An efficient cobalt catalyst for the neutral Diels-Alder reaction of acyclic 1,3-dienes with internal alkynes

Article abstract of DOI:10.1016/S0040-4039(01)00289-1

The efficiently cobalt(I)-catalysed neutral Diels-Alder type reactions of internal alkynes with substituted 1,3-dienes is described. The regiochemistry for the dihydroaromatic products of reactions of isoprene with unsymmetrical reaction partners (2-alkyn

Full text of DOI:10.1016/S0040-4039(01)00289-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2783–2785
An efficient cobalt catalyst for the neutral Diels–Alder reaction
of acyclic 1,3-dienes with internal alkynes
Gerhard Hilt* and Tobias J. Korn
Department Chemie, Ludwig-Maximilians Universit a¨ t M u¨ nchen, Butenandtstraße 5-13, 81377 Munich, Germany
Received 20 February 2001
Abstract—The efficiently cobalt(I)-catalysed neutral Diels–Alder type reactions of internal alkynes with substituted 1,3-dienes is
described. The regiochemistry for the dihydroaromatic products of reactions of isoprene with unsymmetrical reaction partners
(
2-alkynes and 1-trimethylsilyl-1-hexyne) is investigated. The dihydroaromatic reaction products are easily oxidised electrochemi-
cally to the corresponding functionalised durene and isodurene derivatives. © 2001 Elsevier Science Ltd. All rights reserved.
The transition metal-catalysed Diels–Alder reactions of
,3-dienes with non-activated internal alkynes as
dienophiles is of special interest for the preparation of
The reactions are generally complete within 2–4 h (GC
analysis) when 2–3 mol% of the cobalt catalyst is
employed. The dihydroaromatic products are easy to
isolate via filtration through silica gel, but are some-
what sensitive towards oxidation, giving the corre-
sponding aromatic compounds. The rate of the
reactions with sterically more demanding dienes, such
as 2-methyl-1,3-pentadiene, is somewhat diminished so
that the reactions are complete within 12–16 h. This can
be explained by the higher steric demand of the 1,3-
pentadiene substrate while coordinated to the cobalt
centre during the carbonꢀcarbon bond formation pro-
cess. Nonetheless, unfunctionalised as well as function-
alised polysubstituted 1,4-cyclohexadiene derivatives
can be generated in a simple and efficient way and these
1
1
1
,4-dihydroaromatic systems. Whilst the thermal
Diels–Alder reaction of simple olefins and alkynes pro-
ceeds only under drastic conditions, transition metal
complexes can catalyse such reactions under much
milder conditions. These catalysts are mostly cobalt-,
2
rhodium-, nickel- or iron-based complexes (Scheme 1).
As we reported earlier, the CoBr (dppe)/ZnI /Bu NBH
4
2
2
4
system serves as an excellent catalyst for the homo
Diels–Alder reaction of norbornadiene with alkynes, as
well as for the neutral Diels–Alder reaction of acyclic
3
1,3-dienes with terminal alkynes.
5
compounds can be used for further transformations.
Herein we wish to report the use of internal symmetri-
cal and unsymmetrical alkynes as dienophiles in the
neutral Diels–Alder reaction with symmetrical and
unsymmetrical 1,3-dienes. The reaction of the symmet-
rical alkynes 3-hexyne (Table 1, entries 1–3,) and 1,4-
dimethoxy-2-butyne (entries 4–6) with different
We then investigated the reactions of unsymmetrical
alkynes with isoprene in order to determine the regiose-
lectivity of the reactions (see Table 2). Whilst the
regiochemistry of the reaction of isoprene with 2-
hexyne (Table 2, entry 1) could not be influenced by the
addition of cosolvents (benzene, toluene, THF, dioxane
or diethyl ether afforded only slightly different regiose-
1
,3-dienes furnished the corresponding products in
excellent yields and under very mild conditions.
R1
R1
R1
R5
R2
R3
R2
R3
R5
R6
R2
R3
R6
R5
Catalyst
+
+
R6
R4
R4
R4
Scheme 1.
*
Corresponding author. Fax: +(49) 89 21807425; e-mail: gerhard.hilt@cup.uni-muenchen.de
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00289-1

2
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G. Hilt, T. J. Korn / Tetrahedron Letters 42 (2001) 2783–2785
4
Table 1. Neutral Diels–Alder reactions with internal symmetrical alkynes
run
starting materials
product
yield [%]
1
2
99
98
3
4
5
84
98
94
OMe
OMe
MeO
MeO
OMe
OMe
OMe
OMe
OMe
OMe
6
87
MeO
OMe
4
Table 2. Results of neutral Diels–Alder reactions of isoprene with internal unsymmetrical alkynes
entry
starting material
products
ratio
yield [%]
1
70:30
92
82:18
85
2
3
4
>98:<2
>98:<2
72
97
TMS
TMS
TMS
6
lectivities), the ratio of regioisomers could be signifi-
cantly influenced by using sterically more hindered
alkynes. Complete regiocontrol was observed when t-
butyl- and trimethylsilyl-functionalised alkynes were
employed (entries 3 and 4). In these experiments the
regioisomer with less steric hindrance was formed with
good to excellent regioselectivity. Again, for these steri-
cally more demanding alkynes the rate of the reaction is
somewhat diminished; however, the reactions are still
generally complete within 16 h when 2–3 mol% of
cobalt catalyst is used.
The oxidation of these dihydroaromatic systems can be
performed under very mild conditions in a quasi-
divided electrochemical cell (2–3 F/mol) using a glassy
carbon anode and a platinum wire cathode in
dichloromethane (0.1 M tetrabutylammonium tetra-
fluoroborate as supporting electrolyte) to generate the
7
corresponding aromatic compounds. The electrochemi-
cal oxidation was preferred over aerobic oxidation
because, by further electrochemical oxidation in the
presence of nucleophiles, it opens up further possibili-
ties for functionalisation of the generated arene com-

G. Hilt, T. J. Korn / Tetrahedron Letters 42 (2001) 2783–2785
2785
OMe
OMe
OMe
OMe
CoI
anode
OMe
OMe
MeO
OMe
OMe
OMe
Scheme 2.
8
pounds. The reactions can not only be performed
sequentially as shown above but also in a one pot
procedure. The goal for further investigations is the
electrochemical generation of the reactive Co(I) species
in combination with the electrochemical oxidation of
the dihydroaromatic reaction products. The attractive-
ness in this approach lies in the easy synthesis of
well-defined substituted arene derivatives, particularly
durene and isodurene aromatic systems, which are
Chem. 1998, 63, 10077–10080; (f) Duan, I.-F.; Cheng,
C.-H.; Shaw, J.-S.; Cheng, S.-S.; Liou, K. F. Chem. Com-
mun. 1991, 1347–1348.
3. Hilt, G.; du Mesnil, F.-X. Tetrahedron Lett. 2000, 41,
6757–6761.
1
13
4. All products were characterised by H and C NMR, and
MS; for a general experimental procedure see Ref. 3.
5. The conversion to areneꢀruthenium complexes is currently
under investigation in our laboratory.
9
difficult to obtain by other methods (Scheme 2).
6. The regiochemistry was determined by HMBC and
HMQC NMR experiments. The ratios of regioisomers
13
The synthesis of the dimethoxy derivatives of isodurene
and durene (80 and 78% isolated yield over two steps,
respectively) illustrates the usefulness of the key reac-
tion in furnishing polysubstituted arenes with well-
defined substitution and functionalisation patterns.
were determined by integration over quantitative
C
NMR spectra of the crude reaction mixture and/or by gas
chromatography.
7. Representative procedure for the electrochemical oxidation
of the dihydroaromatic compounds:
In
a 50 mL beaker cell under nitrogen, 1,2-bis-
methoxymethyl-4,5-dimethyl-cyclohexa-1,4-diene (368 mg,
1.88 mmol) was dissolved in dichloromethane (20 mL)
Acknowledgements
containing Bu NBF4 (0.1 M) as supporting electrolyte.
4
The solution was electrolysed at a constant current (100
2
This work was supported by grants from the German
Science Foundation.
mA) on a glassy carbon anode (15 cm ) and a platinum
wire cathode until the starting material was consumed (GC
analysis, generally 2–3 F/mol). The solvent was evaporated
and the residue was filtered through a small amount of
silica gel (pentane:diethyl ether=10:1). The product 1,2-
bis-methoxymethyl-4,5-dimethyl-benzene (304 mg, 1.56
mmol, 83%; 78% over the two steps) was obtained as a
colourless oil after column chromatography on silica gel
with pentane as eluent.
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