Up the hill: Selective double-bond isomerization of terminal 1,3-dienes towards Z-1,3-dienes or 2Z,4E-dienes

Article abstract of DOI:10.1002/anie.201107512

Against all odds: Two different cobalt catalyst systems led to the selective isomerization of 1,3-dienes. In the case of the [CoBr ₂(py-imine)]-catalyzed reaction, the Z-1,3-diene was formed in a highly selective manner (see scheme). When the catalyst precursor [CoBr ₂(dpppMe₂)] was applied, a double-bond migration and selective isomerization towards the 2Z,4E-configured 2,4-dienes were observed Copyright

Full text of DOI:10.1002/anie.201107512

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DOI: 10.1002/anie.201107512
Synthetic Methods
Up the Hill: Selective Double-Bond Isomerization of Terminal 1,3-
Dienes towards Z-1,3-Dienes or 2Z,4E-Dienes**
Florian Pꢀnner, Anastasia Schmidt, and Gerhard Hilt*
Carbon–carbon double bonds are among the most versatile
functional groups in organic chemistry. Many reactions have
been established for the synthesis of double bonds,[1] while
only a relative small number of methods are available for the
isomerization of double bonds. A selective isomerization of
double bonds towards a uniform olefin geometry can be
accomplished utilizing photochemical[2] and in some cases
Scheme 2. Double-bond isomerization for the stereoselective genera-
tion of (Z)-4a.
radical[3] or transition-metal-catalyzed methods.[4] Stepwise
chemical methods, such as the reaction sequence described by
Reetz,[5c] involving epoxidation of an olefin, ring-opening by a
silyl anion, and Peterson-type olefination, are also available
for the inversion of the double bond geometry.[5]
reaction could be expanded to a number of other 1,3-dienes.
The results of this investigation are summarized in Table 1.
The isomerization reaction tolerates aliphatic and aro-
matic substituted 1,3-dienes as well as an additional isolated
terminal double bond (Table 1, entry 4). Esters, ethers, and
silyloxy functional groups were accepted as substrates as well
In the course of our ongoing investigation into atom-
economic transformations for the generation of carbon–
carbon bonds utilizing low-valent cobalt complexes, we found
a catalyst system enabling the synthesis of 1,3,6-trienes of type
3. Starting from an aryl-substituted 1,3-diene (1) and a 2,3-
disubstituted 1,3-diene (2), this 1,4-hydrobutadienylation is
accomplished in
a stereo- and regioselective fashion
(Scheme 1).[6]
Table 1: Results of the cobalt-catalyzed isomerization to Z-1,3-dienes.[a]
Entry
Product
Yield [%]
1
75
2
3
4
5
69
59
44
73
Scheme 1. 1,4-Hydrobutadienylation.
During the screening process for suitable catalysts, we
identified a cobalt complex that led to isomerization of the
initial 1:1 ratio of the 1,3-butadiene derivative (E/Z)-4, which
was generated by a stereo-unspecific Wittig olefination of
octanal. In the absence of 2, the E/Z mixture of 4 is converted
selectively into (Z)-4a by utilizing a catalyst system compris-
ing [CoBr2(py-imine)], zinc powder, and ZnI2 within 17 h
reaction time in good yield (Scheme 2). This isomerization
6
75
7
8
9
71
50
54
[*] Dipl.-Chem. F. Pꢀnner, Dipl.-Chem. A. Schmidt, Prof. Dr. G. Hilt
Fachbereich Chemie, Philipps-Universitꢁt Marburg
Hans-Meerwein-Strasse, 35043 Marburg (Germany)
E-mail: hilt@chemie.uni-marburg.de
10
64
[**] Financial support from the Deutsche Forschungsgemeinschaft is
gratefully acknowledged. We thank Prof. R. W. Hoffmann and Prof.
M. T. Reetz for helpful discussions.
[a] [CoBr2(py-imine)] (5–10 mol%), zinc powder (10–20 mol%), zinc
iodide (10–20 mol%), 5–120 h, CH2Cl2, ambient temperature. TBS=tert-
butyldimethylsilyl.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201107512.
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(Table 1, entries 3 and 8–10). The relatively high volatility of
many of the products led to diminished yields when the
solvent was removed after workup. Also, in some cases
polymer-type side-products were obtained after prolonged
reaction times. Noteworthy is that the deprotected product 4h
was previously used as an intermediate in the synthesis of a
pheromone[7a] and can be found in different species in form of
corresponding esters.[7b,c]
We also identified a modified cobalt catalyst system
comprising [CoBr2(dpppMe2)], zinc powder, and ZnI2, which
migrated diene double bonds inward by only one position
(Scheme 3). Thereby, product 6a was generated exclusively as
the 2Z,4E isomer by a 1,5-hydrogen shift.[8]
For this isomerization reaction, aliphatic and aromatic
substituents and protected alcohols were tolerated. The
terminal double bond in 6c remains unchanged, indicating
the high chemoselectivity of the catalyst system for the
isomerization of 1,3-dienes. The mild reaction conditions also
allowed the selective synthesis of 6 f without additional
isomerization towards the corresponding conjugated product.
In contrast, we were not able to generate 1-phenyl-2,4-
pentadiene selectively by a Wittig olefination to investigate
the cobalt-catalyzed isomerization with this derivative. Under
the reaction conditions of the Wittig olefination (in analogy to
Scheme 2) of phenyl acetaldehyde, the double bonds sponta-
neously migrated towards the conjugated system. Accord-
ingly, the cobalt-catalyzed isomerization reaction is well-
suited to generate 1,3-dienes with benzyl-CH2 or aryl-CH2
substituents, thus avoiding isomerization towards the unde-
sired aryl–diene conjugated products.
Of note, some long-chained 2Z,4E-configured dienes have
been found in nature, mostly as pheromones or as part of
more complex natural products, such as product 6a or a
compound related to product 6g.[9] Accordingly, applications
of this new method in natural product synthesis can be
envisaged.
Scheme 3. Double-bond migration for the stereoselective generation of
(2Z,4E)-6a.
The isomerization reactions described herein are unpre-
cedented because thermodynamically less-favored isomers
are formed. Therefore, both reactions cannot be the result of
a transformation in its thermodynamic equilibrium. The
formation of the Z double bond in 4 and 6 must therefore
be a result of kinetic effects.
Remarkably, no further isomerization of the double bonds
in 6a along the chain or the E,E isomer was observed. The
cobalt catalyst system converts both isomers (Z)-4a and (E)-
4a into 2Z,4E-configured isomer 6a in a stereoconvergent
fashion under mild reaction conditions. The scope of the
reaction was expanded towards several 1,3-dienes, and the
results of this investigation are summarized in Table 2.
Control experiments have shown that the reaction does
proceed in the dark but does not proceed when any of the
cobalt catalyst components is absent. The yields remain
unchanged when varying amounts of zinc powder and zinc
iodide were used. Furthermore, the isolated isomers (Z)-4a or
(2Z,4E)-6a could not be converted into the isomers (E)-4a or
(2E,4E)-6a at elevated temperatures (up to 508C in a sealed
tube) when retreated with the catalyst systems [CoBr2(py-
imine)] or [CoBr2(dpppMe2)], respectively, with Zn and ZnI2.
We are well aware that the findings are in apparent
conflict with the concept of microscopic reversibility of
reactions in equilibrium, but these are the facts. When pure
(E)-4b was used under the reaction conditions, apart from the
desired (Z)-4b, only polymerization side-products were
observed. Therefore, the E isomers are either isomerized or
polymerized under the applied reaction conditions. Accord-
ingly, we propose that both isomerization reactions must
proceed by coordination of the 1,3-diene to the cobalt center
and that the decomplexation of the Z-configured products is
kinetically irreversible. In the case of the [CoBr2(py-imine)]-
catalyzed reaction, it seems plausible that the s-cis conforma-
tion of the complexed 1,3-diene in complex 7b results in a
kinetically less-stable complex, leading to the decomplexation
of (Z)-4 (Scheme 4). The free diene (Z)-4 will also adopt the
more favorable s-trans conformation, leading to the accumu-
lation of the product.
Table 2: Results of the cobalt-catalyzed isomerization to (2Z,4E)-2,4-
dienes.[a]
Entry
Product
Yield [%]
67
1
2
3
67
61
4
5
58[b]
43[b,c]
6
89
7
8
67
78
Nevertheless, the exact process for the isomerization from
7a to 7b remain undetermined and a detailed quantum
chemical investigation concerning the coordination mode of
the 1,3-diene to the catalyst (s-cis versus s-trans),[10] the
[a] [CoBr2(dpppMe2)] (5–20 mol%), zinc powder (10–40 mol%), zinc
iodide (10–40 mol%), 18–72 h, CH2Cl2, ambient temperature. [b] Both
1,3-diene units were isomerized. [c] Increased amounts of polymeric
side-products were formed.
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configured 2,4-diene subunit can be found in several natural
products, and with our method a new approach for the
synthesis of such structures seems possible.
Experimental Section
Representative procedure 1 (Table 1, entry 1): [CoBr2(py-imine)]
(20 mg, 0.05 mmol, 5 mol%), anhydrous zinc iodide (32 mg,
0.10 mmol, 10 mol%), and zinc powder (6.5 mg, 0.10 mmol,
10 mol%) were suspended under argon atmosphere in anhydrous
dichloromethane (1 mL), and undeca-1,3-diene (152 mg, 1.0 mmol,
1 equiv) was added. The reaction mixture was stirred for 17 h at
ambient temperature and after addition of n-pentane (1 mL) filtered
over silica gel. The solvent was removed and the residue was purified
by column chromatography on silica gel (eluent: n-pentane). The
product (Z)-undeca-1,3-diene was obtained as colorless, pungent oil
(114 mg, 0.75 mmol, 75%). 1H NMR (CDCl3, 300 MHz): d = 6.72–
6.58 (m, 1H), 6.00 (t, J = 10.9 Hz, 1H), 5.51–5.41 (m, 1H), 5.18 (dd,
J = 16.9, 2.0 Hz, 1H), 5.08 (d, J = 10.2 Hz, 1H), 2.23–2.14 (m, 2H),
1.41–1.22 (m, 10H), 0.89 ppm (t, J = 6.7 Hz, 3H). 13C NMR (CDCl3,
75 MHz): d = 133.0, 132.4, 129.1, 116.6, 31.8, 29.6, 29.2, 29.2, 27.7, 22.6,
14.1 ppm. IR (film: n˜ = 3086, 3009, 2957, 2926, 2855, 1807, 1644, 1593,
1465, 1435, 1378, 996, 961, 901, 784, 723, 655, 611, 413 cmÀ1. MS (EI):
m/z (%) = 152 ([M+], 18), 95 (16), 81 (42), 67 (73), 54 (100). HRMS
(EI): m/z (%) calculated for C11H20: 152.1565; found: 152.1559.
Representative procedure 2 (Table 2, entry 1): [CoBr2-
(dpppMe2)] (66 mg, 0.10 mmol, 10 mol%), anhydrous zinc iodide
(64 mg, 0.20 mmol, 20 mol%), and zinc powder (13 mg, 0.20 mmol,
20 mol%) were suspended under argon atmosphere in anhydrous
dichloromethane (1 mL), and undeca-1,3-diene (152 mg, 1.0 mmol,
1 equiv) was added. The reaction mixture was stirred at ambient
temperature for 72 h and after addition of n-pentane (1 mL) filtered
over silica gel. The solvent was removed and the residue was purified
by column chromatography over silica gel (eluent: n-pentane). The
product (2Z,4E)-undeca-2,4-diene was obtained as colorless, pungent
oil (102 mg, 0.67 mmol, 67%). 1H NMR (CDCl3, 300 MHz): d = 6.33
(ddq, J = 15.1, 10.9, 1.2 Hz, 1H), 5.98 (dt, J = 10.9, 1.4 Hz, 1H), 5.67
(dt, J = 15.0, 7.0 Hz, 1H), 5.43–5.31 (m, 1H), 2.11 (dt, J = 7.1, 7.0 Hz,
2H), 1.74 (dd, J = 7.1, 1.6 Hz, 3H), 1.44–1.22 (m, 8H), 0.89 (t, J =
6.7 Hz, 3H). 13C NMR (CDCl3, 75 MHz): d = 134.6, 129.6, 125.3, 32.9,
31.8, 29.4, 28.9, 22.6, 14.1, 13.2. IR (film): n˜ = 3020, 2958, 2926, 2855,
1654, 1614, 1458, 1409, 1377, 980, 944, 920, 833, 710, 609, 425 cmÀ1. MS
(EI): m/z (%) = 152 ([M+], 29), 95 (11), 81 (64), 68 (100), 53 (10).
HRMS (EI): m/z (%) = calculated for C11H20: 152.1565; found:
152.1550.
Scheme 4. Rationale for the accumulation of product (Z)-4.
possibility of cobalt hydrides as catalytically active species
and the steric factors responsible for the preferential for-
mation of the Z double bonds is underway.
On the other hand, the isomerization process leading to
products of type 6 utilizing the bidentate dpppMe2 ligand is
much more easily rationalized (Scheme 5). The free coordi-
Scheme 5. Rationale for the formation of the 2Z,4E-configured prod-
ucts of type 6.
nation site on the cobalt center in the cobaltacycle 8b allows
the b-hydride elimination from the adjacent CH2 group for
the formation of the s-bonded cobalt hydride intermediate
9.[11,12] A reductive elimination regenerates the active catalyst
and furnishes the 2Z-configured double bond in (2Z,4E)-6.
The overall reaction is a formal 1,5-hydogen shift, and the 4E-
configured double bond is formed exclusively for steric
reasons, whereas the 2Z-configured double bond is predeter-
mined in the cobaltacycle 8b. The irreversible decomplex-
ation of the product (2Z,4E)-6 is in accordance with the
observation that no conversion of 1,4-disubstituted 1,3-diene
derivatives could be accomplished with cobalt catalyst
systems in our laboratory to date.
In conclusion, we have presented a new isomerization of
double bonds by applying a tridentate ligand system for the
selective formation of Z-configured 1,3-dienes. The double
bond migration and isomerization initiated by a bidentate
phosphine ligand system led to the stereoconvergent synthesis
of 2Z,4E-configured products. These reactions are the first
examples of a transition-metal-catalyzed isomerization to the
thermodynamically less stable isomers. Especially the 2Z,4E-
Received: October 25, 2011
Published online: December 15, 2011
Keywords: cobalt · dienes · double-bond migration ·
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isomerization · stereoselectivity
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