Palladium-catalyzed cyclocarbonylation of trifluoromethyl propargylic alcohols producing 3-trifluoromethyl-2(5H)-furanones (γ-lactones)

Article abstract of DOI:10.1016/S0040-4039(01)02006-8

The reaction of trifluoromethyl propargylic alcohols 1, CO and H₂ in the presence of catalytic Pd(OAc)₂ and PPh₃ afforded 3-trifluoromethyl-2(5H)-furanones 2 in high yields.

Full text of DOI:10.1016/S0040-4039(01)02006-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 9051–9053
Palladium-catalyzed cyclocarbonylation of trifluoromethyl
propargylic alcohols producing 3-trifluoromethyl-2(5H)-furanones
(g-lactones)
Zhong-Xing Jianga and Feng-Ling Qinga,b,
*
aLaboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China
bCollege of Chemistry and Chemical Engineering, Donghua University, 1882 West Yanan Lu, Shanghai 200051, China
Received 16 August 2001; revised 8 October 2001; accepted 19 October 2001
Abstract—The reaction of trifluoromethyl propargylic alcohols 1, CO and H2 in the presence of catalytic Pd(OAc)2 and PPh3
afforded 3-trifluoromethyl-2(5H)-furanones 2 in high yields. © 2001 Published by Elsevier Science Ltd.
The high electronegativity and small atomic volume of
fluorine have been used to probe reactivity, especially
that of biologically important molecules.1 The develop-
ment of new preparative methods and exploring the
utility of specifically fluorinated compounds in biologi-
cal systems are of great importance.2 2(5H)-Furanones
are a class of interesting compounds that are com-
prised of a structural moiety frequently present in bio-
logically active natural products and can be further
transformed into other important structural moieties
in organic synthesis.3 Although a number of 2(5H)-
furanones have been prepared, to the best of our
knowledge, there is no report on the synthesis of 3-
trifluoromethyl-2(5H)-furanones. Very recently, we
developed a practical route to 3-trifluoromethyl-2(5H)-
furanones through the palladium-catalyzed cyclocar-
bonylation of (Z)-3-iodo-3-trifluoromethyl allylic
alcohols (Scheme 1).4 Recently, Alper et al. described
the transition metal-catalyzed cyclocarbonylation of
alkynols to 2(5H)-furanones.5 Accordingly, we were
interested in testing the feasibility of the synthesis
of 3-trifluoromethyl-2(5H)-furanones by palladium-
catalyzed cyclocarbonylation of trifluoromethylated
alkynols 1.
Scheme 1.
Keywords: cyclocarbonylation; g-lactones; trifluoromethyl-containing compounds.
* Corresponding author. Fax: 86-21-64166128; e-mail: flq@pub.sioc.ac.cn
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)02006-8

9052
Z.-X. Jiang, F.-L. Qing / Tetrahedron Letters 42 (2001) 9051–9053
Trifluoromethyl propargylic alcohols 1 were easily pre-
pared from 2-bromo-3,3,3-trifluoropropene and ketones
(aldehydes) in the presence of 2 equiv. LDA (Scheme 1).6
Compound 4,4,4-trifluoro-1-cyclohexyl-2-butyn-1-ol 1a
was used as a model substrate to explore the cyclocar-
bonylation reaction conditions (Scheme 2 and Table 1).
Firstly, treatment of 1a with 30 atm of CO and 10 atm
of H2 in the presence of 0.05 equiv. of Pd(OAc)2 and 0.1
equiv. of PPh3 in CH2Cl2 at 50°C for 30 h resulted in no
reaction and compound 1a was recovered (entry 1).
When the reaction temperature was increased to 85°C
under the conditions of entry 1, 19F NMR showed that
the starting material 1a was totally converted and 3-tri-
fluoromethyl-2(5H)-furanone 2a was isolated in 65%
yield. To find out the optimal reaction conditions, we
studied the effect of various reaction parameters (cata-
lyst, solvent, pressure of CO and H2) on the outcome of
the reaction. Pd(OAc)2/PPh3 was more active than
Pd(PPh3)4 and Pd(dba)2 in cyclocarbonylation under
similar reaction conditions (entries 3, 4). Gabriele et al.
reported that PdI2/KI was an effective catalyst for the
oxidative carbonylation of alkynols, producing g-lac-
tones.7 However, when PdI2/KI was used as the catalyst
instead of Pd(OAc)2/PPh3 for the cyclocarbonylation of
1a under the conditions of entry 1, 2a was obtained in
very low yield (entry 5). Fortunately, when the pressure
of CO/H2 was increased to 60/20 under the conditions
of entry 1, 1a was completely converted to 2a in 90%
isolated yield (entry 6). The nature of the solvent was an
important factor. There was no reaction using THF as
solvent (entry 7). The reaction conditions described in
entry 6 (60 atm of CO, 20 atm of H2, 5% mol Pd(OAc)2
and 10% mol PPh3 in CH2Cl2) were chosen as optimized
conditions for the cyclocarbonylation of 1a.8
Scheme 2.
Table 1. Cyclocarbonylation optimization using 1a
Entry
Catalyst (5 mol%)
Solvent
Temperature (0°C)
Pressure (atm) CO:H2
Isolated yield (%)
1
2
3
4
5
6
7
Pd(OAc)2+PPh3
Pd(OAc)2+PPh3
Pd(PPh3)4
Pd(dba)2+PPh3
PdI2+KI
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
50
85
85
85
85
85
85
30:10
30:10
30:10
30:10
30:10
60:20
60:20
0
65
18
23
21
90
0
Pd(OAc)2+PPh3
Pd(OAc)2+PPh3
Table 2. Palladium-catalyzed cyclocarbonylation of tertiary alkynols 1 to 3-trifluoromethyl-2(5H)-furanones 2

Z.-X. Jiang, F.-L. Qing / Tetrahedron Letters 42 (2001) 9051–9053
9053
Scheme 3.
3. (a) Knight, D. W. Contemp. Org. Synth. 1994, 1, 287; (b)
Corey, E. J.; Cheng, X. M. The Logic of Chemical Synthe-
sis; John Wiley & Sons: New York, 1989; (c) Nagao, Y.;
Dai, W.; Ochiai, M. J. Org. Chem. 1989, 54, 5211; (d)
Rao, Y. S. Chem. Rev. 1976, 76, 5; (e) Handa, S. Tetra-
hedron: Asymmetry 1996, 7, 1281; (f) Rodriguez, A. D.;
Shi, J. G.; Huang, S. D. J. Org. Chem. 1998, 63, 4425.
4. Qing, F. L.; Jiang, Z. X. Tetrahedron Lett. 2001, 42, 5933.
5. (a) El Ali, B.; Alper, H. Synlett 2000, 161; (b) Van Den
Hoven, B. G.; El Ali, B.; Alper, H. J. Org. Chem 2000, 65,
4131; (c) Yu, W. Y.; Alper, H. J. Org. Chem. 1997, 62,
6584; (d) Gabriele, B.; Costa, M.; Salerno, G.; Chiusoli, G.
P. J. Chem. Soc., Chem. Commun. 1994, 1429; (e) Yoshio,
I.; Kunihiro, O.; Yen, I. F.; Shin, I. Bull. Chem. Soc. Jpn.
1989, 62, 3518.
Under the optimized conditions established for 1a, the
cyclocarbonylation of various trifluoromethyl propar-
gylic alcohols 1 has been investigated. Tertiary alkynols
can be converted to the corresponding 3-trifluoro-
methyl-2(5H)-furanone (Table 2). In contrast, when
secondary phenyl substituted alkynol 1g was treated
with CO/H2 in the presence of Pd(OAc)2/PPh3 under
the typical cyclocarbonylation conditions, the product
was ketone 3 which was isolated in 14% yield (Scheme
3). Interestingly, the cyclocarbonylation of secondary
alkyl substituted alkynol 1h led to the hydrogenated
product 4 as a single product in 85% yield (Scheme 3).
In conclusion, we have developed a convenient route to
3-trifluoromethyl-2(5H)-furanone through palladium-
catalyzed cyclocarbonylation of 3-trifluoromethyl
alkynols.
6. (a) Yamazaki, T.; Mizutani, K.; Kitazume, T. J. Org.
Chem. 1995, 60, 6046; (b) Katritzky, A. R.; Qi, M.; Wells,
A. P. J. Fluorine Chem. 1996, 80, 145.
7. Gabriele, B.; Salerno, G.; De Pascali, F.; Coata, M.;
Chiusoli, G. P. J. Chem. Soc., Perkin Trans. 1 1997, 147.
8. Typical cyclocarbonylation procedure: Into an autoclave
with a glass liner and stirring bar was placed a mixture of
1a (192 mg, 1 mmol), Pd(OAc)2 (11 mg, 0.05 mmol), PPh3
(26 mg, 0.1 mmol) and CH2Cl2 (3 ml). The autoclave was
flushed four times with hydrogen, pressurized to 20 atm,
and then carbon monoxide and pressurized to 80 atm. The
autoclave was placed in an oil bath at 85°C for 30 h and
then allowed to cool to room temperature. The autoclave
was depressurized, the reaction mixture filtered through
Celite and the solvent removed by rotary evaporation. The
resulting residue was purified by flash silica gel chromato-
graphy to afford 2a (198 mg, 90% yield). 1H NMR (CDCl3,
300 MHz): l 7.84 (s, 1H), 1.75 (m, 10H); 19F NMR
(CDCl3, 282 MHz, CF3CO2H as an external standard,
upfield positive): l −12.3 (s); IR: 1756, 1668, 1362, 1175
cm−1; MS m/z 220 (M+, 17), 122 (100); HRMS for
C10H11O2F3: 220.07479. Found: 220.07295.
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