Gold(I)-catalyzed formation of furans from Y-acyloxyalkynyl ketones

Article abstract of DOI:10.3762/bjoc.9.206

Various γ-acyloxyalkynyl ketones were efficiently converted into highly substituted furans with 2.5 mol % of triflimide (triphenyl-phosphine) gold(I) as a catalyst in dichloroethane at 70 °C.

Full text of DOI:10.3762/bjoc.9.206

Gold(I)-catalyzed formation of furans from
γ-acyloxyalkynyl ketones
Marie Hoffmann, Solène Miaskiewicz, Jean-Marc Weibel, Patrick Pale*
and Aurélien Blanc*
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 1774–1780.
Laboratoire de Synthèse, Réactivité Organiques et Catalyse, Institut
de Chimie, UMR 7177 associé au CNRS, Université de Strasbourg, 4
rue Blaise Pascal, 67070 Strasbourg, France
doi:10.3762/bjoc.9.206
Received: 25 June 2013
Accepted: 08 August 2013
Published: 30 August 2013
Email:
Patrick Pale* - ppale@unistra.fr; Aurélien Blanc* - ablanc@unistra.fr
This article is part of the Thematic Series "Gold catalysis for organic
synthesis II".
* Corresponding author
Keywords:
Guest Editor: F. D. Toste
alkynyl ketones; cycloisomerization; furans; gold-catalysis;
1,2-migration
© 2013 Hoffmann et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
Various γ-acyloxyalkynyl ketones were efficiently converted into highly substituted furans with 2.5 mol % of triflimide (triphenyl-
phosphine)gold(I) as a catalyst in dichloroethane at 70 °C.
Introduction
Furans are an important class of aromatic compounds. They are allenyl ketones [8-14], enynes or diynes [15-17], alkynes and
found in many natural products, in pharmaceutical and agro- sulfur ylides [18,19], alkynyl oxiranes [20-26], alkynyl ketones
chemical compounds as well as in flavor and fragrance indus- [27-35], alkynyl alcohols [36-46], and alkynyl ethers [47,48].
tries [1]. Furans are also routinely used as building blocks in Very recently, a three-component coupling reaction toward
organic synthesis [2,3]. Therefore, a large number of synthetic furans catalyzed by gold(III) has been reported starting
methods has been developed to construct the furan motif [4,5]. from terminal alkenes, glyoxal derivatives and secondary
Among them, late transition metal-catalyzed intra- or intermole- amines [49].
cular cyclizations of oxygenated functionalities on unsaturated
carbon–carbon bonds proved to be powerful synthetic methods In this emerging research area, we have been focusing our effort
due to their mildness, efficiency and diversity [6,7]. In the last on the development of furan motifs from alkynyl epoxides
decade, gold catalysts with their carbophilic character have [21,22,50,51] and new precursors, i.e. γ-acyloxyalkynyl ke-
emerged as a new tool for furan preparation. As summarized in tones. The latter have already been described to rearrange into
Scheme 1, furans could now be obtained by either gold(I) or furans by using copper catalysts. Indeed, Gevorgyan et al.
gold(III) catalysis from various types of substrates such as showed that the combination of copper(I) chloride and triethyl-
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Beilstein J. Org. Chem. 2013, 9, 1774–1780.
Scheme 1: Gold(I) or gold(III)-catalyzed furan syntheses with or without nucleophiles.
amine catalyzed the 1,2-migration/cycloisomerization of
γ-acyloxyalkynyl ketones in dimethylacetamide (DMA) at
130 °C (Scheme 2) within 1–46 h [31,52,53]. Despite the rela-
tive harsh reaction conditions, furans could be obtained in good
to excellent yields. However, one major limitation was ascribed
to the types of the employed ketones (R3 in Scheme 2), as only
phenyl and tert-butyl alkynyl ketones were able to furnish
Scheme 2: Copper(I)-catalyzed 1,2-migration/cycloisomerization of
γ-acyloxyalkynyl ketones.
acceptable yields.
We herein report that gold(I) can overcome these limitations,
providing a general, fast and very efficient transformation of Results and Discussion
γ-acyloxyalkynyl ketones into trisubstituted and functionalized In order to find the most appropriate conditions, we applied
furans.
various gold catalysts in different solvents at different tempera-
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Beilstein J. Org. Chem. 2013, 9, 1774–1780.
Table 1: Screening of the catalysts and the conditions.
Entry
Catalyst (mol %)
Solvent
T (°C)
Time (h)
Yield 2a (%)
Yield 3 (%)
1
2
3
4
5
6
7
8
9
CuCl (5)
Et3N/DMAa
DCEc
DCE
130
rt
17
86b
44
65
71
97
95
91
–e
–
Ph3PAuCl/AgSbF6 (5)
Ph3PAuNTf2 (5)
Ph3PAuCl/AgSbF6 (5)
Ph3PAuNTf2 (5)
Ph3PAuNTf2 (2.5)
Ph3PAuNTf2 (1)
AgNTf2 (5)
1
22
27
–
rt
2.5
0.1
0.25
0.5
0.7
16
DCE
70
70
70
70
70
70
DCE
–
DCE
–
DCE
<5d
15d
9d
DCE
[Cu(MeCN)4]NTf2 (5)
DCE
16
44
aDimethylacetamide. bReported yield from ref [52]. cDichloroethane. dEstimated yield based on the 1H NMR of the crude mixture. eDegradation
occurs.
tures to the easily available ynone 1a (Table 1), which has been With these conditions in hand (Table 1, entry 6), we started
reported to afford furan 2a in 86% yield under Gevorgyan’s investigating the scope of the reaction by preparing various
conditions (Table 1, entry 1). We started our catalyst screening acyloxyalkynyl ketones (Table 2). As for the phenyl alkynyl
by using the classical combination of Ph3PAuCl/AgSbF6 and ketone 1a, the corresponding tert-butyl alkynyl ketone 1b
the Gagosz’s catalyst [54], i.e. (triphenylphosphine)gold(I) turned out to be a good substrate for this transformation
triflimide, in dichloroethane at room temperature. In both cases, confirming Gevorgyan’s results (Table 2, entry 1 versus entry
a fast consumption of the starting material 1a was observed 2). Despite its bulkiness, full conversion was achieved within
compared to the copper(I) catalysis, but lower yields of furans, 30 min and 2.5 mol % of Ph3PAuNTf2, affording furan 2b in
44% and 65% respectively, were obtained mostly due to the for- 93% yield. We also evaluated the influence of the alkynyl
mation of the hydration product 3 (Table 1, entries 2 and 3 substitution by increasing the size of the R1 group. To imple-
versus entry 1). We found out that running the reaction at 70 °C ment this, we introduced secondary and tertiary carbon centers
instead of at room temperature completely prevented the next to the acyloxy function by preparing compounds 1c (R1 =
byproduct formation. At this temperature good to quantitative 2-decyl) and 1d (R1 = tert-butyl). Compound 1c, similar to 1a,
yields of furans 2a were achieved in less than 30 min, and rearranged under these conditions, furnishing the furan 2c in
5 mol % of Ph3PAuNTf2 turned out to be the more efficient 90% yield (Table 2, entry 3). However, the presence of the ster-
catalyst (Table 1, entries 2 and 3 versus entries 4 and 5). We ically demanding tert-butyl group in 1d drastically affected the
then verified that the hydrate product was not a transient inter- reaction (Table 2, entry 1 and 3 versus entry 4). Even running
mediate in this rearrangement by subjecting pure compound 3 the reaction with 5 mol % of catalyst to avoid the hydration
to the latter reaction conditions and, even after 3 h at 70 °C, no product, the reaction took 6 h to reach almost full conversion.
trace of furan 2a could be detected by 1H NMR analysis. Inter- Beside the expected furan 2d, its corresponding regioisomer 2d’
estingly, decreasing the catalytic loading from 5 to 1 mol % still arising from 1,3-migration of the pivaloyl group is formed in
provided the furan in less than 1 h and in high yields (Table 1, this reaction and both products were obtained in a combined
entries 6 and 7 versus entry 5). However, hydration started to yield of 68% (Table 2, entry 4). We next varied the nature of
compete again at low loading, as evidenced by tiny amounts of the migratory acyloxy group. We synthetized similar substrates
3 in the NMR spectrum of the crude (Table 1, entry 7). Control 1e–1h bearing pivaloyl, benzoyl, acetyl and 2-phenylacetyl
experiments revealed that other triflimide salts of coinage groups, respectively. These compounds were engaged in the
metals were not suited for this transformation. Indeed, silver(I) gold-catalyzed process affording the furans 2e–2h in the same
triflimide resulted mainly in degradation (Table 1, entry 8) range of yields (70–80%), suggesting that the nature of the
and tetrakis(acetonitrile)copper(I) triflimide furnished the furan acyloxy group had no crucial influence on the rearrangement.
2a in only modest yield even after prolonged reaction time Indeed, the slight differences in terms of yield could be ascribed
(Table 1, entry 9).
to the formation of hydration products (5–15%), and the reac-
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Beilstein J. Org. Chem. 2013, 9, 1774–1780.
tion times of each reaction were inferior or equal to 1 h substituents adjacent to the ketone, i.e. without enolizable pos-
(Table 2, entries 5–8). We then turned our attention to the prob- ition, were tolerated under copper(I)-catalyzed reaction condi-
lematic R3 position in which only phenyl and tert-butyl tions. We were pleased to observe that various other
Table 2: Scope of the gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones.
Entry
Substrates 1
Time (h)
0.5
Furans 2
Yield (%)
1
95
2a
1a
1b
1c
1d
1e
1f
2
3
4
5
6
7
0.5
0.75
6
93
90
2b
2c
68a
78
2d/2d’
1
2e
0.5
0.75
81
2f
70
2g
1g
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Beilstein J. Org. Chem. 2013, 9, 1774–1780.
Table 2: Scope of the gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones. (continued)
8
9
1
75
2h
1h
1i
0.33
77
68
2i
2j
10
0.5
1j
11
12
0.33
0.33
74
65
2k
1k
1l
2l
aCumulative yield of furans 2d and 2d’; reaction performed with 5 mol % of catalyst.
substituents, such as methyl, propyl, 2-phenylethyl, 3-benzy- carbonyl function on the carbon bearing the R1 substituent to
loxypropyl (Table 2, entries 9–12), were fully compatible with afford the oxygenated five-membered ring E. Furan would
our gold-catalysis giving furans 2i–l in good yields.
finally be formed after tautomerization and protodemetalation
of intermediate E.
Two different mechanistic hypotheses could be envisaged in the
rearrangement of γ-acyloxyalkynyl ketones into furans based on Conclusion
multifaceted gold-catalyst properties, i.e. the ability of gold We have reported an efficient, very general and regioselective
cations to act as π or σ Lewis acids (Scheme 3) [21,55,56]. In- preparation of functionalized furans through a gold(I)-catalyzed
tramolecular [1,4]-addition of the acyloxy function by oxophilic rearrangement of γ-acyloxyalkynyl ketones under mild condi-
activation of γ-acyloxyalkynyl ketones could lead to the forma- tions. Further work is currently underway in our laboratory to
tion of gold allenolate A, which is in equilibrium with both Z or fully understand this novel rearrangement.
E vinylgold B and C [57]. Intermediate B, which could also be
generated by carbophilic gold activation followed by nucleo- Experimental
philic addition of the acyloxy part, could evolve into the gold General procedure for gold(I)-catalyzed formation of furans
carbenoid species D [31]. Intermediate C, possessing the correct from γ-acyloxyalkynyl ketones. In an oven-dried flask,
stereochemistry, and D might then cyclize by an attack of the γ-acyloxyalkynyl ketone (0.4 mmol) was dissolved in dry
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Beilstein J. Org. Chem. 2013, 9, 1774–1780.
Scheme 3: Mechanistic hypothesis for gold(I)-catalyzed conversion of γ-acyloxyalkynyl ketones into furans.
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stirred solution at 70 °C. The reaction was monitored by thin-
layer chromatography until completion. The solvent was then
removed in vacuo, and the crude residue was purified by silica
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Acknowledgements
The authors thank the CNRS and the French Agency of
Research (grant ANR 11-JS07-001-01 SyntHetAu) for finan-
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Research for a PhD fellowship.
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