A convenient regioselective synthesis of cyclopentadienones via palladium-catalyzed [2+2+1] cyclocarbonylation of alkynes

Article abstract of DOI:10.1039/c3cc48308h

A simple and efficient synthesis of cyclopentadienones via palladium-catalyzed cyclocarbonylation of alkynes under atmospheric pressure of carbon monoxide has been developed. The transformation was carried out under mild and ligand-free conditions, a wide range of substrates and exceptional functional group tolerance.

Full text of DOI:10.1039/c3cc48308h

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A convenient regioselective synthesis of
cyclopentadienones via palladium-catalyzed
[2+2+1] cyclocarbonylation of alkynes†
Cite this: Chem. Commun., 2014,
50, 2488
Received 30th October 2013,
Accepted 6th January 2014
Yanli Xu, Jinwu Zhao, Huoji Chen, Wanqing Wu and Huanfeng Jiang*
DOI: 10.1039/c3cc48308h
www.rsc.org/chemcomm
A simple and efficient synthesis of cyclopentadienones via palladium- As palladium is one of the most effective transition metal
catalyzed cyclocarbonylation of alkynes under atmospheric pressure of catalysts and has a wide range of applications in both industry
carbon monoxide has been developed. The transformation was carried and laboratory,10 our group has also developed a number of
out under mild and ligand-free conditions, a wide range of substrates palladium-catalyzed transformations.11 Herein, we would like to
and exceptional functional group tolerance.
disclose a simple and efficient palladium-catalyzed cyclocarbonyla-
tion of alkynes and CO under atmospheric pressure, affording CPDs
Cyclopentadienones1 (CPDs) are an important class of fascinating in good to excellent yields.
compounds which have been used widely as 2p or 4p components of
cycloaddition reactions in organic synthesis,2 as versatile ligands in
coordination chemistry,3 and as well-performing cross-linking agents
in polymer science.4 They have also been employed in the synthesis
of natural products and drug discovery.5 The transition metal-
mediated [2+2+1]-cocyclization of alkynes and carbon monoxide
(CO) appears to be a promising method by virtue of its starting
material availability, intrinsic atom economy and convergent nature.
This transformation could be achieved by inserting CO into the
metallacyclopentadienes from alkynes; however, in most cases,
stoichiometric metal complexes are needed since the newly formed
cyclopentadienone tends to remain coordinated to the metal, giving
In our initial investigations of the [2+2+1] cycloaddition,
the product as Z4-metal complexes.6 Later, the catalytic version of using diphenylacetylene (1a, 0.22 mmol), ethyl phenylpropiolate
cyclocarbonylation between diynes and CO was also developed by (2a, 0.2 mmol) and PdCl2 (2 mol%) in dichloromethane under an
using methylidynetricobalt,7 or an iridium complex of unique atmosphere of CO at 40 1C for 16 h, the reaction failed to afford
phosphine ligands as a catalyst.8
the desired product 3a (Table 1, entry 1). And when 1 equiv. of
To the best of our knowledge, the three-component cyclo- LiCl was added, the reaction gave only 5% yield of the cross-
carbonylation of two different alkynes with CO could be complicated coupling product 3a, while with the addition of other additives
by the potential formation of up to 10 hetero- and homo-coupling such as LiBr and KI, no desired product was detected (Table 1,
products. However, the chemo- and regioselective protocols have not entries 2–4). To our delight, in the presence of CuCl, 3a was given
been reported yet. And Pearson et al. have described an indirect in 46% yield, and using CuCl2 instead, the yield of product 3a
method to synthesize CPDs from two different alkynes and CO by increased up to 82% (Table 1, entries 5 vs. 6). It should be noted
using temporary silicon tethers, which consists of linking two that the reaction in the presence of CuBr2 alone failed to afford
alkynes into a silyl acetal, subjecting the resulting diyne to cyclo- the desired cyclopentadienone 3a, and the reaction gave 35% yield
carbonylation, disengaging the metal and the tether moiety.9 of 3a when 1 equiv. of LiCl together with CuBr2 was used (Table 1,
entries 7 vs. 8). These results suggested that both chlorine anions
School of Chemistry and Chemical Engineering, South China University of
and copper cations played a crucial role in this process.
Having the optimized conditions in hand, we explored the scope
of the cyclocarbonylation reaction between various phenylpropiolate
esters and alkynes (Table 2). A series of para-substituted phenyl-
propiolate esters, including some with electron-donating groups
Technology, Guangzhou 510640, China. E-mail: jianghf@scut.edu.cn;
Fax: +86 20-87112906; Tel: +86 20-87112906
† 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/c3cc48308h
2488 | Chem. Commun., 2014, 50, 2488--2490
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Table 1 Optimization of reaction conditionsa
Entry
Catalyst
Additive
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8c
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
—
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
0
5
0
0
Scheme 1 Reactions between alkynes 1 and 3-phenylpropiolonitrile.
LiCl
LiBr
KI
CuCl
CuCl2
CuBr2
CuBr2
cyclopentadienones in high yields (3o and 3u). Moreover, substrates
tert-butyl 3-phenylpropiolate and benzyl 3-phenylpropiolate also
reacted smoothly, and the desired products 3v and 3w were obtained
in 62% and 84% yields, respectively. On the whole, aromatic alkynes
(R1 = OMe, Me) having an electron-donating group on the benzene
ring gave the corresponding products in higher yields than alkynes
(R1 = F) possessing an electron-withdrawing group on the benzene
ring. Unfortunately, 4-octyne failed to afford the desired product.
The reaction between 3-phenylpropiolonitrile and 1,2-diphenyl-
ethyne or 1,2-bis(2,4-dimethylphenyl)ethyne afforded the desired
products 4a and 4b in high yields under the standard conditions
(Scheme 1). And when 4-phenylbut-3-yn-2-one was treated with
1,2-diphenylethyne, it gave the desired product 3-acetyl-2,4,5-
triphenylcyclopenta-2,4-dienone in very low GC yield (o5%),
while no desired products could be obtained with other sub-
strates such as 3-phenylpropiolaldehyde, 3-phenylpropiolic acid,
and 3-phenylpropiolamide.
46
92 (82)
0
35
a
Reaction conditions: unless otherwise noted, all reactions were performed
with 1a (0.22 mmol), 2a (0.2 mmol), PdCl2 (2 mol%), additive (0.2 mmol) in
CH2Cl2 (3 mL) at 40 1C (bath temperature) for 16 h. b Determined by GC
using dodecane as the internal standard. Data in parentheses is the yield of
the isolated product. c 1 equiv. of LiCl was added.
Table 2 Cross-coupling reactions between alkynes 1 and phenylpropiolate
esters 2a,b
In addition, this palladium-catalyzed system was also suitable
for the intramolecular carbonylative coupling, and the reaction
of diynes 5 in the presence of 2 mol% PdCl2 and 1 equiv. CuCl2
in dichloromethane proceeded smoothly under an atmosphere
of CO, providing the corresponding bicyclic cyclopentadienones
6 in good yields (Scheme 2).
In summary, we have developed a new and convenient
palladium-catalyzed [2+2+1] cyclocarbonylation of alkynes for the
synthesis of cyclopentadienones. This palladium-catalyzed reaction
system can be carried out under mild and ligand-free conditions and
has a wide range of substrates and exceptional functional group
tolerance. Moreover, the use of readily available starting materials
and atmospheric pressure of carbon monoxide make this practical
and atom-economical approach particularly attractive. Further inves-
tigations on the mechanism and synthetic applications of this
reaction are currently ongoing in our laboratory.
We thank the National Natural Science Foundation of China
(20932002, 21172076, and 21202046), the National Basic
a
The reactions were carried out at 1 atm of CO using alkynes 1
(0.33 mmol), phenylpropiolate esters 2 (0.3 mmol), PdCl2 (2 mol%),
CuCl2 (0.3 mmol), and 3 mL of dichloromethane at 40 1C (bath
temperature) for 16–24 h. Yields of isolated products.
b
(R2 = OMe, Et) and some with electron-withdrawing groups (R2 = F, Cl,
Br, CF3, CN, CH3CO, etc.), were converted into the corresponding
cyclopentanediones in excellent yields (3c–3l). Other substituted
phenylpropiolate esters were also good substrates for this transforma-
tion and afforded the corresponding products 3m and 3n in high
yields. These results showed that this transformation was tolerant
toward electronic and steric effects of the aromatic ring. The
naphthalene substituent was also tolerated to provide the desired
Scheme 2 Synthesis of bicyclic cyclopentadienones 6 via Pd-catalyzed
carbonylative coupling of diynes 5.
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2490 | Chem. Commun., 2014, 50, 2488--2490
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