Silver-catalyzed highly regioselective synthesis of α-carbonyl furans from enynones

Article abstract of DOI:10.1080/00397911.2013.878027

A general and efficient method for the synthesis of a wide range of α-carbonyl furans is described here. The cyclization of enynone is catalyzed by AgBF₄ in a fluorous biphasic system of perfluorodecalin and N,N-dimethylformamide. A variety of chain ketone and cyclic ketone substrates were used to investigate the scope of the reactions.

Full text of DOI:10.1080/00397911.2013.878027

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Silver-Catalyzed Highly Regioselective
Synthesis of α-Carbonyl Furans from
Enynones
Zheng-Wang Chen a , Miao-Ting Luo a , Dong-Nai Ye a , Zhong-Gao
Zhou a , Min Ye a & Liang-Xian Liu a
a School of Chemistry and Chemical Engineering , Gannan Normal
University , Ganzhou , Jiangxi , China
Accepted author version posted online: 18 Mar 2014.Published
online: 14 May 2014.
To cite this article: Zheng-Wang Chen , Miao-Ting Luo , Dong-Nai Ye , Zhong-Gao Zhou , Min Ye &
Liang-Xian Liu (2014) Silver-Catalyzed Highly Regioselective Synthesis of α-Carbonyl Furans from
Enynones, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 44:12, 1825-1831, DOI: 10.1080/00397911.2013.878027
To link to this article: http://dx.doi.org/10.1080/00397911.2013.878027
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Synthetic Communications1, 44: 1825–1831, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.878027
SILVER-CATALYZED HIGHLY REGIOSELECTIVE
SYNTHESIS OF a-CARBONYL FURANS FROM
ENYNONES
Zheng-Wang Chen, Miao-Ting Luo, Dong-Nai Ye, Zhong-Gao
Zhou, Min Ye, and Liang-Xian Liu
School of Chemistry and Chemical Engineering, Gannan Normal University,
Ganzhou, Jiangxi, China
GRAPHICAL ABSTRACT
Abstract A general and efficient method for the synthesis of a wide range of a-carbonyl
furans is described here. The cyclization of enynone is catalyzed by AgBF4 in a fluorous
biphasic system of perfluorodecalin and N,N-dimethylformamide. A variety of chain ketone
and cyclic ketone substrates were used to investigate the scope of the reactions.
Keywords a-Carbonyl furans; enynone; ketone; molecular oxygen; perfluorodecalin
INTRODUCTION
The synthesis of furans has been the subject of intense research, because
they are wildly used as key structural units in many bioactive natural products
and important pharmaceuticals. Moreover, they are useful intermediates for the
preparation of varieties of acyclic and heterocyclic compounds.[1] The search for
efficient routes to multiply substituted furans is an important, continuing goal of
organic synthesis. Recently, several studies have focused on the development of
metal-catalyzed synthesis of furans employing acyclic precursors. These include the
cyclization of allenyl,[2] alkynyl,[3] cyclopropenyl,[4] and cyclopropyl[5] ketone deriva-
tives. Alternative strategies involve the cyclization of alkynols,[6] substituted propar-
gyl vinyl ethers,[7] functionalized oxiranes,[8] 1,3-diynes,[9] and other substrates.[10]
Those methodologies are convenient for constructing polysubstituted furans; how-
ever, only few examples have been reported on the synthesis of a-carbonyl furans.[11]
Received May 19, 2013.
Address correspondence to Zheng-Wang Chen, School of Chemistry and Chemical Engineering,
Gannan Normal University, Ganzhou, Jiangxi 341000, China. E-mail: chenzwang@126.com
1825

1826
Z.-W. CHEN ET AL.
´
´
The fluorous biphase system (FBS), first reported by Horvath and Rabai in
1994,[12] has attracted considerable interest. It bears some potential advantages over
classical homogenous systems, including easy separation and recycling of the catalyst.
Moreover, the perfluorinated hydrocarbons are ideal solvents for organic transform-
ation; for example, they have exceptionally high affinity for dioxygen in the catalytic
oxidation of hydrocarbons.[13] Indeed, a number of organic reactions have achieved in
fluorous media.[14] Very recently, carbonyl ene-yne compounds have been used for
efficient synthesis of multisubstituted furans.[15] Inspired by these results, here we
present a silver-catalyzed highly regioselective synthesis of a-carbonyl furans from
enynones in fluorous media with molecular oxygen as the oxidant.
RESULTS AND DISCUSSION
Table 1 summarizes the results of the reaction of ene-yne-diketone (1a)
with molecular oxygen in the presence of a catalytic amount of silver salts and
Table 1. Optimization of reaction conditions for the synthesis of multisubstituted furana
Entry
Catalyst
Cosolvent
Yield (%)b
1
2
AgCl
DCE
DCE
16
25
AgNO3
AgOAc
AgOTf
AgF
3
DCE
DCE
29
47
4
5
DCE
DCE
8
26
6
Ag2CO3
AgSbF6
AgBF4
7
DCE
DCE
DCE
39
56
8
9
n.r
41
10
11
12
13
14
15
16c
17d
18e
AgBF4
AgBF4
AgBF4
AgBF4
AgBF4
AgBF4
AgBF4
AgBF4
AgBF4
EtOH
Toluene
1,4-Dioxane
DMSO
CH3CN
DMF
DMF
DMF
DMF
53
84.
77
63
87 (83)
56
n.p
43
aReaction conditions: 1a (0.25 mmol), catalyst (10 mol%), O2 (1 atm), cosolvent (0.5 mL), and perfluor-
odecalin (0.5 mL) at 60 ꢀC for 16 h.
bDetermined by GC. Number in parentheses is isolated yield.
cDMF (1 mL) without perfluorodecalin.
dUnder anaerobic conditions.
eAgBF4 (3 mol%).

1827

1828

REGIOSELECTIVE SYNTHESIS OF a-CARBONYL FURANS
1829
perfluorodecalin as solvent to screen the best reaction conditions. First, different
commonly used metal silver salts were used as the catalyst to conduct this reaction.
As can be seen, all silver salts had some effects on the reaction and AgBF4 could
afford the corresponding product in 56% gas chromatographic (GC) yield (Table 1,
entries 1–8). The reaction did not proceed without catalyst (Table 1, entry 9). Then
AgBF4 was used as the catalyst of choice. The reaction showed strong cosolvent
dependence. Among the cosolvents used, dimethylsulfoxide (DMSO), 1,4-dioxane,
and dimethylformamide (DMF) proved appropriate (Table 1, entries 10–15). Control
experiments revealed that perfluorodecalin was important to this transformation
(Table 1, entry 16). It is noteworthy that the reaction did not work without molecular
oxygen (Table 1, entry 17). A decrease of the catalyst dosage led to less satisfactory
results (Table 1, entry 18).
With the optimized conditions in hand (Table 1, entry 15), we next investigated
the scope of the formation of a-carbonyl furans by using a variety of substituted
enynones. As shown in Table 2, almost all substrates could afford corresponding
products with satisfactory yields. Initially, substituents R1 and R2 at the carbonyl
moiety were evaluated under the standardized conditions. For example, the cyclic
substrates could afford a-carbonyl furans in good yields (2b–f). The cyclization reac-
tions showed high functional group tolerance, and the functional groups such as
keto, ester, or amido group were suitable substrates for the transformation (2f–r).
It is noteworthy that the steric hindrance of the tert-butyl group was compatible
to the conditions (2i). Gratifyingly, the challenging substrates 1s–y were also
compatible in the standard conditions and afforded the corresponding products in
moderate to good yields (2s–y). The substituents at the terminal alkyne moiety were
subsequently examined. It was pleasing to discover that both the aryl and the alkyl
substrates provided the a-carbonyl furans in similar isolated yields.
Scheme 1. Plausible mechanism for the synthesis of a-carbonyl furan.

1830
Z.-W. CHEN ET AL.
The possible mechanism was proposed (Scheme 1) on the basis of the previous
mechanism studies and our reaction results.[11] First, the AgBF4 coordinated to the
triple bond of the alkyne moiety and the carbonyl group. Then the carbonyl oxygen
attacked the silver-activated alkyne and the silver carbene intermediate B was
formed. Finally, the carbene intermediate B was oxidized to a-carbonyl furan 2a
with molecular oxygen.
CONCLUSION
In summary, we have developed a highly efficient catalytic system for the
synthesis of multisubstituted a-carbonyl furans via cyclization of enynones with
molecular oxygen in a fluorous biphasic system of perfluorodecalin and N,N-
dimethylformamide. Both the chain ketones and the cyclic ketones are suitable
substrates for the transformations. Further synthetic applications and studies of
the reaction mechanism are in progress.
EXPERIMENTAL
Typical Procedure for the Preparation of the a-Carbonyl Furans
Enynone (0.25 mmol) and AgBF4 (10 mol%) were added to an oven-dried
Schlenk tube. The septum-sealed tube was evacuated and refilled with O2 three times.
DMF (0.5 mL) and perfluorodecalin (0.5 mL) were added via syringe. The samples
were vigorously stirred at 60 ꢀC for 16 h. After the reaction completed, the resulting
mixture was cooled with an ice bath. Then the fluorous layer on the bottom was sepa-
rated for the next reaction. The reaction mixture (organic phase) was diluted with
water (6 mL) and extracted with ether (3 Â 5 mL). The combined organic extracts
were dried with anhydrous MgSO4. The solvent was removed and the crude product
was separated by column chromatography to give the pure sample.
FUNDING
The authors thank the NSFC (21202023 and 21162001), NSF of Jiangxi Prov-
ince (20114BAB213006), and the NSF of Jiangxi Provincial Education Department
(GJJ12579) for financial support.
SUPPORTING INFORMATION
Typical experimental procedure and characterization for all products can
be found in the supplemental data for this article, which can be accessed on the
publisher’s website.
REFERENCES
1. (a) Dean, F. M. Naturally Occurring Oxygen Ring Compounds; Butterworths: London,
1963; pp. 1–28; (b) Donnelly, D. M. X.; Meegan, M. J. In Comprehensive Heterocyclic
Chemistry; A. R. Katrizky (Ed.); Pergamon Press: New York, 1984; Vol. 4, pp. 657–712.

REGIOSELECTIVE SYNTHESIS OF a-CARBONYL FURANS
1831
2. For some selective examples, see (a) Ma, S.; Yu, Z. Angew. Chem. Int. Ed. 2002, 41, 1775;
(b) Peng, L.; Zhang, X.; Ma, M.; Wang, J. Angew. Chem. Int. Ed. 2007, 46, 1905;
(c) Dudnik, A. S.; Gevorgyan, V. Angew. Chem. Int. Ed. 2007, 46, 5195; (d) Sromek,
A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127, 10500; (e) Zhou, C.-Y.;
Chan, P. W. H.; Che, C.-M. Org. Lett. 2006, 8, 325.
3. For some selective examples, see (a) Zhang, J.; Schmalz, H.-G. Angew. Chem. Int. Ed.
2006, 45, 6704; (b) Xiao, Y.; Zhang, J. Angew. Chem. Int. Ed. 2008, 47, 1903; (c) Yao, T.;
Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2004, 126, 11164; (d) Ge, G.-C.; Mo, D.-L.;
Ding, C.-H.; Dai, L.-X.; Hou, X.-L. Org. Lett. 2012, 14, 5756.
4. Ma, S.; Zhang, J. J. Am. Chem. Soc. 2003, 125, 12386.
5. Ma, S.; Lu, L.; Zhang, J. J. Am. Chem. Soc. 2004, 126, 9645.
6. For some selective examples, see (a) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.;
Milton, M. D.; Hidai, M.; Uemura, S. Angew. Chem. Int. Ed. 2003, 42, 2681;
(b) Chen, Y.; Liu, Y. J. Org. Chem. 2011, 76, 5274; (c) Gabriele, B.; Mancuso, R.;
Maltese, V.; Veltri, L.; Salerno, G. J. Org. Chem. 2012, 77, 8657; (d) Mothe, S. R.;
Lauw, S. J. L.; Kothandaraman, P.; Chan, P. W. H. J. Org. Chem. 2012, 77, 6937.
7. (a) Suhre, M. H.; Reif, M.; Kirsch, S. F. Org. Lett. 2005, 7, 3925; (b) Tejedor, D.; Cotos,
´
L.; Garcıa-Tellado, F. Org. Lett. 2011, 13, 4422.
8. (a) Hashmi, A. S. K.; Sinha, P. Adv. Synth. Catal. 2004, 346, 432; (b) Lo, C.-Y.; Guo, H.;
Lian, J.-J.; Shen, F.-M.; Liu, R.-S. J. Org. Chem. 2002, 67, 3930.
9. (a) Kramer, S.; Madsen, J. L. H.; Rottla¨nder, M.; Skrydstrup, T. Org. Lett. 2010, 12,
2758; (b) Jiang, H.; Zeng, W.; Li, Y.; Wu, W.; Huang, L.; Fu, W. J. Org. Chem. 2012,
77, 5179; (c) Zheng, Q.; Hua, R.; Yin, T. Curr. Org. Synth. 2013, 10, 161.
10. For some selective examples, see (a) Zhang, M.; Jiang, H.-F.; Neumann, H.; Beller, M.;
Dixneuf, P. H. Angew. Chem. Int. Ed. 2009, 48, 1681; (b) Barluenga, J.; Riesgo, L.;
Vicente, R.; Lopez, L. A.; Tomas, M. J. Am. Chem. Soc. 2008, 130, 13528; (c) Chen, Z.;
´ ´
Huang, G.; Jiang, H.; Huang, H.; Pan, X. J. Org. Chem. 2011, 76, 1134.
11. (a) Cao, H.; Jiang, H.; Yao, W.; Liu, X. Org. Lett. 2009, 11, 1931–1933; (b) Cao, H.;
Zhan, H.; Cen, J.; Lin, J.; Lin, Y.; Zhu, Q.; Fu, M.; Jiang, H. Org. Lett. 2013, 15,
1080; (c) Jiang, H.; Yao, W.; Cao, H.; Huang, H.; Cao, D. J. Org. Chem. 2010, 75,
5347; (d) Wang, T.; Zhang, J. Dalton Trans. 2010, 39, 4270.
´
12. Horvath, I. T.; Rabai, J. Science 1994, 266, 72.
13. (a) Horvath, I. T. Acc. Chem. Res. 1998, 31, 641; (b) Colonna, S.; Gaggero, N.;
´
´
Montanari, F.; Pozzi, G.; Quici, S. Eur. J. Org. Chem. 2001, 181, and references cited
therein.
14. (a) Zhang, W. Chem. Rev. 2004, 104, 2531; (b) Schneider, S.; Bannwarth, W. Angew.
Chem. Int. Ed. 2000, 39, 4142, and references cited therein.
´
´
´
15. (a) Vicente, R.; Gonzalez, J.; Riesgo, L.; Gonzalez, J.; Lopez, L. A. Angew. Chem. Int. Ed.
2012, 51, 8063; (b) Clark, J. S.; Boyer, A.; Aimon, A.; Garcıa, P. E.; Lindsay, D. M.;
Symington, A. D. F.; Danoy, Y. Angew. Chem. Int. Ed. 2012, 51, 12128.
´