Synthesis of novel trifluoromethylated β-acetal-diols and their application to the synthesis of 3-ethoxy-5-hydroxy-5-trifluoromethyl-pyrrolidin-2-one

Article abstract of DOI:10.1016/S0022-1139(00)00386-9

The synthesis of a series of novel trifluoromethylated β-acetal-gem-diols, 4-alkoxy-4-ethoxy-1,1,1-trifluoro-butane-2,2-diols (4a=methoxy, 4b=ethoxy, 4c=allyloxy, 4d=ynyloxy) and 1-(2-alkoxytetrahydro-furan-3-yl)-2,2,2-trifluoro-ethane-1,1-diols (6a=methoxy, 6b=ethoxy, 6c=allyloxy, 6d=ynyloxy) from the reaction of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (1) and 1-(4,5-dihydro-furan-3-yl)-2,2,2-trifluoro-ethanone (2) with sodium azide in hydro-alcoholic medium, is presented. From these reactions, a small amount (ca. of 20%) of the parent trifluoromethylated β-acetal-ketones, 4-alkoxy-4-ethoxy-1,1,1-trifluoro-butan-2-ones (3a-d) and 2,2,2-trifluoro-1-(2-alkoxy-tetrahydro-furan-3-yl)-ethanones (5a-d) were also obtained. The synthetic potential of the trifluoromethylated β-acetal-diols was demonstrated by its application to the synthesis of 3-ethoxy-5-hydroxy-5-trifluoromethyl-pyrrolidin-2-one (7).

Full text of DOI:10.1016/S0022-1139(00)00386-9

Journal of Fluorine Chemistry 107 (2001) 149±154
Synthesis of novel tri¯uoromethylated b-acetal-diols
and their application to the synthesis of
3-ethoxy-5-hydroxy-5-tri¯uoromethyl-pyrrolidin-2-one
Nilo Zanatta*, Luciana S. da Rosa, Elisiane Loro,
Helio G. Bonacorso, Marcos A.P. Martins
  Â
Nucleo de Quõmica de Heterociclos, Departamento de Quõmica, Universidade Federal de Santa Maria,
97.105-900, Santa Maria, RS, Brazil
Received 24 August 2000; accepted 6 October 2000
Abstract
The synthesis of
a
series of novel tri¯uoromethylated b-acetal-gem-diols, 4-alkoxy-4-ethoxy-1,1,1-tri¯uoro-butane-2,2-diols
(4a ˆ methoxy, 4b ˆ ethoxy, 4c ˆ allyloxy, 4d ˆ ynyloxy) and 1-(2-alkoxytetrahydro-furan-3-yl)-2,2,2-tri¯uoro-ethane-1,1-diols (6a ˆ
methoxy, 6b ˆ ethoxy, 6c ˆ allyloxy, 6d ˆ ynyloxy) from the reaction of 4-ethoxy-1,1,1-tri¯uoro-3-buten-2-one (1) and 1-(4,5-dihydro-
furan-3-yl)-2,2,2-tri¯uoro-ethanone (2) with sodium azide in hydro-alcoholic medium, is presented. From these reactions, a small amount
(ca. of 20%) of the parent tri¯uoromethylated b-acetal-ketones, 4-alkoxy-4-ethoxy-1,1,1-tri¯uoro-butan-2-ones (3a±d) and 2,2,2-tri¯uoro-
1-(2-alkoxy-tetrahydro-furan-3-yl)-ethanones (5a±d) were also obtained. The synthetic potential of the tri¯uoromethylated b-acetal-diols
was demonstrated by its application to the synthesis of 3-ethoxy-5-hydroxy-5-tri¯uoromethyl-pyrrolidin-2-one (7). # 2001 Elsevier
Science B.V. All rights reserved.
Keywords: Diols; Acetals; Pyrrolidinones; Ketones
1. Introduction
The addition of hydrazoic acid to conjugated systems
such as acrolein, methyl acrylate, acrylic acid, acrylonitrile,
mesityl oxide, b-nitrostyrene, and a-vinylpyridine to
give the corresponding dihydro b-azido derivatives, was
reported by Broyer [21] in 1951. More recently, Lakshmi-
pathi and Rao [22] reported a base catalysed addition of
hydrogen azide to enoates to form b-azido esters or lactones.
Applying Broyer's condition to the vinyl ketone 1, a com-
plex mixture of unidenti®ed compounds was obtained.
However, when a solution of sodium azide in water was
added to a solution of 1 in alcohol, the unexpected formation
of tri¯uoromethylated b-acetal-diols was observed. In
this case, the sodium azide acted as a base rather than a
nucleophile.
Tri¯uoromethylated b-acetal-diols have not yet been
reported. This situation prompts us to report the synthesis
of a series of tri¯uoromethylated b-acetal-diols from the
reactions of 4-ethoxy-1,1,1-tri¯uoro-3-buten-2-one (1) and
1-(4,5-dihydro-furan-3-yl)-2,2,2-tri¯uoro-ethanone (2) in
alcohols and treated of sodium azide in water (Scheme 1).
In addition, we are reporting an application of the
4-diethoxy-1,1,1-tri¯uoro-butane-2,2-diol to the synthesis
of 5-hydroxy-5-tri¯uoromethyl-3-ethoxy pyrrolidin-2-one
Organic hydrates (gem-diols) are relatively rare com-
pounds because their synthesis and stability depend on
the existence of strong electron withdrawing groups on
the a-carbonyl position, such as tri¯uoromethyl or trichlor-
omethyl groups [1±6]. 4-Ethoxy-1,1,1-tri¯uoro-3-buten-2-
one (1) and 1-(4,5-dihydro-furan-3-yl)-2,2,2-tri¯uoro-etha-
none (2), which have been used extensively by our research
group in the synthesis of heterocycles of ®ve [7±13], six [14±
18] and seven [19,20] membered rings, show favorable
structural features for their use as tri¯uoromethylated b-
acetal-diols precursors. Compounds 1 and 2 have a tri¯uor-
omethyl group a to a carbonyl that also is conjugated to an
alkoxyvinyl group, allowing a Michael addition of an alco-
hol molecule to the b position of 1 or 2, followed by a
hydration of the carbonyl group.
* Corresponding author.
E-mail address: zanatta@base.ufsm.br (N. Zanatta).
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 0 ) 0 0 3 8 6 - 9

150
N. Zanatta et al. / Journal of Fluorine Chemistry 107 (2001) 149±154
Scheme 1.
as an indication of a possible synthetic usefulness of the
tri¯uoromethylated b-acetal-diols.
b-acetal-ketones (ca. of 20% at room temperature) was
obtained together with the b-acetal-diol. A variable tem-
perature study done by H-NMR on the mixture of com-
1
pounds 3a/4a showed that the ratio of b-acetal-diol/b-acetal-
ketone remains unchanged (ca. 4:1, respectively) from 50
to 408C (see Table 1). However, the mixture of 3a/4a reaches
a ratio of 1:1 at 558C. On cooling the NMR sample to room
temperature, the mixture of products slowly re-establish the
starting population ratio. The mixture of products 3a/4a and
3b/4b, solidi®ed in the refrigerator and were recrystallized
from hexane to obtain the b-acetal-diols 4a and 4b in a pure
form. Tentative of puri®cation of the acetals by acidic silica
gel column chromatography resulted in decomposition,
probably, due to the acid sensitive nature of the products
[23]. 1H- and 13C-NMR data of compounds 3a±d, 4a±d, 5a±
d, and 6a±d, are presented in Tables 2±5, respectively.
The b-acetal-ketones 3a±d and 5a±d resulted from a
Michael addition of an alcohol molecule to the b-carbon
of the ketones 1 and 2 and the b-acetal-diols 4a±d and 6a±b
resulted from a further addition of a water molecule to the
carbonyl of compounds 3a±d and 5a±d.
2. Results and discussion
The synthesis of 4-alkoxy-4-ethoxy-1,1,1-tri¯uoro-
butane-2,2-diols (4a±d) and 1-(2-alkoxytetrahydro-furan-
3-yl)-2,2,2-tri¯uoro-ethane-1,1-diols (6a±d) is carried out
by the reaction of the respective tri¯uoromethyl vinyl
ketones 1 and 2, in the presence of sodium azide in alco-
hol/water, at room temperature (Scheme 1). The ketones 1
and 2 were dissolved in alcohols which were used as the
reaction solvents and a solution of sodium azide in water was
added to the mixture at room temperature. The reaction has
been tested with a series of alcohols, such as methanol,
ethanol, allyl- and propargyl-alcohols (Scheme 1).
The reaction time depended greatly on the structure of the
ketones 1 and 2 and the alcohols, ranging from 30 min to
24 h (see Table 1).
The products are isolated by extraction of the reaction
mixture with dichloromethane and the organic phase dried
with anhydrous magnesium sulfate. A light yellow oil was
obtained which was analyzed by NMR without further
puri®cation. In all reactions, a small amount of the parent
A possible synthetic usefulness of the b-acetal-diol 4b
was investigated. We found that the 4-diethoxy-1,1,1-tri-
¯uoro-butane-2,2-diol (4b) reacted with an aqueous solution
of sodium cyanide furnishing the 3-ethoxy-5-hydroxy-5-
Table 1
Reaction conditions used in the synthesis and IR data of compounds 3a±d, 4a±d, 5a±d, 6a±da
1
Compound
Reaction time (h:min)
Yields (%)b
Reaction product
Ratio (%)c
IR (sol. CCl4) n (cm )
1
1
1
1
2
2
2
2
030
030
63
52
47
43
55
63
54
60
4a ‡ 3a
4b ‡ 3b
4c ‡ 3c
4d ‡ 3d
6a ‡ 5a
6b ‡ 5b
6c ‡ 5c
6d ‡ 5d
80:20
82:18
83:17
81:19
84:16
88:12
75:25
82:18
3365, 1755
3365, 1760
3365, 1750
3375, 1755
3355, 1755
3350, 1750
3380, 1755
3370, 1755
2400
145
110
120
2400
230
a The reactions were carried out at room temperature in a substrate/azide ratio of 1:1.
b The yield of the mixture of compounds 3 and 4 were calculated considering only the molecular weight of the b-acetal-diol.
c Product ratio was determined by 1H-NMR integrals at 278C. The product ratio of 4a/3a remains unchanged from 50 to 408C.

N. Zanatta et al. / Journal of Fluorine Chemistry 107 (2001) 149±154
151
Table 2
1H- and 13C-NMR spectral data of compounds 3a±d
Compound
1H-NMR, dppm (multiplicity, no. of protons, JHz, assignment) 13C-NMR, dppm, JCF (Hz)a
3a
3.04 (d, 2H, J34 ˆ 5.6, H-3), 5.00 (d, b, H-4), 3.78, 3.66 (qua, J56 ˆ 7.0, H-5), 1.28 (t, J65 ˆ 7.0, H-6), 3.44 (s, 3H, H-7)
1 2
115.3 (q, JCF ˆ 291:5, CF3), 187.9 (q, JCF ˆ 36:3, C2), 41.3 (C3), 99.3 (C4), 62.9 (C5), 14.8 (C6), 53.3 (C7)
3b
3c
3.06 (d, 2H, J34 ˆ 5.0, H-3), 5.04 (m, 1H, b, H-4), 3.75, 3.68 (qua, 4H, J56 ˆ 7.0, H-5, H-7), 1.25 (t, 6H, J65 ˆ 7.0, H-6, H-8)
1
2
115.2 (q, JCF ˆ 291:4, CF3), 188.2 (q, JCF ˆ 36:3, C2), 41.7 (C3), 98.3 (C4), 65.5 (C5, C7), 18.0 (C6, C8)
3.09 (d, 2H, J34 ˆ 5.4, H-3), 5.08±5.31 (m, 1H, b, H-4), 3.57±3.76 (m, 2H, b, H-5), 1.24 (t, 3H, J65 ˆ 7.0, H-6), 4.11 (m, 2H, b, H-7),
5.88±6.07 (m, 1H, b, H-8), 5.08±5.32 (m, 1H, b, H-9, H-90)
c (CF3), c (C2), 41.6 (C3), 97.8 (C4), 62.8 (C5), 14.7 (C6), 65.4 (C7), 137.1 (C8), 117.8 (C9)
3.12 (d, 2H, J34 ˆ 5.6, H-3), 5.00 (m, 1H, b, H-4), 3.50±4.20 (m, 2H, b, H-5), 1.15±1.50 (m, 3H, b, H-6), 4.30 (d, 2H, J79 ˆ 2.4, H-7),
2.52 (t, 1H, J97 ˆ 2.4, H-9)
3d
1
122.5(q, JCF ˆ 286:0, CF3), c (C2), 41.5 (C3), 97.4 (C4), 65.4 (C5), 14.7 (C6), 53.8 (C7), 87.1 (C8), 75.2 (C9)
a The NMR spectral data were obtained from the mixture of compounds 3 and 4; b Multiplicity and coupling constants are difficult to obtain because the
signals of compound 3 are totally or partially superimposed with the signal of the corresponding nuclei of compound 4; c Signal was not observed due to the
low signal/noise ratio of the minor isomer.
1
tri¯uoromethyl-pyrrolidin-2-one (7) as the only product of
the reaction in 70% yield (Scheme 2). A mixture of 3-
ethoxy- and 3-methoxy-5-hydroxy-5-tri¯uoromethyl-pyrro-
lidin-2-one was obtained from the reaction of sodium cya-
nide with b-acetal-diols bearing different alkoxy groups,
such as the compound 4a.
signals in both H- and 13C-NMR spectra. The reaction,
however, is highly regioselective furnishing only the pyrro-
lidinone 7 with the exclusion of the 4-ethoxy-5-imino-2-
tri¯uoromethyltetrahydro-furan-2-ol.
In conclusion, we have shown that 4-alkoxy-4-ethoxy-
1,1,1-tri¯uoro-butane-2,2-diols (4a±b), and 1-(2-alkoxyte-
trahydro-furan-3-yl)-2,2,2-tri¯uoro-ethane-1,1-diols (6a±
d), in equilibrium with the parent b-acetal-ketones (3a±d,
and 5a±d) are readily available from the reaction of
4-ethoxy-1,1,1-tri¯uoro-but-3-en-2-one (1) and 1-(4,5-dihy-
dro-furan-3-yl)-2,2,2-tri¯uoro-ethanone (2) with sodium
The pyrrolidinone 7 has two asymmetric carbons and two
diastereoisomers were formed. The reaction shows little
stereoselectivity giving a pair of stereoisomers in a ratio
1
of 60:40% as determined from the H-NMR integrals. The
mixture of diastereoisomers was shown by two sets of
Table 3
1H- and 13C-NMR spectral data of compounds 4a±d
Compound
1H-NMR, dppm (multiplicity, no. of protons, JHz, assignment) 13C-NMR, dppm, JCF (Hz)a
4a
2.11 (d, 2H, J34 ˆ 4.0, H-3), 5.00 (t, 1H, b, H-4), 3.78; 3.66 (m, 2H, b, H-5), 1.28 (t, 3H, J65 ˆ 7.0, H-6), 3.44 (s, 3H, H-7), 5.24 (s, OH)
1 2
122.6 (q, JCF ˆ 285:7, CF3), 92.9 (q, JCF ˆ 32:8, C1), 34.8 (C3), 100.7 (C4), 63.0 (C5), 15.1 (C6), 53.7 (C7)
4b
4c
2.12 (d, 2H, J34 ˆ 5.6, H-3), 5.04 (d, 1H, b, H-4), 3.75, 3.68 (m, 4H, b, H-5, H-7), 1.25 (t, 6H, J65 ˆ 7.0, H-6, H-8), 5.17 (s, OH)
1
2
122.7 (q, JCF ˆ 285:8, CF3), 92.9 (q, JCF ˆ 32:7, C2), 35.4 (C3), 99.8 (C4), 62.8 (C5, C50), 14.9 (C6, C60)
2.09 (d, 2H, J34 ˆ 5.8, H-3), 5.08±5.31 (m, 1H, b, 4-H), 3.57±3.76 (m, 2H, b, H-5), 1.24 (t, 3H, J65 ˆ 7.0, H-6), 4.11 (m, 2H, b, H-7),
5.88±6.07 (m, 1H, b, H-8), 5.08±5.32 (m, 1H, b, H-9, H-90), 5.09 (s, OH)
1
2
122.7 (q, JCF ˆ 285:8, CF3), 92.8 (q, JCF ˆ 32:7, C2), 35.4 (C3), 99.3 (C4), 63.8 (C5), 15.0 (C6), 67.7 (C7), 133.4 (C8), 115.2 (C9)
2.17 (d, 2H, J34 ˆ 5.4, H-3), 5.00 (m, 1H, b, H-4), 3.50-4.20 (m, 2H, b, H-5), 1.15±1.50 (m, 3H, b, H-6), 4.27 (d, 2H, J78 ˆ 2.4, H-7), 2.48
(t, 1H, J97 ˆ 2.4, H-9), 5.60 (s, OH)
4d
1
2
.
122.6 (q, JCF ˆ 286:0, CF3), 92.7 (q, JCF ˆ 32:8, C2), 35.6 (C3), 98.9 (C4), 63.2 (C5), 14.9 (C6), 50.5 (C7), 88.1 (C8), 73.7 (C9)
a The NMR spectral data were obtained from the mixture of compounds 3 and 4; b Multiplicity and coupling constants are difficult to obtain because the

152
N. Zanatta et al. / Journal of Fluorine Chemistry 107 (2001) 149±154
Table 4
1H- and 13C-NMR spectral data of compounds 5a±d
Compound
1H-NMR, dppm (multiplicity, no. of protons, JHz, assignment)a 13C-NMR, dppm, JCF (Hz)b
3.54±3.60 (m, 1H, c, H-3), 5.34 (d, 1H, J43 ˆ 5.6, H-4), 4.00 (t, 2H, J56 ˆ 7.0, H-5), 1.90±2.10 (m, 2H, c, H-6), 3.32 (s, 3H, H-7)
5a
1
2
115.5 (q, JCF ˆ 290:4, CF3), 190.2 (q, JCF ˆ 34:9, C2), 52.8 (C3), 102.8 (C4), 66.8 (C5), 23.3 (C6), 55.0 (C7)
1
2
5a0: 115.4 (q, JCF ˆ 289:9, CF3), 186.7 (q, JCF ˆ 35:5, C2), 51.9 (C3), 102.7 (C4), 66.3 (C5), 23.0 (C6), 54.9 (C7)
3.52±3.60 (m, 1H, c, H-3), 5.48 (d, 1H, J43 ˆ 5.6, H-4), 3.99 (t, 2H, J56 ˆ 8.2, H-5), 2.00±2.15 (m, 2H, c, H-6), 3.69 (m, 2H, c, H-7),
1.22 (m, 3H, c, H-8)
5b
5c
1
2
115.4 (q, JCF ˆ 291:6, CF3), 190.6 (q, JCF ˆ 35:5, C2), 50.1 (C3), 101.4 (C4), 66.1 (C5), 26.6 (C6), 62.0 (C7), 14.7 (C8)
1
5b0: 116.4 (q, JCF ˆ 289:7, CF3), d (C2), 51.8 (C3), 102.0 (C4), 65.5 (C5), 27.0 (C6), 62.5 (C7), 15.6 (C8)
3.52±3.64 (m, 1H, c, H-3), 5.10±5.40 (m, 1H, c, H-4), 3.90±4.10 (m, 2H, c, H-5), 1.90±2.40 (m, 2H, c, H-6), 3.90±4.10 (m, 2H, c, H-7),
5.80±6.10 (m, 1H, c, H-8), 5.10±5.40 (m, 1H, c, H-9, H-90)
2
115.6 (q,1JCF ˆ 291:6, CF3), 190.6 (q, JCF ˆ 35:7, C2), 51.0 (C3), 100.8 (C4), 67.1 (C5), 21.5 (C6), 63.8 (C7), 137.1 (C8), 115.2 (C9)
1
2
5c0: 115.4 (q, JCF ˆ 292:4, CF3), 186.8 (q, JCF ˆ 35:2, C2), 52.9 (C3), 100.8 (C4), 66.4 (C5), 23.4 (C6), 64.5 (C7), 134.8 (C8), 114.3
(C9)
5d
3.56±3.60 (m, 1H, c, H-3), 5.40±5.70 (m, 1H, c, H-4), 3.80±4.10 (m, 2H, c, H-5), 1.90±2.30 (m, 2H, c, H-6), 4.10±4.40 (m, 2H, c, H-7),
2.40±2.50 (m, 1H, c, H-9)
1
2
123.2 (q, JCF ˆ 288:3, CF3), 189.5 (q, JCF ˆ 35:3, C2), 52.6 (C3), 99.6 (C4), 66.6 (C5), 22.9 (C6), 54.4 (C7), 78.1 (C8), 74.8 (C9)
5d0: 122.8 (q, 1JCF ˆ 287:7 (CF3), 186.6 (q, 2JCF ˆ 35:7, C2), 51.7 (C3), 99.5 (C4), 66.1 (C5), 23.2 (C6), 54.0 (C7), 78.2 (C8), 74.4 (C9)
a The NMR spectral data were obtained from the mixture of compounds 5 and 6.
b Signals of the two stereoisomers obtained; c Multiplicity and coupling constants are difficult to obtain because the signals of compound 5 are totally or
partially superimposed with the signal of the corresponding nuclei of compound 6; d Signal was not observed due to the low signal/noise ratio of the minor
isomer.
Table 5
1H- and 13C-NMR spectral data of compounds 6a±d
Compound
1H-NMR, dppm (multiplicity, no. of protons, JHz, assignment)a 13C-NMR, dppm, JCF (Hz)b
6a
2.50±2.67 (m, 1H, c, H-3), 5.14 (d, 1H, J43 ˆ 4.4, H-4), 4.08 (t, 2H, J56 ˆ 7.0, H-5), 2.10±2.23 (m, 2H, c, H-6), 3.43 (s, 3H, H-7), 5.56 (s,
OH)
1
2
122.8 (q, JCF ˆ 285:2, CF3), 94.2 (q, JCF ˆ 32:2, C2), 45.5 (C3), 104.2 (C4), 67.0 (C5), 27.0 (C6), 54.3 (C7)
1
2
6a0: 122.9 (q, JCF ˆ 288:5, CF3), 96.0 (q, JCF ˆ 30:4, C2), 46.7 (C3), 105.1 (C4), 67.3 (C5), 26.8 (C6), 54.3 (C7)
2.50±2.70 (m, 2H, c, H-3), 5.26 (d, 1H, J43 ˆ 4.2, H-4), 4.23 (t, 2H, J56 ˆ 6.20, H-6), 2.00±2.15 (m, 2H, c, H-6), 3.69 (m, 2H, c, H-7), 1.22
(t, 3H, J87 ˆ 7.0, c, H-8), 5.20 (s, OH)
6b
6c
6d
1
2
122.9 (q, JCF ˆ 287:0, CF3), 93.6 (q, JCF ˆ 32:1, C2), 45.5 (C3), 102.7 (C4), 66.8 (C5), 32.6 (C6), 63.0 (C7), 14.6 (C8)
1
2
6b0: 123.3 (q, JCF ˆ 287:8, CF3), 93.2 (q, JCF ˆ 31:3, C2), 46.6 (C3), 103.7 (C4), 66.6 (C5), 30.8 (C6), 63.3 (C7), 14.3 (C8)
2.50-2.60 (m, 1H, H-3), 5.10±5.40 (m, 1H, H-4), 3.90±4.10 (m, 2H, H-5), 1.90±2.40 (m, 2H, H-6), 3.90±4.10 (m, 2H, H-7), 5.80±6.10 (m,
1H, H-8), 5.10±5.40 (m, 1H, H-9, H-90), 5.05 (s, OH)
1
116.5 (q, JCF ˆ 289:8, CF3), 93.8 (q, JCF ˆ 32.2, C2), 45.5 (C3), 102.4 (C4), 67.9 (C5), 26.8 (C6), 62.1 (C7), 133.3 (C8), 117.9 (C9)
1
6c0: 117.1 (q, JCF ˆ 285:9, CF3), d (C2), 46.5 (C3), 103.4 (C4), 68.4 (C5), 27.1 (C6), 61.7 (C7), 133.7 (C8), 117.2 (C9)
2.50±2.70 (m, 1H, c, H-3), 5.40±5.70 (m, 1H, c, H-4), 3.80±4.10 (m, 2H, c, H-5), 1.90±2.30 (m, 2H, c, H-6), 4.10±4.40 (m, 2H, c, H-7),
2.40±2.50 (m, 1H, c, H-9), 5.10 (s, OH)
1
2
115.3 (q, JCF ˆ 292:2, CF3), 93.5 (q, JCF ˆ 32:2, C2), 45.8 (C3), 101.7 (C4), 67.2 (C5), 26.9 (C6), 50.3 (C7), 81.0 (C8), 73.6 (C9)
6d0: 117.0 (q, 1JCF ˆ 280:7, CF3), 96.3 (q, 2JCF ˆ 31:2, C2), 46.4 (C3), 102.8 (C4), 67.0 (C5), 26.6 (C6), 50.1 (C7), 78.1 (C8), 74.0 (C9)
a The NMR spectral data were obtained from the mixture of compounds 5 and 6.
b Signals of the two obtained stereoisomers; c Multiplicity and coupling constants are difficult to obtain because the signals of compound 6 are totally or
partially superimposed with the signal of the corresponding nuclei of compound 5; d Signal was not observed due to the low signal/noise ratio of the minor

N. Zanatta et al. / Journal of Fluorine Chemistry 107 (2001) 149±154
153
Scheme 2.
azide in alcohol±water media. In addition, the b-acetal-diols
and/or the b-acetal-ketones may be important building
blocks for the synthesis of heterocyclic compounds.
without further puri®cation. Selected physical and spectral
data of compound 4a: molecular formula and (weight)
C7H13F3O4 (218.17), elemental analysis: calculated: C
38.53%; H 5.96%; found: C, 38.53%; H, 5.75%; mp: 52±
548C; IR (KBr), n (cm 1): 3365, 3300, 1105.
3. Experimental
Compound 4b: molecular formula and (weight)
C8H15F3O4 (232.19); elemental analysis: calculated: C,
41.38%; H, 6.51%; found: C, 41.20%; H, 6.55%; mp:
53±558C; IR (KBr), n (cm 1): 3365, 3300, 1140.
Unless otherwise indicated, all common reagents and
solvents were used as obtained from commercial suppliers
without further puri®cation. The b-alkoxyvinyl tri¯uoro
methyl ketones (1, 2) were prepared according to reference
[7]. All melting points were determined on a Reichert
Thermovar apparatus and are uncorrected. 1H- and 13C-
NMR spectra were acquired on a Bruker DPX 400 spectro-
meter (1H at 400.13 MHz and 13C at 100.62 MHz) or on a
Bruker DPX 200 spectrometer (1H at 200.13 MHz and 13C at
50.32 MHz) in CDCl3, using TMS as the internal reference.
IR spectra were recorded on a Bruker IFS 28 FT-IR spectro-
meter. Mass spectra were registered in a HP 5973 MSD
connected to a HP 6890 GC and interfaced by a Pentium PC.
The GC was equipped with a split±splitless injector, auto-
sampler, cross-linked HP-5 capillary column (30 m,
0.32 mm of internal diameter), and helium was used as
the carrier gas. Elemental analysis was performed on a
Vario EL Elementar Analysensysteme.
3.2. Synthesis of 5-hydroxy-5-trifluoromethyl-3-ethoxy
pyrrolidin-2-one (7)
To a warm solution (ꢀ608C) of (4b) (0.58 g, 2.5 mmol) in
ethanol (3 ml) a solution of sodium cyanide (0.16 g,
3.25 mmol) in water (3 ml) was added and the reaction
was heated for 4 h at 608C under magnetic stirring. The
reaction was extracted with ethyl ether, dried under anhy-
drous magnesium sulfate and the solvent evaporated. A clear
liquid (0.40 g, 70% yield) was obtained and identi®ed as 3-
ethoxy-5-hydroxy-5-tri¯uoromethyl-pyrrolidin-2-one (7).
1
The product 7 showed two sets of signals in both H- and
13C-NMR spectra, indicating the presence of two diaster-
eoisomers in a ratio of 60:40%. Major isomer; (CDCl3), d:
9.40 (ws, 1H, N±H), 8.40 (s, 1H, OH), 4.14 (t, 1H,
2
3JH3
ˆ 7:8 Hz, H-3), 2.93 (d/d, 1H, JH4
ˆ
H4H40
14:4 Hz, 3JH4
H40
3.1. Synthesis of b-acetal-diols: general procedure
ˆ 8:4 Hz, H-4), 2.15 (d/d, 1H,
3
0
H3
H3
2
0
To a solution of 1 or 2 (5 mmol) in methanol (3 ml), a
solution of sodium azide (5 mmol, 0.39 g) in water (3 ml)
was added under magnetic stirring. The reactions were
carried out at room temperature with reaction times ranging
from 30 min to 24 h (see Table 1). The reaction mixture was
extracted with dichloromethane (3 Â 20 ml) and the com-
bined organic layers were dried with magnesium sulfate.
Evaporation of the solvent afforded a pale yellow oil which
was a mixture of b-acetal-diols and b-acetal-ketones
(ꢀ80:20%), respectively. The products ratio were deter-
JH4
ˆ 14:4 Hz, JH4
ˆ 7:2 Hz, H-40), 3.80±3.60
H4
(m, 2H, ±OCH2 ), 1.23 (t, 3H, 3JH ˆ 7:0 Hz, ±CH ).
H
3
13C-NMR (CDCl3), d: 175.39 (C-2), 123.38 (q,
1JCF ˆ 284 Hz, CF3), 84.31 (q, JCF ˆ 34 Hz, C-5), 75.20
2
(C-3), 67.04 (±OCH2 ), 37.80 (C-4), 14.87 (±CH3). GC/MS
(%), EI (70 eV): 169 (100), 100 (50), 73 (18), 56 (38). IR
(neat), cm 1: 3250, 1717. Analysis: calc. for C7H10F3NO3
(213.16): C, 39.44; H, 4.73; N, 6.57. Found: C, 38.85; H,
4.70; N, 6.39.
Minor isomer: 1H-NMR (CDCl3), d: 9.40 (ws, 1H, N±H),
1
3
H4H40
mined by H-NMR integration, at 278C. The mixture of
8.32 (s, 1H, OH), 4.40 (t, 1H, JH3
2.58 (d/d, 1H, 2JH4
2.29 (d/d, 1H, JH4
ˆ 7:8 Hz, H-3),
ˆ 13:6 Hz, 3JH4
ˆ 8:0 Hz, H-4),
H40
H3
4a/3a and 4b/3b solidi®ed in the refrigerator and were
recrystallized from hexane to obtain pure 4a and 4b. Tenta-
tive of puri®cation by column chromatography resulted in
decomposition of the products. Nonetheless, the crude
mixture of products were comprised by a considerably pure
mixture of b-acetal-diols and b-acetal-ketones and they
were fully characterized by 1H- and 13C-NMR and IR
2
3
0
0
ˆ 13:6 Hz, JH4
ˆ 7:6 Hz, H-
H4
H3
40), 3.80±3.60 (m, 2H, ±OCH2 ), 1.23 (t, 3H, 3JH
ˆ
H
7:0 Hz, ±CH3). 13C-NMR (CDCl3), d: 176.89 (C-2),
1
2
122.93 (q, JCF ˆ 284 Hz, CF3), 84.22 (q, JCF ˆ 34 Hz,
C-5), 74.44 (C-3), 66.48 (±OCH2 ), 36.46 (C-4), 14.96
(±CH3).

154
N. Zanatta et al. / Journal of Fluorine Chemistry 107 (2001) 149±154
[11] M.A.P. Martins, A.F.C. Flores, G.P. Bastos, A. Sinhorin, H.G.
Acknowledgements
Bonacorso, N. Zanatta, Tetrahedron Lett. 41 (2000) 293.
[12] M.A.P. Martins, R. Freitag, A.F.C. Flores, N. Zanatta, J. Heterocycl.
Chem. 32 (1995) 1491.
The authors thank the Conselho Nacional de Desenvol-
Â
Â
vimento Cientõ®co e Tecnologico (CNPq), PADCT-II/
FINEP, and PADCT-III/CNPQ 62.0228/97-0-QEQ, for
®nancial support.
[13] H.G. Bonacorso, M.A. Oliveira, A.P. Wentz, A.D. Wastowski, A.B.
Oliveira, M. HoÈrner, N. Zanatta, M.A.P. Martins, Tetrahedron 55
(1999) 345.
[14] I.L. Pacholski, I. Blanco, N. Zanatta, M.A.P. Martins, J. Braz. Chem.
Soc. 2 (1992) 118.
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