LETTER
Synthesis of Multisubstituted 2-Acyl Furans
1013
first formation of the enynone 3 followed by cyclization.
However, we failed to isolate any intermediates during the
process.
–
CF3CO2I
CF3CO2
I
3a
IO2CF3C
Ph
Ph
Ph
O
+
10
O
Ph
9
PIFA (2 equiv), I2 (2.0 equiv)
NaHCO3 (4.0 equiv)
Ph
hydrolysis
I
–
CF3CO2
I
2a
8
2a
Ph
Ph
Ph
O
THF, r.t., 2 h
O
+
11
O
OCOF3C
Ph
87%
Ph
12
3a
Scheme 4 Possible reaction mechanism for the cyclization of
enynones
Scheme 2 PIFA/I2-mediated cyclization of enynone 3a
On the basis of the above observations, a possible reaction
mechanism for PIFA-mediated reaction of enynols is de-
picted in Scheme 3. Thus, upon mixing the PIFA and io-
dine, iodobenzene and trifluoroacetylhypoiodite are
generated.11,12 The hypoiodite may coordinate with triple
bond to enhance the electrophilicity of the alkyne moiety.
Then the subsequent 5-exo-dig nucleophilic attack of the
hydroxy group on the alkyne would form a 5-ylidene-2,5-
dihydrofuran intermediate 5, which undergoes further io-
dination to give diiodide 7. These steps are accompanied
by loss of protons, which can be neutralized by a base. Hy-
drolysis of either 7 or trifluoroester 8 yields the final 2-
acyl furan 2a. Alternatively, a mechanism which involves
the intermediacy of enynone 3 cannot be ruled out. For the
transformation of enynone 3 to 2-acyl furan, we propose
the following mechanism (Scheme 4). Similarly, attack of
the carbonyl group onto the CF3COOI-coordinated triple
bond renders the oxonium ion 10.
for 2-acyl furans with diverse substitution pattern. The
method described here can be considered as a useful com-
plement of the IBX-mediated oxidative cyclization of
enynols. Further studies to elucidate the mechanism of
this reaction and to extend the scope of synthetic utility
are in progress in our laboratory.
Supporting Information for this article is available online at
Acknowledgment
We thank the National Natural Science Foundation of China (Grant
Nos. 20872163, 20732008, 20821002), Chinese Academy of Sci-
ence, and the Major State Basic Research Development Program
(Grant No. 2006CB806105) for financial support.
References and Notes
PhI(OCOCF3)2
+ I2
(1) (a) Hosoya, T.; Aoyama, H.; Ikemoto, T.; Kihara, Y.;
Hiramatsu, T.; Endo, M.; Suzuki, M. Bioorg. Med. Chem.
2003, 11, 663. (b) Wiesner, J.; Mitsch, A.; Jomaa, H.;
Schlitzer, M. Bioorg. Med. Chem. Lett. 2003, 13, 2159.
(c) Pomel, V.; Klicic, J.; Covini, D.; Church, D. D.; Shaw, J.
P.; Roulin, K.; Burgat-Charvillon, F.; Valognes, D.; Camps,
M.; Chabert, C.; Gillieron, C.; Françon, B.; Perrin, D.;
Leroy, D.; Gretener, D.; Nichols, A.; Vitte, P. A.; Carboni,
S.; Rommel, C.; Schwarz, M. K.; Rückle, T. J. Med. Chem.
2006, 49, 3857. (d) Mugnaini, C.; Rajamaki, S.; Tintori, S.;
Corelli, F.; Massa, S.; Witvrouw, M.; Debyser, Z.;
CF3CO2I
NaHCO3
CF3CO2
I
1a
IO2CF3C
Ph
Ph
Ph
Ph
Ph
O
HO
Ph
–
Ph
5
4
I
I
CF3CO2I
NaHCO3
I
O
O
H
Ph
I+
–
Ph
CF3CO2
base
6
7
Veljkovic, V.; Botta, M. Bioorg. Med. Chem. Lett. 2007, 17,
5370.
(2) For the synthesis of 2-acyl furans, see: (a) Francesconi, I.;
Patel, A.; Boykin, D. W. Synthesis 1999, 61. (b) Bello,
A. M.; Kotra, L. P. Tetrahedron Lett. 2003, 44, 9271.
(c) Tinggaard, M.; Hansen, P.; Mogensen, P. K.; Simonsen,
O.; Becher, J. J. Heterocycl. Chem. 1989, 26, 439.
–
Ph
CF3CO2
hydrolysis
Ph
F3COCO
Ph
O
O
O
F3COCO
8
2a
(d) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(e) McClure, M. S.; Glover, B.; McSorley, E.; Millar, A.;
Osterhout, M. H.; Roschangar, F. Org. Lett. 2001, 3, 1677.
(f) Toshifumi, M.; Tsuyoshi, S. Tetrahedron Lett. 2007, 48,
4849. (g) Barluenga, J.; Riesgo, L.; Vicente, R.; López,
L. A.; Tomás, M. J. Am. Chem. Soc. 2008, 130, 13528.
(h) Cao, H.; Jiang, H.; Yao, W.; Liu, X. Org. Lett. 2009, 11,
1931. (i) Wang, T.; Zhang, J. Dalton Trans. 2010, 39, 4270.
(3) Du, X.; Chen, H.; Liu, Y. Chem. Eur. J. 2008, 14, 9495.
(4) For reviews, see: (a) Stang, P. J.; Zhdankin, V. V. Chem.
Rev. 1996, 96, 1123. (b) Zhdankin, V. V.; Stang, P. J. Chem.
Rev. 2002, 102, 2523. (c) Wirth, T. Angew. Chem. Int. Ed.
Scheme 3 Possible reaction mechanism for the cyclization of enyn-
ols
Nucleophilic addition of trifluoroacetate derived from
PIFA onto 10 affords intermediate 12, which may be
transferred to diester 8 by substitution reaction. Hydroly-
sis of either 12 or 8 furnishes the furan 2a.
In summary, a novel and efficient synthesis of 2-acyl
furans from cis-enynols upon the treatment with a combi-
nation of PIFA, I2, and NaHCO3 has been developed. This
reaction represents a general, simple, and mild procedure
Synlett 2011, No. 7, 1010–1014 © Thieme Stuttgart · New York