Regioselective cobalt-catalyzed Diels-Alder reaction towards 1,3-disubstituted and 1,2,3-trisubstituted benzene derivatives

Article abstract of DOI:10.1055/s-2008-1078450

A straightforward reaction sequence consisting of the Wittig olefmation of aldehydes utilizing allyltriphenylphosphonium bromide for the generation of 1-substituted 1,3-dienes, cobalt-catalyzed neutral Diels-Alder reaction with terminal and internal alkyn

Full text of DOI:10.1055/s-2008-1078450

PAPER
2257
Regioselective Cobalt-Catalyzed Diels–Alder Reaction towards
1,3-Disubstituted and 1,2,3-Trisubstituted Benzene Derivatives
Regioselective
D
ie
e
ls–Alder
R
r
eaction hard Hilt,* Michael Danz
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein Straße, 35043 Marburg, Germany
Fax +49(6421)2825677; E-mail: Hilt@chemie-uni.marburg.de
Received 7 March 2008
Dedicated to Prof. Dr. Reinhard W. Hoffmann on the occasion of his 75th birthday
in the cobalt-catalyzed reaction of a 1-substituted 1,3-di-
ene and a terminal alkyne are described herein.
Abstract: A straightforward reaction sequence consisting of the
Wittig olefination of aldehydes utilizing allyltriphenylphosphoni-
um bromide for the generation of 1-substituted 1,3-dienes, cobalt-
catalyzed neutral Diels–Alder reaction with terminal and internal
alkynes, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)
oxidation of the dihydroaromatic intermediates leads to regiochem-
ically enriched biphenyl, terphenyl, and silyl-functionalized ben-
zene derivatives in good to excellent yields. Starting from a 1,3-
diyne and a 1,3-diene, the reaction sequence consisting of cobalt-
catalyzed Diels–Alder reaction, DDQ oxidation, and cobalt-cata-
lyzed cyclotrimerization with acetylene gave an axially chiral bi-
phenyl-terphenyl product.
To this end, a representative selection of 1-substituted 1,3-
dienes were synthesized utilizing the Wittig olefination of
aldehydes with allyltriphenylphosphonium bromide. The
Wittig olefination reactions were performed on a 10–15
mmol scale to give the required 1-substituted 1,3-dienes
in reasonable quantities as an E/Z mixture. The results of
the olefination reaction are summarized in Table 1.
Table 1 Results of the Wittig Olefination of Aldehydes with Allyl-
triphenylphosphonium Bromide
Key words: alkyne, cobalt, Diels–Alder, diene, Wittig olefination
Entry Aldehyde
Product
Yield (%)
61
1
2
3
n-H15C7CHO
The classical Diels–Alder reaction of unsymmetrical
starting materials under thermal conditions gives regio-
isomers and the regioselectivity of this reaction is con-
trolled by orbital coefficients.1 The observation of
regiochemical preferences in the thermal Diels–Alder re-
action is now known as the ortho/para rule, meaning that
the formation of the meta products 2 and 4 is unlikely and
that the corresponding para products of type 1 or ortho
products of type 3 are formed predominantly (Scheme 1).2
31
63
CHO
F3C
CHO
F3C
4
5
55
86
CHO
R2
R2
+
MeO
CHO
R1
R1
R1
R2
MeO
1
2
R1
R1
R1
R2
R2
The cobalt-catalyzed Diels–Alder reaction with terminal
alkynes was then investigated applying the previously de-
scribed dibromo[1,2-bis(diphenylphosphino)ethane]co-
balt(II) [CoBr2(dppe)] complex as catalyst precursor.4
The transformation turned out to be highly regioselective
and the desired meta-substituted aromatic products of
type 5 were isolated after 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ) oxidation of the dihydroaromatic
intermediates 4 (Scheme 2). The results of the reactions
are summarized in Table 2.
+
R2
3
4
Scheme 1 Regiochemistry of the thermal Diels–Alder reaction
Only recently we were able to describe a simple cobalt
catalyst system for the first regioselective formation of the
meta-substituted products 2 by applying pyridine imine
ligands.3 The results for the alternative approach towards
meta-substituted Diels–Alder adducts of type 4 generated
R1
R1
R1
CoBr2(dppe)
Zn, ZnI2
DDQ
+
R2
R2
R2
SYNTHESIS 2008, No. 14, pp 2257–2263
Advanced online publication: 11.06.2008
x
x.
x
x
.
2
0
0
8
4
5
DOI: 10.1055/s-2008-1078450; Art ID: C00508SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 2 Cobalt-catalyzed Diels–Alder/DDQ oxidation sequence

2258
G. Hilt, M. Danz
PAPER
Table 2 Results of the Cobalt-Catalyzed Diels–Alder Reaction Uti-
lizing Terminal Alkynes
As representative substrates, primary and secondary
alkyl-substituted 1,3-dienes such as undeca-1,3-diene and
1-cyclohexylbuta-1,3-diene were chosen. In terms of aryl-
substituted 1,3-diene substrates bearing an electron-with-
drawing group (CF3) as well as an electron-donating sub-
stituent (OMe) were selected. The results summarized in
Table 2 show that the yields for the transformation with
(trimethylsilyl)acetylene were in all cases better than in
reactions with phenylacetylene. Nevertheless, good to ex-
cellent yields were obtained in all examples. The regiose-
lectivities were very high in almost all cases, indicating
that the regioselectivity of the reaction is mainly governed
by the steric bulk of the substituents.
Entry 1,3-Diene + alkyne Product 5
Yield Ratio
(%)
meta/ortho
1
83
97:3
n-Hept
+
n-Hept
SiMe3
SiMe3
5a
5b
2
3
64
93
81:19
>99:1
n-Hept
+
n-Hept
Ph
Ph
It seems that electronic effects do not play an important
role since the different electronic nature of the substitu-
ents of the aryl-substituted 1,3-dienes had little effect on
the regioselectivity. Comparable yields were obtained for
these transformations (cf. Table 2, entries 5–8). The reac-
tion sequence led to interesting silyl-functionalized prod-
ucts as well as functionalized terphenyl derivatives.
c-Hex
+
c-Hex
SiMe3
SiMe3
5c
4
5
56
93
98:2
c-Hex
+
c-Hex
Further investigation on the application of internal
alkynes led to the generation of 1,2,3-trisubstituted ben-
zenes following the transformation outlined in Scheme 3.
As unsymmetrical internal alkynes 1-(trimethylsi-
lyl)prop-1-yne as well as 1-phenylprop-1-yne were cho-
sen to investigate the regioselectivity when the steric bulk
of the alkyne was increased.
Ph
Ph
5d
>99:1
CF3
CF3
R1
R1
R1
R3
CoBr2(dppe)
Zn, ZnI2
+
R3
R2
R3
R2
DDQ
+
SiMe3
SiMe3
R2
5e
6
7
8
65
87
75
98:2
>99:1
98:2
6
7
CF3
CF3
Scheme 3 Synthesis of trisubstituted arenes
As before, the dihydroaromatic intermediates 6 were oxi-
dized by DDQ to obtain the corresponding aromatic prod-
ucts 7 to simplify the characterization of the products. The
results of these transformations are summarized in
Table 3.
+
Ph
Ph
5f
OMe
OMe
Table 3 Results of the Cobalt-Catalyzed Diels–Alder Reaction Uti-
lizing Internal Alkynes
Entry 1,3-Diene + alkyne Product 7
Yield Ratio
(%)
meta/ortho
+
SiMe3
1
2
56
21:79
48:52
n-Hept
Me
n-Hept
+
SiMe3
Me
5g
OMe
OMe
Ph
Ph
7a
7b
71
Ph
Ph
Me
Me
Ph
+
+
Ph
Ph
Ph
5h
Synthesis 2008, No. 14, 2257–2263 © Thieme Stuttgart · New York

PAPER
Regioselective Diels–Alder Reaction
2259
Table 3 Results of the Cobalt-Catalyzed Diels–Alder Reaction Uti-
lizing Internal Alkynes (continued)
regioselectivities for the silyl-functionalized alkyne were
still excellent. On the other hand, the application of 1-phe-
nylprop-1-yne gave mixtures of products close to a 1:1 ra-
tio in all cases with the two aryl groups in a 1,3- (here
assigned as the meta product) and a 1,2-relation (ortho
product) to each other. Accordingly, the regioselective co-
balt-catalyzed Diels–Alder reaction with internal alkynes
is limited with respect to 1-arylalk-1-ynes while 1-silyl-
alk-1-ynes are broadly applicable.
Entry 1,3-Diene + alkyne Product 7
Yield Ratio
(%)
meta/ortho
3
72
98:2
CF3
CF3
Me
Me
We then turned our attention to the application of 1,3-
diynes as substrates.4b Although we suspected that the re-
gioselectivity for the phenyl-substituted diyne would be
as low as in the previous set of experiments, we were de-
lighted to find that in this reaction product 9a could be ob-
tained in 84% yield as a single regioisomer (Scheme 4).
Obviously the diyne moiety has a positive effect on the re-
gioselectivity based not only on steric demand, but also
because of electronic effects. The results for the silyl-
functionalized 1,3-diyne were even better, giving the de-
sired product 9b in an excellent 95% yield as a single re-
gioisomer.
+
SiMe3
SiMe3
7c
7d
7e
4
5
6
CF3
62
56
72
57:43
CF3
Me
Ph
Me
Ph
+
CF3
CF3
OMe
OMe
OMe
R
Et
Et
Et
Et
R
R
+
CoBr2(dppe)
Zn, ZnI2
DDQ
+
R
R
R
OMe
98:2
OMe
OMe
OMe
9a
R = Ph
9b R = SiMe3 95%
84%
8
Scheme 4 Application of diynes in cobalt-catalyzed Diels–Alder
reactions
Me
Me
+
In the past we have also investigated the use of simple co-
balt catalysts in alkyne cyclotrimerization reactions.5 In
this context 9a caught our attention, because the conver-
sion of this highly substituted internal diarylacetylene 9a
with acetylene under mild reaction conditions at atmo-
spheric pressure would not only transform the internal
alkyne selectively into a 1,2-substituted benzene ring, but
also give rise to an axially chiral product (Scheme 5).
Therefore, we attempted the conversion of 9a as a test
substrate into the racemic product 10 utilizing a catalyst
system consisting of 10 mol% cobalt(II) bromide, 30
mol% zinc powder, and 30 mol% zinc(II) iodide in aceto-
nitrile at elevated temperatures.
SiMe3
SiMe3
7f
7
65
53:47
OMe
Me
Ph
Me
Ph
+
7g
8
51
OMe
Et
Et
OMe
OMe
Et
Et
+
Ph
+
CoBr2, Zn, ZnI2
7h
HC CH
1 bar
MeCN, 60 °C, 4 h
Ph
Unlike the earlier results with terminal alkynes, a signifi-
cant difference between the phenyl and the trimethylsilyl-
substituted alkyne could now be observed. While the
yields for all transformations were somewhat reduced, the
Ph
Ph
99%
9a
10
Scheme 5 Cobalt-catalyzed cyclotrimerization utilizing acetylene
Synthesis 2008, No. 14, 2257–2263 © Thieme Stuttgart · New York

2260
G. Hilt, M. Danz
PAPER
(quint, J = 7.3 Hz, 2 H), 1.45–1.27 (m, 8 H), 0.94 (t, J = 6.7 Hz, 3
H), 0.31 (s, 9 H)
was isolated in almost quantitative yield. Accordingly, ap- 13C NMR (75 MHz, CDCl3): d = 142.0, 140.2, 133.3, 130.5, 128.8,
The transformation to the biphenyl-terphenyl derivative
10 was complete within four hours and a single product
127.6, 36.1, 31.8, 31.6, 29.4, 29.1, 22.6, 14.0, –1.0.
MS (EI): m/z = 248 (M+, 12), 233 (100), 161 (5), 148 (6), 131 (5),
73 (5).
HRMS (EI): m/z [M]+ calcd for C16H28Si: 248.1960; found:
248.1957.
proaches towards chiral derivatives of this type with func-
tional groups replacing the phenyl groups on the diyne
substrate (R ≠ Ph, Scheme 4) can be envisaged utilizing
chiral ligands such as Norphos [1,2-bis(diphenylphoshi-
no)bicyclo[2.2.1]hept-5-ene] in the cyclotrimerization re-
action with acetylene. These investigations are currently
in progress in our laboratory.
3-Heptyl-1,1¢-biphenyl (5b)
Colorless oil; yield: 64%; Rf = 0.27 (pentane). The ratio of isomers
was determined by integration of 1H NMR signals: d = 2.68 (meta)
and 2.57 (ortho).
In conclusion we have presented a facile synthesis of re-
gioselectively substituted 1,3-di- and 1,2,3-trisubstituted
benzene derivatives in a short reaction sequence. Interest-
ing silyl-functionalized benzene and biphenyl products as
well as regiochemically enriched terphenyl products are
accessible. The application of internal alkynes gave excel-
lent results utilizing silyl-functionalized alkynes and the
application of 1,3-diynes in combination with a cobalt-
catalyzed cyclotrimerization using acetylene under atmo-
spheric pressure gave a very interesting chiral biphenyl-
terphenyl product.
IR: 2927, 2855, 1600, 1479, 1455, 1075 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.63–7.58 (m, 2 H, HAr), 7.47–
7.28 (m, 6 H, HAr), 7.22–7.15 (m, 1 H, HAr), 2.68 (t, J = 7.8 Hz, 2 H,
CH2), 1.68 (quint, J = 7.4 Hz, 2 H, CH2), 1.42–1.16 (m, 8 H, CH2),
0.93–0.83 (m, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 143.4, 141.4, 141.1, 128.6, 128.6,
127.3, 127.3, 127.1, 127.0, 124.4, 36.1, 31.8, 31.5, 29.3, 29.2, 22.6,
14.0.
MS (EI): m/z = 252 (M+, 75), 209 (6), 181 (9), 168 (100), 152 (25).
HRMS (EI): m/z [M]+ calcd for C19H24: 252.1878; found: 252.1879.
NMR spectra were recorded on a 300 MHz instrument. Electron im-
pact mass (EI) spectra were recorded on a Varian MAT CH 7A.
High resolution mass spectra were recorded on a Finnigan
MAT95Q instrument. GC and GCMS were recorded on Hewlett
Packard 5890 and on an Agilent 6890N gaschromatograph with a
mass detector Agilent 5973. IR data were recorded on a Bruker IFS
88 interferometer as a film or a KBr pellet. All reagents were of
commercial quality, zinc iodide was dried in vacuo at 150 °C before
use.
1-Cyclohexyl-3-(trimethylsilyl)benzene (5c)
Colorless oil; yield: 93%; Rf = 0.38 (pentane).
IR: 2925, 2851, 1448, 1408, 1247, 1115, 849, 836, 752 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.39–7.36 (m, 2 H), 7.31 (t,
J = 7.5 Hz, 1 H), 7.23 (d, J = 7.7 Hz, 1 H), 2.56–2.50 (m, 1 H),
1.95–1.84 (m, 4 H), 1.78 (d, J = 6.8 Hz, 1 H), 1.53–1.37 (m, 4 H),
1.34–1.25 (m, 1 H), 0.30 (s, 9 H).
13C NMR (125 MHz, CDCl3): d = 147.1, 140.2, 131.9, 130.8,
127.6, 127.1, 44.7, 34.5, 26.9, 26.1, –1.0.
1,3-Dienes by Wittig Olefination; General Procedure
Allyltriphenylphosphonium bromide (1.2 equiv) and t-BuOK were
suspended in THF at 0 °C. After 15 min the aldehyde (1.0 equiv)
was added and the reaction was monitored by TLC control. The re-
action was quenched by addition of sat. aq NH4Cl and extracted
with MTBE (3 ×). The organic phases were dried (MgSO4), the sol-
vent was removed from the residue, and the residue was purified by
column chromatography (silica gel, pentane–MTBE mixtures).
MS (EI): m/z = 232 (M+, 10), 217 (100), 161 (5), 73 (5).
HRMS (EI): m/z [M]+ calcd for C15H24Si: 232.1647; found:
232.1644.
3-Cyclohexyl-1,1¢-biphenyl (5d)
Colorless oil; yield: 56%; Rf = 0.18 (pentane).
IR: 3057, 3031, 2924, 2850, 1599, 1478, 1447, 798, 756, 702 cm–1.
1,3-Disubstituted and 1,2,3-Trisubstituted Benzene Derivatives
by the Diels–Alder Reaction; General Procedure
1H NMR (300 MHz, CDCl3): d = 7.62–7.59 (m, 2 H), 7.47–7.41
(m, 4 H), 7.40–7.33 (m, 2 H), 7.20 (d, J = 7.5 Hz, 1 H), 2.56–2.50
(tt, J = 11.5, 3.3 Hz, 1 H), 1.98–1.93 (m, 2 H), 1.91–1.85 (m, 2 H),
1.81–1.76 (m, 1 H), 1.55–1.39 (m, 4 H), 1.29 (tq, J = 12.5, 3.4 Hz,
1 H).
13C NMR (75 MHz, CDCl3): d = 148.5, 141.6, 141.2, 128.6, 128.6,
127.2, 127.0, 125.8, 125.7, 124.6, 44.7, 34.5, 26.9, 26.1.
A suspension of CoBr2(dppe) (10 mol%), Zn powder (10 mol%),
and ZnI2 (20 mol%) in CH2Cl2 (0.5 mL) was charged with the 1,3-
diene (1.2 mmol) and the alkyne (1 mmol). After complete conver-
sion (up to 2 d), the mixture was filtered through a small pad of sil-
ica gel (MTBE), the solvent was removed and the residual
dihydroaromatic intermediate was oxidized with DDQ (1.1 equiv)
in benzene or toluene (10–20 mL) to give the corresponding aro-
matic product. The solvent was removed and the residue was puri-
fied by column chromatography (silica gel). The ratios of
regioisomers were determined by integration of GC/GC-MS and 1H
NMR signals.
MS (EI): m/z = 236 (M+, 100), 193 (45), 180 (81), 165 (67).
HRMS (EI): m/z [M]+ calcd for C18H20: 236.1565; found: 236.1560.
4-(Trifluoromethyl)-3¢-(trimethylsilyl)-1,1¢-biphenyl (5e)
Colorless oil; yield: 93%; Rf = 0.45 (pentane).
IR: 2957, 1617, 1327, 1250, 1166, 1126, 1072, 1016 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.76–7.71 (m, 5 H), 7.62–7.58
(m, 2 H), 7.52–7.46 (m, 1 H), 0.35 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 145.2, 141.5, 139.2, 133.2, 132.2,
129.3 (q, J = 32 Hz), 128.3, 127.8, 127.6, 125.7 (q, J = 4 Hz), 124.4
(q, J = 272 Hz), –1.1.
1-Heptyl-3-(trimethylsilyl)benzene (5a)
Light yellow oil; yield: 83%; Rf = 0.46 (pentane). The ratio of iso-
mers was determined by integration of 1H NMR signals: d =
0.31 (meta) and 0.38 (ortho).
IR: 2956, 2927, 2856, 1466, 1405, 1248, 1122 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41–7.37 (m, 2 H), 7.32 (t,
J = 7.3 Hz, 1 H), 7.24–7.20 (m, 1 H), 2.65 (t, J = 7.8 Hz, 2 H), 1.67
Synthesis 2008, No. 14, 2257–2263 © Thieme Stuttgart · New York

PAPER
Regioselective Diels–Alder Reaction
2261
MS (EI): m/z = 294 (M+, 18), 279 (100), 263 (9), 214 (5), 165 (5),
139 (5).
HRMS (EI): m/z [M]+ calcd for C16H17F3Si: 294.1052; found:
294.1056.
13C NMR (75 MHz, CDCl3): d = 140.9, 140.7, 136.1, 131.4, 129.3,
128.1, 127.0, 127.0, 126.5, 126.3, 33.5, 31.6, 31.2, 29.3, 28.9, 22.6,
20.9, 14.0.
MS (EI): m/z = 266 (M+, 54), 181 (100), 165 (56), 152 (6).
HRMS (EI): m/z [M]+ calcd for C20H26: 266.2035; found: 266.2041.
4-(Trifluoromethyl)-1,1¢:3¢,1¢¢-terphenyl (5f)
Colorless solid; yield: 65%; Rf = 0.22 (pentane). The ratio of regio-
isomers was determined by integration of GC signals.
IR: 2925, 1614, 1571, 1393, 1335, 1159, 1112, 1073 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.85–7.82 (m, 1 H), 7.81–7.71
(m, 4 H), 7.71–7.63 (m, 3 H), 7.65–7.55 (m, 2 H), 7.55–7.46 (m, 2
H), 7.45–7.38 (m, 1 H).
2¢-Methyl-1,1¢:3¢,1¢¢-terphenyl (7b) and 3¢-Methyl-1,1¢:2¢,1¢¢-ter-
phenyl (7b¢)
Colorless oil; yield: 71%; Rf = 0.14 (pentane). The ratio of isomers
was determined by integration of 1H NMR signals: d = 2.20 (ortho)
and 2.13 (meta).
The analytical data for the mixture are:
13C NMR (75 MHz, CDCl3): d = 144.7, 142.1, 140.9, 140.3, 129.5
(q, J = 32 Hz), 129.4, 128.9, 127.6, 127.2, 127.0, 126.2, 126.2,
125.7 (q, J = 4 Hz), 124.3 (q, J = 272 Hz).
MS (EI): m/z = 298 (M+, 100), 279 (7), 238 (6), 228 (24), 152 (14),
139 (9), 113 (7), 101 (8).
IR: 3056, 3023, 1600, 1574, 1496, 1460, 1441, 1426, 1071 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.46–7.42 (m, 4 H), 7.40–7.35
(m, 6 H), 7.33 (d, J = 7.4 Hz, 1 H), 7.32–7.25 (m, 5 H), 7.24–7.21
(m, 2 H), 7.19–7.10 (m, 4 H,), 7.08–7.04 (m, 4 H), 2.20 (s, 3 H),
2.13 (s, 3 H).
HRMS (EI): m/z [M]+ calcd for C19H13F3: 298.0969; found:
298.0962.
13C NMR (150 MHz, CDCl3): d = 142.8, 142.4, 141.9, 141.5,
140.4, 140.2, 136.4, 132.9, 130.3, 129.8, 129.3, 129.1, 128.9, 128.0,
127.7, 127.6, 127.3, 127.1, 126.7, 126.2, 126.0, 125.2, 21.1, 18.6.
4-Methoxy-3¢-(trimethylsilyl)-1,1¢-biphenyl (5g)
MS (EI): m/z = 244 (M+, 100), 229 (79), 202 (14), 165 (15), 152 (6),
113 (9).
HRMS (EI): m/z [M]+ calcd for C19H16: 244.1252; found: 244.1243.
Colorless oil; yield: 87%; Rf = 0.59 (pentane–MTBE, 10:1).
IR: 2940, 1695, 1508, 1282, 1243, 1178, 1121, 1023 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.70–7.68 (m, 1 H), 7.57–7.52
(m, 3 H), 7.51–7.47 (m, 1 H), 7.45–7.39 (m, 1 H), 7.03–6.97 (m, 2
H), 3.87 (s, 3 H), 0.32 (s, 9 H).
2-Methyl-4¢-(trifluoromethyl)-3-(trimethylsilyl)-1,1¢-biphenyl
(7c)
Colorless solid; yield: 72%; Rf = 0.41 (pentane). The ratio of iso-
mers was determined by integration of H NMR signals: d = 0.43
(meta) and 0.49 (ortho).
IR: 2965, 1614, 1326, 1247, 1157, 1127, 1106, 1070 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.72 (d, J = 8.1 Hz, 2 H), 7.59
(dd, J = 7.1, 1.6 Hz, 1 H), 7.47 (d, J = 8.0 Hz, 2 H), 7.34–7.23 (m,
2 H), 2.38 (s, 3 H), 0.43 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 159.1, 140.9, 140.1, 134.2, 131.7,
1
131.7, 128.3, 128.1, 127.4, 114.2, 55.3, –1.1.
MS (EI): m/z = 256 (M+, 49), 241 (100), 225 (6), 198 (6), 181 (5),
120 (8).
HRMS (EI): m/z [M]+ calcd for C16H20OSi: 256.1283; found:
256.1277.
4-Methoxy-1,1¢:3¢,1¢¢-terphenyl (5h)
13C NMR (75 MHz, CDCl3): d = 146.4, 140.8, 140.4, 139.8, 134.2,
130.7, 129.7, 129.0 (q, J = 32 Hz), 125.1, 125.0 (q, J = 4 Hz), 124.4
(q, J = 272 Hz), 21.0, 0.1.
MS (EI): m/z = 308 (M+, 34), 293 (100), 215 (53), 195 (5), 165 (20),
73 (22).
Colorless solid; yield: 75%; Rf = 0.38 (pentane–MTBE, 20:1). The
ratio of isomers was determined by integration of 1H NMR signals:
d = 3.87 (meta) and 3.86 (ortho).
IR: 2954, 2835, 1606, 1515, 1474, 1286, 1240, 1181, 1028 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.78–7.76 (m, 1 H), 7.67–7.44
(m, 9 H), 7.40–7.34 (m, 1 H), 7.03–6.98 (m, 2 H), 3.87 (s, 3 H).
HRMS (EI): m/z [M]+ calcd for C17H19F3Si: 308.1208; found:
308.1203.
13C NMR (75 MHz, CDCl3): d = 159.3, 141.8, 141.4, 141.3, 133.7,
2-Methyl-4¢-(trifluoromethyl)-1,1¢:3¢,1¢¢-terphenyl (7d) and
3-Methyl-4¢-(trifluoromethyl)-1,1¢:2¢,1¢¢-terphenyl (7d¢)
Colorless oil; yield: 62%; Rf = 0.20 (pentane). The ratio of isomers
was determined by integration of 1H NMR signals: d = 2.14 (meta)
and 2.23 (ortho).
129.1, 128.8, 128.3, 127.3, 127.3, 125.7, 125.7, 125.5, 114.3, 55.4.
MS (EI): m/z = 260 (M+, 100), 245 (25), 215 (18), 202 (12), 189 (6),
130 (8).
HRMS (EI): m/z [M]+ calcd for C19H16O: 260.1201; found:
260.1209.
IR: 3059, 1618, 1403, 1326, 1165, 1068, 1019 cm–1.
meta-Isomer 7d
3-Heptyl-2-methyl-1,1¢-biphenyl (7a) and 2-Heptyl-6-methyl-
1,1¢-biphenyl (7a¢)
Colorless oil; yield: 56%; Rf = 0.31 (pentane). The ratio of isomers
was determined by integration of 1H NMR signals: d = 2.35 (ortho)
and 2.58 (meta).
1H NMR (300 MHz, CDCl3): d = 7.73 (d, J = 8.2 Hz, 2 H), 7.55–
7.15 (m, 10 H), 2.14 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 146.1, 143.2, 142.1, 141.5, 132.8,
129.7, 129.7, 129.3, 129.1 (q, J = 33 Hz) 128.2, 127.4 127.0, 125.5,
125.1 (q, J = 4 Hz), 124.3 (q, J = 272 Hz), 18.6.
ortho-Isomer
IR: 3058, 2926, 2856, 1601, 1581, 1491, 1462, 1378, 1071, 1010
ortho-Isomer 7d¢
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.55–7.15 (m, 10 H), 7.07 (dd,
J = 7.7, 1.8 Hz, 2 H), 2.23 (s, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.47–7.10 (m, 8 H, HAr), 2.35 (t,
J = 7.8 Hz, 2 H, CH2), 2.05 (s, 9 H, CH3), 1.48–1.10 (m, 10 H, CH2),
0.88 (t, J = 7.0 Hz, 3 H, CH3).
13C NMR (75 MHz, CDCl3) resolved signals: d = 145.7, 140.4,
140.1, 139.6, 136.8, 130.2, 130.0, 129.8, 128.7, 127.9, 127.5, 126.6,
124.4 (q, J = 4 Hz), 124.3 (q, J = 272 Hz), 21.1.
Synthesis 2008, No. 14, 2257–2263 © Thieme Stuttgart · New York

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G. Hilt, M. Danz
PAPER
MS (EI): m/z = 312 (M+, 100), 297 (10), 281 (6), 271 (7), 243 (9),
228 (7), 165 (20), 146 (5).
HRMS (EI): m/z [M]+ calcd for C20H15F3: 312.1126; found:
312.1129.
1H NMR (300 MHz, CDCl3): d = 7.26–7.14 (m, 4 H), 7.03 (dd,
J = 6.9, 2.0 Hz, 1 H), 6.97–6.92 (m, 2 H), 3.86 (s, 3 H), 2.75 (q,
J = 7.5 Hz, 2 H), 2.62 (q, J = 7.5 Hz, 2 H), 1.30 (t, J = 7.5 Hz, 3 H),
1.00 (t, J = 7.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 158.4, 142.2, 142.1, 139.8, 135.3,
130.2, 128.1, 127.6, 125.4, 113.2, 55.2, 25.7, 22.4, 15.7, 15.4.
2,3-Diethyl-4¢-(trifluoromethyl)-1,1¢-biphenyl (7e)
Colorless oil; yield: 56%; Rf = 0.34 (pentane).
MS (EI): m/z = 240 (M+, 100), 225 (38), 211 (15), 196 (43), 181
IR: 2970, 2876, 1618, 1464, 1403, 1326, 1165, 1127, 1069, 1017
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.72 (d, J = 8.1 Hz, 2 H), 7.49 (d,
J = 8.1 Hz, 2 H), 7.31–7.23 (m, 2 H), 7.05 (dd, J = 7.3, 1.5 Hz, 1 H),
2.82 (q, J = 7.5 Hz, 2 H), 2.64 (q, J = 7.5 Hz, 2 H), 1.36 (t,
J = 7.5 Hz, 3 H), 1.05 (t, J = 7.5 Hz, 3 H).
(20), 165 (28), 152 (21), 139 (6), 128 (5), 115 (9).
HRMS (EI): m/z [M]+ calcd for C17H20O: 240.1514; found:
240.1516.
4-Methoxy-2¢-(phenylethynyl)-1,1¢:3¢,1¢¢-terphenyl (9a)
Colorless solid; yield: 84%; Rf = 0.42 (pentane–MTBE, 20:1).
13C NMR (75 MHz, CDCl3): d = 146.7, 142.5, 141.0, 139.3, 129.6,
128.9 (q, J = 32 Hz), 128.4, 127.6, 125.6, 124.8 (q, J = 4 Hz), 124.4
(q, J = 272 Hz), 25.6, 22.4, 15.7, 15.4.
IR: 3056, 2834, 1609, 1513, 1456, 1248, 1177, 1030, 835, 803, 759,
732, 700 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.71–7.64 (m, 4 H), 7.51–7.36
(m, 6 H), 7.23–7.19 (m, 3 H), 7.07–7.01 (m, 4 H), 3.90 (s, 3 H).
MS (EI): m/z = 278 (M+, 100), 263 (48), 249 (64), 235 (67), 215
(15), 178 (22), 165 (42).
HRMS (EI): m/z [M]+ calcd for C17H17F3: 278.1282; found:
278.1278.
13C NMR (75 MHz, CDCl3): d = 159.1, 145.0, 144.4, 141.1, 133.5,
131.0, 130.8, 129.6, 128.3, 128.1, 128.1, 128.0, 127.8, 127.7, 127.3,
123.6, 120.1, 113.2, 95.7, 89.1, 55.3.
MS (EI): m/z = 360 (M+, 100), 344 (18), 329 (80), 313 (34), 283
(59), 268 (24), 252 (21), 239 (61), 156 (28), 143 (15).
HRMS (EI): m/z [M]+ calcd for C27H20O: 360.1514; found:
360.1513.
4-Methoxy-2¢-methyl-3¢-(trimethylsilyl)-1,1¢-biphenyl (7f)
Colorless solid; yield: 72%; Rf = 0.50 (pentane–MTBE, 10:1). The
ratio of isomers was determined by integration of 1H NMR signals:
d = 0.41 (meta) and 0.34 (ortho).
IR: 3055, 2954, 2834, 1610, 1513, 1458, 1283, 1246, 1176, 1036
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.54–7.49 (m, 1 H), 7.30–7.25
(m, 4 H), 7.02–6.97 (m, 2 H), 3.90 (s, 3 H), 2.39 (s, 3 H), 0.41 (s, 9
H).
13C NMR (75 MHz, CDCl3): d = 158.4, 141.8, 140.9, 139.3, 135.0,
133.4, 131.2, 124.9, 113.5, 55.3, 21.1, 0.2.
MS (EI): m/z = 270 (M+, 99), 255 (65), 240 (100), 195 (17), 181 (9),
4-Methoxy-3¢-(trimethylsilyl)-2¢-[(trimethylsilyl)ethynyl]-1,1¢-
biphenyl (9b)
Colorless solid; yield: 95%; Rf = 0.58 (pentane–MTBE, 10:1).
IR: 2957, 2898, 2834, 2148, 1610, 1514, 1290, 1251, 1177, 1147,
1027 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.57–7.53 (m, 2 H), 7.45 (dd,
J = 5.8, 2.9 Hz, 1 H), 7.37–7.32 (m, 2 H), 6.97–6.92 (m, 2 H), 3.86
(s, 3 H), 0.42 (s, 9 H), 0.15 (s, 9 H).
165 (34), 152 (18), 127 (17), 73 (22).
HRMS (EI): m/z [M]+ calcd for C17H22OSi: 270.1440; found:
13C NMR (75 MHz, CDCl3): d = 159.0, 144.4, 143.6, 133.3, 132.4,
130.8, 130.0, 127.6, 126.3, 113.0, 106.1, 101.2, 55.3, –0.6, –0.9.
270.1435.
MS (EI): m/z = 352 (M+, 53), 337 (10), 321 (17), 264 (13), 249 (55),
225 (17), 205 (10), 189 (6), 73 (100).
HRMS (EI): m/z [M]+ calcd for C21H28OSi2: 352.1679; found:
352.1667.
4-Methoxy-2¢-methyl-1,1¢:3¢,1¢¢-terphenyl (7g) and 4-Methoxy-
3¢-methyl-1,1¢:2¢,1¢¢-terphenyl (7g¢)
Colorless oil; yield: 65%; Rf = 0.41 (pentane–MTBE, 20:1). The
ratio of isomers was determined by integration of 1H NMR signals:
d = 2.20 (meta) and 2.16 (ortho).
4-Methoxy-3¢-phenyl-1,1¢:2¢,1¢¢:2¢¢,1¢¢¢-quaterphenyl (10)
A suspension of CoBr2 (10 mol%), Zn powder (10 mol%), and ZnI2
(20 mol%) in MeCN (1.5 mL) under an atmosphere of acetylene (1
bar) was charged with 9a (0.2 mmol) and then heated to 60 °C. After
4 h the mixture was purified by column chromatography (pentane)
to give 10 as a colorless solid; yield: 99%; Rf = 0.48 (pentane–
MTBE, 20:1).
IR: 3056, 2955, 2834, 1610, 1514, 1462, 1290, 1247, 1178, 1034
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.48–7.19 (m, 16 H), 7.10–7.06
(m, 2 H), 7.03–6.97 (m, 4 H), 6.73–6.67 (m, 2 H), 3.89 (s, 3 H), 3.75
(s, 3 H), 2.20 (s, 3 H), 2.16 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 158.5, 157.9, 142.9, 142.5, 142.5,
141.1, 140.5, 136.5, 134.8, 134.4, 133.1, 131.6, 130.8, 130.4, 130.4,
129.3, 129.1, 128.8, 128.7, 128.0, 127.7, 127.6, 127.1, 126.7, 126.2,
125.3, 113.5, 112.9, 55.3, 55.0, 21.2, 18.7.
IR: 3050, 2918, 1610, 1514, 1455, 1248, 1177, 809, 752, 697 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41 (dd, J = 8.5, 6.9 Hz, 1 H),
7.30–7.26 (m, 2 H), 7.20–6.96 (m, 10 H), 6.86–6.81 (m, 2 H), 6.76
(dt, J = 8.9, 2.6 Hz, 2 H), 6.73–6.68 (m, 2 H), 6.61 (dt, J = 8.8,
2.5 Hz, 2 H), 3.76 (s, 3 H).
MS (EI): m/z = 274 (M+, 100), 259 (14), 244 (10), 228 (10), 215
(34), 202 (9), 189 (8).
HRMS (EI): m/z [M]+ calcd for C20H18O: 274.1358; found:
274.1348.
13C NMR (75 MHz, CDCl3): d = 157.9, 141.9, 141.7, 141.4, 141.1,
140.8, 137.8, 137.6, 134.1, 133.3, 130.6, 129.7, 129.6, 129.5, 129.3,
128.8, 127.5, 127.4, 127.3, 127.1, 126.3, 126.0, 125.9, 112.8, 55.1.
MS (EI): m/z = 412 (M+, 100), 365 (4), 302 (8), 289 (10).
HRMS (EI): m/z [M]+ calcd for C31H24O: 412.1827; found:
2,3-Diethyl-4¢-methoxy-1,1¢-biphenyl (7h)
Colorless oil; yield: 51%; Rf = 0.36 (pentane–MTBE, 20:1).
412.1828.
IR: 2966, 2933, 2874, 2834, 1610, 1513, 1463, 1289, 1245, 1176,
1043, 1027 cm–1.
Synthesis 2008, No. 14, 2257–2263 © Thieme Stuttgart · New York

PAPER
Regioselective Diels–Alder Reaction
2263
Chem. 2003, 196, 157. (l) Ma, B.; Snyder, J. K.
Organometallics 2002, 21, 4688. (m) Chen, Y.;
Kiattansakul, R.; Ma, B.; Snyder, J. K. J. Org. Chem. 2001,
66, 6932.
References
(1) (a) Vollmer, J. J.; Servis, K. L. J. Chem. Educ. 1970, 47,
491. (b) Seebach, D. Fortschr. Chem. Forsch. 1969, 11,
177. (c) Woodward, R. B.; Hoffmann, R. Angew. Chem. Int.
Ed. 1969, 8, 781.
(2) For a detailed discussion see: Fleming, I. Frontier Orbitals
and Organic Chemical Reactions; Wiley: Chichester, 1976,
121–181.
(5) (a) Hilt, G.; Hess, W.; Vogler, T.; Hengst, C. J. Organomet.
Chem. 2005, 690, 5170. (b) Hilt, G.; Vogler, T.; Hess, W.;
Galbiati, F. Chem. Commun. 2005, 1474. (c) Saino, N.;
Amemiya, F.; Tanabe, E.; Kase, K.; Okamoto, S. Org. Lett.
2006, 8, 1439. (d) Goswami, A.; Ito, T.; Okamoto, S. Adv.
Synth. Catal. 2007, 349, 2368. (e) Doszczak, L.; Tacke, R.
Organometallics 2007, 26, 5722. (f) Doszczak, L.; Fey, P.;
Tacke, R. Synlett 2007, 753. Examples for the cobalt-
catalyzed cyclotrimerization of phenylacetylene: (g) Xu,
B.-H.; Wu, D.-H.; Li, Y.-Z.; Yan, H. Organometallics 2007,
26, 4344. (h) Field, L. D.; Ward, A. J. J. Organomet. Chem.
2003, 681, 91. (i) Yong, L.; Butenschön, H. Chem.
Commun. 2002, 2852. (j) Sugihara, T.; Wakabayashi, A.;
Nagai, Y.; Takao, H.; Imagawa, H.; Nishizawa, M. Chem.
Commun. 2002, 576. (k) Montilla, F.; Aviles, T.; Casimiro,
T.; Ricardo, A. A.; Nunes da Ponte, M. J. Organomet.
Chem. 2001, 632, 113. (l) Field, L. D.; Ward, A. J.; Turner,
P. Aust. J. Chem. 1999, 52, 1085. (m) Sigman, M. S.;
Fatland, A. W.; Eaton, B. E. J. Am. Chem. Soc. 1998, 120,
5130. (n) Rhyoo, H.-Y.; Lee, B. Y.; Yu, H. K. B.; Chung, Y.
K. J. Mol. Catal. 1994, 92, 41. (o) Kotha, S.; Brahmachary,
E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741.
(3) For selected examples of regioselective cobalt-catalyzed
Diels–Alder reactions see: (a) Hilt, G.; Janikowski, J.; Hess,
W. Angew. Chem. Int. Ed. 2006, 45, 5204; Angew. Chem.
2006, 118, 5328. (b) Hilt, G.; Hess, W.; Harms, K. Org. Lett.
2006, 8, 3287. (c) Hilt, G.; Smolko, K. I. Angew. Chem. Int.
Ed. 2003, 42, 2795. (d) Hilt, G.; du Mesnil, F.-X.
Tetrahedron Lett. 2000, 41, 6757.
(4) For functionalized building blocks see: (a) Boron: see ref.
3c. (b) Silicon: Hilt, G.; Smolko, K. I. Synthesis 2002, 686.
(c) Nitrogen: Hilt, G.; Galbiati, F. Synlett 2005, 829. (d)
Phosphorus: Hilt, G.; Hengst, C. Synlett 2006, 3247. (e)
Oxygen: Hilt, G.; Smolko, K. I.; Lotsch, B. V. Synlett 2002,
1081. (f) Sulfur: Hilt, G.; Lüers, S.; Harms, K. J. Org. Chem.
2004, 69, 624. For other cobalt-catalyzed cycloadditons see
also: (g) Achard, M.; Tenaglia, A.; Buono, G. Org. Lett.
2005, 7, 2353. (h) Pardigon, O.; Buono, G. Tetrahedron:
Asymmetry 1993, 4, 1977. (i) Pardigon, O.; Tenaglia, A.;
Buono, G. J. Org. Chem. 1995, 60, 1868. (j) Tenaglia, A.;
Pardigon, O.; Buono, G. J. Org. Chem. 1996, 61, 1129.
(k) Pardigon, O.; Tenaglia, A.; Buono, G. J. Mol. Catal. A:
(p) Yamamoto, Y. Curr. Org. Chem. 2005, 9, 503.
Synthesis 2008, No. 14, 2257–2263 © Thieme Stuttgart · New York