Gold and Br?nsted acid catalyzed isomerization of [3]cumulenols and [3]cumulenones: Efficient syntheses of 1,5-dien-3-ynes and furan derivatives

Article abstract of DOI:10.1016/j.tetlet.2011.02.057

An attractive method for assembling π-conjugated dienynes with high stereoselectivity was achieved by dehydration reaction of TMS-substituted [3]cumulenols catalyzed by TsOH·H₂O. On the other hand, cycloisomerizations of the corresponding [3]cu

Full text of DOI:10.1016/j.tetlet.2011.02.057

Tetrahedron Letters 52 (2011) 1968–1972
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Gold and Brønsted acid catalyzed isomerization of [3]cumulenols
and [3]cumulenones: efficient syntheses of 1,5-dien-3-ynes and furan
derivatives
⇑
Erjuan Wang, Xiaoping Fu, Xin Xie, Jingjin Chen, Hongjun Gao, Yuanhong Liu
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
An attractive method for assembling p-conjugated dienynes with high stereoselectivity was achieved by
Received 9 December 2010
Revised 25 January 2011
Accepted 15 February 2011
Available online 18 February 2011
dehydration reaction of TMS-substituted [3]cumulenols catalyzed by TsOHÁH2O. On the other hand,
cycloisomerizations of the corresponding [3]cumulenones catalyzed by gold(I) complexes afford vinyl
furans through activation of the cumulenic double bond via a
tonation from an alkyl group on cumulene terminus takes place to induce the isomerization.
Ó 2011 Elsevier Ltd. All rights reserved.
p-complex, and during the process, depro-
Keywords:
Cumulenes
Brønsted acids
Gold catalysis
Isomerization
Vinyl furans
[3]Cumulenes have attracted much attention in recent years
since they have potential applications in antitumor drug design1
and as advanced materials with unique electronic and photonic
properties.2 Cumulenes are also versatile synthetic intermediates
in organic synthesis3, such as in Diels–Alder reaction,3a domino
Heck/C–H activation,3b cycloaddition,3c sulfurization,3d as ligands
for metal complexation3e–g, and so on. Although much progress
has been achieved in this field, the reaction chemistry of functional-
ized [3]cumulenes has far less been developed, this may be due to
the limited synthetic methods that are available for these com-
pounds.4 Recently, we have shown that zirconocene–ethylene med-
iated coupling of 1,3-butadiynes with aldehydes or ketones provides
an one-pot efficient method for cis-[3]cumulenols.5 We also found
the diverse reactivity of zirconacyclocumulenes derived by the
coupling of benzynezirconocenes with 1,3-butadiynes toward alde-
hydes or aroyl cyanides, leading to cis-[3]cumulenols and [3]cum-
ulenones, respectively.6 These results prompted us to explore the
synthetic utilization of these oxygen-functionalized [3]cumulenes.
Herein we’d like to report the isomerization reactions of tetra-
substituted cumulenes under the catalysis of Brønsted acids or gold
catalyst. These methods offer the facile syntheses of 1,5-dien-3-ynes
and vinylfurans under mild reaction conditions.
nylethenes, (DEE, (E)-hex-3-ene-1,5-diyne) and 1,5-dien-3-ynes
are attractive compounds and versatile building blocks for the con-
struction of -conjugated polymers and designed nanoarchitec-
tures.7,8 Especially, due to the high
-electron delocalization
behavior in these -conjugated molecules or polymers, they have
shown a wide application in advanced organic materials, such as
in molecular wires, electroluminescence, switches, ferromagne-
tism, nonlinear optics, organic conductors, etc.7 During the course
of our studies on the reactivity of tetra-substituted [3]cumulenols,
we found that 1,5-dien-3-ynes9 could be formed with high stere-
oselectivity via the Brønsted acid catalyzed dehydration of cumule-
nols. Dehydration processes mediated by Brønsted acids or Lewis
acids are well documented reactions. However, a 1,6-elimination
of H2O in which the leaving group and the hydrogen have interven-
p
p
p
ing
p
bonds such as in cumulene derivatives is rare. It was found
catalytic amount of TsOHÁH2O
that in the presence of
a
(10 mol %), the alcohol 1 was smoothly converted into dienynes 2
with high stereoselectivities (Table 1). (1E,5E)-isomer of 2 was ob-
tained as major products as determined by the 1H NMR of the reac-
tion mixtures. The configuration of the dienyne double bond was
determined by a spectroscopic method of product 2a using the
NOESY technique. Representative results are given in Table 1.
The reaction could be readily applied to TMS-substituted cumule-
nols. A wide range of aromatic substituents at C-1 bearing elec-
tron-donating or electron-withdrawing substituents could be
incorporated successfully into the sequence, generating the corre-
sponding dienynes in good selectivity and good yields (74–93%).
Conjugated molecules, such as enynes, enediynes, tetraethyny-
lethenes (TEE, 3,4-diethynylhex-3-ene-1,5-diyne), (E)-1,2-diethy-
⇑
Corresponding author. Tel.: +86 21 54925135; fax: +86 21 64166128.
E-mail address: yhliu@mail.sioc.ac.cn (Y. Liu).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.02.057

E. Wang et al. / Tetrahedron Letters 52 (2011) 1968–1972
1969
Table 1
Bronsted acids catalyzed synthesis of (1E,5E)-1,5-dien-3-ynes
H3C
TMS
TMS
TMS
10% TsOH H2O
Ar
rt, 0.5-4 h, in CH2Cl2
TMS
OH
Ar
1
2
Entry
1
Ar
Product
Yielda (%)
88
Isomeric purityb
H3C
TMS
H
H
NOE
Ph (1a)
2a
>99:1
>99:1
TMS
Ph
H3C
TMS
2b
2
3
4
5
6
p-ClC6H4 (1b)
74
93c
86
TMS
p-ClC6H4
H3C
TMS
TMS
TMS
TMS
2c
2d
2e
2f
p-NO2C6H4 (1c)
p-CNC6H4 (1d)
p-CF3C6H4 (1e)
p-OCH3C6H4 (1f)
TMS
TMS
p-NO2C6H4
H3C
>98:2
>99:1
97:3
p-CNC6H4
H3C
81
TMS
TMS
p-CF3C6H4
H3C
84
p-OCH3C6H4
H3C
TMS
S
S
2g
7
8
80
77
98:2
TMS
(1g)
H3C
TMS
2h
>93:7
(1h)
TMS
Ar
Ar= 4-(phenylethynyl)phenyl
a
b
c
Isolated yields of the pure products.
Determined by the 1H NMR of the crude reaction mixture.
Containing small amount of impurity.
The functionalities of –Cl, –NO2, –CN, CF3, –MeO, and phenylalky-
nyl groups in the aromatic ring were well tolerated during the
reaction. A thienyl group at C-1 was also compatible under the
reaction conditions, furnishing 2g in 80% yield (entry 7). The sim-
plicity of this method should make it valuable to stereodefined
dienynes as well as poly(enynes), which may find potential utilities
in material science.
The utility of TMS-substituted 1,5-dien-3-ynes produced by this
chemistry as useful synthetic intermediates for further elabora-
tions was demonstrated through a Si–I exchange reaction followed
by a Pd-catalyzed Suzuki coupling10 reaction (Scheme 1). Treat-
ment of 2a with 3 equiv of NIS selectively afforded monoiodine
compound 3, which underwent coupling reaction with aryl boronic
acid in the presence of Pd catalyst to give the arylated product 4 in
76% yield and coupling with phenylacetylene to furnish the conju-
gated eneyne product 5 in 61% yield (97% pure). The structure of 3
was confirmed by 2D NMR spectra.
We proceeded to examine the reactivity of TMS-substituted
[3]cumulenones, and concentrated on metal-catalyzed cycloiso-
merization reactions. Although transition-metal-catalyzed cyclo-
isomerizations of allenyl ketones are well known, there is no
report for [3]cumulenones. Metal catalyzed cyclization of allenyl
ketones are attractive methods for the synthesis of furans. For
example, Marshall et al. discovered that allenyl ketones can be
rearranged into furans under mild conditions by Rh(I) or Ag(I) cat-
alysts.11 Hashmi had reported the Pd-catalyzed dimerization of

1970
E. Wang et al. / Tetrahedron Letters 52 (2011) 1968–1972
OMe
H3C
MeO
H3C
1.52 equiv
H3C
I
TMS
3,5-dimethoxyC6H3B(OH)2
3.0 equiv NIS
TMS
TMS
5% Pd(PPh3)4
50 oC, overnight,
in MeCN
TMS
3.0 Cs2CO3, 70 oC
in THF/H2O (10:1), 24 h
2a
3, 61%
4, 76%
Ph
H3C
1.5 equiv
Ph
5% PdCl2(PPh3)2
10% CuI, Et3N, 50 oC, 7 h
TMS
5, 61%
Scheme 1. Transformation of 2a to various functionalized dienynes.
terminal allenyl ketones12 and Au(III)-catalyzed cyclization of alle-
nyl ketones.13 A novel 1,2-migration of functional groups, such as
halogen, acyloxy, phosphatyloxy groups in allenones was also to
be reported by Gevorgyan for the synthesis of furans.14 Except
for 1,2-migration reactions, usually at least one hydrogen substitu-
ent in the allenones employed in these studies is required to in-
duce the isomerization (Scheme 2, Eq. 1). [3]Cumulenyl ketones
can be viewed as an extension of allenyl ketones by incorporation
or desilylated product 8 can be formed selectively under the catal-
ysis of (PPh3)AuCl/AgOTf (Table 2). For example, cumulenone 6c
bearing a p-NO2C6H4 group afforded the corresponding vinyl furan
7c in 67% yield as a 4.3:1 mixture of E and Z isomers at room tem-
perature, along with 24% desilylated product 8c (Table 2, entry 3).
Simply increasing the reaction temperature to 80 °C and using
dichloroethane as solvent resulted in the formation of desilylated
product 8c in 82% yield as a sole product (entry 4). The formation
of 8c is supposed to be the result of a competitive reaction pathway
involving a gold-catalyzed desilylation process. The E-configura-
tion of the major isomers in vinyl furan products has been con-
firmed by NOESY spectra of 7c and 8c. We have chosen the
following reaction conditions: 2 mol % of (PPh3)AuCl/AgOTf in
ClCH2CH2Cl stirred at 80 °C (condition B) for the study of the reac-
tion scope.
To test the generality of this chemistry, a wide variety of
[3]cumulenones have been examined in this cyclization process
(Table 2). The aromatic ring at C-1 bearing electron-withdrawing
as well as electron-donating substituents all reacted very well to
provide the di- or tri-substituted furan products in good to high
yields. Cyclization of a para-chlorophenyl-substituted 6b gener-
ated the corresponding desilylated furan 8b in 86% yield (E/
Z = 10.6:1), and only a trace of any byproducts was formed (Table
2, entry 2). The reaction of 4-CNC6H4 substituted 6d resulted in
the formation of vinyl furan 8d in 84% yield with high stereoselec-
tivity (entry 5, 40:1 of E/Z isomers). Introducing a stronger elec-
tron-withdrawing group such as –CF3 does not influence the
efficiency of this reaction, the corresponding product 8e was ob-
tained in 73% yield upon heating at 80 °C (entry 6). The reaction
also proceeded smoothly with the substrate bearing electron-
donating group at aromatic ring, leading to the products 8f and
8g in 60–64% yields (entries 7 and 8). It is interesting to note that
in the case of vinyl furan 8g, a Z to E isomerization occurs during
of a third cumulated
p bond, which would represent an important
class of suitable substrates for this strategy. Here we found that
gold could catalyze the cycloisomerization of cumulenones to
substituted vinyl furans, in which deprotonation from an alkyl
group on cumulene terminus takes place to induce the isomeriza-
tion (Scheme 2, Eq. 2).
The requisite cumulenones 6 can be easily obtained by oxida-
tion of the corresponding cis-[3]cumulenols by IBX in DMSO in
40–94% yields. However, during the oxidation process, a Z–E isom-
erization occurred, thus cumulenone 6 was used as a mixture of Z/E
isomers. After much effort, we found that vinyl furan derivatives 7
R2
R2
R3
H
cat.
Rh, Ag, Pd, Au etc.
R1
R3
(1)
(2)
R1
R2
O
Ref. [11, 13]
O
deprotonated
R2
R3
R3
cat. Au+
R1
R1
O
this work
O
H
deprotonated
Scheme 2. Metal-catalyzed cycloisomerization reactions of allenones or
cumulenones.
TMS
R
TMS
R
Au
Au
Au+
TMS
R
TMS
TMS
H
TMS
7
O
O
H+
Au+
+
O
9
10
11
Scheme 3. Proposed mechanism for the formation of vinyl furans 7.

E. Wang et al. / Tetrahedron Letters 52 (2011) 1968–1972
1971
Table 2
Gold-catalyzed cyclization of cis-[3]cumulenones to vinyl furans
TMS
R
2% (PPh3)AuCl/
AgOTf
TMS
R
TMS
TMS
or
TMS
R
O
O
conditions
O
7
8
6
Entry
1
R
Conditionsa
B, 2 h
Product
Yieldb (%)
TMS
(8a)
Ph (6a)
82(4.6:1)
O
TMS
(8b)
Cl
2
3
p-ClC6H4 (6b)
B, 3 h
A, 6 h
86(10.6:1)
O
TMS
TMS
TMS
TMS
TMS
TMS
TMS
p-NO2C6H4 (6c)
67(4.3:1)c
(7c)
O2N
O2N
NC
O
(8c)
4
5
6
7
8
(6c)
B, 3 h
82(5.0:1)
84(40:1)
73(2.8:1)
60(6.8:1)
64(8.5:1)
O
(8d)
(8e)
(8f)
p-CNC6H4 (6d)
p-CF3C6H4 (6e)
p-MeOC6H4 (6f)
p-MeC6H4 (6g)
B, 3 h
O
F3C
MeO
Me
B, 2 h
O
O
B, 10 h
B, 2.5 h
(8g)
O
a
b
c
Condition A: room temperature, in CH2Cl2. Condition B: 80 °C, in ClCH2CH2Cl.
Isolated yields. The ratio of E/Z isomer is given in parentheses.
Compound 8c was also isolated in 24% yield as a mixture of two isomers in a ratio of 3:1.
standing in CDCl3 solution at room temperature. For example, a
98:2 mixture of E/Z isomers was obtained after 7 days.
Supplementary data
We propose the following mechanism for this reaction (Scheme
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.02.057.
3). In the first step, the activation of cumulenone by forming a
p-
complex with PPh3Au+ dramatically enhances the electrophilicity
of the cumulenic double bond, which facilitates the nucleophilic
attack by the carbonyl oxygen. Thus the subsequent 5-exo-dig ring
closure occurs followed by deprotonation from the ethyl group to
afford furanyl gold intermediate 11. Deauration furnishes the vinyl
furan product 7. The furan derivatives of 8 might be formed by
gold-assisted desilylation of 7.
In summary, we present here a study on the reactivity of tetra-
substituted [3]cumulenols or [3]cumulenones with Brønsted acids
and gold catalysts. These transformations provide efficient routes
to 1,5-dien-3-ynes with high stereoselectivity and vinyl furans un-
der mild reaction conditions, which are of interest in material sci-
ence and organic synthesis. Further studies to extend the scope and
synthetic utility of functionalized cumulenes are in progress in our
laboratory.
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Acknowledgments
We thank the National Natural Science Foundation of China
(Grant Nos. 20872163, 20732008, 20821002), Chinese Academy
of Science and the Major State Basic Research Development Pro-
gram (Grant No. 2006CB806105) for the financial support.
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