Fluorinated butanolides and butenolides: Part 8. 2-(Trifluoromethyl)butan-4-olides by synthesis from methyl 3,3,3-trifluoropyruvate as building block

Article abstract of DOI:10.1016/S0022-1139(01)00450-X

2-Hydroxy-2-trifluoromethylbutan-4-olides (8-10) were prepared by a four step synthesis starting from a ketone and methyl 3,3,3-trifluoropyruvate (1) as a building block. Uncatalyzed chemospecific aldolization of ketones with 1 afforded 2 hydroxy-4-oxoest

Full text of DOI:10.1016/S0022-1139(01)00450-X

Journal of Fluorine Chemistry 111 ꢀ2001) 175±184
Fluorinated butanolides and butenolides
Part 8. 2-ꢀTri¯uoromethyl)butan-4-olides by synthesis from
$
methyl 3,3,3-tri¯uoropyruvate as buildingblock
*
Oldrich Paleta , Jirõ Palecek, Bohumil Dolensky
Ï
Department of Organic Chemistry, Prague Institute of Chemical Technology, Technicka 5, 16628 Prague 6, Czech Republic
ÏÂ
Ï
Â
Â
Received 21 March 2001; accepted 28 June 2001
Abstract
2-Hydroxy-2-tri¯uoromethylbutan-4-olides ꢀ8±10) were prepared by a four step synthesis startingfrom a ketone and methyl 3,3,3-
tri¯uoropyruvate ꢀ1) as a buildingblock. Uncatalyzed chemospeci®c aldolization of ketones with 1 afforded 2 hydroxy-4-oxoesters 2±4 that
were selectively reduced at the oxo group by sodium borohydride to the corresponding 2,4-dihydroxyesters 5±7. Acid-catalyzed cyclization
of dihydroxysters 5±7 to lactones 8±10 was strongly dependent on their structure. The lactone-ring closure with the hydroxy group at the
hydroxylated cyclopentane ringafforded bicyclic lactone ꢀ 10) with cyclopentane cis-annulation. 2-Hydroxy-2 tri¯uoromethylbutanolides
appeared to be highly resistent to dehydration or eliminations of the corresponding mesylates or tri¯ates. # 2001 Elsevier Science B.V. All
rights reserved.
Keywords: Methyl 3,3,3-tri¯uoropyruvate; Aldolization; Selective hydride reduction; Lactonization; 2-Hydroxy-2-tri¯uoromethyl-butanolides; 4-Phenyl-2-
tri¯uoromethylbut-3-en-4-olide; Bicyclic lactone
1. Introduction
butanolides have generally been synthesized by a build-
ing-block strategy using the following tri¯uoromethylated
synthons: methyl 3,3,3-tri¯uoropyruvate [7,14,51], tri¯uor-
oacetaldehyde [9,10], 3,3,3-tri¯uoropropanoate [11,12] or
2-ꢀtri¯uoromethyl)acrylic acid [13].
As a part of our research of application of methyl 3,3,3-
tri¯uoropyruvate ꢀ1) as a buildingblock [14±16], we have
studied synthetic exploitation of this compound in the
synthesis of tri¯uoromethylated butanolides. The sequence
of synthetic steps is depicted in Scheme 1 and includes:
aldolization of pyruvate 1 with ketones, selective reduction
of aldols 2±4, acid-catalyzed cyclization of dihydroxyesters
5±7 to lactones 9±10 and attempts to prepare 2-tri¯uoro-
methylbut-2-en-4-olides, e.g. 11.
In recent years, there has been considerable interest in
syntheses of tri¯uoromethylated butanolides. One of the
reasons has been, that ¯uoro substituents ꢀsuch as F, CF3,
OCF3, etc.) are powerful modi®ers of chemical, biological
and material properties of organic compounds as documen-
ted by hundreds of pharmaceuticals, biocides and new
materials ꢀe.g. [3±6]. Tri¯uoromethylbutanolides have been
prepared for their potential pharmaceutical properties [7,8],
bioactivity [9,10], as intermediates in syntheses of antibo-
dies, as selective catalysts in organic chemistry [11] and as
dopants for ferroelectric liquid crystals [12], or monomers
for ring-opening polymerization to generate polyesters as
potential piezo-electric materials [13]. Butanolide-ringfor-
mation has been accomplished mostly by acid-catalyzed
cyclization of g-unsaturated acids or esters bearingtri¯-
uoromethyl groups [7,8,11,12,14] and by acid-catalyzed
cyclization of g-hydroxy acids or esters [9,10,14] or by
non-catalyzed lactonization [13,14]. Tri¯uoromethylated
2. Synthesis of 2-trifluoromethylbutan-4-olides
2.1. Aldolization of methyl 3,3,3-trifluoropyruvate
For the preparation of aldols 2±4 we modi®ed a procedure
previously reported in the literature [18]. We obtained
similar results. The yield for 2 was increased by 20% when
the reaction time was doubled. This time-effect is probably
combined with the fact that the concentration of reactive
$ Presented at the 16th International Symposium on Fluorine Chem-
istry, Durham, 16±21 July 2000, UK ꢀPoster 1P-120). Part 7 [1], Part 6 [2].
* Correspondingauthor. Fax: ‡42-0-2431-1082.
E-mail address: oldrich.paleta@vscht.cz ꢀO. Paleta).
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ꢀ 0 1 ) 0 0 4 5 0 - X

176
O. Paleta et al. / Journal of Fluorine Chemistry 111 42001) 175±184
Scheme 2. Selective hydride reduction of aldols 2±4.
selectivity, whereas other methods of reduction failed: a
benzoyl group was successfully reduced at the bicyclic
structure [19], while Wolff±Kishner, Clemmensen and
Meerwein±Ponndorf±Varley methods were unsuccessful
for this structure [19]; similarly, the benzoyl group at
cyclobutane ringwas reduced in hihg yield [20]; also
aliphatic esters, e.g. dialkyl g-oxopimelates, were reduced
smoothly in high yield at low temperatures [21]. Sodium
borohydride proved to be a suf®ciently mild reagent not to
affect carbon±halogen bonds while lithium aluminum
hydride has been found to reduce carbon±¯uorine bonds
including tri¯uoromethyl groups [22]: e.g. C±Cl bonds in
chloro¯uoropropanoates were not affected duringester-
group reduction [23]. The ketone group in methyl 3,3,3-
tri¯uoropyruvate was also selectively reduced by sodium
borohydride in a yield above 90% [24].
Scheme 1. Overview of synthetic steps.
enol form of acetone is approximately half of that as in
cyclopentanone or acetophenone [17]. We also observed
higher stereoselectivity of the aldolization of cyclopentanone
at room temperature in the formation of diastereoisomers 4
than previously reported [18]. First reported 13C NMR
spectra in this paper con®rmed the structure elucidated
Sodium-borohydride reduction of our 4-oxoesters 2±4
was carried out under ice coolingꢀScheme 2). We observed
1
in H and 19F NMR spectra the formation of diastereoiso-
meric 4-hydroxyesters 5 and 6 ꢀTable 1) in the reduction of 2
and 3, but no diastereoisomers were detected in the NMR
spectra of methyl 3,3,3-tri¯uoro-2-hydroxy-2-ꢀ2-hydroxy-
cyclopentyl)propanoate ꢀ7) prepared from 4 ꢀTable 1). We
also observed partial lactonization of hydroxyesters 5 ꢀ15%
conversion of lactone 8) and 6 ꢀ5% conversion of lactone 9)
duringpuri®cation by column chromatography. The attempts
to separate the lactones 8 or 9 from the dihydroxyesters
1
originally only on the basis of H and 19F NMR spectra.
2.2. Selective reduction of carbonyl group in 4-oxoesters 2±4
Sodium borohydride appeared to be a suitable reducing
agent affecting 4-oxo group in 4-oxoesters with complete
Table 1
Products of hydride reduction of aldols 2±4
Startingaldol
Dihydroxyesters 5±7
Triols 12±14
R1
R2
Yield
ꢀ%)
Diastereoisomers ꢀ% rel.)
Yield Diastereoisomers
ꢀ%)
ꢀ% rel.)
2
3
CH3
H
5
6
90
76
78
56
22
44
12
13
5
75
25
47
C6H5
H
6
7
53
52
4
±CH2CH2CH2±
7
64
100a ꢀestimated
50:50, see the text) 50:50, see the text)
100a ꢀestimated
14
48
a Only one diastereoisomer detected by 1H and 19F NMR spectra.

O. Paleta et al. / Journal of Fluorine Chemistry 111 42001) 175±184
177
5 or 6 were not successful. Therefore, microanalytical data
are not given for compounds 5 and 6.
In contrast to the above mentioned reports on the com-
plete sodium borohydride chemoselectivity [19±22,24], we
observed partial reduction of the ester group in the starting
oxoesters 2±4 to afford triols 12±14 in very low yields of 5±
7% ꢀTable 1). As no dihydroxy ketones were detected in the
reaction mixtures it can be concluded that triols 12±14 are
formed subsequently from the correspondingdihydroxy-
esters 5±7. For all triols 12±14 two diastereoisomers are
1
seen in their H and 19F NMR spectra ꢀTable 1), which, in
the case of 12 and 13, are formed in approximately the same
ratio as the correspondingdihydroxyesters 5 and 6. It can be
deduced from this relation that also oxoester 7 consists of
two diastereoisomers in approximate ratio 50:50 ꢀTable 1).
This consideration is supported by the fact that the starting
oxoester 4 consists of two diasteroisomers ꢀ70 and 30% rel.)
and that in the lactonization of 7 only the stereoisomer with a
cis-con®guration reacts, while the trans-stereoisomer
remains unreacted ꢀvide infra).
Scheme 3. Acid-catalyzed lactonization of g-hydroxy esters 5±7.
without any change of the starting material. This result very
probably con®rms a trans-con®guration for the unreactive
diastereoisomer.
2.3. Cyclization of dihydroxyesters 5±7 to lactones
Acid-catalyzed cyclization of g-hydroxyesters belongs to
the so called exo-trig ring-closure type and should be highly
favorable [25,26]. p-Toluenesulfonic acid was used as a
catalyst for lactonization of g-hydroxyesters with less nucleo-
philic phenolic hydroxy group [27] or lactone formation on
piperidine and piperidone rings [28,29]. The lactonization of
previously reported g-hydroxy-a-ꢀtri¯uoromethyl)esters pro-
ceeded spontaneously, usually by acidi®cation of a reaction
mixture [8,9] or duringdistillation of a reaction mixture [13].
As a contrast, our experimental results on the lactonization of
¯uorinated g-hydroxyesters have revealed great differences
in reaction times dependingon the position and number of
¯uoro substituents [30] ꢀTable 2, Scheme 3).
In this study, we observed marked differences in p-tolue-
nesulfonic catalyzed g-lactone ring-closure of g-hydroxye-
sters 5±7, which differ one from another by substituents R1
ꢀ5 and 6), or by annulation of cyclopentane ringꢀ 7):
lactonization of 5 ꢀR1 ˆ Me) was complete after 5 h re¯ux
in dioxane, while the lactonization of 6 ꢀR1 ˆ Me) required
7 days re¯ux. Lactonization on the cyclopentane ringin
compound 7 was very slow and only one stereoisomer,
undoubtedly that with cis-con®guration, reacted to afford
bicyclic lactone 10 after 30 days re¯ux. The unreacted part
of 7 was subjected to lactonization for another 30 days
3. Attempts to prepare but-2-en-4-olides
2-Hydroxy-2-ꢀtri¯uoromethyl)butanolides 8±10 offer to
prepare the correspondingbut-2-en-4-olides by dehydration.
Such compounds would be novel a,b-unsaturated systems
with potentially interestingreactivity.
3.1. Dehydration
Dehydration of hydroxy compounds possessinggeminal
tri¯uoromethyl groups was successfully carried out on
various structures. Phosphorus ꢀV)-oxide was generally used
as dehydrating agent, e.g. of 3-hydroxy-3-tri¯uoromethyl-
butanoate [31], 3-hydroxy-4,4,4-tri¯uorobutanoate [32],
nitroalkanols [33,34], hydroxy-nitroalkanoates [35].
Dehydration of butanolide 9 with phosphorus ꢀV)-oxide
proceeded with dif®culties: heatingof the mixture to 140 8C
afforded 3-phenyl-2-ꢀtri¯uoromethyl)but-3-en-4-olide ꢀ15,
Scheme 4) in low yield instead of the expected 3-phenyl-
2-ꢀtri¯uoromethyl)but-2-en-4-olide "11, Scheme 1). Dehy-
dration under milder conditions in boilingdiethyl ether
afforded the unexpected opened-chain but-3-enoate 16 bear-
ing a double bond in conjugation with the aromatic ring.
Thus, the attempts to prepare but-2-en-4-olide 11 were not
successful.
Table 2
Yields of products 8±10 in the cyclization of g-hydroxy esters 5±7
Product
Yield ꢀ%)
Diastereoisomers ꢀ%)
3.2. Attempts to eliminate acetate, chloride or
sulfonate groups
8
9
89.9
93.1
46.8
87
69
ꢀ100a
13
31
ꢀ0a
10
As the direct transformation of hydroxybutanolide 9 to the
correspondingbut-2-en-4-olide 11 was not satisfactory, we
a Only one diastereoisomer was detected by 1H and 19F NMR spectra.

178
O. Paleta et al. / Journal of Fluorine Chemistry 111 42001) 175±184
of methanesulfonic acid from the mesylate bearinga gem-
inal tri¯uoromethyl group using tert-butoxide in THF took
place easily at room temperature with high yield [40].
However, in the case of mesylate 19, neither this procedure,
nor several other previously described conditions [40±45]
were successful. Similarly, tri¯ate 20 ꢀScheme 5) was pre-
pared easily ꢀsee [46]), but its basic elimination under
various conditions [47±49] afforded no butenolide 11.
4. NMR spectra
1
Two interaction constants J in H NMR spectrum of d
Scheme 4. Results of attempts on acid dehydration of butanolide 9.
compound 5 were not possible to determine owingto overlap
of signals of both diastereosisomers and the lactone 8
present in the sample. Signals of some carbons in 13C
NMR spectra are not seen, viz. signals of the carbon atoms
in the groupings C±CF3 in compounds 2, 4 ꢀdiastereoisomer
B), 6±8, 9 ꢀdiastereoisomer B), 10, 16, 17 and 19, and signals
of the carbon atom in the grouping C±C6F5 in compound 15.
transformed hydroxyl to better leavinggroups ꢀScheme 5).
Acetate 17 was heated to 3008C without any chemical
change, while, in contrast, dihydroisoxazoles [36], tetrahy-
dropyridinones [37] or chromanones [38] with analogous
structures were eliminated easily on heatingwith tri¯uor-
oacetic acid [36] or hydrochloric acid in solvents [37,38].
Another possibility for the introduction of unsaturation
into butanolides 8±10 was basic elimination of halides or
sulfonates. To prepare chloride 18 ꢀScheme 5), the displace-
ment of hydroxyl in 9 by chlorine usingthionyl chloride was
carried out, but afforded only a small amount of 18. This
result is also in contrast with the reaction of 4-hydroxy-2-
phenyl-4-tri¯uoromethyl-2-imidazolin-5-one, which affor-
ded the correspondingchloro derivative in 85% yield
[39]. Mesylate 19 ꢀScheme 5) was easily prepared from 9
in high yield by a modi®ed procedure [40,41]. Elimination
5. Experimental
5.1. General comments
The temperature data were not corrected. Distillations of
high boiling compounds were carried out on a Vacuubrand
RC5 high vacuum oil pump. Column chromatography: CC1:
column 20 cm, d ˆ 2:5 cm; CC2: column 30 cm,
d ˆ 2:5 cm; CC3: column 50 cm, d ˆ 2:5 cm. GC analyses
were performed on a Micromat HRGC 412 ꢀGCa, Nordion
Scheme 5. Precursors for butenolide 11 by pyrolytic or base eliminations.

O. Paleta et al. / Journal of Fluorine Chemistry 111 42001) 175±184
179
analytical; 25 m glass capillary column, SE-30) and Chrom
 ÏÂ
CCl ꢀsilica gel 20 g). Yield of 2: 2.12 gꢀ82%), mp 61±63 8C
ꢀliterature [2]: yield 54%, mp 61±638C).
5 ꢀGCb, Laboratornõ prõstroje, Prague; FID, 380 cm  0:3 cm
packed column, silicone elastomer E-301 on Chromaton N-
AW-DMCS ꢀLachema, Brno), nitrogen) instruments. NMR
spectra were recorded on a Bruker 400 AM ꢀFT, 19F at
1H NMR ꢀCDCl3): d: 2.17 ꢀs, 3H, CH3); 3.11 ꢀd, 1H, CH2,
2
2JHH ˆ 17:6 Hz); 3.21 ꢀd, 1H, CH2, JHH ˆ 17:6 Hz); 3.88
ꢀs, 3H, COOCH3); ꢀs, 1H, OH). 19F NMR ꢀCDCl3): d: À79.7
ꢀs, CF3) ppm. 13C NMR ꢀCDCl3): d: 30.30 ꢀCH3); 44.83
ꢀCH2); 54.03 ꢀCOOCH3); 122.95 ꢀq, CF3, 1JCF ˆ 285:5 Hz);
169.10 ꢀCOOCH3); 203.51 ꢀC=O) ppm.
1
376.5 MHz), Varian Gemini 300 HC ꢀFT, H at 300 MHz,
13C at 75.46 MHz) and a Bruker WP 80 SY ꢀFT, 19F at
75.4 MHz) instruments: TMS and CFCl3 as the internal
standards, chemicalshiftsinppmꢀssinglet, ddoublet, t triplet,
q quadruplet, m multiplet), couplingconstants J in Hz, solvent
CDCl3. MS spectra were scanned on a Hewlett-Packard
MSD 5971A instrument ꢀ1989, EI 70 eV).
5.2.3. Methyl 4-phenyl-2-hydroxy-4-oxo-2-
4trifluoromethyl)butanoate 43)
A mixture of acetophenone ꢀ11.4 g, 95.2 mmol) and 1
ꢀ13 g, 83.5 mmol) was stirred for 14 days. Column chro-
matography CC3 ꢀsilica gel 60 g). Yield of 3: 17.3 gꢀ75%),
mp 85±878C ꢀliterature [2]: yield 85%, mp 85±878C).
1H NMR ꢀCDCl3): d: 3.70 ꢀd, 1H, CH2, 2JHH ˆ 17:6 Hz);
3.77 ꢀd, 1H, CH2, 2JHH ˆ 17:6 Hz); 3.91 ꢀs, 3H, COOCH3);
4.25 ꢀs, 1H, OH); 7.47±7.95 ꢀm, 5H, Ph) ppm. 19F NMR
ꢀCDCl3): d: À79.5 ꢀs, CF3) ppm. 13C NMR ꢀCDCl3) d: 40.74
ꢀCH2); 54.21 ꢀCOOCH3); 74.96 ꢀq, C±CF3, 2JCF ˆ 29:2 Hz
); 123.21 ꢀq, CF3, 1JCF ˆ 285:8 Hz); 128.16, 128.83, 134.09,
135.79 ꢀPh); 169.44 ꢀCOOCH3); 194.85 ꢀC=O) ppm.
Chemicals used were as follows. Methyl 3,3,3-tri¯uoro-
pyruvate was prepared from hexa¯uoropropene-1,2-oxide
accordingto our procedure [50,51]. Silica gel ꢀ60±100 mm,
Merck), acetophenone ꢀAldrich), acetone ꢀLachema, Brno),
cyclopentanone ꢀAldrich), sodium borohydride ꢀLachema,
Brno), p-toluenesulfonic acid monohydrate ꢀLachema,
Brno), acetic anhydride ꢀLachema, Brno), methanesulfonyl
chloride ꢀFluka), tri¯uoromethanesulfonic anhydride
ꢀAldrich), triethylamine ꢀdistilled over NaOH, bp 888C),
pyridine ꢀfractionally distilled, bp 1158C), thionyl chloride
ꢀdistilled, bp 78±798C), phosphorus pentachloride
ꢀLachema, Brno), phosphorus ꢀV)oxide ꢀLachema, Brno),
methanol ꢀfractionally distilled, bp 428C), petroleum ether
ꢀdistilled, bp 40±658C), diethyl ether ꢀdistilled over Na),
chloroform ꢀdistilled over P2O5, bp 618C), hexane ꢀdistilled
over CaCl2, bp 698C), dioxane ꢀdistilled over Na, bp 1028C),
methylene chloride ꢀdistilled, bp 428C), tetrahydrofuran
ꢀpuri®ed and dried accordingto [52]), lithium diisopropy-
lamide ꢀrepared from butyllithium and diisopropylamine at
À788C in THF [53]), sodium hydride ꢀLachema, Brno),
tetrabutylammonium ¯uoride ꢀAldrich, transformed to the
trihydrate by dryingat RT/0.1 mmHgfor 24 h), 1,5-diaza-
bicyclo[4.3.0.]non-5-ene ꢀAldrich), potassium tert-butoxide
ꢀprepared by dissolvingpotassium in dry tert-butyl alcohol,
removingthe alcohol and dryingat RT/0.2 mmHg), potas-
sium carbonate ꢀLachema, Brno).
5.2.4. Methyl 2-hydroxy-2-42-oxocyclopenty1)-3,3,3-
trifluoropropanoate 44)
A mixture of cyclopentanone ꢀ0.84 g, 9.96 mmol) and
1ꢀ1.43 g, 9.16 mmol) was stirred for 14 days.
Column chromatography CC1 ꢀsilica gel 20 g). Yield of 4:
1.81 gꢀ82%), diastereoisomer ratio 70:30, mp 59±60 8C
ꢀliterature [2]: yield 90%, mp 59±608C).
1H NMR ꢀCDCl3): d: diastereoisomer A: 1.64±2.37 ꢀ6H, ±
3
CH2CH2CH2±); 2.95 ꢀdd, 1H, CH, JHH ˆ 8:8 Hz,
3JHH ˆ 12:1 Hz); 3.91 ꢀs, 3H, COOCH3); 4.04 ꢀs, 1H,
OH); diastereoisomer B: 1.64±2.37 ꢀ6H, ±CH2CH2CH2±);
3
3
2.61 ꢀdd,1H, CH, JHH ˆ 8:2 Hz, JHH ˆ 11:5 Hz); 3.80 ꢀs,
3H, COOCH3); 5.24 ꢀs, 1H, OH) ppm. 19F NMR ꢀCDCl3): d:
diastereoisomer A: À76.8 ꢀs, CF3); diastereoisomer B:
À76.9 ꢀs, CF3) ppm. 13C NMR ꢀCDCl3): d: diastereoisomer
A: 20.38, 24.36, 37.77 ꢀ±CH2CH2CH2±); 51.58 ꢀCOOCH3);
2
5.2. Condensation of methyl 3,3,3-trifluropyruvate 41)
with ketones 4products 2±4)
54.27 ꢀCH); 74.96 ꢀq, C±CF3, JCF ˆ 29:2 Hz); 123.15 ꢀq,
1
CF3, JCF ˆ 287:4 Hz); 169.91 ꢀCOOCH3); 215.19 ꢀC=O);
diastereoisomer B: 23.17,25.98, 37.87 ꢀ±CH2CH2CH2±);
50.81 ꢀCOOCH3); 53.57 ꢀCH); 122.56 ꢀq, CF3,
1JCF ˆ 285:7 Hz); 168.13 ꢀCOOCH3); 218.68 ꢀC=O) ppm.
5.2.1. General procedure
The reactions were carried out in a sealed round-bottomed
¯ask ꢀmagnetic spinbar) under an inert atmosphere. A
mixture of tri¯uoropyruvate 1 and ketone was stirred at
room temperature until 1 disappeared. The reaction was
followed by 19F NMR. The reaction mixture was then
separated by column chromatography ꢀsilica gel L-60/
100, petroleum ether Ð diethyl ether or chloroform,
95:5) and the product was crystallized from hexane.
5.3. Borohydride reduction of 2-hydroxy-4-
oxoalkanoates 2±4 4products 5±7 and 12±14)
5.3.1. General procedure
The reaction was carried out at 08C in a round-bottomed
¯ask ꢀ250 ml) equipped with two magnetic spinbars and
dryingtube ®lled with CaCl . A mixture of 2-hydroxy-4-
2
5.2.2. Methyl 2-hydroxy-4-oxo-2-4trifluoromethyl)
pentanoate 42)
A mixture of acetone ꢀ0.89 g, 15.4 mmol) and 1 ꢀ1.88 g,
12 mmol) was stirred for 14 days. Column chromatography
oxoalkanoate, sodium borohydride and diethyl ether ꢀ100 ml)
was reacted and methanol ꢀ2 ml) was added after 30 min
reaction and stirringwas continued at 0 8C until the starting
oxoester disappeared ꢀcheck by TLC, chloroform Ð diethyl

180
O. Paleta et al. / Journal of Fluorine Chemistry 111 42001) 175±184
ether, 9:1). The reaction mixture was then chromatographed
on a short column ꢀCC1, silica gel 10 g, diethyl ether) to
removesaltsandunreacted hydride. 1H and19F NMRanalysis
of the crude product revealed that partial cyclization pro-
ceeded on the chromatographic column to afford the corre-
spondingbutanolide. The attempts to separate products 5±7
from hydroxybutanolides 8±10 were not successful and,
therefore, this mixture was used directly for the next lacto-
nization step.
3JHH ˆ 10:4 Hz); 7.29±7.42 ꢀm, SH, Ph); diastereoisomer
B: 2.40 ꢀdd, 1H, CH2, 2JHH ˆ 14:3 Hz, 3JHH ˆ 8:8 Hz); 2.47
2
3
ꢀdd, IH, CH2, JHH ˆ 14:3 Hz, JHH ˆ 3:9 Hz) 3.80 ꢀs, 3H,
COOCH3); 4.82 ꢀdd, 1H, CHOH 3JHH ˆ 3:9 Hz,
3JHH ˆ 8:8 Hz); 7.29±7.42 ꢀm, SH, Ph) ppm. 19F NMR
ꢀCDCl3): d: diastereoisomer A: À79.2 ꢀs, CF3); diastereoi-
somer B: À79.9 ꢀs, CF3) ppm. 13C NMR ꢀCDCl3): d:
diastereoisomer A: 40.12 ꢀCH2); 53.99 ꢀCOOCH3); 68.75
1
ꢀCH); 123.67 ꢀq, CF3, JCF ˆ 286:9 Hz); 127.61, 128.34,
128.76, 136.82 ꢀPh); 169.24 ꢀCOOCH3); diastereoisomer B:
39.42 ꢀCH2), 53.86 ꢀCOOCH3); 71.17 ꢀCH); 122.98 ꢀq, CF3,
1JCF ˆ 285:1 Hz); 125.69, 125.91, 127.98, 129.29 ꢀPh);
170.76 ꢀCOOCH3) ppm.
5.3.2. Methyl 2,4-dihydroxy-2-4trifluoromethyl)pentanoate
45), 2-4trifluoromethyl)pentane-1,2,4-triol 412)
A mixture of butanoate 2 ꢀ2.12 g, 9.91 mmol), sodium
borohydride ꢀ0.11 g, 2.96 mmol) and diethyl ether was
1H and 19F
Compound 13: 19F NMR ꢀCDCl3): d: diastereoisomer A:
À79.2 ꢀs, CF3); diastereoisomer B: À79.5 ꢀs, CF3) ppm. MS
reacted accordingto the general procedure.
‡
NMR of the end reaction mixture revealed a 15% lactoniza-
tion of the product 5. The yield of 5 ꢀviscous liquid): 1.63 g
ꢀ76%), diastereoisomer ratio 56:44. As a by product, impure
triol 12 was isolated from the chromatographic column
ꢀmethanol); yield: 0.09 g, ꢀ6%), diastereoisomer ratio 53:47.
ꢀMr ˆ 250), m/z/% rel. int.): EI: 250/20ꢀM ), 231/6, 213/3,
201/8, 133/18, 107/97, 105/40, 91/11, 79/100, 78/24, 77/63,
69/8, 51/21, 40/17.
5.3.4. Methyl 3,3,3-trifiuoro-2-hydroxy-2-42-hydroxy-
cyclopenyl)propanoate 47), 3,3,3-trifluoro-2-42-
hydroxycyclopentyl)propane-1,2-diol 414)
1
Compound 5: H NMR ꢀCDCl3): d: diastereoisomer A:
3
1.13 ꢀd, 3H, CH3, JHH ˆ 6 Hz); 1.91 ꢀdd, 1H, CH2); 2.08
ꢀdd, 1H, CH2); 3.81 ꢀs, 3H, COOCH3); 4.10 ꢀm 1H CHOH);
3
A mixture of butanoate 4 ꢀ1.81 g, 7.55 mmol), sodium
borohydride ꢀ0.09 g, 2.27 mmol) and diethyl ether was
diastereoisomer B: 1.14 ꢀd, 3H, CH3, JHH ˆ 6:6 Hz); 1.92
ꢀdd, 1H, CH2); 2.09 ꢀdd, 1H, CH2); 3.76 ꢀs, 3H, COOCH3);
3.85 ꢀm, 1H, CHOH) ppm. 19F NMR ꢀCDCl3): d: diaster-
eoisomer A: À80.1 ꢀs, CF3); diastereoisomer B: À80.2 ꢀs,
CF3) ppm. 13C NMR ꢀCDCl3) diastereoisomer A: 23.49
ꢀCH3); 38.45 ꢀCH2); 53.71 ꢀCOOCH3); 62.62 ꢀCH); 75.97
reacted accordingto the egneral procedure.
1H and 19F
NMR of the end reaction mixture revealed a 0% lactoniza-
tion of the product 7. The yield of 7: 1.17 gꢀ63.9%), mp 67±
788C. As a by product, impure triol 14 was isolated from the
chromatographic column ꢀmethanol); yield: 0.11 g, ꢀ7%),
diastereoisomer ratio 52:48.
Compound 7: analysis ꢀ7): found: C, 44.63 %; H, 5.37%.
C9H13F3O4 requires: C, 44.63%; H, 5.41%. M, 242.2.
1H NMR ꢀCDCl3): d: 1.51±1.99 ꢀ6H, ±CH2CH2CH2±);
2
1
ꢀq, C±CF3, JCF ˆ 28:6 Hz); 123.60 ꢀq, CF3, JCF
ˆ
286:3 Hz); 170.75 ꢀCOOCH3); diastereoisomer B: 23.39
ꢀCH3); 39.72 ꢀCH2); 53.71 ꢀCOOCH3); 65.28 ꢀCH); 78.63
2
1
ꢀq, C±CF3, JCF ˆ 29:7 Hz); 122.92 ꢀq, CF3, JCF
ˆ
3
3
285:7 Hz); 169.53 ꢀCOOCH3) ppm.
Compound 12: 19F NMR ꢀCDCl3): d: diastereoisomer A:
À79.5 ꢀs, CF3); diastereoisomer B: À79.6 ꢀs, CF3) ppm. MS
2.43 ꢀdd,1H, CH, JHH ˆ 8:2 Hz, JHH ˆ 8:2 Hz); 3.88 ꢀs,
3
3H, COOCH3); 4.04 ꢀdd, 1H, CHOH CH JHH ˆ 7:1 Hz,
3JHH ˆ 7:1 Hz) ppm. 19F NMR ꢀCDCl3) À76.8 ꢀs, CF3)
ppm. 13C NMR ꢀCDCl3): d: 21.25, 24.07, 34.39 ꢀ±
CH2CH2CH2±); 49.68 ꢀCH); 53.98 ꢀCOOCH3); 72.95
ꢀCH); 123.58 ꢀq, CF3, 1JCF ˆ 286:9 Hz); 171.29 ꢀCOOCH3)
ppm.
‡
ꢀMr ˆ 188), m/z/% rel. int.): EI: 169/1 ꢀM À 19), 155/1,
147/1, 141/4, 140/2, 125/17, 112/14, 105/7, 93/17, 71/100,
70/30, 69/6, 67/14, 55/49, 44/25, 43/59, 42/24, 41/17.
5.3.3. Methyl 4-phenyl-2,4-dihydroxy-2-4trifluoromethyl)
butanoate 46), 4-phenyl-2-trifluoromethylbutane-
1,2,4-triol 413)
Compound 14: 19F NMR ꢀCDCl3): d: diastereoisomer A:
À77.9 ꢀs, CF3); diastereoisomer B: À79.3 ꢀs, CF3) ppm. MS
‡
ꢀMr ˆ 214), m/z/% rel. int.): EI: 196/5 ꢀM À 18), 167/5,
A mixture of butanoate 3 ꢀ2.25 g, 8.15 mmol), sodium
borohydride ꢀ0.09 g, 2.46 mmol) and diethyl ether was
166/8, 127/17, 125/18, 100/13, 97/35, 95/70, 79/13, 69/16,
67/99, 65/31, 56/33, 55/32, 51/17, 44/38, 43/22, 42/72, 41/
100.
reacted accordingto the general procedure.
1H and 19F
NMR of the end reaction mixture revealed a 5% lactone
8 content in the product 6 ꢀviscous liquid). The yield of 6:
2.05 gꢀ90.2%), diastereoisomer ratio 78:22. As a by pro-
duct, impure triol 13 was isolated from the chromatographic
column ꢀmethanol); yield: 0.09 g, ꢀ5%), diastereoisomer
ratio 75:25.
5.4. Cyclizations of 4-hydroxyesters to lactones
4lactonization)
5.4.1. General procedure for 8±10
The reactions were carried out in a round-bottomed ¯ask
equipped with magnetic spinbar, a Dimroth-type re¯ux
condenser and dryingtube ®led with CaCl . A mixture of
1
Compound 6: H NMR ꢀCDCl3): d: diastereoisomer A:
2
3
2.19 ꢀdd, 1H, CH2, JHH ˆ 14:3 Hz, JHH ˆ 2:2 Hz); 2.51
ꢀdd, 1H, CH2, 2JHH ˆ 14:3 Hz, 3JHH ˆ 11 Hz); 3.91 ꢀs, 3H,
COOCH3); 5.07 ꢀdd, 1H, CHOH, 3JHH ˆ 1:7 Hz,
2
4-hydroxy-alkanoate, p-toluenesulfonic acid and dry diox-
ane was re¯uxed until the starting4-hydroxy-alkanoate

O. Paleta et al. / Journal of Fluorine Chemistry 111 42001) 175±184
181
2
disappeared ꢀcheck by 19F NMR). After coolingto RT, the
reaction mixture was chromato graphed on a short column
ꢀCC1, silica gel, diethyl ether) to remove p-toluenesulfonic
acid. Solvent was then removed by rotary evaporator and
solvent residue was removed from the crude product at 40±
508C/0.2 mmHg.
diastereoisomer B: 2.54 ꢀdd, 1H, CH2, JHH ˆ 14:3 Hz,
2
3JHH ˆ 10:4 Hz); 3.19 ꢀdd, 1H, CH2, JHH ˆ 14:3 Hz,
3JHH ˆ 6:6 Hz); 5.54 ꢀdd, 1H, CH, JHH ˆ 6:6 Hz,
3
3JHH ˆ 10:4 Hz); 7.33±7.47 ꢀm, 5H, Ph) ppm. 19F NMR
ꢀCDC13): d: diastereoisomer A: À80.4 ꢀs, CF3); diastereoi-
somer B: À80.3 ꢀs, CF3) ppm. 13C NMR ꢀCDCl3): d:
diastereoisomer A: 39.26 ꢀCH2); 79.35 ꢀCH); 77.72 ꢀq,
5.4.2. 2-Hydroxy-2-4trifluoromethyl)pentan-4-olide 48)
A mixture of hydroxypentanoate 5 ꢀ1.63 g, 7.53 mmol),
p-toluenesulfonic acid monohydrate ꢀ0.05 g, 0.26 mmol)
and dioxane ꢀ50 ml) was re¯uxed for 5 h. After usingshort
column chromatography ꢀdiethyl ether) and removing the
solvent, the crude product was distilled on a Hickmann-type
microdistillation apparatus to afford product 8, yield 1.43 g
ꢀ89.8%), bp 50±598C/0.2 mmHgꢀliterature [7]: bp 81 8C/
1 mmHg), as a mixture of diastereoisomers A and B
ꢀ87:13% rel.).
C±CF3, 2JCF ˆ 32:5 Hz); 122.84 ꢀq, CF3, 1JCF
ˆ
282:6 Hz); 128.86, 129.16, 129.29, 136.57 ꢀPh); 170.68
ꢀC=O); diastereoisomer B: 39.11 ꢀCH2); 79.02 ꢀCH);
1
123.25 ꢀq, CF3, JCF ˆ 284:3 Hz); 125.55, 125.85,
126.01, 136.88 ꢀPh); 171.91 ꢀC=O) ppm.
5.4.4. Cis-4-hydroxy-4-trifluoromethyl-2-
oxabicyclo[3.3.0]octan-3-one 410)
A mixture of hydroxypropanoate 7 ꢀ1.17 g, 4.82 mmol),
p-toluenesulfonic acid monohydrate ꢀ0.03 g, 0.17 mmol)
and dioxane ꢀ50 ml) was re¯uxed for 30 days. 19F NMR
analysis of the reaction mixture con®rmed that only one
diastereoisomer cyclized. Unreacted 7 and product 10 were
separated by column chromatography ꢀCC2, silica gel 30 g,
chloroform diethyl ether 9:1) and 7 was again subjected to p-
toluenesulfonic acid catalyzed cyclization for another 30
days under re¯ux, but no further product was formed ꢀ19F
and 1H NMR spectra). After removingthe solvent, crude 10
was distilled on a Hickmann-type microdistillation appara-
tus to afford pure product 10, yield 0.48 gꢀ46.8 %), bp 60±
698C/0.02 mmHgꢀno diastereoisomers were detected in
NMR spectra).
Analysis ꢀ8): found: C, 39.74; H, 4.17. C6H7F3O3
requires: C, 39.14; H, 3.83%. M, calcd. 184.12.
1H NMR ꢀCDCl3): d: diastereoisomer A: 1.44 ꢀd, 3H,
3
2
CH3, JHH ˆ 6:6 Hz); 2.13 ꢀdd, 1H, CH2, JHH ˆ 14:3 Hz,
3JHH ˆ 8:8 Hz); 2.54 ꢀdd, 1H, CH2, JHH ˆ 14:3 Hz,
2
3JHH ˆ 6 Hz); 4.83 ꢀddq, 1H, CH, 3JHH ˆ 6 Hz,
3JHH ˆ 8:8 Hz, JHH ˆ 6:6 Hz); diastereoisomer B: 1.46
3
3
ꢀd, 3H, CH3, JHH ˆ 6:6 Hz); 1.95 ꢀdd, 1H, CH2,
2JHH ˆ 14:3 Hz, JHH ˆ 9:3 Hz); 2.82 ꢀdd, 1H, CH2,
3
2JHH ˆ 14:3 Hz, JHH ˆ 6:6 Hz); 4.62 ꢀddq, 1H, CH,
3
3JHH ˆ 6:6 Hz, JHH ˆ 9:3 Hz, JHH ˆ 6:6 Hz; 19F NMR
ꢀCDCl3): diastereoisomer A: À80.4 ꢀs, CF3); diastereoi-
somer B: À80.6 ꢀs, CF3) ppm. 13C NMR ꢀCDCl3): diaster-
eoisomer A: 20.28 ꢀCH3); 38.61 ꢀCH2); 75.21 ꢀCH); 122.84
3
3
Analysis ꢀ10): found: C, 45.56; H, 4.42. C8H9F3O3
requires: C, 45.72; H, 4.32%. M, calcd. 210.15.
1
ꢀq, CF3, JCF ˆ 282:3 Hz); 171.06 ꢀC=O); diastereoisomer
1H NMR ꢀCDCl3): d: 1.51±1.91 ꢀ6H, ±CH2CH2CH2±);
2.63 ꢀdd, 1H, CH, 3JHH ˆ 6:6 Hz, 3JHH ˆ 7:1 Hz); 5.01 ꢀdd,
1H, CH, 3JHH ˆ 6:6 Hz) ppm. 19F NMR ꢀCDCl3): d: À75.4
ꢀs, CF3) ppm. 13C NMR ꢀCDCl3): d: 22.62, 24.64, 32.15 ꢀ±
CH2CH2CH2±); 53.79 ꢀCH); 75.05 ꢀCH); 123.27 ꢀq, CF3,
1JCF ˆ 287:4 Hz); 170.07 ꢀC=O) ppm.
B: 21.12 ꢀCH3); 38.55 ꢀCH2); 74.99 ꢀCH); 123.19 ꢀq, CF3,
1JCF ˆ 285:2 Hz); 171.11 ꢀC=O) ppm. MS ꢀMr ˆ 184), m/z/
‡
% rel. int.): EI: 169/1 ꢀM À 15), 155/1, 141/4, 140/2, 125/
17, 112/13, 105/7, 93/16, 71/100, 69/31, 55/48, 44/23, 43/
57, 42/26, 41/17.
5.4.3. 4-Phenyl-2-hydroxy-2-4trifluoromethyl)butan-4-
olide 49)
5.5. Dehydrations of 4-phenylbutanolide 9 in solvents
A mixture of hydroxybutanoate 6 ꢀ3.97 g, ꢀ50.2 mmol), p-
toluenesulfonic acid monohydrate ꢀ0.31 g, 1.74 mmol) and
dioxane ꢀ150 ml) was re¯uxed for 7d. After usingshort
column chromatography ꢀdiethyl ether) and removing the
solvent, the crude product was second time chromato-
graphed ꢀCC3, silica gel 50 g, chloroform Ð diethyl ether,
9:1). Pure product 9 was obtained by crystallization ꢀhexane
Ð diethyl ether, 100:1) in the yield of 3.27 gꢀ93.1%), mp
54±598C, as a mixture of diastereoisomers A and B ꢀ69:31%
rel.).
5.5.1. 4-Phenyl-2-trifluoromethylbut-3-en-4-olide 415)
The reaction was carried out in a round-bottomed ¯ask
ꢀ25 ml) equipped with magnetic spinbar, a Hickmann-type
distillation head and dryingtube ꢀCaCl 2). A mixture of
butanolide
9 ꢀ0.5 g, 2.03 mmol) and P2O5 ꢀ4.03 g,
28.7 mmol) in a ¯ask was heated on an oil bath to 1408C
for 1 h, then the ¯ask was immersed in oil to the neck and
product 15 was slowly distilled at 160±1808C in the bath.
Yield of 15: 0.07 gꢀ16%), purity 73% ꢀGC±MS).
3
1H NMR ꢀCDCl3): d: 5.82 ꢀd, 1H, CH, JHH ˆ 2:8 Hz);
Analysis ꢀ9): found: C, 53.62; H, 3.85. C11H9F3O3
requires: C, 53.67; H, 3.68%. M, calcd. 246.19.
1H NMR ꢀCDCl3): d: diastereoisomer A: 2.54 ꢀdd, 1H,
4.20 ꢀdq, 1H, CH, 3JHH ˆ 2:8 Hz, 4JHF ˆ 8:2 Hz); 7.23±7.67
ꢀm, 5H, Ph) ppm. 19F NMR ꢀCDCT3): d: À68.2 ꢀd, CF3,
4JHF ˆ 8 Hz) ppm. 13C NMR ꢀCDCl3): d: 95.43 ꢀCH);
2
3
1
CH2, JHH ˆ 14:3 Hz, JHH ˆ 9:3 Hz); 2.85 ꢀdd, 1H, CH2,
122.98 ꢀq, CF3, JCF ˆ 288:3 Hz); 126.09 ꢀCH); 128.90,
2JHH ˆ 14:3 Hz, JHH ˆ 6:1 Hz); 5.71 ꢀdd, 1H, CH,
129.61, 129.95, 131.27 ꢀPh); 169.74 ꢀC=O) ppm. MS
‡
3
3JHH ˆ 6:6 Hz, JHH ˆ 9:3 Hz); 7.33±7.47 ꢀm, 5H, Ph);
ꢀMr ˆ 228), m/z/% rel. int.): EI: 229/100 ꢀM ‡ 1),
3

182
O. Paleta et al. / Journal of Fluorine Chemistry 111 42001) 175±184
2
209/17,201/7, 181/7, 151/8, 123/9, 106/11,105/39, 77/39,
69/5, 51/22.
3JHH ˆ 9:3 Hz); 3.06 ꢀdd, 1H, CH2, JHH ˆ 14:3 Hz,
3JHH ˆ 7:2 Hz); 5.46 ꢀdd, 1H, CH, JHH ˆ 7:7 Hz,
3
3JHH ˆ 9:3 Hz); 7.23±7.42 ꢀm, 5H, Ph) ppm. 19F NMR
ꢀCDCl3): d: diastereoisomer A: À78.9 ꢀs, CF3); diastereoi-
somer B: À78.8 ꢀs, CF3) ppm. 13C NMR ꢀCDCl3): d:
diastereoisomer A: 20.09 ꢀs, 3H, OCOCH3); 37.53 ꢀCH2);
5.5.2. Ethyl 4E)-4-phenyl-2-hydroxy-2-
4trifluoromethyl)but-3-enoate 416)
The reaction was carried out in a round-bottomed ¯ask
equipped with magnetic spinbar, a Dimroth-type re¯ux
condenser and a dryingtube ®led with CaCl .
1
78.58 ꢀCH); 122.48 ꢀq, CF3, JCF ˆ 282:3 Hz); 125.62,
129.03, 129.38, 138.12 ꢀPh); 169.24 ꢀC=O) ppm; diaster-
eoisomer B: owingto low intensity, NMR signals were not
observed.
2
A mixture of butanolide 9 ꢀ0.05 g, 0.2 mmol), P2O5
ꢀ0.5 g, 2.07 mmol) and petroleum ether - diethyl ether mix-
ture ꢀ15 ml, 15:1) was re¯uxed for 7 d ꢀcheck by 19F NMR).
After removingsolvents ꢀrotary evaporator), crude oily 16
was chromatographed on a short column ꢀCC3, silica gel
15 g, chloroform Ð diethyl ether 9:1). Residual solvents
were removed at 40±508C/0.2 mmHgto afford slihgtly
yellow 16 ꢀviscous liquid), yield 0.05 gꢀ87.9%). Almost
the same result was obtained when diethyl ether was the
only solvent for the reaction.
5.6.2. 2-Chloro-4-phenyl-2-4trifluoromethyl)butan-
4-olide 418)
For apparatus, see compound 17.
Procedure A: a mixture of butanolide 9 ꢀ0.05 g, 0.2 mmol),
pyridine ꢀ0.02 g, 0.3 mmol) and SOCl2 ꢀ50 ml) was stirred
for 30 days at RT. The reaction mixture contained ca. 12%
of chloride 18 ꢀcheck by 19F NMR) as a mixture of diaster-
eoisomers A and B ꢀ75:25%).
1H NMR ꢀCDCl3): d: 1.47 ꢀt, 3H, CH3); 4.15 ꢀs, 1H, OH);
3
4.33448 ꢀm, 2H, CH2); 6.38 ꢀd, 1H, CH, JHH ˆ 15:9 Hz);
Procedure B: phosphorus pentachloride in diethyl ether
was used as a chlorination agent at RT to afford the same
result as in Procedure A.
3
7.13 ꢀd, 1H, CH, JHH ˆ 15:9 Hz); 7.21±7.59 ꢀm, SH, Ph)
ppm. 19F NMR ꢀCDCl3): d: À78.6 ꢀs, CF3) ppm. 13C NMR
ꢀCDCl3): d: 13.89 ꢀCH3); 64.31 ꢀCH2); 119.41 ꢀCH); 122.95
19F NMR ꢀCDCl3): d: diastereoisomer A: À78.1 ꢀs, CF3);
1
ꢀCH); 122.88 ꢀq, CF3, JCF ˆ 286:3 Hz); 127.11, 128.69,
diastereoisomer B: À78.2 ꢀs, CF3) ppm. MS ꢀMr ˆ 264), m/
‡
‡
134.80, 135.26 ꢀPh); 168.92 ꢀCOOCH2CH3) ppm. MS
ꢀMr ˆ 274), m/z/% rel. int.): EI 274/18 ꢀM ), 257/0.5,
z/0% rel. int.): EI: 266/13 ꢀM ‡ 2), 265/4 ꢀM ‡ 1), 264/
‡
‡
34 ꢀM ), 197/39, 195/100, 169/16, 167/33, 132131, 123/27,
105/13, 98/11, 93/13, 77/9, 69/24, 67/14, 50/9, 45/4.
228/0.5, 205/2, 202/12, 201/100, 184/10, 183/83, 153/4,
133/31, 131/61, 103/36, 91/4, 77/30, 69/7, 51/17, 43/2.
5.6.3. 4-Phenyl-2-methanesulfonyloxy-2-
4trifluoromethyl)butan-4-olide 419)
The reaction was carried out in a three-necked round-
bottomed ¯ask ꢀ250 ml) equipped with magnetic spinbar,
droppingfunnel and dryingtube ꢀCaCl 2).
5.6. Hydroxy-group derivatives of butanolide 9 for
elimination reactions
5.6.1. 2-Acetoxy-4-phenyl-2-4trifluoromethyl)but-
4-olide 417)
For apparatus, see compound 16.
Butanolide 9 ꢀ0.5 g, 2.03 mmol) was dissolved in diethyl
ether ꢀ50 ml) in the reaction ¯ask and triethylamine
ꢀ1.38 g, 13.6 mmol) was added. To the stirred mixture, a
solution of methanesulfonyl chloride ꢀ0.59 g, 5.14 mmol)
in diethyl ether ꢀ50 ml) was added dropwise while cooled
to 08C ꢀice bath). The progress of the reaction was fol-
lowed by TLC ꢀdichloromethane). After completion of the
reaction, precipitate was ®ltered off, ®ltrate was washed
with saturated solution of NaCl ꢀ20 ml then with 0.1 M-
HCl ꢀ20 ml), then with a 0% water solution of NaHCO3
ꢀ20 ml) ®ltrate and was dried over MgSO4. After ®ltering
off the drier, solvent was removed ꢀrotary evaporator) and
crude product 19 was chromatographed ꢀCC2, silica gel
ꢀ30 g), dichioromethane). Pure mesylate 19 was obtained by
crystallization ꢀhexane), yield 0.58 gꢀ87.9%), mp 97±101 8C,
as a mixture of diastereoisomers A and B ꢀ75:25% rel.).
Analysis ꢀ19): found: C, 44.65; H, 3.76. C12H11F3O5S
requires: C, 44.45; H, 3.42%. M, calcd. 324.28.
Butanolide 9 ꢀ0.15 g, 0.61 mmol) was dissolved in
dichloromethane ꢀ5 ml) in the reaction ¯ask and pyridine
ꢀ0.1 g, 1.22 mmol) and acetic anhydride ꢀ100 ml) was added
to the solution. The mixture was re¯uxed for 48 h on an oil
bath, then, after cooling, the reaction mixture was diluted
with dichioromethane ꢀ200 ml) and extracted with water
ꢀ3 ml  200 ml). Methylene chloride and residual acetic
acid were then removed ꢀrotary evaporator) and the residue,
crude product 17, was chromatographed ꢀCC2, silica gel,
30 g, dichloromethane). Pure product 17 was obtained by
crystallization ꢀhexane) in the yield of 0.145 gꢀ82.3%), mp
79±838C, as a mixture of diastereoisomers A and B
ꢀ75:25%).
Analysis ꢀ17): found: C, 54.02; H, 4.03. C13H11F3O4
requires: C, 54.18; H, 3.85%. M, calcd. 288.20.
1H NMR ꢀCDCl3): d: diastereoisomer A: 2.23 ꢀs, 3H,
3
3
OCOCH3); 2.69 ꢀdd, 1H, CH2, JHH ˆ 15:4 Hz, JHH
ˆ
1H NMR ꢀCDCl3): d: diastereoisomer A: 2.78 ꢀdd, 1H,
2
3
2
3
7:7 Hz); 2.89 ꢀdd, 1H, CH2, JHH ˆ 15:4 Hz, JHH
ˆ
CH2, JHH ˆ 15:9 Hz, JHH ˆ 8:2 Hz); 3.25 ꢀdd, 1H, CH2,
3
3
3
8:2 Hz); 5.85 ꢀdd, 1H, CH, JHH ˆ 7:7 Hz, JHH ˆ 8:2
2JHH ˆ 15:9 Hz, JHH ˆ 7:7 Hz); 3.35 ꢀs, 3H, OSO2CH3)
3
3
Hz); 7.23±7.42 ꢀm, 5H, Ph); diastereoisomer B: 2.21 ꢀs,
2
5.86 ꢀt ! dd, JHH ˆ 7:7 Hz, JHH ˆ 8:2 Hz); 7.26±7.45
3H, OCOCH3); 2.89 ꢀdd, 1H, CH2, JHH ˆ 14:3 Hz,
ꢀm, 5H, Ph); diastereoisomer B: 3.20 ꢀdd, 1H, CH2,

O. Paleta et al. / Journal of Fluorine Chemistry 111 42001) 175±184
183
3
2JHH ˆ 14:3 Hz, JHH ˆ 9:9 Hz); 3.25 ꢀdd, 1H, CH2,
References
2JHH ˆ 14:3 Hz, JHH ˆ 7:1 Hz); 3.41 ꢀs, 3H, OSO2CH3)
3
3
3
Â
[1] O. Paleta, Z. Duda, A. Holy, Mendeleev Commun. ꢀ2001) 17.
Â
5.46 ꢀt ! dd, 1H, JHH ˆ 7:1 Hz, JHH ˆ 9:9 Hz); 7.26±
7.45 ꢀm, 5H, Ph) ppm. 19F NMR ꢀCDCl3): d: diastereoi-
somer A: À78.8 ꢀs, CF3); diastercoisomer B: À79.1 ꢀs, CF3)
ppm. 13C NMR ꢀCDCl3): d: diastereoisomer A: 38.67 ꢀCH2);
41.04 ꢀOSO2CH3); 78.60 ꢀCH); 121.57 ꢀq, CF3,
1JCF ˆ 283:4 Hz); 125.62, 129.15, 129.42, 136.85 ꢀPh);
165.93 ꢀC=O) ppm; diastereoisomer B: owingto low inten-
sity, NMR signals were not observed.
ÂÏ Â
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5.6.4. 4-Phenyl-2-4trifluoromethanesulfonyl)oxy-2-
4trifluoromethyl)butan-4-olide 420)
For apparatus, see compound 19.
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Butanolide 9 ꢀ1 g, 4.06 mmol) was dissolved in diethyl
ether ꢀ50 ml) in the reaction ¯ask and triethylamine
ꢀ1.72 g, 17 mmol) was then added. To the stirred mixture,
a solution of tri¯uoromethanesulfonic anhydride ꢀ3.32 g,
11.8 mmol) in diethyl ether ꢀ50 ml) was added dropwise
while cooled to 08C ꢀice bath). The progress of the reaction
was followed by TLC ꢀdichloromethane). After completion
of the reaction, dichloromethane was added ꢀ200 ml),
precipitate was ®ltered off, ®ltrate was washed with water
ꢀ3 ml  100 ml) and dried over MgSO4. After ®lteringoff
the drier, solvent was removed ꢀrotary evaporator) and
crude product 20 was chromatographed ꢀCC3, silica gel
ꢀ50 g), dichloromethane Ð petroleum ether 1:1) to afford
pure mesylate 20 ꢀviscous liquid), yield 1.05 gꢀ88.2%) as
a mixture of diastereoisomers A and B ꢀ83:17% rel.).
Analysis ꢀ20): found: C, 37.80; H, 2.35. C12H8F6O5S
requires: C, 38.08; H, 2.13%. M, calcd. 378.49.
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147.
Ï
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the Abstracts of the 16th International Symposium on Fluorine
Chemistry, University of Durham, UK, 16±21 July 2000, pp. 1P±
120.
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Â
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Lett. 37 ꢀ1996) 6939.
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1H NMR ꢀCDCl3): d: diastereoisomer A: 2.91 ꢀdd, 1H,
CH2, 2JHH ˆ 16:4 Hz); 3.32 ꢀdd, 1H, CH2, 2JHH ˆ 16:4 Hz,
3JHH ˆ 6:6 Hz); 5.82 ꢀt, 1H, 3JHH ˆ 7:7 Hz); 7.31±7.49 ꢀm,
5H, Ph); diastereoisomer B: 3.05 ꢀdd, 1H, CH2,
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Akad. Nauk. SSSR, Ser. Khim. 9 ꢀ1989) 2127.
3
2JHH ˆ 14:6 Hz, JHH ˆ 6:6 Hz); 3.32 ꢀdd, 1H, CH2,
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3
2JHH ˆ 14:6 Hz, JHH ˆ 9:9 Hz); 5.53 ꢀdd, 1H JHH
ˆ
3
6:6 Hz, JHH ˆ 9:9 Hz)7.31±7.49 5H, Ph) ppm. 19F NMR
ꢀCDCl3): d: diastereoisomer A: À78.6 ꢀs, CF3); À73.9 ꢀs,
CF3SO2); diastereoisomer B: À78.3 ꢀs, CF3); À74.2 ꢀs,
CF3SO2) ppm. 13C NMR ꢀCDCl3): d: diastereoisomer A:
37.82 ꢀCH2); 78.37 ꢀCH); 85.59 ꢀq, C±CF3, 2JCF ˆ 34:9 Hz);
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117.98 ꢀq, CF3, JCF ˆ 320:7 Hz); 120.87 ꢀq, CF3,
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163.30 ꢀC=O); diastereoisomer B: 37.58 ꢀCH2); 78.72
1
ꢀCH); 85.91 ꢀq, C±CF3, JCF ˆ 34:5 Hz); 117.91 ꢀq, CF3);
1
121.00 ꢀq, CF3, JCF ˆ 285:2 Hz); 126.16, 129.24, 130.06,
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