Facile synthesis of dibranched conjugated dienes via palladium-catalyzed oxidative coupling of N-tosylhydrazones

Article abstract of DOI:10.1039/c3cc43593h

A facile and highly regioselective Pd-catalyzed oxidative coupling of N-tosylhydrazones providing efficient access to 2,3-disubstituted-1,3-butadienes has been developed. This process features readily available starting materials and mild reaction conditions. Further transformations of the obtained dibranched 1,3-dienes, through Diels-Alder reactions and indene synthesis, are also demonstrated, which reveal their great potential for synthetic utility.

Full text of DOI:10.1039/c3cc43593h

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Facile synthesis of dibranched conjugated dienes
via palladium-catalyzed oxidative coupling
of N-tosylhydrazones†
Cite this: Chem. Commun., 2013,
49, 9218
Received 14th May 2013,
Accepted 6th August 2013
Huanfeng Jiang,* Li He, Xianwei Li, Huoji Chen, Wanqing Wu and Wei Fu
DOI: 10.1039/c3cc43593h
www.rsc.org/chemcomm
A facile and highly regioselective Pd-catalyzed oxidative coupling scope of these reactions seems limited to the linear 1,3-dienes,
of N-tosylhydrazones providing efficient access to 2,3-disubstituted- while highly selective formation of dibranched 1,3-dienes is
1,3-butadienes has been developed. This process features readily seldom reported.7 Obviously, a highly regioselective synthetic
available starting materials and mild reaction conditions. Further methodology for 2,3-disubstituted-1,3-butadienes from simple
transformations of the obtained dibranched 1,3-dienes, through and readily available starting materials is significantly desirable.
Diels–Alder reactions and indene synthesis, are also demonstrated,
which reveal their great potential for synthetic utility.
Recently, enormous efforts have been made to develop
Pd-catalyzed carbene cross-coupling reactions based on N-tosyl-
hydrazones,8,9 which are easily generated from the inexpensive
Conjugated dienes are one of the most important scaffolds to carbonyl compounds, and the reaction can be regarded as a cross-
increase molecular complexity in organic synthesis,1 and they coupling of carbonyl groups. Nevertheless, palladium-catalyzed
are abundant in a wide range of natural products.2 Thus, facile, oxidative coupling reactions using N-tosylhydrazones as the coupling
mild and selective methods for the preparation of 1,3-dienes in partner are rare.8h,10 With relation to our interest in Pd-catalyzed
high regioselectivity are undoubtedly of great significance. oxidative coupling chemistry,11 we herein disclose a facile
Traditional routes to 1,3-dienes include Wittig reactions Pd-catalyzed oxidative coupling of N-tosylhydrazones to construct
(Scheme 1a),3 reduction of 1,3-diynes or 1,3-enyne,4 transition 2,3-disubstituted-1,3-butadienes with high regioselectivity.
metal-catalyzed cross-coupling reactions5 (Scheme 1b) and
Initially, we explored the Pd-catalyzed oxidative coupling
1,2- or 1,4-elimination of allylic alcohols.6 Despite the versatility reaction of N-tosylhydrazone 1a. Intriguingly, conjugated diene
of these transformations, certain limitations still exist. For instance, product 2a could be observed when the reaction was conducted
some of these synthetic methods require harsh reaction conditions
and highly functionalized starting materials. Furthermore, the
Table 1 Optimization of reaction conditionsa
Entry
Catalyst
Oxidant
Yieldb (%)
1
2
3
4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Pd(PPh3)4
Pd(PPh3)4
—
Air
27
71
75
Trace
Trace
83 (70)
28
23
0
O2 (1 atm)
BQ (2 equiv.)
DDQ (2 equiv.)
Cu(OAc)2 (2 equiv.)
O2 (1 atm)
O2 (1 atm)
O2 (1 atm)
—
5
6c
7c
8c
9
Scheme 1 Selected synthetic methods for dibranched dienes.
10c
11c
O2 (1 atm)
N2 (1 atm)
0
School of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou 510640, China. E-mail: jianghf@scut.edu.cn; Fax: +86 20-87112906;
Tel: +86 20-87112906
Pd(OAc)2
Trace
a
Reaction conditions: 1a (0.25 mmol, 72 mg), [Pd] (5 mol%) in the
t
† Electronic supplementary information (ESI) available: Experimental section,
characterization of all compounds, and copies of 1H and 13C NMR spectra for
selected compounds. See DOI: 10.1039/c3cc43593h
presence of BuOLi (3.5 equiv., 70 mg) and 4 Å M.S. (60 mg) in 2 mL of
DMSO for 14 h. b Determined by GC. Number in parentheses is isolated
yield. c Adding BQ (20 mol%).
c
9218 Chem. Commun., 2013, 49, 9218--9220
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under an air atmosphere (Table 1, entry 1), which inspired us to afforded the corresponding 2,3-diaryl-1,3-dienes in good to
screen for more suitable reaction conditions. Therefore, a number excellent yields (2a–f, 2n–p, 2r and 2s), while the substrates
of oxidants, such as O2, benzoquinone (BQ), 2,3-dichloro-5,6- bearing electron-withdrawing groups just led to the desired
dicyano-1,4-benzoquinone (DDQ), and Cu(OAc)2, were examined products in diminished yields (2g–i). It is noteworthy that
(Table 1, entries 2–6). Gratifyingly, performing the reaction using halide substituents could survive in the reaction (2j–m, 2q),
molecular oxygen (1 atm) as the oxidant led to exclusively selective which implied that the reaction started from PdII, and could be
formation of the desired dibranched product 2a, while no linear further transformed into more complex structures. In addition,
1,3-diene was detected. In addition, using BQ (2 equiv.) as the the reaction with para-, ortho-, meta-substituted functional
oxidant in the reaction also gave the desired product 2a in good groups on the aromatic rings of substrates proceeded efficiently
yield. However, employing oxidants DDQ and Cu(OAc)2 only (2m–s). Furthermore, naphthyl N-tosylhydrazones also reacted
provided a trace amount of product 2a (Table 1, entries 4 and 5). smoothly, leading to the corresponding products 2t and 2u in
Unexpectedly, the best yield of product 2a was observed when moderate yields. Finally, heterocyclic N-tosylhydrazone was also
conducting the reaction using the O2 oxidant (1 atm) combined a suitable substrate for this transformation (2v).
with BQ (20 mol%) (Table 1, entry 6). Subsequently, other
Cyclization reactions are of significant value in the synthesis
catalysts, such as PdCl2 and Pd(PPh3)4 were found to be less of complex structures.1c To illustrate the synthetic applications
effective in this reaction (Table 1, entries 7 and 8). It should be of the resulting dibranched 1,3-dienes, the synthesis of indenes
noted that no desired product was generated when the reaction 3 via Lewis acid-catalyzed cyclization of the dibranched dienes
was carried out using Pd(PPh3)4 but without oxidants (Table 1, was demonstrated, affording the cyclization products 3 in good
entry 9), which indicated that the reaction was started by PdII. to excellent yields (Scheme 2, 3a–d). Moreover, Diels–Alder
Finally, control experiments revealed that no desired product reactions of the generated dibranched dienes with dienophiles,
formation occurred in the absence of a catalyst or oxidants including methyl acrylate, dimethyl acetylenedicarboxylate,
(Table 1, entries 10 and 11).
maleic anhydride and N-phenylmaleimide, were also carried
With the optimized conditions in hand, we then studied the out to give the corresponding cycloadducts 4–6 (6a, 6b) and 7
scope of the Pd-catalyzed oxidative coupling of the N-tosyl- (7a–c) in good to excellent yields (Scheme 2).
hydrazone reactions. As illustrated in Table 2, the oxidative
To gain further insights into the reaction mechanism, a
coupling reactions proceeded smoothly over a wide range of Pd-catalyzed oxidative cross-coupling reaction of N-tosylhydr-
substrates with moderate to excellent yields. When employing azones 1a and 1c was performed. As illustrated in Scheme 3, the
the substrates with electron-donating groups, the reactions cross-coupling product 2a–c could be obtained under standard
conditions, though the yield was only 38%.
Although the exact mechanism for the product formation is
not clear at the present stage, a plausible mechanism for the
Table 2 Pd-catalyzed oxidative coupling reaction of N-tosylhydrazones 1 to 2a,b
oxidative cross-coupling reaction is proposed in Scheme 4.
Decomposition of the diazo compounds A, which are trans-
formed in situ from N-tosylhydrazones 1 in the presence of a
base,12 via a palladium catalyst generates the Pd–carbene B.13
a
Unless otherwise noted, the reaction conditions are as follows:
1 (0.25 mmol), Pd(OAc)2 (5 mol%), oxidant (BQ: 20 mol%; O2: 1 atm),
tBuOLi (3.5 equiv.) and 4 Å M.S. (60 mg) in DMSO (2 mL) at 90 1C for
14 h. Determined by GC.
b
Scheme 2 Selected transformations of dibranched 1,3-dienes 2.a,b
Chem. Commun., 2013, 49, 9218--9220 9219
c
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Program of China (973 Program) (2011CB808600), the
Changjiang Scholars and Innovation Team Project of Ministry
of Education, the Guangdong Natural Science Foundation
(10351064101000000), China Postdoctoral Science Foundation
(2012T50673) and the Fundamental Research Funds for the
Central Universities (2012ZP0003).
Notes and references
Scheme 3 Cross-coupling reaction between 1a and 1c.a,b
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In summary, we have described a facile, mild and highly
regioselective synthesis of 2,3-substituted-1,3-butadiene by a
Pd-catalyzed oxidative coupling reaction of N-tosylhydrazones.
Moreover, the generated dibranched 1,3-dienes showed great
reactivity in Diels–Alder reactions and indene synthesis. In view
of the readily available starting materials, simple operation of
the process, as well as high regioselectivity, this methodology
may become a useful tool for the synthesis of dibranched
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c
9220 Chem. Commun., 2013, 49, 9218--9220
This journal is The Royal Society of Chemistry 2013