Cobalt-catalyzed 1,4-hydrobutadienylation of 1-aryl-1,3-dienes with 2,3-dimethyl-1,3-butadiene

Article abstract of DOI:10.1002/anie.201103613

Round and round the olefin goes! A cobalt-catalyzed 1,4- hydrobutadienylation of a 1-aryl-substituted 1,3-diene with 2,3-dimethyl-1,3- butadiene yields 1,3,6-triene derivatives in excellent yield and chemoselectivity. The application of a bulky ligand (SchmalzPhos) leads to the selective formation of a single regio- and stereoisomer. Copyright

Full text of DOI:10.1002/anie.201103613

DOI: 10.1002/anie.201103613
Synthetic Methods
Cobalt-Catalyzed 1,4-Hydrobutadienylation of 1-Aryl-1,3-dienes with
2,3-Dimethyl-1,3-butadiene**
˘
Martin A. Bohn, Anastasia Schmidt, Gerhard Hilt,* Mehmet Dindaroglu, and Hans-
Gꢀnther Schmalz
The application of cobalt-based catalysts for the construction
of new carbon–carbon bonds, beyond simple cross-coupling,
is of increasing interest and opens access to a wide range of
products.[1] The CoBr2-ligand-Zn-ZnI2 system has been iden-
tified as a versatile precatalyst for the controlled and atom-
economical transformation of unsaturated organic molecules.
Two broad classes of reactions, which are promoted by this
fascinating transition metal and differ by the starting materi-
als and ligands, are discernable (Scheme 1). The first class
concerns transformations of alkynes such as the Alder-ene
reaction between internal alkynes and terminal olefins (A),[2]
the [2+2] cycloaddition between internal alkynes and cyclo-
pentene (B),[3] and the [2+2+2] trimerization of alkynes
(C).[4] The second class involves reactions based upon the 1,3-
butadiene motif. These reactions are the Diels–Alder reaction
(a para- or meta-selective version) of alkynes and 1,3-dienes
(D),[5] the [4+2+2] cycloaddition leading to eight-membered
rings (E),[6] and the 1,4-hydrovinylation reaction,[7] which
leads to 1,4-dienes starting from 1,3-dienes and terminal
olefins (F). The cobalt-catalyzed 1,4-hydrovinylation reaction
is complementary to an iron-based transformation which
delivers the corresponding linear 1,4-hydrovinylation prod-
ucts.[8]
During our ongoing investigations into the rich chemistry
of cobalt-catalyzed reactions of 1,3-dienes we recently came
across a novel reaction pathway. Initial studies carried out
with 1-alkyl-1,3-dienes showed the predominant formation of
dimers 1 and 2, resulting from unprecedented cobalt-cata-
lyzed [4+2] and [4+4] cycloadditions, respectively
(Scheme 2).[9,10] Actually, the product 1 corresponds to the
long sought-after Diels–Alder reaction with neutral electron
demand. Thus, the potential of the cobalt-catalyzed reactions
of 1-substituted 1,3-dienes deserves further investigation.
Scheme 2. Cobalt-catalyzed [4+2] and [4+4] cycloaddition of 1,3-nona-
diene.
Scheme 1. Portfolio of atom-economical cobalt-catalyzed reactions uti-
lizing unsaturated starting materials.
Interestingly, when 1-aryl-substituted 1,3-dienes
3
(Scheme 3) were reacted under the same reaction conditions
little to no dimerization products 1 and 2 were observed.[11]
Instead, the cobalt-catalyzed reaction of such aryldienes with
2,3-dimethyl-1,3-butadiene afforded linear (E,E)-1,3,6-tri-
enes 4, which result from a 1,4-hydrobutadienylation, that is,
from the addition of the 1-aryl-1,3-diene 3 to 2,3-dimethyl-
1,3-butadiene (DMB).
[*] Dipl.-Chem. M. A. Bohn, Dipl.-Chem. A. Schmidt, Prof. Dr. G. Hilt
Fachbereich Chemie, Philipps-Universitꢀt Marburg
Hans-Meerwein-Strasse, 35043 Marburg (Germany)
E-mail: hilt@chemie.uni-marburg.de
˘
Dipl.-Chem. M. Dindaroglu, Prof. Dr. H.-G. Schmalz
Department fꢁr Chemie, Universitꢀt zu Kçln
Greinstrasse 4, 50939 Kçln (Germany)
We were intrigued by this complete change of reactivity,
which led to the unexpected formation of 4, and so sought to
identify the reason for this change. While the overall reaction
[**] This work was supported by the Deutsche Forschungsgemeinschaft.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201103613.
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Table 1: Results of the cobalt-catalyzed 1,4-hydrobutadienylation reac-
tion.[a]
Entry Ar
Product (4)
Yield [%]
(4/5)[b]
91
(6.0:1)
1
2
Ph
93
4-MeOC6H4
(8.5:1)
72[c]
Scheme 3. Cobalt-catalyzed formation of a 1,3,6-triene 4.
84
(8.2:1)
3
4
4-EtO2CC6H4
4-F3CC6H4
2-MeC6H4
75
(5.8:1)
is related to the 1,4-hydrovinylation (F) we considered it
remarkable that the 1-aryl-1,3-diene selectively acts as the
alkene component in the presence of the 2,3-disubstituted 1,3-
butadiene, to which it is added in a 1,4-fashion. As indicated
in Scheme 3, the linear 1,3,6-triene (4) is the major product,
whereas the branched product (5) is detected only as a minor
component (up to ca. 10%). The separation of the two
isomers 4 and 5 could not be accomplished utilizing flash
column chromatography on silica gel.
85
(4.0:1)
5
6
(3,4-OCH2O)
C6H4
86
(7.5:1)
94
Obviously, the catalyst is able to discriminate with an
excellent degree of precision between the 1-mono- and the
2,3-disubstituted 1,3-diene as no products corresponding to
the inverted reaction were observed. The precatalyst system
applied was identical to the one used before in the 1,4-
hydrovinylation reaction: cobalt (1,2-bis-(diphenylphosphi-
no)ethane) bromide ([CoBr2(dppe)]), zinc iodide, and zinc
powder suspended in anhydrous dichloromethane.
7
8
9
2-furanyl
2-thienyl
(6.9:1)
67[c,d]
68[c,d]
(11.7:1)
N-tosyl-2-pyr-
rolyl
36[c,d]
(4.6:1)
To probe the scope of the method, we tested a series of 1-
aryl-1,3-butadienes, which were prepared by the Wittig
reaction of allyltriphenylphosphonium bromide and the
respective aromatic aldehydes. The cobalt-catalyzed trans-
formation of the aryldienes proceeded smoothly, when using
3 equivalents of 2,3-dimethyl-1,3-butadiene (DMB), to give
the products 4 in moderate to excellent yields (Table 1). As
shown in the case of 4b a decrease of the amount of DMB to
1.5 equivalents resulted in lower yields. We briefly assessed
the effect of the configuration and the stereochemical purity
of the 1-aryl-1,3-dienes 3 on the outcome of the reaction. As
the diene moiety of 3 is formally carried over into the triene
product 4, the question was whether the reaction would
proceed with retention of stereochemical information or not.
Therefore, we compared the outcome of the reaction of an
E/Z mixture (1:2.7) of 3 (Table 1, entry 7) with the outcome of
the reaction of the pure E isomer. As the resulting mixtures of
4g and 5g showed identical NMR spectra we can conclude
that both the E and the Z isomer of 3 are acceptable
substrates and both give E,E-4 as the main product. However,
to avoid any uncertainty the E isomers were used throughout,
unless specified otherwise (Table 1).[12]
49
(6.1:1)
10
11
ferrocenyl
(C6H5)2
89
(3.8:1)
[a] Reaction conditions: 1-Aryl-1,3-butadiene (1.0 equiv), 2,3-dimethyl-
1,3-butadiene (3.0 equiv), [CoBr2(dppe)] (10 mol%), ZnI2 (20 mol%), Zn
(20 mol%), dichloromethane, ambient temperature, 4–18 h. [b] Ratio
1
determined by H NMR spectroscopy by comparison of the integrals of
the newly formed methylene moiety of the 1,3,6-triene system. [c] Only
1.5 equiv of 2,3-dimethyl-1,3-butadiene were used. [d] Starting materials
applied as a mixture of E and Z isomers.
The reactions of a range of 1-aryl-substituted 1,3-dienes
with DMB were examined (Table 1). Electron-rich and
electron-deficient phenyl derivatives were both viable reac-
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tion partners. Excellent yields were obtained when electron-
rich aryls were used.
tene (CoIII) intermediate 6 through oxidative cyclization. The
terminal double bond of the 1-substituted 1,3-diene subse-
quently inserts into the cobalt–carbon s bond of 6, thus
leading to the key intermediate 7. At this point the
regiochemistry of the subsequent product has already been
decided. The alternative carbon–carbon bond formation, in
which the insertion of the terminal double bond of the 1-
substituted 1,3-diene occurs with the opposite regiochemistry
to give the branched product 5, is omitted from Scheme 4 for
clarity.[13]
The isomerization of the double bond of the mixture of E
and Z isomers of the 1-substituted 1,3-diene can be rational-
ized by intermediate 8, which leads predominantly to the E-
configured intermediate 9 by s–p–s equilibrium of cobalta-
cycles 7–9. A b-hydride elimination generates 10 and a
reductive elimination gives the acyclic 1,3,6-triene product 4
together with regeneration of the low-valent cobalt catalyst.
A tentative explanation for the preferential formation of the
linear product 4 in the 1,4-hydrobutadienylation reaction is
the possibility of an attractive interaction between the second
double bond of the 1-substituted 1,3-diene and the transition
metal in the step from intermediate 6 to 7. This secondary
attractive interaction might be influential enough during the
precoordination of the reaction partners to explain how the
more-substituted carbon atom ends up in the sterically more-
congested position next to the cobalt atom.
Both 1-phenyl- and 1-(4-methoxyphenyl)-1,3-butadiene
lead to nearly quantitative yields of the target 1,3,6-trienes 4a
and 4b, respectively (Table 1, entries 1 and 2). Electron-poor
and sterically hindered aryl substituents proved to be slightly
less reactive; nevertheless very satisfactory yields were
obtained for all the reactions.
Ester- and trifluoromethyl-substituted aromatic systems
led to slightly diminished yields (84% for 4c, 75% for 4d).
When 1,1-diphenyl-1,3-butadiene reacted with DMB, 4k was
obtained in excellent yield, which is noteworthy as the diene
system is sterically quite congested. In addition, in the case of
4e, which has an ortho-tolyl substituent, a yield of 85%
demonstrates that steric bulk adjacent to the diene moiety is
acceptable. Heteroaryl-substituted dienes are equally viable
starting materials as was demonstrated when the furan- and
thiophene-substituted products 4g and 4h were obtained in
good to excellent yields. However, the 2-(N-tosyl)-pyrrolyl
derivative 4i was isolated in only 36% yield. The yields for 4h
and 4i are acceptable especially considering the fact that
these compounds were only reacted with 1.5 equivalents of
DMB. With regards to the selectivity of the reaction for the
linear products 4 over the branched products 5, a clear
preference for the linear products was observed; in no case
was the branched product the major component. The ratio of
the two isomers for the reactions of monosubstituted 1,3-
dienes 3 varied from 4.0:1 to 11.7:1 (4/5) with no simple trends
presenting themselves.
During the course of our investigation of the 1,4-hydro-
butadienylation reaction, reported herein, a brief ligand
screening was carried out. Use of the common bisdiphenyl-
phosphino-type chelating ligands, dppp and dppb,[14] did not
lead to any significant improvement. However, when the
taddol-derived bidentate ligand 11 (SchmalzPhos), which has
proven useful in several other cases,[15] was tested the linear
product was produced exclusively (Scheme 5) without the
formation of any other side products.
The postulated mechanism for the 1,4-hydrobutadienyla-
tion reaction is relatively straightforward (Scheme 4). In
analogy to the mechanism proposed by us for the 1,4-
hydrovinylation reaction,[7,8] the initial step after the forma-
tion of the catalytically active cationic cobalt(I) species
(abbreviated as CoI) is the formation of a cobaltacyclopen-
Scheme 5. Cobalt-catalyzed formation of 1,3,6-trienes using the
SchmalzPhos ligand.
Although the yields are somewhat diminished when
utilizing 5 mol% of the [CoBr2(SchmalzPhos)] catalyst, the
products 4a, 4b, and 4d could be isolated as single regio- and
double-bond isomers, thus constituting a significant improve-
ment. When unsymmetrical electron-rich 1,3-dienes, such as
2-trimethylsilyloxy-1,3-butadiene (12), were used, the [CoBr2-
(dppe)] catalyst precursor led to a mixture of 13 and the
corresponding branched 1,4-hydrobutadienylation product in
43% yield (ratio: 4.3:1), as well as a [4+2] cycloaddition
Scheme 4. Postulated mechanism for the cobalt-catalyzed 1,4-hydro-
butadienylation.
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Communications
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[CoBr2(SchmalzPhos)] catalyst precursor gave the desired
product 13 with a disappointing yield of 30%, the strong
preference for the linear product remained unchanged.[16]
Therefore, in principle the 1,4-hydrobutadienylation could
be expanded to unsymmetrical starting materials, and out of
the many possible 1,4-hydrobutadienylation products that
could be formed 13 should be the preferred isomer.
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Scheme 6. Cobalt-catalyzed formation of a 1,3-diene-7-one (13).
This high degree of selectivity is encouraging and our
future efforts will include a detailed examination of the
reactivity of unsymmetrical mono- and disubstituted 1,3-
butadiene systems and an improved ligand design for regio-
and chemoselective bond-formation processes for the syn-
thesis of linear triene products.
In conclusion, we have reported herein a new carbon–
carbon bond-forming process, which uses easily obtainable
starting materials and exploits a well-known reactive cobalt-
based system. The active catalyst exhibits exquisite discrim-
ination of the two different 1,3-diene types applied, with only
the 1-aryl-substituted 1,3-butadiene acting as the alkene
component. Linear 1,3,6-trienes 4 are the predominant
products when the simple, readily available [CoBr2(dppe)]
catalyst precursor is used, whereas the use of the somewhat
more elaborate complex [CoBr2(SchmalzPhos)] leads to
exclusive formation of the linear product 4, with no formation
of the branched side product 5.
[8] B. Moreau, J. Y. Wu, T. Ritter, Org. Lett. 2009, 11, 337.
[9] dppm = 1,1-bis(diphenylphosphino)methane, py-imine = 2,4,6-
trimethyl-N-(pyridin-2-ylmethylene)aniline.
[10] The reaction for the formation of 1 was performed utilizing
[CoBr2(dppm)] (10 mol%), Zn powder (20 mol%), ZnI2
(20 mol%) in dichloromethane at ambient temperature. Product
1 was obtained in 73% yield as a colorless oil. The reaction for
the formation of 2 was performed utilizing [CoBr2(py-imine)]
(10 mol%) under otherwise identical reaction conditions. Prod-
uct 2 was obtained in 27% yield as a colorless oil. The NMR data
for 1 and 2 did not allow unambiguous assignments of the
regiochemistry for 1 or the differentiation between the cis and
trans diastereomers for both products 1 and 2.
[11] When 1,3-nonadiene was reacted with 2,3-dimethyl-1,3-buta-
diene in the presence of [CoBr2(dppm)] as catalyst precursor, the
mixed [4+2] cycloaddition product was isolated in 43% yield.
Utilizing the [CoBr2(dppe)] catalyst precursor led to an insep-
arable mixture of 1,4-hydrobutadienylation and [4+2] cyclo-
addition products.
[12] A number of compounds were available as the (E)-3-arylpro-
penal, which could be converted into the (E)-1-aryl-1,3-dienes
by the Wittig reaction. For cases where the respective propenals
were not commercially available a procedure by Battistuzzi et al.
lead to the desired intermediates starting from the aryl bromides
and acrolein diethyl acetale: G. Battistuzzi, S. Cacchi, G. Fabrizi,
Org. Lett. 2003, 5, 777.
Received: May 26, 2011
Published online: August 31, 2011
Keywords: alkenes · cobalt · homogeneous catalysis ·
.
hydrobutadienylation · polyenes
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1,3-diene myrcene with a 1-aryl-1,3-diene the corresponding
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two products (ratio = 1.0:1.7) were obtained in a combined yield
of 59%.
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