An improved cobalt catalyst for homo Diels-Alder reactions of acyclic 1,3-dienes with alkynes

Article abstract of DOI:10.1016/S0040-4039(00)01163-1

An efficient cobalt(I)-catalysed homo Diels - Alder reaction of acyclic 1,3-dienes and acetylene derivatives is described. The catalyst system consists of a mixture of a readily available CoBr₂(dppe) complex, zinc iodide as a cocatalyst, and te

Full text of DOI:10.1016/S0040-4039(00)01163-1

Tetrahedron Letters 41 (2000) 6757±6761
An improved cobalt catalyst for homo Diels±Alder reactions
of acyclic 1,3-dienes with alkynesy
Gerhard Hilt* and Francois-Xavier du Mesnil
Department Chemie, Ludwig-Maximilians Universitat Munchen, Butenandtstr. 5-13, 81377 Munchen, Germany
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Received 28 June 2000; accepted 7 July 2000
Abstract
An ecient cobalt(I)-catalysed homo Diels±Alder reaction of acyclic 1,3-dienes and acetylene derivatives
is described. The catalyst system consists of a mixture of a readily available CoBr2(dppe) complex, zinc
iodide as a cocatalyst, and tetrabutylammonium borohydride as reducing agent. This system increases the
reactivity of the cobalt(I) catalyst, so that acyclic dienes and acetylenes can be transformed to the
1,4-dihydroaromatic products in good yield and excellent purity. The regioselectivity of the homo Diels±
Alder reaction greatly favours the 1,4-substitution pattern of the formed product. # 2000 Elsevier Science
Ltd. All rights reserved.
The usefulness of the Diels±Alder reaction in complexity increasing transformation has been
well-established in organic synthesis. While two new carbon±carbon bonds are formed, the
regiochemistry and stereochemistry of the cycloaddition can well be controlled and predicted.1
These statements are especially true for reactions where the two starting materials have di€erent
electronical properties. Problems arise when substrates of equal electronic behaviour (homo
Diels±Alder reaction), and without the functionality to incorporate a Lewis acid activation, are
chosen. In these cases, drastic reaction conditions must be applied and quite often polymerisation
is an accompanying side reaction.2
The known cobalt(I)-catalysed homo Diels±Alder reactions are mostly limited towards the
cycloaddition between 2,5-norbornadiene and acetylene derivatives. The reactive cobalt(I)
catalyst is generated in situ from readily available cobalt(II) (CoI2/PR3/Zn)3 or cobalt(III)
precursors (Co(acac)3/PR3/Et2AlCl).4
In an attempt to generate a more reactive system starting from cobalt(II) iodide, we have
substituted zinc as a reducing agent towards other single electron sources or hydride donors for
* Corresponding author. Fax: +49 89 21807425; e-mail: gerhard.hilt@cup.uni-muenchen.de
y
In memoriam Professor Eberhard Steckhan.
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01163-1

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the cycloaddition between 2,5-norbornadiene (1) and phenylacetylene (2) (Scheme 1). Reducing
agents such as manganese, Devarda reagent, lithium naphthalenide, electrochemical reduction
(carbon electrode), borohydrides, and aluminium hydrides were used, but to our surprise, even
for prolonged reaction times, no or little product could be detected and only in the cases where
the original elemental zinc or alanes (DIBAL) were used could the desired product be isolated in
reasonable yields.
Scheme 1.
We therefore assumed that the addition of a Lewis acid as a cocatalyst to the reaction mixture
might be useful. When zinc iodide was used as an additive, the reaction of 1 and 2 proceeded
smoothly with lithium triethoxyaluminiumhydride (LiAlH(OEt)3) or sodium borohydride
(NaBH4) as reducing agent. In addition, even cobalt bromide and cobalt chloride triphenylphosphine
complexes, unreactive under the original conditions, catalysed the cycloaddition between 1 and 2
after the addition of several equivalents of zinc iodide.
In a series of reactions with di€erent ratios of zinc iodide and the cobalt(II) complex, it was
found that the best results were obtained in the presence of 3.0 mol equivalents of ZnI2, while at
higher catalysts to the zinc iodide ratios no further increase in reactivity was observed. The
reaction also showed an induction phase (colour changed from green towards a brown solution)
whose length was dependent on the reducing agent used. While zinc had a somewhat long
induction period, the colour change was observed within minutes for lithium triethoxy
aluminiumhydride and immediately for tetrabutylammonium borohydride (Bu4NBH4), which is
the best soluble reducing agent in dichloromethane used in this series of experiments. We
therefore chose a system consisting of CoBr2(dppe), ZnI2, and Bu4NBH4 as a catalyst mixture for
homo Diels±Alder reactions. As expected, the reaction of 1 with various alkynes was successfully
catalysed by our catalyst system and the products could be obtained in comparable good yields
and purities (Scheme 2).4
Scheme 2.
Conversely, the homo Diels±Alder reaction failed for other cyclic 1,3- and 1,4-dienes (such as
1,3-and 1,4-cyclohexadiene, 1,3- and 1,5-cyclooctadiene) with 2a as dienophile. Such reactions
are to our knowledge also not described for the original catalyst systems (CoI2/PR3/Zn) and
(Co(acac)3/PR3/Et2AlCl). However, the reaction of acyclic 1,3-dienes like 2,3-dimethyl-1,3-butadiene,

6759
isoprene, and myrcene with various terminal alkynes proceeded smoothly to form the corresponding
dihydroaromatic systems in >90% conversion (GC-control). Although the products were quite
sensitive towards oxidation, dicult to isolate and purify via repeated column chromatography
on silica gel with pentane as eluent (especially when myrcene and/or trimethylsilylacetylene are
used as starting materials) we were able to isolate the products in good yields and in good GC
purity (generally >95%).
The products of the homo Diels±Alder reaction can easily be oxidised by air, so that the
corresponding aromatic derivatives are obtained. Thereby the high degree of 1,4- over 1,3-selectivity
(generally >15:1) in the cases of isoprene derivatives as diene and terminal acetylenes as
dienophile can be established (Scheme 3).
Scheme 3. Reaction conditions: CoBr2(dppe) (40 mg), ZnI2 (63 mg), Bu4NBH4 (15±17 mg), CH2Cl2 (2.0 mL), diene
(0.5 mL), alkyne (0.5 mL), ambient temperature, 12±16 h5
When activated alkynes (ethyl propiolate) and activated alkenes (acrylonitrile) were used as
dienophiles precipitates of polymeric nature formed after a short period of time and after
complete conversion of the dienophile only traces of the desired product could be detected by
GCMS. For example, in the case of the reaction of 1 with ethyl propiolate 5% of the desired homo
Diels±Alder product 11 could be isolated as well as 36% of the trimerised 1,2,4-trisubstituted ester
12 and traces of the 1,3,5-substituted triester (Scheme 4).6
Scheme 4.

6760
Therefore, the starting material, as in the case of acrylonitrile, is most probably polymerised
and could not be detected by GC or isolated after column chromatography.
We then turned our attention towards the possibility of tandem Diels±Alder reactions, since the
reaction of 1-ethynyl-cyclohexene (2c) with a 1,3-diene under these circumstances provided a new
1,3-diene substructure which could be trapped with reactive dienophiles like tetracyanoethylene or
maleic anhydride. Such a tandem Diels±Alder reaction generated polyfunctionalised polycyclic
compounds 13 and 14 in good yield, high purity and excellent regiochemistry, which were also
much more stable than the dihydroaromatic intermediates and with the polar substituents much
easier to purify by chromatography (SiO2/pentane:Et2O=2:1 for 13 and diethyl ether for 14)
(Scheme 5).7
Scheme 5.
We are currently investigating the possibility of using our catalyst system in combination with
a tandem Diels±Alder reaction or other functional group transformation to prepare
polyfunctionalised polycyclic precursors for natural product synthesis.
Acknowledgements
This work was supported by a grant from the Deutsche Forschungsgemeinschaft.
References
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5. Representative procedure for the homo Diels±Alder reaction: In a 50 mL round-bottomed ¯ask under nitrogen,
CoBr2(dppe) (40 mg, 64.8 mmol), and ZnI2 (63. mg, 197.4 mmol) were suspended in dry dichloromethane (2.0 mL)
and 2,3-dimethyl-1,3-butadiene (0.5 mL, 363 mg, 4.42 mmol) and phenylacetylene (0.5 mL, 465 mg, 4.55 mmol)
were added. To this green mixture 15±17 mg of Bu4NBH4 were added until the colour changed to a light brown
and the reaction mixture was stirred at ambient temperature for 12 h. After addition of pentane (5 mL), the
mixture was ®ltered through a small amount of silica gel and the solvents evaporated. The product (684 mg, 3.71
mmol, 84%) was obtained as a colourless oil after column chromatography on silica gel with pentane as eluent.
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