Au(III)-catalyzed ring opening reaction of 1-cyclopropyl-2-yn-1-ols with nucleophiles: Highly efficient approach to (Z)-conjugated enynes

Article abstract of DOI:10.1039/b714511j

A highly efficient approach to (Z)-conjugated enynes has been developed by utilizing an Au(III)-catalyzed ring opening reaction of 1-cyclopropyl-2-yn-1-ols with nucleophiles under mild conditions; the method is valuable due to the excellent yield and high

Full text of DOI:10.1039/b714511j

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LETTER
www.rsc.org/njc | New Journal of Chemistry
Au(III)-catalyzed ring opening reaction of 1-cyclopropyl-2-yn-1-ols with
nucleophiles: highly efficient approach to (Z)-conjugated enynesw
Hui-quan Xiao,ac Xing-zhong Shu,a Ke-gong Ji,a Chen-ze Qic and
Yong-min Liang*ab
Received (in Montpellier, France) 21st September 2007, Accepted 29th October 2007
First published as an Advance Article on the web 8th November 2007
DOI: 10.1039/b714511j
A highly efficient approach to (Z)-conjugated enynes has been
developed by utilizing an Au(III)-catalyzed ring opening reaction
of 1-cyclopropyl-2-yn-1-ols with nucleophiles under mild condi-
tions; the method is valuable due to the excellent yield and high
regio- and stereoselectivity.
90%) of 2aa was obtained after 1 h (entry 2). With other gold
catalysts, such as Bu4N[AuCl4],7 AuCl3 and AuCl, no superior
results were obtained (entries 3–5). When TsOH was used as
the catalyst, only 58% yield was obtained (entry 6). PtCl2 and
AgSbF6 were also applied to the reaction, however little or no
trace of the product 2aa was observed (entries 7 and 8). Thus,
the use of HAuCl4 Á 4H2O (3 mol%) at room temperature was
found to be the most efficient and used as the standard
conditions.
Conjugated enynes are one of the most versatile intermedi-
ates in organic synthesis.1 Among a variety of approaches for
their preparation, highly selective preparation of conjugated
enynes is quite limited due to the competitive formation of
undesired regio- and stereoisomers.2 So a novel and efficient
method for selective preparation of conjugated enynes should
be developed from a synthetic viewpoint.
To probe the scope of the reaction, the relative reactivities of
propargylic alcohols with different R1, R2 and R3 groups were
examined under optimal conditions, as shown in Table 2.
Various aryl substituents on the three-membered ring, includ-
ing phenyl, electron-rich, and electron-poor aryls, were com-
patible with this reaction, and generally good yields of the
corresponding enynes were obtained (entries 1–3). Cyclo-
propane with heteroaromatic groups such as 2-furanyl also
proceeded smoothly (entry 4). Substitution on the a-position
of cyclopropyl carbinols was also tolerated (entries 5–7).
Alkynes with different aryl groups as well as heteroaromatic
groups such as 2-thienyl all afforded good yields of desired
products (entries 8–10). When aliphatic and terminal alkynes
were used, the reaction proceeded faster, furnishing the
corresponding products in high yields within 0.5 h (entries
11 and 12). Although both electron-rich and electron-deficient
Recently, gold has emerged as a powerful homogeneous
catalyst for the electrophilic activation of alkynes, alkenes and
many other groups to afford a variety of C–C and C–X
bonds.3 However, little attention as been paid so far to gold-
catalyzed reactions with three-membered rings and, in parti-
cular, cyclopropane.4 Examples of gold-catalyzed ring opening
reactions through nucleophilic attack on a cyclopropane ring
are scarce.4c Consequently, the use of gold catalysts in the area
of cyclopropanes remains largely unexplored. We envisioned
that cyclopropanes with a hydroxy group at the a-position
might undergo ring opening reaction after being activated by a
gold catalyst in the presence of a nucleophile. Herein, we
disclose the first results on the corresponding Au(III)-catalyzed
nucleophilic attack reaction of 1-cyclopropyl-2-yn-1-ols with
nucleophiles to afford (Z)-conjugated enynes with complete
regio- and stereoselectivity.
Table 1 Effect of catalysts on the reaction of 1a to 2aaa
We began our investigation with 1-cyclopropyl-2-yn-1-ol
1a5 (0.3 mmol) and MeOH (1.0 mL) using a variety
of catalysts at room temperature without exclusion of moist-
ure or air (Table 1). In the presence of 1 mol% of
HAuCl4 Á 4H2O, the reaction proceeded efficiently to afford
(Z)-enyne 2aa6 in 60% yield after 3 h (entry 1). On increasing
the amount of catalyst to 3 mol%, an excellent yield (up to
Entry
Catalyst (mol%)
Time/h
Yield (%)b
1
2
3
4
5
6
7
8
a
HAuCl4 Á 4H2O (1)
HAuCl4 Á 4H2O (3)
Bu4N[AuCl4] (3)
AuCl (3)
AuCl3 (3)
TsOH (10)
3
1
6
1
1
4
24
12
60
90
50
80
75
58
a State Key Laboratory of Applied Organic Chemistry, Lanzhou
University, Lanzhou 730000, P. R. China. E-mail:
liangym@lzu.edu.cn; Fax: (+86) 931 8912582; Tel: (+86) 931
8912593
b State Key Laboratory of Solid Lubrication, Lanzhou Institute of
Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000,
P. R. China
PtCl2 (3)
AgSbF6 (3)
0
Trace
c Institute of Applied Chemistry, Shaoxing College of Arts and
Sciences, Shaoxing 312000, P. R. China
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization data. See DOI: 10.1039/b714511j
Unless noted, all reactions were carried out using 1a (0.3 mmol) with
b
3 mol% of catalyst in MeOH (1.0 mL) at room temperature. Isolated
yield.
ꢀc
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Table 2 HAuCl4 Á 4H2O-catalyzed synthesis of substituted conjugated enynes by treatment of 1-cyclopropyl-2-propyn-1-ols with methanola
Entry
1
R1
R2
R3
Time/h
2 (Yield %)b
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
Ph
p-CH3O–C6H4
p-Cl–C6H4
2-Furanyl
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
1
0.5
1
1
1
0.5
0.5
1
1
1
2aa (90)
2ba (89)
2ca (92)
2da (85)
2ea (82)
2fa (85)
2ga (92)
2ha (92)
2ia (90)
2ja (89)
2ka (90)
2la (75)
p-Br–C6H4
p-CH3O–C6H4
CH3
Ph
Ph
Ph
Ph
Ph
p-CH3–C6H4
p-Cl–C6H4
2-Thienyl
n-C5H11
H
9
10
11
12
a
1j
1kc
1l
Ph
Ph
0.5
0.5
Unless noted, all reactions were carried out using 1 (0.3 mmol) with 3 mol% of HAuCl4 Á 4H2O in MeOH (1.0 mL) at room temperature.
b
c
Isolated yield. cis substrate of 1k was explored.
aryl groups were well accommodated in the reaction, the
former reacted much faster, which might be due to
the electronic activation of cyclopropane ring (entries 2 vs. 3,
5 vs. 6).
Then, we examined the scope of different nucleophiles in the
ring opening reactions under the optimal conditions. It was
found that, in addition to methanol, a variety of alcohols
could be used as effective nucleophiles (Table 3), and the
corresponding enynes were obtained in good yields with a
complete regioselectivity. Treatment of 1a with ethanol re-
sulted in the formation of 2ab in 82% yield (entry 2). More
sterically hindered alcohols such as i-PrOH, and t-BuOH also
Scheme 1 Synthesis of enediyne compound 2ma from 1m.
proceeded smoothly to afford the corresponding products in
88% and 80% yields, respectively (entries 3 and 4). Functional
alcohols, such as 2-chloroethanol, allylic alcohol and pro-
pargylic alcohol, were effective nucleophiles (entries 5–7). In
addition, benzylic alcohol could also be readily reacted in
good yield (entry 8).
Furthermore, we examined the reaction of compound 1m
with methanol under the same conditions. The reaction pro-
ceeded efficiently to afford the corresponding enediyne 2ma in
80% yield after 4 h with complete regio- and stereoselectivity
(Scheme 1). Enediyne compounds can be used not only to
study their mechanism of function in antitumor antibiotics8
such as dynemicin, neocarzinostatin, and esperamicin, but also
are utilized in the synthesis of oligoenynes and oligoenediynes
as well as p-conjugated polymers for electronic and photonic
applications.9
Table 3 Synthesis of (Z)-conjugated enynes using different nucleo-
philesa
Entry
Nucleophile
Time/h
Yield (%)b
Very interestingly, when terminal alkyne 1l was employed,
carbonyl compound 2lb could be obtained in 78% yield after
8 h in the presence of 3 mol% of HAuCl4 Á 4H2O at room
temperature (Scheme 2). In this two-step one-pot reaction,
cyclopropane 1l undergoes a facile ring opening reaction to
afford enyne 2la, which further undergoes a hydration reaction
of alkynes10 to provide the corresponding product 2lb. This
mechanism was also confirmed by our experiment. Conjugated
enyne 2la could be obtained in 75% isolated yield by using
cyclopropane 1l in the presence of 3 mol% of HAuCl4 Á 4H2O
at room temperature for 0.5 h. Then compound 2la was
employed at the same condition for 8 h to afford the desired
product 2lb in 85% yield.
1
2
3
4
5
CH3OH
0.5
1
1.5
3
2aa (90)
2ab (82)
2ac (88)
2ad (80)c
2ae (85)
C2H5OH
i-PrOH
t-BuOH
ClCH2CH2OH
1
6
7
1
2af (82)
1
2
2ag (78)
2ah (80)
8
PhCH2OH
a
Unless noted, all reactions of were carried out by using 0.3 mmol of
1a in 1 mL of alcohols in the presence of 3 mol% of HAuCl4 Á 4H2O at
b
c
room temperature. Isolated yield. At 60 1C.
ꢀc
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Acknowledgements
The authors thank the NSF (NSF-20621091, NSF-20672049)
for financial support.
References
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Scheme 2 Transformation of 1l to 2la and 2lb.
In summary, we have successfully developed an efficient
approach to (Z)-conjugated enynes through the gold-catalyzed
ring opening reaction of cyclopropanes with various nucleo-
philes. The first example of a nucleophilic attack reaction of
cyclopropane induced by gold activated propargylic alcohols
was disclosed. The reaction proceeded under very mild condi-
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5 In the reaction, the cis/trans mixture of 1-cyclopropyl-2-propyn-1-
ol (1a) was used. All of the propargylic alcohols (1a–1j) used in the
reaction were cis/trans mixtures.
6 Only (Z)-enyne was obtained, and the structure of 2fa was
determined by an NOE study. (The NOE spectrum of 2fa can be
seen in the ESIw)
General experimental procedure for the synthesis of
1-cyclopropyl-2-propyn-1-ols (1a–1l) from the corresponding
ketones
To a stirring solution of the appropriate terminal alkyne
(1.2 equiv.) in THF (1.0 M) was added ethylmagnesium
bromide (1.0 M in THF, 1.1 equiv.) at room temperature.
The resulting solution was stirred for 1 h at 50 1C. Then the
corresponding ketone (1.0 equiv.) in THF (0.35 M) was added
slowly by syringe to the resulting solution at room temperature
and stirred for 3 h. The reaction mixture was quenched by
addition of saturated aqueous ammonium chloride (40 mL)
and extracted with diethyl ether (2 Â 40 mL). The combined
organic layers were washed with brine, dried over Na2SO4 and
concentrated under reduced pressure. The crude material was
purified by chromatography on silica gel to obtain the pure 1-
cyclopropyl-2-propyn-1-ol 1 as a mixture of diastereoisomers
in 82% yield (petroleum ether–ethyl acetate, 20 : 1).
.
General experimental procedure for the preparation of
(Z)-conjugated enynes
7 Recently we have reported that Bu4N[AuCl4] is an efficient
gold catalyst in the synthesis of highly substituted furans.
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Perkin Trans. 1, 1976, 1983.
To a solution of a cis/trans mixtures of 1-cyclopropyl-2-
propyn-1-ols 15 (0.3 mmol) in alcohols (1 mL) was added
3 mol% of HAuCl4 Á 4H2O under air at room temperature.
When the reaction was considered complete as determined by
TLC analysis, 30 mL of diethyl ether was added and the
mixture was washed with water, saturated brine, dried over
Na2SO4 and evaporated under reduced pressure. The residue
was purified by chromatography on silica gel to afford the
corresponding conjugated enynes (petroleum ether–ethyl
acetate, 40 : 1).
ꢀc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
New J. Chem., 2007, 31, 2041–2043 | 2043