Synthesis and structure of nitrones derived from 2-trifluoromethyl bornane 3-imines

Article abstract of DOI:10.1016/j.jfluchem.2010.01.001

Upon treatment with (trifluoromethyl)trimethylsilane (CF₃SiMe₃), 3-(N-alkyl or 3-N-aryl)imines of camphorquinone of type 1 smoothly undergo stereoselective conversion to yield 2-endo-trifluoromethylated 1:1 adducts 2, which, after subsequent desilylation with sodium borohydride in boiling alcoholic solutions, were converted into imino alcohols 3. Unexpectedly, oxidation of 3 with m-CPBA resulted in the formation of a new type of trifluoromethylated nitrones 5 (and not the expected oxaziridines) in a stereoselective manner. In the case of 5a, the (Z)-configuration of the C{double bond, long}N double bond of the nitrone unit was unambiguously established by an X-ray crystal-structure determination. However, photolysis of 5a led to the exo,exo/exo,endo mixture of the isomeric oxaziridine 7; the two stereoisomers were separated chromatographically.

Full text of DOI:10.1016/j.jfluchem.2010.01.001

Journal of Fluorine Chemistry 131 (2010) 578–583
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis and structure of nitrones derived from 2-trifluoromethyl
bornane 3-imines
a,**
*
Grzegorz Mloston
, Emilia Obijalska a,1, Anthony Linden b, Heinz Heimgartner b,
a Department of Organic and Applied Chemistry, University of Lodz, Tamka 12, PL-91-403 Lodz, Poland
b Organisch-chemisches Institut der Universita¨t Zu¨rich, Winterthurerstrasse 190, CH-8057 Zu¨rich, Switzerland
A R T I C L E I N F O
A B S T R A C T
Article history:
Upon treatment with (trifluoromethyl)trimethylsilane (CF3SiMe3), 3-(N-alkyl or 3-N-aryl)imines of
camphorquinone of type 1 smoothly undergo stereoselective conversion to yield 2-endo-trifluoro-
methylated 1:1 adducts 2, which, after subsequent desilylation with sodium borohydride in boiling
alcoholic solutions, were converted into imino alcohols 3. Unexpectedly, oxidation of 3 with m-CPBA
resulted in the formation of a new type of trifluoromethylated nitrones 5 (and not the expected
oxaziridines) in a stereoselective manner. In the case of 5a, the (Z)-configuration of the C55N double bond
of the nitrone unit was unambiguously established by an X-ray crystal-structure determination.
However, photolysis of 5a led to the exo,exo/exo,endo mixture of the isomeric oxaziridine 7; the two
stereoisomers were separated chromatographically.
Received 16 November 2009
Received in revised form 31 December 2009
Accepted 5 January 2010
Available online 11 January 2010
Keywords:
Imines
Nitrones
Oxaziridines
Oxidations
ß 2010 Elsevier B.V. All rights reserved.
Trifluoromethylbornan-2-ols
1. Introduction
hydroxy)ketone. On the other hand, the reduction of 3 with DIBAL-
H afforded the a-trifluoromethylated b-amino alcohols 4, and the
In spite of the fact that camphor and its derivatives attract
attention as readily available, enantiomerically pure building
blocks and ligands for stereocontrolled synthesis [1,2], very little is
known about fluorinated derivatives of camphor. Fluorination of
camphor-3-carboxylic acid used as an endo/exo mixture with SF4 at
room temperature was reported to give, depending on the reaction
conditions, the corresponding acid fluoride or 3-(trifluoromethyl)-
camphor as a mixture of endo and exo isomers [3]. On the other
hand, isoketopinic acid, treated with SF4 at 100 8C, was converted
into the corresponding 2,2-difluorocarboxylic acid fluoride. In this
case, no trifluoromethylated derivative was reported.
Recently, we showed that camphorquinone monoimines 1
smoothly undergo a nucleophilic trifluoromethylation with the
Ruppert-Prakash reagent (CF3SiMe3) to give the corresponding (2-
trifluoromethyl)imine silylethers 2 in a diastereoselective manner.
The latter products, upon treatment with sodium borohydride,
were converted into imino alcohols 3 in excellent yields [4]
(Scheme 1). As shown in the same paper, acidic hydrolysis of the
major products were identified as the cis-isomers.
Oxidation reactions of N-substituted camphor imines have been
extensively studied, and the formation of oxaziridines as the
exclusive products was reported [5]. Typically, the oxidations were
performed with peroxides and gave the endo-oxaziridines as the
major or exclusive product. The so-called ‘Davis oxaziridine’ has
gained special importance as an excellent chiral O-transfer
reagent, used in enantioselective oxidation reactions [6].
Nitrones are isomers of oxaziridines and belong to the group of
well-known and widely explored 1,3-dipoles. It is worth mention-
ing that under photochemical or thermal conditions, the isomeric
nitrones and oxaziridines can be interconverted [7]. Interestingly,
the N-methyl nitrones derived from camphorquinone were
obtained via a non-oxidative method by the treatment of its
monooxime with diazomethane [8].
The aim of the present study was the synthesis of oxaziridines
and/or nitrones containing the trifluoromethylated camphor
skeleton via oxidation of imino alcohols 3. To the best of our
knowledge, this type of optically active nitrones (or oxaziridines)
has not been reported so far.
primary adducts 2 gave the corresponding trifluoromethylated (a-
2. Results and discussion
* Corresponding author. Tel.: +41 44 635 42 82; fax: +41 44 635 68 12.
** Corresponding author. Tel.: +48 42 635 57 61; fax: +48 42 665 51 62.
E-mail addresses: gmloston@uni.lodz.pl (G. Mloston), heimgart@oci.uzh.ch
(H. Heimgartner).
The trifluoromethylated imino alcohols
according to the method described earlier [4]. The structures of
the racemic N-methyl and N-ethyl derivatives 3a,b had previously
3 were prepared
1
Part of the planned PhD Thesis of E. Obijalska, University of Lodz.
0022-1139/$ – see front matter ß 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2010.01.001

G. Mloston et al. / Journal of Fluorine Chemistry 131 (2010) 578–583
579
Scheme 1.
Scheme 2.
been established by X-ray crystallography [4]. Oxidation of 3a–h
with m-CPBA in dichloromethane at room temperature afforded,
after ca. 2 h reaction time, only one product in each case in 82–94%
yield. In the case of the reaction with 3a, the 19F NMR spectrum of
the crude product displayed only one signal located at ꢀ67.1 ppm,
indicating that the reaction occurred stereoselectively. In addition,
the IR and the 13C NMR spectra revealed the presence of a C55N
group (1642 cmꢀ1 and 153.1 ppm, respectively). After crystal-
lisation, the elemental analysis corresponded with the formula
with 3a, carried out at lower temperature (0 8C and ꢀ30 8C), led to
the same result.
Analogously, treatment of 3b–h afforded crystalline products,
which displayed similar spectroscopic data. In all cases, the
structure of the corresponding nitrone of type 5 was proposed for
the isolated product. Finally, the structure of 5g with (Z)-
configuration was unambiguously established by X-ray crystal-
lography (Fig. 1). The crystal-structure shows that the hydroxy
group forms an intramolecular hydrogen bond with the nitrone O-
atom. This interaction creates a six-membered loop that can be
described by a graph set motif [9] of S(6).
C12H18F3NO2, i.e., a monoxidated product. These data indicated
that the obtained product was the nitrone 5a and not the
corresponding oxaziridine (Scheme 2). Oxidation experiments
In addition to the presented reactions with imines 3, the
oxidation of the trimethylsilyloxy derivative 2a with m-CPBA in
CH2Cl2 solution was performed at ca. 0–5 8C, and the product
isolated after typical workup was identified as the silylated nitrone
derivative 6 (Scheme 2). The 13C NMR spectrum revealed the
expected absorption of the C55N group at 150.2 ppm. The
subsequent desilylation with TBAF yielded the known product 5a.
The typical procedures applied for the synthesis of nitrones are
the condensation of hydroxylamines with carbonyl compounds or
the methylation of monooximes of 1,2-diketones with diazo-
methane [2b,11]. On the other hand, the oxidation of imines is a
known protocol for the preparation of oxaziridines [7,12].
Therefore, the formation of nitrones 5 from the imino alcohols 3
is an unexpected result. Considering the reaction pathway, the
initial formation of the corresponding oxaziridines and subsequent
ring opening under the reaction conditions cannot be excluded.
It is worth mentioning that the oxidation of N-alkylaminoace-
tonitriles with excess m-CPBA leads to the N-oxide of the
corresponding cyanomethylidene amines (nitrones) [13]. In this
case, electron-deficient cyanomethylidene amines are likely
intermediates. Based on this result, we propose that the strongly
electron-withdrawing CF3 group is responsible for the formation of
nitrones 3 and not oxaziridines from the imino derivatives of type 3
and the O-silylated analogue 2a.
In order to prepare an oxaziridine derivative, the nitrone 5a was
irradiated in methanolic solution with UV-light (mercury lamp),
and the progress of the reaction was controlled by means of TLC.
Fig. 1. ORTEP-plot [10] of the molecular structure of 5g (50% probability ellipsoids,
arbitrary numbering of the atoms).

580
G. Mloston et al. / Journal of Fluorine Chemistry 131 (2010) 578–583
NMR spectra were recorded in CDCl3 with TMS or CCl3F as the
internal standards using Bruker AC-200 or Bruker ARX-300
spectrometers. Assignments of signals in 13C NMR spectra were
made on the basis of DEPT 135 experiments. The IR spectra were
measured using a NEXUS FT-IR spectrophotometer. The MS spectra
(CI, EI, ESI) were obtained using LKB-2091, Finnigan MAT-95, or
Bruker Esquire LC spectrometers. Optical rotations were measured
Scheme 3.
on a PERKIN-ELMER 241 MC spectropolarimeter for
l = 589 nm.
Elemental analyses were performed in the Microanalytical
Laboratory of the Centre of Molecular and Macromolecular Studies
PAS in Lodz.
After 60 min, the irradiation was stopped, and the crude product
was analyzed by 19F NMR spectroscopy. Along with two main
products disclosing two singlets located at ꢀ70.5 and ꢀ71.3 ppm,
respectively, some smaller signals indicated the presence of non-
identified minor products resulting from photodecompositions.
After chromatographic separation, two main fractions were
isolated as colourless solids in 70% overall yield. The IR spectra of
4.2. Materials
Commercial 70% m-chloroperbenzoic acid (m-CPBA) was
purchased from Sigma–Aldrich and the 1 M solution of tetra-
both compounds confirmed the absence of
a
C55N group.
butylammonium fluoride (TBAF) in THF from Fluka. The a-
Correspondingly, in the 13C NMR spectra, no absorption above
125 ppm was observed (absence of C55N), and the characteristic
signals at 92.3 ppm (major product) and 93.4 ppm (minor product)
were attributed to the C(3)-atom of the oxaziridines 7 (Scheme 3).
These chemical shifts fit satisfactorily with values reported for a
series of oxaziridines (79.2–85.2 ppm) [13].
trifluoromethylated imino alcohols 3 were prepared according
to published protocols [4].
4.3. Oxidation of trifluoromethylated imino alcohols 3a–h with m-
CPBA—general procedure
In the 19F NMR spectra of the separated isomers 7, the presence of
only one signal in each case confirmed the purity of the samples. In
thecaseofthemainisomer,thesignallocatedatꢀ70.5 ppmappeared
as a broad one, whereas the minor isomer showed a sharp singlet at
ꢀ71.3 ppm. The broadening of the signal in the first case may result
from a through-space interaction of the CF3 group with the endo-
oriented MeN group. Based on this assumption, the structure of the
major isomer is proposed as 2-exo,3-exo-7 (Scheme 3).
The attempted photo-isomerisation of the Ph substituted
nitrone 5g resulted in the formation of a complex mixture and,
after column chromatography only unidentified decomposition
products were isolated.
To a solution of the corresponding imino alcohol 3 (1 mmol) in
CH2Cl2 (2 mL), m-CPBA (1.1 mmol) was added, and the mixture
was stirred for 2 h at room temperature. Then, the mixture was
diluted with CH2Cl2 and washed with a saturated aqueous solution
of Na2CO3 in order to remove the excess of m-CPBA and m-
chlorobenzoic acid. The separated organic layers were collected
and dried over anhydrous MgSO4. After filtration, the solutions
were evaporated to dryness. Purification of the crude products was
achieved mainly by crystallisation, but in the case of 5c–5e,
preceding column chromatography was applied.
(Z)-N-Methyl-[(1R,2S)-2-(trifluoromethyl)bornan-2-ol-3-yliden]-
amine N-oxide (5a). The pure product was obtained by crystal-
Nitrones are widely explored as useful building blocks in
organic synthesis, and their [2 + 3]-cycloaddition reactions with
diverse dipolarophiles are well documented [11b,c]. In order to
check if trifluoromethylated nitrones of type 5, derived from
camphor, are able to react with typical C55N or C55C dipolarophiles,
in analogy to already described reactions with similar systems
[2b,11d], THF solutions containing equimolar amounts of 5a and
phenyl isocyanate or 5g and fumaronitrile, respectively, were
heated under reflux for 10 h. After this time, in both cases, the
starting materials were recovered unchanged in nearly quantita-
tive yields. Apparently, steric hindrance in nitrones 5 prevents the
formation of the corresponding [2 + 3]-cycloadduct.
lisation. Yield: 220 mg (82%). Colourless crystals, m.p. 248–250 8C
+162.4 (c 0.010, CHCl3). 1H NMR
25
(CH2Cl2/hexane);
(200 MHz, CDCl3):
[
a
d
]
D
0.98, 1.08, 1.13 (9H, 3s, 3CH3), 1.56–1.98
3
(4H, m, 2CH2), 2.63 (1H, d, JH,H = 4.4 Hz, CH), 3.70 (3H, s, CH3N),
6.61 (1H, s, OH). 13C NMR (50 MHz, CDCl3):
9.5, 19.2, 20.9 (3CH3),
22.4, 28.7 (2CH2), 49.0 (CH), 50.7, 53.3 (2Cq), 52.3 (CH3N), 81.1 (q,
2JC,F = 28.9 Hz, Cq), 124.9 (q, 1JC,F = 289.4 Hz, CF3), 153.1 (C55N). 19
NMR (188 MHz, CDCl3): 3227m (br,
d
F
d
ꢀ67.1 (s, CF3). IR (KBr):
v
OH), 1990s, 2964s, 2942s, 1642s (C55N), 1493m, 1447m, 1393m,
1374m, 1308s, 1258vs, 1233s, 1208s, 1173vs, 1119vs, 1070m,
1012s, 993s, 956m, 925s, 870m, 832s, 740m, 596m cmꢀ1. EI-MS m/z
(rel. int.): 265 (59, M+), 248 (40), 220 (13), 196 (13), 182 (100), 166
(23), 140 (12), 138 (16), 95 (31), 83 (15). Anal. Calcd for
3. Conclusions
C12H18F3NO2 (265.29): C, 54.33; H, 6.84; N, 5.28. Found: C,
54.22; H, 6.67; N, 5.21.
The trifluoromethylated imino alcohols 3 undergo oxidation
with m-CPBA yielding the corresponding nitrones 5 instead of the
corresponding oxaziridines. This rather unexpected result is
probably caused by the substitution pattern of the imine, and
the influence of the CF3 group may play a crucial role. The new type
of trifluoromethylated nitrones, which can be prepared conve-
niently in enantiomerically pure form, can be further explored for
stereocontrolled reactions. Moreover, they can be tested as a new
type of ligands for organocatalysis.
(Z)-N-Ethyl-[(1R,2S)-2-(trifluoromethyl)bornan-2-ol-3-yliden]-
amine N-oxide (5b). The pure product was obtained by crystal-
lisation. Yield: 250 mg (89%). Colourless crystals, m.p. 147–149 8C
(Et2O); [a] d
25 +167.8 (c 0.010, CHCl3). 1H NMR (200 MHz, CDCl3):
D
0.96, 1.05, 1.10 (9H, 3s, 3CH3), 1.44 (3H, t, 3JH,H = 7.3 Hz, CH3CH2),
1.52–1.99 (4H, m, 2CH2), 2.64 (1H, d, 3JH,H = 4.5 Hz, CH), 3.87 (2H, q,
3JH,H = 7.3 Hz, CH3CH2N), 6.62 (1H, s, OH). 13C NMR (50 MHz,
CDCl3):
d 9.5, 12.3, 19.2, 21.3 (4CH3), 22.6, 28.7 (2CH2), 50.6, 53.1
(2Cq), 51.7 (CH), 56.4 (CH3CH2N), 81.2 (q, 2JC,F = 28.8 Hz, Cq), 124.9
1
(q, JC,F = 290.3 Hz, CF3), 151.8 (C55N). 19F NMR (188, CDCl3):
d
4. Experimental
ꢀ66.9 (s, CF3). IR (KBr):
v 3267m (br, OH), 3016m, 2991s, 2963s,
2883m, 1620m (C55N), 1495w, 1458m, 1395m, 1375m, 1308m,
1261s, 1232m, 1172vs, 1159vs, 1128s, 1114vs, 1093m, 1025m,
1011w, 998w, 979w, 954m, 922w, 829w, 740m, 641w cmꢀ1. EI-MS
m/z (rel. int.): 279 (54, M+), 262 (41), 210 (15), 196 (100), 180 (19),
168 (11), 154 (11), 152 (12), 95 (27), 83 (11). Anal. Calcd for
4.1. General experimental procedures
Melting points were determined on a Melt-Temp. II apparatus
(Aldrich) in capillaries and are uncorrected. The 1H, 13C{1H} and 19
F

G. Mloston et al. / Journal of Fluorine Chemistry 131 (2010) 578–583
581
2
C13H20F3NO2 (279.31): C, 55.90; H, 7.56; N, 5.01. Found: C, 55.95;
H, 7.85; N, 5.01.
(1H, q, JH,H = 6.7 Hz, CH3CH), 6.52 (1H, s, OH), 7.26–7.51 (5H, m,
C6H5). 13C NMR (50 MHz, CDCl3):
d 9.5, 19.2, 19.6 (3CH3), 20.9
(Z)-N-Isopropyl-[(1R,2S)-2-(trifluoromethyl)bornan-2-ol-3-
yliden]amine N-oxide (5c). The crude product was purified by
column chromatography on silica gel using first CH2Cl2/hexane
(2:1) and then CH2Cl2 with increasing amounts of ethyl acetate
(0–5%) as eluents. The product was isolated as a yellowish oil. An
(CH3CH), 22.7, 28.7 (2CH2), 51.1 (CH), 50.7, 53.0 (2Cq), 69.0
(CH3CH), 81.5 (q, 2JC-F = 28.8 Hz, Cq), 125.1 (q, 1JC,F = 290.0 Hz, CF3),
126.9, 128.5, 128.6 (5CH arom.), 137.8 (Cq arom.), 151.6 (C55N). 19
F
NMR (188 MHz, CDCl3):
d
ꢀ66.6 (s, CF3). IR (KBr):
v
3600ꢀ3100w
(br, OH), 3014m, 2989m, 2957m, 2891w, 1771w, 1595m, 1495m,
1457m, 1441w, 1424w, 1399w, 1295m, 1263s, 1233m, 1174s,
1162s, 1149vs, 1127w, 1114s, 1056m, 1012m, 982m, 957m, 923w,
866w, 835w, 765w, 736m, 720m, 705m, 641m cmꢀ1. EI-MS m/z (rel.
int.): 355 (0.8, M+), 338 (0.3), 251 (0.7), 234 (0.6), 218 (0.4), 136
(1.3), 106 (10), 105 (100), 104 (4), 103 (5), 79 (6), 77 (6). HR-EI-MS:
Calcd for C19H24F3NO2: 355.1759; found: 355.1758.
analytically pure sample was obtained by crystallisation. Yield:
25
260 mg (82%). Colourless crystals, m.p. 40–43 8C (hexane); [
a]
D
+158.2 (c 0.2, CHCl3). 1H NMR (200 MHz, CDCl3):
d
1.00, 1.10, 1.14
(9H, 3s, 3CH3), 1.37–1.45 (6H, m, (CH3)2CH), 1.58–2.03 (4H, m,
3
2CH2), 2.75 (1H, d, JH,H = 4.5 Hz, CH), 4.27–4.40 (1H, m,
(CH3)2CHN), 6.68 (1H, s, OH). 13C NMR (50 MHz, CDCl3):
d 9.6,
19.1, 20.0 (3CH3), 19.4 (CH2), 21.6, 22.9 ((CH3)2CH), 28.8 (CH2),
50.7, 53.0 (2Cq), 51.5 (CH), 60.7 ((CH3)2CH), 81.6 (q, 2JC,F = 28.6 Hz,
Cq), 125.2 (q, 1JC,F = 28.6 Hz, CF3), 150.9 (C55N). 19F NMR (188 MHz,
(Z)-N-Phenyl-[(1R,2S)-2-(trifluoromethyl)bornan-2-ol-3-yliden]-
amine N-oxide (5g). The pure product was obtained by crystal-
lisation. Yield: 300 mg (90%). Colourless crystals, m.p. 160–163 8C
CDCl3):
d
ꢀ66.8 (s, CF3). IR (KBr):
v
3432m (br, OH), 2981m, 2941m,
(CH2Cl2/hexane);
(200 MHz, CDCl3):
[a
]
D
+58.78 (c 0.010, CHCl3). 1H NMR
25
2883w, 1611m (C55N), 1497w, 1455m, 1395m, 1378m, 1296m,
1261s, 1203s, 1183s, 1157vs, 1112s, 1076m, 1015m, 994w, 961m,
927w, 868w, 834w, 738m, 645m cmꢀ1. CI-MS (NH3) m/z (rel. int.):
294 (100, [M+1]+), 278 (30), 276 (14). HR-ESI-MS (NaI): Calcd for
d 0.87, 1.10, 1.12 (9H, 3s, 3CH3), 1.62–1.95
(4H, m, 2CH2), 2.42 (1H, d, JH,H = 4.2 Hz, CH), 6.93 (1H, s, OH),
7.42–7.48 (5H, m, C6H5). 13C NMR (50 MHz, CDCl3):
9.5, 19.2, 21.1
2
d
(3CH3), 22.7, 28.7 (2CH2), 51.2, 53.2 (2Cq), 53.3 (CH), 81.5 (q,
1
C14H22F3NO2Na: 316.1500; found: 316.1504.
2JC,F = 29.0 Hz, Cq), 125.0 (q, JC,F = 289.9 Hz, CF3), 122.9, 129.2,
(Z)-N-tert-Butyl-[(1R,2S)-2-(trifluoromethyl)bornan-2-ol-3-yli-
130.2 (5CH arom.), 145.2 (Cq arom.), 154.7 (C55N). 19F NMR
den]amine N-oxide (5d). The crude product was purified by column
chromatography on silica gel using first a mixture of CH2Cl2/
hexane (2:1) and then CH2Cl2 with increasing amounts of ethyl
acetate (0–5%) as eluents. The product was isolated as a yellowish
oil. An analytically pure sample was obtained by crystallisation.
Yield: 290 mg (94%). Colourless crystals, m.p. 54–58 8C (hexane);
(188 MHz, CDCl3):
d
ꢀ67.0 (s, CF3). IR (KBr):
v
3600ꢀ2880w (br,
OH), 106w, 3077w, 3018m, 3002s, 2989m, 2977s, 2944m, 2926m,
2881w, 1887w, 1806w, 1606m, 1584m, 1489s, 1459m, 1401m,
1382m, 1320m, 1287s, 1267vs, 1233m, 1198vs, 1179s, 1164vs,
1150vs, 1117s, 1107s, 1073m, 1010m, 979m, 953m, 919m, 866w,
830w, 773s, 739m, 720m, 692s, 637m cmꢀ1. EI-MS m/z (rel. int.):
327 (63, M+), 311 (22), 310 (38), 244 (72), 228 (13), 213 (22), 212
(18), 202 (12), 200 (18), 158 (10), 130 (100), 104 (65), 91 (27), 77
(59). Anal. Calcd for C17H20F3NO2 (327.35): C, 62.38; H, 6.16; N,
4.28. Found: C, 62.52; H, 5.89; N, 4.25.
[a
]
D
25 +154.5 (c 0.2, CHCl3). 1H NMR (300 MHz, CDCl3):
d
0.97, 1.07,
1.13 (9H, 3s, 3CH3), 1.55 (9H, s, (CH3)3C), 1.55–2.00 (4H, m, 2CH2),
3
3.06 (1H, d, JH,H = 4.8 Hz, CH). 13C NMR (75.5 MHz, CDCl3):
d 9.6,
19.5, 21.8 (3CH3), 22.7 (CH2), 28.2 ((CH3)3C), 28.6 (CH2), 50.9, 52.0
(2Cq), 52.2 (CH), 71.0 ((CH3)3CN), 83.2 (q, 2JC,F = 28.8 Hz, Cq), 125.3
(Z)-N-(4-Methoxyphenyl)-[(1R,2S)-2-(trifluoromethyl)bornan-2-
ol-3-yliden]amine N-oxide (5h). The pure product was obtained by
(q, 1JC,F = 290.0 Hz, CF3), 151.0 (C55N). 19F NMR (188 MHz, CDCl3):
d
ꢀ66.2 (s, CF3). IR (KBr):
v
3448m (br, OH), 2985m, 2942m, 2884w,
crystallisation. Yield: 320 mg (90%). Colourless crystals, m.p. 164–
+69.50 (c 0.012, CHCl3). 1H NMR
25
1582w, 1459w, 1395w, 1372w, 1293w, 1274w, 1257m, 1229m,
1200m, 1186m, 1164vs, 1151vs, 1125s, 1110s, 1008w, 983w, 960w,
833w, 731w, 656w cmꢀ1. CI-MS (NH3) m/z (rel. int.): 309 (17), 308
(100, [M+1]+), 252 (89). Anal. Calcd for C15H24F3NO2 (307.36): C,
58.62; H, 7.77. Found: C, 58.27; H, 7.72.
167 8C (CH2Cl2/hexane); [
(200 MHz, CDCl3):
2CH2), 2.45 (1H, d, 2JH,H = 4.0 Hz, CH), 3.81 (3H, s, CH3O), 7.05 (1H,
s, OH), 6.89–7.36 (4H, m, C6H4). 13C NMR (50 MHz, CDCl3):
9.5,
a
]
D
d
0.86, 1.08 (6H, 3s, 3CH3), 1.68–2.00 (4H, m,
d
19.2, 21.0 (3CH3), 22.7, 28.7 (2CH2), 51.2, 53.0 (2Cq), 53.5 (CH), 55.4
(CH3O), 81.50 (q, 2JC,F = 29.0 Hz, Cq), 125.1 (q, 1JC,F = 289.8 Hz, CF3),
114.1, 124.2 (4CH arom.), 138.4, 154.0 (2Cq arom.), 160.7 (C55N).
(Z)-N-Cyclohexyl-[(1R,2S)-2-(trifluoromethyl)bornan-2-ol-3-yli-
den]amine N-oxide (5e). The crude product was purified by column
chromatography on silica gel using CH2Cl2/hexane (2:1) and then
CH2Cl2 with increasing amounts of ethyl acetate (0–5%) as eluents.
The product was isolated as a yellowish oil. An analytically pure
sample was obtained by crystallisation. Yield: 310 mg (93%).
Colourless crystals, m.p. 74–76 8C (hexane); [
CHCl3). 1H NMR (300 MHz, CDCl3):
19F NMR (188 MHz, CDCl3):
d
ꢀ68.1 (s, CF3). IR (KBr):
v
3600ꢀ3450w (br, OH), 3119w, 3001w, 2987w, 2941w, 2846w,
1611w, 1599m, 1507s, 1459w, 1323w, 1285w, 1258s, 1198m,
1168vs, 1146s, 1110s, 1024w, 1009w, 977w, 954w, 917w, 845m,
812w, 732w, 608w cmꢀ1. EI-MS m/z (rel. int.): 357 (56, M+), 341
(41), 340 (25), 274 (32), 258 (11), 257 (23), 243 (11), 242 (17), 230
(21), 188 (18), 161 (11), 160 (70), 135 (11), 134 (100), 124 (33), 123
(24), 122 (11), 120 (47), 109 (18), 108 (12), 107 (17), 95 (26), 92
(14), 77 (25). HR-EI-MS: Calcd for C18H22F3NO2: 357.1552; found:
357.1554. Anal. Calcd for C18H22F3NO2 (357.38): C, 60.49; H, 6.21;
N, 3.92. Found: C, 60.41; H, 5.83; N, 3.90.
25
a]
D
+168.0 (c 0.2,
d
0.98, 1.08, 1.12 (9H, 3s, 3CH3),
3
1.15–1.40 (3H, m), 1.52–2.15 (11H, m), 2.72 (1H, d, JH,H = 4.7 Hz,
CH), 3.84–3.98 (1H, m, CHN), 6.71 (1H, OH). 13C NMR (75.5 MHz,
CDCl3):
d 9.6, 19.4, 21.6 (3CH3), 23.0, 24.7, 28.8, 28.9, 29.9 (7CH2),
50.6, 53.0 (2Cq), 51.4 (CH), 68.6 (CHN), 83.9 (q, 2JC,F = 28.6 Hz, Cq),
125.2 (q, JC,F = 290.0 Hz, CF3), 150.9 (C55N). 19F NMR (188 MHz,
1
CDCl3):
d
ꢀ67.9 (s, CF3). IR (KBr):
v
3432m (br, OH), 2997m, 2938vs,
(Z)-N-Methyl-[(1R,2S)-2-(trifluoromethyl)-2-(trimethylsilyloxy)-
bornan-3-yliden]amine N-oxide (6). The crude product was purified
by column chromatography on silica gel using first CH2Cl2/hexane
(3:2) and then CH2Cl2 with increasing amounts of ethyl acetate (0–
50%) as eluents. The product was isolated as a yellowish oil. Yield:
2866m, 1607m (C55N), 1496w, 1461s, 1395m, 1372w, 1296s,
1260vs, 1170vs, 1156vs, 1189s, 1111vs, 1024w, 1005w, 962s, 928w,
836w, 739w, 652m cmꢀ1. CI-(NH3) m/z (rel. int.): 335 (19), 334
(100, [M+1]+), 316 (11). Anal. Calcd for C17H26F3NO2 (333.39): C,
61.24; H, 7.86. Found: C, 61.25; H, 7.86.
270 mg (80%). An analytically pure sample was obtained by
25
(Z)-N-[(10R)-10-Phenylethyl]-[(1R,2S)-2-(trifluoromethyl)bornan-
crystallisation. Colourless crystals, m.p. 74–76 8C (hexane); [
+133.2 (c 0.008, CHCl3). 1H NMR (300 MHz, CDCl3):
a]
D
2-ol-3-yliden]amine N-oxide (5f). The pure product was obtained by
d
0.18 (9H, s,
crystallisation. Yield: 290 mg (81%). Colourless crystals, m.p. 124–
(CH3)3Si), 0.93, 1.01, 1.09 (9H, 3s, 3CH3), 1.40–2.00 (4H, m, 2CH2),
+131.5 (c 0.010, CHCl3). 1H NMR (200 MHz,
2.60 (1H, JH,H = 4.4 Hz, CH), 3.68 (3H, s, CH3N). 13C NMR
25
3
125 8C (Et2O); [
CDCl3):
1.77 (3H, d, 2JH,H = 6.7 Hz, CH3), 2.82 (1H, d, 2JH,H = 4.4 Hz, CH), 5.21
a
]
D
d
0.61, 0.85, 1.00 (9H, 3s, 3CH3), 1.52–1.97 (4H, m, 2CH2),
(75.5 MHz, CDCl3):
d 1.9 ((CH3)3Si), 10.7, 19.6, 21.9 (3CH3), 23.8,
27.9 (2CH2), 48.8, 55.9 (2Cq), 52.6 (CH), 81.4 (q, 2JC,F = 29.3 Hz, Cq),

582
G. Mloston et al. / Journal of Fluorine Chemistry 131 (2010) 578–583
1
124.6 (q, JC,F = 290.6 Hz, CF3), 150.2 (C55N). 19F NMR (188 MHz,
4.6. X-ray crystal-structure determination of 5g
CDCl3): 3022w 3022w, 2988w, 2959m,
d
ꢀ64.9 (s, CF3). IR (KBr):
v
1632w (C55N), 1460w, 1393w, 1327m, 1263s, 1251s, 1179vs,
1141vs, 1106m, 1020m, 1011m, 963w, 898m, 869m, 845s, 760w
cmꢀ1. CI-MS (NH3) m/z (rel. int.): 338 (100, [M+1]+, 322 (20). HR-
All measurements were performed on a Nonius KappaCCD
area-detector diffractometer [14] using graphite-monochro-
˚
a radiation (l 0.71073 A) and an Oxford Cryosys-
mated Mo K
ESI-MS (NaI): Calcd for
360.1583.
C
15H26F3NO2SiN: 360.1582; found:
tems Cryostream 700 cooler. The data collection and refinement
parameters are given below [15] and a view of the molecule is
shown in Fig. 1. Data reduction was performed with HKL Denzo
and Scalepack [16]. The intensities were corrected for Lorentz and
polarization effects, but not for absorption. Equivalent reflections
were merged. The structures were solved by direct methods
using SIR92 [17] 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 remain-
ing H-atoms were placed in geometrically calculated positions
and refined by using a riding 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 structures was carried out on F2
4.4. Desilylation of nitrone 6
To a solution of nitrone 6 (337 mg, 1 mmol) in CH2Cl2 (1 mL),
2 mL (2 mmol) of a TBAF solution in THF were added and the
mixture was stirred for 72 h at room temperature. Then the
mixture was diluted with CH2Cl2 and washed with water. The
separated organic layers were collected and dried over anhydrous
MgSO4. After filtration, the solutions were evaporated to dryness.
The pure product was obtained by crystallisation. (Z)-N-Methyl-
[(1R,2S)-2-(trifluoromethyl)bornan-2-ol-3-yliden]amine
N-oxide
(5a). Yield: 236 mg (89%). Colourless crystals, m.p. 246–249 8C
25
(CH2Cl2/hexane); [
a]
+162.4 (c 0.010, CHCl3).
D
4.5. Photo-isomerisation of nitrone 5a
using full-matrix least-squares procedures, which minimized the
2
function
S
wðFo2 ꢀ Fc2Þ . A correction for secondary extinction was
A solution of 5a (260 mg, 1 mmol) in methanol (100 mL) was
stirred magnetically in a quartz flask, while a stream of argon was
bubbled through the solution, which was irradiated with a high-
pressure mercury lamp. After 1 h, the reaction was complete (TLC),
and the solvent was evaporated in vacuo. The semi-solid residue
was purified by column chromatography on silica gel using hexane
with increasing amounts of CH2Cl2 (0–40%) as the eluent. Two
main fractions containing the separated diastereoisomers 2-exo,3-
endo- and 2-exo,3-exo-7 were isolated in an overall yield of 182 mg
(70%).
applied. Neutral atom scattering factors for non-H-atoms were
taken from Ref. [18], and the scattering factors for H-atoms were
taken from Ref. [19] Anomalous dispersion effects were included
in Fc [20]; the values for f0 and f00 were those of Ref. [21]. The
values of the mass attenuation coefficients are those of Ref. [22].
All calculations were performed using the SHELXL97 [23]
program.
Crystal data for 5g: C17H20F3NO2, M = 327.34, crystallised from
CH2Cl2/hexane, colourless, prism, crystal dimensions 0.15 mm
ꢁ 0.18 mm ꢁ 0.28 mm, orthorhombic, space group P212121, Z = 4,
(1R,2S,3S)-2-Hydroxy-20-methyl-2-(trifluoromethyl)spiro[bor-
nan-3,30-oxaziridine] (2-exo,3-endo-7). Isolated as the less polar
fraction. Yield: 70 mg (27%). Pure product was obtained by
reflections for cell determination 2089,
˚
2
u
range for cell
˚
determination
4–558,
a = 7.2990(3) A,
b = 12.8005(5)ꢀA3,
3
˚
˚
c = 16.8843(6) A, V = 1577.5(1) A , T = 160(1) K, DX = 1.378 g cm
m
,
crystallisation. Colourless crystals, m.p. 107–108 8C (hexane);
(Mo K
reflections measured 22,221, symmetry independent reflections
2080, reflections with I > 2 (I) 1707, reflections used in refine-
a f and v, 2u(max) = 558, total
) = 0.113 mmꢀ1, scan type
25
[
a]
ꢀ28.5 (c 0.2, CHCl3). 1H NMR (200 MHz, CDCl3):
d 0.97,
D
1.06, 1.15 (9H, 3s, 3CH3), 1.57–1.89 (4H, m, 2CH2), 1.95 (1H, d,
s
2JH,H = 4.2 Hz, CH), 1.93–1.97 (1H, m, CH), 2.79 (3H, s, CH3N), 3.06
ment 2080, parameters refined 216; R(F) [I > 2
s
(I) reflec-
(1H, s, OH). 13C NMR (50 MHz, CDCl3):
d
9.8, 19.2, 21.6 (3CH3), 21.1,
tions] = 0.0479,
wRðF2Þ
[all
data] = 0.1117
(w ¼ ½
s
ðFo2Þ
2
28.7 (2CH2), 42.9 (CH), 44.6 (CH3N), 48.0, 52.7 (2Cq), 80.3 (q,
þð0:0633PÞ þ 0:0664Pꢂꢀ1, where P = (Fo2 þ 2Fc2=3), goodness of
1
ꢀ3
,
2JC,F = 25.9 Hz, Cq), 93.4 (OCN); 124.7 (q, JC,F = 287.8 Hz, CF3). 19F
fit 1.107, final Dmax
/
s
0.001, Dr (max; min) = 0.38; ꢀ0.33 e A
˚
NMR (188 MHz, CDCl3):
3013m, 2994m, 2971m, 2937m, 2891m, 1636w, 1460m, 1432m,
1396m, 1387m, 1338w, 1289s, 1281s, 1242w, 1227w, 1167 s,
d
ꢀ71.3 (s, CF3). IR (KBr):
v
3447s (br, OH),
secondary extinction coefficient = 0.123(8).
v
Acknowledgments
1151s, 1126s, 1111m, 1015m, 1000m, 973m, 953m, 924w, 854m,
811w, 710m, 621w cmꢀ1. CI-MS (NH3) m/z (rel. int.): 267 (13), 266
(100, [M+1]+). HR-ESI-MS (NaI): Calcd for C12H18F3NO2Na:
288.1187; found: 288.1187.
(1R,2S,3R)-2-Hydroxy-20-methyl-2-(trifluoromethyl)spiro[bor-
nan- 3,30-oxaziridine] (2-exo,3-exo-7). Isolated as the more polar
fraction. Yield: 122 mg (43%). Pure product was obtained by
The authors thank the Polish Ministry for Science and Higher
Education for a grant (Grant # N N204 130335) (G.M. and E.O.), and
financial support by F. Hoffmann-La Roche AG, Basel, is gratefully
acknowledged (H.H.).
References
crystallisation. Colourless crystals, m.p. 88–90 8C (hexane);
[1] Th. Money, in: T. Hudlicky (Ed.), Organic Synthesis Theory and Applications, vol.
3, JAI Press Inc., Greenwich, London, 1996, pp. 1–83.
[2] (a) M.P. Bonner, E.R. Thornton, J. Am. Chem. Soc. 113 (1991) 1299–1308;
(b) T. Berranger, Y. Langlois, J. Org. Chem. 60 (1995) 1720–1726.
[3] W. Dmowski, J. Fluorine Chem. 109 (2001) 33–37.
ꢀ73.5 (c 0.2, CHCl3). 1H NMR (200 MHz, CDCl3):
d 0.98,
25
[
a
]
D
1.08, 1.16 (9H, 3s, 3CH3), 1.45–1.95 (4H, m, 2CH2), 1.98–2.02
(1H, m, CH), 2.65 (1H, s, OH), 2.81 (3H, s, CH3N). 13C NMR
(50 MHz, CDCl3):
(CH); 46.2 (CH3N); 48.6, 52.7 (2Cq); 80.4 (q, JC,F = 26.5 Hz, Cq);
92.3 (OCN); 125.0 (q, JC,F = 287.7 Hz, CF3). 19F NMR (188 MHz,
d 9.9, 19.5, 21.4 (3CH3); 20.6, 28.5 (2CH2); 42.7
[4] G. Mloston, E. Obijalska, A. Linden, H. Heimgartner, Tetrahedron: Asym. 19 (2008)
1676–1683.
2
1
[5] (a) D. Mostowicz, C. Bełz˙ ecki, J. Org. Chem. 42 (1977) 3917–3921;
(b) W.H. Pirkle, P.L. Rinaldi, J. Org. Chem. 43 (1978) 4475–4480;
(c) A. Forni, I. Moretti, G. Torre, E. Vignudelli, Tetrahedron Lett. (1979) 907–910;
(d) P.C.B. Page, V.L. Murrell, C. Limousin, D.D.P. Laffan, D. Bethell, A.M.Z. Slawin,
T.A.D. Smith, J. Org. Chem. 65 (2000) 4204–4207.
[6] (a) I.J. Li, Name Reactions, Springer, Heidelberg, Berlin, 2007, p. 185;
(b) F.A. Davis, B.-C. Chen, Chem. Rev. 92 (1992) 919–934;
(c) J.C. Towson, M.C. Weismiller, G.S. Lal, A.C. Sheppard, A. Kumar, F.A. Davis, Org.
Synth. 69 (1990) 158–168.
CDCl3):
d
ꢀ70.5 (s, CF3). IR (KBr):
v 3490s (br, OH), 2983m,
2971m, 2938m, 1636w, 1467w, 1460w, 1435w, 1397m, 1389m,
1379m, 1281s, 1163vs, 1128s, 1122s, 1011w, 988w, 976m, 953w,
912m, 820w, 754w, 686w cmꢀ1. CI-MS (NH3) m/z (rel. int.): 267
(12), 266 (100, [M+1]+). HR-ESI-MS (NaI): Calcd for
C12H18F3NO2Na: 288.1187; found: 288.1184.

G. Mloston et al. / Journal of Fluorine Chemistry 131 (2010) 578–583
583
[7] (a) J. Aube´, Chem. Soc. Rev. 26 (1997) 269–277;
[15] CCDC-711311 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.
(b) E. Bourguret, J.-L. Baneres, J.-P. Girard, J. Parello, J.-P. Vidal, X. Lusinchi, J.-P.
Declerq, Org. Lett. 3 (2001) 3067–3070;
(c) K.M. Partridge, M.E. Anzovino, T.P. Yoon, J. Am. Chem. Soc. 130 (2008) 2920–
2921.
[8] L.L. Rodina, J. Kurucz, I.K. Korobitsyna, Zh. Org. Khim. 17 (1981) 1916–1929;
L.L. Rodina, J. Kurucz, I.K. Korobitsyna, Russ. J. Org. Chem. 17 (1981) 1711–1722.
[9] J. Bernstein, R.E. Davis, L. Shimoni, N.-L. Chang, Angew. Chem. Int. Ed. Engl. 34
(1995) 1555–1573.
[16] Z. Otwinowski, W. Minor, in: C.W. Carter, Jr., R.M. Sweet (Eds.), Methods in
Enzymology, Vol. 276, Macromolecular Crystallography, Part A, Academic Press,
New York, 1997, pp. 307–326.
[17] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M.C. Burla, G. Polidori, M.
Camalli, SIR92, J. Appl. Crystallogr. 27 (1994) 435.
[18] 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.
[10] C. K. Johnson, ORTEP II, Report ORNL-5138, Oak Ridge National Laboratory, Oak
Ridge, Tennessee, 1976.
[11] (a) J. Hamer, A. Macaluso, Chem. Rev. 64 (1964) 473–495;
(b) E. Breuer, in: S. Patai, Z. Rappoport (Eds.), Nitrones, Nitronates and Nitroxides,
J. Wiley & Sons, New York, 1989, pp. 287–291, Chapter 3;
(c) R.C.F. Jones, J.N. Martin, in: A. Padwa, W.H. Pearson (Eds.), Synthetic Applica-
tion of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural
Products, J. Wiley & Sons, New York, 2002, pp. 1–82;
(d) A.F. Amado, C. Kouklovsky, Y. Langlois, Synlett (2005) 103–106.
[12] W.D. Emmons, J. Am. Chem. Soc. 79 (1957) 5739–5754.
[13] N. De Kimpe, B. De Corte, Tetrahedron 48 (1992), 7345–5754.
[14] R. Hooft, Kappa CCD Collect Software, Nonius BV, Delft, The Netherlands, 1999.
[19] R.F. Stewart, E.R. Davidson, W.T. Simpson, J. Chem. Phys. 42 (1965) 3175–3187.
[20] J.A. Ibers, W.C. Hamilton, Acta Crystallogr. 17 (1964) 781–782.
[21] 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.
[22] D.C. Creagh, J.H. Hubbell, Dordrecht, in: A.J.C. Wilson (Ed.), International
Tables for Crystallography, vol. C, Kluwer Academic, 1992 , pp. 200–206,
Table 4.2.4.3.
[23] G.M. Sheldrick, SHELXL97, Program for the Refinement of Crystal Structures,
University of Go¨ttingen, Germany, 1997.