Diastereoselective synthesis of cyclic 1,3-aminoalcohols bearing CF3(CCl3)-groups

Article abstract of DOI:10.1016/j.jfluchem.2008.05.005

An aldol-type reaction of cyclic imines and cyclic lactims with carbonyl compounds activated by electron withdrawing trifluoromethyl or trichloromethyl groups proceeded without any catalyst under mild condition. β-Hydroxymethyl substituted cyclic imines or imidates are formed as a result of the reaction. The reduction of the prepared imines leads stereoselectively to the cyclic 1,3-aminoalcohols. Application of methyl trifluoropyruvate in this transformation opens an opportunity for the synthesis of γ-aminoacids derivatives which contain pyrrolidine moiety.

Full text of DOI:10.1016/j.jfluchem.2008.05.005

Journal of Fluorine Chemistry 129 (2008) 637–644
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Diastereoselective synthesis of cyclic 1,3-aminoalcohols bearing CF3(CCl3)-groups
a
Nikolay E. Shevchenko a, Gerd-Volker Ro¨schenthaler b, , Alexander S. Mitiaev ,
*
a,**
Enno Lork b, Valentine G. Nenajdenko
a Department of Chemistry, Moscow State University, Moscow 119899, Russia
b Institute of Inorganic & Physical Chemistry, University of Bremen, Leobener Strasse, D-28334, Germany
A R T I C L E I N F O
A B S T R A C T
Article history:
An aldol-type reaction of cyclic imines and cyclic lactims with carbonyl compounds activated by electron
withdrawing trifluoromethyl or trichloromethyl groups proceeded without any catalyst under mild
Received 13 April 2008
Received in revised form 5 May 2008
Accepted 5 May 2008
condition.
b-Hydroxymethyl substituted cyclic imines or imidates are formed as a result of the reaction.
The reduction of the prepared imines leads stereoselectively to the cyclic 1,3-aminoalcohols. Application
Available online 13 May 2008
of methyl trifluoropyruvate in this transformation opens an opportunity for the synthesis of
aminoacids derivatives which contain pyrrolidine moiety.
g-
Keywords:
ß 2008 Elsevier B.V. All rights reserved.
Diastereoselectivity
Aldol reaction
Reduction
Cyclic imines
Methyl trifluoropyruvate
Azaheterocycles
Trihalomethylcarbinols
1. Introduction
and piperidine fragment is an especially important structural unit
of many natural compounds, for example, proline, pipecolinic acid
and some alkaloids. We have previously reported that acyclic
imines react smoothly with some trifluoromethylketones to give
There is a significant importance of the substances containing in
their structures fluorinated moiety especially a trifluoromethyl
group due to their potent usefulness for medicinal chemistry and
material science [1]. The numerous successful strategies for
syntheses of such compounds have been previously described
[2]. However, the development of new methods that allow facile
introduction of fluorinated fragments into organic molecules is still
a topical task of modern organic synthesis.
b
-hydroxy-b-trifluoromethyl imines in good yields [5]. In this
study we investigated the reactions of cyclic aliphatic imines and
lactim ethers with hexafluoroacetone, methyl trifluoropyruvate,
chloral and demonstrated that this approach provides a convenient
and efficient synthesis of nitrogen heterocycles bearing
trihalomethylcarbinol moiety.
a
In the recent years studies of the aldol reaction involving
fluorine-containing carbonyl compounds have received a signifi-
cant attention, especially the diastereo- and enantio-selective
version of such transformations [3]. However, to the best of our
knowledge, this methodology has never been applied to the
reaction of fluorinated ketones with imines where C N bound is
incorporated in a ring. These imines are very promising building
blocks from the synthetic point of view and some examples of their
transformations have been recently published [4]. The pyrrolidine
2. Results and discussion
In the framework of our ongoing study of the synthetic
potential of cyclic imines we propose that the using of these imines
in aldol-type condensation with certain halogenated carbonyl
compounds opens the opportunity for a facile incorporation of
trihalomethylcarbinol fragments at the
b-position of nitrogen
heterocycles. To examine this hypothesis, different starting 2-
substituted pyrrolines 1 have been obtained accordingly to two
main strategies (Scheme 1) which are usually applied for this
purpose in the literature [6,7]. The variability of the synthetic
approach to these imines together with accessibility and cheap-
ness of starting N-vinyl pyrrolidone permit to synthesize a wide
variety of requested imines 1a–g.
* Corresponding author. Tel.: +49 421 2189200; fax: +49 421 2184267.
** Corresponding author. Tel.: +7 495 9392276; fax: +7 495 9328846.
E-mail addresses: gvr@chemie.uni-bremen.de (G.-V. Ro¨schenthaler),
nen@acylium.chem.msu.ru (V.G. Nenajdenko).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.05.005

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N.E. Shevchenko et al. / Journal of Fluorine Chemistry 129 (2008) 637–644
Scheme 3. Reactions of cyclic imines 1a–g with methyl trifluoropyruvate and
trichloroacetaldehyde.
Scheme 1. Synthesis of the starting imines 1: (i) RCO2Et and NaH, then HCl (aq.) (1a,
1b, 1g); (ii) RLi, then HCl (aq.) (1b–f).
reaction to afford the substituted
b-hydroxyimines (Scheme 3) in
high yield and good diastereoselectivity (up to 97% de) (Table 1).
The diastereomeric excesses of iminoalcohols 4a–g and 5a–g were
measured by 19F for fluorine-contained compound and by 1H
together with 13C NMR spectroscopy for others.
To establish the relative configuration of predominate diaster-
eomer X-ray structural study was performed. Accordingly to the X-
ray structural data [14] the configuration of the major diastereoi-
somer of 4e is syn (erythro) (Figs. 2 and 3) [15]. Analogous to the
molecular structure of iminoalcohol 2a there is no intramolecular
hydrogen bond between OH group and nitrogen atom in the
structure of syn 4e. Another structural feature of iminoalcohol 4e is
almost planar pyrroline ring and normal lengths of C N double
bond. As it may be concluded based on similarity of NMR spectral
data for main stereoisomers of iminoalcohols 4 the configuration of
all major diastereomers in these series are syn and several
assumptions can be made to rationalize the observed stereo-
selectivity.
Scheme 2. Reactions of imines 1a, c with HFA.
In the beginning of our investigation hexafluoroacetone (HFA)
was allowed to react with model imines 1a and 1c in order to check
their reactivity. It has been found that the reaction of both alkyl 1a
and aryl 1c pyrrolines starts at low temperature (below À30 8C)
and gives iminoalcohols 2a, c in good yields during 6 h at ambient
temperature (Scheme 2). Consequently, the reaction proceeds
under extremely mild conditions without any catalyst in contrast
to literature examples of aldol-type reaction of imines with
carbonyl compounds. Usually such transformation demands acids
or bases to complete the reaction [8]. The nature of solvents plays
not significant role in this transformation, therefore, THF, DCM and
toluene can be used, however, the usage of diethyl ether as a
solvent permits to obtain products as crystalline solids directly
from reaction mixtures. It should be noted that the crystalline
products 2a and 2c are stable at air but they absorb water quickly
in solution which results in destruction of the imine ring in spite of
the fact that cyclic imines 1a, c itself are stable even in water
solution [9]. Indeed, treatment of the sterically hindered adduct 2a
with water led to the acyclic hemi-aminal 3 in 1/2 h which can be
alternatively obtained by direct interaction between 1a and
hexafluoroacetone hydrate. These transformations illustrate the
reversibility of the HFA addition to imine 1a what is well known for
classical aldol reaction under certain condition [10]. The formation
of 3 using hexafluoroacetone hydrate opens the possibility of mild
protection of the amino-group.
The control of the stereochemistry of the classical aldol reaction
in diastereoselective manner has a subject of intensive researches
especially over the last two decades [16], but a little is known
about stereochemical behavior of cyclic imines in aldol reaction.
Following the Zimmerman–Traxler rule, valid for the kinetically
Besides NMR and MS data the molecular structure of adduct 2a
was established by the X-ray analysis (Fig. 1) [11]. Interestingly,
the OH group forms no intramolecular hydrogen bridge towards
the imino nitrogen whereas the 1,3-iminoalkohols often exhibits a
strong intramolecular hydrogen bond between hydroxyl-group
and nitrogen atom, inducing an almost planar six-membered ring
[5]. Also normal C N bond length 128 pm were observed [12].
Then we try to involve in the reaction with cyclic imines 1 other
activated carbonyl compounds such as chloral and methyl
trifluoropyruvate. The reaction of methyl trifluoropyruvate can
open a very interesting possibility to construct the derivatives of g-
aminoacids which may be interesting from biochemical point of
view. On the other hand the reaction with trichloroacetaldehyde
can led to the trichloromethylcarbinols which are very remarkable
and diverse synthetic building blocks [13].
Similar to the reaction of HFA, cyclic imines 1 react with methyl
trifluoropyruvate and chloral at room temperature in an aldol-type
Fig. 1. The molecular structure of 2a (thermal ellipsoids with 50% probability).
Selected bond lengths (pm) and bond angels [11]: N(1)–C(2) 128.1(2), N(1)–C(4)
147.0(3), C(3)–C(13) 155.8(3), O(10)–C(13) 138.8(2); C(2)–N(1)–C(4) 110.81(2),
N(1)–C(2)–C(6) 120.57(2), N(1)–C(2)–C(3) 113.01(2), C(5)–C(3)–C(13) 116.81(2),
C(2)–C(3)–C(13) 116.66(2), O(10)–C(13)–C(18) 108.40(2), O(10)–C(13)–C(19)
108.26(2), O(10)–C(13)–C(3) 106.91(2).

N.E. Shevchenko et al. / Journal of Fluorine Chemistry 129 (2008) 637–644
639
Scheme 4. The imine–enamine equilibrium and Zimmerman–Traxler transition
state.
Table 1
Results of the reactions via Scheme 3
Entry
R
Product
Yield (%)
de (%)
1
2
tert-Bu
4a
4b
4c
4d
4e
4f
71
81
90
89
92
78
91
69
87
85
85
84
75
90
94
89
90
93
74
94
88
96
92
94
95
80
97
90
C6H5
3
4-Me–C6H4
4-MeO–C6H4
4-F–C6H4
2-Furyl
4
5
6
Fig. 2. The molecular structure of major diastereoisomer 4e (thermal ellipsoids with
50% probability). Selected bond lengths (pm) and bond angels [14]: O(1)–C(1)
119.9(1), C(6)–C(7) 153.1(4), C(7)–N(1) 147.5(7), C(1)–C(3) 154.7(5), N(1)–C(8)
127.8(0), O(2)–C(2) 145.7(6), C(8)–C(9) 148.2(1), C(3)–O(3) 139.3(7); O(1)–C(1)–
O(2) 124.96(1), N(1)–C(7)–C(6) 105.32(1), C(8)–N(1)–C(7) 109.84(1), O(3)–C(3)–
C(4) 107.53(1), O(3)–C(3)–C(1) 114.53(1), C(4)–C(3)–C(1) 105.77(1), O(3)–C(3)–
C(5) 109.27(1), C(4)–C(3)–C(5) 114.32(1), C(1)–C(3)–C(5) 105.57(1).
7
4-Py
4g
5a
5b
5c
5d
5e
5f
8
tert-Bu
9
C6H5
10
11
12
13
14
4-Me–C6H4
4-MeO–C6H4
4-F–C6H4
2-Furyl
4-Py
5g
hol (Scheme 4). This prediction coincides with the observed
stereoselectivity.
However, we suggest that syn-adducts 4 are thermodynami-
cally controlled products. Although some details of the reaction
deserve further study, the reversibility of the aldol reaction of
cyclic imines 1 as it was pointed out above for iminoalcohol 2a may
confirms our assumption. Moreover, realization of the Zimmer-
man–Traxler six-membered chairlike transition state in case of
rigid cyclic imines 1 should be difficult for sterical reasons. For the
same reasons an intramolecular hydrogen bond between OH group
and nitrogen atom in the structure of iminoalcohols 4e and 2a is
Fig. 3. Visualization of the molecular structure of syn 4e in an extended manner (zig-
zag).
not observed whereas analogous linear b-iminoalcohols exhibits a
controlled product, the stereochemistry of aldol product is
determined by the configuration of the enolate or, in our case,
by the configuration of the enamine. Incorporation of the enamine
double bond to five-membered cycle makes possible generation
only Z-enamine which should preferably gives the syn iminoalco-
strong intramolecular hydrogen bond inducing a six-membered
ring [5]. The observed configuration of main diastereoisomers
corresponds obviously to the most favorable isomers since the
more sterically bulky group CO2Me and C(R) N fragment of the
pyrroline cycle are the most distant from each other (Figs. 2 and 3).
Scheme 5. Reduction of 4 and 5 with NaBH4 and NOESY data for 7d.

640
N.E. Shevchenko et al. / Journal of Fluorine Chemistry 129 (2008) 637–644
Table 2
and, probably now, it is impossible to make well-founded
assumption to explain this fact.
Results of the reduction via Scheme 4
Entry
R
Product
Yield (%)
trans (%)
3. Conclusion
1
2
3
4
5
6
7
4-MeO–C6H4
4-F–C6H4
2-Furyl
6d
6e
6f
82
87
80
89
91
89
67
57
82
78
71
70
72
88
In summary, we have studied the interactions of some cyclic
imines and lactims with carbonyl compounds activated by electron
withdrawing trifluoromethyl or trichloromethyl groups in an
aldol-type reaction at mild condition and the absence of a catalyst.
4-MeO–C6H4
4-F–C6H4
2-Furyl
7d
7e
7f
4-Py
7g
The products of the reaction are corresponding
b-hydroxy imines
which can be simply reduced to the 1,3-aminoalcohols. The using
of methyl trifluoropyruvate in analogous transformation permits
The prepared imines 4 and 5 are very favorable precursors for
the preparation of substituted pyrrolidines bearing trihalomethyl-
carbinol fragment. We found that simple reduction of the imine
double bond of the iminoalcohol 4 and 5 with sodium borohydride
to obtain g-aminoacids with moderate diastereoselectivity.
4. Experimental
in methanol is appreciable (Scheme 5). As
a
result one
4.1. General experimental procedures
diastereomer is formed preferentially. Moreover, the carrying
out of the reaction under low temperature permits to achieve the
moderate diastereoselectivity. It is clear from Table 2 that the
nature of the substituent at position 2 of pyrroline ring does not
significantly influence on the selectivity of the reduction.
The vicinal H–H constants between the protons at C-2 and C-3
carbon atoms of pyrrolidine ring are equal 7.3 Hz in both series of
main stereoisomers of cyclic amines 6 and 7. However, to prove the
geometry of relative position of substituents at pyrrolidine cycle
2D NOE experiment for aminoalcohol 7d was performed. As it is
clear from the obtained results (Scheme 5) the aryl group and
trichloromethylcarbinol fragment are placed in relative trans-
location of pyrrolidine ring to minimize steric interactions
between these bulky groups. It is notable that pyrrolidine alcohols
6 and 7 may be isolated as single diastereomers with 95+% purity
just by double or in cases of 7d–f single recrystallization of crude
products from ethylacetate/hexane mixture.
NMR spectra were obtained on a Bruker DPX-200 (200.1 MHz
for 1H; 188.3 MHz for 19F; 50.32 MHz for 13C) or a Bruker AM-360
(360.1 MHz for 1H; 90.5 MHz for 13C) spectrometers, chemical
shifts for 1H NMR data are referenced internally to tetramethylsi-
lane (0.0); chemical shifts for 13C NMR data are referenced to
corresponding CDCl3 (77.2), (CD3)2SO (39.5); chemical shifts for 19
F
NMR data are referenced to CFCl3 (0.0) or PhCF3 (À63.90). High-
resolution mass spectra (HRMS) and mass spectra (MS) were
recorded using a Varian MAT CH7A instrument at 70 eV. Chemical
ionization mass spectra (CIMS) were obtained on the same
equipment with ammonia or isobutane as the reagent gas. The
X-ray structural study was carried out on
diffractometer using graphite monochromated Mo K
= 71.073 pm). The structures were solved by direct method and
a
Siemens P4
a
radiation
(
l
anisotropically refined based on F2 using the SHELX-97 program
package [19]. The C–H hydrogen atoms were placed in calculated
position, assigned common isotropic thermal parameters and
allowed to ride on their parent atoms. Melting points are
uncorrected. Ether was distilled from sodium/benzophenone prior
to use. All other commercially available reagents and solvents were
employed without further purification. The starting imines 1a, 1b
and 1g were prepared by the reaction of ethyl ester of the
appropriate carboxylic acids with N-vinylpyrrolidin-2-one accord-
ing to the described procedure [7,20]. Cyclic imines 1c–f were
obtained by the reaction of corresponding lithium compounds
with N-vinylpyrrolidin-2-one [6]. The requested lactim ethers
were synthesized from the corresponding lactams by the reaction
with dimethyl sulphate [21].
Our interest in further investigation of cyclic imines led us to
study cyclic lactim ethers. Cyclic lactim ethers are useful building
blocks for large variety of practically important organics [17]. It has
been shown that acyclic lactim ethers are very active in aldol
reaction with chloral and bromal and low stereoselectivity is
observed in this reaction [18].
We found that cyclic lactims 8 react with electron-deficient
methyl trifluoropyruvate and chloral at room temperature to
afford the substituted
b-hydroxylactims in good yield (Scheme 6,
Table 3). As one would expect the five-membered lactim ethers
react with methyl trifluoropyruvate and chloral with lower
diastereoselectivity compared to the reaction with cyclic imines
1 (Table 3 entries 1 and 3). Surprisingly, the diastereomeric excess
of products 9b and 10b is very good (94 and 88% correspondingly)
4.2. General procedure for the reaction of cyclic imines with
hexafluoroacetone
A solution of corresponding cyclic imine (10 mmol) in 30 ml of
ether was placed into pressure-suitable ampoule, cooled to
À190 8C and pumped off in vacuo. Then measured amount of
gaseous hexafluoroacetone (12 mmol) was placed to the ampoule,
the mixture warmed up to the ambient temperature and was
stirred for 6 h. The crystal solid was filtered and dried in dry box at
room temperature.
Scheme 6. Reactions of cyclic lactims 8 with methyl trifluoropyruvate and chloral.
1,1,1,3,3,3-Hexafluoro-2-[5-(4-methylphenyl)-3,4-dihydro-2H-
pyrrol-4-yl]propan-2-ol (2c), white crystals, mp 148–149 8C, 1H
Table 3
Results of the reaction via Scheme 6
NMR (200 MHz, CDCl3):
CH3)), 3.82–4.23 (4H, m), 7.10–7.17 (2H, m, Ar–H), 7.52–7.59 (2H,
m, Ar–H). 13C NMR (50 MHz, CDCl3):
d 2.17–2.52 (5H, m, incl. 2.35 (3H, s, Ar–
Entry
Product
Yield (%)
Main diastereomer (%)
1
2
3
4
9a
9b
91
84
97
89
56
97
65
94
d
21.9 (Ar–CH3), 25.0, 49.8,
2
60.7 (CH2N), 78.6 (sp, JCF = 28.5 Hz, (CF3)2C), 123.0 (q,
10a
10b
1JCF = 289.0 Hz, CF3), 123.4 (q, JCF = 288.4 Hz, CF3), 128.6 (Ar),
1
129.7 (Ar), 133.3 (Ar), 141.4 (Ar), 171.2 (C N). 19F NMR (188 MHz,

N.E. Shevchenko et al. / Journal of Fluorine Chemistry 129 (2008) 637–644
641
CDCl3):
d
À75.2 (3F, q, 4JFF = 8.6 Hz, CF3), À74.1 (3F, q, 4JFF = 8.6 Hz,
Methyl
dihydro-2H-pyrrol-4-yl]propanoate (4c), white crystals, mp 148–
150 8C, 1H NMR (200 MHz, CDCl3):
2.03–2.31 (2H, m), 2.36 (3H, s,
Ar–CH3), 3.85 (3H, s, OCH3), 3.95–4.08 (3H, m), 7.13–7.21 (2H, m,
Ar–H), 7.54–7.62 (2H, m, Ar–H). 13C NMR (50 MHz, CDCl3):
21.36
3,3,3-trifluoro-2-hydroxy-2-[5-(4-methylphenyl)-3,4-
CF3). EIMS 70 eV, m/z (rel. int.): 325 [M]+ (25), 306 [M–F]+ (5), 256
[M–CF3]+ (6), 131 [M–194]+ (100). HRMS (EI): calcd. for
d
C14H13F6NO (M) 325.0901; found 325.0891.
2-(5-tert-Butyl-3,4-dihydro-2H-pyrrol-4-yl)-1,1,1,3,3,3-hexa-
fluoropropan-2-ol (2a), white crystals, mp 192–193 8C (dec.), 1H
NMR (200 MHz, CD3CN):
3.52–3.97 (3H, m), 5.68 (1H, bs, OH). 13C NMR (50 MHz, CD3CN):
d
(Ar–CH3), 26.0, 50.4, 53.7 (OCH3), 61.2 (CH2N), 79.4 (q,
1
d
1.28 (9H, s, C(CH3)3), 2.03–2.30 (2H, m),
2JCF = 28.5 Hz, CF3C), 123.7 (q, JCF = 287.9 Hz, CF3), 127.8 (Ar),
d
128.8 (Ar), 131.8 (Ar), 140.2 (Ar), 169.1 (CO2CH3), 170.9 (C N). 19
F
26.4, 30.9 ((CH3)3C), 38.5((CH3)3C, 49.8 (CH2), 59.9 (CH2N), 78.2
(sp, 2JCF = 27.3 Hz, (CF3)2C), 124.6 (q, 1JCF = 289.5 Hz, CF3), 124.8 (q,
NMR (188 MHz, CDCl3):
d
À74.4 (s, CF3). EIMS 70 eV, m/z (rel. int.):
315 [M]+ (11), 256 [M–CO2CH3]+ (11), 158 [M–F3CC(OH)CO2CH3]+
(58), 131 [M-184]+ (100). HRMS (EI): calcd. for C15H16F3NO3 (M)
315.1082; found 315.1076.
1JCF = 290.3 Hz, CF3), 182.1 (C N). 19F NMR (188 MHz, CD3CN):
d
4
4
À75.6 (3F, q, JFF = 9.1 Hz, CF3), À73.7 (3F, q, JFF = 9.1 Hz, CF3).
EIMS 70 eV, m/z (rel. int.): 291 [M]+ (10), 276 [M–CH3]+ (100), 222
[M–CF3]+ (4), 206 [M-119]+ (15). HRMS (EI): calcd. for C11H15F6NO
(M) 291.1058; found 291.1049.
Methyl 3,3,3-trifluoro-2-hydroxy-2-[5-(4-methoxyphenyl)-3,4-
dihydro-2H-pyrrol-4-yl]propanoate (4d), white crystals, mp 157–
158 8C (dec.), 1H NMR (200 MHz, (CD3)2SO):
d 1.93–2.20 (2H, m),
2,2-Dimethyl-6-{[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethy-
l)ethyl]amino}hexan-3-one (3). The hexafluoroacetone hydrate
(12 mmol) was added to a stirred solution of imine 1a (10 mmol)
in 25 ml of THF under cooling in ice-bath. After addition the cooling
bath was removed and mixture was stirred at room temperature
for 1 h. Then the solvent was removed under vacuum, the residue
was carefully washed with dry ether and dried in dry box at room
temperature. The product was obtained as white crystals, mp 79–
3.69 (3H, s, OCH3), 3.77 (3H, s, OCH3), 3.84–4.05 (3H, m), 6.89–6.93
(2H, m, Ar–H), 7.58–7.62 (2H, m, Ar–H). 13C NMR (50 MHz,
(CD3)2SO): 28.8, 51.1, 54.5 (OCH3), 56.4 (OCH3), 60.5 (CH2N), 80.7
2
1
(q, JCF = 26.5 Hz, CF3C), 114.3 (Ar), 125.0 (q, JCF = 288.6 Hz, CF3),
129.8 (Ar), 130.7 (Ar), 161.6 (Ar), 169.9 (CO2CH3), 171.5 (C N). 19
NMR (188 MHz, (CD3)2SO):
À72.9 (s, CF3). Anal. Calcd. for
15H16F3NO4: C, 54.4; H, 4.9. Found: C, 54.4; H, 4.9.
Methyl 3,3,3-trifluoro-2-hydroxy-2-[5-(4-fluorophenyl)-3,4-dihy-
dro-2H-pyrrol-4-yl]propanoate (4e), white crystals, mp 146–147 8C
(dec.), 1H NMR (200 MHz, CDCl3):
1.97–2.28 (2H, m), 3.70 (3H, s,
F
d
C
81 8C, 1H NMR (200 MHz, (CD3)2CO):
1.78 (2H, m, CH2), 2.47–2.52 (2H, m, CH2–CO), 3.63–3.67 (2H, m,
CH2–N), 8.80 (2H, bs, OH and NH). 13C NMR (50 MHz, (CD3)2CO):
22.5, 27.9 ((CH3)3C), 32.7 (CH2–CO), 35.4 ((CH3)3C), 59.7 (CH2N),
d 1.09 (9H, s, C(CH3)3), 1.73–
d
d
OCH3), 3.80–3.95 (3H, m), 6.93–7.02 (2H, m, Ar–H), 7.58–7.66 (2H,
m, Ar–H). 13C NMR (50 MHz, CDCl3): 25.4, 50.5, 52.3 (OCH3), 60.5
2
1
2
90.2 (sp, JCF = 32.3 Hz, (CF3)2C), 121.3 (q, JCF = 290.3 Hz, 2CF3),
185.1 (C O). 19F NMR (188 MHz, (CD3)2CO):
(CH2N), 78.5 (q, JCF = 27.6 Hz, CF3C), 114.5 (Ar), 124.2 (q,
d
À81.8 (s, 2CF3). Anal.
1JCF = 288.6 Hz, CF3), 129.6 (Ar), 130.8 (Ar), 166.4 (d,
1JCF = 248.8 Hz, CAr–F), 167.9 (CO2CH3), 170.0 (C N). 19F NMR
Calcd. for C11H17F6NO2Á2H2O: C, 38.3; H, 6.1. Found: C, 38.5; H, 6.0.
(188 MHz, CDCl3):
d
À107.0 (1F, bs, Ar–F), À72.9 (3F, s, CF3). Anal.
4.3. General procedure for the reaction of cyclic imines with
methyl trifluoropyruvate
Calcd. for C14H13F4NO3: C, 52.7; H, 4.1. Found: C, 52.5; H, 4.2.
Methyl 3,3,3-trifluoro-2-hydroxy-2-[5-(2-furyl)-3,4-dihydro-2H-
pyrrol-4-yl]propanoate (4f), white crystals, mp 134–135 8C, 1H
A solution of methyl trifluoropyruvate (10 mmol) in 5 ml of
ether was added dropwise to a stirred solution of corresponding
cyclic imine (10 mmol) in 25 ml of appropriate solvent (ether for
4a, 1/1 mixture of hexane and ether for 4b–f, and 1/1 mixture of
ether and dichloromethane for 4g) at 0 8C under dry atmosphere.
The cooling bath was removed and mixture was stirred at room
temperature for 12 h. Then the reaction mixture was cooled again
to 0 8C, the crystal solid was filtered and dried in dry box at room
temperature.
NMR (200 MHz, (CD3)2SO): d 1.94–2.10 (1H, m), 2.15–2.34 (1H, m),
3
3.59 (3H, s, OCH3), 3.77–3.98 (3H, m), 6.57 (1H, dd, JHH = 3.4 Hz,
3JHH = 1.6 Hz, Ar–H), 6.81 (1H, d, 3JHH = 3.4 Hz, Ar–H), 7.09 (1H, bs,
3
OH), 6.81 (1H, d, JHH = 1.6 Hz, Ar–H). 13C NMR (50 MHz,
(CD3)2SO):
d 25.6, 50.9, 53.5 (OCH3), 60.2 (CH2N), 79.2 (q,
2JCF = 29.5 Hz, CF3C), 111.8 (Ar), 112.4 (Ar), 124.2 (q,
1JCF = 288.6 Hz, CF3), 144.7 (Ar), 149.3 (Ar), 160.7 (C N), 168.3
(CO2CH3). 19F NMR (188 MHz, (CD3)2SO):
d
À72.2 (s, CF3). EIMS
70 eV, m/z (rel. int.): 291 [M]+ (21), 232 [M–CO2CH3]+ (5), 134 [M-
157]+ (100). HRMS (EI): calcd. for C12H12F3NO4 (M) 291.0718;
found 291.0718.
Methyl
fluoro-2-hydroxypropanoate (4a), white crystals, mp 147–148 8C,
1H NMR (200 MHz, CDCl3):
1.22 (9H, s, C(CH3)3), 1.91–2.12 (1H,
m), 2.36–2.46 (1H, m), 3.47–3.55 (1H, m), 3.68–4.04 (5H, m, incl.
3.83 (3H, s, OCH3)). 13C NMR (50 MHz, CDCl3):
28.0, 29.2
2-(5-tert-butyl-3,4-dihydro-2H-pyrrol-4-yl)-3,3,3-tri-
d
Methyl 3,3,3-trifluoro-2-hydroxy-2-[5-(4-pyridyl)-3,4-dihydro-
2H-pyrrol-4-yl]propanoate (4g), yellowish crystals, mp 138–
d
139 8C, 1H NMR (200 MHz, (CD3)2SO):
d 1.93–2.27 (2H, m), 3.73
(C(CH3)3), 37.1 (C(CH3)3), 50.6, 54.2 (OCH3), 59.1 (CH2N), 79.5 (q,
2JCF = 28.4 Hz, CF3C), 118.8 (q, 1JCF = 288.2 Hz, CF3), 159.0 (CO2CH3),
(3H, s, OCH3), 3.78–3.95 (2H, m, CH2N), 4.12 (1H, d, 3JHH = 10.2 Hz,
CH–C N), 7.25 (1H, bs, OH), 7.60 (2H, d, 3JHH = 6.1 Hz, Ar–H), 8.61
162.6 (C N). 19F NMR (188 MHz, CDCl3):
d
À75.6 (s, CF3). EIMS
(2H, d, JHH = 6.1 Hz, Ar–H). 13C NMR (90 MHz, (CD3)2SO):
d
28.3,
3
70 eV, m/z (rel. int.): 281 [M]+ (17), 266 [M–CH3]+ (100), 222 [M–
CO2CH3]+ (14). HRMS (EI): calcd. for C12H18F3NO3 (M) 281.1239;
found 281.1244.
51.2, 54.6 (OCH3), 61.6 (CH2N), 80.4 (q, 2JCF = 27.3 Hz, CF3C), 123.5
(2C, Ar), 124.9 (q, 1JCF = 287.8 Hz, CF3), 144.7 (Ar), 150.7 (Ar), 169.5
(CO2CH3), 171.3 (C N). 19F NMR (188 MHz, (CD3)2SO):
CF3). Anal. Calcd. for C13H13F3N2O3: C, 51.6; H, 4.3. Found: C, 51.0;
H, 4.3.
d
À73.3 (s,
Methyl 3,3,3-trifluoro-2-hydroxy-2-(5-phenyl-3,4-dihydro-2H-
pyrrol-4-yl)propanoate (4b), white crystals, mp 156–158 8C, 1H
NMR (200 MHz, CDCl3):
3.90–4.16 (3H, m), 7.35–7.45 (3H, m, Ar–H), 7.66–7.71 (2H, m, Ar–
H). 13C NMR (50 MHz, CDCl3):
27.9, 49.8, 54.4 (OCH3), 60.4
(CH2N), 79.7 (q, 2JCF = 29.7 Hz, CF3C), 123.2 (q, 1JCF = 288.4 Hz, CF3),
127.9 (Ar), 128.0 (Ar), 130.0 (Ar), 169.6 (CO2CH3), 171.4 (C N). 19
NMR (188 MHz, CDCl3):
301 [M]+ (8), 242 [M–CO2CH3]+ (9), 144 [M–F3CC(OH)CO2CH3]+
(64), 117 [M-184]+ (100). HRMS (EI): calcd. for C14H14F3NO3 (M)
301.0926; found 301.0918.
d 2.07–2.38 (2H, m), 3.85 (3H, s, OCH3),
4.4. General procedure for the reaction of cyclic imines with
trichloroacetaldehyde
d
F
A solution of trichloroacetaldehyde (10 mmol) in 5 ml of ether
was added dropwise to a stirred solution of corresponding cyclic
imine (10 mmol) in 25 ml of ether at 0 8C under dry atmosphere.
The cooling bath was removed and mixture was stirred at room
temperature for 12 h. Then the reaction mixture was cooled again
d
À74.3 (s, CF3). EIMS 70 eV, m/z (rel. int.):

642
N.E. Shevchenko et al. / Journal of Fluorine Chemistry 129 (2008) 637–644
to 0 8C, the crystal solid was filtered and dried in dry box at room
temperature.
2,2,2-Trichloro-1-(5-pyridin-4-yl-3,4-dihydro-2H-pyrrol-4-
yl)ethanol (5g), white crystals, mp 192–194 8C (dec.), 1H NMR
1-(5-tert-Butyl-3,4-dihydro-2H-pyrrol-4-yl)-2,2,2-trichloroetha-
nol (5a), white crystals, mp 169–170 8C, 1H NMR (200 MHz,
(200 MHz, (CD3)2SO): d 1.94–2.13 (1H, m), 2.53–2.64 (1H, m),
3.96–4.01 (2H, m), 4.15–4.22 (2H, m, incl. 4.18 (1H, d, 3JHH = 6.4 Hz,
3
(CD3)2SO):
(1H, m), 3.54–3.72 (3H, m), 4.52 (1H, d, JHH = 6.4 Hz, HO–CH)),
6.66 (1H, d, 3JHH = 6.4 Hz, HO–CH). 13C NMR (50 MHz, (CD3)2SO):
d
1.20 (9H, s, C(CH3)3), 1.64–1.84 (1H, m), 2.46–2.65
HO–CH)), 6.94 (1H, d, JHH = 6.4 Hz, HO–CH), 7.71 (2H, d,
3
3
3JHH = 5.9 Hz, Ar–H), 8.72 (2H, d, JHH = 5.9 Hz, Ar–H). 13C NMR
d
(90 MHz, (CD3)2SO): d 24.3, 50.6, 63.0 (NCH2), 80.9 (CCl3C), 105.3
24.9, 30.3 (C(CH3)3), 36.9, 50.2, 60.8 (NCH2), 81.1 (CCl3C), 105.2
(CCl3), 183.1 (C N). EIMS 70 eV, m/z (rel. int.): 256 [M–CH3]+ (7),
236 [M–Cl]+ (34), 154 [M–CCl3]+ (14), 71 [M-200]+ (100). HRMS
(EI): calcd. for C10H1635Cl2NO (M–Cl) 236.0616; found 236.0609.
2,2,2-Trichloro-1-(5-phenyl-3,4-dihydro-2H-pyrrol-4-yl)ethanol
(5b), white crystals, mp 203–204 8C (dec.), 1H NMR (200 MHz,
(CCl3), 123.3 (Ar), 141.8 (Ar), 151.7 (Ar), 172.4 (C N). EIMS 70 eV,
m/z (rel. int.): 292 [M]+ (13), 257 [M–Cl]+ (12), 175 [M–CCl3]+ (40),
71 [M-221]+ (100). HRMS (EI): calcd. for C11H1135Cl3N2O (M)
291.9937; found 291.9931.
4.5. General procedure for the reduction of compounds 4d–f and 5d–g
(CD3)2SO):
d 1.92–2.11 (1H, m), 2.54–2.66 (1H, m), 3.84–4.04 (2H,
m), 4.16–4.21 (1H, m), 4.26 (1H, d, 3JHH = 6.4 Hz, HO–CH), 6.90 (1H,
d, 3JHH = 6.4 Hz, HO–CH), 7.47–7.51 (3H, m, Ar–H), 7.80–7.85 (2H,
Sodium borohydride (0.5 g, 13 mmol) was portion wise added
to a stirred solution of corresponding adducts 4 or 5 (5 mmol) in
15 ml of methanol at À25 8C under nitrogen atmosphere. After
stirring for 3 h at this temperature the cooling bath was removed
and mixture was stirred for additional 3 h at room temperature.
Then methanol was removed in vacuum, the residue was quenched
with saturated NaHCO3 and extracted with ethylacetate. The
extract was dried under Na2SO4, solvent was removed and residual
solid was dried in vacuum.
m, Ar–H). 13C NMR (50 MHz, (CD3)2SO):
d 23.6, 49.8, 61.8 (NCH2),
80.6 (CCl3C), 105.0 (CCl3), 128.5 (Ar), 129.3 (Ar), 130.9 (Ar), 133.9
(Ar), 172.9 (C N). EIMS 70 eV, m/z (rel. int.): 291 [M]+ (10), 174
[M–CCl3]+ (26), 144 [M–Cl3CCHOH]+ (10), 71 [M-220]+ (100).
HRMS (EI): calcd. for C12H12Cl3NO (M) 290.9985; found 290.9995.
2,2,2-Trichloro-1-[5-(4-methylphenyl)-3,4-dihydro-2H-pyrrol-4-
yl]ethanol (5c), white crystals, mp 197–198 8C (dec.), 1H NMR
(200 MHz, (CD3)2SO):
d
1.88–2.08 (1H, m), 2.23 (3H, s, Ar–CH3),
Methyl 3,3,3-trifluoro-2-hydroxy-2-[2-(4-methoxyphenyl)-pyr-
roidinel-3-yl]propanoate (6d), white crystals, mp 137–138 8C, 1H
NMR (200 MHz, (CD3)2SO): d 1.80–1.90 and (1H, m), 1.24–2.41 (1H,
2.54–2.69 (1H, m), 3.84–3.95 (2H, m), 4.07–4.12 (1H, m), 4.26 (1H,
d, 3JHH = 6.4 Hz, HO–CH)), 6.74 (1H, d, 3JHH = 6.4 Hz, HO–CH), 7.22
3
3
(2H, d, JHH = 7.8 Hz, Ar–H), 7.69 (2H, d, JHH = 7.8 Hz, Ar–H). 13C
m), 2.64–2.77 (1H, m), 2.88–3.02 (1H, m), 3.20 (3H, s, Ar–OCH3),
3.70 (3H, s, OCH3), 3.22–3.28 (1H, m, CH-3), 4.32 (1H, d,
3JHH = 7.3 Hz, CH-2), 6.72–6.76 (2H, m, Ar–H), 7.08–7.13 (2H, m,
Ar–H). 13C NMR (50 MHz, (CD3)2SO): 25.4, 45.2, 48.1, 52.4
NMR (50 MHz, (CD3)2SO): d 20.9 (CH3–Ar), 22.9, 49.0, 60.9 (NCH2),
80.0 (CCl3C), 104.3 (CCl3), 127.8 (Ar), 129.2 (Ar), 130.4 (Ar), 140.1
(Ar), 172.1 (C N). EIMS 70 eV, m/z (rel. int.): 305 [M]+ (12), 188
[M–CCl3]+ (28), 131 [M-174]+ (54), 118 [M-187]+ (100). HRMS (EI):
calcd. for C13H1435Cl2NO (M–Cl) 305.0141; found 305.0142.
2,2,2-Trichloro-1-[5-(4-methoxyphenyl)-3,4-dihydro-2H-pyrrol-
4-yl]ethanol (5d), white crystals, mp 183–184 8C (dec.), 1H NMR
2
(CO2CH3), 54.9 (Ar–OCH3), 61.1 (CH2N), 77.5 (q, JCF = 26.9 Hz,
1
CF3C), 112.4 (Ar), 125.1 (q, JCF = 289.6 Hz, CF3), 130.2 (Ar), 134.7
(Ar), 134.7 (Ar), 167.2 (CO2CH3). 19F NMR (188 MHz, (CD3)2SO):
d
À76.0 (s, CF3). EIMS 70 eV, m/z (rel. int.): 333 [M]+ (31), 274 [M–
CO2CH3]+ (94), 264 [M–CF3]+ (30), 148 [M-185]+ (100). HRMS (EI):
calcd. for C15H18F3NO4 (M) 333.1188; found 315.1172.
(200 MHz, (CD3)2SO): d 1.86–2.06 (1H, m), 2.42–2.61 (1H, m), 3.79
(3H, s, OCH3), 3.84–3.91 (2H, m), 4.08–4.12 (1H, m), 4.25 (1H, d,
3JHH = 6.5 Hz, HO–CH), 6.88 (1H, d, 3JHH = 6.5 Hz, HO–CH), 7.02 (2H,
Methyl 3,3,3-trifluoro-2-[2-(4-fluorophenyl)-pyrrolidin-3-yl]-2-
hydroxypropanoate (6e), white crystals, mp 117–118 8C, 1H NMR
3
3
d, JHH = 8.3 Hz, Ar–H), 7.77 (2H, d, JHH = 8.3 Hz, Ar–H). 13C NMR
(50 MHz, (CD3)2SO):
d
24.4, 50.3, 56.6 (OCH3), 62.3 (NCH2), 81.5
(200 MHz, CDCl3): d 1.82–1.91 (1H, m), 2.23–2.53 (1H, m), 2.74–
3
(CCl3C), 105.8 (CCl3), 115.4 (Ar), 127.0 (Ar), 130.8 (Ar), 162.1 (Ar),
172.6 (C N). EIMS 70 eV, m/z (rel. int.): 321 [M]+ (34), 204 [M–
CCl3]+ (28), 131 [M-174]+ (52), 134 [M-187]+ (100). HRMS (EI):
calcd. for C13H1435Cl3NO2 (M) 321.0090; found 321.0093.
2,2,2-Trichloro-1-[5-(4-fluorophenyl)-3,4-dihydro-2H-pyrrol-4-
yl]ethanol (5e), white crystals, mp 181–182 8C (dec.), 1H NMR
3.04 (3H, m), 3.24 (3H, s, OCH3), 4.33 (1H, d, JHH = 7.3 Hz, CH-2),
6.95–7.03 (2H, m, Ar–H), 7.19–7.26 (2H, m, Ar–H). 13C NMR
(50 MHz, CDCl3): 25.8, 45.2, 48.0, 52.4 (OCH3), 60.8 (CH2N), 77.5 (q,
2JCF = 26.8 Hz, CF3C), 113.5 (d, 2JCF = 21.2 Hz, C-3 and C-5 Ar), 124.3
1
2
(q, JCF = 289.7 Hz, CF3), 130.5 (d, JCF = 7.1 Hz, C-2 and C-6 Ar),
139.2 (Ar), 161.0 (d, JCF = 243.0 Hz, CAr–F), 167.9 (CO2CH3). 19F
1
(200 MHz, (CD3)2SO):
d
1.89–2.09 (1H, m), 2.52–2.64 (1H, m),
NMR (188 MHz, CDCl3):
d
À117.2 (1F, bs, Ar–F), À75.9 (3F, s, CF3).
3.82–4.02 (2H, m), 4.11–4.22 (2H, m, incl. 4.20 (1H, d, 3JHH = 6.8 Hz,
HO–CH)), 6.91 (1H, d, 3JHH = 6.8 Hz, HO–CH), 7.27–7.37 (2H, m, Ar–
EIMS 70 eV, m/z (rel. int.): 321 [M]+ (8), 262 [M–CO2CH3]+ (36), 252
[M–CF3]+ (9), 135 [M-186]+ (100). HRMS (EI): calcd. for
C14H15F4NO3 (M) 321.0988; found 321.0967.
H), 7.82–7.89 (2H, m, Ar–H). 13C NMR (50 MHz, (CD3)2SO):
d 22.9,
49.0, 61.0 (NCH2), 79.7 (CCl3C), 104.0 (CCl3), 115.5 (d,
Methyl 3,3,3-trifluoro-2-[2-(2-furyl)-pyrrolidin-3-yl]-2-hydroxy-
propanoate (6f), white crystals, mp 117–118 8C, 1H NMR (200 MHz,
(CD3)2SO): d 1.85–1.87 (1H, m), 2.03–2.18 (1H, m), 2.83–2.90 (2H,
2
2JCF = 22.0 Hz, C-5 and C-3 Ar), 129.7 (Ar), 130.0 (d, JCF = 8.8 Hz,
C-2 and C-6 Ar), 163.0 (d, 1JCF = 248.1 Hz, CAr–F), 170.9 (C N). 19
F
NMR (188 MHz, CD3CN):
d
À110.99 (m, Ar–F). EIMS 70 eV, m/z (rel.
m), 3.11–3.15 (1H, m, CH-3), 3.68 (3H, s, OCH3), 4.21 (1H, d,
3JHH = 7.4 Hz, CH-2), 6.08 (1H, d, 3JHH = 3.4 Hz, Ar–H), 6.28 (1H, dd,
3JHH = 3.4 Hz, 3JHH = 1.6 Hz, Ar–H), 7.45 (1H, d, 3JHH = 1.6 Hz, Ar–H).
int.): 309 [M]+ (28), 192 [M–CCl3]+ (79), 135 [M-174]+ (100). HRMS
(EI): calcd. for C12H1135Cl3NO (M) 308.9890; found 308.9887.
2,2,2-Trichloro-1-[5-(2-furyl)-3,4-dihydro-2H-pyrrol-4-yl]etha-
nol (5f), white crystals, mp 172–173 8C (dec.), 1H NMR (200 MHz,
13C NMR (50 MHz, (CD3)2SO):
d 25.4, 45.0, 45.4, 53.5 (OCH3), 57.0
(CH2N), 77.7 (q, JCF = 27.3 Hz, CF3C), 108.0 (Ar), 110.4 (Ar), 124.6
2
(CD3)2SO):
d
1.87–1.96 (1H, m), 2.45–2.60 (1H, m), 3.84–3.94 (3H,
(q, 1JCF = 289.7 Hz, CF3), 142.0 (Ar), 154.9 (Ar), 168.8 (CO2CH3). 19
NMR (188 MHz, (CD3)2SO):
int.): 293 [M]+ (17), 234 [M–CO2CH3]+ (33), 224 [M–CF3]+ (9), 115
[M-178]+ (100). HRMS (EI): calcd. for C12H14F3NO4 (M) 293.0875;
found 293.0874.
F
3
m), 4.47 (1H, d, JHH = 6.3 Hz, HO–CH), 6.62–6.65 (1H, m, Ar–H),
6.94–6.98 (2H, m, 1Ar–H and HO–CH), 7.85 (1H, bs, Ar–H). 13C
d
À75.6 (s, CF3). EIMS 70 eV, m/z (rel.
NMR (50 MHz, (CD3)2SO):
d 22.6, 49.9, 61.4 (NCH2), 80.3 (CCl3C),
104.1 (CCl3), 111.9 (Ar), 112.9 (Ar), 145.1 (Ar), 148.9 (Ar) 162.7
(C N). EIMS 70 eV, m/z (rel. int.): 281 [M]+ (22), 164 [M–CCl3]+
(51), 107 [M-174]+ (45), 71 [M-288]+ (100). HRMS (EI): calcd. for
2,2,2-Trichloro-1-[2-(4-methoxyphenyl)-pyrrolidin-3-yl]ethanol
(7d), white crystals, mp 147–148 8C, 1H NMR (200 MHz, (CD3)2SO):
d 1.79–1.93 (1H, m), 2.22–2.33 (1H, m), 2.73–2.85 (2H, m), 3.04–
C
10H1035Cl237ClNO2 (M) 282.9748; found 282.9751.

N.E. Shevchenko et al. / Journal of Fluorine Chemistry 129 (2008) 637–644
643
3.14 (1H, m, CH-3), 3.56 (1H, bs, HOCH), 3.74 (3H, s, OCH3), 4.15
1H NMR (200 MHz, CD3CN):
m), 3.18–3.37 (2H, m), 3.42–3.55 (4H, m, incl. 3.47 (3H, s, CO2CH3)),
3.84 (3H, s, OCH3), 4.66 (1H, s, OH). 13C NMR (50 MHz, CD3CN):
d
1.40–1.60 (1H, m), 1.69–1.92 (3H,
3
(1H, d, JHH = 7.3 Hz, CH-2), 6.37 (1H, bs, OH), 6.89 (2H, d,
3
3JHH = 8.3 Hz, Ar–H), 7.75 (2H, d, JHH = 8.3 Hz, Ar–H). 13C NMR
d
(50 MHz, (CD3)2SO):
d
25.8, 43.9, 45.3, 54.9 (OCH3), 65.3 (NCH2),
22.6, 22.8, 42.3, 46.1 (OCH3), 52.5 (OCH3), 54.4 (CH2N), 79.4 (q,
79.5 (CCCl3), 105.5 (CCl3), 113.4 (Ar), 128.7 (Ar), 133.0 (Ar), 158.0
(Ar–OMe). EIMS 70 eV, m/z (rel. int.): 323 [M]+ (4), 206 [M + H–
CCl3]+ (100). HRMS (EI): calcd. for C13H1635Cl3NO2 (M) 323.0247;
found 321.0249.
2,2,2-Trichloro-1-[2-(4-fluorophenyl)-pyrrolidin-3-yl]ethanol
(7e), white crystals, mp 136–137 8C (dec.), 1H NMR (200 MHz,
2JCF = 27.9 Hz, CF3C), 124.7 (q, 1JCF = 288.1 Hz, CF3), 158.3 (CO2CH3),
170.7 (C N). 19F NMR (188 MHz, CD3CN):
d
À74.1 (s, CF3). EIMS
70 eV, m/z (rel. int.): 269 [M]+ (34), 210 [M–CO2CH3]+ (100), 196
[M-73]+ (52). HRMS (EI): calcd. for C10H14F3NO4 (M) 269.0875;
found 269.0871.
2,2,2-Trichloro-1-(5-methoxy-3,4-dihydro-2H-pyrrol-4-yl)etha-
nol (10a), white crystals, mp 183–184 8C (dec.), 1H NMR (200 MHz,
(CD3)2SO):
d 1.79–1.95 (1H, m), 2.23–2.39 (1H, m), 2.75–2.88 (2H,
m), 3.01–3.15 (1H, m, CH-3), 3.51 (1H, d, 3JHH = 0.9 Hz, HOCH), 4.23
CDCl3):
3.81 (3H, s, OCH3), 4.59 (1H, bs), 5.34 (1H, bs, OH). 13C NMR
(50 MHz, CDCl3): 23.3, 45.7, 53.7 (OCH3), 56.0 (NCH2), 79.7
d 2.05–2.20 (1H, m), 2.46–2.65 (1H, m), 3.47–3.75 (3H, m),
3
(1H, d, JHH = 7.3 Hz, CH-2), 7.10–7.19 (2H, m, Ar–H), 7.32–7.40
(2H, m, Ar–H). 13C NMR (50 MHz, (CD3)2SO):
d
25.8, 43.9, 45.3, 65.0
d
(NCH2), 79.3 (CCl3C), 105.4 (CCl3), 114.7 (d, 2JCF = 21.2 Hz, C-5 and
C-3 Ar), 129.5 (d, 2JCF = 7.1 Hz, C-2 and C-6 Ar), 137.6 (Ar), 161.0 (d,
(CCl3C), 103.2 (CCl3), 171.7 (C N). EIMS 70 eV, m/z (rel. int.): 245
[M]+ (1), 210 [M–Cl]+ (100), 128 [M–CCl3]+ (37). HRMS (EI): calcd.
for C7H1035Cl2NO2 (M–Cl) 210.0089; found 210.0092.
2,2,2-Trichloro-1-(2-methoxy-3,4,5,6-tetrahydropyridin-3-
yl)ethanol (10b), white crystals, mp 191–192 8C (dec.), 1H NMR
1JCF = 241.6 Hz, Ar–F). 19F NMR (188 MHz, CD3CN):
d
À116.7 (m,
Ar–F). EIMS 70 eV, m/z (rel. int.): 311 [M]+ (3), 194 [M–CCl3]+ (100),
136 [M-175]+ (42). HRMS (EI): calcd. for C12H1335Cl37Cl2FNO (M)
314.9988; found 314.9977.
(200 MHz, (CD3)2SO):
d 1.28–1.47 (1H, m), 1.59–2.12 (3H, m),
2,2,2-Trichloro-1-[2-(2-furyl)-pyrrolidin-3-yl]ethanol (7f), white
3.00–3.08 (1H, m), 3.18–3.43 (2H, m), 3.53 (3H, s, OCH3), 4.66 (1H,
crystals, mp 162–163 8C (dec.), 1H NMR (200 MHz, (CD3)2SO):
d
dd, 3JHH = 6.9 Hz, 3JHH = 1.5 Hz, HO–CH), 6.92 (1H, d, 3JHH = 6.9 Hz,
1.79–1.93 (1H, m), 2.07–2.26 (1H, m), 2.61–2.86 (3H, m), 2.91–3.07
HO–CH). 13C NMR (50 MHz, (CD3)2SO):
d 20.2, 21.5, 39.3, 45.6
(NCH2), 52.0 (OCH3), 80.2 (CCl3C), 103.9 (CCl3), 160.0 (C N). EIMS
70 eV, m/z (rel. int.): 224 [M–Cl]+ (100), 142 [M–CCl3]+ (6). HRMS
(EI): calcd. for C8H1235Cl2NO2 (M–Cl) 224.0245; found 224.0248.
3
(1H, m, CH-3), 3.69 (1H, d, JHH = 2.8 Hz, HOCH), 4.26 (1H, d,
3JHH = 7.3 Hz, CH-2), 6.25–6.26 (1H, m, Ar–H), 6.54 (1H, bs, OH),
6.39 (1H, m, Ar–H), 7.57 (1H, bs, Ar–H). 13C NMR (50 MHz,
(CD3)2SO):
d 27.2, 45.5, 45.9, 60.2 (NCH2), 80.9 (CCl3C), 106.2
(CCl3), 107.9 (Ar), 111.0 (Ar), 142.8 (Ar), 156.5 (Ar). EIMS 70 eV, m/z
(rel. int.): 283 [M]+ (19), 165 [M–CCl3]+ (40), 107 [M-176]+ (45), 71
[M-212]+ (100). HRMS (EI): calcd. for C10H1235Cl37Cl2NO2 (M)
286.9875; found 286.9871.
Acknowledgment
The authors thank the Deutsche Forschungsgemeinschaft (436
RUS 113/812/0-1) for financial support of this work.
2,2,2-Trichloro-1-(2-pyridin-4-ylpyrrolidin-3-yl)ethanol
white crystals, mp 193–194 8C (dec.), 1H NMR (200 MHz,
(CD3)2SO): 1.87–1.95 (1H, m), 2.23–2.32 (1H, m), 2.78–2.91
(7g),
References
d
(3H, m), 3.08–3.14 (1H, m, CH-3), 3.49 (1H, bs, HOCH), 4.25 (1H, d,
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3
3JHH = 7.3 Hz, CH-2), 6.44 (1H, bs, OH), 7.77 (2H, d, JHH = 5.0 Hz,
3
Ar–H), 8.5 (2H, d, JHH = 5.0 Hz, Ar–H). 13C NMR (90 MHz,
(CD3)2SO):
d 25.8, 43.9, 45.5, 64.5 (NCH2), 79.3 (CCl3C), 105.3
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d 1.80–1.93 (1H, m), 2.03–2.24 (1H, m),
d
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2
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