Nucleophilic trifluoromethylation of aziridinyl ketones: A convenient access to fluorinated aziridinyl alcohols

Article abstract of DOI:10.1016/j.jfluchem.2013.09.011

A convenient synthesis of α-(aziridin-2-yl)-α-(trifluoromethyl) alcohols starting with ethyl aziridine-2-carboxylates is reported. Grignard reaction with the corresponding Weinreb amides led to aziridin-2-yl ketones, and subsequent treatment with Ruppert-Prakash reagent gave the trimethylsilylated target compounds as mixtures of diastereoisomers, which were desilylated with TBAF. In the case of ethyl 1-((S)-1-phenylethyl)aziridine-2-carboxylate, (S,S)- and (S,R)-aziridin-2-yl ketones were obtained, separated chromatographically and transformed into the desired enantiomerically pure α-trifluoromethylated alcohols.

Full text of DOI:10.1016/j.jfluchem.2013.09.011

Journal of Fluorine Chemistry 156 (2013) 192–197
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Nucleophilic trifluoromethylation of aziridinyl ketones: A convenient
access to fluorinated aziridinyl alcohols
a,
a
a
a
*
´
Grzegorz Mloston , Emilia Obijalska , Paulina Zie˛bacz , Krzysztof Matyszewski ,
Katarzyna Urbaniak a, Anthony Linden b, Heinz Heimgartner b
a
´
´
´
Department of Organic and Applied Chemistry, University of Ło´dz, Tamka 12, PL-91-403 Łodz, Poland
b Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
A R T I C L E I N F O
A B S T R A C T
Article history:
A convenient synthesis of a-(aziridin-2-yl)-a-(trifluoromethyl) alcohols starting with ethyl aziridine-2-
Received 22 July 2013
carboxylates is reported. Grignard reaction with the corresponding Weinreb amides led to aziridin-2-yl
ketones, and subsequent treatment with Ruppert-Prakash reagent gave the trimethylsilylated target
compounds as mixtures of diastereoisomers, which were desilylated with TBAF. In the case of ethyl 1-
((S)-1-phenylethyl)aziridine-2-carboxylate, (S,S)- and (S,R)-aziridin-2-yl ketones were obtained,
Received in revised form 12 September 2013
Accepted 18 September 2013
Available online 27 September 2013
separated chromatographically and transformed into the desired enantiomerically pure
methylated alcohols.
a-trifluoro-
Keywords:
Aziridines
ß 2013 Elsevier B.V. All rights reserved.
Aziridinyl ketones
Aziridinyl alcohols
(Trifluoromethyl)trimethylsilane
Nucleophilic trifluoromethylation
1. Introduction
efficient method for the preparation of a-(aziridin-2-yl)-a-
trifluoromethyl alcohols, including enantiomerically pure exam-
ples.
An important group of aziridine derivatives are aziridinyl
alcohols. They find numerous applications as building blocks for
the preparation of natural compounds [1] and drugs [2]. In
addition, enantiomerically pure aziridinyl alcohols are extensively
used as a new type of potent ligands for asymmetric synthesis [3].
The introduction of fluorine atoms into a molecule of an organic
compound results in significant modifications of its chemical,
physicochemical and biological properties [4]. Fluorinated azir-
idines are rare, and to the best of our knowledge, trifluoromethy-
lated aziridinyl alcohols are not known to date. The nucleophilic
trifluoromethylation with Ruppert–Prakash reagent, i.e., (trifluoro-
methyl)trimethylsilane (CF3SiMe3), is a common procedure for the
2. Results and discussion
The starting aziridinyl ketones were prepared using aziridine-
2-carboxylates 1 [7], which are easily available via the two-step
synthesis outlined in Scheme 1. The second step, leading to the
aziridine, comprises the treatment of 2,3-dibromopropanoate with
benzylamine and (S)-a-methylbenzylamine, respectively.
In both reactions, the required aziridines were obtained in good
yields. The diastereoselectivity in the case of the formation of 1b
was very low and comparable amounts of (S,S)- and (S,R)-1b were
isolated after column chromatography.
conversion of
a-amino aldehydes and a-amino ketones into b-
amino- -trifluoromethyl alcohols [5], an important class of
a
In order to convert aziridine-2-carboxylates
1 into the
fluorinated organic compounds.
corresponding aziridinyl ketones, they were transformed into
their Weinreb amides 2 (Scheme 1) by aminolysis with methoxy
(methyl)amine in dichloromethane at 10 8C [1d]. Subsequent
reaction of 2 with an appropriate Grignard reagent (MeMgBr,
PhMgBr), led to the corresponding aziridinyl ketones 3 [1d,10–12].
After column chromatography they were obtained as pure
substances in satisfactory yields.
Aziridinyl ketones are attractive building blocks, which found
diverse applications in the synthesis of aziridinyl-functionalized
products, including aziridinyl alcohols [1a,6]. However, they have
never been explored for the preparation of fluorinated represen-
tatives. The goal of the present study was the elaboration of an
The nucleophilic trifluoromethylation of C55X bonds (X55O, N, S)
has been studied extensively and excellent reviews related to this
problem appeared over the last two decades [13]. Typically,
*
Corresponding author. Tel.: +48 42 635 57 61.
E-mail address: gmloston@uni.lodz.pl (G. Mloston´ ).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.09.011

G. Mloston´ et al. / Journal of Fluorine Chemistry 156 (2013) 192–197
193
O
OMe
CO2Et
N
Br
.
Br2
Me(MeO)NH HCl
Ph(R)CHNH2
Et3N, MeOH
N
N
Me
Br
CO2Et
CO2Et
85%
CCl4
AlMe3, CH2Cl2
R
Ph
R
Ph
1a R = H (76%)
(S,S)/(S,R)-1b R = Me (40%/41%)
2a R = H (85%) [8]
(1'S,2S)-2b R = Me (96%) [9]
(1'S,2R)-2b R = Me (86%)
THF, -78 oC
R'MgBr
O
R'
N
R
Ph
3a R = H, R' = Me (44%) [10]
3b R = H, R' = Ph (55%) [8, 11]
(1'S,2S)-3c R = R' = Me (28%) [1d]
(1'S,2S)-3d R = Me, R' = Ph (33%) [1d]
(1'S,2R)-3e R = Me, R' = Ph (42%) [12]
Scheme 1. Synthesis of aziridinyl ketones 3.
reactions of CF3SiMe3 with ketones are performed in THF solution
using tetrabutylammonium fluoride (TBAF) as a catalyst. However,
an alternative protocol, based on the use of cesium fluoride (CsF) as
a catalyst, without any solvent, is also known [14]. For example,
(minor) was detected at Rf = 0.10 (developed in CH2Cl2/pentane
(1:4) mixture). Based on this observation, the mixtures of the
diastereoisomeric products 4 were separated by column chroma-
tography, and some of them were desilylated by treatment with
tetrabutylammonium fluoride (TBAF) in THF solution yielding the
non-protected alcohols 5 (Scheme 2). These products decomposed
during attempted chromatography on a silica gel column, and
distillation under reduced pressure was applied to obtain
analytically pure samples.
The typical protocol for desilylation of trifluoromethylated
ethers 4 using aqueous hydrochloric acid [14] could not be applied
as aziridine derivatives are known to undergo a ring opening
reaction upon treatment with strong acids [15].
under these conditions,
a,b-unsaturated ketones are converted
into trifluoromethylated alcohols in a regioselective manner [14c].
In our study, the trifluoromethylation of ketones 3 was performed
in absolute dimethoxyethane (DME) with CF3SiMe3 using dry CsF
as a catalyst. In all cases, the silylated alcohols 4 (Scheme 2) were
obtained as mixtures of diastereoisomers, and the dr values (1:1–
8:2) were determined by 19F NMR or 1H NMR spectroscopy. The
highest value was found in the case of 4a and 4b (59%) (Table 1).
The preliminary TLC analysis (SiO2) of the crude mixtures showed
that the isomeric products 4 differ in polarity and can be separated
chromatographically. For example, in the case of the mixture 4c/
4c0, the fast (major) isomer 4c showed Rf = 0.22 and the slow
In the IR spectrum of 5c, a characteristic broad absorption of the
OH group was observed at 3416 cmꢀ1. In the 13C NMR spectrum of
5c, the absorptions of the aziridine C-atoms appeared at 29.8 (CH2)
OH
CF3
R'
O
OSiMe3
CF3
R'
TBAF
CF3SiMe3
CsF, DME
R'
N
N
N
THF, room temp.
R
Ph
R
R
Ph
Ph
5a
5a'
5b
5b'
4a R = H, R' = Me (fast)
4a' R = H, R' = Me (slow)
4b R = H, R' = Ph (fast)
R = H, R' = Me
R = H, R' = Me
R = H, R' = Ph
R = H, R' = Ph
3a R = H, R' = Me
3b R = H, R' = Ph
(1'S,2S)-3c R = R' = Me
4b' R = H, R' = Ph (slow)
(1'S,2S)-3d R = Me, R' = Ph
(1'S,2R)-3e R = Me, R' = Ph
5c
(1''S,2'S,2S)-4c R = R' = Me (fast)
(1''S,2'S,2R)-4c' R = R' = Me (slow)
(1''S,2'S,1S)-4d R = Me, R' = Ph (fast)
(1''S,2'S,1R)-4d' R = Me, R' = Ph (slow)
(1''S,2'R,1S)-4e R = Me, R' = Ph (fast)
(1''S,2'R,1R)-4e' R = Me, R' = Ph (slow)
(1''S,2'S,2S)-
R = R' = Me
5d
5d'
5e
(1''S,2'S,1S)-
(1''S,2'S,1R)-
(1''S,2'R,1S)-
R = Me, R' = Ph
R = Me, R' = Ph
R = Me, R' = Ph
Scheme 2. Nucleophilic trifluoromethylation of aziridinyl ketones 3 with Ruppert-Prakash reagent.

194
G. Mloston´ et al. / Journal of Fluorine Chemistry 156 (2013) 192–197
Table 1
hydrogen bonds. One is an intramolecular interaction with the
N-atom forming a loop with a graph set motif [18] of S(5). The
other is an intermolecular interaction with the N-atom of a
neighboring molecule, which links pairs of molecules into C2-
symmetric dimers and can be described by a graph set motif of
R22ð10Þ. Both interactions considered together form a R22ð4Þ loop.
Trifluoromethylation of aziridinyl ketones 3 and desilylation of ethers 4.
Substrate
dr (4:40)a
Yield (%)
Total
Yield (%)
4 (fast)b
5
50
40 (slow)b
3a
2:8
2:8
6:4
5:5
8:2
59
64
49
64
46
10
49
41
45
3. Conclusions
3b
20
44
33
24
The results of this study show that the nucleophilic trifluoro-
methylation of aziridinyl ketones using the Ruppert–Prakash
reagent opens a convenient access to trifluoromethylated azir-
idinyl alcohols. In the case of aziridinyl ketones bearing the
(10S,2S)-3c
(10S,2S)-3d
(10S,2R)-3e
31
18c
71
–
34
30
28
33
stereochemically defined
a-methylbenzyl residue at the N-atom,
44
2c
88
–
the trifluoromethylation occurs diastereoselectively, with higher
dr values in the case of the phenyl ketones. The obtained
trifluoromethylated aziridinyl alcohols and their O-silylated
derivatives are potentially useful, new ligands for asymmetric
synthesis. Moreover, due to the usefulness of aziridines in the
synthesis of more complex heterocycles [19], products 4 and 5 can
be considered as attractive building blocks for the preparation of
fluorinated heterocycles.
a
dr Values were determined spectroscopically (19F NMR or 1H NMR).
b ‘Fast’ relates to the less polar fraction isolated after chromatographic separation on
silica gel, and ‘slow’ relates to the more polar fraction, respectively.
c
Compound was isolated as a minor product contaminated with substantial
amounts of the appropriate isomer of fast-4.
and 40.8 (CH) ppm. The signal of the C–OH group was detected as a
2
quartet with JF,C = 28.5 Hz at 70.0 ppm, and the CF3 group
4. Experimental part
1
absorbed at 125.9 ppm as a quartet with JF,C = 282.1 Hz. The
ESI-MS showed the [M+1]+ peak at m/z = 260, which confirms the
molecular formula C13H16F3NO.
4.1. General information
Finally, the structure of the aziridinyl alcohol 5c, obtained from
the faster moving (TLC) trimethylsilyl-protected precursor 4c, was
established by X-ray crystallography (Fig. 1). The space group
permits the compound in the crystal to be enantiomerically pure,
but the absolute configuration of the molecule has not been
determined. The enantiomer used in the refinement was based on
The 1H, 13C{1H} and 19F NMR spectra were recorded on a Bruker
Avance III 600 spectrometer using the solvent signal as a reference.
Assignments of signals in 13C NMR spectra were made on the basis
of HMQC experiments. The IR spectra were measured using a
NEXUS FT-IR spectrophotometer. The ESI-MS spectra were
obtained using a Varian 500 MS LC Ion Trap spectrometer. Optical
rotation was measured on a Perkin-Elmer 241 MC polarimeter at
the known (S)-configuration of the
a-methylbenzyl substituent at
N(1), which had been introduced into the molecule as (S)-
a
-
l = 589 nm in CHCl3. Melting points were determined in capillaries
methylbenzylamine (Scheme 1). On this basis, the configuration of
5c is (100S,20S,2S) [17]. The hydroxy group forms bifurcated
on a Melt-Temp II apparatus.
4.2. Materials
Commercial ethyl acrylate, benzylamine, (S)-1-phenylethyl-
amine, O-methylhydroxylamine hydrochloride, tetrabutylammo-
nium fluoride (1 M, solution in THF), methylmagnesium bromide
(3 M, solution in THF) and trimethylaluminium were purchased
from Sigma–Aldrich and (trifluoromethyl)trimethylsilane from
Fluorochem. Aziridinyl carboxylates 1 and the corresponding
Weinreb amides 2 were prepared according to the method
described in Ref. [1d]. Benzaldehyde was distilled prior to use.
Solvents used in the study (THF, DME, toluene, and benzene) were
dried over sodium, CH2Cl2 over sodium hydride, and freshly
distilled prior to use. The aziridine amides 2a, (S,S)- and (S,R)-2b
were prepared according to known procedures [8,9].
4.3. Reactions of Weinreb amides with Grignard reagents – general
procedure
A Weinreb amide 2 (10 mmol) was dissolved in an anhydrous
solvent (15 ml) (THF for reactions with MeMgBr or Et2O for
reactions with PhMgBr) and placed in a three-neck round-bottom
flask equipped with a mechanic stirrer. In each reaction, a three-
fold molar amount of Grignard reagent was used. The reaction flask
was cooled to ꢀ78 8C in a cooling bath and subsequently a solution
of Grignard reagent was added drop-wise. After 0.5 h, the cooling
bath was removed and the solution was slowly warmed to room
temperature. The progress of the reaction was monitored by TLC
(AcOEt). The reaction was quenched with a saturated aqueous
solution of NaCl and extracted with Et2O (3 ꢁ 50 ml), the combined
Fig. 1. ORTEP Plot [16] of the molecular structure of aziridinyl alcohol (100S,20S,2S)-
5c (50% probability ellipsoids; arbitrary numbering of atoms).

G. Mloston´ et al. / Journal of Fluorine Chemistry 156 (2013) 192–197
195
organic layers were dried over MgSO4, filtered, and the solvents
were removed under reduced pressure. Products were purified by
column chromatography on silica gel with AcOEt/hexane (1:9) (for
compounds 3a,c,e) or AcOEt/petroleum ether (2:8) (for compounds
3b,d,f) as eluent.
4a,b and 4a0,b0 or CH2Cl2/pentane (1:4) for derivatives 4c–e and
4c0–e0.
4.5. Desilylation of trimethylsilyl ethers with tetrabutylammonium
fluoride (TBAF) – general procedure
2-Acetyl-1-benzylaziridine (3a) [10]. Yield: 0.77 g (44%). Brown
oil. Spectroscopic data in agreement with Ref. [10]. 1H NMR (CDCl3,
The corresponding silyl ether 4 (1.0 mmol) was dissolved in
anhydrous THF, and a solution of TBAF (1.1 ml, 1.1 mmol) was
added dropwise while the reaction flask was cooled in an ice-bath.
The progress of the reaction was monitored by TLC. Subsequently,
the reaction was quenched with a sat. aqueous solution of NaCl
(10 ml), and the obtained mixture was extracted with CH2Cl2
(3 ꢁ 15 ml). The organic layers were combined and dried over
anhydrous MgSO4. After filtration, the solvents were evaporated,
and the crude products were purified by microdistillation (external
temperature 150–160 8C, p = 0.1 hPa, Kugelrohr).
2
3
600 MHz):
d 1.83 (dd, 1H, JH,H = 2.5 Hz, JH,H = 5.2 Hz, H(B)C(3)),
2.07 (s, 3H, CH3CO), 2.23–2.24 (m, 2H, H(A)C(3), HC(2)), 3.47, 3.57
(AB-system, 2H, 2JH,H = 13.2 Hz, CH2Ph), 7.30–7.34 (m, 5 arom. CH).
2-Benzoyl-1-benzylaziridine (3b) [8,11]. Yield: 1.31 g (55%).
Brown oil. Spectroscopic data in agreement with Ref. [11]. 1H-
NMR (CDCl3, 600 MHz): d
1.93 (dd, 1H, 2JH,H = 1.3 Hz, 3JH,H = 6.4 Hz,
H
(B)C(3)), 2.44 (dd, 1H, 2JH,H = 1.4 Hz, 3JH,H = 3.2 Hz, H(A)C(3)), 2.99
(dd, 1H, 2JH,H = 3.2 Hz, 3JH,H = 6.5 Hz, HC(2)), 3.54, 3.83 (AB system,
2
2H, JH,H = 13.8 Hz, CH2Ph), 7.26–7.56 and 7.92–7.94 (2 m, 10
arom. CH).
2-Acetyl-(10S,2S)-1-(10-phenylethyl)aziridine ((S,S)-3c) [1d].
4.6. Spectroscopic data are given for the diastereoisomers of the
desilylated products
Yield: 0.54 g (28%). Brown oil. 1H-NMR (CDCl3, 600 MHz):
d
1.42
(d, JH,H = 6.6 Hz, 3H, PhCHCH3), 1.66 (d, JH,H = 6.8 Hz, 1H,
(B)C(3)), 2.06 (d, 3JH,H = 2.9 Hz, 1H, H(A)C(3)), 2.08 (s, 3H, CH3CO),
3
3
H
1-Benzyl-2-[2,2,2-trifluoro-1-methyl-1-(trimethylsilyloxy)ethyl]-
aziridine (fast, 4a). Yield: 75 mg (10%), colorless oil (contaminated
by ca. 9% of 4a0).
3
3
2.21 (dd, JH,H = 3.1 Hz, JH,H = 6.8 Hz, 1H, HC(2)), 2.55 (q, 1H,
3JH,H = 6.5 Hz, PhCHCH3), 7.25–7.39 (m, 5 arom. CH). 13C-NMR
(CDCl3, 150 MHz):
(CH), 69.5 (PhCHCH3); 126.7, 127.3, 128.4 (5 arom. CH), 143.9 (1
d
23.3 (CH3), 24.6 (PhCHCH3), 34.2 (CH2), 45.8
2-(1-Benzylaziridin-2-yl)-1,1,1-trifluoropropan-2-ol (5a). Yield:
100 mg (41%). Colorless crystals, m.p. 68–72 8C (contaminated by
arom. C), 207.6 (C55O). IR (KBr):
n
3027m, 2966s, 1701vs (C55O),
ca. 6% of 5a0). 1H NMR (CDCl3, 600 MHz):
d
1.14 (s, 3H, CH3), 1.62 (d,
1583m, 1494m, 1352s, 1264s, 700vs cmꢀ1. HR-ESI-MS (MeOH+-
1H, CH2CH, JH,H = 6.6 Hz), 1.77 (dd, 1H, CH2CH, JH,H = 3.0 Hz,
3JH,H = 6.6 Hz), 2.13 (d, 1H, CH2CH, 3JH,H = 3.0 Hz), 3.25 (s, 1H, OH),
3.24, 3.32 (AB system, 2H, CH2Ph, 2JH,H = 13.2 Hz), 7.30–7.37 (m, 5
3
3
NaI): 212.10454 (212.10459 calcd. for C12H15NaNO, [M+Na]+).
½
a 2D5
ꢂ
¼ ꢀ129:1 (c = 0.5; CHCl3).
2-Benzoyl-(10S,2S)-1-(10-phenylethyl)aziridine ((S,S)-3d) [1d].
Yield: 0.86 g (33%). Brown oil. 1H NMR (CDCl3, 600 MHz):
1.52
arom. CH). 13C NMR (CDCl3, 150 MHz):
d 22.0 (CH3), 30.6 (CH2CH),
d
39.9 (CH2CH), 63.5 (CH2Ph), 70.0 (q, COH, 2JC,F = 28.5 Hz), 126.7 (q,
3
2
1
(d, 3H, JH,H = 6.5 Hz, PhCHCH3), 1.80 (dd, 1H, JH,H = 1.4 Hz,
CF3, JC,F = 282.2 Hz), 127.7, 128.6, 128.6 (5 arom. CH), 138.0 (1
3JH,H = 6.5 Hz, H(B)C(3)), 2.28 (dd, 1H, JH,H = 1.3 Hz, JH,H = 3.1 Hz,
arom. C). 19F NMR (CDCl3, 565 MHz):
d
ꢀ81.0 (s, CF3). IR (KBr)
n
2
3
3
H
(A)C(3)), 2.27 (q, 1H, JH,H = 6.6 Hz, PhCHCH3), 3.05 (dd, 1H,
3422m (O–H), 3067m, 3038m, 3004m, 2952m, 2897m, 2839m,
1499m, 1455m, 1165s (C–F), 1152s (C–F), 1123s (C–F), 1084m,
1027m, 990m, 746s, 701s cmꢀ1. ESI-MS: 245.0 (M+, 100), 244.3
([Mꢀ1]+, 90), 243.2 ([Mꢀ2]+, 38); HR-ESI-MS (MeOH+NaI):
246.10995 (246.11003 calcd. for C12H15F3NO, [M+H]+).
3JH,H = 3.1 Hz, JH,H = 6.5 Hz, HC(2)), 7.28–7.61 and 8.12–8.13 (m,
10 arom. CH). 13C-NMR (CDCl3, 150 MHz):
23.5 (CH3), 36.1 (CH2),
42.0 (CH), 70.3 (PhCHCH3); 127.0, 127.3, 128.4, 128.5, 128.7, 133.2
(10 arom. CH), 136.9, 143.6 (2 arom. C), 196.2 (C55O). IR (KBr):
3
d
n
3032m, 2973s, 1677vs (C55O), 1597m, 1447s, 1230vs, 1013s, 697vs
1-Benzyl-2-[2,2,2-trifluoro-1-methyl-2-(trimethylsilyloxy)ethyl]-
aziridine (slow, 4a0). Yield: 121 mg (49%), colorless oil.
cmꢀ1. HR-ESI-MS (MeOH+NaI): 274.12032 (274.12024 calcd. for
C
17H17NNaO, [M+Na]+). ½a D25
ꢂ
¼ ꢀ65:5 (c = 0.5; CHCl3).
2-(1-Benzylaziridin-2-yl)-1,1,1-trifluoropropan-2-ol (5a0). Yield:
2-Benzoyl-(10S,2R)-1-(10-phenylethyl)aziridine ((S,R)-3e) [12].
110 mg (45%). Colorless oil. 1H-NMR (CDCl3, 600 MHz):
d
1.30 (s,
3
Spectroscopic data in agreement with Ref. [12]. Yield: 1.08 g
(42%). Brown oil. 1H NMR (CDCl3, 600 MHz):
1.56 (d, 3H,
3JH,H = 6.5 Hz, PhCHCH3), 1.97 (dd, 1H, 2JH,H = 1.4 Hz, 3JH,H = 6.4 Hz,
(B)C(3)), 2.59 (dd, 1H, 2JH,H = 1.4 Hz, 3JH,H = 3.2 Hz, H(A)C(3)), 2.74
3H, CH3), 1.48 (d, 1H, CH2CH, JH,H = 6.6 Hz), 1.79 (d, 1H, CH2CH,
3
3
d
3JH,H = 3.6 Hz), 2.00 (dd, 1H, CH2CH, JH,H = 3.6 Hz, JH,H = 6.6 Hz),
3.22, 3.96 (AB system, 2H, CH2Ph, 2JH,H = 13.2 Hz), 3.65 (s, 1H, OH),
7.28–7.34 (m, 5 arom. CH). 13C-NMR (CDCl3, 150 MHz):
d 18.5
H
(q, 1H, 3JH,H = 6.6 Hz, PhCHCH3), 2.91 (dd, 3JH,H = 3.1 Hz,
(CH3), 27.6 (CH2CH), 39.4 (CH2CH), 62.1 (CH2Ph), 69.4 (q, COH,
3JH,H = 6.4 Hz, HC(2)), 7.25–7.40 (m, 5 arom. CH). ½a 2D5
ꢂ
¼ þ23:2
2JC,F = 27.7 Hz), 126.2 (q, CF3, JC,F = 284.5 Hz), 127.5, 128.4, 128.4
1
(c = 0.5; CHCl3).
(5 arom. CH), 137.6 (1 arom. C). 19F-NMR (CDCl3, 565 MHz):
d
ꢀ82.5 (s, CF3). IR (film):
n 3392w (O–H), 3089m, 3065m, 3032m,
4.4. Reactions of aziridinyl ketones with
2997m, 2947m, 1497m, 1455m, 1184s (C–F), 1151s (C–F), 1106s
(C–F), 1072m, 1029m, 1007m, 897m, 742s, 698s cmꢀ1. ESI-MS:
244.9 (M+, 100), 243.0 ([Mꢀ2]+, 20); HR-ESI-MS (MeOH+NaI):
246.11013 (246.11003 calcd. for C12H15F3NO, [M+H]+).
(trifluoromethyl)trimethylsilane – general procedure
A solution of the corresponding aziridinyl ketone 3 (1.0 mmol)
in anhydrous DME (1.0 ml), was placed in a dry, two-necked flask,
equipped with a tube filled with CaCl2. Next, a catalytic amount of
freshly dried CsF was added, and subsequently, (trifluoromethyl)-
trimethylsilane (230 mg, 1.6 mmol) was added dropwise. The
mixture was stirred magnetically for ca. 1 h, and the progress of the
reaction was monitored by TLC (CH2Cl2). Next, the reaction was
quenched with a sat. aqueous solution of NaCl (10 ml), and the
mixture was extracted with CH2Cl2 (3 ꢁ 15 ml). The organic layers
were combined and dried over anhydrous MgSO4. After filtration,
the solvents were evaporated. The diastereoisomeric products
were purified and separated by column chromatography on silica
gel by using a mixture of hexane/AcOEt (4.9:0.1) for compounds
1-Benzyl-2-[2,2,2-trifluoro-1-phenyl-1-(trimethylsilyloxy)ethyl]-
aziridine (fast, 4b). Yield: 77 mg (20%). Colorless oil.
1-(1-Benzylaziridin-2-yl)-2,2,2-trifluoro-1-phenylethanol (5b).
Yield: 101 mg (33%). Colorless crystals, m.p. 77–79 8C. 1H-NMR
(CDCl3, 600 MHz):
CH2CH, JH,H = 3.0 Hz), 2.40 (dd, 1H, CH2CH, JH,H = 3.0 Hz,
3JH,H = 6.0 Hz), 3.42, 3.55 (AB-system, JH,H = 12.6 Hz, 2H, CH2Ph),
d
1.73 (d, 1H, CH2CH, 3JH,H = 6.0 Hz), 2.29 (d, 1H,
3
3
2
3.88 (s, 1H, OH), 7.03–7.05, 7.12–7.15, 7.30–7.32, 7.55–7.57 (4m,
10 arom. CH). 13C-NMR (CDCl3, 150 MHz):
d 30.4 (CH2CH), 40.8
(CH2CH), 62.7 (CH2Ph), 73.0 (q, COH, 2JC,F = 28.4 Hz), 125.1 (q, CF3,
1JC,F = 283.2 Hz), 126.3, 127.3, 127.9, 128.2, 128.3, 128.4 (10 arom.
CH), 137.4, 138.5 (2 arom. C). 19F-NMR (CDCl3, 565 MHz):
d
ꢀ77.2

196
G. Mloston´ et al. / Journal of Fluorine Chemistry 156 (2013) 192–197
(s, CF3). IR (KBr)
n
3239m (O–H), 3111m, 3090m, 3072m, 3030m,
(100S,20S,1R)-1-(1-Phenylethyl)-2-[2,2,2-trifluoro-1-phenyl-1-(tri-
methylsilyloxy)ethyl]aziridine (slow, 4d0). Yield: 118 mg (30%).
Colorless oil.
3007m, 2963m, 2924m, 2869m, 1497m, 1456m, 1191s (C–F), 1171s
(C–F), 1148s (C–F), 1085m, 1072m, 1038m, 904m, 743s, 703s cmꢀ1
.
ESI-MS m/z 306.3 ([Mꢀ1]+, 100), 305.2 ([Mꢀ2]+, 60); HR-ESI-MS
(MeOH+NaI): 308.12579 (308.12568 calcd. for C17H17F3NO,
[M+H]+).
1-Benzyl-2-[2,2,2-trifluoro-1-phenyl-1-(trimethylsilyloxy)ethyl]-
aziridine (slow, 4b0). Yield: 167 mg (44%). Colorless oil.
1-(1-Benzylaziridin-2-yl)-2,2,2-trifluoro-1-phenylethanol (5b0).
Yield: 74 mg (24%). Colorless crystals, m.p. 103–106 8C (hexane/
(100S,20S,1R)-1-[1-(1-Phenylethyl)aziridin-2-yl)-2,2,2-trifluoro-1-
phenylethanol (5d0). Yield: 106 mg (33%). Colorless crystals, m.p.
98–104 8C. 1H-NMR (CDCl3, 600 MHz):
d
1.36 (d, 3JH,H = 6.6 Hz, 1H,
3
3
CH2CH), 1.44 (d, JH,H = 3.0 Hz, 1H, CH2CH), 1.51 (d, JH,H = 6.6 Hz,
3
3
3H, CH3CHPh), 2.60 (dd, JH,H = 3.0 Hz, JH,H = 6.6 Hz, 1H, CH2CH),
3
2.92 (q, JH,H = 6.6 Hz, 1H, CH3CHPh), 4.45 (s, 1H, OH), 7.27–7.29,
7.33–7.39, 7.58–7.90 (3m, 10 arom. CH). 13C-NMR (CDCl3,
CH2Cl2). 1H-NMR (CDCl3, 600 MHz):
d
1.52 (d, 1H, CH2CH,
150 MHz): d 22.9 (CH3CHPh), 28.1 (CH2CH), 40.6 (CH2CH), 68.0
3
2
1
3JH,H = 6.6 Hz), 1.60 (d, 1H, CH2CH, JH,H = 3.6 Hz,), 2.56 (dd, 1H,
(CH3CHPh), 72.5 (q, JC,F = 27.75 Hz, COH), 125.6 (q, JC,F = 261 Hz,
3
3
CH2CH, JH,H = 3.6 Hz, JH,H = 6.6 Hz), 3.34, 4.08 (AB-system,
2JH,H = 13.2 Hz, 2H, CH2Ph), 4.44 (s, 1H, OH), 7.29–7.39, 7.57–
CF3), 126.1, 126.7, 127.4, 128.2, 128.5, 128.5 (10 arom. CH), 136.7,
143.6 (2 arom. C). 19F-NMR (CDCl3, 565 MHz):
(KBr) n 3281w (O–H), 3088m, 3063m, 3034m, 2977m, 2930m,
d
ꢀ78.5 (s, CF3). IR
7.58 (2m, 10 arom. CH). 13C-NMR (CDCl3, 150 MHz):
d
28.5
(CH2CH), 39.6 (CH2CH), 61.9 (CH2Ph), 72.2 (q, COH, 2JC,F = 28.2 Hz),
2872m, 1495m, 1452s, 1189s (C–F), 1159s (C–F), 1151s (C–F),
1073m, 1037m, 1016m, 905m, 758s, 700s cmꢀ1. ESI-MS: m/z 320.0
([Mꢀ1]+, 60), 319.2 ([Mꢀ2]+, 100); HR-ESI-MS: (MeOH+NaI):
1
125.5 (q, CF3, JC,F = 285.5 Hz), 126.3, 127.6, 128.1, 128.4, 128.5,
128.6 (10 arom. CH), 136.5, 137.4 (2 arom. C). 19F-NMR (CDCl3,
565 MHz):
d
ꢀ79.9 (s, CF3). IR (KBr)
n
3241m (O–H), 3087m, 3073m,
322.14121 (322.14133 calcd. for C18H19F3NO, [M+H]+). ½a D25
¼
ꢂ
3028m, 3008m, 2997m, 2961m, 2927m, 1496m, 1454m, 1181s (C–
F), 1160s (C–F), 1148s (C–F), 1088m, 1072m, 1036m, 907m, 745s,
697s cmꢀ1. ESI-MS: m/z 305.6 ([Mꢀ1]+, 100), 305.2 ([Mꢀ2]+, 75);
HR-ESI-MS (MeOH+NaI): 308.12542 (308.12568 calcd. for
þ12:1 (c = 2.3, CHCl3).
(100S,20R,1S)-1-(1-Phenylethyl)-2-[2,2,2-trifluoro-1-phenyl-1-(tri-
methylsilyloxy)ethyl]aziridine (fast, 4e). Yield: 163 mg (44%).
Colorless oil.
C
17H17F3NO, [M+H]+).
(100S,20S,2S)-1-(1-Phenylethyl)-2-[2,2,2-trifluoro-1-methyl-1-(tri-
(100,20R,1S)-1-[1-(1-Phenylethyl)aziridin-2-yl)-2,2,2-trifluoro-1-
phenylethanol (5e). Yield: 282 mg (88%). Colorless crystals, m.p.
methylsilyloxy)ethyl]aziridine (fast, Rf = 0.22, 4c). Yield: 104 mg
(31%). Colorless oil.
72–73 8C. 1H-NMR (CDCl3, 600 MHz):
d
1.37 (d, 3JH,H = 6.6 Hz, 3H,
3
CH3CHPh), 1.69 (d, JH,H = 6.1 Hz, 1H, CH2CH), 2.28 (dd,
3
2
(100S,20S,2S)-2-[1-(1-Phenylethyl)aziridin-2-yl]-1,1,1-trifluoropro-
2JH,H = 3.3 Hz, JH,H = 6.1 Hz, 1H, CH2CH), 2.31 (dd, JH,H = 1.0 Hz,
3
pan-2-ol (5c). Yield: 196 mg (71%). Colorless crystals, m.p. 34–
3JH,H = 3.3 Hz, 1H, CH2CH), 2.71 (q, JH,H = 6.6 Hz, 1H, CH3CHPh),
37 8C. 1H-NMR (CDCl3, 600 MHz):
d
1.45–1.47 (m, 3H+1H,
3.84 (s, 1H, OH), 6.85–6.96, 7.04–7.10, 7.26–7.28 (3m, 10 arom.
3
CH3CHPh, CH2CH), 1.56 (d, JH,H = 1.0 Hz, 3H, CH3), 1.85 (dd,
CH). 13C-NMR (CDCl3, 150 MHz):
d 22.7 (CH3CHPh), 30.2 (CH2CH),
3
3JH,H = 3.3 Hz, 1H, CH2CH), 2.75 (q, JH,H = 6.5 Hz, 1H, CH3CHPh),
39.8 (CH), 68.6 (CH3CHPh), 72.9 (q, 2JC,F = 28.5 Hz, COH), 125.1 (d,
1JC,F = 283.5 Hz, CF3), 126.1, 126.4, 127.1, 127.73, 127.9, 128.0 (10
3.28 (s, 1H, OH), 7.28–7.30, 7.32–7.34 (2m, 5 arom. CH). 13C-NMR
(CDCl3, 150 MHz):
d
22.5 (CH3CHPh), 23.6 (CH3), 29.8 (CH2CH),
arom. CH), 138.1, 142.4 (2 arom. C). 19F-NMR (CDCl3, 565 MHz):
d
40.8 (CH2CH), 68.1 (CH3CHPh), 70.0 (d, 2JC,F = 28.4 Hz, COH), 126.6,
127.4, 128.5 (5 arom. CH), 125.8 (q, 1JC,F = 282.1 Hz, CF3), 143.6 (1
ꢀ77.4 (s, CF3). IR (KBr):
n 3443m (O–H), 3088m, 3063m, 3031m,
2983m, 2963m, 2925m, 2867m, 1495m, 1450m, 1256s (C–F), 1167s
(C–F), 1157s (C–F), 1099m, 1070m, 1017m, 756s, 699s cmꢀ1. ESI-
MS: 322 ([M+1]+, 100), 344 ([M+Na]+, 7.5); HR-ESI-MS (MeOH+-
NaI): 322.14174 (322.14133 calcd. for C18H19F3NO, [M+H]+).
arom. C). 19F-NMR (CDCl3, 565 MHz):
d
ꢀ80.83 (s, CF3ꢀ). IR (KBr):
d
3416 (O–H), 2985m, 2979m, 1456m, 1383s, 1200m, 1164s (C–F),
1151s (C–F), 1102m, 1078m, 703s cmꢀ1. ESI-MS: 282 ([M++Na]+,
27), 260 ([M+1]+, 100); HR-ESI-MS: 260.12589 (260.12568 calcd.
½
a 2D5
ꢂ
¼ ꢀ50:0 (c = 1.0, CHCl3).0
for C13H17F3NO, [M+H]+). ½a D25
¼ ꢀ33:0 (c = 0.5, CHCl3).
ꢂ
(100S,20R,1R)-1-(1-Phenylethyl)-2-[2,2,2-trifluoro-1-phenyl-1-(tri-
(100S,20S,2R)-1-[(1-Phenylethyl)-2-[2,2,2-trifluoro-1-methyl-1-
(trimethylsilyloxy)ethyl]aziridine (slow, Rf = 0.09, 4c0). This com-
pound was isolated as a minor product (ca. 18% yield) contami-
nated with substantial amounts of 4c and has not been used for
desilylation.
methylsilyloxy)ethyl]aziridine (slow, 4e0). This compound was
isolated as a minor product (ca. 2% yield) contaminated with
substantial amounts of 4e and has not been used for desilylation.
4.7. X-ray crystal-structure determination of 5c
(100S,20S,1S)-1-(1-Phenylethyl)-2-[2,2,2-trifluoro-1-phenyl-1-(tri-
methylsilyloxy)ethyl]aziridine (fast, 4d). Yield: 134 mg (34%).
Colorless semi-solid.
All measurements were performed on a Nonius KappaCCD area-
detector diffractometer [20] using graphite-monochromated
˚
MoK radiation (l 0.71073 A) and an Oxford Cryosystems Cryo-
a
(100S,20S,1S)-1-[1-(1-Phenylethyl)aziridin-2-yl)-2,2,2-trifluoro-1-
phenylethanol (5d). Yield: 96 mg (28%). Colorless solid, m.p. 84–
stream 700 cooler. The data collection and refinement parameters
are given below [21] and a view of the molecule is shown in Fig. 1.
Data reduction was performed with HKL Denzo and Scalepack [22].
The intensities were corrected for Lorentz and polarization effects,
but not for absorption. Equivalent reflections were merged. The
structure was solved by direct methods using SHELXS97 [23],
which revealed the positions of all non-H-atoms. The non-H-atoms
were refined anisotropically. The hydroxy H-atom was placed in
the position indicated by a difference electron density map and its
position was allowed to refine together with an isotropic
displacement parameter. All remaining H-atoms were placed in
geometrically calculated positions and refined by using a riding
3
86 8C. 1H-NMR (CDCl3, 600 MHz):
d
0.83 (d, JH,H = 6.0 Hz, 3H,
CH3CHPh), 1.60 (d, 3JH,H = 6.6 Hz, 1H, CH2CH), 2.15 (d,
3JH,H = 3.0 Hz, 1H, CH2CH), 2.38 (dd, JH,H = 3.0 Hz, JH,H = 6.6 Hz,
1H, CH2CH), 2.71 (q, 3JH,H = 6.0 Hz, 1H, CH3CHPh), 4.11 (s, 1H, OH),
7.25–7.28, 7.31–7.34, 7.38–7.41, 7.43–7.47, 7.74–7.76 (5m, 10
arom. CH). 13C-NMR (CDCl3, 150 MHz):
(CH2CH), 42.2 (CH2CH), 67.7 (CH3CHPh), 73.0 (q, JC,F = 28.8 Hz,
3
3
d 23.1 (CH3CHPh), 30.0
2
1
COH), 125.2 (q, JC,F = 282.9 Hz, CF3), 126.4, 126.5, 127.4, 128.3,
128.4, 128.6 (10 arom. CH), 138.9, 143.4 (2 arom. C). 19F-NMR
(CDCl3, 565 MHz):
d
ꢀ76.9 (s, CF3). IR (KBr)
n 3383m, 3063m,
3025m, 2966m, 2925m, 2869m, 1496m, 1456m, 1192s (C–F), 1173s
(C–F), 1150s (C–F), 1096m, 1071m, 1024m, 757s, 698s cmꢀ1. ESI-
MS: 319.7 ([Mꢀ1]+, 95], 318.6 ([Mꢀ2]+, 100); HR-ESI-MS
(MeOH+NaI): 322.14111 (322.14133 calcd. for C18H19F3NO,
model where each H-atom was assigned
a fixed isotropic
displacement parameter with a value equal to 1.2Ueq of its parent
C-atom (1.5Ueq for the methyl groups). The refinement of the
structure was carried out on F2 using full-matrix least-squares
[M+H]+). ½a 2D5
¼ ꢀ30:5 (c = 1.0, CHCl3).
ꢂ

G. Mloston´ et al. / Journal of Fluorine Chemistry 156 (2013) 192–197
197
2
procedures, which minimized the function
S
wðFo2 ꢀ Fc2Þ .
A
(e) M. Rachwalski, T. Leenders, P. Kiełbasin´ ski, S. Les´niak, F.P.J.T. Rutjes, Org.
Biomol. Chem. 11 (2013) 4207–4213;
correction for secondary extinction was applied. One reflection,
whose intensity was considered to be an extreme outlier, was
omitted from the final refinement. Neutral atom scattering factors
for non-H-atoms were taken from Ref. [24], and the scattering
factors for H-atoms were taken from Ref. [25]. Anomalous
dispersion effects were included in Fc [26]; the values for f0 and
f00 were those of Ref. [27]. The values of the mass attenuation
coefficients are those of Ref. [28]. All calculations were performed
using the SHELXL97 [23] program.
(f) M. Rachwalski, Sz. Jarzyn´ ski, S. Les´niak, Tetrahedron: Asymmetry 24 (2013)
421–425.
[4] (a) A.A. Gakh, K.L. Kirk (Eds.), Fluorinated Heterocycles, ACS Symposium Series
1003, Am. Chem. Soc., Washington, DC, 2009;
(b) V. Henajdenko (Ed.), Fluorine in Heterocyclic Chemistry, Springer Verlag,
Berlin, 2013.
´
[5] G. Mloston, E. Obijalska, H. Heimgartner, J. Fluorine Chem. 131 (2010) 829–843.
[6] V.A. Chebanov, A.I. Zbruyev, S.M. Desenko, V.D. Orlov, F.G. Yaremenko, Curr. Org.
Chem. 12 (2008) 792–812.
[7] T. Ishikawa, Heterocycles 85 (2012) 2837–2877.
[8] J.H. Kim, S.B. Lee, W.K. Lee, D.-H. Yoon, H.-J. Ha, Tetrahedron 67 (2011) 3553–
3558.
[9] D.-H. Yoon, P. Kang, W.K. Lee, Y. Kim, H.-J. Ha, Org. Lett. 14 (2012) 429–431.
[10] J.M. Mahoney, C.R. Smith, J.N. Johnston, J. Am. Chem. Soc. 127 (2005) 1354–1355.
[11] D. Borel, Y. Gelas-Mialhe, R. Vessie`re, Can. J. Chem. 54 (1976) 1582–1589.
[12] B.C. Kim, W.K. Lee, Tetrahedron 52 (1996) 12117–12124.
[13] (a) G.K.S. Prakash, A.K. Yudin, Chem. Rev. 97 (1997) 757–786;
(b) R.P. Singh, J.N.M. Shreeve, Tetrahedron 56 (2000) 7613–7632;
(c) G.K.S. Prakash, M. Mandal, J. Fluorine Chem. 112 (2001) 123–131;
(d) J.-A. Ma, D. Cahard, J. Fluorine Chem. 128 (2007) 975–996;
(e) N. Shibata, S. Mizuta, H. Kawai, Tetrahedron: Asymmetry 19 (2008) 2633–
2644;
(f) A.D. Dilman, V.V. Levin, Eur. J. Org. Chem. (2011) 831–841.
[14] (a) R. Krishnamurti, D.R. Bellew, G.K.S. Prakash, J. Org. Chem. 56 (1991)
984–989;
(b) R.P. Singh, G. Cao, R.L. Kirchmeier, J.M. Shreeve, J. Org. Chem. 64 (1999) 2873–
2876;
(c) R.P. Singh, R.L. Kirchmeier, J.M. Shreeve, Org. Lett. 1 (1999) 1047–1049.
[15] (a) O.C. Dermer, G.E. Ham, Ethylenimine and Other Aziridines, Academic Press,
New York, 1969;
Crystal data for 5c: C13H16F3NO, M = 259.27, crystallized from
hexane, colorless, prism, crystal dimensions 0.17 mm ꢁ 0.23 mm
ꢁ 0.30 mm, orthorhombic, space group P212121, Z = 4, reflections for
cell determination 1728, 2
u range for cell determination 4–558,
3
˚
˚
˚
˚
a = 10.3719(2) A, b = 14.9112(3) A, c = 8.4315(2) A, V = 1303.99(9) A ,
T = 160(1) K, DX = 1.321 g cmꢀ3 (MoK ) = 0.112 mmꢀ1, scan type
and , 2 (max) = 558, total reflections measured 16513, symmetry
independent reflections 1720, reflections with I > 2 (I) 1537, reflec-
(I)
,
m
f
a
v
u
s
tions used in refinement 1719, parameters refined 170; R(F) [I > 2
s
reflections] = 0.0350, wR(F2) [all data] = 0.0902 (w = [s2(Fo2) +
(0.0497P)2 + 0.1876P]ꢀ1, where P = (Fo2 + 2Fc2)/3), goodness of fit
ꢀ3
˚
1.049, final
secondary extinction coefficient = 0.023(5).
D
/
max s 0.002, Dr (max; min) = 0.19; ꢀ0.16 e A
,
Acknowledgements
(b) W.H. Pearson, B.N. Lian, S.C. Bergmeier, in: A.R. Katritzky, C.W. Reese, E.F.
Scriven (Eds.), Comprehensive Heterocyclic Chemistry II, vol. 1A, Pergamon,
Oxford, 1996, pp. 19–21 (chapter 1.01.6.2).
E.O. acknowledges the National Science Center (Poland) for
financial support (Grant ‘SONATA’ # DEC 2011/03/D/ST5/05231)
and the authors thank PD Dr. L. Bigler, University of Zurich, for ESI-
HR-MS
[16] C.K. Johnson, ORTEP II: Report ORNL-5138, Oak Ridge National Laboratory, Oak
Ridge, Tennessee, 1976.
[17] Based on the (100S,20S,2S)-configuration of 5c, the configuration of the faster
moving isomer 4c is also (100S,20S,2S). In analogy, the configurations of 5d and
5e, obtained from the faster moving isomers 4d and 4e (TLC), were assigned as
(100S,20S,2S) and (100S,2’R,2S), respectively. Thus, the configuration of 5d’ must be
(100S,20S,2R).
References
[18] J. Bernstein, R.E. Davis, L. Shimoni, N.-L. Chang, Angew. Chem. Int. Ed. Engl. 34
(1995) 1555–1573.
[19] A.K. Yudin (Ed.), Aziridines and Epoxides in Organic Synthesis, Wiley-VCH Verlag,
Weinheim, 2006.
[20] R. Hooft, KappaCCD Collect Software, Nonius BV, Delft, The Netherlands, 1999.
[21] CCDC-947548 contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from the Cambridge Crystallographic
Data Centre, via www.ccdc.cam.ac.uk/data_request/cif.
[22] Z. Otwinowski, W. Minor, Methods in Enzymology, in: C.W. Carter, Jr., R.M. Sweet
(Eds.), Macromolecular Crystallography, Part A, vol. 276, Academic Press, New
York, 1997, pp. 307–326.
[1] (a) K.M. Lee, J.C. Kim, P. Kang, W.K. Lee, H. Eum, H.-J. Ha, Tetrahedron 68 (2012)
883–893;
(b) A. Singh, H.-J. Ha, J. Park, J.H. Kim, W.K. Lee, Bioorg. Med. Chem. 19 (2011)
6174–6181;
(c) H.-J. Ha, M.C. Hong, S.W. Ko, Y.W. Kim, W.K. Lee, J. Park, Bioorg. Med. Chem.
Lett. 16 (2006) 1880–1883;
(d) J.M. Yun, T.B. Sim, H.S. Hahm, W.K. Lee, H.-J. Ha, J. Org. Chem. 68 (2003) 7675–
7680;
(e) H.J. Yoon, Y.-W. Kim, B.K. Lee, W.K. Lee, Y. Kim, H.-J. Ha, Chem. Commun.
(2007) 79–81;
[23] G.M. Sheldrick, Acta Crystallogr. A 64 (2008) 112–122.
[24] E.N. Maslen, A.G. Fox, M.A. O‘Keefe, in: A.J.C. Wilson (Ed.), International Tables
for Crystallography, vol. C, Kluwer Academic, Dordrecht, 1992, pp. 477–486,
Table 6.1.1.1.
[25] R.F. Stewart, E.R. Davidson, W.T. Simpson, J. Chem. Phys. 42 (1965) 3175–3187.
[26] J.A. Ibers, W.C. Hamilton, Acta Crystallogr. 17 (1964) 781–782.
(f) G. Fronza, A. Mele, G. Pedrocchi-Fantoni, D. Pizzi, S. Servi, J. Org. Chem. 55
(1990) 6216–6219.
[2] (a) Allergan Inc., WO 2006/81252 A2 (2006).;
(b) Allergan Inc., WO 2008/109287 A1 (2008).
[3] (a) M. Rachwalski, M. Kwiatkowska, J. Drabowicz, M. Kłos, W.M. Wieczorek, M.
Szyrei, L. Sieron´ , P. Kiełbasin´ ski, Tetrahedron: Asymmetry 19 (2008) 2096–2101;
(b) S. Les´niak, M. Rachwalski, E. Sznajder, P. Kiełbasin´ ski, Tetrahedron: Asymme-
try 20 (2009) 2311–2314;
[27] D.C. Creagh, W.J. McAuley, in: A.J.C. Wilson (Ed.),
International Tables
for Crystallography, vol. C, Kluwer Academic, Dordrecht, 1992, pp. 219–222,
Table 4.2.6.8.
[28] D.C. Creagh, J.H. Hubbell, in: A.J.C. Wilson (Ed.), International Tables for Crystal-
lography, vol. C, Kluwer Academic, Dordrecht, 1992, pp. 200–206, Table 4.2.4.3.
(c) M. Rachwalski, S. Les´niak, P. Kiełbasin´ ski, Tetrahedron: Asymmetry 21 (2010)
2687–2689;
(d) M. Rachwalski, S. Les´niak, P. Kiełbasin´ ski, Tetrahedron: Asymmetry 22 (2011)
1325–1327;