Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

Article abstract of DOI:10.3762/bjoc.9.288

Gold-catalyzed O-vinylation of cyclic 1,3-diketones has been achieved for the first time, which provides direct access to various vinyl ethers. A catalytic amount of copper triflate was identified as the significant additive in promoting this transformation. Both aromatic and aliphatic alkynes are suitable substrates with good to excellent yields.

Full text of DOI:10.3762/bjoc.9.288

Ambient gold-catalyzed O-vinylation of cyclic
1,3-diketone: A vinyl ether synthesis
Yumeng Xi, Boliang Dong and Xiaodong Shi*
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 2537–2543.
C. Eugene Bennett Department of Chemistry, West Virginia
University, Morgantown, West Virginia 26506, United States
doi:10.3762/bjoc.9.288
Received: 30 June 2013
Email:
Accepted: 29 October 2013
Published: 18 November 2013
Xiaodong Shi* - xiaodong.shi@mail.wvu.edu
* Corresponding author
This article is part of the Thematic Series "Gold catalysis for organic
synthesis II".
Keywords:
alkyne; copper salt; diketone; gold catalysis; vinyl ether
Guest Editor: F. D. Toste
© 2013 Xi et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
Gold-catalyzed O-vinylation of cyclic 1,3-diketones has been achieved for the first time, which provides direct access to various
vinyl ethers. A catalytic amount of copper triflate was identified as the significant additive in promoting this transformation. Both
aromatic and aliphatic alkynes are suitable substrates with good to excellent yields.
Introduction
The past decade has witnessed the fast growth of homogeneous vinyl ether then collapsed to give a ketone as the final product
gold catalysis as one of the important branches in transition- [13-17].
metal chemistry [1-9]. The utility of cationic gold(I) complexes
as π-carbophilic acids toward alkyne and allene activation A vinyl ether is a common and versatile building block in
renders them as essential tools in organic synthesis. Generally organic synthesis as well as polymer chemistry. Typical
with the unique reactivity and mild reaction conditions, this methods for the preparation of a vinyl ether involve elimination,
type of transformation has found widespread applications in olefination of esters, addition of alcohols to alkynes, as well as
complex molecule synthesis [10,11]. Among those reactions, transition metal-mediated cross-coupling reactions [18]. Based
the gold-catalyzed hydration of alkynes is regarded as one of on the π-carbophilicity of gold(I), the addition of alcohol to
the signature reactions in the field (known as Teles hydration) alkyne should provide direct access to the corresponding vinyl
[12]. This reaction usually utilized the combination of methanol ether. However, most of the reported gold-catalyzed O-nucleo-
and water, wherein methanol served as the nucleophile to attack phile additions to alkynes are intramolecular reactions. No
the triple bond, forming the vinyl ether intermediate. This general protocol for vinyl ether synthesis using gold has been
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Beilstein J. Org. Chem. 2013, 9, 2537–2543.
reported to date [17]. Nevertheless, there have been examples that TA-Au complexes might have different binding ability
regarding the intermolecular addition of carboxylic acids toward water activation, we wondered whether the intermolec-
[19,20], phenols [21,22] as well as phosphoric acids [23-25] to ular O-addition could be achieved through ligand tuning. In this
alkynes. In this context, we report a gold(I)-catalyzed O-vinyla- report, we focus on the cyclic 1,3-diketone nucleophiles due to
tion of 1,3-diketones with unactivated alkynes at ambient A) the transformation is challenging and has never been
temperature.
reported in the past, B) vinyl ether products are highly func-
tional materials, which can be easily extended to complex mole-
cules through simple transformations.
Results and Discussion
As indicated in Scheme 1, the main challenge for the intermole-
cular O-nucleophile addition to alkynes is the competitive 1,3-Cyclohexanedione and phenylacetylene were used as the
hydration side reaction. Although, theoretically, strictly anhy- model substrates for the evaluation of various gold catalysts. As
drous conditions shall prevent the water addition, new effective shown in Table 1, the use of Ph3PAuCl/AgOTf (5%) gave an
catalytic systems that can avoid the “precautionary” treatment acceptable yield (59%) of the desired vinyl addition product 3a.
of solvents and substrates are much more practical and highly Thermally-stable Ph3PAu(TA)OTf (TA-Au, 5%) slightly im-
desirable.
proved the performance, yielding 63% of the desired product
and less hydration byproduct 4. When changing the primary
From literature reported examples, a gold activated water inter- ligand from triphenylphosphine to a NHC, the yield slightly
mediate, [L-Au-(H2O)]+, has been proposed in helping the decreased. However, the corresponding TA-Au complexes indi-
water addition to the alkyne besides the typical π-acid acti- cated significantly improved selectivity towards the diketone
vation [12-17]. Our group has developed the 1,2,3-triazole co- addition over the hydration (Table 1, entry 4). Finally, the appli-
ordinated gold complexes (TA-Au) as stable catalysts for cation of the XPhos ligand and the corresponding TA-Au com-
alkyne activation in the past several years [26-30]. Considering plex largely promoted this reaction, giving 3a in 85% yield with
Scheme 1: Intermolecular O-addition to alkynes: challenge and opportunity.
Table 1: Screening of gold catalysts.a,b
Entry
[Au] cat.
2a (equiv)
Loading Time (h)
Conversion of 2a (%)
Yield of 3a (%)
Yield of 4 (%)
1
2
3
4
5
6
7
8
9
PPh3AuCl/AgOTf
PPh3Au(TA)OTf
IPrAuCl/AgOTf
1.0
1.0
1.0
1.0
1.0
1.0
1.2
1.2
1.2
5%
5%
5%
5%
5%
5%
5%
3%
1%
17
17
17
17
10
10
10
17
20
81
59
17
82
63
11
100
64
55
34
IPrAu(TA)OTf
50
5
XPhosAuCl/AgOTf
XPhosAu(TA)OTf
XPhosAu(TA)OTf
XPhosAu(TA)OTf
XPhosAu(TA)OTf
100
100
100
100
100
76
22
85
12
99
n.d.
n.d.
n.d.
99
98 (95)
aGeneral conditions: 1 (0.2 mmol), 2a (1 or 1.2 equiv), and catalyst in CDCl3 (0.4 mL), rt. bYield and conversion are determined by using 1,3,5-
trimethoxybenzene as the internal standard. Isolated yield is given in parenthesis.
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Beilstein J. Org. Chem. 2013, 9, 2537–2543.
12% hydration byproduct. Notably, the reaction occurred at amount of acid from chloroform decomposition was crucial for
room temperature with no need for “careful” condition control the optimal performance, which likely helped the protodeaura-
(open to the air and untreated solvent). The fact that TA-Au tion. Other Lewis acids have also been screened and the
complexes generally gave improved selectivity of diketone ad- Cu(OTf)2 was identified [31] as the optimal choice due to the
dition over hydration (compared with the corresponding practical reasons (easy to weigh and less hygroscopic) and
[L-Au]+ complexes) supported our hypothesis and made the excellent reactivity. Cu(OTf)2 and HOTf itself could not
TA-Au catalysts important for this transformation. Slightly catalyze the reaction, suggesting that it is indeed a gold-
increasing the ratio of alkyne to 1.2 equivalents (relative to the catalyzed process. Finally, it is worth noting that the use of
nucleophile) increased the formation of the desired vinyl ester 1 mol % Echavarren catalyst t-BuXPhosAu(MeCN)SbF6 gave a
to a near quantitative yield (98% NMR yield, 95% isolated slightly lower yield (71%), and the combination of 1 mol %
yield), even with only 1% catalyst loading.
t-BuXPhosAu(MeCN)SbF6 and 1 mol % Cu(OTf)2 gave 86%
yield (under otherwise identical conditions). This result high-
Given the encouraging results associated with the XPhosAu-TA lights the synthetic utility of TA-Au catalyst in the transforma-
catalysts, we explored the reaction scope. However, surpris- tion.
ingly, significantly slower reaction was observed when conduct-
ing the reaction in dichloromethane (DCM) or 1,2- With this optimal conditions in hand, we embarked on the eval-
dichloroethane (DCE), though selectivity for the diketone addi- uation of the substrate scope for this transformation. A variety
tion over hydration was maintained as shown in Table 1. of aromatic alkynes were initially tested as summarized in
Solvent screening shown in Scheme 2 proved that the trace Table 2.
Scheme 2: Acid as the critical additive for optimal performance.
Table 2: Reaction scope of alkynes.a
Entry
1
Substrate
Product
Yieldb
95%
2a
2b
3a
3b
2
88%
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Beilstein J. Org. Chem. 2013, 9, 2537–2543.
Table 2: Reaction scope of alkynes.a (continued)
3
2c
2d
3c
3d
89%
87%
4
5
2e
2f
3e
3f
59%
68%
6
7
2g
2h
3g
3h
86%
70%
8c
aGeneral conditions: 1 (0.4 mmol), 2 (1.2 equiv), 1 mol % XPhosAu(TA)OTf and 1 mol % Cu(OTf)2 in dry DCM (0.8 mL), rt. bIsolated yield.
c1 (0.4 mmol), 2 (2 equiv), 3 mol % XPhosAu(TA)OTf and 3 mol % Cu(OTf)2.
This reaction tolerated both electron-rich (2b) and electron-defi- in good yield, which highlighted the mild conditions of this
cient (2c) alkynes. Aromatic alkynes with substitutents at meta catalytic system and potential applications of this gold catalyst
(2e) and ortho (2f) positions also worked well, although giving in other metal containing compound syntheses. A series of ali-
slightly lower yields. Electron-rich heterocycle-containing phatic alkynes were also tested for this reaction. Alkynes
alkynes (2g) were also suitable substrates for this transforma- containing 6-, 5- and 3-membered rings worked well, giving
tion. However, electron-poor alkynes, such as 2- and 3-pyridyl- good to excellent yields (Table 3). Notably, the cyclopropyl-
acetylenes, did not undergo the reaction, likely caused by the acetylene formed the direct O-addition adduct (6c) with no ring
low reactivity of the C–C triple bonds. Interestingly, the addi- opening product observed. In addition, the conjugate enyne
tion to the ethynylferrocene gave the corresponding vinyl ether could undergo this reaction, giving the interesting electron-rich
Table 3: Reaction scope with aliphatic alkynes.a
Entry
1
Substrate
Product
Yieldb
89%
5a
5b
6a
6b
2c
80%
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Beilstein J. Org. Chem. 2013, 9, 2537–2543.
Table 3: Reaction scope with aliphatic alkynes.a (continued)
3
5c
6c
86%
4
5
5d
5e
6d
6e
86%
67%
aGeneral conditions: 1 (0.4 mmol), 5 (2 equiv), 1 mol % XPhosAu(TA)OTf and 1 mol % Cu(OTf)2 in dry DCM (0.8 mL), rt. bIsolated yield. cA ratio of
1:0.4 is observed for terminal/internal alkene mixtures. Combined yield.
conjugated diene (6d). In some cases, thermodynamically more expected, no reaction occurred at room temperature under the
stable internal alkenes were also observed along with the kinetic optimal conditions. To our delight, the desired products 8
product terminal alkene, likely through olefin isomerization were obtained while refluxing at 60 °C for 48 h, though
[22].
in low yield. Two regioisomers were isolated, which were
assigned as 8a and 8b (Scheme 3A). Diphenylacetylene gave
The internal alkyne (1-phenyl-1-propyne), which was usually trace amounts of the desired product under the identical condi-
much less reactive than the terminal alkyne, was also tested. As tions.
Scheme 3: Reactions of internal alkyne and other O-nucleophiles. Isolated yields are given in paranthesis. aA ratio of 1:2.6 is observed for terminal/
internal alkene mixtures. Combined yield.
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philes. The 1,3-cyclohexanedione derivative worked well,
giving the vinyl ether 10a in good yield. The five-membered
diketone, 1,3-cyclopentadione could also yield the desired
O-vinylation product (10b–10d) in excellent yield, under
similar conditions. Elevated temperature (50 °C) was required
for good results due to the poor solubility of 1,3-cyclopenta-
dione in DCM at room temperature. Finally and notably, all
tested acyclic 1,3-diketones as well as 1,2-diketones gave no
O-addition products under the current reaction conditions, likely
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In this letter, we report the first successful gold(I)-catalyzed
intermolecular O-vinylation of cyclic 1,3-diketones with unacti-
vated alkynes. The reaction tolerates a large scope of alkynes,
giving the desired O-addition products in good to excellent
yields. The triazole coordinated gold catalysts gave improved
reactivity compared with the typical [L-Au]+ by overcoming the
undesired hydration. This discovery will likely benefit many
future developments that currently suffer from the common
hydration side reaction. The application of copper(II) triflate as
the effective additive not only improves the reactivity, but also
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We thank the NSF (CAREER-CHE-0844602 and CHE-
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1228336) for financial support.
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