Tetrahedron Letters
Diversified assembly of perfluoroalkyl-substituted furans
and 2,5-dihydrofuran-2-ols
⇑
Guofei Chen, Guangke He, Can Xue, Chunling Fu, Shengming Ma
Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
We have developed a facile and effective synthesis of 3-iodofurans from 3-monosubstituted 1,2-allenyl
perfluoroalkyl ketones or 2-hydroxy-4-iodo-2,5-dihydrofurans from 3,3-disubstituted 1,2-allenyl per-
fluoroalkyl ketones. The perfluoroalkyl substituent and the amount of water in the solvent are important
for the success of this electrophilic cyclization.
Received 10 September 2010
Revised 12 October 2010
Accepted 15 October 2010
Available online 9 November 2010
Ó 2010 Elsevier Ltd. All rights reserved.
As one of the most important classes of heterocyclic com-
pounds, furans are not only significant components in many natu-
ral products but also useful building blocks in organic synthesis. On
the other hand, many attentions have been paid to the electrophilic
reaction of allenes,1,2 especially the electrophilic cyclization of
allenoates,3 allenoic acids4, and allenols5 with electrophiles such
as I2, Br2, PhSeCl, we envisioned that electrophiles such as I2, NIS,
and NBS would react with 1,2-allenyl ketones 1 to form intermedi-
ates M1. Then if R2 is equal to hydrogen, the intermediates M1
would form furans 2 through aromatization by releasing H+; if R2
is not equal to hydrogen, H2O would attack the C@O double bond
to form 2-hydroxy-2,5-dihydrofurans 3. This may open a new
access to synthesis of polysubstituted furans or 2,5-dihydrofuran-
2-ols (Scheme 1). However, we had very limited success on such
electrophilic cyclization of 1,2-allenyl ketones. The reason is obvi-
ous: 1,2-allenyl ketones are too electron-deficient. Recently, we
without decreasing the yield, but an unidentified byproduct was
formed which could not be separated from the main product 2a
(entries 2–3, Table 1). According to the previous experiences, we
know that water may play a critical role in such reaction.10 We
used CH3CN with the addition of 1.0 equiv of water as the reaction
media to test the reaction. Fortunately, the 2a was formed in 99%
NMR yield within 36 h at room temperature (entry 4, Table 1).
However, adding more equiv of water to CH3CN (5.0 equiv) ham-
pered the reaction and gave the product 2a in low yields (entry
5, Table 1). Other solvents such as DMSO, DMA, THF, Et2O were also
examined without better results (entries 6–9, Table 1).
Having established an optimal protocol, we next investigated
the generality and the scope of the reactions with the results being
summarized in Table 2. Excellent yields were given when R1 is a
phenyl group (entries 1–3, Table 2) while moderate to good yields
were given when R1 is an alkyl group (entries 4–7, Table 2). When
R3 was propyl group, a higher temperature (60 °C) or I2 (4.0 equiv)
was necessary to consume the starting allenone completely (com-
pare entry 3 with entry 1, entry 7 with entry 5, Table 2). The reac-
tivity of n-perfluorohexyl ketone 1f with a longer perfluoroalkyl
chain is low, and thus 4.0 equiv of I2 were needed to complete
the reaction (compare entry 6 with entry 4, Table 2). When
1,3,3-trisubstituted ketones 1h–j were applied to the reactions,
4-iodo-2,5-dihydrofuran-2-ols 3h–j were formed as expected (en-
tries 8–10, Table 2). When the reaction of 1j was conducted at
aqueous CH3CN (CH3CN/H2O = 20/1), the yield of the product 3j
was improved to 88% yield (entry 11, Table 2).
have developed
a useful synthesis of allenyl perfluoroalkyl
ketones.6 We observed that the Rf-substituted carbonyl group is
not very reactive toward nucleophilic reagents, such as Grignard
reagent, indicating a nature of less electron-withdrawing of the
RfCO group, which promoted us to study the corresponding elec-
trophilic cyclization reaction. As we know fluoroalkyl-substituted
furans are important unit in some biologically active compounds
showing anticancer, antibacterial, and antiparasite activities
(Fig. 1).7,8 Herein, we wish to report our recent studies on the elec-
trophilic cyclization of perfluoroalkyl allenyl ketones.
We initiated this study with the electrophilic cyclization of
1-phenylbuta-1,2-dien-3-yl n-perfluorobutyl ketone 1a with I2.
Interestingly, when the reaction of 1a was carried out at room tem-
perature in anhydrous CH3CN,9 the expected n-perfluorobutyl-
substituted iodofuran 2a was formed in 93% NMR yield with 2%
recovery of 1a in 36 h (entry 1, Table 1). At a higher temperature
such as 40 °C or 60 °C, the reaction time could be shortened
In conclusion, we have developed a facile and effective synthe-
sis of 3-iodofurans from 3-monosubstituted 1,2-allenyl perfluoro-
alkyl ketones or 2-hydroxy-4-iodo-2,5-dihydrofurans from 3,3-
disubstituted 1,2-allenyl perfluoroalkyl ketones. The presence of
the perfluoroalkyl substituent is important for the success of the
electrophilic cyclization. Since the normal 1,2-allenyl ketones did
not work on this type of electrophilic iodocyclization, this protocol
may be informative for further study in this area. Further studies in
this area are being pursued in our laboratory.
⇑
Corresponding author.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
Chen, Guofei
