Cobalt(I)-catalyzed neutral Diels-Alder reactions of 1,3-diynes with acyclic 1,3-dienes

Article abstract of DOI:10.1055/s-2002-23547

The cobalt catalyzed neutral Diels-Alder reaction of various acyclic 1,3-dienes and norbornadiene with 1,3-diynes can be controlled to give the 1:1 adduct, whereas the 1:2 adducts are only formed with sterically less hindered 1,3-dienes. With unsymmetrica

Full text of DOI:10.1055/s-2002-23547

686
FEATURE ARTICLE
Cobalt(I)-catalyzed Neutral Diels–Alder Reactions of 1,3-Diynes with Acyclic
1,3-Dienes
C
obalt(I)-catalyze
e
d
N
eutral
D
r
iels–Ald
h
er Reactions
a
of 1,3-Diy
r
nes
w
ith
d
A
cyclic 1,3-Diene
H
s
ilt,* Konstantin I. Smolko
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5–13, 81377 München, Germany
Fax +49(89)21807425; E-mail: Gerhard.Hilt@cup.uni-muenchen.de
Received 10 January 2002
nadiene, as well as at elevated temperatures, the 1:1 ad-
Abstract: The cobalt catalyzed neutral Diels–Alder reaction of var-
ious acyclic 1,3-dienes and norbornadiene with 1,3-diynes can be
controlled to give the 1:1 adduct, whereas the 1:2 adducts are only
formed with sterically less hindered 1,3-dienes. With unsymmetri-
cal 1,3-diynes the regiochemistry is mainly controlled by steric fac-
tors for unfunctionalized diynes, whereas the regiodirecting
methoxymethyl substituent favors the Diels–Alder reaction at the
closest triple bond. The combination of steric effects and the meth-
oxymethyl substituent exclusively generates one of the two possible
neutral Diels–Alder products. The mild oxidation of the dihydroar-
omatic products by stoichiometric amounts of DDQ, or alternative-
ly under electrochemical regeneration of the spent oxidizing agent
at the anode, generates phenylacetylene derivatives, from the 1:1
adduct, or biphenyl derivatives, from the 1:2 adduct, respectively.
duct is formed selectively besides norbornadiene dimers
as by-product when an excess of norbornadiene is used,
while no double addition products could be detected.
R3
R2
R1
R3
R1
CoI
CoI
R1
R3
R4
R2
R2
R4
Scheme 1
Key words: cobalt, neutral Diels–Alder reaction, 1,3-diyne, 1,3-di-
ene, dihydroaromatic compounds
R
CoI
+
1-3
Transition metal catalyzed neutral Diels–Alder reactions
and other cycloaddition processes have been extensively
studied and among these several Fe, Co, Ti or Ni cata-
lyzed neutral Diels-Alder type reactions are described.1
Recently, we have investigated cobalt(I)-catalyzed neu-
tral Diels–Alder reactions between terminal as well as in-
ternal alkynes and acyclic 1,3-dienes and found that a
catalyst system consisting of Co(dppe)Br2/ZnI2/Bu4NBH4
proved to be highly effective in the generation of dihy-
droaromatic compounds under mild reaction conditions in
good to excellent yields.2
R
R
R
Scheme 2
Table 1 Cobalt(I)-catalyzed Neutral Homo Diels–Alder Reactions
of Symmetrical 1,3-Diynes with Norbornadiene
Entry
R
Product
Time
(Temp) (%)
Yield
Herein we describe our investigations into the use of 1,3-
diynes as double dienophiles in neutral homo Diels–Alder
type reactions with norbornadiene and neutral Diels–
Alder type reactions with acyclic 1,3-dienes. While in the
presence of a slight excess of the diyne at room tempera-
ture the cobalt catalyzed formation of a 1:1 adduct is ob-
served (Scheme 1), the degree of formation of the
corresponding 1:2 adducts strongly depends on the substi-
tution pattern of the 1,3-diene, determining its steric hin-
derance, and to a lesser degree on the reaction
temperature.
1
TMS
1
2
3
16 h
20 °C
76
82
47
TMS
TMS
2
3
Ph
16 h
20 °C
Ph
Ph
The cobalt(I)-catalyzed neutral homo Diels–Alder reac-
tion of norbornadiene with symmetrical 1,3-diynes leads
selectively to the formation of the 1:1 adducts (see
Table 1). Even in the presence of a large excess of norbor-
CH2OMe
1 h
20 °C
MeO
OMe
Synthesis 2002, No. 5, 08 04 2002. Article Identifier:
1437-210X,E;2002,0,05,0686,0692,ftx,en;Z01102SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

FEATURE ARTICLE
Cobalt(I)-catalyzed Neutral Diels–Alder Reactions of 1,3-Diynes with Acyclic 1,3-Dienes
687
The reactions of simple, sterically less demanding acyclic formed along with regioisomeric 1:2 adducts, even when
1,3-dienes, such as isoprene and 2,3-dimethyl-1,3-butadi- an excess of diyne is used. However, with the correspond-
ene, can be performed at room temperature in a short pe- ing THP protected diyne (entry 7), the regioselectivity can
riod of time, while the reaction with 1,3-dienes that are be controlled, so that the 1:1 adduct is formed exclusively.
substituted at a terminal position requires longer reaction However, the regiocontrol for this neutral Diels-Alder re-
times for the formation of a 1:1 adduct in good yields. The action is only moderate, with an inseparable 5:2 mixture
dihydroaromatic compounds generated by this method of regioisomers being formed in favour of the product
can either be isolated under strict exclusion of air and with the methyl and the CH2OTHP substituent in a para
avoiding strong acidic or basic conditions, or the interme- relationship. For the higher homologue (entry 8) the 1:1
diates can immediately be oxidized to the corresponding adduct is also formed exclusively, while the regiochemis-
aromatic derivatives. These oxidations can either be real- try is comparable to the previous case, with a 4:1 mixture
ized using stoichiometric amounts of DDQ or with cata- of regioisomers being formed.
lytic amounts of the oxidizing agent under
The reactions with sterically less hindered 1,3-dienes re-
electrochemical reoxidation of the reduced DDQH2 (see
sult in the formation of the 1:2 adducts with somewhat
Scheme 3) under galvanostatic conditions (100 mA) until
longer reaction times than the formation of the 1:1 adduct.
2.2 F/mol are consumed. The aromatic products are then
The primary products are again readily oxidized to the
corresponding aromatic biaryl derivatives, which can be
easily isolated by column chromatography.
easily purified and characterized. The regiochemical out-
come of the reactions to form the 1:1 adducts as well as
anode
R
the formation of the 1:2 adducts is mostly influenced by
the steric demand of the substituents as outlined in an ear-
lier report.2b However, for the formation of the 1:2 adducts
the steric bulk is alterned, so that unsymmetrical biaryl
type products are formed. For the first neutral Diels–Alder
reaction in this sequence, the n-butyl group is sterically
more demanding (M = medium) than the alkyne substruc-
ture (S = small), so that excellent 1,4-selectivity for the re-
action with unsymmetrical 1,3-dienes is observed (see
Table 2). For the subsequent neutral Diels–Alder reaction,
the large steric demand of the dihydroaromatic system
(L = large) over the n-butyl substituent (M = medium) is
again responsible for the excellent 1,4-selective regio-
chemical outcome of the second addition, forming unsym-
metrical biaryl products after mild DDQ oxidation.
CoI
DDQ (cat.)
DDQH2
R
R
or
DDQ (1.1 equiv.)
R
R
R
Scheme 3
Following the reaction sequence outlined in Schemes 2
and 3 we were able to use a variety of different acyclic
1,3-dienes in the neutral Diels–Alder type reaction to gen-
erate the 1:1 adducts with symmetrical 1,3-diynes under
mild reaction conditions, affording good yields of the cor-
responding aromatic compounds.
With the methoxy functionalized 1,3-diyne (Table 2, en-
try 6), a complex mixture of 1:1 adduct regioisomers is
Biographical Sketches
Gerhard Hilt (right) was fellow with M. F. Sem- sity in Munich. His
born in Andernach (Ger- melhack (Princeton, research interests are elec-
many) in 1968. He studied U.S.A.) on stoichiometric tron transfer activated
chemistry in Bonn, where organometallic chemistry (transition-)metal comple-
he obtained his diploma in and from 1998–99 in the xes by (electro-)chemical
1992 and his Ph.D. with E. group of R. Noyori methods and their use in
Steckhan on indirect elec- (Nagoya, Japan) on mech- organic synthesis, such as
trochemical regeneration anistic investigations in electrochemical regenera-
of enzymatic cofactors in asymmetric catalysis. In tion of low valent metals
asymmetric biosynthesis. late 1999 he started his and Co(I)-catalyzed pro-
From 1996–1998 he ‘Habilitation’ at the Lud- cesses.
worked as a postdoctoral wig-Maximilians-Univer-
Konstantin Smolko (left) in Moscow and obtained regeneration of low valent
was born in Chelyabinsk his diploma in 1999. He indium reagents and their
(Russia) in 1977. He stud- joined the Hilt group in use in organic synthesis
ied chemistry at the 2000 and is working in the and Co(I)-catalyzed neu-
Lomonossov University fields of electrochemical tral Diels–Alder reactions.
Synthesis 2002, No. 5, 686–692 ISSN 0039-7881 © Thieme Stuttgart · New York

688
G. Hilt, K. I. Smolko
FEATURE ARTICLE
Table 2 Cobalt(I)-catalyzed Neutral Diels–Alder Reactions of
Symmetrical 1,3-Diynes with 1,3-Dienes
Entry R
Diene
Product
Time Yield
(%)
1. CoI / Isoprene
CoI
2. DDQ-Oxidation
1
1 h 91
1 h 98
nBu
4
nBu
2
M
nBu
L
R
R
CoI
CoI
5
nBu
R
M
R
L
S
M
S
3
4
5
nBu
16 h 84
16 h 87
1 h 80
M
nBu
nBu
6
7
nBu
nBu
Scheme 4
Besides mono-substituted 1,3-dienes such as isoprene and
oxy-substituted dienes, the disubstituted diene 2,3-dime-
thyl-1,3-butadiene also underwent the reaction to form the
1:2 adducts in good yield.
TMSO
HO
Me
nBu
8
To our dismay, when sterically more hindered dienes,
with substituents at the terminal position of the 1,3-buta-
diene substructure, were used as staring materials, very
little or no conversion to the desired bis-dihydroaromatic
compounds was observed. Therefore, any possible asym-
metric induction by chiral phosphine ligands, to generate
chiral atropisomeric biaryl compounds, has so far not
been realized.
nBu
6
7
8
MeOCH2
0.2 h -a
OMe
OMe
9
Me
Me
THPOCH2
BnOCH2CH2
0.5 h 53b
1 h 53c
OTHP
OTHP
OBn
10
However, we then turned our attention to the neutral
Diels–Alder reaction of unsymmetrical 1,3-diynes
(Scheme 5) and we found that the products were mainly
directed by the steric bulk of the substituents involved.
OBn
11
Me3SiO
HO
9
SiMe3
16 h 68
SiMe3
12
Table 3 Cobalt(I)-catalyzed Double Neutral Diels–Alder Reaction
of 1,3-Diynes with 1,3-Dienes
SiMe3
Entry
R
Diene Product
Time Yield
(%)
a A complex mixture of regioisomeric 1:1 and 1:2 adducts were
formed.
b A mixture of regioisomers in a 5:2 ratio is formed.
c A mixture of regioisomers in a 4:1 ratio is formed.
n
Bu
1
nBu
5 h
76
13
The situation becomes more complex with higher substi-
tuted 1,3-dienes. Thus, with a methyl group in the termi-
nal position, such as in 1,3-pentadiene, the neutral Diels–
Alder reactions gave lower regioselectivities compared to
reactions with isoprene as the 1,3-diene.3 This suggests
that the substituent in the 2-position is much more direct-
ing than the substituent in 1-position. Therefore, the sub-
stitution pattern of the products formed with 2-methyl-
1,3-pentadiene or 3-methyl-1,3-pentadiene (Table 2, en-
tries 3 and 4) is directed by the isoprene-like methyl group
rather than the methyl group in the terminal position.
nBu
n
Bu
2
3
nBu
5 h
2 h
86
14
nBu
MeO
CH2OMe
51a
15
OMe
a Combined yield of a mixture of regioisomers.
Synthesis 2002, No. 5, 686–692 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE
Cobalt(I)-catalyzed Neutral Diels–Alder Reactions of 1,3-Diynes with Acyclic 1,3-Dienes
689
R1
In summary, we have shown that our cobalt catalyst sys-
tem is able to generate polysubstituted and polyfunction-
alized arene systems in good yields after DDQ oxidation
of the dihydroaromatic intermediates. The selective for-
mation of 1:1 adducts can either be controlled by steric
factors, for higher substituted 1,3-diene systems, or by the
use of a slight excess of the 1,3-diyne, for mono-substitut-
ed butadiene derivatives. The regioselectivity for the reac-
tion of unsymmetrical 1,3-dienes is generally good to
excellent for symmetrical as well as unsymmetrical 1,3-
diynes, with the exception of methoxymethyl substituted
diynes, where the reactivity is higher as for other diynes
resulting in a lower degree of regioselectivity. However,
the regiodirecting effect of the methoxymethyl substituent
combined with other sterically bulky substituents resulted
in complete regioselectivity when unsymmetrical diynes
were used. While the synthesis of atropisomeric biaryl
compounds could not be realized, the reaction sequence
presented herein provides a method of generating highly
substituted biaryl derivatives in an efficient and regiose-
lective fashion.
CoI
R1
DDQ-Oxidation
R1
R2
R2
R2
Scheme 5
Table 4 Regioselective Neutral Diels–Alder Reaction with Unsym-
metrical 1,3-Diynes
Entry R1
R2
Product
Yield
(%)
Hex
n
1
2
3
4
n-Hex
Ph
58
67b
53
64
16
MeO
nHex
CH2OMe
CH2OMe
CH2OMe
n-Hex
Ph
17
MeO
NMR spectra were recorded on 200, 300 or 500 MHz instruments.
IR spectra were recorded on a Nicolet 510 or a Perkin-Elmer 281
spectrometer. Electron impact mass (EI) spectra were recorded on a
Varian MAT CH 7A. High resolution mass spectra were recorded
on a Finnigan MAT95Q instrument. All reagents were of commer-
cial quality, zinc iodide was dried in vacuo at 150 °C before use.
Diynes were synthesized according to literature procedures.4,5
18
MeO
Me3Si
SiMe3
19
Co(I)-catalyzed Neutral Diels–Alder Reaction; Typical Proce-
dure
a The reaction time was in all cases 1 h.
b Combined yield of the regioisomers.
Under a N2 atmosphere a 10 mL Schlenk-tube was charged with the
CoBr2(dppe) complex (62 mg, 0.1 mmol, 10 mol%) and ZnI2 (100
mg, 0.31 mmol). The materials were suspended in CH2Cl2 (3 mL),
1,3-diyne (1 mmol) and 1,3-diene (1.1 mmol) (for the generation of
the 1:1 adduct) or alternately1,3-diene (2.3 mmol)(when the 1:2 ad-
ducts was synthesized). After the addition of tetrabutylammomium
borohydride, the reaction mixture was stirred at r.t. The progress of
the reaction was monitored by GC (1:1 adduct) or TLC (2:1 adduct).
After completion of the reaction the solvent was removed in vacuo
and the residue was taken up in benzene (20 mL). The mixture was
filtered through cotton wool and DDQ (1.1 mmol or 2.3 mmol) was
added as a solid in small portions over 5 min. After stirring for an
additional 10 min and dilution with Et2O, the mixture was washed
with sat. Na2S2O3 (0.5 M), aq NaOH solution (0.5 M, 25 mL) until
the aq layer became colourless. The aq phase was extracted with
Et2O (2 20 mL), the combined organic layer was then dried over
Na2SO4 and the solvents were removed in vacuo. The residue was
purified by column chromatography to yield the desired product.
While the formation of 16 starting from the unfunctional-
ized 1,3-diyne is controlled by steric factors, for the meth-
oxymethyl functionalized diyne (Table 4, entry 2) a
regiodirecting effect of the methoxy substituent can be
proposed, favoring the formation of 17 over its regioiso-
mer. Although the regioselectivity for the formation of 17
is not excellent, (4:1 ratio of separable regioisomers),
combined with sterically demanding substituents (entries
3 and 4) the regioselectivities are complete, with the prod-
ucts (18 and 19) being formed in good yield.
Since the formation of 1:2 adducts with higher substituted
1,3-dienes was not successful, the primary product can be
isolated and further converted with another 1,3-diene,
such as isoprene (Scheme 6), to the unsymmetrical biaryl
compound 20 in excellent yield after oxidation with DDQ.
Indirect Electrochemical DDQ-catalyzed Oxidation
The dihydroaromatic compound was dissolved in CH2Cl2 (30 mL)
containing tetrabutylammonium tetrafluoroborate (0.1 M) in a bea-
ker type cell (50 mL) and a catalytic amount of DDQ (10–20 mol%)
was added. The mixture was electrolyzed at constant current (100
mA) using two glassy carbon electrodes (8 cm2 each) until 2.0 F/
mol were consumed. The products were then isolated as described
above.
CoI
DDQ
Bu
Bu
Bu
16h
Bu
Bu
20
89%
(2 steps)
6
Bu
Scheme 6
Synthesis 2002, No. 5, 686–692 ISSN 0039-7881 © Thieme Stuttgart · New York

690
G. Hilt, K. I. Smolko
FEATURE ARTICLE
HRMS: (m/z) calcd for C17H24, 228.1878; found, 228.1869.
Trimethyl{1,4,5-metheno-3-[(trimethylsilyl)ethynyl]-1,3a,4,5,
6,6a-hexahydro-2-pentalenyl}silane (1)
Eluent: pentane; colorless solid; yield: 217 mg (0.76 mmol, 76%).
1-Butyl-2-(1-hexynyl)-4,5-dimethylbenzene (5)
Eluent: pentane; colorless liquid; yield: 237 mg (0.98 mmol, 98%).
IR (KBr): 2957 (s), 2136 (w), 1739 (s), 1681 (m), 1415 (m), 1248
(s), 844 (s) cm–1.
1H NMR (300 MHz, CDCl3): = 0.15 [s, 9 H, Si(CH3)3], 0.17 [s, 9
H, Si(CH3)3], 1.14–1.19 (m, 1 H), 1.37–1.42 (m, 1 H), 1.50–1.53
(m, 2 H), 1.63–1.66 (m, 1 H), 1.94 (br s, 1 H), 2.66–2.70 (m, 2 H).
13C NMR (75 MHz, CDCl3): = –1.1, –0.1, 22.1, 22.9, 24.9, 32.6,
53.2, 55.6, 56.6, 99.0, 104.4, 137,9, 157.6.
MS (EI): m/z (%) = 286 (M+,99), 271 (24), 212 (22), 197 (100), 183
IR (KBr): 2958 (s), 2931 (s), 2859 (s), 2229 (w), 1613 (w), 1455 (s),
881 (m), 801 (m) cm–1.
1H NMR (300 MHz, CDCl3): = 0.93 (t, 3 H, J = 7.1 Hz, CH3),
0.94 (t, 3 H, J = 7.1 Hz, CH3), 1.28–1.64 (m, 8 H, CH2), 2.16 (s, 3
H, CH3Ar), 2.20 (s, 3 H, CH3Ar), 2.41 (t, 2 H, J = 6.9 Hz, CH2C C),
2.67 (t, 2 H, J = 7.7 Hz, CH2Ar), 6.92 (s, 1 H, Ar), 7.14 (s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): = 14.0, 14.4, 19.4, 19.6, 20.0, 22.4,
23.0, 31.4, 33.5, 34.3, 79.8, 92.9, 120.9, 130.4, 133.4, 133.9, 136.4,
142.5.
(31), 73 (34).
HRMS: (m/z) calcd for C17H26Si2, 286.1573; found, 286.1577.
MS (EI): m/z (%) = 242 (M+, 88), 199 (61), 171 (36), 157 (100),
142 (34), 119 (19), 77 (4).
1,2,4-Metheno-5-phenyl-6-(phenylethynyl)-1,2,3,3a,4,6a-
hexahydropentalene (2)
HRMS: (m/z) calcd for C18H26, 242.2035; found, 242.2044.
Eluent: pentane–Et2O, 100:1; colorless solid; yield: 241 mg. (0.82
mmol, 82%).
2-Butyl-1-(1-hexynyl)-3,5-dimethylbenzene (6)
Eluent: pentane; colorless liquid; yield: 203 mg (0.84 mmol, 84%).
IR (KBr): 3056 (s), 2928 (s), 2859 (s), 2190 (m), 1680 (m), 1598
(m), 1486 (s), 1265 (s), 769 (s), 754 (s), 690 (s) cm–1.
1H NMR (300 MHz, CDCl3): = 1.52–1.56 (m, 2 H), 1.60–1.65 (m,
2 H), 1.76–1.80 (m, 1 H), 2.21 (m, 1 H), 2.91 (m, 1 H), 3.14 (m, 1
H), 7.20–7.47 (m, 8 H, Ar), 7.82–7.87 (m, 2 H, Ar).
13C NMR (75 MHz, CDCl3): = 22.6, 23.3, 24.7, 51.6, 54.7, 55.3,
88.3, 96.5, 122.4, 124.0, 126.4, 127.3, 128.2, 128.3, 131.3, 136.2,
151.6.
IR (KBr): 2956 (s), 2931 (s), 1606 (w), 1466 (m), 1230 (m), 855 (w)
cm–1.
1H NMR (300 MHz, CDCl3): = 0.93 (t, 3 H, J = 7.2 Hz, CH3),
0.94 (t, 3 H, J = 7.3 Hz, CH3), 1.34–1.63 (m, 8 H, CH2), 2.21 (s, 3
H, CH3Ar), 2.25 (s, 3 H, CH3Ar), 2.42 (t, 2 H, J = 7.0 Hz,
CH2C C), 2.73 (t, 3 H, J = 7.8 Hz, CH2Ar), 6.85 (s, 1 H, Ar), 7.03
(s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): = 16.3, 16.6, 21.9, 22.2, 23.3, 24.6,
25.8, 33.5, 33.6, 34.6, 82.6, 95.2, 126.2, 133.1, 133.2, 137.2, 138.3,
142.8.
MS (EI): m/z (%) = 294 (M+,100), 278 (20), 265 (13), 252 (13), 215
(49), 202 (22), 138 (7), 91 (6).
HRMS: (m/z) calcd for C23H18, 294.1409; found, 294.1406.
MS (EI): m/z (%) = 242 (M+, 100), 199 (84), 185 (14), 171 (24),
157 (100), 142 (28), 128 (14).
1,2,4-Metheno-5-(methoxymethyl)-6-(3-methoxy-1-propynyl)-
1,2,3,3a,4,6a-hexahydropentalene (3)
HRMS: (m/z) calcd for C18H26, 242.2035; found, 242.2022.
Eluent: pentane–Et2O, 20:1; colorless liquid; yield: 108 mg (0.47
mmol, 47%) unstable.
1-Butyl-2-(1-hexynyl)-3,4-dimethylbenzene (7)
Eluent: pentane; colorless liquid; yield: 210 mg (0.87 mmol, 87%).
IR (KBr): 2957 (s), 2930 (s), 2859 (s), 2225 (w), 1665 (w), 1456
(m), 1107 (m) cm–1.
1H NMR (300 MHz, CDCl3): = 1.33–1.47 (m, 2 H), 1.48–1.53 (m,
2 H), 1.68–1.73 (m, 1 H), 2.00–2.05 (m, 1 H), 2.63–2.67 (m, 1 H),
2.69–2.73 (m, 1 H), 3.28 (s, 3 H), 3.37 (s, 3 H), 4.07 (d, 1 H,
J = 12.4 Hz), 4.14 (d, 1 H, J = 12.4 Hz), 4.25 (s, 2 H).
13C NMR (75 MHz, CDCl3): = 22.5, 22.7, 25.3, 32.4, 50.1, 53.6,
55.9, 57.5, 57.8, 60.6, 68.9, 85.1, 91.0, 125.8, 152.8.
MS (EI): m/z (%) = 230 (M+,70), 215 (5), 199 (12), 165 (59), 153
IR (KBr): 2957 (s), 2859 (s), 2872 (s), 2225 (w), 1594 (w), 1456 (s),
814 (m) cm–1.
1H NMR (300 MHz, CDCl3): = 0.93 (t, 3 H, J = 7.2 Hz, CH3),
0.95 (t, 3 H, J = 7.2 Hz, CH3), 1.31–1.66 (m, 8 H, CH2), 2.22 (s, 3
H, CH3Ar), 2.36 (s, 3 H, CH3Ar), 2.49 (t, 2 H, J = 6.8 Hz,
CH2C C), 2.72 (t, 3 H, J = 7.8 Hz, CH3Ar), 6.89 (d, 1 H, J = 7.7
Hz, Ar), 6.96 (d, 1 H, J = 7.7 Hz, Ar).
13C NMR (75 MHz, CDCl3): = 14.0, 14.3, 18.0, 19.7, 20.5, 22.4,
23.1, 31.5, 33.3, 35.1, 78.8, 98.1, 123.7, 125.9, 128.9, 133.9, 138.7,
142.8.
(100), 141 (41), 128 (37), 115 (45), 91 (21), 77 (16).
HRMS: (m/z) calcd for C15H18O2, 230.1307; found, 230.1310.
MS (EI): m/z (%) = 242 (M+,59), 199 (54), 185 (10), 171 (22), 157
(100), 141 (31), 128 (16).
1-Butyl-2-(1-hexynyl)-4-methylbenzene (4)
Eluent: pentane; colorless liquid; yield: 207 mg (0.91 mmol, 91%).
HRMS: (m/z) calcd for C18H26, 242.2035; found, 242.2021.
IR (KBr): 2957 (s), 2930 (s), 2226 (w), 1610 (w), 1496 (m), 1465
(m), 1387 (w), 883 (w), 816 (m) cm–1.
4-Butyl-3-(1-hexynyl)phenol (8)
Eluent: pentane–Et2O, 10:1; colorless oil; yield: 184 mg (0.8 mmol,
80%).
1H NMR (300 MHz, CDCl3): = 0.93 (t, 3 H, J = 7.3 Hz, CH3),
0.94 (t, 3 H, J = 7.2 Hz, CH3,), 1.30–1.64 (m, 8 H, CH2,), 2.26 (s, 3
H, CH3Ar), 2.43 (t, 2 H, J = 6.3 Hz, CH2C C), 2.71 (t, 2 H, J = 7.5
Hz, CH2Ar), 6.98 (dd, 1 H, J = 7.8, 1.2 Hz, Ar), 7.04 (d, 1 H, J = 7.8
Hz, Ar), 7.18 (1 H, br s, Ar).
13C NMR (75 MHz, CDCl3): = 14.0, 14.4, 19.6, 21.1, 22.4, 23.0,
31.4, 33.4, 34.3, 79.8, 93.6, 123.5, 128.7, 128.9, 133.0, 135.2,
142.1.
IR (KBr): 3369 (s), 2957 (s), 2872 (s), 2228 (w), 1656 (w), 1465 (s),
1290 (s), 1175 (s), 870 (m), 819 (m) cm–1.
1H NMR (300 MHz, CDCl3): = 0.92 (t, 3 H, J = 7.3 Hz, CH3),
0.94 (t, 3 H, J = 7.1 Hz, CH3), 1.29–1.63 (m, 8 H, CH2), 2.42 (t, 2
H, J = 6.9 Hz, CH2C C), 2.66 (t, 2 H, J = 7.7 Hz, CH2Ar), 4.83 (br
s, 1 H, HOAr), 6.67 (dd, 1 H, J = 8.3, 2.7 Hz, Ar), 6,84 (d, 1 H,
J = 2.7 Hz, Ar), 6.98 (d, 1 H, J = 8.3 Hz, Ar).
MS (EI): m/z (%) = 228 (M+, 57), 185 (49), 157 (28), 143 (100),
128 (39), 115 (17).
Synthesis 2002, No. 5, 686–692 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE
Cobalt(I)-catalyzed Neutral Diels–Alder Reactions of 1,3-Diynes with Acyclic 1,3-Dienes
691
13C NMR (75 MHz, CDCl3): = 12.9, 12.9, 18.1, 20.9, 21.5, 29.8,
32.0, 32.4, 78.1, 92.6, 114.0, 117.5, 123.2, 128.6, 136.0, 152.1.
MS (EI): m/z (%) = 230 (M+, 40), 187 (100), 145 (61), 127 (19), 115
4-(Trimethylsilyl)-3-[(trimethylsilyl)ethynyl]phenol (12)
Eluent: pentane–Et2O, 10:1; colorless oil; yield: 178 mg (0.68
mmol, 68%).
(30), 77 (7).
IR (KBr): 3391 (m), 2958 (m), 2154 (m), 1589 (m), 1249 (s), 842
(s), 760 (m) cm–1.
1H NMR (300 MHz, CDCl3): = 0.24 [s, 9 H, Si(CH3)3], 0.33 [s, 9
H, Si(CH3)3), 5.05 (s, 1 H, OHAr], 6.77 (dd, 1 H, J = 8.1, 2.5 Hz,
Ar), 6.96 (d, 1 H, J = 2.5 Hz, Ar), 7.32 (d, 1 H, J = 8.1 Hz, Ar).
13C NMR (75 MHz, CDCl3): = –1.0, –0.3, 97.1, 106.2, 115.2,
119.6, 129.7, 134.1, 135.6, 155.7.
MS (EI): m/z (%) = 262 (M+,20), 247 (100), 231 (10), 161 (7), 116
HRMS: (m/z) calcd for C16 H22O, 230.1671; found, 230.1660.
Tetrahydro-2-{[3-(5-methyl-2-{[(tetrahydro-2H-pyran-2-yl)-
oxy]methyl}phenyl)-2-propynyl]oxy}-2H-pyran (10) and Tetra-
hydro-2-{[3-(4-methyl-2-{[(tetrahydro-2H-pyran-2-yl)oxy]me-
thyl}phenyl)-2-propynyl]oxy}-2H-pyran (Regioisomer of 10)
The reaction gave an inseperable mixture of regioisomers in a ratio
of ~5: 2 in a combined yield: of 183 mg, (0.53 mmol, 53%).
(18), 73 (31).
Eluent: pentane–Et2O 20:1; colorless oil.
HRMS: (m/z) calcd for C14H22OSi2, 262.1209; found, 262.1191.
IR (KBr): 2942 (s), 2870 (s), 2224 (s), 1610 (w), 1453 (m), 1441
(m), 1348 (m), 1118 (s), 1026 (s), 870 (m), 816 (m) cm–1.
2,2’-Dibutyl-4,5 -dimethyl-1,1 -biphenyl (13)
Eluent: pentane–Et2O, 50:1; colorless liquid, yield: 223 mg (0.76
mmol, 76%).
1H NMR (300 MHz, CDCl3) major isomer: = 1.38–1.97 (m, 12 H,
CH2THP), 2.29 (s, 3 H, CH3), 3.37–3.67 (m, 2 H, CH2OTHP), 3.75–
4.02 (m, 2 H, CH2OTHP), 4.50 (s, 2 H, CH2Bn), 4.63 (d, 1 H,
J = 12.7 Hz, CH2C C), 4.72–4.78 (m, 1 H, CHO2THP), 4.84 (d, 1
H, J = 12.7 Hz, CH2C C), 4.88–4.94 (m, 1 H, CHO2THP), 7.12 (d,
1 H, J = 7.8 Hz, Ar), 7.27 (br s, 1 H, Ar), 7.34 (d, 1 H, J = 7.8 Hz,
Ar).
IR (KBr): 2927 (s), 2871 (s), 2859 (s), 1612 (w), 1488 (m), 1456
(m), 887 (w), 820 (m) cm–1.
1H NMR (300 MHz, CDCl3): = 0.77 (t, 3 H, J = 7.2 Hz, CH3),
1.11–1.24 (m, 4 H, CH2Me), 1.34–1.46 (m, 4 H, CH2), 2.22–2.40
(m, 4 H, 2 CH2Ar), 2.31 (s, 3 H, CH3Ar), 2.37 (s, 3 H, CH3Ar),
6.89–7.16 (m, 6 H, Ar).
13C NMR (75 MHz, CDCl3): = 14.2, 14.3, 21.3, 21.6, 22.9, 22.9,
32.7, 33.0, 33.4, 33.5, 126.2, 128.0, 128.9, 129.7, 130.1, 131.2,
134.7, 136.8, 138.6, 140.8, 141.3.
Additional signals of minor isomer: = 2.34 (s, CH3Ar), 4.49 (s,
CH2Ar), 7.02 (d, J = 7.8 Hz, Ar), 7.28 (br s, Ar).
13C NMR (75 MHz, CDCl3): = 19.1, 19.3, 20.8, 21.5, 25.4, 25.5,
30.3, 30.6, 54.7, 62.1, 67.2, 67.4, 83.6, 83.7, 88.8, 89.1 96.7, 96.8,
98.4, 98.5, 118.3, 121.2, 127.6, 127.9, 128.2, 129.4, 132.3, 132.9,
136.8, 137.4, 138.7, 140.2.
MS (EI): m/z (%) = Major isomer: 344 (M+, 0.1), 242 (11), 229
(13), 159 (68), 141 (24), 129 (21), 115 (24), 85 (100). Minor isomer:
344 (M+, 0.1), 242 (16), 229 (16), 176 (7), 159 (87), 141 (25), 129
(24), 115 (27), 85 (100).
MS (EI): m/z (%) = 294 (M+, 82), 251 (23), 237 (25), 209 (15), 195
(100), 180 (19), 165 (15).
HRMS: (m/z) calcd for C22H30, 294.2348; found, 294.2363.
2,2’-Dibutyl-4,4 ,5,5 -tetramethyl-1,1 -biphenyl (14)
Eluent: pentane–Et2O, 50:1; colorless liquid; yield: 276 mg (0.86
mmol, 86%).
1H NMR (300 MHz, CDCl3): = 0.77 (t, 6 H, J = 7.2 Hz, CH3),
1.12–1.24 (m, 4 H, CH2Me), 1.33–1.45 (m, 4 H, CH2), 2.17–2.37
(m, 4 H, CH2Ar), 2.21 (s, 6 H, CH3Ar), 2.28 (s, 6 H, CH3Ar), 6.84
(s, 2 H, Ar), 7.02 (s, 2 H, Ar).
HRMS: (m/z) calcd for C21H28O4 (major isomer), 344.1988; found
344.2013. HRMS: (m/z) calcd for C21H28O4 (minor isomer),
344.1988; found 344.2018.
2-[4-(Benzyloxy)-1-butynyl]-1-[2-(benzyloxy)ethyl]-4-methyl-
benzene (11) and 1-[4-(Benzyloxy)-1-butynyl]-2-[2-(benzyl-
oxy)ethyl]-4-methylbenzene (Regioisomer of 11)
The reaction gave an inseparable mixture of two regioisomers in a
ratio of ~4:1 in a combined yield: of 271 mg (0.74 mmol, 74%).
13C NMR (75 MHz, CDCl3): = 14.3, 19.6, 19.9, 22.9, 32.6, 33.6,
130.2, 131.7, 133.3, 135.2, 138.3, 138.9.
IR (KBr): 2956 (s), 2871 (s), 2860 (s), 1691 (w), 1490 (m), 1454 (s),
1105 (s), 886 (w) cm–1.
Eluent: pentane–Et2O, 10:1; colorless liquid.
MS (EI): m/z (%) = 322 (M+, 72), 279 (11), 265 (17), 223 (100),
208 (26), 193 (19).
IR (KBr): 3063 (m), 2962 (m), 2858 (m), 1609 (w), 1495 (m), 1261
(s), 1095 (s), 801 (s), 734 (m), 696 (m) cm–1.
1H NMR (300 MHz, CDCl3) major isomer: = 2.40 (s, 3 H,
CH3Ar), 2.72 (t, 2 H, J = 7.1 Hz, CH2C C), 3.04 (t, 2 H, J = 7.3 Hz,
CH2Ar), 3.67 (t, 2 H, J = 7.1 Hz, BnOCH2), 3.68 (t, 2 H, J = 7.2 Hz,
BnOCH2), 4.50 (s, 2 H, CH2Bn), 4.57 (s, 2 H, CH2Bn), 7.01 (d, 1 H,
J = 8.1 Hz, Ar), 7.11 (d, 1 H, J = 8.1 Hz, Ar), 7.20 (br s, 1 H, Ar),
7.27–7.40 (m, 10 H, Ar).
HRMS: (m/z) calcd for C24H34, 322.2661; found, 322.2660.
1-Hexyl-4,5-dimethyl-2-(phenylethynyl)benzene (16)
Eluent: pentane; colorless liquid; yield: 89 mg (0.30 mmol, 58%).
1H NMR (300 MHz, CDCl3): = 0.87 (t, 3 H, J = 7.1 Hz, CH3),
1.26–1.42 (m, 6 H, CH2), 1.62–1.72 (m, 2 H, CH2), 2.22 (s, 3 H,
CH3Ar), 2.25 (s, 3 H, CH3Ar), 2.78 (t, 2 H, J = 7.5 Hz, CH2Ar), 6.98
(s, 1 H, Ar), 7.28 (s, 1 H, Ar), 7.30–7.53 (m, 5 H, Ph).
Additional signals of minor isomer: = 2.30 (s, CH3Ar), 4.51 (s,
CH2Bn), 6.97 (d, J = 8.3 Hz, Ar).
13C NMR (75 MHz, CDCl3): = 20.8, 21.0, 34.5, 68.7, 70.4, 72.8,
73.0, 80.1, 89.9, 126.9, 127.5, 127.6, 127.7, 128.3, 128.4, 128.7,
129.3, 130.2, 132.1, 132.8, 133.7, 135.6, 137.5, 138.2, 138.6.
13C NMR (75 MHz, CDCl3): = 14.1, 19.1, 19.8, 22.6, 29.3, 31.0,
31.8, 24.3, 88.7, 91.8, 119.7, 123.9, 127.8, 128.3, 130.2, 131.4,
133.1, 133.8, 137.15, 142.5.
MS (EI): m/z (%) = 384 (M+, 0.1), 293 (23), 275 (7), 247 (8), 219
(13), 187 (7), 142 (31), 115 (10), 91 (100).
IR (KBr): 2954 (s), 2925 (s), 2856 (s), 2210 (w), 1597 (w), 1497
(m), 1453 (m), 880 (m), 754 (s), 689 (s).
MS (EI): m/z (%) = 290 (M+, 100), 233 (34), 219 (66), 203 (35),
HRMS: (m/z) calcd for C27H28O2, 384.2089; found, 384.2089.
189 (18).
HRMS: (m/z) calcd for C22H26, 290.2034; found, 290.2036.
Synthesis 2002, No. 5, 686–692 ISSN 0039-7881 © Thieme Stuttgart · New York

692
G. Hilt, K. I. Smolko
FEATURE ARTICLE
1-(Methoxymethyl)-4,5-dimethyl-2-(1-octynyl)-benzene (17)
The reaction gave a mixture of 17 and its regioisomer in a combined
yield: of 67% (172 mg), from which pure 17 (41%) and its regioiso-
mer (12%) could be separated by extended chromatography.
13C NMR (75 MHz, CDCl3): = 19.1, 19.7, 58.4, 72.4, 97.5, 103.1,
119.2, 129.0, 133.2, 135.6, 137.6, 137.6.
MS (EI): m/z (%) = 246 (M+, 36), 231 (55), 201 (100), 173 (34), 157
(21), 73 (51).
Eluent: pentane–Et2O, 50:1; colorless liquid; yield: 105 mg (0.41
mmol, 41%).
HRMS: (m/z) calcd for C15H22OSi 246.1440; found 246.1455.
IR (KBr): 2927 (s), 2226 (w), 1596 (w), 1453 (s), 1118 (s), 1091 (s),
881 (m) cm–1.
1H NMR (300 MHz, CDCl3): = 0.89 (t, 3 H, J = 7.2 Hz, CH3),
1.28–1.64 (m, 8 H, CH2), 2.19 (s, 3 H, CH3Ar), 2.22 (s, 3 H,
CH3Ar), 2.41 (t, 2 H, J = 7.0 Hz, CH2C C), 3.40 (s, 3 H, CH3O),
4.54 (s, 2 H, OCH2Ar), 7.15 (s, 2 H, Ar).
13C NMR (75 MHz, CDCl3): = 14.0, 19.2, 19.5, 19.6, 22.5, 28.6,
28.8, 31.3, 58.3, 72.5, 78.3, 93.7, 120.0, 128.8, 133.0, 135.5, 136.4,
136.9.
2,2’-Dibutyl-3,4 ,5-trimethyl-1,1 -biphenyl (20)
Eluent: pentane–Et2O, 50:1; colorless liquid; yield: 274 mg (0.89
mmol, 89%).
IR (KBr): 2956 (s), 2871 (s), 2859 (s), 1611 (w), 1465 (s), 857 (m),
822 (m) cm–1.
1H NMR (300 MHz, CDCl3): = 0.75 (t, 3 H, J = 7.1 Hz, CH3),
0.81 (t, 3 H, J = 7.1 Hz, CH3), 1.10–1.50 (m, 8 H, CH2), 2.17–2.47
(m, 4 H, CH2Ar), 2.30 (s, 3 H, CH3Ar), 2.37 (s, 3 H, CH3Ar), 2.40
(s, 3 H, CH3Ar), 6.77 (br s, 1 H, Ar), 6.98 (br s, 1 H, Ar), 7.01 (s, 1
H, Ar), 7.02 (s, 1 H, Ar), 7.10 (s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): = 13.7, 13.9, 19.8, 20.8, 21.3, 22.6,
23.0, 29.7, 32.0, 32.7, 33.0, 125.7, 128.7, 129.2, 129.7, 129.9,
134.0, 135.9, 136.2, 136.4, 138.8, 140.2, 141.2.
MS (EI): m/z (%) = 258 (M+,60), 243 (22), 229 (9), 197 (54), 187
(100), 173 (24), 157 (65), 141 (28), 128 (23), 115 (15).
HRMS: (m/z) calcd for C18H26O, 258.1984; found, 258.1962.
1-Hexyl-2-(3-methoxy-1-propynyl)-4,5-dimethyl-benzene (Re-
gioisomer of 17)
MS (EI): m/z (%) = 308 (M+,74), 293 (5), 265 (40), 251 (23), 223
(8), 209 (100), 194 (23), 179 (16), 165 (4).
Eluent: pentane– Et2O, 50:1; colorless liquid; yield: 32 mg (0.12
mmol, 12%).
HRMS: (m/z) calcd for C23H32 308.2504; found 308.2518.
IR (KBr): 2926 (s), 2857 (s), 2223 (w), 2182 (w), 1609 (w), 1453
(s), 1110 (s), 882 (m) cm–1.
Acknowledgements
1H NMR (300 MHz, CDCl3): = 0.87 (t, 3 H, J = 7.1 Hz, CH3),
1.22–1.65 (m, 8 H, CH2), 2.17 (s, 3 H, CH3Ar), 2.22 (s, 3 H,
CH3Ar), 2.68 (t, 3 H, J = 7.6 Hz, CH2Ar), 3.44 (s, 3 H, CH3O), 4.34
(s, 3 H, MeOCH2), 6.94 (s, 1 H, Ar), 7.18 (s, 1 H, Ar).
We thank the German science foundation (DFG - Emmy Noether
program) for the financial support. We also thank Bettina Lotsch
and Sebastian Braun for their help during the advanced organic che-
mistry course in our laboratory.
13C NMR (75 MHz, CDCl3): = 14.1, 19.0, 19.7, 22.6, 29.2, 30.9,
31.7, 34.1, 57.4, 60.5, 85.5, 87.1, 119.1, 130.1, 133.4, 133.7, 137.2,
142.5.
References
MS (EI): m/z (%) = 258 (M+,36), 169 (21), 157 (100), 141 (29), 128
(19), 115 (14).
(1) For reviews see: (a) Trost, B. M. Pure Appl. Chem. 1988,
60, 1615. (b) Rigby, J. H. In Comprehensive Organic
Chemistry, Vol. 5; Trost, B. M.; Fleming, I., Eds.;
Pergamon: Oxford, 1991, 593–615. (c) Ateep, H. S. Pure
Appl. Chem. 1994, 66, 2029. (d) Especially for neutral
Diels–Alder reactions see: Lautens, M.; Klute, W.; Tam, W.
Chem. Rev. 1996, 96, 49. (e) Ojima, I.; Tzamarioudaki, M.;
Li, Z.; Donovan, R. J. Chem. Rev. 1996, 96, 635.
(f) Frühauf, H.-W. Chem. Rev. 1997, 97, 523. (g) Rigby, J.
H. Tetrahedron 1999, 55, 4521. (h) Yet, L. Chem. Rev.
2000, 100, 2963. (i) Wender, P.; Zhang, L. Org. Lett. 2000,
2, 2323.
(2) (a) Hilt, G.; du Mesnil, F.-X. Tetrahedron Lett. 2000, 41,
6757. (b) Hilt, G.; Korn, T. J. Tetrahedron Lett. 2001, 42,
2783. (c) For other cycloadditions catalyzed by Co(dppe)-
complexes see: Chen, Y.; Kiattansakul, B. M.; Snyder, K. J.
Org. Chem. 2001, 66, 6932.
(3) The regioselectivity for the neutral Diels–Alder reactions of
1,3-pentadiene with unsymmetrical alkynes and 1,3-diynes
is quite low, generally in the range of 60:40.
(4) Unsymmetrical diynes were synthesized following the
procedure described in: Cai, C.; Vasella, A. Helv. Chim.
Acta 1995, 78, 2053; using Pd(CH3CN)2Cl2 as the palladium
precursor instead of Pd2(dba)3.
HRMS: (m/z) calcd for C18H26O, 258.1984; found, 258.1961.
1-(Methoxymethyl)-4,5-dimethyl-2-(phenylethynyl)benzene
(18)
Eluent: pentane–Et2O, 15:1; colorless liquid; yield: 132 mg, (0.53
mmol, 53%, unstable).
IR (KBr): 2974 (s), 2921 (s), 2212 (w), 1776 (s), 1691 (s), 1598 (s),
1497 (s), 1450 (s), 882 (m), 756 (s), 691 (s) cm–1.
1H NMR (300 MHz, CDCl3): = 2.23 (s, 3 H, CH3Ar), 2.27 (s, 3 H,
CH3Ar), 3.45 (s, 3 H, CH3O), 4.64 (s, 2 H, MeOCH2), 7.22–7.54 (m,
7 H, Ar).
13C NMR (75 MHz, CDCl3): = 19.2, 19.8, 58.4, 72.5, 87.9, 119.2,
123.5, 128.1, 128.3, 128.5, 129.1, 131.4, 131.6, 133.0, 135.8, 137.2,
137.5.
MS (EI): m/z (%) = 250 (M+, 35), 235 (100), 219 (12), 202 (17), 192
(21), 178 (6), 165 (6), 115 (5).
{[2-(Methoxymethyl)-4,5-dimethylphenyl]ethynyl}(trimeth-
yl)silane (19)
Eluent: pentane–Et2O, 50:1; colorless liquid; yield: 157 mg (0.64
mmol, 64%).
(5) For symmetrical diynes see: (a) Smith, E. H.; Whittall, J.
Organometallics 1994, 13, 5169. (b) Ghosal, S.; Luke, G.
P.; Kyler, K. S. J. Org. Chem. 1987, 52, 19. (c) Huang, X.;
Wang, J.-H. Synth. Commun. 2000, 30, 9. (d) Blanksby, S.
J.; Dua, S.; Bowie, J. H.; Schroeder, D.; Schwarz, H. J. Phys.
Chem. A 1998, 102, 9949. (e) Ziegler, C. B.; Harris, S. M.;
Baldwin, J. E. J. Org. Chem. 1987, 52, 443.
IR (KBr): 2959 (s), 2862 (s), 2156 (s), 1609 (w), 1489 (s), 1452 (s),
1247 (s), 1117 (s), 842 (s) cm–1.
1H NMR (300 MHz, CDCl3): = 0.24 [s, 9 H, Si(CH3)3], 2.19 [s, 3
H, CH3Ar], 2.24 (s, 3 H, CH3Ar), 3.41 (s, 3 H, CH3O), 4.56 (s, 2 H,
MeOCH2), 7.17 (s, 1 H, Ar), 7.23 (s, 1 H, Ar).
Synthesis 2002, No. 5, 686–692 ISSN 0039-7881 © Thieme Stuttgart · New York