s, 4H; H2); 13C NMR (75 MHz, CDCl3): d=22.6 (Me), 130.6 (C2),
136.3 ppm (C1); IR (film): n˜ =3045, 2921, 1516, 1452 cmÀ1
1-Ethyl-2-methylbenzene (3d): Colorless liquid (86%); n2D0 =1.5048 (lit.
1.5046)[20] 1H NMR (300 MHz, CDCl3): d=1.48 (t, J=7.8 Hz, 3H; 8H),
6.88 (m, 2H; H2, H6), 6.93 (d, J=7.7 Hz, 1H; H4), 7.19 ppm (dd, J=
7.7 Hz, 1H; H5); 13C NMR (75 MHz, CDCl3): d=21.2 (q, JC,F =2 Hz;
C7), 112.3 (d, JC,F =21 Hz; C6), 116.0 (d, JC,F =21 Hz; C2), 124.8, (d,
;
.
J
C,F =3 Hz; C4), 129.6 (d, JC,F =8 Hz; C5), 140.6 (s, JC,F =8 Hz; C3),
163.1 ppm (s, JC,F =243 Hz; C1); IR (film): n˜ =3041, 2924, 1518, 1489,
1251 cmÀ1
1-Ethyl-3-fluorobenzene (3n): Colorless liquid (90%); n2D0 =1.4557 (lit.
1.4556)[22] 1H NMR (300 MHz, CDCl3): d=1.22 (t, J=7.2 Hz, 3H; H8),
;
.
2.56 (s, 3H; 9H), 2.87 (q, J=7.8 Hz, 2H; 7H), 7.09–7.26 ppm (m, 4H;
Ar); 13C NMR (75 MHz, CDCl3): d=16.4 (C8), 23.8 (C9), 28.9 (C7),
125.8 (C5), 126. 0 (C4), 128.8 (C6), 129.7 (C3), 135.1 (C2), 142.7 ppm
;
2.63 (q, J=7.2 Hz, 2H; H7), 6.83–6.90 (m, 2H; H2, H6), 6.95 (d, J=
7.5 Hz, 1H; H4), 7.21 ppm (dd, J=7.5 Hz, 1H; H5); 13C NMR (75 MHz,
CDCl3): d=15.2 (C8), 28.6 (C7), 112.3 (d, JC,F =21 Hz, C6), 114.7 (d,
(C1); IR (film): n˜ =3017, 2934, 1598, 1459 cmÀ1
.
1-Ethyl-3-methylbenzene (3e): Colorless liquid (38%); n2D0 =1.49595 (lit.
1.4966)[20] 1H NMR (300 MHz, CDCl3): d=1.14 (t, J=7.6 Hz, 3H; H8),
;
JC,F =21 Hz, C2), 123.5 (d, JC,F =3 Hz, C4), 129.6 (d, JC,F =8 Hz, C5),
Chem. Eur. J. 2009, 15, 12082 – 12091
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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12089

T. Linker et al.
140.7 (s, JC,F =15.1 Hz, C3), 163.4 ppm (s, JC,F =732 Hz, C1); IR (film):
n˜ =3039, 2968, 1589, 1256, 1139 cmÀ1
3-Fluoro-1-isopropylbenzene (3o): Colorless liquid (85%); n2D0 =1.4659
(lit. 1.4690)[23] 1H NMR (300 MHz, CDCl3): d=1.18 (d, J=7.1 Hz, 6H;
IR (film): n˜ =3036, 2982, 1762 (C=O), 1450, 1279 cmÀ1; elemental analy-
sis calcd (%) for C11H16O2: C 73.30, H 895; found: C 72.96, H 8.94.
.
Lactone 4k: Colorless oil (53%); Rf =0.43 (hexane/EtOAc, 4:1);
1H NMR (300 MHz, CDCl3): d=0.85 (t, J=6.8 Hz, 3H; H12), 1.25–1.45
(m, 8H; H8–11), 1.46 (s, 3H; H13), 1.60–1.80 (m, 2H; H7), 1.84 (d, J=
10.9 Hz, 1H; H2), 1.93 (d, J=10.9 Hz, 1H; H2’), 2.40–2.43 (m, 2H; H4),
5.68 (dt, J=9.4, 1.5 Hz, 1H; H6), 5.74 ppm (dt, J=9.4, 2.6 Hz, 1H; H5);
13C NMR (75 MHz, CDCl3): d=13.9 (C12), 22.4, 24.5, 29.5, 31.5, 32.0
(C7, C8, C9, C10, C11), 25.1 (C13), 37.5, 43.2 (C2, C4), 48.2 (C1), 81.2
(C3), 127.5, 132.0 (C5, C6), 177.7 ppm (COO); IR (film): n˜ =3034, 2928,
1769 (C=O), 1455, 1275 cmÀ1; elemental analysis calcd (%) for C14H22O2:
C 75.63, H 9.97; found: C 75.65, H 10.09.
;
H8), 2.79 (sept, J=7.1 Hz, 1H; H7), 6.80–6.90 (m, 2H; H2, H6), 6.95 (d,
J=7.6 Hz, 1H; H4), 7.21 ppm (dd, J=7.6 Hz, 1H; H5); 13C NMR
(75 MHz, CDCl3): d=21.6 (C8), 33.6 (C7), 112.6 (d, JC,F =21 Hz, C6),
115.4 (d, JC,F =21 Hz, C2), 123.9 (d, JC,F =3 Hz, C4), 130.1 (d, JC,F =8 Hz,
C5), 140.8 (s, JC,F =15.1 Hz, C3), 163.2 ppm (s, JC,F =622 Hz, C1); IR
(film): n˜ =3023, 2959, 1563, 1263, 1137 cmÀ1
4-Methylbenzylamine (3p): Colorless liquid (87%); n2D0 =1.5376 (lit.
1.5345)[24] 1H NMR (300 MHz, CDCl3): d=1.52 (brs, 2H; NH2), 2.33 (s,
.
;
Lactone 4u: Colorless oil (92%); Rf =0.24 (hexane/EtOAc, 4:1);
1H NMR (300 MHz, CDCl3): d=1.68–1.70 (m, 3H; H9), 2.09 (ddd, J=
13.2, 7.2, 5.0 Hz, 1H; H7), 2.52 (dt, J=13.2, 8.5 Hz, 1H; H7’), 2.60–2.80
(m, 1H; H4), 4.30–4.40 (m, 1H; H8), 5.59 (dt, J=9.9, 2.1 Hz, 1H; H6),
5.65–5.70 (m, 1H; H3), 5.90 ppm (dtd, J=9.9, 3.5, 1.3 Hz, 1H; H5);
13C NMR (75 MHz, CDCl3): d=19.2 (C9), 26.6 (C7), 34.7 (C4), 48.3
(C1), 65.4 (C8), 124.0, 124.6, 126.2 (C3, C5, C6), 129. 4 (C2), 177.8 ppm
(COO); IR (film): n˜ =2973, 2918, 1762 (C=O), 1450, 1152 cmÀ1; elemen-
tal analysis calcd (%) for C10H12O2: C 73.15, H 7.37; found: C 72.89, H
7.31.
3H; H6), 3.82 (s, 2H; H5), 7.14 (d, J=7.9 Hz, 2H; H2), 7.19 ppm (d, J=
7.9 Hz, 2H; H3); 13C NMR (75 MHz, CDCl3): d=21.0 (C6), 46.2 (C5),
126.9 (C3), 129.1 (C2), 136.1 (C1), 140.5 ppm (C4); IR (film): n˜ =3093,
2922, 1514, 1453, 967 cmÀ1
.
4-Ethylbenzylamine (3q): Colorless liquid (77%); n2D0 =1.5298 (lit.
1.5314)[25] 1H NMR (300 MHz, CDCl3): d=1.23 (t, J=7.6 Hz, 3H; 7-H),
;
1.47 (brs, 2H; NH2), 2.63 (q, J=7.6 Hz, 2H; H6), 3.83 (s, 2H; H5), 7.17
(d, J=7.9 Hz, 2H; H2), 7.22 ppm (d, J=7.9 Hz, 2H; H3); 13C NMR
(75 MHz, CDCl3): d=16.1 (C7), 29.1 (C6), 45.3 (C5), 127.2 (C2), 131.5
(C3), 138.9 (C1), 141.8 ppm (C4); IR (film): n˜ =3280, 2931, 1578, 1340,
813 cmÀ1
4-Isopropylbenzylamine (3r): Colorless liquid (76%); n2D0 =1.5195 (lit.
1.5182)[26] 1H NMR (300 MHz, CDCl3): d=1.15 (d, J=6.9 Hz, 6H; H7),
.
1-Methylnaphthalene (9a): Colorless liquid (90%); Rf =0.81 (cyclohex-
ane/EtOAc, 10:1); n2D0 =1.6145 (lit. 1.6149)[29]
;
1H NMR (300 MHz,
CDCl3): d=2.61 (s, 3H; H11), 7.24–7.90 ppm (m, 7H; Ar); 13C NMR
(75 MHz, CDCl3): d=19.8 (C11), 124.6, 125.1, 125.8, 126.1, 126.7, 127.0,
128.9 (Ar), 133.0, 134.0, 137.7 ppm (Ar); IR (film): n=3038, 1462,
1164 cmÀ1; elemental analysis calcd (%) for C11H10: C 92.91, H 7.09;
found: C 92.64, H 7.01.
;
2.82 (sept, J=6.9 Hz, 1H; H6), 3.76 (s, 2H; H5), 7.11–7.15 ppm (m, 4H;
H2, H3); 13C NMR (75 MHz, CDCl3): d=25.2 (C7), 35.8 (C6), 46.2 (C5),
127.2, 128.3 (C2, C3), 133.8 (C1), 140.3 ppm (C4); IR (film): n˜ =3285,
2965, 1591, 1317, 813 cmÀ1
.
1-Ethylnaphthalene (9b): Colorless liquid (95%); Rf =0.73 (hexane/
2-Benzyl-toluene (3s): Colorless liquid (95%); n2D0 =1.5756 (lit.
EtOAc, 4:1); n2D0 =1.6060 (lit. 1.6065)[29] 1H NMR (300 MHz, CDCl3):
;
1
1.5752)[27]; H NMR (300 MHz, CDCl3): d=2.23 (s, 3H; Me), 4.03 (s, 2H;
d=1.51 (t, J=6.8 Hz, 3H; H12), 3.22 (q J=6.8 Hz, 2H; H11), 7.34–
8.20 ppm (m, 7H; Ar); 13C NMR (75 MHz, CDCl3): d=15.0 (C12), 25.8
(C11), 123.4, 124.6, 124.8, 125.1, 126.4, 126.7, 128.1 (Ar), 133.3, 138.3,
140.2 ppm (Ar); IR (film): n˜ =3046, 2964 (C=CH), 1453, 1164 cmÀ1; ele-
mental analysis calcd (%) for C12H12: C 92.26, H 7.74; found: C 91.97, H
8.00.
CH2), 7.11–7.35 ppm (m, 9H; Ar); 13C NMR (75 MHz, CDCl3): d=20.1
(Me), 39.9 (CH2), 126.3, 126.4, 126.9, 128.8, 129.2, 130.4, 130.7 (Ar),
137.1, 139.4, 140.8 ppm (Ar); IR (film): n˜ =3061, 2922, 1601, 1492,
742 cmÀ1
.
2-Methoxycarbonyltoluene (3v): Colorless liquid (87%); nn2D0 =1.5069
1
(lit. 1.5085)[28]; H NMR (300 MHz, CDCl3): d=2.31 (s, 3H; Me), 3.64 (s,
1-Isopropylnaphthalene (9c): Colorless liquid (98%); Rf =0.87 (hexane/
2H; CH2), 3.69 (s, 3H; OMe), 7.15–7.20 ppm (m, 4H; Ar); 13C NMR
(75 MHz, CDCl3): d=19.5 (Me), 39.0 (CH2), 51.9 (OMe), 126.1, 127.4,
130.1, 130.3 (Ar), 132.7, 136.8 (Ar), 171.9 ppm (COOMe); IR (film): n˜ =
EtOAc, 4:1); n2D0 =1.5945 (lit. 1.5952)[30] 1H NMR (300 MHz, CDCl3):
;
d=1.55 (d, J=6.8 Hz, 6H; H12), 3.89 (sept, J=6.8 Hz, 1H; H11), 7.52–
8.30 ppm (m, 7H; Ar); 13C NMR (75 MHz, CDCl3): d=23.5 (C12), 28.5
(C11), 121.7, 123.3, 125.2, 125.6, 125.7, 126.3, 128.9 (Ar), 131.4, 134.0,
144.6 ppm (Ar); IR (film): n˜ =3047, 2961 (C=CH), 1461, 1181 cmÀ1; ele-
mental analysis calcd (%) for C13H14: C 91.71, H 8.23; found: C 91.48, H
8.21.
3021, 2952, 1737 (C=O), 1435, 1257, 1012 cmÀ1
.
Lactone 4b: White solid (53%); Rf =0.51 (hexane/EtOAc, 8:2); m.p.
478C; 1H NMR (300 MHz, CDCl3): d=1.33 (s, 3H; H7), 1.48 (s, 3H;
H8), 1.88 (d, J=10.3 Hz, 1H; H2), 1.93 (d, J=10.3 Hz, 1H; H2’), 2.31–
2.36 (m, 2H; H4), 5.66–5.78 ppm (m, 2H; H5, H6); 13C NMR (75 MHz,
CDCl3): d=18.7 (C7), 25.6 (C8), 37.8 (C2), 44.6 (C1), 46.5 (C4), 81.7
(C3), 127.8 (C5), 133.1 (C6), 178.9 ppm (COO); IR (KBr): n˜ =3036,
2935, 1762 (C=O), 1450, 1279 cmÀ1; elemental analysis calcd (%) for
C9H12O2: C 71.03, H 7.95; found: C 71.26, H 7.74.
1-Hexylnaphthalene (9d): Colorless liquid (87%); Rf =0.78 (hexane/
EtOAc 10:1); n2D0 =1.5620 (lit. 1.5626)[29] 1H NMR (300 MHz, CDCl3):
;
d=1.01 (t, J=6.7 Hz, 3H; H16), 1.45–1.60 (m, 6H; H13, H14, H15), 1.90
(quint, J=7.8 Hz, 2H; H12), 3.21 (t, J=7.8 Hz, 2H; H11), 7.44–8.20 ppm
(m, 7H; Ar); 13C NMR (75 MHz, CDCl3): d=14.1 (C16), 22.7 (C11),
29.5, 30.8, 31.8, 33.1 (C12, C13, C14, C15), 123.9, 125.3, 125.5, 125.6,
125,8, 126.4, 128.7 (Ar), 132.0, 133.4, 139.0 ppm (Ar); IR (film): n˜ =3042,
1460, 1180 cmÀ1; elemental analysis calcd (%) for C16H20: C 90.51, H
9.49; found: C 90.32, H 9.42.
Lactone 4e: Colorless oil (52%); Rf =0.52 (hexane/EtOAc, 8:2);
1H NMR (300 MHz, CDCl3): d=0.95 (t, J=7.4 Hz, 3H; H8), 1.43 (s, 3H;
H9), 1.66 (dq, J=15.0, 7.4 Hz, H7), 1.74 (dq, J=15.0, 7.4 Hz, 1H; H7’),
1.79 (dd, J=10.9, 1.8 Hz, 1H; H2), 1.89 (dd, J=10.9, 1.8 Hz, 1H; H2’),
2.26 (dt, J=18.9, 2.8 Hz, 1H; H4), 2.31 (dt, J=18.9, 2.8 Hz, 1H; H4’),
5.65 (dtt, J=9.4, 1.8, 1.8 Hz, 1H; H6), 5.71 ppm (dt, J=9.4, 2.8 Hz, 1H;
H5); 13C NMR (75 MHz, CDCl3): d=10.4 (C8), 26.5 (C7), 26.9 (C9), 39.2
(C2), 44.3 (C1), 50.4 (C4), 83.0 (C3), 129.5, 133.3 (C5, C6), 179.5 ppm
(COO); IR (film): n˜ =3035, 2968, 1771 (C=O), 1462, 1272 cmÀ1; elemen-
tal analysis calcd (%) for C10H14O2: C 72.26, H 8.49; found: C 71.95, H
8.41.
1-Benzylnaphthalene (9e): Colorless oil (91%); Rf =0.53 (hexane/
EtOAc, 10:1); 1H NMR (300 MHz, CDCl3): d=4.52 (s, 2H; H11), 7.20–
8.00 ppm (m, 12H; Ar); 13C NMR (75 MHz, CDCl3): d=39.5 (C11),
124.7, 126.0, 126.4, 126.5, 127.6, 127.8, 128.7, 128.9, 129.1, 129.2 (Ar),
132.6, 134.4, 137.1, 141.1 ppm (Ar); IR (film): n˜ =3022, 2905 (C=CH),
1493, 1029, 790 cmÀ1; elemental analysis calcd (%) for C17H14: C 93.54, H
6.46; found: C 93.17, H 6.44.
Lactone 4h: Yellow oil (49%); Rf =0.51 (hexane/EtOAc, 8:2); 1H NMR
(300 MHz, CDCl3): d=0.95 (d, J=6.8 Hz, 6H; H8), 1.48 (s, 3H; H9),
1.71 (d, J=10.8 Hz, 1H; H2), 1.98 (d, J=10.8 Hz, 1H; H’), 2.16 (sept.,
J=6.8 Hz, 1H; H7), 2.33 (brs, 2H; H4), 5.76 ppm (brs, 2H; H5, H6);
13C NMR (75 MHz, CDCl3): d=18.1 (C8), 25.7 (C9), 29.4 (C7), 38.2, 39.1
(C2, C4), 53.1 (C1), 81.3 (C3), 128.2 (C5), 132.3 (C6), 177.6 ppm (COO);
Lactone 9g: Colorless oil (98%); Rf =0.40 (hexane/EtOAc, 10:1);
1H NMR (300 MHz, CDCl3): d=2.49 (ddd, J=13.0, 7.1, 5.7 Hz, 1H;
H11), 2.68 (dt, J=13.0, 7.7 Hz, 1H; H11’), 3.44 (ddd, J=21.8, 3.7, 2.2 Hz,
1H; H4), 3.56 (ddd, J=21.8, 3.7, 2.2 Hz, 1H; H4’), 4.48–4.55 (m, 2H;
H12), 5.88 (dt, J=9.9, 2.2 Hz, 1H; H2), 6.21 (dt, J=9.9, 3.7 Hz, 1H; H3),
7.16–7.28 ppm (m, 4H; H5, H6, H7, H8); 13C NMR (75 MHz, CDCl3):
12090
www.chemeurj.org
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 12082 – 12091

Regioselective Arene Functionalization
FULL PAPER
d=29.8 (C11), 39.4 (C4), 48.4 (C1), 65.5 (C12), 125.7, 126.1, 127.0, 127.4,
127.5, 128.8 (C2, C3, C5, C6, C7, C8), 134.2, 134.9 (C9, C10), 178.5 ppm
(COO); IR (film): n˜ =2915 (C=CH), 1761 (C=O), 1488, 1209 cmÀ1; ele-
mental analysis calcd (%) for C13H12O2: C 77.98, H 6.04; found: C 77.58,
H 5.87.
34, 624–629; c) B. D. Sherry, A. Fꢀrstner, Acc. Chem. Res. 2008, 41,
1500–1531.
[6] G. Cahiez, L. Foulgoc, A. Moyeux, Angew. Chem. 2009, 121, 3013–
3016; Angew. Chem. Int. Ed. 2009, 48, 2969–2972.
[7] Review: L. J. Gooßen, N. Rodriguez, K. Gooßen, Angew. Chem.
2008, 120, 3144–3164; Angew. Chem. Int. Ed. 2008, 47, 3100–3120.
[8] a) T. Linker, L. Frçhlich, Angew. Chem. 1994, 106, 2064–2066;
Angew. Chem. Int. Ed. Engl. 1994, 33, 1971–1972; b) T. Linker, L.
Frçhlich, J. Am. Chem. Soc. 1995, 117, 2694–2697; more recent ap-
plications in material sciences: D. Zehm, W. Fudickar, T. Linker,
Angew. Chem. 2007, 119, 7833–7836; Angew. Chem. Int. Ed. 2007,
46, 7689–7692; D. Zehm, W. Fudickar, M. Hans, U. Schilde, A. Kel-
ling, T. Linker, Chem. Eur. J. 2008, 14, 11429–11441.
[9] a) T. Linker, K. Vorndran, DE 198193750, 1998; b) K. Vorndran, T.
Linker, Angew. Chem. 2003, 115, 2593–2595; Angew. Chem. Int. Ed.
2003, 42, 2489–2491.
[10] Reviews: a) P. W. Rabideau, Tetrahedron 1989, 45, 1579–1603;
b) P. W. Rabideau, Z. Marcinow, Org. React. 1992, 42, 1–334;
c) G. S. R. Subba-Rao, Pure Appl. Chem. 2003, 75, 1443–1451.
[11] a) H. van Bekkum, C. B. van den Bosch, G. van Minnen-Pathuis,
J. C. de Mos, A. M. van Wijk, Recl. Trav. Chim. Pays-Bas 1971, 90,
137–149; b) M. Acheson, R. F. Flowerday, J. Chem. Soc., Perkin
1-Methoxycarbonylmethylnaphthalene (9h): Colorless liquid (89%); Rf =
0.60 (hexane/EtOAc, 4:1); 1H NMR (300 MHz, CDCl3): d=3.71 (s, 3H;
OMe), 4.12 (s, 2H; H11), 7.24–7.90 ppm (m, 7H; Ar); 13C NMR
(75 MHz, CDCl3): d=38.9 (C11), 51.9 (OMe), 123.7, 125.4, 125.7, 126.3,
127.9, 128.0, 128.7 (Ar), 130.5, 132.1, 133.8 (Ar), 171.8 (COOMe); IR
(film): n˜ =3046, 2950 (C=CH), 1731 (C=O), 1434, 1194 cmÀ1; elemental
analysis calcd (%) for C13H12O2: C 77.98, H 6.04; found: C 77.67, H 6.11.
1,4-Diethylnaphthalene (9i): Colorless oil (92%); Rf =0.69 (cyclohexane/
EtOAc, 10:1); 1H NMR (300 MHz, CDCl3): d=1.49 (t, J=7.5 Hz, 6H;
H12), 3.20 (q, J=7.5 Hz, 4H; H11), 7.38 (s, 2H; H2), 7.61 (dd, J=6.5,
3.3 Hz, 2H; H5), 8.20 ppm (dd, J=6.5, 3.3 Hz, 2H; H6); 13C NMR
(75 MHz, CDCl3): d=15.6 (C12), 26.4 (C11), 124.9, 125.2, 125.7 (C2, C5,
C6), 132.6, 138.8 ppm (C1, C9); IR (film): n˜ =2963, 2930, 2872 (C=CH),
1596, 1451, 1061 cmÀ1; elemental analysis calcd (%) for C14H16: C 91.25,
H 8.75; found: C 91.14, H 8.82.
1,4-Diisopropylnaphthalene (9j): Colorless oil (94%); Rf =0.75 (hexane/
EtOAc, 10:1); 1H NMR (300 MHz, CDCl3): d=1.44 (d, J=6.8 Hz, 12H;
H12), 3.78 (sept, J=6.8 Hz, 2H; H11), 7.44 (s, 2H; H2), 7.55 (dd, J=6.6,
3.3 Hz, 2H; H5), 8.22 ppm (dd, J=6.6, 3.3 Hz, 2H; H6); 13C NMR
(75 MHz, CDCl3): d=24.1 (C12), 28.8 (C11), 121.9, 124.5, 125.4 (C2, C5,
C6), 132.1, 142.8 ppm (C1, C9); IR (film): n˜ =3075, 2960, 2870 (C=CH),
1596, 1458, 1021 cmÀ1; elemental analysis calcd (%) for C16H20: C 90.51,
H 9.49; found: C 90.30, H 9.59.
Trans.
1 1974, 2339–2342; c) J. Slobbe, J. Chem. Soc., Chem.
Commun. 1977, 82–83.
[12] P. W. Rabideau, J. W. Paschal, L. E. Patterson, J. Am. Chem. Soc.
1975, 97, 5700–5704.
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Received: June 26, 2009
Published online: September 24, 2009
Chem. Eur. J. 2009, 15, 12082 – 12091
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
12091