Phenyliodine(III) triflate mediated synthesis of 5-benzoyldihydro-2(3H)- furanones

Article abstract of DOI:10.1002/jccs.200500144

A direct and efficient method for the preparation of 5-benzoyldihydro-2(3H) -furanones was realized by cyclization of 4-benzoylbutyric acids in the presence of phenyliodine(III) triflate.

Full text of DOI:10.1002/jccs.200500144

Journal of the Chinese Chemical Society, 2005, 52, 1029-1032
1029
Phenyliodine(III) Triflate Mediated Synthesis of
5-Benzoyldihydro-2(3H)-furanones
Rei-Sheu Houa (
Yu-Chien Linb (
), Huey-Min Wanga (
),
) and Ling-Ching Chenb* (
)
aChung Hwa College of Medical Technology, Tainan 717, Taiwan, R.O.C.
bGraduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University,
Kaohsiung 807, Taiwan, R.O.C.
A direct and efficient method for the preparation of 5-benzoyldihydro-2(3H)-furanones was realized by
cyclization of 4-benzoylbutyric acids in the presence of phenyliodine(III) triflate.
Keywords: Phenyliodine(III) diacetate; Trifluoromethanesulfonic acid; a-Keto triflate.
INTRODUCTION
Lactonization methodology plays an important role in
bonyl group represents an increasingly important entity in
both mechanistic5 and synthetic6 organic chemistry. One of
the reasons for this is that the triflate group is a good leaving
group, and this accounts for the considerable synthetic utility
associated with these groups in functionalization of carbonyl
compounds. Due to the triflate having better leaving ability
than the corresponding halide, a-keto triflate reacts rapidly
with carboxyl group without assistance of Lewis acid to give
furanones.
modern organic synthetic chemistry not only because lac-
tones occur in nature in great abundance and variety,1 but also
because they constitute a particularly useful class of syn-
thons.2 The preparation of lactones was via intramolecular
cyclization of acyclic olefinic carboxylic acids.3 Recently,
hypervalent iodine reagents have been extensively used in or-
ganic syntheses due to their low toxicity, ready availability,
and easy handling.4 As a continuation of our studies concern-
ing hypervalent iodine(III) chemistry and its application to
the synthesis of heterocycles, we report here a new and direct
method for the conversion of 4-benzoylbutyric acids (1) to
5-benzoyldihydro-2(3H)-furanones (3) by the reaction with
phenyliodine(III) triflate [generated in situ by reaction of
phenyliodine(III) diacetate (PIDA) with trifluoromethane-
sulfonic acid] at room temperature (Scheme I).
As shown in Table 1, various 5-benzoyldihydro-2(3H)-
furanones were prepared in good to high yields. Gratifyingly,
Table 1. Yields of 5-benzoyldihydro-2(3H)-furanones prepared
Furanone
Ar
Yield (%)
3a
3b
3c
3d
3e
3f
3g
3h
3i
Ph
4-MeC6H4
4-OMeC6H4
4-ClC6H4
4-BrC6H4
4-i-prC6H4
2,4-Me2C6H3
2,5-Me2C6H3
2,4,6-Me3C6H2
81
78
76
80
75
82
72
77
85
RESULTS AND DISCUSSION
The triflate group positioned in the a position to a car-
Scheme I
O
O
COOH
PIDA, CF3SO3H
CH2Cl2, rt
COOH
Ar
Ar
O
O
OSO2CF3
Ar
O
3
2
1

1030 J. Chin. Chem. Soc., Vol. 52, No. 5, 2005
Hou et al.
Scheme II
O
COOH
OH
O
PhI(OSO2CF3)2
Ar
Ph
COOH
COOH
I
Ar
Ar
OSO2CF3
4
1
O
Ar
COOH
O
O
Ar
O
OSO2CF3
2
3
the reactions were completed at room temperature for 0.5 h
300 instrument.
and found to be clean in all cases. The structures of 3 spec-
1
tral were identified by their IR, H NMR, and MS spectral
General procedure for the preparation of 5-benzoyl-
dihydro-2(3H)-furanones 3a-i
data.
A reasonable pathway of the above transformations
may be explained as follows: The electrophilic addition of
phenyliodine(III) triflate to the enolic form of the ketone (1)
gave intermediate 4. Step 4 to a-keto triflate (2) can occur
through displacement of the iodobenzene by 1,2 shift of the
-OSO2CF3 group. The preparation of 5-benzoyldihydro-
2(3H)-furanones (3) was via intramolecular cyclization of
a-keto triflates (2) (Scheme II).
To a stirred solution of the phenyliodine diacetate (242
mg, 0.75 mmol) in CH2Cl2 (20 mL) was added CF3SO3H (225
mg, 1,50 mmol), and the mixture was stirred at room temper-
ature for 10 min. To the reaction mixture, 4-benzoylbutyric
acid (0.5 mmol) was added and stirring was continued at
room temperature for 0.5 h. The reaction mixture was washed
with saturated aqueous NaHCO3 solution, dried over MgSO4,
and concentrated under reduced pressure. The residue was
purified by chromatography on a silica gel column with
CHCl3-AcOEt (9:1) as eluent to give the products 3a-i.
The above results can be rationalized by the formation
of phenyliodine(III) triflate in situ by the action of trifluoro-
methanesulfonic acid on PIDA (eq. 1).
5-Benzoyldihydro-2(3H)-furanone (3a)
PhI(OAc)2 + 2CF3SO3H ®
mp 77-78 °C (CHCl3/hexane) (lit.,7 78-79 °C). IR (neat)
1
PhI(OSO2CF3)2 + 2AcOH
(1)
n: 1780, 1687, 1245, 1060 cm-1. H NMR (CDCl3) d: 2.44-
2.62 (m, 4H), 5.79-5.82 (m, 1H), 7.50-7.55 (m, 2H), 7.63-
7.67 (m, 1H), 7.98 (dd, J = 1.2, 8.8 Hz, 2H). 13C NMR (CDCl3)
d: 24.9, 26.6, 78.1, 128.5, 128.8, 133.3, 134.1, 176.3, 194.4.
EI-MS: 105, 77.
In summary, the method described herein provides a
good approach for the direct transformation of 5-benzoyl-
dihydro-2(3H)-furanones by using the reaction of 4-benzoyl-
butyric acids with phenyliodine(III) triflate at room tempera-
ture.
5-(4-Methylbenzoyl)dihydro-2(3H)-furanone (3b)
mp 89-90 °C (CHCl3/hexane) (lit.,8 90-91 °C). IR (neat)
n: 1768, 1689, 1229, 1066 cm-1. 1H NMR (CDCl3) d: 2.44 (s,
3H), 2.44-2.62 (m, 4H), 5.76-5.79 (m, 1H), 7.31 (d, J = 8.4
Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3) d: 21.7,
25.0, 26.8, 78.1, 128.8, 128.9, 129.6, 129.7, 131.0, 145.4,
176.3, 193.9. EI-MS: 204 (M+), 119, 91.
EXPERIMENTAL SECTION
All melting points are uncorrected. The IR spectra were
1
recorded on a Shimadzu IR-27 G spectrophotometer. H
NMR and 13C NMR spectra were recorded on a Varian Unity
Plus 400 MHz. Chemical shifts were measured in ppm (d)
with respect to TMS. MS were obtained on a JEOL JMS D-
5-(4-Methoxybenzoyl)dihydro-2(3H)-furanone (3c)
mp 121-123 °C (CHCl3/hexane) (lit.,7 122-124 °C). IR

Synthesis of 5-Benzoyldihydro-2(3H)-furanones
J. Chin. Chem. Soc., Vol. 52, No. 5, 2005 1031
(neat) n: 1773, 1683, 1244, 1071 cm-1. 1H NMR (CDCl3) d:
2.48-2.65 (m, 4H), 3.89 (s, 3H), 5.73-5.76 (m, 1H), 6.98 (d, J
= 8.8 Hz, 2H), 7.97 (d, J = 8.8 Hz, 2H). 13C NMR (CDCl3) d:
25.0, 26.9, 55.6, 78.1, 114.2, 126.6, 131.2, 164.4, 176.4,
192.7. EI-MS: 220 (M+), 135, 77.
137.2, 176.4, 197.8. EI-MS: 218 (M+), 133, 105. HRMS (EI)
Calcd for C13H14O3: 218.0943. Found: 218.0946.
5-(2,4,6-Trimethylbenzoyl)dihydro-2(3H)-furanone (3i)
Oily compound. IR (neat) n: 1787, 1707, 1609, 1251,
1
1063 cm-1. H NMR (CDCl3) d: 2.17 (s, 6H), 2.24 (s, 3H),
5-(4-Chlorobenzoyl)dihydro-2(3H)-furanone (3d)
mp 92-93 °C (CHCl3/hexane) (lit.,8 93-94 °C). IR (neat)
2.16-2.61 (m, 4H), 5.23-5.26 (m, 1H), 6.78 (s, 2H). 13C NMR
(CDCl3) d: 19.5, 21.0, 24.5, 24.6, 26.9, 81.8, 128.8, 130.6,
134.0, 134.9, 137.3, 139.9, 176.0, 205.6. EI-MS: 232 (M+),
149, 147, 121, 105. HRMS (EI) Calcd for C14H16O3: 232.1099.
Found: 232.1097.
1
n: 1773, 1694, 1282, 1071 cm-1. H NMR (CDCl3) d: 2.54-
2.59 (m, 4H), 5.69-5.74 (m, 1H), 7.49 (dd, J = 2.0, 6.4 Hz,
2H), 7.95 (dd, J = 2.0, 6.8 Hz, 2H). 13C NMR (CDCl3) d: 24.6,
26.8, 78.2, 129.3, 130.2, 131.9, 140.9, 175.9, 193.2. EI-MS:
141, 139.
ACKNOWLEDGEMENT
5-(4-Bromobenzoyl)dihydro-2(3H)-furanone (3e)
mp 71-73 °C (CHCl3/hexane) (lit.,8 70-72 °C). IR (neat)
We gratefully acknowledge the National Science Coun-
cil of the Republic of China for the financial support of this
work (Grant No. 93-2113-M-037-010).
1
n: 1780, 1690, 1244, 1064 cm-1. H NMR (CDCl3) d: 2.45-
2.63 (m, 4H), 5.79-5.82 (m, 1H), 7.63-7.68 (m, 2H), 7.97-
8.00 (m, 2H). 13C NMR (CDCl3) d: 24.9, 26.7, 78.2, 128.7,
128.9, 130.2, 132.3, 133.4, 134.2, 176.3, 194.3. EI-MS: 271,
269 (M+), 185, 183, 155, 77.
Received January 26, 2005.
5-(4-Isopropylbenzoyl)dihydro-2(3H)-furanone (3f)
mp 81-83 °C (CHCl3/hexane). IR (KBr) n: 1770, 1687,
1601, 1225, 1072 cm-1. 1H NMR (CDCl3) d: 1.28 (d, J = 6.8
Hz, 6H), 2.45-2.64 (m, 4H), 2.95-3.02 (m, 1H), 5.77-5.80 (m,
1H), 7.36 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 8.4 Hz, 2H). 13C
NMR (CDCl3) d: 23.4, 24.9, 26.7, 34.2, 78.1, 126.9, 128.9,
131.2, 176.2, 193.8. EI-MS: 147, 91. Anal. Calcd for C14H16O3:
C, 72.39; H, 6.94. Found: C, 72.43; H, 6.85.
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