Palladium-catalyzed formation of C=C bonds: A regioselective strategy for the synthesis of 2-vinylfurans by 1,2-H shift of palladium-carbene complexes

Article abstract of DOI:10.1002/ejoc.201300016

A convenient method to synthesize vinylfurans through a palladium-catalyzed cyclization/1,2-H shift sequence under mild conditions is described. This is an efficient strategy to synthesize 2-vinylfurans from ene-yne ketones, and the corresponding products

Full text of DOI:10.1002/ejoc.201300016

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201300016
Palladium-Catalyzed Formation of C=C Bonds: A Regioselective Strategy for
the Synthesis of 2-Vinylfurans by 1,2-H Shift of Palladium–Carbene
Complexes
Haiying Zhan,[a] Xiulian Lin,[a] Yanying Qiu,[a] Zuodong Du,[a] Peixian Li,[a] Yongjian Li,[a]
and Hua Cao*[a]
Keywords: Synthetic methods / Palladium / Oxygen heterocycles / Carbenes / Ene–yne ketones / Cyclization
A convenient method to synthesize vinylfurans through a
palladium-catalyzed cyclization/1,2-H shift sequence under
mild conditions is described. This is an efficient strategy to
synthesize 2-vinylfurans from ene–yne ketones, and the cor-
responding products are obtained in good yields.
Introduction
Results and Discussion
Furans represent a ubiquitous structural motif in nature
and are also present in many natural products.[1] Furans
and related compounds belong to one of the most impor-
tant members of the family of heterocycles, and they find
a variety of applications in pharmaceuticals, flavors, and
fragrances.[2] Currently, two general approaches are com-
monly used for the construction of multisubstituted furan
derivatives: (1) Paal–Knorr synthesis and (2) transition-
metal-catalyzed cyclization of allenyl ketones,[3] alkynyl
ketone,[4] alkynyl epoxides,[5] enynols,[6] or propargyl
ethers.[7] Prominent among these processes are palladium-
catalyzed organic transformations.[8] The historical, mech-
anistic, theoretical, and practical aspects of these processes
have been amply discussed.[9] In addition, the development
of new methodologies to synthesize multisubstituted furan
derivatives under mild conditions is of extraordinary inter-
est.
Initially, oct-2-ynal (1a) and pentane-2,4-dione (2a) were
used as model substrates to optimize the reaction condi-
tions (Table 1). The intermediate product, 3a, was easily
prepared through Knoevenagel condensation of 1a with 2a
in the presence of AcOH in DMF at room temperature for
1 h. Subsequently, our study focused on the cyclization of
Table 1. Optimization of the reaction conditions.[a]
Entry Catalyst
T
t
Solvent
Yield
[%][b]
Recently, elegant studies were reported by Herndon,[10]
Uemura,[11] and Vicente and López[12] for the synthesis of
furans through the cyclization of ene–yne ketones. In par-
ticular, Herndon described an efficient method for the cou-
pling of enyne aldehydes or ketones with methylcarbene
complexes for the synthesis of vinylfurans. However,
palladium-catalyzed direct synthesis of vinylfurans from
ene–yne ketones has not been disclosed. Here, we report a
more direct approach with the use of ene–yne ketones as
starting materials for the synthesis of 2-vinylfurans through
a palladium-catalyzed cyclization/1,2-H shift sequence.
[°C] [h]
1
2
3
4
5
6
7
8
Pd(OAc)2
PdCl2
60
60
60
60
80
100
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
12 DMF
12 DMF
12 DMF
12 DMF
12 DMF
12 DMF
12 DMF
24 DMF
16
9
trace
11
Pd(dba)2
Pd(CH3CN)Cl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
–
6
trace
81
80
81
74
79
84
87
82
9
6
4
6
6
6
6
6
6
DMF
DMF
10
11
12
13
14
15
16
toluene
CH2Cl2
CH3OH
CH3CN
dioxane
CH3OH
[a] School of Chemistry and Chemical Engineering, Guangdong
Pharmaceutical University,
77
Guangzhou 510006, P. R. China
n.p.[c]
Fax: +86-760-88207939
E-mail: caohua@gdput.edu.cn
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), catalyst
(2.5 mol-%), solvent (2.0 mL), r.t. to 100 °C. [b] GC yield. [c] n.p.
= no product.
Homepage: http://www.gdpu.edu.cn/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300016.
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Eur. J. Org. Chem. 2013, 2284–2287

Palladium-Catalyzed Formation of C=C Bonds
3a by testing various Pd catalysts (Table 1, entries 1–4). 81% yield (Table 1, entry 7). Thus, this transformation is
Pd(OAc)2 was a better Pd catalyst than other Pd catalysts, temperature sensitive. Subsequently, we attempted to im-
and it gave corresponding product 4a in 16% yield (Table 1, prove the yields by adjusting the reaction time and the sol-
entry 1). We thought that product 4a was obtained in very vent. It was pleasing to find that 4a was generated in 81%
low yield because of the decomposition of intermediate yield after only 6 h. Among the solvents tested, including
product 3a at the high temperature at which the reaction DMF, toluene, CH2Cl2, THF, CH3CN, and 1,4-dioxane,
was performed. Thus, the effects of the temperature were CH3OH was clearly the best solvent (Table 1, entry 13).
next examined (Table 1, entries 5–7). To our delight, when These preliminary results revealed that Pd(OAc)2 acts as a
the reaction was carried out at room temperature with good catalyst for the cyclization of 3a in CH3OH at 60 °C
Pd(OAc)2 (2.5 mol-%) in DMF, product 4a was formed in for 6 h.
Table 2. Pd-catalyzed synthesis of furans.[a]
[a] Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), Pd(OAc)2 (2.5 mol-%), CH3OH (2 mL), r.t., 6 h. [b] Isolated yield.
Eur. J. Org. Chem. 2013, 2284–2287
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H. Zhan, X. Lin, Y. Qiu, Z. Du, P. Li, Y. Li, H. Cao
SHORT COMMUNICATION
With the optimal reaction conditions in hand, we ex- Table 3. Formation of 2-carbonylfurans.
plored the scope of this Pd(OAc)2-catalyzed approach, and
the results are outlined in Table 2. We used 1a as a fixed
substrate to examine the reactions with various types of 1,3-
dicarbonyl compounds. First, open-chain 1,3-dicarbonyl
compounds were treated with 1a under the optimized reac-
tion conditions, and the desired vinylfurans were obtained
in good yields (Table 2, entries 1–8). Notably, when sub-
strates 2f, 2g, and 2h were employed in the reaction, corre-
sponding products 4f, 4g, and 4h were obtained in 84, 86,
and 87% yield, respectively (Table 2, entries 6–8). All these
cases showed high functional group tolerance [R2 = CH3,
CH3O, EtO, (CH3)3CO, o-CH3-PhNH, p-CH3O-PhNH, p-
Cl-PhNH; R3 = CH3, Ph]. We were next interested in evalu-
ating the scope of this Pd(OAc)2-catalyzed transformation
by using commercially available cyclohexane 1,3-diones as
substrates. It was pleasing to find that the reactions of cyclic
1,3-dicarbonyl compounds 2i–m proceeded smoothly in
CH3OH with Pd(OAc)2 at room temperature to afford the
corresponding products in good yields (Table 2, entries 9–
13). These results indicated that both open and cyclic 1,3-
dicarbonyl compound are suitable partners in this process
[a] Isolated yield.
and that the catalytic system is applicable for this cycliza-
tion strategy to prepare 2-vinylfurans. Importantly, when
the reaction was performed with unsymmetrical 1,3-dione
2n, product 4n was obtained in 80% yield with complete
control of regiochemistry (Table 2, entry 14). No other re-
gioisomers were detected in the process, which clearly shows
that this cyclization is regioselective and chemoselective.
Extending the investigation further, substrate 1b was also
tested, and the results showed that the cycloisomerization/
carbene oxidation sequence allowed the formation of the
corresponding α-carbonyl furan, which represents a new ap-
proach to the construction of C–O bonds. Interestingly, this
strategy was achieved perfectly by treatment of intermediate
products 3 in the presence of Pd(OAc)2 (2.5 mol-%) at room
temperature in CH3OH (Table 3). Both open-chain 1,3-di-
carbonyl compounds and a cyclohexane 1,3-dione were
suitable for this transformation, and corresponding prod-
ucts 5a, 5b, and 5c were obtained in 48, 42, and 41% yield,
respectively. These results were obtained because 1a pos-
sesses two hydrogen atoms at C-4, which undergo 1,2-H
shift, whereas substrate 1b does not contain any hydrogen
atoms at this position. Thus, the shift is difficult in 1b, as it
would destroy conjugation of the benzene ring, and instead
carbene oxidation occurs easily.
The most plausible Pd-catalyzed reaction mechanism for
the cyclization of the ene–yne ketones is illustrated in
Scheme 1. Intermediate product 3a is easily formed by
AcOH-catalyzed intermolecular dehydration of 1a with 2a.
Scheme 1. Proposed mechanism.
Conclusions
In conclusion, we have developed an efficient one pot
Pd(OAc)2-catalyzed cyclization reaction of ene–yne ketones.
This is a new approach for synthesis of α-vinylfurans
through a palladium-catalyzed cyclization/1,2-H shift se-
quence. The reaction provides a convergent approach to the
formation of C=C and C–O bonds for the synthesis of
furan derivatives in good to excellent yields. Further studies
will focus on utilizing ene–yne ketones in organic synthesis
and will be reported in future publications.
Supporting Information (see footnote on the first page of this arti-
Product 3a reacts with palladium metal to generate the pal- cle): Experimental procedures and characterizations of compounds
4a–4n, 5a–5b.
ladium(II)–alkyne complex, which undergoes nucleophilic
attack by the carbonyl oxygen atom to afford zwitterionic
vinylpalladium complex B, which is a resonance structure
of C. Finally, product 4a is formed by 1,2-H migration of
Pd–carbene complex C.[13] A similar carbene intermediate
and transformation has been mentioned in previous stud-
ies.[14]
Acknowledgments
The work was financially supported by the Foundation for Distin-
guished Young Talents in Higher Education of Guangdong, China
(grant number LYM11083).
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Received: January 5, 2013
Published Online: March 7, 2013
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