Oxidative ring opening of 2,5-diarylfurans by Selectfluor

Article abstract of DOI:10.1016/j.tetlet.2006.07.071

Attempted fluorination of some 2,5-diarylfurans with the N-F reagent Selectfluor has led instead to oxidative ring opening of the furan ring to give the cis-enedione, along with traces of the trans isomer, in good isolated yield.

Full text of DOI:10.1016/j.tetlet.2006.07.071

Tetrahedron Letters 47 (2006) 6849–6850
Oxidative ring opening of 2,5-diarylfurans by Selectfluorâ
Stephen J. Blank and Chad E. Stephens*
Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303, USA
Received 27 June 2006; revised 12 July 2006; accepted 13 July 2006
Available online 4 August 2006
Abstract—Attempted fluorination of some 2,5-diarylfurans with the N–F reagent SelectfluorÒ has led instead to oxidative ring open-
ing of the furan ring to give the cis-enedione, along with traces of the trans isomer, in good isolated yield.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
hydrogen peroxide/methyltrioxorhenium combination
(UHP/MTO)12 and has been quite useful in the synthe-
sis of some complex molecules.8,13 The ring opening is
also known to occur upon reaction with halogenating
reagents such as Br2 or NBS,8,13 although the reaction
of 2,5-diphenylfuran 1b with NBS reportedly gives the
3,4-dibromofuran analog.14 Furan ring opening by
the SelectfluorÒ reagent has not been reported. In
this letter we wish to describe our results with this
reaction.
As part of a drug discovery effort, we were recently
interested in preparing various 3-fluoro or 3,4-difluoro
2,5-diarylfurans by direct fluorination of the parent
heterocycles. Our first attempt at this chemistry involved
the reaction of furan 1a with SelectfluorÒ, an N–F
reagent that has seen much use in recent years for the
fluorination of aromatics.1–4 Instead of giving ring
fluorination, the reaction led to oxidative ring opening
Cl
N
R2
R2
N
2BF4
R2
R2
F
O
(Selectfluor®)
R1
R1
O O
R1
R1
2a-c
1a R1 = Br, R2 = H
1b R1 = R2 = H
1c R1 = Br, R2 = CH3
+ trace of trans isomer
of the furan to yield primarily the cis-enedione. Such
ring opening of furans is known to occur with reagents
such as nitric acid,5 hydrogen peroxide,6 lead tetraace-
tate,7 meta-chloroperoxybenzoic acid (MCPBA),8 mag-
nesium monoperoxyphthalate (MMPP),9 Mo(CO)6/
cumyl hydroperoxide,10 MoO5-HMPA,11 and a urea
2. Results
Our preliminary attempt at fluorinating furan 1a
involved reaction with SelectfluorÒ (2 equiv) in DMF
at about 70–80 °C for a few hours. This led to complete
consumption of starting material according to TLC,
with formation of two products (one major, one very
minor) in near quantitative yield. Separation of these
two products by silica gel chromatography and charac-
terization by 1H NMR, IR, and mp showed that we had
obtained cis-enedione 2a as a major product, along with
a trace amount of the trans isomer. Mechanistically, this
most likely involves a 1,4-addition of HOF to the furan,
Keywords: Furan; Oxidative ring opening; Fluorination; SelectfluorÒ;
cis-Enedione.
*
Corresponding author at present address: Department of Chemistry
and Physics, Augusta State University, Augusta, GA 30904, USA.
Tel.: +1 706 667 4995; fax: +1 706 667 4519; e-mail: cstephe7@aug.
edu
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.071

6850
S. J. Blank, C. E. Stephens / Tetrahedron Letters 47 (2006) 6849–6850
followed by ring opening and elimination of fluoride.
The water apparently came from traces present in the
DMF solvent or the SelectfluorÒ reagent itself.
References and notes
1. Lal, G. S.; Pez, G. P.; Syvret, R. G. Chem. Rev. 1996, 96,
1737.
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3. Hart, J. J.; Syvret, R. G. J. Fluorine Chem. 1999, 100, 157.
4. Nyffeler, P. T.; Duron, S. G.; Burkart, M. D.; Vincent, S.
P.; Wong, C.-H. Angew. Chem., Int. Ed. 2005, 44, 192.
5. Lutz, R. E.; Wilder, F. N. J. Am. Chem. Soc. 1934, 56,
978.
6. Lutz, R. E.; Dien, C.-K. J. Org. Chem. 1958, 23, 1861.
7. Dien, C.-K.; Lutz, R. E. J. Org. Chem. 1957, 22, 1355.
8. Lipshutz, B. H. Chem. Rev. 1986, 86, 795.
In an attempt to optimize this potentially useful reac-
tion, we replaced the DMF solvent with aqueous
THF. With this solvent, the reaction of furan 1a with
Selectfluor (2 equiv) at 60–70 °C for 3 h also gave com-
plete/quantitative ring opening. Purification by chroma-
tography to remove the traces of trans isomer (structure
confirmed by TLC comparison with authentic sample
and 1H NMR of the crude sample) resulted in a 58% iso-
lated yield of cis-enedione 2a.
9. Dominguez, C.; Csaky, A. G.; Plumet, J. Tetrahedron
Lett. 1990, 31, 7669.
10. Massa, A.; Acocella, M. R.; De Rosa, M.; Soriente, A.;
Villano, R.; Scettri, A. Tetrahedron Lett. 2003, 44, 835.
11. Chien, C.-S.; Kowasaki, T.; Sakamoto, M. Chem. Pharm.
Bull. 1985, 33, 5071.
12. Finlay, J.; McKervey, M. A.; Gunaratne, H. Q. N.
Tetrahedron Lett. 1998, 39, 5651.
13. Harris, J. M.; O’Doherty, G. A. Tetrahedron Lett. 2002,
43, 8195.
14. Duan, X.-L.; Perrins, R.; Reese, C. W. J. Chem. Soc.,
Perkins Trans. 1 1997, 11, 1617.
15. Representative procedure and notes: To a solution of
2,5-diphenylfuran (1b) (Lancaster Synthesis) (0.22 g,
1.0 mmol) in tetrahydrofuran (THF) (4 ml) was added 1-
chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane
bis(tetrafluoroborate) (SelectfluorÒ) (0.71 g, 2.0 mmol)
followed by 10 drops of water (Pasteur pipette) and the
mixture was stirred at room temperature until the starting
material was consumed by TLC (2 h). Aqueous extraction
with EtOAc followed by silica gel column chromatogra-
phy eluting with 1–2% EtOAc in hexanes gave the pure cis-
enedione 2b (cis-1,2-dibenzoylethylene) as an off white
solid (0.163 g, 69% yield), mp 132–133.5 °C; lit. mp 131–
132 °C16 and 134 °C.17 IR (cmÀ1): 3086.2, 3065.5, 3021.6,
1664.1, 1599.1, 1232.2, 1015.1. 1H NMR (CDCl3,
300 MHz): 7.15 (s, 2H), 7.45 (t, 4H), 7.55 (t, 4H), 7.95
(d, 2H). Dibromo cis-enedione 2a, obtained as a white
solid by heating as noted in the text, had mp 120–122 °C;
lit. mp 122–123 °C.18 Starting furans 1a and 1c were
prepared according to the literature.19
In a limited effort to examine the scope of this reaction,
two other furans were subjected to the ring opening. The
reaction of the parent 2,5-diphenylfuran 1b with Select-
fluorÒ was found to proceed fully at room temperature
in just 2 h to give cis-enedione 2b in 69% purified yield.15
A similar reaction with the 3,4-dimethyl analog 1c also
gave complete ring opening (in essentially quantitative
crude yield); however, we were unable to separate out
the trace of trans product by chromatography, possibly
due to isomerization between the two isomers on the
column (which has been observed by others).16
3. Conclusion
In conclusion, attempted fluorination of some 2,5-
diarylfurans with the N–F reagent SelectfluorÒ has led
to oxidative ring opening of the furan ring to give
predominantly the cis-enedione. Considering that many
of the other reagents typically used for furan ring
opening (i.e., HNO3, MCPBA, UHP/MTO, etc.) are
likely stronger oxidizers than SelectfluorÒ, this N–F
reagent may represent a milder alternative for this
conversion.
Acknowledgements
16. Zimmerman, H. E.; Durr, H. G.; Givens, R. S.; Lewis, R.
G. J. Am. Chem. Soc. 1967, 89, 1863.
17. Conant, J. B.; Lutz, R. E. J. Am. Chem. Soc. 1923, 45,
1303.
18. Campbell, K. J. Chem. Soc. 1949, 33, 35.
19. Das, B. P.; Boykin, D. W. J. Med. Chem. 1977, 20, 531.
Support for this research was provided by the Depart-
ment of Chemistry, Georgia State University. Select-
fluorÒ was a gift from Air Products and Chemicals,
Inc.